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Sample records for pneumonia induced severe

  1. Clinical Features of Severe or Fatal Mycoplasma pneumoniae Pneumonia

    PubMed Central

    Izumikawa, Koichi

    2016-01-01

    Mycoplasma pneumoniae is one of the most common causes of community-acquired pneumonia in children and young adults. The incidence of fulminant M. pneumoniae pneumonia (MPP) is relatively rare despite the high prevalence of M. pneumoniae infection. This literature review highlights the clinical features of fulminant MPP by examining the most recent data in epidemiology, clinical presentation, pathogenesis, and treatment. Fulminant MPP accounts for 0.5–2% of all MPP cases and primarily affects young adults with no underlying disease. Key clinical findings include a cough, fever, and dyspnea along with diffuse abnormal findings in radiological examinations. Levels of inflammatory markers such as white blood cells and C-reactive protein are elevated, as well as levels of lactate dehydrogenase, IL-18, aspartate transaminase, and alanine transaminase. The exact pathogenesis of fulminant MPP remains unclear, but theories include a delayed hypersensitivity reaction to M. pneumoniae and the contribution of delayed antibiotic administration to disease progression. Treatment options involve pairing the appropriate anti-mycoplasma agent with a corticosteroid that will downregulate the hypersensitivity response, and mortality rates are quite low in this treatment group. Further research is necessary to determine the exact pathogenesis of severe and fulminant types of MPP. PMID:27313568

  2. Burden of Severe Pneumonia, Pneumococcal Pneumonia and Pneumonia Deaths in Indian States: Modelling Based Estimates

    PubMed Central

    Farooqui, Habib; Jit, Mark; Heymann, David L.; Zodpey, Sanjay

    2015-01-01

    The burden of severe pneumonia in terms of morbidity and mortality is unknown in India especially at sub-national level. In this context, we aimed to estimate the number of severe pneumonia episodes, pneumococcal pneumonia episodes and pneumonia deaths in children younger than 5 years in 2010. We adapted and parameterized a mathematical model based on the epidemiological concept of potential impact fraction developed CHERG for this analysis. The key parameters that determine the distribution of severe pneumonia episode across Indian states were state-specific under-5 population, state-specific prevalence of selected definite pneumonia risk factors and meta-estimates of relative risks for each of these risk factors. We applied the incidence estimates and attributable fraction of risk factors to population estimates for 2010 of each Indian state. We then estimated the number of pneumococcal pneumonia cases by applying the vaccine probe methodology to an existing trial. We estimated mortality due to severe pneumonia and pneumococcal pneumonia by combining incidence estimates with case fatality ratios from multi-centric hospital-based studies. Our results suggest that in 2010, 3.6 million (3.3–3.9 million) episodes of severe pneumonia and 0.35 million (0.31–0.40 million) all cause pneumonia deaths occurred in children younger than 5 years in India. The states that merit special mention include Uttar Pradesh where 18.1% children reside but contribute 24% of pneumonia cases and 26% pneumonia deaths, Bihar (11.3% children, 16% cases, 22% deaths) Madhya Pradesh (6.6% children, 9% cases, 12% deaths), and Rajasthan (6.6% children, 8% cases, 11% deaths). Further, we estimated that 0.56 million (0.49–0.64 million) severe episodes of pneumococcal pneumonia and 105 thousand (92–119 thousand) pneumococcal deaths occurred in India. The top contributors to India’s pneumococcal pneumonia burden were Uttar Pradesh, Bihar, Madhya Pradesh and Rajasthan in that order. Our

  3. Streptococcus pneumoniae and Pseudomonas aeruginosa pneumonia induce distinct host responses

    PubMed Central

    McConnell, Kevin W.; McDunn, Jonathan E.; Clark, Andrew T.; Dunne, W. Michael; Dixon, David J.; Turnbull, Isaiah R.; DiPasco, Peter J.; Osberghaus, William F.; Sherman, Benjamin; Martin, James R.; Walter, Michael J.; Cobb, J. Perren; Buchman, Timothy G.; Hotchkiss, Richard S.; Coopersmith, Craig M.

    2009-01-01

    Objective Pathogens that cause pneumonia may be treated in a targeted fashion by antibiotics, but if this therapy fails, treatment involves only non-specific supportive measures, independent of the inciting infection. The purpose of this study was to determine whether host response is similar following disparate infections with similar mortalities. Design Prospective, randomized controlled study. Setting Animal laboratory in a university medical center. Interventions Pneumonia was induced in FVB/N mice by either Streptococcus pneumoniae or two different concentrations of Pseudomonas aeruginosa. Plasma and bronchoalveolar lavage fluid from septic animals was assayed by a microarray immunoassay measuring 18 inflammatory mediators at multiple timepoints. Measurements and Main Results The host response was dependent upon the causative organism as well as kinetics of mortality, but the pro- and anti- inflammatory response was independent of inoculum concentration or degree of bacteremia. Pneumonia caused by different concentrations of the same bacteria, Pseudomonas aeruginosa, also yielded distinct inflammatory responses; however, inflammatory mediator expression did not directly track the severity of infection. For all infections, the host response was compartmentalized, with markedly different concentrations of inflammatory mediators in the systemic circulation and the lungs. Hierarchical clustering analysis resulted in the identification of 5 distinct clusters of the host response to bacterial infection. Principal components analysis correlated pulmonary MIP-2 and IL-10 with progression of infection while elevated plasma TNFsr2 and MCP-1 were indicative of fulminant disease with >90% mortality within 48 hours. Conclusions Septic mice have distinct local and systemic responses to Streptococcus pneumoniae and Pseudomonas aeruginosa pneumonia. Targeting specific host inflammatory responses induced by distinct bacterial infections could represent a potential therapeutic

  4. [Severe stomatitis caused by Mycoplasma pneumoniae infection].

    PubMed

    Barfod, T S; Pedersen, C

    1999-11-15

    Mycoplasma pneumoniae infection is sometimes followed by systemic reactions such as erythema multiforme major/Stevens-Johnsons syndrome. In the described case, a 30 year-old man developed severe inflammation of the oral mucous membranes following respiratory infection with Mycoplasma pneumoniae. There was also conjunctivitis and diarrhoea, and a target-like eruption was seen on the penis, but apart from slight perioral erythema and periorbital swelling, no further skin involvement was seen. The patient was treated with macrolide antibiotics for 14 days and gradually recovered. PMID:10611837

  5. Inflammation-inducing Factors of Mycoplasma pneumoniae

    PubMed Central

    Shimizu, Takashi

    2016-01-01

    Mycoplasma pneumoniae, which causes mycoplasmal pneumonia in human, mainly causes pneumonia in children, although it occasionally causes disease in infants and geriatrics. Some pathogenic factors produced by M. pneumoniae, such as hydrogen peroxide and Community-Acquired Respiratory Distress Syndrome (CARDS) toxin have been well studied. However, these factors alone cannot explain this predilection. The low incidence rate of mycoplasmal pneumonia in infants and geriatrics implies that the strong inflammatory responses induced by M. pneumoniae coordinate with the pathogenic factors to induce pneumonia. However, M. pneumoniae lacks a cell wall and does not possess an inflammation-inducing endotoxin, such as lipopolysaccharide (LPS). In M. pneumoniae, lipoproteins were identified as an inflammation-inducing factor. Lipoproteins induce inflammatory responses through Toll-like receptors (TLR) 2. Because Mycoplasma species lack a cell wall and lipoproteins anchored in the membrane are exposed, lipoproteins and TLR2 have been thought to be important for the pathogenesis of M. pneumoniae. However, recent reports suggest that M. pneumoniae also induces inflammatory responses also in a TLR2-independent manner. TLR4 and autophagy are involved in this TLR2-independent inflammation. In addition, the CARDS toxin or M. pneumoniae cytadherence induces inflammatory responses through an intracellular receptor protein complex called the inflammasome. In this review, the inflammation-inducing factors of M. pneumoniae are summarized. PMID:27065977

  6. Clozapine-Induced Late Agranulocytosis and Severe Neutropenia Complicated with Streptococcus pneumonia, Venous Thromboembolism, and Allergic Vasculitis in Treatment-Resistant Female Psychosis

    PubMed Central

    Voulgari, Christina; Giannas, Raphael; Paterakis, Georgios; Kanellou, Anna; Anagnostopoulos, Nikolaos; Pagoni, Stamata

    2015-01-01

    Clozapine is a second-generation antipsychotic agent from the benzodiazepine group indicated for treatment-resistant schizophrenia and other psychotic conditions. Using clozapine earlier on once a case appears to be refractory limits both social and personal morbidity of chronic psychosis. However treatment with second-generation antipsychotics is often complicated by adverse effects. We present a case of a 33-year-old Caucasian woman with a 25-year history of refractory psychotic mania after switching to a 2-year clozapine therapy. She presented clozapine-induced absolute neutropenia, agranulocytosis, which were complicated by Streptococcus pneumonia and sepsis. Clozapine-induced thromboembolism of the common femoral and right proximal iliac vein, as well as allergic vasculitis, was diagnosed. She achieved full remission on granulocyte-colony stimulating factor and specific antibiotic treatment. Early detection of severe clozapine-induced absolute neutropenia and agranulocytosis enabled the effective treatment of two among its most severe complications. Additional evidence to the previously reported possible causal relation between clozapine and venous thromboembolism is offered. Finally, clozapine-induced allergic vasculitis is confirmed as a late adverse effect of clozapine therapy. PMID:25755670

  7. Decreased Interleukin-10 Responses in Children with Severe Mycoplasma pneumoniae Pneumonia

    PubMed Central

    Chen, Wei; Fang, Yuan; Liu, Boyu; Liu, Yan; Fei, Guanghe; Wang, Linding

    2016-01-01

    Several cytokines may play roles in the immunological pathogenesis of mycoplasmal pneumonia caused by Mycoplasma pneumoniae. In this study, we investigated serum cytokine profiles in children with mycoplasmal pneumonia. The serum levels of interleukin (IL)-8, IL-10, and IL-18 were examined using ELISA kits in 34 patients with M. pneumoniae infection (Group 1, 11 with severe mycoplasmal pneumonia; Group 2, 13 with mild mycoplasmal pneumonia; Group 3, 10 with asthma) and 32 age-matched, non-infected controls. The serum levels of IL-8, IL-10, and IL-18 increased significantly in patients with mycoplasmal pneumonia compared with those in controls (P<0.01). The serum levels of IL-10 decreased significantly in Group 1 compared with those in Group 2 (P<0.01). The serum levels of IL-18 increased significantly in Group 1 compared with those in Group 2 (P<0.01). The serum levels of IL-10 and IL-18 decreased significantly in 10 M. pneumoniae-infected patients with asthma compared with those in 24 M. pneumoniae-infected patients without asthma (P<0.01). We examined the level of interleukins (IL-8, IL-10 and IL-18) after the patients started therapy. The data showed that IL-18 were lower after therapy (P<0.01). Collectively, our data suggested that these cytokines may be involved in the pathogenesis of mycoplasmal pneumonia. PMID:26751073

  8. [Antibiotic therapy of severe community-acquired pneumonia].

    PubMed

    Molchanova, O V; Suleĭmanov, S Sh; Ostrovskiĭ, A B

    2009-01-01

    Combined antibiotic therapy, including the use of intravenous cefotaxime (a beta-lactam) and azithromycin (a macrolide) was shown advantageous from both clinical and economic viewpoints in the treatment of severe community-acquired pneumonia. PMID:19711847

  9. [THREE CASES OF DRUG-INDUCED PNEUMONIA CAUSED BY MESALAZINE].

    PubMed

    Akiyama, Norimichi; Yokomura, Koshi; Nozue, Tsuyoshi; Abe, Takefumi; Matsui, Takashi; Suda, Takafumi

    2015-12-01

    We report three cases of drug-induced pneumonia caused by mesalazine. They were all diagnosed as ulcerative colitis and treated with mesalazine orally. Our three cases and literature review revealed that mesalazine-induced pneumonia resemble like eosinophilic pneumonia or organizing pneumonia and that have good prognosis with drug cessation or administration of corticosteroid. The patient of ulcerative colitis is increasing every year and it is anticipated that the patient with mesalazine-induced pneumonia may also increase. In the treatment of ulcerative colitis with mesalazine, we should pay attention with patient's cough or fever for early detection of drug-induced pneumonia. PMID:26727138

  10. Systemic steroid treatment for severe expanding pneumococcal pneumonia.

    PubMed

    Lavi, Eran; Shoseyov, David; Simanovsky, Natalia; Brooks, Rebecca

    2015-01-01

    The treatment of bacterial community-acquired pneumonia (CAP) is based on appropriate antibiotic therapy and supportive care such as intravenous fluids and supplemental oxygen. There is no available data regarding the use of steroids in CAP in children. We present an unusual case of a child with severe respiratory distress, on the brink of mechanical ventilation, due to a rapidly expanding pneumococcal pneumonia. The administration of systemic steroids resulted in a dramatic response with rapid improvement of clinical and radiological abnormalities followed by improvement of laboratory abnormalities. This case report should raise the awareness of the potential benefits of steroids in the treatment of severe pneumonia in children. Prospective randomized trials are needed to confirm the efficacy of steroids in this setting and to determine which patients would benefit most from this. PMID:25815231

  11. Systemic Steroid Treatment for Severe Expanding Pneumococcal Pneumonia

    PubMed Central

    Lavi, Eran; Shoseyov, David; Simanovsky, Natalia; Brooks, Rebecca

    2015-01-01

    The treatment of bacterial community-acquired pneumonia (CAP) is based on appropriate antibiotic therapy and supportive care such as intravenous fluids and supplemental oxygen. There is no available data regarding the use of steroids in CAP in children. We present an unusual case of a child with severe respiratory distress, on the brink of mechanical ventilation, due to a rapidly expanding pneumococcal pneumonia. The administration of systemic steroids resulted in a dramatic response with rapid improvement of clinical and radiological abnormalities followed by improvement of laboratory abnormalities. This case report should raise the awareness of the potential benefits of steroids in the treatment of severe pneumonia in children. Prospective randomized trials are needed to confirm the efficacy of steroids in this setting and to determine which patients would benefit most from this. PMID:25815231

  12. Recommendations for treatment of childhood non-severe pneumonia.

    PubMed

    Grant, Gavin B; Campbell, Harry; Dowell, Scott F; Graham, Stephen M; Klugman, Keith P; Mulholland, E Kim; Steinhoff, Mark; Weber, Martin W; Qazi, Shamim

    2009-03-01

    WHO recommendations for early antimicrobial treatment of childhood pneumonia have been effective in reducing childhood mortality, but the last major revision was over 10 years ago. The emergence of antimicrobial resistance, new pneumonia pathogens, and new drugs have prompted WHO to assemble an international panel to review the literature on childhood pneumonia and to develop evidence-based recommendations for the empirical treatment of non-severe pneumonia among children managed by first-level health providers. Treatment should target the bacterial causes most likely to lead to severe disease, including Streptoccocus pneumoniae and Haemophilus influenzae. The best first-line agent is amoxicillin, given twice daily for 3-5 days, although co-trimoxazole may be an alternative in some settings. Treatment failure should be defined in a child who develops signs warranting immediate referral or who does not have a decrease in respiratory rate after 48-72 h of therapy. If failure occurs, and no indication for immediate referral exists, possible explanations for failure should be systematically determined, including non-adherence to therapy and alternative diagnoses. If failure of the first-line agent remains a possible explanation, suitable second-line agents include high-dose amoxicillin-clavulanic acid with or without an affordable macrolide for children over 3 years of age. PMID:19246022

  13. Inducible epithelial resistance protects mice against leukemia-associated pneumonia.

    PubMed

    Leiva-Juárez, Miguel M; Ware, Hayden H; Kulkarni, Vikram V; Zweidler-McKay, Patrick A; Tuvim, Michael J; Evans, Scott E

    2016-08-18

    Despite widespread infection prevention efforts, pneumonia remains the leading cause of death among patients with acute leukemia, due to complex disease- and treatment-dependent immune defects. We have reported that a single inhaled treatment with a synergistic combination of Toll-like receptor 2/6 (TLR 2/6) and TLR9 agonists (Pam2-ODN) induces protective mucosal defenses in mice against a broad range of pathogens. As Pam2-ODN-induced protection persists despite depletion of several leukocyte populations, we tested whether it could prevent pneumonia in a mouse model of acute myeloid leukemia (AML) remission induction therapy. Pam2-ODN prevented death due to pneumonia caused by Pseudomonas aeruginosa, Streptococcus pneumoniae, and Aspergillus fumigatus when mice were heavily engrafted with leukemia cells, had severe chemotherapy-induced neutropenia or both. Pam2-ODN also extended survival of pneumonia in NSG mice engrafted with primary human AML cells. Protection was associated with rapid pathogen killing in the lungs at the time of infection and with reduced pathogen burdens at distant sites at the end of observation. Pathogen killing was inducible directly from isolated lung epithelial cells and was not abrogated by the presence of leukemia cells or cytotoxic agents. Pam2-ODN had no discernible effect on replication rate, total tumor population, or killing by chemotherapy of mouse or human leukemia cells, either in vitro or in vivo. Taken together, we report that therapeutic stimulation of lung epithelial defenses robustly protects against otherwise lethal pneumonias despite the profound immune dysfunction associated with acute leukemia and its treatment. These findings may suggest an opportunity to protect this population during periods of peak vulnerability. PMID:27317793

  14. Imipenem/cilastatin-induced acute eosinophilic pneumonia.

    PubMed

    Foong, Kap Sum; Lee, Ashley; Pekez, Marijeta; Bin, Wei

    2016-01-01

    Drugs, toxins, and infections are known to cause acute eosinophilic pneumonia. Daptomycin and minocycline are the commonly reported antibiotics associated with acute eosinophilic pneumonia. In this study, we present a case of imipenem/cilastatin-induced acute eosinophilic pneumonia. The patient presented with fever, acute hypoxic respiratory distress, and diffuse ground-glass opacities on the chest CT a day after the initiation of imipenem/cilastatin. Patient also developed peripheral eosinophilia. A reinstitution of imipenem/cilastatin resulted in recurrence of the signs and symptoms. A bronchoscopy with bronchoalveolar lavage showed 780 nucleated cells/mm(3) with 15% eosinophil. The patient's clinical condition improved significantly after the discontinuation of imipenem/cilastatin therapy and the treatment with corticosteroid. PMID:26944380

  15. Atherosclerosis Induced by Chlamydophila pneumoniae: A Controversial Theory.

    PubMed

    Honarmand, Hamidreza

    2013-01-01

    More than a century ago, inflammation and infection were considered to have atherogenic effects. The old idea that coronary heart disease (CHD) possibly has an infectious etiology has only reemerged in recent years. Atherosclerosis is the main pathological process involved in CHD and is, logically, the first place to look for infectious etiology. The process of atherosclerosis itself provides the first hints of potential infectious cause. Smooth muscle proliferation, with subsequent intimal thickening, luminal narrowing, and endothelial degeneration, constitutes the natural history of atherosclerosis, being with the severity and speed of these changes. Both viral and bacterial pathogens have been proposed to be associated with the inflammatory changes found in atherosclerosis. Recently, Chlamydophila pneumoniae (C. pneumoniae) has been implicated as a possible etiologic agent of coronary artery disease and atherosclerosis. New evidence which supports a role for C. pneumoniae in the pathogenesis of atherosclerosis has emerged. C. pneumoniae has been detected in atherosclerotic arteries by several techniques, and the organism has been isolated from both coronary and carotid atheromas. Recent animal models have suggested that C. pneumoniae is capable of inducing atherosclerosis in both rabbit and mouse models of atherosclerosis. Furthermore, human clinical treatment studies which examined the use of antichlamydial macrolide antibiotics in patients with coronary atherosclerosis have been carried out. The causal relationship has not yet been proven, but ongoing large intervention trials and research on pathogenetic mechanisms may lead to the use of antimicrobial agents in the treatment of CHD in the future. PMID:23956742

  16. Pulmonary tuberculosis in severely-malnourished or HIV-infected children with pneumonia: a review.

    PubMed

    Chisti, Mohammod Jobayer; Ahmed, Tahmeed; Pietroni, Mark A C; Faruque, Abu S G; Ashraf, Hasan; Bardhan, Pradip K; Hossain, Iqbal; Das, Sumon Kumar; Salam, Mohammed Abdus

    2013-09-01

    Presentation of pulmonary tuberculosis (PTB) as acute pneumonia in severely-malnourished and HIV-positive children has received very little attention, although this is very important in the management of pneumonia in children living in communities where TB is highly endemic. Our aim was to identify confirmed TB in children with acute pneumonia and HIV infection and/or severe acute malnutrition (SAM) (weight-for-length/height or weight-for-age z score <-3 of the WHO median, or presence of nutritional oedema). We conducted a literature search, using PubMed and Web of Science in April 2013 for the period from January 1974 through April 2013. We included only those studies that reported confirmed TB identified by acid fast bacilli (AFB) through smear microscopy, or by culture-positive specimens from children with acute pneumonia and SAM and/or HIV infection. The specimens were collected either from induced sputum (IS), or gastric lavage (GL), or broncho-alveolar lavage (BAL), or percutaneous lung aspirates (LA). Pneumonia was defined as the radiological evidence of lobar or patchy consolidation and/or clinical evidence of severe/ very severe pneumonia according to the WHO criteria of acute respiratory infection. A total of 17 studies met our search criteria but 6 were relevant for our review. Eleven studies were excluded as those did not assess the HIV status of the children or specify the nutritional status of the children with acute pneumonia and TB. We identified only 747 under-five children from the six relevant studies that determined a tubercular aetiology of acute pneumonia in children with SAM and/or positive HIV status. Three studies were reported from South Africa and one each from the Gambia, Ethiopia, and Thailand where 610, 90, 35, and 12 children were enrolled and 64 (10%), 23 (26%), 5 (14%), and 1 (8%) children were identified with active TB respectively, with a total of 93 (12%) children with active TB. Among 610 HIV-infected children in three studies

  17. Pneumonia

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Pneumonia KidsHealth > For Teens > Pneumonia Print A A A ... having to go to the hospital. What Is Pneumonia? Pneumonia (pronounced: noo-MOW-nyuh) is an infection ...

  18. A case of vildagliptin-induced interstitial pneumonia

    PubMed Central

    Kuse, Naoyuki; Abe, Shinji; Kuribayashi, Hidehiko; Inomata, Minoru; Saito, Hitoshi; Fukuda, Yuh; Gemma, Akihiko

    2016-01-01

    A 65-year-old Japanese male with type 2 diabetes mellitus was admitted to our hospital with a productive cough and worsening dyspnea. He had started receiving vildagliptin, which is one of the dipeptideylpeptidase-4 (DPP-4) inhibitors, several days before the appearance of his symptoms. Laboratory findings revealed markedly elevated levels of immunoglobulin E and Krebs von den Lungen-6. Chest computed tomography revealed ground-glass opacity with irregular reticulation throughout both lungs. Biopsy specimens by transbronchial lung biopsy showed subacute interstitial pneumonia and an organizing pneumonia pattern with acute alveolar injury. The drug lymphocyte stimulation test showed a positive result for vildagliptin. Withdrawal of vildagliptin and administration of glucocorticoid treatment improved his respiratory condition and radiological findings. Therefore, we diagnosed the patient with vildagliptin-induced interstitial pneumonia based on both his clinical course and pathological findings. Interstitial pneumonia as a side effect of vildagliptin is rare. It may be necessary to monitor the respiratory condition of patients upon administration of DPP-4 inhibitors until further evidence is obtained. PMID:27144110

  19. A case of vildagliptin-induced interstitial pneumonia.

    PubMed

    Kuse, Naoyuki; Abe, Shinji; Kuribayashi, Hidehiko; Inomata, Minoru; Saito, Hitoshi; Fukuda, Yuh; Gemma, Akihiko

    2016-01-01

    A 65-year-old Japanese male with type 2 diabetes mellitus was admitted to our hospital with a productive cough and worsening dyspnea. He had started receiving vildagliptin, which is one of the dipeptideylpeptidase-4 (DPP-4) inhibitors, several days before the appearance of his symptoms. Laboratory findings revealed markedly elevated levels of immunoglobulin E and Krebs von den Lungen-6. Chest computed tomography revealed ground-glass opacity with irregular reticulation throughout both lungs. Biopsy specimens by transbronchial lung biopsy showed subacute interstitial pneumonia and an organizing pneumonia pattern with acute alveolar injury. The drug lymphocyte stimulation test showed a positive result for vildagliptin. Withdrawal of vildagliptin and administration of glucocorticoid treatment improved his respiratory condition and radiological findings. Therefore, we diagnosed the patient with vildagliptin-induced interstitial pneumonia based on both his clinical course and pathological findings. Interstitial pneumonia as a side effect of vildagliptin is rare. It may be necessary to monitor the respiratory condition of patients upon administration of DPP-4 inhibitors until further evidence is obtained. PMID:27144110

  20. Treatment of Severe Hypervolemic Hyponatremia in a Child With Pneumonia.

    PubMed

    Genoni, Teresa; Tenconi, Rossana; Bertolozzi, Giuseppe; Laicini, Emanuela Anna; Tardini, Giacomo; Vianello, Federica; Leva, Ernesto; Milani, Gregorio Paolo; Fossali, Emilio Filippo

    2016-06-01

    A 21-month-old boy came to our attention because of pneumonia. His weight increased before presentation, and his blood test results showed hyponatremia (116 mEq/L), low plasma osmolarity (241 mOsm/L), and high urine osmolarity (435 mOsm/L). He was treated with 0.9% sodium chloride solution and intravenous furosemide, and sodium levels rose up to 135 mEq/L in 36 hours. No standard treatment is available for severe hyponatremia in children. The use of vaptans in pediatric patients is described in literature, but it lacks evidence about safety and effectiveness. We suggest that furosemide administration plus salt replacement is effective in restoring normal values of plasma sodium concentration in severe euvolemic and hypervolemic hyponatremia. PMID:27253356

  1. A severe case of acute exogenous lipoid pneumonia treated with systemic corticosteroid.

    PubMed

    Yasui, Hideki; Yokomura, Koshi; Suda, Takafumi

    2016-01-01

    Acute exogenous lipoid pneumonia is a rare disorder in adults. A treatment of choice for lipoid pneumonia has not been established, and systemic corticosteroid use remains controversial. We report the case of a 32-year-old man with schizophrenia who presented with kerosene-induced acute exogenous lipoid pneumonia that was treated with a systemic corticosteroid. In this case, supportive therapy did not improve the patient's condition, so systemic corticosteroid therapy was commenced four days after he ingested the kerosene. After corticosteroid commencement, the patient's symptoms and hypoxia improved within a few days. Although some radiological characteristics of this disorder have been reported previously, the process of radiological improvement of exogenous lipoid pneumonia is not well known. In this case, computed tomography findings changed dramatically after corticosteroid therapy was initiated. Extensive bilateral consolidations that were observed on admission improved. Although pneumatoceles developed two weeks after corticosteroid commencement, they were nearly gone after two months of the treatment. While corticosteroid therapy is not suitable for all cases, it should be considered for severe or refractory cases. PMID:27222789

  2. A severe case of acute exogenous lipoid pneumonia treated with systemic corticosteroid

    PubMed Central

    Yasui, Hideki; Yokomura, Koshi; Suda, Takafumi

    2016-01-01

    Acute exogenous lipoid pneumonia is a rare disorder in adults. A treatment of choice for lipoid pneumonia has not been established, and systemic corticosteroid use remains controversial. We report the case of a 32-year-old man with schizophrenia who presented with kerosene-induced acute exogenous lipoid pneumonia that was treated with a systemic corticosteroid. In this case, supportive therapy did not improve the patient's condition, so systemic corticosteroid therapy was commenced four days after he ingested the kerosene. After corticosteroid commencement, the patient's symptoms and hypoxia improved within a few days. Although some radiological characteristics of this disorder have been reported previously, the process of radiological improvement of exogenous lipoid pneumonia is not well known. In this case, computed tomography findings changed dramatically after corticosteroid therapy was initiated. Extensive bilateral consolidations that were observed on admission improved. Although pneumatoceles developed two weeks after corticosteroid commencement, they were nearly gone after two months of the treatment. While corticosteroid therapy is not suitable for all cases, it should be considered for severe or refractory cases. PMID:27222789

  3. The Definition of Pneumonia, the Assessment of Severity, and Clinical Standardization in the Pneumonia Etiology Research for Child Health Study

    PubMed Central

    Wonodi, Chizoba; Moïsi, Jennifer C.; Deloria-Knoll, Maria; DeLuca, Andrea N.; Karron, Ruth A.; Bhat, Niranjan; Murdoch, David R.; Crawley, Jane; Levine, Orin S.; O’Brien, Katherine L.; Feikin, Daniel R.

    2012-01-01

    To develop a case definition for the Pneumonia Etiology Research for Child Health (PERCH) project, we sought a widely acceptable classification that was linked to existing pneumonia research and focused on very severe cases. We began with the World Health Organization’s classification of severe/very severe pneumonia and refined it through literature reviews and a 2-stage process of expert consultation. PERCH will study hospitalized children, aged 1–59 months, with pneumonia who present with cough or difficulty breathing and have either severe pneumonia (lower chest wall indrawing) or very severe pneumonia (central cyanosis, difficulty breastfeeding/drinking, vomiting everything, convulsions, lethargy, unconsciousness, or head nodding). It will exclude patients with recent hospitalization and children with wheeze whose indrawing resolves after bronchodilator therapy. The PERCH investigators agreed upon standard interpretations of the symptoms and signs. These will be maintained by a clinical standardization monitor who conducts repeated instruction at each site and by recurrent local training and testing. PMID:22403224

  4. Severe Sepsis in Severely Malnourished Young Bangladeshi Children with Pneumonia: A Retrospective Case Control Study

    PubMed Central

    Chisti, Mohammod Jobayer; Salam, Mohammed Abdus; Bardhan, Pradip Kumar; Faruque, Abu S. G.; Shahid, Abu S. M. S. B.; Shahunja, K. M.; Das, Sumon Kumar; Hossain, Md Iqbal; Ahmed, Tahmeed

    2015-01-01

    Background In developing countries, there is no published report on predicting factors of severe sepsis in severely acute malnourished (SAM) children having pneumonia and impact of fluid resuscitation in such children. Thus, we aimed to identify predicting factors for severe sepsis and assess the outcome of fluid resuscitation of such children. Methods In this retrospective case-control study SAM children aged 0–59 months, admitted to the Intensive Care Unit (ICU) of the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh from April 2011 through July 2012 with history of cough or difficult breathing and radiologic pneumonia, who were assessed for severe sepsis at admission constituted the study population. We compared the pneumonic SAM children with severe sepsis (cases = 50) with those without severe sepsis (controls = 354). Severe sepsis was defined with objective clinical criteria and managed with fluid resuscitation, in addition to antibiotic and other supportive therapy, following the standard hospital guideline, which is very similar to the WHO guideline. Results The case-fatality-rate was significantly higher among the cases than the controls (40% vs. 4%; p<0.001). In logistic regression analysis after adjusting for potential confounders, lack of BCG vaccination, drowsiness, abdominal distension, acute kidney injury, and metabolic acidosis at admission remained as independent predicting factors for severe sepsis in pneumonic SAM children (p<0.05 for all comparisons). Conclusion and Significance We noted a much higher case fatality among under-five SAM children with pneumonia and severe sepsis who required fluid resuscitation in addition to standard antibiotic and other supportive therapy compared to those without severe sepsis. Independent risk factors and outcome of the management of severe sepsis in our study children highlight the importance for defining optimal fluid resuscitation therapy aiming at reducing the case

  5. Streptococcus pneumoniae capsule determines disease severity in experimental pneumococcal meningitis

    PubMed Central

    Grandgirard, Denis; Valente, Luca G.; Täuber, Martin G.; Leib, Stephen L.

    2016-01-01

    Streptococcus pneumoniae bacteria can be characterized into over 90 serotypes according to the composition of their polysaccharide capsules. Some serotypes are common in nasopharyngeal carriage whereas others are associated with invasive disease, but when carriage serotypes do invade disease is often particularly severe. It is unknown whether disease severity is due directly to the capsule type or to other virulence factors. Here, we used a clinical pneumococcal isolate and its capsule-switch mutants to determine the effect of capsule, in isolation from the genetic background, on severity of meningitis in an infant rat model. We found that possession of a capsule was essential for causing meningitis. Serotype 6B caused significantly more mortality than 7F and this correlated with increased capsule thickness in the cerebrospinal fluid (CSF), a stronger inflammatory cytokine response in the CSF and ultimately more cortical brain damage. We conclude that capsule type has a direct effect on meningitis severity. This is an important consideration in the current era of vaccination targeting a subset of capsule types that causes serotype replacement. PMID:27009189

  6. Pulmonary Tuberculosis in Severely-malnourished or HIV-infected Children with Pneumonia: A Review

    PubMed Central

    Ahmed, Tahmeed; Pietroni, Mark A.C.; Faruque, Abu S.G.; Ashraf, Hasan; Bardhan, Pradip K.; Hossain, Md. Iqbal; Das, Sumon Kumar; Salam, Mohammed Abdus

    2013-01-01

    Presentation of pulmonary tuberculosis (PTB) as acute pneumonia in severely-malnourished and HIV-positive children has received very little attention, although this is very important in the management of pneumonia in children living in communities where TB is highly endemic. Our aim was to identify confirmed TB in children with acute pneumonia and HIV infection and/or severe acute malnutrition (SAM) (weight-for-length/height or weight-for-age z score <-3 of the WHO median, or presence of nutritional oedema). We conducted a literature search, using PubMed and Web of Science in April 2013 for the period from January 1974 through April 2013. We included only those studies that reported confirmed TB identified by acid fast bacilli (AFB) through smear microscopy, or by culture-positive specimens from children with acute pneumonia and SAM and/or HIV infection. The specimens were collected either from induced sputum (IS), or gastric lavage (GL), or broncho-alveolar lavage (BAL), or percutaneous lung aspirates (LA). Pneumonia was defined as the radiological evidence of lobar or patchy consolidation and/or clinical evidence of severe/very severe pneumonia according to the WHO criteria of acute respiratory infection. A total of 17 studies met our search criteria but 6 were relevant for our review. Eleven studies were excluded as those did not assess the HIV status of the children or specify the nutritional status of the children with acute pneumonia and TB. We identified only 747 under-five children from the six relevant studies that determined a tubercular aetiology of acute pneumonia in children with SAM and/or positive HIV status. Three studies were reported from South Africa and one each from the Gambia, Ethiopia, and Thailand where 610, 90, 35, and 12 children were enrolled and 64 (10%), 23 (26%), 5 (14%), and 1 (8%) children were identified with active TB respectively, with a total of 93 (12%) children with active TB. Among 610 HIV-infected children in three studies

  7. Severe Community-Acquired Pneumonia Caused by Human Adenovirus in Immunocompetent Adults: A Multicenter Case Series

    PubMed Central

    Tong, Fei; Yao, Dongqi; Walline, Joseph; Xu, Jun; Yu, Xuezhong

    2016-01-01

    Background Severe community-acquired pneumonia (CAP) caused by human adenovirus (HAdV), especially HAdV type 55 (HAdV-55) in immunocompetent adults has raised increasing concerns. Clinical knowledge of severe CAP and acute respiratory distress syndrome induced by HAdV-55 is still limited, though the pathogen has been fully characterized by whole-genome sequencing. Methods We conducted a multicentre retrospective review of all consecutive patients with severe CAP caused by HAdV in immunocompetent adults admitted to the Emergency Department Intensive Care Unit of two hospitals in Northern China between February 2012 and April 2014. Clinical, laboratory, radiological characteristics, treatments and outcomes of these patients were collected and analyzed. Results A total of 15 consecutive severe CAP patients with laboratory-confirmed adenovirus infections were included. The median age was 30 years and all cases were identified during the winter and spring seasons. HAdV-55 was the most frequently (11/15) detected HAdV type. Persistent high fever, cough and rapid progression of dyspnea were typically reported in these patients. Significantly increased pneumonia severity index (PSI), respiratory rate, and lower PaO2/FiO2, hypersensitive CRP were reported in non-survivors compared to survivors (P = 0.013, 0.022, 0.019 and 0.026, respectively). The rapid development of bilateral consolidations within 10 days after illness onset were the most common radiographic finding, usually accompanied by adjacent ground glass opacities and pleural effusions. Total mortality was 26.7% in this study. Corticosteroids were prescribed to 14 patients in this report, but the utilization rate between survivors and non-survivors was not significant. Conclusions HAdV and the HAdV-55 sub-type play an important role among viral pneumonia pathogens in hospitalized immunocompetent adults in Northern China. HAdV should be tested in severe CAP patients with negative bacterial cultures and a lack of

  8. Early non-invasive ventilation treatment for severe influenza pneumonia.

    PubMed

    Masclans, J R; Pérez, M; Almirall, J; Lorente, L; Marqués, A; Socias, L; Vidaur, L; Rello, J

    2013-03-01

    The role of non-invasive ventilation (NIV) in acute respiratory failure caused by viral pneumonia remains controversial. Our objective was to evaluate the use of NIV in a cohort of (H1N1)v pneumonia. Usefulness and success of NIV were assessed in a prospective, observational registry of patients with influenza A (H1N1) virus pneumonia in 148 Spanish intensive care units (ICUs) in 2009-10. Significant variables for NIV success were included in a multivariate analysis. In all, 685 patients with confirmed influenza A (H1N1)v viral pneumonia were admitted to participating ICUs; 489 were ventilated, 177 with NIV. The NIV was successful in 72 patients (40.7%), the rest required intubation. Low Acute Physiology and Chronic Health Evaluation (APACHE) II, low Sequential Organ Failure Assessment (SOFA) and absence of renal failure were associated with NIV success. Success of NIV was independently associated with fewer than two chest X-ray quadrant opacities (OR 3.5) and no vasopressor requirement (OR 8.1). However, among patients with two or more quadrant opacities, a SOFA score ≤7 presented a higher success rate than those with SOFA score >7 (OR 10.7). Patients in whom NIV was successful required shorter ventilation time, shorter ICU stay and hospital stay than NIV failure. In patients in whom NIV failed, the delay in intubation did not increase mortality (26.5% versus 24.2%). Clinicians used NIV in 25.8% of influenza A (H1N1)v viral pneumonia admitted to ICU, and treatment was effective in 40.6% of them. NIV success was associated with shorter hospital stay and mortality similar to non-ventilated patients. NIV failure was associated with a mortality similar to those who were intubated from the start. PMID:22404211

  9. Pneumonia

    MedlinePlus

    ... en español Neumonía You're out in the rain, jumping around in puddles, and somebody yells, "Get ... you really catch it from playing in the rain? What Is Pneumonia? Pneumonia (say: noo-MOW-nyuh) ...

  10. Hypervirulent Klebsiella pneumoniae induced ventilator-associated pneumonia in mechanically ventilated patients in China.

    PubMed

    Yan, Q; Zhou, M; Zou, M; Liu, W-e

    2016-03-01

    The purpose of this study was to investigate the clinical characteristics of hypervirulent K. pneumoniae (hvKP) induced ventilator-associated pneumonia (VAP) and the microbiological characteristics and epidemiology of the hvKP strains. A retrospective study of 49 mechanically ventilated patients with K. pneumoniae induced VAP was conducted at a university hospital in China from January 2014 to December 2014. Clinical characteristics and K. pneumoniae antimicrobial susceptibility and biofilm formation were analyzed. Genes of capsular serotypes K1, K2, K5, K20, K54 and K57 and virulence factors plasmid rmpA(p-rmpA), iroB, iucA, mrkD, entB, iutA, ybtS, kfu and allS were also evaluated. Multilocus sequence typing (MLST) and random amplified polymorphic DNA (RAPD) analyses were used to study the clonal relationship of the K. pneumoniae strains. Strains possessed p-rmpA and iroB and iucA were defined as hvKP. Of 49 patients, 14 patients (28.6 %) were infected by hvKP. Antimicrobial resistant rate was significantly higher in cKP than that in hvKP. One ST29 K54 extended-spectrum-beta-lactamase (ESBL) producing hvKP strain was detected. The prevalence of K1 and K2 in hvKP was 42.9 % and 21.4 %, respectively. The incidences of K1, K2, K20, p-rmpA, iroB, iucA, iutA, Kfu and alls were significantly higher in hvKP than those in cKP. ST23 was dominant among hvKP strains, and all the ST23 strains had identical RAPD pattern. hvKP has become a common pathogen of VAP in mechanically ventilated patients in China. Clinicians should increase awareness of hvKP induced VAP and enhance epidemiologic surveillance. PMID:26753990

  11. Cost of management of severe pneumonia in young children: systematic analysis

    PubMed Central

    Zhang, Shanshan; Sammon, Peter M.; King, Isobel; Andrade, Ana Lucia; Toscano, Cristiana M.; Araujo, Sheila N; Sinha, Anushua; Madhi, Shabir A.; Khandaker, Gulam; Yin, Jiehui Kevin; Booy, Robert; Huda, Tanvir M; Rahman, Qazi S; El Arifeen, Shams; Gentile, Angela; Giglio, Norberto; Bhuiyan, Mejbah U.; Sturm–Ramirez, Katharine; Gessner, Bradford D.; Nadjib, Mardiati; Carosone–Link, Phyllis J.; Simões, Eric AF; Child, Jason A; Ahmed, Imran; Bhutta, Zulfiqar A; Soofi, Sajid B; Khan, Rumana J; Campbell, Harry; Nair, Harish

    2016-01-01

    Background Childhood pneumonia is a major cause of childhood illness and the second leading cause of child death globally. Understanding the costs associated with the management of childhood pneumonia is essential for resource allocation and priority setting for child health. Methods We conducted a systematic review to identify studies reporting data on the cost of management of pneumonia in children younger than 5 years old. We collected unpublished cost data on non–severe, severe and very severe pneumonia through collaboration with an international working group. We extracted data on cost per episode, duration of hospital stay and unit cost of interventions for the management of pneumonia. The mean (95% confidence interval, CI) and median (interquartile range, IQR) treatment costs were estimated and reported where appropriate. Results We identified 24 published studies eligible for inclusion and supplemented these with data from 10 unpublished studies. The 34 studies included in the cost analysis contained data on more than 95 000 children with pneumonia from both low– and–middle income countries (LMIC) and high–income countries (HIC) covering all 6 WHO regions. The total cost (per episode) for management of severe pneumonia was US$ 4.3 (95% CI 1.5–8.7), US$ 51.7 (95% CI 17.4–91.0) and US$ 242.7 (95% CI 153.6–341.4)–559.4 (95% CI 268.9–886.3) in community, out–patient facilities and different levels of hospital in–patient settings in LMIC. Direct medical cost for severe pneumonia in hospital inpatient settings was estimated to be 26.6%–115.8% of patients’ monthly household income in LMIC. The mean direct non–medical cost and indirect cost for severe pneumonia management accounted for 0.5–31% of weekly household income. The mean length of stay (LOS) in hospital for children with severe pneumonia was 5.8 (IQR 5.3–6.4) and 7.7 (IQR 5.5–9.9) days in LMIC and HIC respectively for these children. Conclusion This is the most

  12. Severe pneumonia in the elderly: a multivariate analysis of risk factors

    PubMed Central

    Li, Wei; Ding, Cheng; Yin, Shaojun

    2015-01-01

    Pneumonia is the second leading reason for hospitalization of medicare beneficiaries. The mortality rate is high, especially in the elderly. In this study, we aimed to determine the risk factors associated with severe pneumonia in the elderly. Retrospective study was conducted and data of old patients with severe pneumonia were collected. They were divided into two groups: the experiment group (death group) and the control (living group). The general situation, underlying diseases, laboratory tests, types of etiology, imaging analysis and treatment situation of patients were analyzed and compared. Univariate analysis and logistic multivariate regression analysis were used to screen the related and independent risk factors for the diagnosis of severe pneumonia in the elderly. In univariate analysis, there were many factors had statistical significance including chronic kidney disease, electrolyte disturbance, low phosphorus and so on. Result of logistic multivariate regression analysis showed pro-BNP level and serum prealbumin were independent risk factors. In sputum culture, the relevance ratio of acinetobacter baumannii was the highest in gram negative bacteria followed by klebsiella pneumoniae. In gram positive bacteria, the relevance ratio of staphylococcus aureus was the highest. In conclusion, the analysis on risk factors for severe pneumonia has great clinical significance on improving the prognosis. PMID:26550157

  13. Severe pneumonia in the elderly: a multivariate analysis of risk factors.

    PubMed

    Li, Wei; Ding, Cheng; Yin, Shaojun

    2015-01-01

    Pneumonia is the second leading reason for hospitalization of medicare beneficiaries. The mortality rate is high, especially in the elderly. In this study, we aimed to determine the risk factors associated with severe pneumonia in the elderly. Retrospective study was conducted and data of old patients with severe pneumonia were collected. They were divided into two groups: the experiment group (death group) and the control (living group). The general situation, underlying diseases, laboratory tests, types of etiology, imaging analysis and treatment situation of patients were analyzed and compared. Univariate analysis and logistic multivariate regression analysis were used to screen the related and independent risk factors for the diagnosis of severe pneumonia in the elderly. In univariate analysis, there were many factors had statistical significance including chronic kidney disease, electrolyte disturbance, low phosphorus and so on. Result of logistic multivariate regression analysis showed pro-BNP level and serum prealbumin were independent risk factors. In sputum culture, the relevance ratio of acinetobacter baumannii was the highest in gram negative bacteria followed by klebsiella pneumoniae. In gram positive bacteria, the relevance ratio of staphylococcus aureus was the highest. In conclusion, the analysis on risk factors for severe pneumonia has great clinical significance on improving the prognosis. PMID:26550157

  14. Minocycline-induced acute eosinophilic pneumonia: A case report and review of the literature☆

    PubMed Central

    Hung, Sharon W.

    2015-01-01

    Acute eosinophilic pneumonia (AEP) can be a challenging diagnosis and is often initially misdiagnosed as one of the more common pneumonia syndromes such as acute respiratory distress syndrome. Early bronchoalveolar lavage (BAL) is critical in distinguishing the diagnosis to initiate proper management. The etiology of AEP is unknown, though many drugs have been implicated, including minocycline. Minocycline is commonly used for pneumonia, acute bronchitis, urinary tract infections, and acne and is likely the cause of AEP in our patient. There are 26 case reports of minocycline-induced AEP. In most cases, outcomes were favorable and symptoms rapidly resolved upon discontinuation of minocycline, with 11 cases employing steroids, one case twelve hours of CPAP and another 5 days of intubation. None resulted in mortality. Although it is difficult to evaluate without further studies, steroids should be recommended for minocycline-induced AEP, especially for those with severe or persistent symptoms. PMID:26236618

  15. Pneumonia

    MedlinePlus

    ... the flu Your doctor will use your medical history, a physical exam, and lab tests to diagnose pneumonia. Treatment depends on what kind you have. If bacteria are the cause, antibiotics should help. If you ...

  16. Case Report of Low Virulence Francisella tularensis Presented as Severe Bacteremic Pneumonia

    PubMed Central

    Su, Ting-Yi; Shie, Shian-Sen; Chia, Ju-Hsin; Huang, Ching-Tai

    2016-01-01

    Abstract Tularemia is a zoonotic infection seen primarily in the Northern Hemisphere. It is caused by the bacteria Francisella tularensis. Although the ulceroglandular form of the disease is the more common manifestation of infection, F tularensis is known to cause pneumonia. F tularensis has two predominant subspecies, namely subsp. tularensis (type A) and subsp. holarctica (type B). Type B tularemia is considered to be much less virulent than type A and barely caused lethal disease and pneumonia. We reported a case with a 68-year-old man immune-compromised patient diagnosed with bacteremic pneumonia engendered by type B tularemia with initial presentation of high fever, pneumonia with pleural effusion; the diagnosis was performed using 16S rRNA gene sequence analysis. The patient's fever, pneumonia, and pleural effusion were resolved with appropriate antibiotics for tularemia. This case involving severe bacteremic pneumonia in an immune-compromised patient is rare. This case suggests that low virulence F tularensis should be included in the differential diagnoses of bacteremic pneumonia for endemic tularemia. PMID:27175638

  17. High prevalence of Pneumocystis jirovecii pneumonia among Mozambican children <5 years of age admitted to hospital with clinical severe pneumonia.

    PubMed

    Lanaspa, M; O'Callaghan-Gordo, C; Machevo, S; Madrid, L; Nhampossa, T; Acácio, S; de la Horra, C; Friaza, V; Campano, E; Alonso, P L; Calderón, E J; Roca, A; Bassat, Q

    2015-11-01

    We aimed to describe Pneumocystis jirovecii pneumonia (PCP) prevalence and features in children from sub-Saharan Africa and to investigate PCP-associated risk factors. During 2006-2007 we used molecular methods to test children younger than 5 years old admitted with severe pneumonia to a hospital in southern Mozambique for Pneumocystis infection. We recruited 834 children. PCP prevalence was 6.8% and HIV prevalence was 25.7%. The in-hospital and delayed mortality were significantly higher among children with PCP (20.8% vs. 10.2%, p 0.021, and 11.5% vs. 3.6%, p 0.044, respectively). Clinical features were mostly overlapping between the two groups. Independent risk factors for PCP were age less than a year (odds ratio (OR) 6.34, 95% confidence interval (CI) 1.86-21.65), HIV infection (OR 2.99, 95% CI 1.16-7.70), grunting (OR 2.64, 95% CI 1.04-6.73) and digital clubbing (OR 10.75, 95% CI 1.21-95.56). PCP is a common and life-threatening cause of severe pneumonia in Mozambican children. Mother-to-child HIV transmission prevention should be strengthened. Better diagnostic tools are needed. PMID:26231980

  18. Validity of Antibodies in Lymphocyte Supernatant in Diagnosing Tuberculosis in Severely Malnourished Children Presenting with Pneumonia

    PubMed Central

    Chisti, Mohammod Jobayer; Salam, Mohammed Abdus; Raqib, Rubhana; Banu, Sayera; Shahid, Abu ASMSB; Shahunja, KM; Sharmin, Lazina; Ashraf, Hasan; Faruque, Abu Syed Golam; Bardhan, Pradip Kumar; Ahmed, Tahmeed

    2015-01-01

    Background The diagnosis of tuberculosis (TB) in young children can be challenging, especially in severely malnourished children. There is a critical need for improved diagnostics for children. Thus, we sought to evaluate the performance of a technique that measures antibodies in lymphocyte supernatant (ALS) for the diagnosis of TB in severely malnourished children presenting with suspected pneumonia. Methods Children less than 5 years with severe acute malnutrition and radiological features of pneumonia admitted to the Dhaka Hospital of International Centre for Diarrhoeal Disease Research, Bangladesh, were enrolled consecutively following informed written consent. In addition to clinical and radiological assessment, samples taken for TB diagnosis included gastric lavage fluid and induced sputum for microbiological confirmation. ALS was measured from venous blood, and results were evaluated in children classified as “confirmed”, “non-confirmed TB” or “not TB”. Results Among 224 children who had ALS analysis, 12 (5.4%) children had microbiologically “confirmed TB”, a further 41 (18%) had clinically diagnosed “non-confirmed TB” and the remaining 168 (75%) were considered not to have TB. ALS was positive in 89 (40%) and negative in 85 (39%) of children, with a large number (47 or 21%) reported as “borderline”. These proportions were similar between the three diagnostic groups. The sensitivity and specificity of ALS when comparing “Confirmed TB” to “Not TB” was only 67% (95% CI: 31–91%) and 51% (95% CI: 42–60%), respectively. Conclusions and Significance Our data suggest that ALS is not sufficiently accurate to improve the diagnosis of TB in children with severe malnutrition. PMID:26020966

  19. Influence of porcine circovirus type 2 vaccination on the probability and severity of pneumonia detected postmortem

    PubMed Central

    Raith, J.; Kuchling, S.; Schleicher, C.; Schobesberger, H.; Köfer, J.

    2015-01-01

    To evaluate the influence of porcine circovirus type 2 vaccination (PCV-2) on the probability and severity of pneumonia, postmortem findings of 247,505 pigs slaughtered between 2008 and 2011 were analysed by applying a cumulative link mixed model. Three major effects could be observed: (1) PCV-2 vaccination significantly (P<0.01) reduced the odds (coefficient: −0.05) of postmortem findings of mild, moderate and severe pneumonia for vaccinated pigs. (2) Pigs from fattening farms were less likely (coefficient: −0.44; P<0.05) to exhibit signs of pneumonia at slaughter than pigs from farrow-to-finish farms. (3) When vaccinated, the odds of detecting postmortem signs showed an even more pronounced reduction (coefficient: −0.19; P<0.001) for pigs from fattening farms. Combining PCV-2 vaccination, farm type and interaction effects between these two factors, a pig vaccinated against PCV-2 from a fattening farm had only half the chance (OR 0.51) of pneumonia being detected at postmortem than a non-vaccinated pig from a farrow-to-finish farm. The study demonstrates the benefit of a vaccination programme against PCV-2 as an important tool to reduce the risk of postmortem pneumonia findings and the severity of pneumonia in pigs at slaughter. PMID:25413158

  20. Epidemiology and outcome of severe pneumococcal pneumonia admitted to intensive care unit: a multicenter study

    PubMed Central

    2012-01-01

    Introduction Community-acquired pneumonia (CAP) account for a high proportion of ICU admissions, with Streptococcus pneumoniae being the main pathogen responsible for these infections. However, little is known on the clinical features and outcomes of ICU patients with pneumococcal pneumonia. The aims of this study were to provide epidemiological data and to determine risk factors of mortality in patients admitted to ICU for severe S. pneumoniae CAP. Methods We performed a retrospective review of two prospectively-acquired multicentre ICU databases (2001-2008). Patients admitted for management of severe pneumococcal CAP were enrolled if they met the 2001 American Thoracic Society criteria for severe pneumonia, had life-threatening organ failure and had a positive microbiological sample for S. pneumoniae. Patients with bronchitis, aspiration pneumonia or with non-pulmonary pneumococcal infections were excluded. Results Two hundred and twenty two patients were included, with a median SAPS II score reaching 47 [36-64]. Acute respiratory failure (n = 154) and septic shock (n = 54) were their most frequent causes of ICU admission. Septic shock occurred in 170 patients (77%) and mechanical ventilation was required in 186 patients (84%); renal replacement therapy was initiated in 70 patients (32%). Bacteraemia was diagnosed in 101 patients. The prevalence of S. pneumoniae strains with decreased susceptibility to penicillin was 39.7%. Although antibiotherapy was adequate in 92.3% of cases, hospital mortality reached 28.8%. In multivariate analysis, independent risk factors for mortality were age (OR 1.05 (95% CI: 1.02-1.08)), male sex (OR 2.83 (95% CI: 1.16-6.91)) and renal replacement therapy (OR 3.78 (95% CI: 1.71-8.36)). Co-morbidities, macrolide administration, concomitant bacteremia or penicillin susceptibility did not influence outcome. Conclusions In ICU, mortality of pneumococcal CAP remains high despite adequate antimicrobial treatment. Baseline demographic data

  1. Pneumonia-induced sepsis in mice: temporal study of inflammatory and cardiovascular parameters

    PubMed Central

    Sordi, Regina; Menezes-de-Lima, Octávio; Della-Justina, Ana M; Rezende, Edir; Assreuy, Jamil

    2013-01-01

    The aim of the present work is to provide a better comprehension of the pneumonia-induced sepsis model through temporal evaluation of several parameters, and thus identify the main factors that determine mortality in this model. Klebsiella pneumoniae was inoculated intratracheally in anesthetized Swiss male mice. Inflammatory and cardiovascular parameters were evaluated 6, 24 and 48 h after the insult. The results show that severity of infection and the mortality correlated with the amount of bacteria. Six, 24 and 48 h after inoculation, animals presented pathological changes in lungs, increase in cell number in the bronchoalveolar lavage, leukopenia, increase in TNF-α and IL-1β levels, hypotension and hyporesponsiveness to vasoconstrictors, the two latter characteristics of severe sepsis and septic shock. Significant numbers of bacteria in spleen and heart homogenates indicated infection spreading. Interestingly, NOS-2 expression appeared late after bacteria inoculation, whereas levels of NOS-1 and NOS-3 were unchanged. The high NOS-2 expression coincided with an exacerbated NO production in the infection focus and in plasma, as judging by nitrate + nitrite levels. This study shows that K. pneumoniae inoculation induces a systemic inflammatory response and cardiovascular alterations, which endures at least until 48 h. K. pneumoniae-induced lung infection is a clinically relevant animal model of sepsis and a better understanding of this model may help to increase the knowledge about sepsis pathophysiology. PMID:23441627

  2. Outcomes of Early Administration of Cidofovir in Non-Immunocompromised Patients with Severe Adenovirus Pneumonia

    PubMed Central

    Kim, Se Jin; Kim, Kang; Park, Sung Bum; Hong, Duck Jin; Jhun, Byung Woo

    2015-01-01

    The benefits of treatment with antiviral therapy for severe adenovirus (AdV) pneumonia are not well established. We described the clinical characteristics and treatment outcomes of early cidofovir treatment of severe AdV pneumonia in non-immunocompromised patients. We retrospectively reviewed the medical records of all patients diagnosed with severe AdV pneumonia between 2012 and 2014. A total of seven non-immunocompromised patients with severe AdV pneumonia were identified, and all isolates typed (n = 6) were human AdV-B55. All patients had progressive respiratory failure with lobar consolidation with or without patchy ground glass opacity. Three patients required vasopressors and mechanical ventilation. All patients had abnormal laboratory findings including: leukopenia, thrombocytopenia, or elevated liver enzymes. After admission, all patients received antiviral therapy with cidofovir, and the median time from admission to cidofovir administration was 48 h and median the time from onset of symptoms to cidofovir administration was 7.1 days. After cidofovir administration, complete symptomatic improvement occurred after a median of 12 days and radiographic resolution occurred after a median of 21 days. Consequently, all patients completely improved without complications. Our data suggest that early administration of cidofovir in the course of treatment for respiratory failure as a result of AdV pneumonia in non-immunocompromised patients could be a treatment strategy worth considering, especially in cases of HAdV-55 infection. PMID:25875735

  3. Terlipressin Induced Severe Hyponatremia.

    PubMed

    Šíma, Martin; Pokorný, Miroslav; Paďour, František; Slanař, Ondřej

    2016-01-01

    Terlipressin is a vasopressin analogue used for its vasoconstrictor effect in the treatment of variceal bleeding. Despite its good safety profile compared to vasopressin, some adverse reactions may occur during its use - e.g. hyponatremia. We describe a case of a cirrhotic patient with active variceal bleeding treated during two separate hospitalizations with terlipressin. In both drug treatment periods, severe laboratory hyponatremia developed. After terlipressin discontinuation, mineral disbalance corrected rapidly. Positive dechallenge and rechallenge corresponding to the drug administration schedule confirms the causality between terlipressin administration and hyponatremia. Hyponatremia was preceded with substantial fluid retention in both episodes. In this case report we want to highlight the need for fluid balance monitoring immediately after first terlipressin dose, which may individually predict the patient risk for the development of hyponatremia as other risk factors have rather limited predictive value in real clinical settings. PMID:26995205

  4. Mortality of Community-Acquired Pneumonia in Korea: Assessed with the Pneumonia Severity Index and the CURB-65 Score

    PubMed Central

    Kim, Hye In; Chang, Hyun Ha; Cha, Seung Ick; Lee, Jae Hee; Ki, Hyun Kyun; Cheong, Hae Suk; Yoo, Kwang Ha; Ryu, Seong Yeol; Kwon, Ki Tae; Lee, Byung Kee; Choo, Eun Ju; Kim, Do Jin; Kang, Cheol-In; Chung, Doo Ryeon; Peck, Kyong Ran; Song, Jae Hoon; Suh, Gee Young; Shim, Tae Sun; Kim, Young Keun; Kim, Hyo Youl; Moon, Chi Sook; Lee, Hyun Kyung; Park, Seong Yeon; Oh, Jin Young; Jung, Sook In; Park, Kyung Hwa; Yun, Na Ra; Yoon, Sung Ho; Sohn, Kyung Mok; Kim, Yeon-Sook; Jung, Ki Suck

    2013-01-01

    The pneumonia severity index (PSI) and CURB-65 are widely used tools for the prediction of community-acquired pneumonia (CAP). This study was conducted to evaluate validation of severity scoring system including the PSI and CURB-65 scores of Korean CAP patients. In the prospective CAP cohort (participated in by 14 hospitals in Korea from January 2009 to September 2011), 883 patients aged over 18 yr were studied. The 30-day mortalities of all patients were calculated with their PSI index classes and CURB scores. The overall mortality rate was 4.5% (40/883). The mortality rates per CURB-65 score were as follows: score 0, 2.3% (6/260); score 1, 4.0% (12/300); score 2, 6.0% (13/216); score 3, 5.7% (5/88); score 4, 23.5% (4/17); and score 5, 0% (0/2). Mortality rate with PSI risk class were as follows: I, 2.3% (4/174); II, 2.7% (5/182); III, 2.3% (5/213); IV, 4.5% (11/245); and V, 21.7% (15/69). The subgroup mortality rate of Korean CAP patients varies based on the severity scores and CURB-65 is more valid for the lower scores, and PSI, for the higher scores. Thus, these variations must be considered when using PSI and CURB-65 for CAP in Korean patients. PMID:24015030

  5. Streptoccocus pyogenes: a forgotten cause of severe community-acquired pneumonia.

    PubMed

    Birch, C; Gowardman, J

    2000-02-01

    We report a case of severe community-acquired pneumonia caused by Streptococcus pyogenes (Lancefield Group A streptoccocus) that was complicated by a streptococcal toxic shock syndrome. Although this micro-organism is an uncommon cause of community-acquired pneumonia, previously well individuals may be infected and the clinical course may be fulminant. A household contact was the likely point of infection. Invasive group A streptococcal disease continues to remain an important cause of morbidity and mortality in the community and therefore will continue to be encountered by intensive care physicians. Treatment of Group A streptococcal infection remains penicillin; however, clindamycin should be added in severe infection. PMID:10701045

  6. Respiratory viruses from hospitalized children with severe pneumonia in the Philippines

    PubMed Central

    2012-01-01

    Background Pneumonia remains a leading cause of child death in developing countries. The viruses in severe pneumonia remain poorly defined. Methods The study was conducted at the Eastern Visayas Regional Medical Center in Tacloban City, Philippines from May 2008 to May 2009. Patients aged 8 days to 13 years old who were admitted to the Department of Pediatrics with severe pneumonia were enrolled for the study. Upon admission, polymerase chain reaction was performed using nasopharyngeal swabs and blood cultures to detect respiratory viruses and bacteria, respectively. Result Among the 819 patients enrolled, at least one virus was detected in 501 cases (61.2%). In addition, 423 cases were positive for a single virus while bacteria were detected in the blood culture sample of 31 cases. The most commonly detected viruses were human rhinoviruses (n = 189), including types A (n = 103), B (n = 17), and C (n = 69), and respiratory syncytial virus (RSV) (n = 165). Novel viruses such as human metapneumovirus, human coronavirus NL63, human bocavirus, and human polyomaviruses WU and KI were also detected. There were 70 deaths, and one or more viruses were detected in 35 (50%) of these cases. Positivity only for influenza A virus (OR = 4.3, 95% CI = 1.3-14.6) was significantly associated with fatal outcome. From the blood culture, Burkholderia cepacia group (n = 9), Streptococcus pneumoniae (n = 4), Staphylococcus aureus (n = 4), Haemophilus influenzae (n = 1), and Salmonella C1 (n = 1) were also isolated. Conclusion Viruses were commonly detected in children with severe pneumonia in the Philippines. Hence, viral etiologies should be considered while developing better effective strategies to reduce child pneumonia-related deaths in developing countries. PMID:23092190

  7. Acute fibrinous and organising pneumonia: a rare histopathological variant of chemotherapy-induced lung injury.

    PubMed

    Gupta, Arjun; Sen, Shiraj; Naina, Harris

    2016-01-01

    Bleomycin-induced lung injury is the most common chemotherapy-associated lung disease, and is linked with several histopathological patterns. Acute fibrinous and organising pneumonia (AFOP) is a relatively new and rare histological pattern of diffuse lung injury. We report the first known case of bleomycin-induced AFOP. A 36-year-old man with metastatic testicular cancer received three cycles of bleomycin, etoposide and cisplatin, before being transitioned to paclitaxel, ifosfamide and cisplatin. He subsequently presented with exertional dyspnoea, cough and pleuritic chest pain. CT of the chest demonstrated bilateral ground glass opacities with peribronchovascular distribution and pulmonary function tests demonstrated a restrictive pattern of lung disease with impaired diffusion. Transbronchial biopsy revealed intra-alveolar fibrin deposits with organising pneumonia, consisting of intraluminal loose connective tissue consistent with AFOP. The patient received high-dose corticosteroids with symptomatic and radiographic improvement. AFOP should be recognised as a histopathological variant of bleomycin-induced lung injury. PMID:27053543

  8. Streptococcus pneumoniae capsule determines disease severity in experimental pneumococcal meningitis.

    PubMed

    Hathaway, Lucy J; Grandgirard, Denis; Valente, Luca G; Täuber, Martin G; Leib, Stephen L

    2016-03-01

    Streptococcus pneumoniaebacteria can be characterized into over 90 serotypes according to the composition of their polysaccharide capsules. Some serotypes are common in nasopharyngeal carriage whereas others are associated with invasive disease, but when carriage serotypes do invade disease is often particularly severe. It is unknown whether disease severity is due directly to the capsule type or to other virulence factors. Here, we used a clinical pneumococcal isolate and its capsule-switch mutants to determine the effect of capsule, in isolation from the genetic background, on severity of meningitis in an infant rat model. We found that possession of a capsule was essential for causing meningitis. Serotype 6B caused significantly more mortality than 7F and this correlated with increased capsule thickness in the cerebrospinal fluid (CSF), a stronger inflammatory cytokine response in the CSF and ultimately more cortical brain damage. We conclude that capsule type has a direct effect on meningitis severity. This is an important consideration in the current era of vaccination targeting a subset of capsule types that causes serotype replacement. PMID:27009189

  9. Loss of CARD9-mediated innate activation attenuates severe influenza pneumonia without compromising host viral immunity.

    PubMed

    Uematsu, Takayuki; Iizasa, Ei'ichi; Kobayashi, Noritada; Yoshida, Hiroki; Hara, Hiromitsu

    2015-01-01

    Influenza virus (IFV) infection is a common cause of severe viral pneumonia associated with acute respiratory distress syndrome (ARDS), which is difficult to control with general immunosuppressive therapy including corticosteroids due to the unfavorable effect on viral replication. Studies have suggested that the excessive activation of the innate immunity by IFV is responsible for severe pathologies. In this study, we focused on CARD9, a signaling adaptor known to regulate innate immune activation through multiple innate sensor proteins, and investigated its role in anti-IFV defense and lung pathogenesis in a mouse model recapitulating severe influenza pneumonia with ARDS. We found that influenza pneumonia was dramatically attenuated in Card9-deficient mice, which showed improved mortality with reduced inflammatory cytokines and chemokines in the infected lungs. However, viral clearance, type-I interferon production, and the development of anti-viral B and T cell immunity were not compromised by CARD9 deficiency. Syk or CARD9-deficient DCs but not macrophages showed impaired cytokine but not type-I interferon production in response to IFV in vitro, indicating a possible role for the Syk-CARD9 pathway in DCs in excessive inflammation of IFV-infected lungs. Therefore, inhibition of this pathway is an ideal therapeutic target for severe influenza pneumonia without affecting viral clearance. PMID:26627732

  10. Loss of CARD9-mediated innate activation attenuates severe influenza pneumonia without compromising host viral immunity

    PubMed Central

    Uematsu, Takayuki; Iizasa, Ei’ichi; Kobayashi, Noritada; Yoshida, Hiroki; Hara, Hiromitsu

    2015-01-01

    Influenza virus (IFV) infection is a common cause of severe viral pneumonia associated with acute respiratory distress syndrome (ARDS), which is difficult to control with general immunosuppressive therapy including corticosteroids due to the unfavorable effect on viral replication. Studies have suggested that the excessive activation of the innate immunity by IFV is responsible for severe pathologies. In this study, we focused on CARD9, a signaling adaptor known to regulate innate immune activation through multiple innate sensor proteins, and investigated its role in anti-IFV defense and lung pathogenesis in a mouse model recapitulating severe influenza pneumonia with ARDS. We found that influenza pneumonia was dramatically attenuated in Card9-deficient mice, which showed improved mortality with reduced inflammatory cytokines and chemokines in the infected lungs. However, viral clearance, type-I interferon production, and the development of anti-viral B and T cell immunity were not compromised by CARD9 deficiency. Syk or CARD9-deficient DCs but not macrophages showed impaired cytokine but not type-I interferon production in response to IFV in vitro, indicating a possible role for the Syk-CARD9 pathway in DCs in excessive inflammation of IFV-infected lungs. Therefore, inhibition of this pathway is an ideal therapeutic target for severe influenza pneumonia without affecting viral clearance. PMID:26627732

  11. Lack of BCG vaccination and other risk factors for bacteraemia in severely malnourished children with pneumonia.

    PubMed

    Chisti, M J; Salam, M A; Ahmed, T; Shahid, A S M S B; Shahunja, K M; Faruque, A S G; Bardhan, P K; Hossain, M I; Islam, M M; Das, S K; Huq, S; Shahrin, L; Huq, E; Chowdhury, F; Ashraf, H

    2015-03-01

    We sought to examine the factors associated with bacteraemia and their outcome in children with pneumonia and severe acute malnutrition (SAM). All SAM children of either sex, aged 0-59 months, admitted to the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh with radiologically confirmed pneumonia from April 2011 to July 2012 were enrolled (n = 405). Comparison was made between pneumonic SAM children with (cases = 18), and without (controls = 387) bacteraemia. The death rate was significantly higher in cases than controls (28% vs. 8%, P < 0·01). In logistic regression analysis, after adjusting for potential confounders, the SAM children with pneumonia and bacteraemia more often had a history of lack of bacillus Calmette-Guérin (BCG) vaccination (odds ratio 7·39, 95% confidence interval 1·67-32·73, P < 0·01). The results indicate the importance of continuation of BCG vaccination which may provide benefit beyond its primary purpose. PMID:24892696

  12. Severe adenovirus community-acquired pneumonia in immunocompetent adults: chest radiographic and CT findings

    PubMed Central

    Tan, Dingyu; Fu, Yangyang; Wang, Zhiwei; Cao, Jian; Walline, Joseph; Zhu, Huadong

    2016-01-01

    Background Severe adenovirus pneumonia and its associated imaging features are well-described in immunocompromised patients but are rare and poorly understood in immunocompetent adults. We sought to describe the radiographic and CT findings of severe adenovirus community-acquired pneumonia (CAP) in eight immunocompetent adults. Methods We reviewed systematically chest imaging manifestations of laboratory-confirmed severe adenovirus pneumonia in eight immunocompetent adults from April 2012 to April 2014. Results All patients showed abnormal results on initial chest radiograph and CT, with the exception of one normal initial chest radiograph. The abnormalities of the initial chest radiographs were unilateral (n=4) or bilateral (n=3), including consolidation (n=4), dense patchy opacity (n=3), ground glass opacity (GGO) (n=1), and pleural effusion (n=1). The initial CT findings consisted of unilateral (n=5) and bilateral (n=3) abnormalities, including consolidation (n=8), GGO (n=2), pleural effusion (n=3) and small nodules (n=1). Focal consolidation was the predominant finding in six patients whose initial CT scans were examined within one week after illness onset. Follow-up radiologic findings showed rapid development of bilateral consolidation within ten days after illness onset, usually accompanied by adjacent ground-glass opacity and pleural effusion. The parenchymal abnormalities began to absorb around two weeks after illness onset, with no appearances of fibrosis. Conclusions Severe adenovirus CAP in immunocompetent adults mainly appears as focal consolidation followed by rapid progression to bilateral consolidation, usually accompanied by adjacent GGO and pleural effusion, which may resemble bacterial pneumonia. Adenovirus should be considered in severe pneumonia cases with negative cultures and failure to respond to antibiotics. PMID:27162658

  13. Zinc supplementation for the treatment of severe pneumonia in hospitalized children: A randomized controlled trial

    PubMed Central

    Shehzad, Nazia; Anwar, Muhammd Irfan; Muqaddas, Tahira

    2015-01-01

    The objectives of this randomized controlled trial (RCT) were to compare the mean duration of hospital stay and mean time to relieve severe pneumonia signs and symptoms with or without zinc supplementation in hospitalized young children. This RCT was conducted from Oct 2011 to Mar 2012. in the paediatric department, PGM/Lahore General Hospital. Three hundred children (150 in each group) were randomly allocated to two groups: group A received zinc syrup (20 mg/day q 12 hourly) till discharge and group B received placebo syrup. This in addition to the antibiotic treatment. Data for severe pneumonia signs and symptoms i.e. oxygen saturation, respiratory rate, temperature and chest indrawing were recorded. The mean age of participants was 16.65+4.23 months in Group-A and15.96+5.11 months in Group-B. We found that the mean duration to relieve severe pneumonia signs and symptoms was 44.62+2.56 hours in Group-A and 48.73+3.124 hours in Group-B (p-value 0.023).Duration of hospital stay was 128.31+3.71 hours in Group-A and 137.67+2.56 in Group-B (p-value 0.001). We conclude that zinc supplementation for the treatment of children with pneumonia is an effective therapy along with standard treatment.

  14. Clinical Outcomes and Microbiological Characteristics of Severe Pneumonia in Cancer Patients: A Prospective Cohort Study

    PubMed Central

    Rabello, Ligia S. C. F.; Silva, Jose R. L.; Azevedo, Luciano C. P.; Souza, Ivens; Torres, Viviane B. L.; Rosolem, Maíra M.; Lisboa, Thiago; Soares, Marcio; Salluh, Jorge I. F.

    2015-01-01

    Introduction Pneumonia is the most frequent type of infection in cancer patients and a frequent cause of ICU admission. The primary aims of this study were to describe the clinical and microbiological characteristics and outcomes in critically ill cancer patients with severe pneumonia. Methods Prospective cohort study in 325 adult cancer patients admitted to three ICUs with severe pneumonia not acquired in the hospital setting. Demographic, clinical and microbiological data were collected. Results There were 229 (71%) patients with solid tumors and 96 (29%) patients with hematological malignancies. 75% of all patients were in septic shock and 81% needed invasive mechanical ventilation. ICU and hospital mortality rates were 45.8% and 64.9%. Microbiological confirmation was present in 169 (52%) with a predominance of Gram negative bacteria [99 (58.6%)]. The most frequent pathogens were methicillin-sensitive S. aureus [42 (24.9%)], P. aeruginosa [41(24.3%)] and S. pneumonia [21 (12.4%)]. A relatively low incidence of MR [23 (13.6%)] was observed. Adequate antibiotics were prescribed for most patients [136 (80.5%)]. In multivariate analysis, septic shock at ICU admission [OR 5.52 (1.92–15.84)], the use of invasive MV [OR 12.74 (3.60–45.07)] and poor Performance Status [OR 3.00 (1.07–8.42)] were associated with increased hospital mortality. Conclusions Severe pneumonia is associated with high mortality rates in cancer patients. A relatively low rate of MR pathogens is observed and severity of illness and organ dysfunction seems to be the best predictors of outcome in this population. PMID:25803690

  15. Predictors of Severe Sepsis among Patients Hospitalized for Community-Acquired Pneumonia

    PubMed Central

    Torres, Antoni; Reyes, Soledad; Méndez, Raúl; Zalacaín, Rafael; Capelastegui, Alberto; Rajas, Olga; Borderías, Luis; Martin-Villasclaras, Juan; Bello, Salvador; Alfageme, Inmaculada; Rodríguez de Castro, Felipe; Rello, Jordi; Molinos, Luis; Ruiz-Manzano, Juan

    2016-01-01

    Background Severe sepsis, may be present on hospital arrival in approximately one-third of patients with community-acquired pneumonia (CAP). Objective To determine the host characteristics and micro-organisms associated with severe sepsis in patients hospitalized with CAP. Results We performed a prospective multicenter cohort study in 13 Spanish hospital, on 4070 hospitalized CAP patients, 1529 of whom (37.6%) presented with severe sepsis. Severe sepsis CAP was independently associated with older age (>65 years), alcohol abuse (OR, 1.31; 95% CI, 1.07–1.61), chronic obstructive pulmonary disease (COPD) (OR, 1.75; 95% CI, 1.50–2.04) and renal disease (OR, 1.57; 95% CI, 1.21–2.03), whereas prior antibiotic treatment was a protective factor (OR, 0.62; 95% CI, 0.52–0.73). Bacteremia (OR, 1.37; 95% CI, 1.05–1.79), S pneumoniae (OR, 1.59; 95% CI, 1.31–1.95) and mixed microbial etiology (OR, 1.65; 95% CI, 1.10–2.49) were associated with severe sepsis CAP. Conclusions CAP patients with COPD, renal disease and alcohol abuse, as well as those with CAP due to S pneumonia or mixed micro-organisms are more likely to present to the hospital with severe sepsis. PMID:26727202

  16. Post-Discharge Mortality in Children with Severe Malnutrition and Pneumonia in Bangladesh

    PubMed Central

    Chisti, Mohammod Jobayer; Graham, Stephen M.; Duke, Trevor; Ahmed, Tahmeed; Faruque, Abu Syed Golam; Ashraf, Hasan; Bardhan, Pradip Kumar; Shahid, Abu S. M. S. B.; Shahunja, K. M.; Salam, Mohammed Abdus

    2014-01-01

    Background Post-discharge mortality among children with severe illness in resource-limited settings is under-recognized and there are limited data. We evaluated post-discharge mortality in a recently reported cohort of children with severe malnutrition and pneumonia, and identified characteristics associated with an increased risk of death. Methods Young children (<5 years of age) with severe malnutrition (WHO criteria) and radiographic pneumonia on admission to Dhaka Hospital of icddr,b over a 15-month period were managed according to standard protocols. Those discharged were followed-up and survival status at 12 weeks post-discharge was determined. Verbal autopsy was requested from families of those that died. Results Of 405 children hospitalized with severe malnutrition and pneumonia, 369 (median age, 10 months) were discharged alive with a follow-up plan. Of these, 32 (8.7%) died in the community within 3 months of discharge: median 22 (IQR 9–35) days from discharge to death. Most deaths were reportedly associated with acute onset of new respiratory or gastrointestinal symptoms. Those that died following discharge were significantly younger (median 6 [IQR 3,12] months) and more severely malnourished, on admission and on discharge, than those that survived. Bivariate analysis found that severe wasting on admission (OR 3.64, 95% CI 1.66–7.97) and age <12 months (OR 2.54, 95% CI 1.1–8.8) were significantly associated with post-discharge death. Of those that died in the community, none had attended a scheduled follow-up and care-seeking from a traditional healer was more common (p<0.001) compared to those who survived. Conclusion and Significance Post-discharge mortality was common in Bangladeshi children following inpatient care for severe malnutrition and pneumonia. The underlying contributing factors require a better understanding to inform the potential of interventions that could improve survival. PMID:25225798

  17. Alveolar-arterial oxygen gradient, pneumonia severity index and outcomes in patients hospitalized with community acquired pneumonia.

    PubMed

    Moammar, Mahmoud Q; Azam, Hamad M; Blamoun, Adel I; Rashid, Ashraf O; Ismail, Medhat; Khan, M Anees; DeBari, Vincent A

    2008-09-01

    The alveolar-arterial oxygen gradient (DeltaA-a) provides a useful assessment of ventilation/perfusion (V/Q) abnormalities. The objectives of the present study were to: (i) examine the correlation between the DeltaA-a and the pneumonia severity index (PSI); and (ii) determine whether these measures were comparable in predicting clinical outcomes. The present study was conducted at a 750-bed teaching hospital. It examined a retrospective cohort of 255 patients with community acquired pneumonia (CAP) over a 2 year period. Association between the CAP and DeltaA-a was investigated by regression models and correlation, as well as two logistic models for subjects bifurcated by low-risk/moderate-to-high risk. The decision levels (DL) for both PSI and DeltaA-a were then compared as predictors of both length of stay (LOS) and survival. The correlation between PSI and DeltaA-a was strong (rho = 0.76; P < 0.0001) and was best modelled by a curvilinear relationship. Both logistic models indicated a strong association (P < 0.001) between DeltaA-a and PSI and yielded an optimal DL for the DeltaA-a of < 89 mmHg. Inter-test agreement of DeltaA-a with PSI was 76.9% (kappa = 0.60; 95% confidence interval 0.47-0.72; P < 0.0001). At < 89 mmHg, the odds ratios for LOS were similar to those at PSI = 90 in predicting LOS in the range 3-7 days, inclusive. There was no significant difference in the ability of DeltaA-a and PSI to predict survival for either the low- or high-risk group (P = 0.363 and P = 0.951, respectively). The DeltaA-a correlates well with PSI and performs comparably in predicting two major outcomes in subjects hospitalized with CAP. PMID:18518885

  18. Assessment of Treatment of Community Acquired Severe Pneumonia by Two Different Antibiotics

    PubMed Central

    Bilal, Jalal Ali; Eldouch, Widad; Abdin, Ali

    2016-01-01

    Introduction Pneumonia is common presentation in the emergency room and is still a cause of morbidity and mortality. The rationale of this study was to test the trend of paediatricians to achieve rapid response facing severe pneumonia, the lack of agreed on plan for the management of community acquired pneumonia (CAP) and the few experiences regarding injectable form of β-lactam antimicrobial. Materials and Methods This is a prospective case control study, purposive randomized sampling, three patients were excluded since their information was incomplete, 132 patients were randomly divided into groups, one group named control group (penicillin according to the guidelines of WHO 2013), 33 patients; second group treated by β-lactam inhibitors (Augmentin IV) 50 patients; and third group treated by 3rd generation cephalosporin (ceftriaxone) 49 patients. The study was conducted at the main tertiary care and paediatrics teaching hospital in Khartoum capital of Sudan. The study was completed within the duration from 2010 to 2011. Results Both group showed more or less similar results regarding response, as well as the failure rate however, the Augmentin and ceftriaxone groups showed a little bit better survival than the control group. Conclusion Antibiotics decrease the mortality rate among the pneumonia patients provided that it is given early in the disease. PMID:27437318

  19. Severity assessment tools in ICU patients with 2009 influenza A (H1N1) pneumonia.

    PubMed

    Pereira, J M; Moreno, R P; Matos, R; Rhodes, A; Martin-Loeches, I; Cecconi, M; Lisboa, T; Rello, J

    2012-10-01

    The aim of this study was to determine if severity assessment tools (general severity of illness and community-acquired pneumonia specific scores) can be used to guide decisions for patients admitted to the intensive care unit (ICU) due to pandemic influenza A pneumonia. A prospective, observational, multicentre study included 265 patients with a mean age of 42 (±16.1) years and an ICU mortality of 31.7%. On admission to the ICU, the mean pneumonia severity index (PSI) score was 103.2 ± 43.2 points, the CURB-65 score was 1.7 ± 1.1 points and the PIRO-CAP score was 3.2 ± 1.5 points. None of the scores had a good predictive ability: area under the ROC for PSI, 0.72 (95% CI, 0.65-0.78); CURB-65, 0.67 (95% CI, 0.59-0.74); and PIRO-CAP, 0.64 (95% CI, 0.56-0.71). The PSI score (OR, 1.022 (1.009-1.034), p 0.001) was independently associated with ICU mortality; however, none of the three scores, when used at ICU admission, were able to reliably detect a low-risk group of patients. Low risk for mortality was identified in 27.5% of patients using PIRO-CAP, but above 40% when using PSI (I-III) or CURB65 (<2). Observed mortality was 13.7%, 13.5% and 19.4%, respectively. Pneumonia-specific scores undervalued severity and should not be used as instruments to guide decisions in the ICU. PMID:22264290

  20. MicroRNAs Constitute a Negative Feedback Loop in Streptococcus pneumoniae-Induced Macrophage Activation.

    PubMed

    Griss, Kathrin; Bertrams, Wilhelm; Sittka-Stark, Alexandra; Seidel, Kerstin; Stielow, Christina; Hippenstiel, Stefan; Suttorp, Norbert; Eberhardt, Martin; Wilhelm, Jochen; Vera, Julio; Schmeck, Bernd

    2016-07-15

    Streptococcus pneumoniae causes high mortality as a major pneumonia-inducing pathogen. In pneumonia, control of innate immunity is necessary to prevent organ damage. We assessed the role of microRNAs (miRNAs) as regulators in pneumococcal infection of human macrophages. Exposure of primary blood-derived human macrophages with pneumococci resulted in transcriptional changes in several gene clusters and a significant deregulation of 10 microRNAs. Computational network analysis retrieved miRNA-146a as one putatively important regulator of pneumococci-induced host cell activation. Its induction depended on bacterial structural integrity and was completely inhibited by blocking Toll-like receptor 2 (TLR-2) or depleting its mediator MyD88. Furthermore, induction of miRNA-146a release did not require the autocrine feedback of interleukin 1β and tumor necrosis factor α released from infected macrophages, and it repressed the TLR-2 downstream mediators IRAK-1 and TRAF-6, as well as the inflammatory factors cyclooxygenase 2 and interleukin 1β. In summary, pneumococci recognition induces a negative feedback loop, preventing excessive inflammation via miR-146a and potentially other miRNAs. PMID:26984146

  1. Treatment Failure and Mortality amongst Children with Severe Acute Malnutrition Presenting with Cough or Respiratory Difficulty and Radiological Pneumonia

    PubMed Central

    Chisti, Mohammod Jobayer; Salam, Mohammed Abdus; Bardhan, Pradip Kumar; Faruque, Abu S. G.; Shahid, Abu S. M. S. B.; Shahunja, K. M.; Das, Sumon Kumar; Hossain, Md Iqbal; Ahmed, Tahmeed

    2015-01-01

    Background Appropriate intervention is critical in reducing deaths among under-five, severe acutely malnourished (SAM) children with danger signs of severe pneumonia; however, there is paucity of data on outcome of World Health Organisation (WHO) recommended interventions of SAM children with severe pneumonia. We sought to evaluate outcome of the interventions in such children. Methods We prospectively enrolled SAM children aged 0–59 months, admitted to the Intensive Care Unit (ICU) or Acute Respiratory Infection (ARI) ward of the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), between April 2011 and June 2012 with cough or respiratory difficulty and radiological pneumonia. All the enrolled children were treated with ampicillin and gentamicin, and micronutrients as recommended by the WHO. Comparison was made among pneumonic children with (n = 111) and without WHO defined danger signs of severe pneumonia (n = 296). The outcomes of interest were treatment failure (if a child required changing of antibiotics) and deaths during hospitalization. Further comparison was also made among those who developed treatment failure and who did not and among the survivors and deaths. Results SAM children with danger signs of severe pneumonia more often experienced treatment failure (58% vs. 20%; p<0.001) and fatal outcome (21% vs. 4%; p<0.001) compared to those without danger signs. Only 6/111 (5.4%) SAM children with danger signs of severe pneumonia and 12/296 (4.0%) without danger signs had bacterial isolates from blood. In log-linear binomial regression analysis, after adjusting for potential confounders, danger signs of severe pneumonia, dehydration, hypocalcaemia, and bacteraemia were independently associated both with treatment failure and deaths in SAM children presenting with cough or respiratory difficulty and radiological pneumonia (p<0.01). Conclusion and Significance The result suggests that SAM children with cough or

  2. Effect of nitric oxide inhalation on gas exchange in acute severe pneumonia.

    PubMed

    Gómez, Federico P; Amado, Veronica M; Roca, Josep; Torres, Antoni; Nicolas, Josep M; Rodriguez-Roisin, Robert; Barberà, Joan A

    2013-06-15

    Inhaled nitric oxide (NO) causes selective pulmonary vasodilatation and may improve gas exchange. The study was aimed to evaluate the acute effects of inhaled NO on pulmonary gas exchange in severe unilateral pneumonia, where hypoxemia results from increased intrapulmonary shunt. We studied 8 patients without preexisting lung disease (59±18 yr; 4M/4F) with early unilateral severe pneumonia and respiratory failure. Pulmonary and systemic hemodynamics and gas exchange, including ventilation-perfusion (V;A/Q;) distributions, were measured at baseline and while breathing 5 and 40 parts per million (ppm) of NO. Inhaled NO caused a dose-dependent fall in pulmonary vascular resistance (by 12% and 21%, with 5 and 40ppm, respectively; p<0.01, each) and improvement of PaO2 (by 25% and 23%; p<0.05, each), owing to the reduction of intrapulmonary shunt (by 23% and 27%; p<0.05, each), without changes in the amount of perfusion to low V;A/Q; ratio alveolar units. Patients with greater baseline intrapulmonary shunt exhibited greater improvement in arterial oxygenation (r(2)=0.55, p<0.05). We conclude that low doses of inhaled NO improve pulmonary gas exchange in acute severe pneumonia. PMID:23537586

  3. Receptor for Advanced Glycation End Products (RAGE) Serves a Protective Role during Klebsiella pneumoniae - Induced Pneumonia.

    PubMed

    Achouiti, Ahmed; de Vos, Alex F; van 't Veer, Cornelis; Florquin, Sandrine; Tanck, Michael W; Nawroth, Peter P; Bierhaus, Angelika; van der Poll, Tom; van Zoelen, Marieke A D

    2016-01-01

    Klebsiella species is the second most commonly isolated gram-negative organism in sepsis and a frequent causative pathogen in pneumonia. The receptor for advanced glycation end products (RAGE) is expressed on different cell types and plays a key role in diverse inflammatory responses. We here aimed to investigate the role of RAGE in the host response to Klebsiella (K.) pneumoniae pneumonia and intransally inoculated rage gene deficient (RAGE-/-) and normal wild-type (Wt) mice with K. pneumoniae. Klebsiella pneumonia resulted in an increased pulmonary expression of RAGE. Furthermore, the high-affinity RAGE ligand high mobility group box-1 was upregulated during K. pneumoniae pneumonia. RAGE deficiency impaired host defense as reflected by a worsened survival, increased bacterial outgrowth and dissemination in RAGE-/- mice. RAGE-/- neutrophils showed a diminished phagocytosing capacity of live K. pneumoniae in vitro. Relative to Wt mice, RAGE-/- mice demonstrated similar lung inflammation, and slightly elevated-if any-cytokine and chemokine levels and unchanged hepatocellular injury. In addition, RAGE-/- mice displayed an unaltered response to intranasally instilled Klebsiella lipopolysaccharide (LPS) with respect to pulmonary cell recruitment and local release of cytokines and chemokines. These data suggest that (endogenous) RAGE protects against K. pneumoniae pneumonia. Also, they demonstrate that RAGE contributes to an effective antibacterial defense during K. pneumoniae pneumonia, at least partly via its participation in the phagocytic properties of professional granulocytes. Additionally, our results indicate that RAGE is not essential for the induction of a local and systemic inflammatory response to either intact Klebsiella or Klebsiella LPS. PMID:26824892

  4. Receptor for Advanced Glycation End Products (RAGE) Serves a Protective Role during Klebsiella pneumoniae - Induced Pneumonia

    PubMed Central

    Achouiti, Ahmed; de Vos, Alex F.; van ‘t Veer, Cornelis; Florquin, Sandrine; Tanck, Michael W.; Nawroth, Peter P.; Bierhaus, Angelika; van der Poll, Tom; van Zoelen, Marieke A. D.

    2016-01-01

    Klebsiella species is the second most commonly isolated gram-negative organism in sepsis and a frequent causative pathogen in pneumonia. The receptor for advanced glycation end products (RAGE) is expressed on different cell types and plays a key role in diverse inflammatory responses. We here aimed to investigate the role of RAGE in the host response to Klebsiella (K.) pneumoniae pneumonia and intransally inoculated rage gene deficient (RAGE-/-) and normal wild-type (Wt) mice with K. pneumoniae. Klebsiella pneumonia resulted in an increased pulmonary expression of RAGE. Furthermore, the high-affinity RAGE ligand high mobility group box-1 was upregulated during K. pneumoniae pneumonia. RAGE deficiency impaired host defense as reflected by a worsened survival, increased bacterial outgrowth and dissemination in RAGE-/- mice. RAGE-/- neutrophils showed a diminished phagocytosing capacity of live K. pneumoniae in vitro. Relative to Wt mice, RAGE-/- mice demonstrated similar lung inflammation, and slightly elevated—if any—cytokine and chemokine levels and unchanged hepatocellular injury. In addition, RAGE-/- mice displayed an unaltered response to intranasally instilled Klebsiella lipopolysaccharide (LPS) with respect to pulmonary cell recruitment and local release of cytokines and chemokines. These data suggest that (endogenous) RAGE protects against K. pneumoniae pneumonia. Also, they demonstrate that RAGE contributes to an effective antibacterial defense during K. pneumoniae pneumonia, at least partly via its participation in the phagocytic properties of professional granulocytes. Additionally, our results indicate that RAGE is not essential for the induction of a local and systemic inflammatory response to either intact Klebsiella or Klebsiella LPS. PMID:26824892

  5. Drug-induced lymphocyte stimulation test is not useful for the diagnosis of drug-induced pneumonia.

    PubMed

    Matsuno, Osamu; Okubo, Toshiyuki; Hiroshige, Shigeo; Takenaka, Rhyuichi; Ono, Emiko; Ueno, Takuya; Nureki, Shinichi; Ando, Masaru; Miyazaki, Eishi; Kumamoto, Toshihide

    2007-05-01

    Diagnosis of drug-induced pneumonia, which represents pulmonary toxicity caused by certain drugs, is difficult, as a large number of different drugs can elicit various immune-mediated diseases with distinct pathomechanisms. The drug-induced lymphocyte stimulation test (DLST) is widely used for diagnosing drug-induced pneumonia in Japan. Recent reports, however, indicate that DLST is not reliable for diagnosis of drug-induced pneumonia. To diagnose drug-induced pneumonia, a provocation test with the suspected drug is the most reliable method of assessing the relationship between the drug and pneumonia. We examined the correlation between the DLST and the provocation test in 6 cases of suspected drug-induced pneumonia. DLST was performed in all of the patients. The causes of pneumonia in all patients were confirmed by a provocation test. The DLST was positive in 3 of 6 cases of suspected drug-induced pneumonia, but the suspected drugs were ruled out by the provocation test. If we had relied solely on the DLST, these 3 cases would have been labeled as false allergy. The results of the DLST did not coincide with the results of the provocation test in any of the cases. Our results suggest that the DLST is not useful for the diagnosis of drug-induced pneumonia. Following provocation with the causative drug, reappearance of pulmonary infiltration was not observed in any of the cases. These findings indicate that a carefully performed provocation test is the safe and most reliable method. PMID:17464103

  6. Molecular Inflammatory Responses Measured in Blood of Patients with Severe Community-Acquired Pneumonia

    PubMed Central

    Fernández-Serrano, Silvia; Dorca, Jordi; Coromines, Mercè; Carratalà, Jordi; Gudiol, Francesc; Manresa, Frederic

    2003-01-01

    In order to analyze the characteristics of the inflammatory response occurring in blood during pneumonia, we studied 38 patients with severe community-acquired pneumonia. Venous and arterial blood samples were collected at study entry and on days 1, 2, 3, 5, and 7 after inclusion. The concentrations of proinflammatory (tumor necrosis factor alpha [TNF-α], interleukin 1β [IL-1β], IL-6, and IL-8) and anti-inflammatory (IL-10) cytokines were determined in order to detect differences related to the origin of the sample, the causative organism, the clinical variables, and the final outcome of the episode. Legionella pneumonia infections showed higher concentrations of TNF-α, IL-6, IL-8, and IL-10. After 24 h, plasma IL-6, IL-8, and IL-10 concentrations in pneumococcal episodes increased, whereas in the same time interval, cytokine concentrations in Legionella episodes markedly decreased. The characteristics of the inflammatory response in bacteremic pneumococcal episodes were different from those in nonbacteremic episodes, as indicated by the higher plasma cytokine concentrations in the former group. Finally, our analysis of cytokine concentrations with regard to the outcome—in terms of the need for intensive care unit admittance and/or mechanical ventilation as well as mortality—suggests that there is a direct relationship between the intensity of the inflammatory response measured in blood and the severity of the episode. PMID:12965910

  7. Severe amiodarone induced pulmonary toxicity

    PubMed Central

    Nacca, Nicholas; Yuhico, Luke S; Pinnamaneni, Sowmya; Szombathy, Tamas

    2012-01-01

    A known complication of Amiodarone therapy is Amiodarone induced Pulmonary Toxicity (APT). Several features of this adverse effect make it difficult to diagnosis and treat. The case of a 63-year-old male with classic radiographic and histologic findings of APT is discussed. Clinical presentation, pathophysiology, diagnostic findings, and treatment strategies are reviewed. The patient was successfully managed with pulse high dose steroid therapy. PMID:23205299

  8. Association between hospital case volume and mortality in non-elderly pneumonia patients stratified by severity: a retrospective cohort study

    PubMed Central

    2014-01-01

    Background The characteristics and aetiology of pneumonia in the non-elderly population is distinct from that in the elderly population. While a few studies have reported an inverse association between hospital case volume and clinical outcome in elderly pneumonia patients, the evidence is lacking in a younger population. In addition, the relationship between volume and outcome may be different in severe pneumonia cases than in mild cases. In this context, we tested two hypotheses: 1) non-elderly pneumonia patients treated at hospitals with larger case volume have better clinical outcome compared with those treated at lower case volume hospitals; 2) the volume-outcome relationship differs by the severity of the pneumonia. Methods We conducted the study using the Japanese Diagnosis Procedure Combination database. Patients aged 18–64 years discharged from the participating hospitals between July to December 2010 were included. The hospitals were categorized into four groups (very-low, low, medium, high) based on volume quartiles. The association between hospital case volume and in-hospital mortality was evaluated using multivariate logistic regression with generalized estimating equations adjusting for pneumonia severity, patient demographics and comorbidity score, and hospital academic status. We further analyzed the relationship by modified A-DROP pneumonia severity score calculated using the four severity indices: dehydration, low oxygen saturation, orientation disturbance, and decreased systolic blood pressure. Results We identified 8,293 cases of pneumonia at 896 hospitals across Japan, with 273 in-hospital deaths (3.3%). In the overall population, no significant association between hospital volume and in-hospital mortality was observed. However, when stratified by pneumonia severity score, higher hospital volume was associated with lower in-hospital mortality at the intermediate severity level (modified A-DROP score = 2) (odds ratio (OR) of very low vs

  9. Pore-Forming Toxins Induce Macrophage Necroptosis during Acute Bacterial Pneumonia

    PubMed Central

    González-Juarbe, Norberto; Gilley, Ryan Paul; Hinojosa, Cecilia Anahí; Bradley, Kelley Margaret; Kamei, Akinobu; Gao, Geli; Dube, Peter Herman; Bergman, Molly Ann; Orihuela, Carlos Javier

    2015-01-01

    Necroptosis is a highly pro-inflammatory mode of cell death regulated by RIP (or RIPK)1 and RIP3 kinases and mediated by the effector MLKL. We report that diverse bacterial pathogens that produce a pore-forming toxin (PFT) induce necroptosis of macrophages and this can be blocked for protection against Serratia marcescens hemorrhagic pneumonia. Following challenge with S. marcescens, Staphylococcus aureus, Streptococcus pneumoniae, Listeria monocytogenes, uropathogenic Escherichia coli (UPEC), and purified recombinant pneumolysin, macrophages pretreated with inhibitors of RIP1, RIP3, and MLKL were protected against death. Alveolar macrophages in MLKL KO mice were also protected during S. marcescens pneumonia. Inhibition of caspases had no impact on macrophage death and caspase-1 and -3/7 were determined to be inactive following challenge despite the detection of IL-1β in supernatants. Bone marrow-derived macrophages from RIP3 KO, but not caspase-1/11 KO or caspase-3 KO mice, were resistant to PFT-induced death. We explored the mechanisms for PFT-induced necroptosis and determined that loss of ion homeostasis at the plasma membrane, mitochondrial damage, ATP depletion, and the generation of reactive oxygen species were together responsible. Treatment of mice with necrostatin-5, an inhibitor of RIP1; GW806742X, an inhibitor of MLKL; and necrostatin-5 along with co-enzyme Q10 (N5/C10), which enhances ATP production; reduced the severity of S. marcescens pneumonia in a mouse intratracheal challenge model. N5/C10 protected alveolar macrophages, reduced bacterial burden, and lessened hemorrhage in the lungs. We conclude that necroptosis is the major cell death pathway evoked by PFTs in macrophages and the necroptosis pathway can be targeted for disease intervention. PMID:26659062

  10. Genetic variants associated with severe pneumonia in A/H1N1 influenza infection.

    PubMed

    Zúñiga, J; Buendía-Roldán, I; Zhao, Y; Jiménez, L; Torres, D; Romo, J; Ramírez, G; Cruz, A; Vargas-Alarcon, G; Sheu, C-C; Chen, F; Su, L; Tager, A M; Pardo, A; Selman, M; Christiani, D C

    2012-03-01

    The A/H1N1 influenza strain isolated in Mexico in 2009 caused severe pulmonary illness in a small number of exposed individuals. Our objective was to determine the influence of genetic factors on their susceptibility. We carried out a case-control association study genotyping 91 patients with confirmed severe pneumonia from A/H1N1 infection and 98 exposed but asymptomatic household contacts, using the HumanCVD BeadChip (Illumina, San Diego, CA, USA). Four risk single-nucleotide polymorphisms were significantly (p<0.0001) associated with severe pneumonia: rs1801274 (Fc fragment of immunoglobulin G, low-affinity IIA, receptor (FCGR2A) gene, chromosome 1; OR 2.68, 95% CI 1.69-4.25); rs9856661 (gene unknown, chromosome 3; OR 2.62, 95% CI 1.64-4.18); rs8070740 (RPA interacting protein (RPAIN) gene, chromosome 17; OR 2.67, 95% CI 1.63-4.39); and rs3786054 (complement component 1, q subcomponent binding protein (C1QBP) gene, chromosome 17; OR 3.13, 95% CI 1.89-5.17). All SNP associations remained significant after adjustment for sex and comorbidities. The SNPs on chromosome 17 were in linkage disequilibrium. These findings revealed that gene polymorphisms located in chromosomes 1 and 17 might influence susceptibility to development of severe pneumonia in A/H1N1 infection. Two of these SNPs are mapped within genes (FCGR2A, C1QBP) involved in the handling of immune complexes and complement activation, respectively, suggesting that these genes may confer risk due to increased activation of host immunity. PMID:21737555

  11. Community-acquired pneumonia: economics of inpatient medical care vis-à-vis clinical severity*,**

    PubMed Central

    Cupurdija, Vojislav; Lazic, Zorica; Petrovic, Marina; Mojsilovic, Slavica; Cekerevac, Ivan; Rancic, Nemanja; Jakovljevic, Mihajlo

    2015-01-01

    Objective: To assess the direct and indirect costs of diagnosing and treating community-acquired pneumonia (CAP), correlating those costs with CAP severity at diagnosis and identifying the major cost drivers. Methods: This was a prospective cost analysis study using bottom-up costing. Clinical severity and mortality risk were assessed with the pneumonia severity index (PSI) and the mental Confusion-Urea-Respiratory rate-Blood pressure-age ≥ 65 years (CURB-65) scale, respectively. The sample comprised 95 inpatients hospitalized for newly diagnosed CAP. The analysis was run from a societal perspective with a time horizon of one year. Results: Expressed as mean ± standard deviation, in Euros, the direct and indirect medical costs per CAP patient were 696 ± 531 and 410 ± 283, respectively, the total per-patient cost therefore being 1,106 ± 657. The combined budget impact of our patient cohort, in Euros, was 105,087 (66,109 and 38,979 in direct and indirect costs, respectively). The major cost drivers, in descending order, were the opportunity cost (lost productivity); diagnosis and treatment of comorbidities; and administration of medications, oxygen, and blood derivatives. The CURB-65 and PSI scores both correlated with the indirect costs of CAP treatment. The PSI score correlated positively with the overall frequency of use of health care services. Neither score showed any clear relationship with the direct costs of CAP treatment. Conclusions: Clinical severity at admission appears to be unrelated to the costs of CAP treatment. This is mostly attributable to unwarranted hospital admission (or unnecessarily long hospital stays) in cases of mild pneumonia, as well as to over-prescription of antibiotics. Authorities should strive to improve adherence to guidelines and promote cost-effective prescribing practices among physicians in southeastern Europe. PMID:25750674

  12. Dynamic regulation of cardiolipin by the lipid pump Atp8b1 determines the severity of lung injury in experimental pneumonia.

    PubMed

    Ray, Nancy B; Durairaj, Lakshmi; Chen, Bill B; McVerry, Bryan J; Ryan, Alan J; Donahoe, Michael; Waltenbaugh, Alisa K; O'Donnell, Christopher P; Henderson, Florita C; Etscheidt, Christopher A; McCoy, Diann M; Agassandian, Marianna; Hayes-Rowan, Emily C; Coon, Tiffany A; Butler, Phillip L; Gakhar, Lokesh; Mathur, Satya N; Sieren, Jessica C; Tyurina, Yulia Y; Kagan, Valerian E; McLennan, Geoffrey; Mallampalli, Rama K

    2010-10-01

    Pneumonia remains the leading cause of death from infection in the US, yet fundamentally new conceptual models underlying its pathogenesis have not emerged. We show that humans and mice with bacterial pneumonia have markedly elevated amounts of cardiolipin, a rare, mitochondrial-specific phospholipid, in lung fluid and find that it potently disrupts surfactant function. Intratracheal cardiolipin administration in mice recapitulates the clinical phenotype of pneumonia, including impaired lung mechanics, modulation of cell survival and cytokine networks and lung consolidation. We have identified and characterized the activity of a unique cardiolipin transporter, the P-type ATPase transmembrane lipid pump Atp8b1, a mutant version of which is associated with severe pneumonia in humans and mice. Atp8b1 bound and internalized cardiolipin from extracellular fluid via a basic residue-enriched motif. Administration of a peptide encompassing the cardiolipin binding motif or Atp8b1 gene transfer in mice lessened bacteria-induced lung injury and improved survival. The results unveil a new paradigm whereby Atp8b1 is a cardiolipin importer whose capacity to remove cardiolipin from lung fluid is exceeded during inflammation or when Atp8b1 is defective. This discovery opens the door for new therapeutic strategies directed at modulating the abundance or molecular interactions of cardiolipin in pneumonia. PMID:20852622

  13. CAUSATIVE AGENTS OF SEVERE COMMUNITY ACQUIRED VIRAL PNEUMONIA AMONG CHILDREN IN EASTERN THAILAND.

    PubMed

    Pratheepamornkull, Thitikarn; Ratanakorn, Woranart; Samransamruajkit, Rujipat; Poovorawan, Yong

    2015-07-01

    Pneumonia is a leading cause of morbidity and mortality among infants and young children. The most common causes of pneumonia in children are respiratory viruses. In Thailand, the epidemiology of the viruses causing community-acquired pneumonia (CAP) among children is poorly defined. In this cross sectional study we used nasopharyngeal samples collected from hospitalized children diagnosed with severe CAP in accordance with WHO criteria between June 2013 and May 2014 to determine the causes of infection. The samples were analyzed for respiratory syncytial virus (RSV), parainfluenza viruses (PIV) types 1,2 and 3, adenovirus, rhinovirus, influenza viruses types A and B and coronavirus by polymerase chain reaction (PCR) and reverse transcriptase-polymerase chain reaction (RT-PCR). Of 102 cases of severe CAP, samples were obtained in 91 cases and 48 (52.7%) were positive for respiratory viruses. The most common viruses were RSV (n = 22; 45.8%), rhinovirus (n = 11; 22.9%) and adenovirus (n = 9; 18.7%). Patients were aged 1 month to 4 years 5 months, with a median age of 1 year 1 month. Thirty-seven (77.1%) were male. Asthma was the most common co-morbidity affecting 5 (10.4%) of the 48 cases with an identified virus. The peak prevalence occurred during October (n = 17). All patients required oxygen therapy and 17 (35.4%) required mechanical ventilation. The median length of hospitalization was 11 days. Preterm infants had a significantly higher rate of RSV infection than other respiratory viruses (8 of 21; 38% vs 3 of 27; 11.1%) (p = 0.02). Viruses were most commonly associated with severe CAP among children aged less than 1 year. The peak prevalence occurred during the rainy season. Our findings suggest that young and preterm infants with CAP should be monitored closely due to their high risk for developing serious complications. PMID:26867384

  14. A definite case of (L)-carbocisteine-induced pneumonia with CATCH22 syndrome.

    PubMed

    Kudo, Kenichiro; Ichihara, Eiki; Hisamoto, Akiko; Hotta, Katsuyuki; Miyahara, Nobuaki; Tanimoto, Yasushi; Akagi, Sadaharu; Kato, Katsuya; Tanimoto, Mitsune; Kiura, Katsuyuki

    2013-01-01

    A 32-year-old male with CATCH22 syndrome presented with a high fever and productive cough after taking drugs for acute bronchitis, including (L)-carbocisteine. Chest radiography revealed ground-glass opacities in the bilateral lung fields. He had a history of similar pneumonia. Under the assumption of drug-induced pneumonia, or bacterial or viral pneumonia, all drugs including (L)-carbocisteine were discontinued, and antibiotics were started. A drug-induced lymphocyte stimulation test was positive only for (L)-carbocisteine. The only drug in common between this and the previous episode of pneumonia was (L)-carbocisteine. We thus concluded that this was a definite case of (L)-carbocisteine-induced pneumonia in a patient with CATCH22 syndrome. PMID:23291681

  15. Value of bacterial antigen detection in the diagnostic yield of transthoracic needle aspiration in severe community acquired pneumonia.

    PubMed Central

    Bella, F.; Tort, J.; Morera, M. A.; Espaulella, J.; Armengol, J.

    1993-01-01

    BACKGROUND--Transthoracic needle aspiration (TNA) with an ultrathin needle is a safe and highly specific procedure for obtaining a diagnosis in bacterial pneumonias, but its sensitivity is at best 70%. A study was performed to assess whether Streptococcus pneumoniae and Haemophilus influenzae type b antigen detection by latex agglutination from the TNA sample enhanced the diagnostic yield. METHODS--Blood cultures, TNA with an ultrathin needle (culture, Gram stain, and latex agglutination), serological tests, and pneumococcal antigen detection in the urine by counterimmunoelectrophoresis were performed in samples from 18 of 23 consecutive patients with severe community acquired pneumonia. RESULTS--The causative organism was identified in 16 cases (88%): S pneumoniae (10 cases), S pneumoniae plus H influenzae (two cases), Legionella pneumophila (three cases), and Mycoplasma pneumoniae (one case). The investigation of antigens by latex agglutination in the pulmonary aspirate increased the diagnostic yield of TNA from 50% to 78% and provided a rapid diagnosis (in less than two hours) with therapeutic implications in seven cases. Its effectiveness was not modified by prior antibiotic therapy. CONCLUSIONS--A latex agglutination test on the pulmonary aspirate enhances the diagnostic yield of TNA in severe community acquired pneumonia. PMID:8303628

  16. Assessment of Mycoplasma hyopneumoniae-induced Pneumonia using Different Lung Lesion Scoring Systems: a Comparative Review.

    PubMed

    Garcia-Morante, B; Segalés, J; Fraile, L; Pérez de Rozas, A; Maiti, H; Coll, T; Sibila, M

    2016-01-01

    Mycoplasma hyopneumoniae is the primary aetiological agent of swine enzootic pneumonia (EP) and one of the major contributors to the porcine respiratory disease complex (PRDC). Gross lung lesions in pigs affected by EP consist of cranioventral pulmonary consolidation (CVPC), usually distributed bilaterally in the apical, intermediate, accessory and cranial parts of the diaphragmatic lobes. Several lung scoring methods are currently in place for the evaluation of CVPC. The aims of this study were (1) to review the lung lesion scoring systems used to assess pneumonia associated with M. hyopneumoniae infection, and (2) to evaluate eight of these scoring systems by applying them to the lungs of 76 pigs with experimentally-induced M. hyopneumoniae pneumonia. A significant correlation between all lung lesion scoring systems was observed and the coefficients of determination in a regression analysis were very high between each pair-wise comparison, except for a unique scoring system based on image analysis. A formula of equivalence between lung scoring methods was developed in order to compare the results obtained with these methods. The present review provides a basis for comparison (even retrospectively) of lesions evaluated using different lung scoring systems. PMID:26774274

  17. Exogenous lipoid pneumonia induced by aspiration of insecticide.

    PubMed

    Ishimatsu, Keisuke; Kamitani, Takeshi; Matsuo, Yoshio; Hatakenaka, Masamitsu; Sunami, Shunya; Jinnouchi, Mikako; Nagao, Michinobu; Yabuuchi, Hidetake; Honda, Hiroshi

    2012-01-01

    Exogenous lipoid pneumonia is a rare disorder caused by inhalation and/or aspiration of oil-based substances. The confirmed diagnosis of exogenous lipoid pneumonia is difficult, especially in cases for which it is impossible to ascertain a history of inhalation or aspiration. We present a case of exogenous lipoid pneumonia due to aspiration of insecticide, for which the computed tomography findings of fat attenuation within the lesion were helpful in reaching a correct diagnosis. PMID:21952608

  18. Mechanisms of methicillin-resistant Staphylococcus aureus pneumonia-induced intestinal epithelial apoptosis.

    PubMed

    Perrone, Erin E; Jung, Enjae; Breed, Elise; Dominguez, Jessica A; Liang, Zhe; Clark, Andrew T; Dunne, W Michael; Burd, Eileen M; Coopersmith, Craig M

    2012-07-01

    Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia-induced sepsis is a common cause of morbidity in the intensive care unit. Although pneumonia is initiated in the lungs, extrapulmonary manifestations occur commonly. In light of the key role the intestine plays in the pathophysiology of sepsis, we sought to determine whether MRSA pneumonia induces intestinal injury. FVB/N mice were subjected to MRSA or sham pneumonia and killed 24 h later. Septic animals had a marked increase in intestinal epithelial apoptosis by both hematoxylin-eosin and active caspase 3 staining. Methicillin-resistant S. aureus-induced intestinal apoptosis was associated with an increase in the expression of the proapoptotic proteins Bid and Bax and the antiapoptotic protein Bcl-xL in the mitochondrial pathway. In the receptor-mediated pathway, MRSA pneumonia induced an increase in Fas ligand but decreased protein levels of Fas, FADD, pFADD, TNF-R1, and TRADD. To assess the functional significance of these changes, MRSA pneumonia was induced in mice with genetic manipulations in proteins in either the mitochondrial or receptor-mediated pathways. Both Bid-/- mice and animals with intestine-specific overexpression of Bcl-2 had decreased intestinal apoptosis compared with wild-type animals. In contrast, Fas ligand-/- mice had no alterations in apoptosis. To determine if these findings were organism-specific, similar experiments were performed in mice subjected to Pseudomonas aeruginosa pneumonia. Pseudomonas aeruginosa induced gut apoptosis, but unlike MRSA, this was associated with increased Bcl-2 and TNF-R1 and decreased Fas. Methicillin-resistant S. aureus pneumonia thus induces organism-specific changes in intestinal apoptosis via changes in both the mitochondrial and receptor-mediated pathways, although the former may be more functionally significant. PMID:22592747

  19. Mechanisms of methicillin-resistant Staphylococcus aureus pneumonia-induced intestinal epithelial apoptosis

    PubMed Central

    Perrone, Erin E.; Jung, Enjae; Breed, Elise; Dominguez, Jessica A.; Liang, Zhe; Clark, Andrew T.; Dunne, W. Michael; Burd, Eileen M.; Coopersmith, Craig M.

    2012-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia-induced sepsis is a common cause of morbidity in the intensive care unit. Although pneumonia is initiated in the lungs, extrapulmonary manifestations occur commonly. In light of the key role the intestine plays in the pathophysiology of sepsis, we sought to determine whether MRSA pneumonia induces intestinal injury. FVB/N mice were subjected to MRSA or sham pneumonia and sacrificed 24 hours later. Septic animals had a marked increase in intestinal epithelial apoptosis by both H&E and active caspase-3 staining. MRSA-induced intestinal apoptosis was associated with an increase in the expression of the pro-apoptotic proteins Bid and Bax and the anti-apoptotic protein Bcl-xL in the mitochondrial pathway. In the receptor-mediated pathway, MRSA pneumonia induced an increase in Fas-ligand but decreased protein levels of Fas, FADD, pFADD, TNF-R1 and TRADD. To assess the functional significance of these changes, MRSA pneumonia was induced in mice with genetic manipulations in proteins in either the mitochondrial or receptor-mediated pathways. Both Bid−/− mice and animals with intestine specific overexpression of Bcl-2 had decreased intestinal apoptosis compared to wild type animals. In contrast, Fas-ligand−/− mice had no alterations in apoptosis. To determine if these findings were organism-specific, similar experiments were performed in mice subjected to Pseudomonas aeruginosa pneumonia. P. aeruginosa induced gut apoptosis, but unlike MRSA, this was associated with increased Bcl-2 and TNF-R1 and decreased Fas. MRSA pneumonia thus induces organism-specific changes in intestinal apoptosis via changes in both the mitochondrial and receptor-mediated pathways although the former may be more functionally significant. PMID:22592747

  20. Bevacizumab‐induced chronic interstitial pneumonia during maintenance therapy in non‐small cell lung cancer

    PubMed Central

    Sekimoto, Yasuhito; Shukuya, Takehiko; Koyama, Ryo; Nagaoka, Tetsutaro; Takahashi, Kazuhisa

    2016-01-01

    Abstract Bevacizumab is a monoclonal antibody targeting the vascular endothelial growth factor receptor and a key drug for advanced non‐small cell lung cancer. There are few reports describing bevacizumab‐induced chronic interstitial pneumonia. A 62‐year‐old man with advanced non‐small cell lung cancer was admitted to our hospital with dyspnea. He previously received four courses of carboplatin plus paclitaxel with bevacizumab combination therapy and thereafter received four courses of maintenance bevacizumab monotherapy. A chest‐computed tomography scan on admission revealed diffuse ground glass opacity. He had not received any other drugs and did not have pneumonia. Thus, he was diagnosed with bevacizumab‐induced chronic interstitial pneumonia and was treated with a high dose of corticosteroids. After steroid treatment, his dyspnea and radiological findings improved. This case report is the first description of bevacizumab‐induced chronic interstitial pneumonia during maintenance therapy in a patient with non‐small cell lung cancer. PMID:27081491

  1. Streptococcus pneumoniae induces pyroptosis through the regulation of autophagy in murine microglia.

    PubMed

    Kim, Ji-Yun; Paton, James C; Briles, David E; Rhee, Dong-Kwon; Pyo, Suhkneung

    2015-12-29

    Streptococcus pneumoniae is responsible for significant mortality and morbidity worldwide and causes invasive pneumococcal diseases including pneumococcal meningitis. Pyroptosis is caspase-1-dependent inflammatory cell death and is known to be induced by various microbial infections. In the present study, we investigated the molecular mechanisms that regulate pyroptosis induced by S. pneumoniae in microglia. Our results revealed that S. pneumoniae induced pyroptosis through caspase-1 activation and IL-1β production. We also found that the activation of caspase-1 and the maturation of IL-1β and IL-18 in the S. pneumoniae-triggered pyroptotic cell death process were mediated by NLRP3 inflammasome. In addition, pneumococcal infection increased the expression of autophagy-related genes and induced autophagosome formation. We also showed that the inhibition of autophagy promoted pneumococcus-induced pyroptosis. Furthermore, ROS was generated by pneumococcal infection and inhibited caspase-1 activation within 4 h of infection. However, in the late phase of infection, IL-1β secretion and caspase-1-dependent cell death were induced by ROS. These results suggest that autophagy induction transiently delay pyroptosis induced by S. pneumoniae in microglia. Our study also revealed that the activation of caspase-1 and the production of IL-1β were induced by pneumolysin and that pneumolysin triggered pyroptosis in microglial cells. Similar to the in vitro results, S. pneumoniae induced caspase-1 activation and caspase-1-dependent cytokine maturation in the mouse meningitis model. Thus, the present data demonstrate that S. pneumoniae induces pyroptosis in murine microglia and that NLRP3 inflammasome is critical for caspase-1 activation during the process. Furthermore, the induction of autophagy could transiently protect microglia from pyroptosis. PMID:26683708

  2. Streptococcus pneumoniae induces pyroptosis through the regulation of autophagy in murine microglia

    PubMed Central

    Kim, Ji-Yun; Paton, James C.; Briles, David E.; Rhee, Dong-Kwon; Pyo, Suhkneung

    2015-01-01

    Streptococcus pneumoniae is responsible for significant mortality and morbidity worldwide and causes invasive pneumococcal diseases including pneumococcal meningitis. Pyroptosis is caspase-1-dependent inflammatory cell death and is known to be induced by various microbial infections. In the present study, we investigated the molecular mechanisms that regulate pyroptosis induced by S. pneumoniae in microglia. Our results revealed that S. pneumoniae induced pyroptosis through caspase-1 activation and IL-1β production. We also found that the activation of caspase-1 and the maturation of IL-1β and IL-18 in the S. pneumoniae-triggered pyroptotic cell death process were mediated by NLRP3 inflammasome. In addition, pneumococcal infection increased the expression of autophagy-related genes and induced autophagosome formation. We also showed that the inhibition of autophagy promoted pneumococcus-induced pyroptosis. Furthermore, ROS was generated by pneumococcal infection and inhibited caspase-1 activation within 4 h of infection. However, in the late phase of infection, IL-1β secretion and caspase-1-dependent cell death were induced by ROS. These results suggest that autophagy induction transiently delay pyroptosis induced by S. pneumoniae in microglia. Our study also revealed that the activation of caspase-1 and the production of IL-1β were induced by pneumolysin and that pneumolysin triggered pyroptosis in microglial cells. Similar to the in vitro results, S. pneumoniae induced caspase-1 activation and caspase-1-dependent cytokine maturation in the mouse meningitis model. Thus, the present data demonstrate that S. pneumoniae induces pyroptosis in murine microglia and that NLRP3 inflammasome is critical for caspase-1 activation during the process. Furthermore, the induction of autophagy could transiently protect microglia from pyroptosis. PMID:26683708

  3. Severe community-acquired pneumonia: timely management measures in the first 24 hours.

    PubMed

    Phua, Jason; Dean, Nathan C; Guo, Qi; Kuan, Win Sen; Lim, Hui Fang; Lim, Tow Keang

    2016-01-01

    Mortality rates for severe community-acquired pneumonia (CAP) range from 17 to 48 % in published studies.In this review, we searched PubMed for relevant papers published between 1981 and June 2016 and relevant files. We explored how early and aggressive management measures, implemented within 24 hours of recognition of severe CAP and carried out both in the emergency department and in the ICU, decrease mortality in severe CAP.These measures begin with the use of severity assessment tools and the application of care bundles via clinical decision support tools. The bundles include early guideline-concordant antibiotics including macrolides, early haemodynamic support (lactate measurement, intravenous fluids, and vasopressors), and early respiratory support (high-flow nasal cannulae, lung-protective ventilation, prone positioning, and neuromuscular blockade for acute respiratory distress syndrome).While the proposed interventions appear straightforward, multiple barriers to their implementation exist. To successfully decrease mortality for severe CAP, early and close collaboration between emergency medicine and respiratory and critical care medicine teams is required. We propose a workflow incorporating these interventions. PMID:27567896

  4. Semi-automated method to measure pneumonia severity in mice through computed tomography (CT) scan analysis

    NASA Astrophysics Data System (ADS)

    Johri, Ansh; Schimel, Daniel; Noguchi, Audrey; Hsu, Lewis L.

    2010-03-01

    Imaging is a crucial clinical tool for diagnosis and assessment of pneumonia, but quantitative methods are lacking. Micro-computed tomography (micro CT), designed for lab animals, provides opportunities for non-invasive radiographic endpoints for pneumonia studies. HYPOTHESIS: In vivo micro CT scans of mice with early bacterial pneumonia can be scored quantitatively by semiautomated imaging methods, with good reproducibility and correlation with bacterial dose inoculated, pneumonia survival outcome, and radiologists' scores. METHODS: Healthy mice had intratracheal inoculation of E. coli bacteria (n=24) or saline control (n=11). In vivo micro CT scans were performed 24 hours later with microCAT II (Siemens). Two independent radiologists scored the extent of airspace abnormality, on a scale of 0 (normal) to 24 (completely abnormal). Using the Amira 5.2 software (Mercury Computer Systems), a histogram distribution of voxel counts between the Hounsfield range of -510 to 0 was created and analyzed, and a segmentation procedure was devised. RESULTS: A t-test was performed to determine whether there was a significant difference in the mean voxel value of each mouse in the three experimental groups: Saline Survivors, Pneumonia Survivors, and Pneumonia Non-survivors. It was found that the voxel count method was able to statistically tell apart the Saline Survivors from the Pneumonia Survivors, the Saline Survivors from the Pneumonia Non-survivors, but not the Pneumonia Survivors vs. Pneumonia Non-survivors. The segmentation method, however, was successfully able to distinguish the two Pneumonia groups. CONCLUSION: We have pilot-tested an evaluation of early pneumonia in mice using micro CT and a semi-automated method for lung segmentation and scoring system. Statistical analysis indicates that the system is reliable and merits further evaluation.

  5. Severe sepsis facilitates intestinal colonization by extended-spectrum-β-lactamase-producing Klebsiella pneumoniae and transfer of the SHV-18 resistance gene to Escherichia coli during antimicrobial treatment.

    PubMed

    Guan, Jun; Liu, Shaoze; Lin, Zhaofen; Li, Wenfang; Liu, Xuefeng; Chen, Dechang

    2014-01-01

    Infections caused by multidrug-resistant pathogens are frequent and life threatening in critically ill patients. To investigate whether severe sepsis affects gut colonization by resistant pathogens and genetic exchange between opportunistic pathogens, we tested the intestinal-colonization ability of an extended-spectrum beta-lactamase-producing Klebsiella pneumoniae strain carrying the SHV-18 resistance gene and the transfer ability of the resistance gene to endogenous Escherichia coli under ceftriaxone treatment in rats with burn injury only or severe sepsis induced by burns plus endotoxin exposure. Without ceftriaxone treatment, the K. pneumoniae strain colonized the intestine in both septic and burned rats for a short time, with clearance occurring earlier in burn-only rats but never in sham burn rats. In both burned and septic rats, the colonization level of the challenge strain dropped at the beginning and then later increased during ceftriaxone treatment, after which it declined gradually. This pattern coincided with the change in resistance of K. pneumoniae to ceftriaxone during and after ceftriaxone treatment. Compared with burn-only injury, severe sepsis had a more significant effect on the change in antimicrobial resistance to ceftriaxone. Only in septic rats was the resistance gene successfully transferred from the challenge strain to endogenous E. coli during ceftriaxone treatment; the gene persisted for at least 4 weeks after ceftriaxone treatment. We concluded that severe sepsis can facilitate intestinal colonization by an exogenous resistant pathogen and the transfer of the resistance gene to a potential endogenous pathogen during antimicrobial treatment. PMID:24277046

  6. Immunosuppressant dose reduction and long-term rejection risk in renal transplant recipients with severe bacterial pneumonia

    PubMed Central

    Shih, Chia-Jen; Tarng, Der-Cherng; Yang, Wu-Chang; Yang, Chih-Yu

    2014-01-01

    INTRODUCTION Due to lifelong immunosuppression, renal transplant recipients (RTRs) are at risk of infectious complications such as pneumonia. Severe pneumonia results in respiratory failure and is life-threatening. We aimed to examine the influence of immunosuppressant dose reduction on RTRs with bacterial pneumonia and respiratory failure. METHODS From January 2001 to January 2011, 33 of 1,146 RTRs at a single centre developed bacterial pneumonia with respiratory failure. All patients were treated using mechanical ventilation and aggressive therapies in the intensive care unit. RESULTS Average time from kidney transplantation to pneumonia with respiratory failure was 6.8 years. In-hospital mortality rate was 45.5% despite intensive care and aggressive therapies. Logistic regression analysis indicated that a high serum creatinine level at the time of admission to the intensive care unit (odds ratio 1.77 per mg/dL, 95% confidence interval 1.01–3.09; p = 0.045) was a mortality determinant. Out of the 33 patients, immunosuppressive agents were reduced in 17 (51.5%). We found that although immunosuppressant dose reduction tended to improve in-hospital mortality, this was not statistically significant. Nevertheless, during a mean follow-up period of two years, none of the survivors (n = 18) developed acute rejection or allograft necrosis. CONCLUSION In RTRs with bacterial pneumonia and respiratory failure, higher serum creatinine levels were a mortality determinant. Although temporary immunosuppressant dose reduction might not reduce mortality, it was associated with a minimal risk of acute rejection during the two-year follow-up. Our results suggest that early immunosuppressant reduction in RTRs with severe pneumonia of indeterminate microbiology may be safe even when pathogens are bacterial in nature. PMID:25091886

  7. Low Rates of Treatment Failure in Children Aged 2–59 Months Treated for Severe Pneumonia: A Multisite Pooled Analysis

    PubMed Central

    Fox, Matthew P.; Thea, Donald M.; Sadruddin, Salim; Bari, Abdul; Bonawitz, Rachael; Hazir, Tabish; Bin Nisar, Yasir; Qazi, Shamim A.

    2013-01-01

    Background. Despite advances in childhood pneumonia management, it remains a major killer of children worldwide. We sought to estimate global treatment failure rates in children aged 2–59 months with World Health Organization–defined severe pneumonia. Methods. We pooled data from 4 severe pneumonia studies conducted during 1999–2009 using similar methodologies. We defined treatment failure by day 6 as death, danger signs (inability to drink, convulsions, abnormally sleepy), fever (≥38°C) and lower chest indrawing (LCI; days 2–3), LCI (day 6), or antibiotic change. Results. Among 6398 cases of severe pneumonia from 10 countries, 564 (cluster adjusted: 8.5%; 95% confidence interval [CI], 5.9%–11.5%) failed treatment by day 6. The most common reasons for clinical failure were persistence of fever and LCI or LCI or fever alone (75% of failures). Seventeen (0.3%) children died. Danger signs were uncommon (<1%). Infants 6–11 months and 2–5 months were 2- and 3.5-fold more likely, respectively, to fail treatment (adjusted OR [AOR], 1.8 [95% CI, 1.4–2.3] and AOR, 3.5 [95% CI, 2.8–4.3]) as children aged 12–59 months. Failure was increased 7-fold (AOR, 7.2 [95% CI, 5.0–10.5]) when comparing infants 2–5 months with very fast breathing to children 12–59 months with normal breathing. Conclusions. Our findings demonstrate that severe pneumonia case management with antibiotics at health facilities or in the community is associated with few serious morbidities or deaths across diverse geographic settings and support moves to shift management of severe pneumonia with oral antibiotics to outpatients in the community. PMID:23264361

  8. Mycoplasma ovipneumoniae - A Primary Cause of Severe Pneumonia Epizootics in the Norwegian Muskox (Ovibos moschatus) Population

    PubMed Central

    Handeland, Kjell; Tengs, Torstein; Kokotovic, Branko; Vikøren, Turid; Ayling, Roger D.; Bergsjø, Bjarne; Sigurðardóttir, Ólöf G.; Bretten, Tord

    2014-01-01

    The Norwegian muskox (Ovibos moschatus) population lives on the high mountain plateau of Dovre and originates from animals introduced from Greenland. In the late summers of 2006 and 2012, severe outbreaks of pneumonia with mortality rates of 25-30% occurred. During the 2012 epidemic high quality samples from culled sick animals were obtained for microbiological and pathological examinations. High throughput sequencing (pyrosequencing) of pneumonic lung tissue revealed high concentrations of Mycoplasma ovipneumoniae in all six animals examined by this method and Pasteurella multocida subsp. multocida in four animals, whereas no virus sequences could be identified. Mycoplasma ovipneumoniae and P. multocida multocida were also isolated by culture. Using real time PCR on lung swabs, M. ovipneumoniae was detected in all of the 19 pneumonic lungs examined. Gross pathological examination revealed heavy consolidations primarily in the cranial parts of the lungs and it also identified one case of otitis media. Histologically, lung lesions were characterized as acute to subacute mixed exudative and moderately proliferative bronchoalveolar pneumonia. Immunohistochemical (IHC) examination revealed high load of M. ovipneumoniae antigens within lung lesions, with particularly intensive staining in the neutrophils. Similar IHC finding were observed in archived lung tissue blocks from animals examined during the 2006 epidemic. An M. ovipneumoniae specific ELISA was applied on bio-banked muskox sera from stray muskoxen killed in the period 2004–2013 and sick muskoxen culled, as well as sera from wild reindeer (Rangifer tarandus tarandus) on Dovre and muskoxen from Greenland. Serology and mycoplasma culturing was also carried out on sheep that had been on pasture in the muskox area during the outbreak in 2012. Our findings indicated separate introductions of M. ovipneumoniae infection in 2006 and 2012 from infected co-grazing sheep. Salt licks shared by the two species were a

  9. R-roscovitine reduces lung inflammation induced by lipoteichoic acid and Streptococcus pneumoniae.

    PubMed

    Hoogendijk, Arie J; Roelofs, Joris J T H; Duitman, Janwillem; van Lieshout, Miriam H P; Blok, Dana C; van der Poll, Tom; Wieland, Catharina W

    2012-01-01

    Bacterial pneumonia remains associated with high morbidity and mortality. The gram-positive pathogen Streptococcus pneumoniae is the most common cause of community-acquired pneumonia. Lipoteichoic acid (LTA) is an important proinflammatory component of the gram-positive bacterial cell wall. R-roscovitine, a purine analog, is a potent cyclin-dependent kinase (CDK)-1, -2, -5 and -7 inhibitor that has the ability to inhibit the cell cycle and to induce polymorphonuclear cell (PMN) apoptosis. We sought to investigate the effect of R-roscovitine on LTA-induced activation of cell lines with relevance for lung inflammation in vitro and on lung inflammation elicited by either LTA or viable S. pneumoniae in vivo. In vitro R-roscovitine enhanced apoptosis in PMNs and reduced tumor necrosis factor (TNF)-α and keratinocyte chemoattractant (KC) production in MH-S (alveolar macrophage) and MLE-12/MLE-15 (respiratory epithelial) cell lines. In vivo R-roscovitine treatment reduced PMN numbers in bronchoalveolar lavage fluid during LTA-induced lung inflammation; this effect was reversed by inhibiting apoptosis. Postponed treatment with R-roscovitine (24 and 72 h) diminished PMN numbers in lung tissue during gram-positive pneumonia; this step was associated with a transient increase in pulmonary bacterial loads. R-roscovitine inhibits proinflammatory responses induced by the gram-positive stimuli LTA and S. pneumoniae. R-roscovitine reduces PMN numbers in lungs upon LTA administration by enhancing apoptosis. The reduction in PMN numbers caused by R-roscovitine during S. pneumoniae pneumonia may hamper antibacterial defense. PMID:22692577

  10. In vitro subminimum inhibitory concentrations of macrolide antibiotics induce macrolide resistance in Mycoplasma pneumoniae

    PubMed Central

    Ou, G; Liu, Y; Tang, Y; You, X; Zeng, Y; Xiao, J; Chen, L; Yu, M; Wang, M; Zhu, C

    2015-01-01

    Aim: This study aims to investigate the inducing effect of subminimum inhibitory concentrations of macrolide antibiotics on Mycoplasma pneumoniae (M. pneumoniae) resistance to drugs. Materials and Methods: One M. pneumoniae reference strain M129 (ATCC 29342) and 104 clinical isolates were incubated at 37C for 6-8 days. Genomic DNA of M. pneumoniae was extracted using TIANamp Bacteria DNA kit and amplified by polymerase chain reaction (PCR). Results: Ten sensitive isolates obtained from 104 M. pneumoniae clinical isolates were induced by subminimum inhibitory concentrations of macrolide antibiotics. Among them, three were found to possess mutations in L4 and L22 ribosomal proteins. Two cases carried simultaneously the C162A and A430G mutations of L4 and the T279C mutation of L22. In addition, one case had only the A209T mutation of L4. Conclusions: Repeated in vitro exposure to subminimum inhibitory concentrations of macrolide antibiotics could induce selective mutations in ribosomal genes of M. pneumoniae clinical isolates that cause resistance to macrolide antibiotics. Hippokratia 2015, 19 (1): 57-62. PMID:26435649

  11. Early Diagnosis of Pneumonia in Severe Stroke: Clinical Features and the Diagnostic Role of C-Reactive Protein

    PubMed Central

    Warusevitane, Anushka; Karunatilake, Dumin; Sim, Julius; Smith, Craig; Roffe, Christine

    2016-01-01

    Background Accurate diagnosis of pneumonia complicating severe stroke is challenging due to difficulties in physical examination, altered immune responses and delayed manifestations of radiological changes. The aims of this study were to describe early clinical features and to examine C-reactive protein (CRP) as a diagnostic marker of post-stroke pneumonia. Methods Patients who required nasogastric feeding and had no evidence of pneumonia within 7 days of stroke onset were included in the study and followed-up for 21 days with a daily clinical examination. Pneumonia was diagnosed using modified British Thoracic Society criteria. Results 60 patients were recruited (mean age 77 years, mean National Institutes of Health Stroke Scale Score 19.47). Forty-four episodes of pneumonia were identified. Common manifestations on the day of the diagnosis were new onset crackles (43/44, 98%), tachypnoea>25/min (42/44, 95%), and oxygen saturation <90% (41/44, 93%). Cough, purulent sputum, and pyrexia >38°C were observed in 27 (61%), 25 (57%) and 15 (34%) episodes respectively. Leucocytosis (WBC>11,000/ml) and raised CRP (>10 mg/l) were observed in 38 (86%) and 43 (97%) cases of pneumonia respectively. The area under the ROC curve for CRP was 0.827 (95% CI 0.720, 0.933). The diagnostic cut-off for CRP with an acceptable sensitivity (>0.8) was 25.60 mg/L (Youden index (J) 0.515; sensitivity 0.848; specificity 0.667). A cut-off of 64.65 mg/L had the highest diagnostic accuracy (J 0.562; sensitivity 0.636; specificity 0.926). Conclusion Patients with severe stroke frequently do not manifest key diagnostic features of pneumonia such as pyrexia, cough and purulent sputum early in their illness. The most common signs in this group are new-onset crackles, tachypnoea and hypoxia. Our results suggest that a CRP >25 mg/L should prompt investigations for pneumonia while values >65 mg/L have the highest diagnostic accuracy to justify consideration of this threshold as a diagnostic marker of

  12. Immunoprotective potential of polysaccharide-tetanus toxoid conjugate in Klebsiella pneumoniae induced lobar pneumonia in rats.

    PubMed

    Chhibber, S; Rani, Mamta; Vanashree, Yadav

    2005-01-01

    The polysaccharide (PS) derived from K. pneumoniae NCTC 5055 lipopolysaccharide (LPS) was covalently linked to tetanus toxoid by using carbodimide with adipic acid dihydrazide as a spacer molecule. The conjugate was found to be non-toxic and non-pyrogenic at 100 microg dose level. At a similar dose, the conjugate did not elicit any local skin reaction on intradermal preparatory injection in rabbits. The conjugate was immunoprotective as was evident from the decrease in relative colonization of bacteria in lungs of immunized rats as compared to the control animals. Immunization with the conjugate resulted in alveolar macrophage activation in terms of their ability to phagocytose bacteria in vitro. PMID:15691064

  13. Mycoplasma pneumoniae induces cytotoxic activity in guinea pig bronchoalveolar cells

    SciTech Connect

    Kist, M.; Koester, H.; Bredt, W.

    1985-06-01

    Precultured guinea pig alveolar macrophages (AM) and freshly harvested alveolar cells (FHAC) activated by interaction with Mycoplasma pneumoniae were cytotoxic for xenogeneic /sup 75/selenomethionine-labeled tumor target cells. Phagocytosis of whole opsonized or nonopsonized M. pneumoniae cells was more effective in eliciting cytotoxicity than uptake of sonicated microorganisms. The addition of living mycoplasma cells to the assay system enhanced the cytotoxic effect considerably. Target cells were significantly more susceptible to the cytotoxic action of phagocytes if they were coated with mycoplasma antigen or cocultured together with M. pneumoniae. The activation of the phagocytes could be inhibited by 2-deoxy-D-glucose but not by antimicrobial substances suppressing mycoplasma protein synthesis. It was accompanied by /sup 51/Cr release without detectable signs of cell damage. The supernatants of activated cells were cytotoxic for approximately 24 h. Inhibition, release, and cytotoxic activity indicate the necessity of an intact metabolism of the effector cells and suggest a secretion of cytotoxic substances.

  14. Frequency and trajectory of abnormalities in respiratory rate, temperature and oxygen saturation in severe pneumonia in children.

    PubMed

    Izadnegahdar, Rasa; Fox, Matthew P; Thea, Donald M; Qazi, Shamim A

    2012-08-01

    The frequency or trajectory of vital sign abnormalities in children with pneumonia has not been described. In a cohort of 2714 patients with severe pneumonia identified and treated as per the World Health Organization definition and recommendations, tachypnea, fever and hypoxia were found in 68.9%, 23.6% and 15.5% of children, respectively. Median oxygen saturation returned to a normal range by 10 hours following initiation of treatment, followed by temperature at 12 hours and respiratory rate at 22 hours for subjects <12 months and at 48 hours for those ≥ 12 months of age. PMID:22531236

  15. Severe Community-Acquired Pneumonia with Bacteremia Caused by Herbaspirillum aquaticum or Herbaspirillum huttiense in an Immune-Competent Adult

    PubMed Central

    Kimball, Joanna; Smith, L. Patrick; Salzer, William

    2015-01-01

    Herbaspirillum spp. are Gram-negative bacteria that inhabit soil and water. Infections caused by these organisms have been reported in immunocompromised hosts. We describe severe community-acquired pneumonia and bacteremia caused by Herbaspirillum aquaticum or H. huttiense in an immunocompetent adult male. PMID:26179298

  16. Soluble RAGE as a severity marker in community acquired pneumonia associated sepsis

    PubMed Central

    2012-01-01

    Background Community-acquired pneumonia (CAP) is considered the most important cause of death from infectious disease in developed countries. Severity assessment scores partially address the difficulties in identifying high-risk patients. A lack of specific and valid pathophysiologic severity markers affect early and effective sepsis therapy. HMGB-1, sRAGE and RAGE have been involved in sepsis and their potential as severity markers has been proposed. The aim of this study was to evaluate HMGB-1, RAGE and sRAGE levels in patients with CAP-associated sepsis and determine their possible association with clinical outcome. Method We evaluated 33 patients with CAP-associated sepsis admitted to the emergency room and followed in the medical wards. Severity assessment scores (CURB-65, PSI, APACHE II, SOFA) and serologic markers (HMGB-1, RAGE, sRAGE) were evaluated on admission. Results Thirty patients with a diagnosis of CAP-associated sepsis were enrolled in the study within 24 hours after admission. Fourteen (46.6%) had pandemic (H1N1) influenza A virus, 2 (6.6%) had seasonal influenza A and 14 other diagnoses. Of the patients in the study group, 16 (53.3%) had a fatal outcome. ARDS was observed in 17 (56.6%) and a total of 22 patients had severe sepsis on admission (73%). The SOFA score showed the greatest difference between surviving and non-surviving groups (P = .003) with similar results in ARDS patients (P = .005). sRAGE levels tended to be higher in non-surviving (P = .058) and ARDS patients (P = .058). Logistic regression modeling demonstrated that SOFA (P = .013) and sRAGE (P = .05) were the only variables that modified the probability of a fatal outcome. Conclusion The association of elevated sRAGE with a fatal outcome suggests that it may have an independent causal effect in CAP. SOFA scores were the only clinical factor with the ability to identify surviving and ARDS patients. PMID:22264245

  17. Mesalazine-induced eosinophilic pneumonia with bone marrow infiltration: a case report and literature review

    PubMed Central

    Zhang, Yunjian; Luo, Ling; Wang, Xiaofang; Liu, Xiaoyang; Wang, Xiaoyan; Ding, Yi

    2016-01-01

    Mesalazine-induced eosinophilic pneumonia has been rarely reported. We reported a case of mesalazine-induced eosinophilic pneumonia in a 56-year-old female who took mesalazine without a prescription for suspected ulcerative colitis. She had an elevated eosinophil count in peripheral blood and bronchoalveolar lavage fluid. Eosinophil infiltration was also noted in bone marrow aspirates. Chest radiograph and computed tomography demonstrated bilateral upper lung predominant infiltrates and spirometry showed a restrictive ventilatory defect with a reduced diffusion capacity. The patient recovered after cessation of mesalazine therapy. Mesalazine-induced lung damage should be considered in patients who develop unexplained respiratory symptoms while taking this agent. PMID:27366075

  18. Severe Hypothyroidism-Induced Volvulus.

    PubMed

    Khan, Rafay; Ahmed, Amar; Tulpule, Sunil; Regeti, Kalyani; Sen, Shuvendu; Mathew, Teena

    2015-12-01

    Thyroid disorders have been found to be associated with multiple organ systems and thus have a broad spectrum of presenting symptoms and clinical conditions. Certain aspects of the gastrointestinal (GI) system have yet to be fully understood and documented. Hypothyroidism and even hyperthyroidism have been identified in patients with motility symptoms involving the GI tract. These symptoms can vary and can be a complication of undertreated or undiagnosed condition involving the thyroid. Unfortunately, the mechanism in which these hormones can impact intestinal motility remains poorly understood and not well documented. In this case report, we discuss the presentation of a 71-year-old female with poorly managed hypothyroidism presenting with significant abdominal distention and pain secondary to underlying volvulus formation. By better understanding the complications induced by hypothyroidism, physicians may be able to prevent further life-threatening outcomes with early management and intervention. PMID:26566414

  19. Trimethoprim/Sulfamethoxazole-Induced Severe Lactic Acidosis

    PubMed Central

    Bulathsinghala, Marie; Keefer, Kimberly; Van de Louw, Andry

    2016-01-01

    Abstract Propylene glycol (PG) is used as a solvent in numerous medications, including trimethoprim/sulfamethoxazole (TMP/SMX) and lorazepam, and is metabolized in the liver to lactic acid. Cases of lactic acidosis related to PG toxicity have been described and always involved large doses of benzodiazepines and PG. We present the first case of severe lactic acidosis after a 3-day course of TMP/SMX alone, involving allegedly safe amounts of PG. A 31-year-old female with neurofibromatosis and pilocytic astrocytoma, receiving temozolomide and steroids, was admitted to the intensive care unit for pneumonia and acute respiratory failure requiring intubation. Her initial hemodynamic and acid–base statuses were normal. She was treated with intravenous TMP/SMX for possible Pneumocystis jirovecii pneumonia and was successfully extubated on day 2. On day 3, she developed tachypnea and arterial blood gas analysis revealed a severe metabolic acidosis (pH 7.2, PCO2 19 mm Hg, bicarbonates 8 mEq/L) with anion gap of 25 mEq/L and lactate of 12.1 mmol/L. TMP/SMX was discontinued and the lactate decreased to 2.9 mmol/L within 24 hours while her plasma bicarbonates normalized, without additional intervention. The patient never developed hypotension or severe hypoxia, and her renal and liver functions were normal. No other cause for lactic acidosis was identified and it resolved after TMP/SMX cessation alone, suggesting PG toxicity. Although PG-related lactic acidosis is well recognized after large doses of lorazepam, clinicians should bear in mind that TMP/SMX contains PG as well and should suspect PG toxicity in patients developing unexplained metabolic acidosis while receiving TMP/SMX. PMID:27124045

  20. Successful desensitization therapy for a patient with isoniazid-induced hypersensitivity pneumonia.

    PubMed

    Chihara, Yuichi; Takahashi, Ken-Ichi; Sakai, Naoki; Sato, Atsuo; Tsuboi, Tomomasa

    2016-01-01

    A 57-year-old male was diagnosed with mycobacterium tuberculoma and was treated with isoniazid, rifampicin, ethambutol, and pyrazinamide. Three weeks after initiation of treatment, he presented with fever and appetite loss. Chest radiograph showed diffuse micronodular shadows on both lung fields. High-resolution chest computed tomography findings were diffuse parenchymal micronodules in both lungs, which was consistent with hypersensitivity pneumonia. Because drug-induced pneumonia was suspected, the antituberculous regimen was discontinued. The symptoms and diffuse micronodular shadows improved. A drug lymphocyte stimulation test was only positive for isoniazid, so we suspected that the pneumonia was induced by isoniazid. Rifampicin and ethambutol were reintroduced without any recurrence of the abnormal shadows. Next, we tried desensitization to isoniazid over a period of two weeks, which was successful without any adverse events. Although isoniazid-induced pneumonia is extremely rare, it is important to recognize that isoniazid can cause such an adverse reaction. In addition, drug desensitization may be useful in drug-induced pneumonia. PMID:27330958

  1. Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial (PROSPECT): A Feasibility Clinical Trial

    ClinicalTrials.gov

    2016-03-16

    Ventilator Associated Pneumonia (VAP); Other Infections; Antibiotic-Associated Diarrhea; C-Difficile; Duration of Mechanical Ventilation; Length of ICU Stay; Length of Hospital Stay; ICU and Hospital Mortality

  2. Severe lipoid pneumonia following aspiration of machine oil: successful treatment with steroids.

    PubMed

    Indumathi, C K; Vikram, Kumar S; Paul, Prima; Lewin, Sanjiv

    2012-01-01

    Lipoid pneumonia in children follows mineral oil aspiration and may result in acute respiratory failure. Majority of the patients recover without long-term morbidity, though a few may be left with residual damage to the lungs. We report a case of a two-and-a-half-year-old child with persistent lipoid pneumonia following accidental inhalation of machine oil, who was successfully treated with steroids. PMID:23008930

  3. Analysis of the 8.1 ancestral MHC haplotype in severe, pneumonia-related sepsis.

    PubMed

    Aladzsity, István; Madách, Krisztina; Szilágyi, Agnes; Gál, János; Pénzes, István; Prohászka, Zoltán; Fust, George

    2011-06-01

    The most frequent Caucasian MHC haplotype, AH8.1 - associated with numerous immunopathological differences and certain autoimmune diseases - was recently linked to the delayed onset of bacterial colonization in cystic fibrosis. Based on this observation, we hypothesized that the carriers of AH8.1 have lower risk for a worse outcome in sepsis. AH8.1 carrier state was determined in 207 Caucasian patients with severe, pneumonia-related sepsis. Our data showed that in patients without chronic obstructive pulmonary disease (COPD), septic shock - a serious consequence of the bacterial infection - occurred significantly less frequently (OR=0.3383; 95% CI=0.1141-0.995; p=0.043) in carriers of AH8.1, than in non-carriers. According to the multivariate logistic regression analysis, this haplotype had an independent protective role against septic shock in all patients (OR=0.315; 95% CI=0.100-0.992; p=0.048), particularly in COPD-free patients (OR=0.117; 95% CI=0.025-0.554; p=0.007). These results indicate that AH8.1 may confer protection against the progression of bacterial infection, and this could explain, at least partially, its high frequency in the Caucasian population. PMID:21414845

  4. Using data-driven rules to predict mortality in severe community acquired pneumonia.

    PubMed

    Wu, Chuang; Rosenfeld, Roni; Clermont, Gilles

    2014-01-01

    Prediction of patient-centered outcomes in hospitals is useful for performance benchmarking, resource allocation, and guidance regarding active treatment and withdrawal of care. Yet, their use by clinicians is limited by the complexity of available tools and amount of data required. We propose to use Disjunctive Normal Forms as a novel approach to predict hospital and 90-day mortality from instance-based patient data, comprising demographic, genetic, and physiologic information in a large cohort of patients admitted with severe community acquired pneumonia. We develop two algorithms to efficiently learn Disjunctive Normal Forms, which yield easy-to-interpret rules that explicitly map data to the outcome of interest. Disjunctive Normal Forms achieve higher prediction performance quality compared to a set of state-of-the-art machine learning models, and unveils insights unavailable with standard methods. Disjunctive Normal Forms constitute an intuitive set of prediction rules that could be easily implemented to predict outcomes and guide criteria-based clinical decision making and clinical trial execution, and thus of greater practical usefulness than currently available prediction tools. The Java implementation of the tool JavaDNF will be publicly available. PMID:24699007

  5. Using Data-Driven Rules to Predict Mortality in Severe Community Acquired Pneumonia

    PubMed Central

    Wu, Chuang; Rosenfeld, Roni; Clermont, Gilles

    2014-01-01

    Prediction of patient-centered outcomes in hospitals is useful for performance benchmarking, resource allocation, and guidance regarding active treatment and withdrawal of care. Yet, their use by clinicians is limited by the complexity of available tools and amount of data required. We propose to use Disjunctive Normal Forms as a novel approach to predict hospital and 90-day mortality from instance-based patient data, comprising demographic, genetic, and physiologic information in a large cohort of patients admitted with severe community acquired pneumonia. We develop two algorithms to efficiently learn Disjunctive Normal Forms, which yield easy-to-interpret rules that explicitly map data to the outcome of interest. Disjunctive Normal Forms achieve higher prediction performance quality compared to a set of state-of-the-art machine learning models, and unveils insights unavailable with standard methods. Disjunctive Normal Forms constitute an intuitive set of prediction rules that could be easily implemented to predict outcomes and guide criteria-based clinical decision making and clinical trial execution, and thus of greater practical usefulness than currently available prediction tools. The Java implementation of the tool JavaDNF will be publicly available. PMID:24699007

  6. Characteristic of the Oxidative Stress in Blood of Patients in Dependence of Community-Acquired Pneumonia Severity

    PubMed Central

    Muravlyova, Larissa; Molotov–Luchankiy, Vilen; Bakirova, Ryszhan; Klyuyev, Dmitriy; Demidchik, Ludmila; Lee, Valentina

    2016-01-01

    BACKGROUND: At the present time the alternation of the oxidative metabolism is considered as one of the leading pathogenic mechanisms in the development and progression of community-acquired pneumonia (CAP). However the nature and direction of the oxidative protein changes in CAP patient’s blood had been almost unexplored. AIM: To define oxidative and modified proteins in erythrocytes and blood plasma of CAP patients. MATERIAL AND METHODS: Blood plasma and erythrocytes obtained from: 42 patients with moderate severity pneumonia, 12 patients with grave severity pneumonia and 32 healthy volunteers. Content of advanced oxidation protein products, malondialdehyde and reactive carbonyl derivatives were estimated as indicators of the oxidative stress and oxidative damage of proteins. RESULTS: In patients with grave severity the level of oxidative proteins and MDA in erythrocytes exceeded both: control values and similar meanings in CAP patients with moderate severity. The further growth of MDA in this group patients’ blood plasma was observed, but the level of oxidative proteins decreased in comparison with those in CAP patients with moderate severity. CONCLUSION: To sum up, our derived data show, that injury of erythrocytes’ redox-status and blood plasma components plays an essential role in development and progression CAP. PMID:27275344

  7. Modified IDSA/ATS Minor Criteria for Severe Community-Acquired Pneumonia Best Predicted Mortality

    PubMed Central

    Li, Hai-yan; Guo, Qi; Song, Wei-dong; Zhou, Yi-ping; Li, Ming; Chen, Xiao-ke; Liu, Hui; Peng, Hong-lin; Yu, Hai-qiong; Chen, Xia; Liu, Nian; Lü, Zhong-dong; Liang, Li-hua; Zhao, Qing-zhou; Jiang, Mei

    2015-01-01

    Abstract It is not clear whether the IDSA/ATS minor criteria for severe community-acquired pneumonia (CAP) could be simplified or even be modified to orchestrate improvements in predicting mortality. A retrospective cohort study of 1230 CAP patients was performed to simplify and to modify the scoring system by excluding 4 noncontributory or infrequent variables (leukopenia, hypothermia, hypotension, and thrombocytopenia) and by excluding these variables and then adding age ≥65 years, respectively. The simplification and modification were tested against a prospective 2-center validation cohort of 1409 adults with CAP. The increasing numbers of IDSA/ATS, simplified, and modified minor criteria present in the retrospective cohort were positively associated with the mortality, showing significant increased odds ratios for mortality of 2.711, 4.095, and 3.755, respectively. The validation cohort confirmed a similar pattern. The sensitivity, specificity, positive predictive value, and Youden index of modified minor criteria for mortality prediction were the best pattern in the retrospective cohort. High values of corresponding indices were confirmed in the validation cohort. The highest accuracy of the modified version for predicting mortality in the retrospective cohort was illustrated by the highest area under the receiver operating characteristic curve of 0.925 (descending order: modified, simplified, and IDSA/ATS minor criteria). The validation cohort confirmed a similar paradigm. The IDSA/ATS minor criteria could be simplified to 5 variables and then be modified to orchestrate improvements in predicting mortality in CAP patients. The modified version best predicted mortality. These were more suitable for clinic and emergency department. PMID:26356705

  8. Expanded CURB-65: a new score system predicts severity of community-acquired pneumonia with superior efficiency

    PubMed Central

    Liu, Jin-liang; Xu, Feng; Hui Zhou; Wu, Xue-jie; Shi, Ling-xian; Lu, Rui-qing; Farcomeni, Alessio; Venditti, Mario; Zhao, Ying-li; Luo, Shu-ya; Dong, Xiao-jun; Falcone, Marco

    2016-01-01

    Aim of this study was to develop a new simpler and more effective severity score for community-acquired pneumonia (CAP) patients. A total of 1640 consecutive hospitalized CAP patients in Second Affiliated Hospital of Zhejiang University were included. The effectiveness of different pneumonia severity scores to predict mortality was compared, and the performance of the new score was validated on an external cohort of 1164 patients with pneumonia admitted to a teaching hospital in Italy. Using age ≥ 65 years, LDH > 230 u/L, albumin < 3.5 g/dL, platelet count < 100 × 109/L, confusion, urea > 7 mmol/L, respiratory rate ≥ 30/min, low blood pressure, we assembled a new severity score named as expanded-CURB-65. The 30-day mortality and length of stay were increased along with increased risk score. The AUCs in the prediction of 30-day mortality in the main cohort were 0.826 (95% CI, 0.807–0.844), 0.801 (95% CI, 0.781–0.820), 0.756 (95% CI, 0.735–0.777), 0.793 (95% CI, 0.773–0.813) and 0.759 (95% CI, 0.737–0.779) for the expanded-CURB-65, PSI, CURB-65, SMART-COP and A-DROP, respectively. The performance of this bedside score was confirmed in CAP patients of the validation cohort although calibration was not successful in patients with health care-associated pneumonia (HCAP). The expanded CURB-65 is objective, simpler and more accurate scoring system for evaluation of CAP severity, and the predictive efficiency was better than other score systems. PMID:26987602

  9. Pneumococcal Surface Protein A Plays a Major Role in Streptococcus pneumoniae-Induced Immunosuppression.

    PubMed

    Saumyaa; Pujanauski, Lindsey; Colino, Jesus; Flora, Michael; Torres, Raul M; Tuomanen, Elaine; Snapper, Clifford M

    2016-05-01

    Intact, inactivated Streptococcus pneumoniae [including the unencapsulated S. pneumoniae, serotype 2 strain (R36A)] markedly inhibits the humoral immune response to coimmunized heterologous proteins, a property not observed with several other intact Gram-positive or Gram-negative bacteria. In this study, we determined the nature of this immunosuppressive property. Because phosphorylcholine (PC), a major haptenic component of teichoic acid in the S. pneumoniae cell wall, and lipoteichoic acid in the S. pneumoniae membrane were previously reported to be immunosuppressive when derived from filarial parasites, we determined whether R36A lacking PC (R36A(pc-)) was inhibitory. Indeed, although R36A(pc-) exhibited a markedly reduced level of inhibition of the IgG response to coimmunized chicken OVA (cOVA), no inhibition was observed when using several other distinct PC-expressing bacteria or a soluble, protein-PC conjugate. Further, treatment of R36A with periodate, which selectively destroys PC residues, had no effect on R36A-mediated inhibition. Because R36A(pc-) also lacks choline-binding proteins (CBPs) that require PC for cell wall attachment, and because treatment of R36A with trypsin eliminated its inhibitory activity, we incubated R36A in choline chloride, which selectively strips CBPs from its surface. R36A lacking CBPs lost most of its inhibitory property, whereas the supernatant of choline chloride-treated R36A, containing CBPs, was markedly inhibitory. Coimmunization studies using cOVA and various S. pneumoniae mutants, each genetically deficient in one of the CBPs, demonstrated that only S. pneumoniae lacking the CBP pneumococcal surface protein A lost its ability to inhibit the IgG anti-cOVA response. These results strongly suggest that PspA plays a major role in mediating the immunosuppressive property of S. pneumoniae. PMID:27029587

  10. Oxygen-driving and atomized mucosolvan inhalation combined with holistic nursing in the treatment of children severe bronchial pneumonia.

    PubMed

    Yang, Fang

    2015-07-01

    This paper aimed to discuss the method, effect and safety of oxygen-driving and atomized Mucosolvan inhalation combined with holistic nursing in the treatment of children severe bronchial pneumonia. Totally 90 children with severe bronchial pneumonia who were treated in our hospital from March 2013 to November 2013 were selected as the research objects. Based on randomized controlled principle, those children were divided into control group, test group I and test group II according to the time to enter the hospital, 30 in each group. Patients in control group was given conventional therapy; test group I was given holistic nursing combined with conventional therapy; test group II was given oxygen-driving and atomized Mucosolvan inhalation combined with holistic nursing on the basis of conventional therapy. After test, the difference of main symptoms in control group, test group I and II was of no statistical significance (P>0.05). Test group II was found with the best curative effect, secondary was test group I and control group was the last. It can be concluded that, oxygen-driving and atomized Mucosolvan inhalation combined with holistic nursing has certain effect in the treatment of children severe bronchial pneumonia and is better than holistic nursing only. PMID:26431648

  11. Rhodococcus equi hyperimmune plasma decreases pneumonia severity after a randomised experimental challenge of neonatal foals.

    PubMed

    Sanz, M G; Loynachan, A; Horohov, D W

    2016-03-12

    Since a vaccine is not available against Rhodococcus equi, R equi-specific hyperimmune plasma (HIP) is commonly used, although its efficacy remains controversial. The objective of this study was to evaluate the ability of a commercially available HIP to prevent clinical rhodococcal pneumonia in neonatal foals after experimental challenge. PMID:26932206

  12. Prokinetic Therapy Reduces Aspiration Pneumonia in Tube-Fed Patients With Severe Developmental Disabilities

    ERIC Educational Resources Information Center

    Pareek, Namita; Williams, John; Hanna, Deborah; Johnson, William D.; Minocha, Anil; Abell, Thomas L.

    2007-01-01

    To evaluate the clinical benefit of prokinetic therapy in aspiration pneumonia in patients with developmental disabilities, we conducted a retrospective study; records of 22 tube-fed patients were reviewed from December 1990 to October 1998 for a mean of 22.7 months before and 38.9 months during Cisapride therapy. Numbers of hospital admissions…

  13. Nivolumab-induced organizing pneumonia in a melanoma patient.

    PubMed

    Sano, Tasuku; Uhara, Hisashi; Mikoshiba, Yasutomo; Kobayashi, Aya; Uchiyama, Ryuhei; Tateishi, Kazunari; Yamamoto, Hiroshi; Okuyama, Ryuhei

    2016-03-01

    We report the case of a 70-year-old woman with vaginal melanoma and multiple metastases in the lung. After the third dose of nivolumab, decreased room-air resting arterial oxygen saturation with bilateral basal fine crackles on auscultation developed despite the absence of respiratory symptoms. Computed tomography showed ground-glass opacities with airspace consolidations scattered with a peculiar distribution, and most were observed around the existing metastatic tumors in the lung. From the 42nd day to the 56th day after the last administration of nivolumab, she received dexamethasone 1-2 mg/body for the prevention of adverse events after stereotactic radiation for brain metastasis. At 3 months after the last administration of nivolumab, a computed tomography scan revealed improvement of the pneumonia and a decreased size and number of metastatic lesions in the lung, although some lesions showed enlargement. Further examination is needed to clarify the relationship between the pattern of pneumonia after Nivo therapy and clinical effects. PMID:26759348

  14. Comparison of severe acute respiratory illness (sari) and clinical pneumonia case definitions for the detection of influenza virus infections among hospitalized patients, western Kenya, 2009-2013.

    PubMed

    Makokha, Caroline; Mott, Joshua; Njuguna, Henry N; Khagayi, Sammy; Verani, Jennifer R; Nyawanda, Bryan; Otieno, Nancy; Katz, Mark A

    2016-07-01

    Although the severe acute respiratory illness (SARI) case definition is increasingly used for inpatient influenza surveillance, pneumonia is a more familiar term to clinicians and policymakers. We evaluated WHO case definitions for severe acute respiratory illness (SARI) and pneumonia (Integrated Management of Childhood Illnesses (IMCI) for children aged <5 years and Integrated Management of Adolescent and Adult Illnesses (IMAI) for patients aged ≥13 years) for detecting laboratory-confirmed influenza among hospitalized ARI patients. Sensitivities were 84% for SARI and 69% for IMCI pneumonia in children aged <5 years and 60% for SARI and 57% for IMAI pneumonia in patients aged ≥13 years. Clinical pneumonia case definitions may be a useful complement to SARI for inpatient influenza surveillance. PMID:27219455

  15. Atypical pneumonia

    MedlinePlus

    ... that cause typical pneumonia. These include Legionella pneumophila , Mycoplasma pneumoniae , and Chlamydophila pneumoniae . Atypical pneumonia also tends to have milder symptoms than typical pneumonia. Causes Mycoplasma pneumonia is a type of atypical pneumonia. It ...

  16. Chlamydophila pneumoniae induces a sustained airway hyperresponsiveness and inflammation in mice

    PubMed Central

    Blasi, Francesco; Aliberti, Stefano; Allegra, Luigi; Piatti, Gioia; Tarsia, Paolo; Ossewaarde, Jacobus M; Verweij, Vivienne; Nijkamp, Frans P; Folkerts, Gert

    2007-01-01

    Background It has been reported that Chlamydophila (C.) pneumoniae is involved in the initiation and promotion of asthma and chronic obstructive pulmonary diseases (COPD). Surprisingly, the effect of C. pneumoniae on airway function has never been investigated. Methods In this study, mice were inoculated intranasally with C. pneumoniae (strain AR39) on day 0 and experiments were performed on day 2, 7, 14 and 21. Results We found that from day 7, C. pneumoniae infection causes both a sustained airway hyperresponsiveness and an inflammation. Interferon-γ (IFN-γ) and macrophage inflammatory chemokine-2 (MIP-2) levels in bronchoalveolar lavage (BAL)-fluid were increased on all experimental days with exception of day 7 where MIP-2 concentrations dropped to control levels. In contrast, tumor necrosis factor-α (TNF-α) levels were only increased on day 7. From day 7 to 21 epithelial damage and secretory cell hypertrophy was observed. It is suggested that, the inflammatory cells/mediators, the epithelial damage and secretory cell hypertrophy contribute to initiation of airway hyperresponsiveness. Conclusion Our study demonstrates for the first time that C. pneumoniae infection can modify bronchial responsiveness. This has clinical implications, since additional changes in airway responsiveness and inflammation-status induced by this bacterium may worsen and/or provoke breathlessness in asthma and COPD. PMID:18021431

  17. A Prospective Study of the Prevalence of Tuberculosis and Bacteraemia in Bangladeshi Children with Severe Malnutrition and Pneumonia Including an Evaluation of Xpert MTB/RIF Assay

    PubMed Central

    Chisti, Mohammod Jobayer; Graham, Stephen M.; Duke, Trevor; Ahmed, Tahmeed; Ashraf, Hasan; Faruque, Abu Syed Golam; La Vincente, Sophie; Banu, Sayera; Raqib, Rubhana; Salam, Mohammed Abdus

    2014-01-01

    Background Severe malnutrition is a risk factor for pneumonia due to a wide range of pathogens but aetiological data are limited and the role of Mycobacterium tuberculosis is uncertain. Methods We prospectively investigated severely malnourished young children (<5 years) with radiological pneumonia admitted over a 15-month period. Investigations included blood culture, sputa for microscopy and mycobacterial culture. Xpert MTB/RIF assay was introduced during the study. Study children were followed for 12 weeks following their discharge from the hospital. Results 405 eligible children were enrolled, with a median age of 10 months. Bacterial pathogens were isolated from blood culture in 18 (4.4%) children, of which 72% were Gram negatives. Tuberculosis was confirmed microbiologically in 7% (27/396) of children that provided sputum - 10 by culture, 21 by Xpert MTB/RIF assay, and 4 by both tests. The diagnostic yield from induced sputum was 6% compared to 3.5% from gastric aspirate. Sixty (16%) additional children had tuberculosis diagnosed clinically that was not microbiologically confirmed. Most confirmed tuberculosis cases did not have a positive contact history or positive tuberculin test. The sensitivity and specificity of Xpert MTB/RIF assay compared to culture was 67% (95% CI: 24–94) and 92% (95% CI: 87–95) respectively. Overall case-fatality rate was 17% and half of the deaths occurred in home following discharge from the hospital. Conclusion and Significance TB was common in severely malnourished Bangladeshi children with pneumonia. X-pert MTB/RIF assay provided higher case detection rate compared to sputum microscopy and culture. The high mortality among the study children underscores the need for further research aimed at improved case detection and management for better outcomes. PMID:24695758

  18. Severe rhinovirus pneumonia in a young woman taking performance-enhancing drugs.

    PubMed

    Mayer, Kristina Nadine; Wyder, Daniel; Spasic, Danijela; Herren, Thomas

    2016-01-01

    A 22-year-old woman presented to the emergency room of a local hospital with pleuritic chest pain. She regularly worked out and admitted to taking performance-enhancing drugs (PEDs). Clinical findings and further diagnostic work up revealed a diagnosis of perimyocarditis, and adequate therapy was initiated. During the course of the first day, the patient had to be intubated and mechanically ventilated. A diagnosis of bilateral pneumonia and acute respiratory distress syndrome (ARDS) due to an infection by rhinovirus spp was made. A smoking habit, the intense physical training and the use of PED's may have exacerbated the course of the viral pneumonia. After 12 days the patient could be extubated. The length of stay in the intensive care unit was 16 days. After hospital discharge, the patient went to a pulmonary rehabilitation facility for 2 weeks. The outcome was favourable and the patient resumed her strength and endurance training. PMID:26740273

  19. A comparison of human metapneumovirus and respiratory syncytial virus WHO-defined severe pneumonia in Moroccan children.

    PubMed

    Jroundi, I; Mahraoui, C; Benmessaoud, R; Moraleda, C; Tligui, H; Seffar, M; El Kettani, S E C; Benjelloun, B S; Chaacho, S; Muñoz-Almagro, C; Ruiz, J; Alonso, P L; Bassat, Q

    2016-02-01

    Acute respiratory infections remain the principal cause of morbidity and mortality in Moroccan children. Besides bacterial infections, respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are prominent among other viruses due to their high prevalence and association with severe clinical episodes. We aimed to describe and compare RSV- and hMPV-associated cases of WHO-defined severe pneumonia in a paediatric population admitted to Morocco's reference hospital. Children aged 2-59 months admitted to the Hôpital d'Enfants de Rabat, Morocco meeting WHO-defined severe pneumonia criteria were recruited during 14 months and thoroughly investigated to ascertain a definitive diagnosis. Viral prevalence of RSV, hMPV and other viruses causing respiratory symptoms was investigated in nasopharyngeal aspirate samples through the use of molecular methods. Of the 683 children recruited and included in the final analysis, 61/683 (8·9%) and 124/683 (18·2%) were infected with hMPV and RSV, respectively. Besides a borderline significant tendency for higher age in hMPV cases, patients infected with either of the viruses behaved similarly in terms of demographics, patient history, past morbidity and comorbidity, vaccination history, socioeconomic background and family environment. Clinical presentation on arrival was also similar for both viruses, but hMPV cases were associated with more severity than RSV cases, had a higher risk of intensive care need, and received antibiotic treatment more frequently. RSV and hMPV are common and potentially life-threatening causes of WHO-defined pneumonia in Moroccan children. Both viruses show indistinctive clinical symptomatology, but in Moroccan children, hMPV was associated with a more severe evolution. PMID:26143933

  20. Sociodemographic, Epidemiological, and Clinical Risk Factors for Childhood Pulmonary Tuberculosis in Severely Malnourished Children Presenting With Pneumonia

    PubMed Central

    Ahmed, Tahmeed; Shahid, Abu S. M. S. B.; Shahunja, K. M.; Bardhan, Pradip Kumar; Faruque, Abu Syeed Golam; Das, Sumon Kumar; Salam, Mohammed Abdus

    2015-01-01

    We aimed to evaluate sociodemographic, epidemiological, and clinical risk factors for pulmonary tuberculosis (PTB) in children presenting with severe acute malnutrition (SAM) and pneumonia. Children aged 0 to 59 months with SAM and radiologic pneumonia from April 2011 to July 2012 were studied in Bangladesh. Children with confirmed PTB (by culture and/or X-pert MTB/RIF) (cases = 27) and without PTB (controls = 81; randomly selected from 378 children) were compared. The cases more often had the history of contact with active PTB patient (P < .01) and exposure to cigarette smoke (P = .04) compared with the controls. In logistic regression analysis, after adjusting for potential confounders, the cases were independently associated with working mother (P = .05) and positive tuberculin skin test (TST; P = .02). Thus, pneumonia in SAM children is a common presentation of PTB and further highlights the importance of the use of simple TST and/or history of contact with active TB patients in diagnosing PTB in such children, especially in resource-limited settings. PMID:27335971

  1. Interstitial pneumonia induced by sorafenib in a patient with hepatocellular carcinoma: An autopsy case report

    PubMed Central

    YAMAGUCHI, TAKASHI; SEKI, TOSHIHITO; MIYASAKA, CHIKA; INOKUCHI, RYOSUKE; KAWAMURA, RINAKO; SAKAGUCHI, YUUTAKU; MURATA, MIKI; MATSUZAKI, KOICHI; NAKANO, YORIKA; UEMURA, YOSHIKO; OKAZAKI, KAZUICHI

    2015-01-01

    Sorafenib is a multikinase inhibitor currently approved in Japan for the treatment of unresectable hepatocellular carcinoma. Interstitial pneumonia induced by sorafenib may have a fatal outcome, and therefore, has recently been the focus of many studies. The current report presents an autopsy case of diffuse alveolar damage (DAD) that occurred in a 59-year-old male, who had been treated with sorafenib. The patient had been given sorafenib for six months and had exhibited no respiratory symptoms during this time. However, 19 days after sorafenib treatment was resumed, acute interstitial pneumonia developed. In previously reported cases, the first symptoms of pulmonary toxicity appeared following a limited treatment duration with sorafenib; this was in contrast to the patient in the current study, who developed the first symptoms after eight months. We therefore conclude that physicians must be aware of interstitial pneumonia as a potential pulmonary toxicity associated with sorafenib treatment when treatment with sorafenib is resumed, even after prolonged use. In addition, to best of our knowledge, this is the first case of a postmortem examination reported in patient with interstitial pneumonia induced by sorafenib treatment. PMID:25789013

  2. Indoor Air Pollution and Delayed Measles Vaccination Increase the Risk of Severe Pneumonia in Children: Results from a Case-Control Study in Mwanza, Tanzania

    PubMed Central

    PrayGod, George; Mukerebe, Crispin; Magawa, Ruth; Jeremiah, Kidola; Török, M. Estée

    2016-01-01

    Background Mortality due to severe pneumonia during childhood in resource-constrained settings is high, but data to provide basis for interventions to improve survival are limited. The objective of this study was to determine the risk factors for severe pneumonia in children aged under five years old in Mwanza, Tanzania. Methods We conducted a case-control study of children aged 2 to 59 months at Sekou-Toure regional hospital in Mwanza City, north-western, Tanzania from May 2013 to March 2014. Cases were children with severe pneumonia and controls were children with other illnesses. Data on demography, social-economical status, nutritional status, environmental factors, vaccination status, vitamin A supplementation and deworming, and nasopharyngeal carriage were collected and analysed using logistic regression. Results 117 patients were included in the study. Of these, 45 were cases and 72 controls. Cases were younger than controls, but there were no differences in social-economic or nutritional status between the two groups. In multiple regression, we found that an increased risk of severe pneumonia was associated with cooking indoors (OR 5.5, 95% CI: 1.4, 22.1), and delayed measles vaccination (OR 3.9, 95% CI: 1.1, 14.8). The lack of vitamin A supplementation in the preceding six month and Enterobacter spp nasopharyngeal carriage were not associated with higher risk of severe pneumonia. Age ≥24 months (OR 0.2, 95% CI: 0.04, 0.8) and not receiving antibiotics before referral (OR 0.3, 95% CI 0.1, 0.9) were associated with lower risk for severe pneumonia. Conclusions Indoor air pollution and delayed measles vaccination increase the risk for severe pneumonia among children aged below five years. Interventions to reduce indoor air pollution and to promote timely administration of measles vaccination are urgently needed to reduce the burden of severe pneumonia in children in Tanzania PMID:27508389

  3. The History of Mycoplasma pneumoniae Pneumonia

    PubMed Central

    Saraya, Takeshi

    2016-01-01

    In the United States in the 1930s, although the pathogen was not known, atypical pneumonia was clinically distinguished from pneumococcal pneumonia by its resistance to sulfonamides. Reimann (1938) reported seven patients with an unusual form of tracheo bronchopneumonia and severe constitutional symptoms. He believed the clinical picture of this disease differed from that of the disease caused by influenza viruses or known bacteria and instead suspected “primary atypical pneumonia.” For many years, the responsible infectious agent was tentatively classified as a filterable virus that could pass through a Seitz filter to remove bacteria and was reported to be a psittacosis-like or new virus. After that, Eaton et al. (1942, 1944, 1945) identified an agent that was the principal cause of primary atypical pneumonia using cotton rats, hamsters, and chick embryos. Eaton et al. (1942, 1944, 1945) did not perform an inoculation study in human volunteers. During the 1940s, there were three groups engaged in discovering the etiology of the primary atypical pneumonia. (1) Commission on Acute Respiratory Diseases Diseases directed by John Dingle, (2) Dr. Monroe Eaton’s group, the Virus Research Laboratory of the California State Public Health Department, (3) The Hospital of the Rockefeller Institute for Medical Research directed by Horsfall. During 1940s, the members of the Commission on Acute Respiratory Diseases concluded that the bacteria-free filtrates obtained from the patients, presumably containing a virus, could induce primary atypical pneumonia in human volunteers via Pinehurst trials. During 1950s, serological approaches for identification of the Eaton agent developed such as Fluorescent-Stainable Antibody, and at the beginning of the1960s, the Eaton agent successfully grew in media, and finally accepted as a cause of primary atypical pneumonia. Thus, technical difficulties with visualizing the agent and failure to recognize the full significance of the

  4. The History of Mycoplasma pneumoniae Pneumonia.

    PubMed

    Saraya, Takeshi

    2016-01-01

    In the United States in the 1930s, although the pathogen was not known, atypical pneumonia was clinically distinguished from pneumococcal pneumonia by its resistance to sulfonamides. Reimann (1938) reported seven patients with an unusual form of tracheo bronchopneumonia and severe constitutional symptoms. He believed the clinical picture of this disease differed from that of the disease caused by influenza viruses or known bacteria and instead suspected "primary atypical pneumonia." For many years, the responsible infectious agent was tentatively classified as a filterable virus that could pass through a Seitz filter to remove bacteria and was reported to be a psittacosis-like or new virus. After that, Eaton et al. (1942, 1944, 1945) identified an agent that was the principal cause of primary atypical pneumonia using cotton rats, hamsters, and chick embryos. Eaton et al. (1942, 1944, 1945) did not perform an inoculation study in human volunteers. During the 1940s, there were three groups engaged in discovering the etiology of the primary atypical pneumonia. (1) Commission on Acute Respiratory Diseases Diseases directed by John Dingle, (2) Dr. Monroe Eaton's group, the Virus Research Laboratory of the California State Public Health Department, (3) The Hospital of the Rockefeller Institute for Medical Research directed by Horsfall. During 1940s, the members of the Commission on Acute Respiratory Diseases concluded that the bacteria-free filtrates obtained from the patients, presumably containing a virus, could induce primary atypical pneumonia in human volunteers via Pinehurst trials. During 1950s, serological approaches for identification of the Eaton agent developed such as Fluorescent-Stainable Antibody, and at the beginning of the1960s, the Eaton agent successfully grew in media, and finally accepted as a cause of primary atypical pneumonia. Thus, technical difficulties with visualizing the agent and failure to recognize the full significance of the Pinehurst

  5. Effect of ganciclovir for the treatment of severe cytomegalovirus-associated pneumonia in children without a specific immunocompromised state

    PubMed Central

    2013-01-01

    Background This study aimed to evaluate the effectiveness of gancyclovir (GCV) treatment for severe cytomegalovirus (CMV)-associated pneumonia in immunocompetent children. Method We enrolled patients with CMV-associated severe pneumonia admitted to the Vietnam National Hospital of Pediatrics, Hanoi, Vietnam, from January 2010 to December 2011. On admission, though respiratory bacteria and viruses were not detected in tracheal aspirates, more than 5 × 103 copies/mL of CMV-DNA were detected in both tracheal aspirates and in blood plasma. GCV was given intravenously at a dose of 10 mg/kg/24 h for a duration of 14 days at most. The dose was then reduced to 5 mg/kg/24 h until CMV-DNA was not detected in plasma. The main study variables included clinical symptoms, complete blood count, hepatic and renal function, chest X-ray, CMV viral load, duration of GCV treatment and outcome. Results Forty-three patients were enrolled in the study. The median age of patients was 57 (interquartile range [IQR] 45–85) days. Clinical and laboratory findings included anemia (67.4%), leukocytosis (90.7%), hepatosplenomegaly (60.5%), elevated liver enzymes (74.4%), decreased ratio of CD4: CD8-positive T lymphocytes (69.4%), and decreased serum IgG concentration (25.7%). The median duration of GCV treatment was 12 days (IQR 7-21). Thirty-seven patients (86.0%) showed normal chest X-rays at the end of treatment. One infant died (2.3%); the other children (97.7%) were discharged in good condition. There was no severe toxicity associated with GCV treatment. Conclusion GCV is safe and effective for the treatment of severe CMV-associated pneumonia in children. PMID:24010978

  6. Deciphering tissue-induced Klebsiella pneumoniae lipid A structure.

    PubMed

    Llobet, Enrique; Martínez-Moliner, Verónica; Moranta, David; Dahlström, Käthe M; Regueiro, Verónica; Tomás, Anna; Cano, Victoria; Pérez-Gutiérrez, Camino; Frank, Christian G; Fernández-Carrasco, Helena; Insua, José Luis; Salminen, Tiina A; Garmendia, Junkal; Bengoechea, José A

    2015-11-17

    The outcome of an infection depends on host recognition of the pathogen, hence leading to the activation of signaling pathways controlling defense responses. A long-held belief is that the modification of the lipid A moiety of the lipopolysaccharide could help Gram-negative pathogens to evade innate immunity. However, direct evidence that this happens in vivo is lacking. Here we report the lipid A expressed in the tissues of infected mice by the human pathogen Klebsiella pneumoniae. Our findings demonstrate that Klebsiella remodels its lipid A in a tissue-dependent manner. Lipid A species found in the lungs are consistent with a 2-hydroxyacyl-modified lipid A dependent on the PhoPQ-regulated oxygenase LpxO. The in vivo lipid A pattern is lost in minimally passaged bacteria isolated from the tissues. LpxO-dependent modification reduces the activation of inflammatory responses and mediates resistance to antimicrobial peptides. An lpxO mutant is attenuated in vivo thereby highlighting the importance of this lipid A modification in Klebsiella infection biology. Colistin, one of the last options to treat multidrug-resistant Klebsiella infections, triggers the in vivo lipid A pattern. Moreover, colistin-resistant isolates already express the in vivo lipid A pattern. In these isolates, LpxO-dependent lipid A modification mediates resistance to colistin. Deciphering the lipid A expressed in vivo opens the possibility of designing novel therapeutics targeting the enzymes responsible for the in vivo lipid A pattern. PMID:26578797

  7. Deciphering tissue-induced Klebsiella pneumoniae lipid A structure

    PubMed Central

    Llobet, Enrique; Martínez-Moliner, Verónica; Moranta, David; Dahlström, Käthe M.; Regueiro, Verónica; Tomás, Anna; Cano, Victoria; Pérez-Gutiérrez, Camino; Frank, Christian G.; Fernández-Carrasco, Helena; Insua, José Luis; Salminen, Tiina A.; Garmendia, Junkal; Bengoechea, José A.

    2015-01-01

    The outcome of an infection depends on host recognition of the pathogen, hence leading to the activation of signaling pathways controlling defense responses. A long-held belief is that the modification of the lipid A moiety of the lipopolysaccharide could help Gram-negative pathogens to evade innate immunity. However, direct evidence that this happens in vivo is lacking. Here we report the lipid A expressed in the tissues of infected mice by the human pathogen Klebsiella pneumoniae. Our findings demonstrate that Klebsiella remodels its lipid A in a tissue-dependent manner. Lipid A species found in the lungs are consistent with a 2-hydroxyacyl-modified lipid A dependent on the PhoPQ-regulated oxygenase LpxO. The in vivo lipid A pattern is lost in minimally passaged bacteria isolated from the tissues. LpxO-dependent modification reduces the activation of inflammatory responses and mediates resistance to antimicrobial peptides. An lpxO mutant is attenuated in vivo thereby highlighting the importance of this lipid A modification in Klebsiella infection biology. Colistin, one of the last options to treat multidrug-resistant Klebsiella infections, triggers the in vivo lipid A pattern. Moreover, colistin-resistant isolates already express the in vivo lipid A pattern. In these isolates, LpxO-dependent lipid A modification mediates resistance to colistin. Deciphering the lipid A expressed in vivo opens the possibility of designing novel therapeutics targeting the enzymes responsible for the in vivo lipid A pattern. PMID:26578797

  8. Lung epithelial cells are essential effectors of inducible resistance to pneumonia

    PubMed Central

    Cleaver, Jeffrey O.; You, Dahui; Michaud, Danielle R.; Guzmán Pruneda, Francisco A.; Leiva Juarez, Miguel M.; Zhang, Jiexin; Weill, Patrick M.; Adachi, Roberto; Gong, Lei; Moghaddam, Seyed; Poynter, Matthew E.; Tuvim, Michael J.; Evans, Scott E.

    2013-01-01

    Infectious pneumonias are a leading cause of death worldwide, particularly among immunocompromised patients. Therapeutic stimulation of the lungs’ intrinsic defenses with a unique combination of inhaled Toll-like receptor agonists broadly protects mice against otherwise lethal pneumonias. As the survival benefit persists despite cytotoxic chemotherapy-related neutropenia, the cells required for protection were investigated. The inducibility of resistance was tested in mice with deficiencies of leukocyte lineages due to genetic deletions and in wild type mice with leukocyte populations significantly reduced by antibodies or toxins. Surprisingly, these serial reductions in leukocyte lineages did not appreciably impair inducible resistance, but targeted disruption of Toll-like receptor signaling in the lung epithelium resulted in complete abrogation of the protective effect. Isolated lung epithelial cells were also induced to kill pathogens in the absence of leukocytes. Proteomic and gene expression analyses of isolated epithelial cells and whole lungs revealed highly congruent antimicrobial responses. Taken together, these data indicate that lung epithelial cells are necessary and sufficient effectors of inducible resistance. These findings challenge conventional paradigms about the role of epithelia in antimicrobial defense and offer a novel potential intervention to protect patients with impaired leukocyte-mediated immunity from fatal pneumonias. PMID:23632328

  9. Lung epithelial cells are essential effectors of inducible resistance to pneumonia.

    PubMed

    Cleaver, J O; You, D; Michaud, D R; Pruneda, F A Guzmán; Juarez, M M Leiva; Zhang, J; Weill, P M; Adachi, R; Gong, L; Moghaddam, S J; Poynter, M E; Tuvim, M J; Evans, S E

    2014-01-01

    Infectious pneumonias are the leading cause of death worldwide, particularly among immunocompromised patients. Therapeutic stimulation of the lungs' intrinsic defenses with a unique combination of inhaled Toll-like receptor (TLR) agonists broadly protects mice against otherwise lethal pneumonias. As the survival benefit persists despite cytotoxic chemotherapy-related neutropenia, the cells required for protection were investigated. The inducibility of resistance was tested in mice with deficiencies of leukocyte lineages due to genetic deletions and in wild-type mice with leukocyte populations significantly reduced by antibodies or toxins. Surprisingly, these serial reductions in leukocyte lineages did not appreciably impair inducible resistance, but targeted disruption of TLR signaling in the lung epithelium resulted in complete abrogation of the protective effect. Isolated lung epithelial cells were also induced to kill pathogens in the absence of leukocytes. Proteomic and gene expression analyses of isolated epithelial cells and whole lungs revealed highly congruent antimicrobial responses. Taken together, these data indicate that lung epithelial cells are necessary and sufficient effectors of inducible resistance. These findings challenge conventional paradigms about the role of epithelia in antimicrobial defense and offer a novel potential intervention to protect patients with impaired leukocyte-mediated immunity from fatal pneumonias. PMID:23632328

  10. Role of CD 11/CD 18 in neutrophil emigration during acute and recurrent Pseudomonas aeruginosa-induced pneumonia in rabbits.

    PubMed Central

    Kumasaka, T.; Doyle, N. A.; Quinlan, W. M.; Graham, L.; Doerschuk, C. M.

    1996-01-01

    This study examined CD11/CD18-mediated adhesion in neutrophil emigration during acute and recurrent Pseudomonas aeruginosa-induced pneumonia. Neutrophil emigration during acute pneumonia was studied in anti-CD18 antibody or murine-IgG-pretreated rabbits 4 hours after intrabronchial instillation of P. aeruginosa. To examine emigration in recurrent pneumonias, rabbits given P. aeruginosa on day 0 received anti-CD18 antibody or IgG on day 7. A second instillate was placed either at the initial site or in a separate lobe, and emigration into alveolar spaces was quantitated morphometrically after 4 hours. The results show that CD11/CD18 was required for neutrophil emigration in acute pneumonias and in recurrent pneumonias that occurred at a site distant from the initial infection. However, when the recurrent pneumonia occurred in the previously inflamed site, CD11/CD18 was not required. When the same number of organisms were instilled on days 0 and 7, emigration was reduced to 15 to 20 percent of the number that migrated initially and only CD18-independent adhesion pathways were used. Increasing the concentration of organisms threefold increased emigration through both CD18-dependent and CD18-independent pathways. These data indicate that P. aeruginosa induces CD11/CD18-dependent emigration during acute pneumonia and recurrent pneumonia at previously uninflamed sites. However, adhesion pathways are altered in regions of chronic inflammation, and a greater proportion of neutrophil emigration occurs through CD11/CD18-independent pathways. PMID:8644870

  11. Association of Respiratory Viruses with Outcomes of Severe Childhood Pneumonia in Botswana

    PubMed Central

    Kelly, Matthew S.; Smieja, Marek; Luinstra, Kathy; Wirth, Kathleen E.; Goldfarb, David M.; Steenhoff, Andrew P.; Arscott-Mills, Tonya; Cunningham, Coleen K.; Boiditswe, Sefelani; Sethomo, Warona; Shah, Samir S.; Finalle, Rodney; Feemster, Kristen A.

    2015-01-01

    Background The highest incidence of childhood acute lower respiratory tract infection (ALRI) is in low- and middle-income countries. Few studies examined whether detection of respiratory viruses predicts ALRI outcomes in these settings. Methods We conducted prospective cohort and case-control studies of children 1-23 months of age in Botswana. Cases met clinical criteria for pneumonia and were recruited within six hours of presentation to a referral hospital. Controls were children without pneumonia matched to cases by primary care clinic and date of enrollment. Nasopharyngeal specimens were tested for respiratory viruses using polymerase chain reaction. We compared detection rates of specific viruses in matched case-control pairs. We examined the effect of respiratory syncytial virus (RSV) and other respiratory viruses on pneumonia outcomes. Results Between April 2012 and August 2014, we enrolled 310 cases, of which 133 had matched controls. Median ages of cases and controls were 6.1 and 6.4 months, respectively. One or more viruses were detected from 75% of cases and 34% of controls. RSV and human metapneumovirus were more frequent among cases than controls, but only enterovirus/rhinovirus was detected from asymptomatic controls. Compared with non-RSV viruses, RSV was associated with an increased risk of treatment failure at 48 hours [risk ratio (RR): 1.85; 95% confidence interval (CI): 1.20, 2.84], more days of respiratory support [mean difference (MD): 1.26 days; 95% CI: 0.30, 2.22 days], and longer duration of hospitalization [MD: 1.35 days; 95% CI: 0.20, 2.50 days], but lower in-hospital mortality [RR: 0.09; 95% CI: 0.01, 0.80] in children with pneumonia. Conclusions Respiratory viruses were detected from most children hospitalized with ALRI in Botswana, but only RSV and human metapneumovirus were more frequent than among children without ALRI. Detection of RSV from children with ALRI predicted a protracted illness course but lower mortality compared with non

  12. Mycoplasma pneumoniae Modulates STAT3-STAT6/EGFR-FOXA2 Signaling To Induce Overexpression of Airway Mucins

    PubMed Central

    Hao, Yonghua; Kuang, Zhizhou; Jing, Jia; Miao, Jinfeng; Mei, Li Yu; Lee, Ryan J.; Kim, Susie; Choe, Shawn; Krause, Duncan C.

    2014-01-01

    Aberrant mucin secretion and accumulation in the airway lumen are clinical hallmarks associated with various lung diseases such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis. Mycoplasma pneumoniae, long appreciated as one of the triggers of acute exacerbations of chronic pulmonary diseases, has recently been reported to promote excessive mucus secretion. However, the mechanism of mucin overproduction induced by M. pneumoniae remains unclear. This study aimed to determine the mechanism by which M. pneumoniae induces mucus hypersecretion by using M. pneumoniae infection of mouse lungs, human primary bronchial epithelial (NHBE) cells cultured at the air-liquid interface, and the conventionally cultured airway epithelial NCI-H292 cell line. We demonstrated that M. pneumoniae induced the expression of mucins MUC5AC and MUC5B by activating the STAT6-STAT3 and epidermal growth factor receptor (EGFR) signal pathways, which in turn downregulated FOXA2, a transcriptional repressor of mucin biosynthesis. The upstream stimuli of these pathways, including interleukin-4 (IL-4), IL-6, and IL-13, increased dramatically upon exposure to M. pneumoniae. Inhibition of the STAT6, STAT3, and EGFR signaling pathways significantly restored the expression of FOXA2 and attenuated the expression of airway mucins MUC5AC and MUC5B. Collectively, these studies demonstrated that M. pneumoniae induces airway mucus hypersecretion by modulating the STAT/EGFR-FOXA2 signaling pathways. PMID:25287927

  13. A new mechanism of vitamin C effects on A/FM/1/47(H1N1) virus-induced pneumonia in restraint-stressed mice.

    PubMed

    Cai, Ying; Li, Yi-Fang; Tang, Lu-Ping; Tsoi, Bun; Chen, Min; Chen, Huan; Chen, Xiao-Mei; Tan, Rui-Rong; Kurihara, Hiroshi; He, Rong-Rong

    2015-01-01

    It is well known that vitamin C could protect against influenza infection, but little is known about the mechanisms. This study aimed to investigate the influence and possible mechanisms of vitamin C on pneumonia induced by influenza virus in stressed mice. Results showed that restraint stress significantly increased the mortality and the severity of pneumonia in mice caused by A/FM/1/47(H1N1) virus infection, which was attenuated by oral administration of vitamin C (125 and 250 mg/kg). Moreover, vitamin C administration significantly decreased expression of susceptibility genes, including mitochondrial antiviral signaling (MAVS) and interferon regulatory factor 3 (IRF3), and increased expression of NF-κB. These work in conjunction to induce type I interferons (IFNs) and elicit innate antiviral response as key factors in RIG-I-mediated signal transduction pathway. The above effects of vitamin C were further found to relate with inhibition of excess CORT synthesis by regulating steroid hydroxylating enzymes in adrenal gland. In conclusion, the protective effects of vitamin C on influenza virus-caused pneumonia might be related to its inhibition of CORT synthesis, which reduces the susceptibility to influenza viral infection in restraint-stressed mice. These findings provide a new mechanism for the effects of vitamin C on influenza virus-induced pneumonia in restraint-stressed mice. PMID:25710018

  14. A New Mechanism of Vitamin C Effects on A/FM/1/47(H1N1) Virus-Induced Pneumonia in Restraint-Stressed Mice

    PubMed Central

    Cai, Ying; Li, Yi-Fang; Tang, Lu-Ping; Tsoi, Bun; Chen, Min; Chen, Huan; Chen, Xiao-Mei; Tan, Rui-Rong; Kurihara, Hiroshi; He, Rong-Rong

    2015-01-01

    It is well known that vitamin C could protect against influenza infection, but little is known about the mechanisms. This study aimed to investigate the influence and possible mechanisms of vitamin C on pneumonia induced by influenza virus in stressed mice. Results showed that restraint stress significantly increased the mortality and the severity of pneumonia in mice caused by A/FM/1/47(H1N1) virus infection, which was attenuated by oral administration of vitamin C (125 and 250 mg/kg). Moreover, vitamin C administration significantly decreased expression of susceptibility genes, including mitochondrial antiviral signaling (MAVS) and interferon regulatory factor 3 (IRF3), and increased expression of NF-κB. These work in conjunction to induce type I interferons (IFNs) and elicit innate antiviral response as key factors in RIG-I-mediated signal transduction pathway. The above effects of vitamin C were further found to relate with inhibition of excess CORT synthesis by regulating steroid hydroxylating enzymes in adrenal gland. In conclusion, the protective effects of vitamin C on influenza virus-caused pneumonia might be related to its inhibition of CORT synthesis, which reduces the susceptibility to influenza viral infection in restraint-stressed mice. These findings provide a new mechanism for the effects of vitamin C on influenza virus-induced pneumonia in restraint-stressed mice. PMID:25710018

  15. Procalcitonin levels and bacterial aetiology among COPD patients admitted to the ICU with severe pneumonia: a prospective cohort study

    PubMed Central

    2009-01-01

    Background Serum procalcitonin (PCT) is considered useful in predicting the likeliness of developing bacterial infections in emergency setting. In this study, we describe PCT levels overtime and their relationship with bacterial infection in chronic obstructive pulmonary disease (COPD) critically ill patients with pneumonia. Methods We conducted a prospective cohort study in an ICU of a University Hospital. All consecutive COPD patients admitted for pneumonia between September 2005 and September 2006 were included. Respiratory samples were tested for the presence of bacteria and viruses. Procalcitonin was sequentially assessed and patients classified according to the probability of the presence of a bacterial infection. Results Thirty four patients were included. The PCT levels were assessed in 32/34 patients, median values were: 0.493 μg/L [IQR, 0.131 to 1.471] at the time of admission, 0.724 μg/L [IQR, 0.167 to 2.646] at six hours, and 0.557 μg/L [IQR, 0.123 to 3.4] at 24 hours. The highest PCT (PCTmax) levels were less than 0.1 μg/L in 3/32 (9%) patients and greater than 0.25 μg/L in 22/32 (69%) patients, suggesting low and high probability of bacterial infection, respectively. Fifteen bacteria and five viruses were detected in 15/34 (44%) patients. Bacteria were not detected in patients with PCTmax levels < 0.1 μg/L. In contrast, bacteria were detected in 4/7 (57%) patients estimated unlikely to have a bacterial infection by PCT levels (PCTmax > 0.1 and < 0.25 μg/L). Conclusion Based on these results we suggest that a PCT level cut off > 0.1 μg/L may be more appropriate than 0.25 μg/L (previously proposed for non severe lower respiratory tract infection) to predict the probability of a bacterial infection in severe COPD patients with pneumonia. Further studies testing procalcitonin-based antibiotic strategies are needed in COPD patients with severe pneumonia. PMID:19772586

  16. Infection with Mycoplasma pneumoniae is not related to asthma control, asthma severity, and location of airway obstruction

    PubMed Central

    Ansarin, Khalil; Abedi, Siavoush; Ghotaslou, Reza; Soroush, Mohammad Hossein; Ghabili, Kamyar; Chapman, Kenneth R

    2011-01-01

    Background Mycoplasma pneumoniae is an organism that reportedly has a strong relationship to asthma. However, asthma severity and location of airway obstruction have not been compared between asthmatic patients with and without evidence for remote mycoplasma infection. Objectives The aim of this research was to study the relationship between previous M. pneumoniae infections in asthmatic patients and presence of any predilection for the involvement of central or peripheral airways, the severity of the disease, and asthma control. Methods Sixty-two patients with asthma were assessed by a validated asthma control test (ACT). All patients underwent spirometry and lung volume studies by body plethysmography. The forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), total lung capacity (TLC), residual volume (RV), and functional residual capacity (FRC) were measured. An oropharyngeal swab was obtained for polymerase chain reaction analysis to detect the mycoplasma antigen. Moreover, blood samples were obtained to measure the titration of antimycoplasma immunoglobulin M (IgM) and IgG antibodies. The asthmatic patients with a positive IgG for mycoplasma and negative PCR and negative IgM antibody were considered to have remote history of mycoplasma infection. The relationship between the asthma control using ACT score and pulmonary function variables were compared in patients with and without evidence for remote mycoplasma infection. Results The incidence of postnasal drip was higher among the patients with asthma who had no evidence for remote mycoplasma infection (61.3% vs 32%, P = 0.035). The median ACT score was 16.5 (11–22) and 20 (13.75–24) in patients with and without remote M. pneumoniae infection, respectively (P > 0.05). In addition, the medians of the predicted values of the pulmonary function test parameters (FEV1, FEV1/FVC, FRC, FRC/TLC, RV/TLC, maximal mean expiratory flow 25%–75%, forced expiratory flow [FEF] 50%, and FEF 75%) and

  17. Evaluation of the efficacy of a bacteriophage in the treatment of pneumonia induced by multidrug resistance Klebsiella pneumoniae in mice.

    PubMed

    Cao, Fang; Wang, Xitao; Wang, Linhui; Li, Zhen; Che, Jian; Wang, Lili; Li, Xiaoyu; Cao, Zhenhui; Zhang, Jiancheng; Jin, Liji; Xu, Yongping

    2015-01-01

    Multidrug-resistant Klebsiella pneumoniae (MRKP) has steadily grown beyond antibiotic control. However, a bacteriophage is considered to be a potential antibiotic alternative for treating bacterial infections. In this study, a lytic bacteriophage, phage 1513, was isolated using a clinical MRKP isolate KP 1513 as the host and was characterized. It produced a clear plaque with a halo and was classified as Siphoviridae. It had a short latent period of 30 min, a burst size of 264 and could inhibit KP 1513 growth in vitro with a dose-dependent pattern. Intranasal administration of a single dose of 2×10(9) PFU/mouse 2 h after KP 1513 inoculation was able to protect mice against lethal pneumonia. In a sublethal pneumonia model, phage-treated mice exhibited a lower level of K. pneumoniae burden in the lungs as compared to the untreated control. These mice lost less body weight and exhibited lower levels of inflammatory cytokines in their lungs. Lung lesion conditions were obviously improved by phage therapy. Therefore, phage 1513 has a great effect in vitro and in vivo, which has potential to be used as an alternative to an antibiotic treatment of pneumonia that is caused by the multidrug-resistant K. pneumoniae. PMID:25879036

  18. Evaluation of the Efficacy of a Bacteriophage in the Treatment of Pneumonia Induced by Multidrug Resistance Klebsiella pneumoniae in Mice

    PubMed Central

    Cao, Fang; Wang, Xitao; Wang, Linhui; Li, Zhen; Che, Jian; Wang, Lili; Li, Xiaoyu; Cao, Zhenhui; Zhang, Jiancheng; Jin, Liji; Xu, Yongping

    2015-01-01

    Multidrug-resistant Klebsiella pneumoniae (MRKP) has steadily grown beyond antibiotic control. However, a bacteriophage is considered to be a potential antibiotic alternative for treating bacterial infections. In this study, a lytic bacteriophage, phage 1513, was isolated using a clinical MRKP isolate KP 1513 as the host and was characterized. It produced a clear plaque with a halo and was classified as Siphoviridae. It had a short latent period of 30 min, a burst size of 264 and could inhibit KP 1513 growth in vitro with a dose-dependent pattern. Intranasal administration of a single dose of 2 × 109 PFU/mouse 2 h after KP 1513 inoculation was able to protect mice against lethal pneumonia. In a sublethal pneumonia model, phage-treated mice exhibited a lower level of K. pneumoniae burden in the lungs as compared to the untreated control. These mice lost less body weight and exhibited lower levels of inflammatory cytokines in their lungs. Lung lesion conditions were obviously improved by phage therapy. Therefore, phage 1513 has a great effect in vitro and in vivo, which has potential to be used as an alternative to an antibiotic treatment of pneumonia that is caused by the multidrug-resistant K. pneumoniae. PMID:25879036

  19. Severe leukopenia in Staphylococcus aureus-necrotizing, community-acquired pneumonia: risk factors and impact on survival

    PubMed Central

    2013-01-01

    Background Necrotizing pneumonia attributed to Panton-Valentine leukocidin-positive Staphylococcus aureus has mainly been reported in otherwise healthy children and young adults, with a high mortality rate. Erythroderma, airway bleeding, and leukopenia have been shown to be predictive of mortality. The objectives of this study were to define the characteristics of patients with severe leukopenia at 48-h hospitalization and to update our data regarding mortality predicting factors in a larger population than we had previously described. Methods It was designed as a case-case study nested in a cohort study. A total of 148 cases of community-acquired, necrotizing pneumonia were included. The following data were collected: basic demographic information, medical history, signs and symptoms, radiological findings and laboratory results during the first 48 h of hospitalization. The study population was divided into 2 groups: (1) with severe leukopenia (leukocyte count ≤3,000 leukocytes/mL, n=62) and (2) without severe leukopenia (>3,000 leukocytes/mL, n=86). Results Median age was 22 years, and the male-to-female gender ratio was 1.5. The overall in-hospital mortality rate was 41.2%. Death occurred in 75.8% of severe leukopenia cases with median survival time of 4 days, and in 16.3% of cases with leukocyte count >3,000/mL (P<0.001). Multivariate analysis indicated that the factors associated with severe leukopenia were influenza-like illness (adjusted odds ratio (aOR) 4.45, 95% CI (95% confidence interval) 1.67-11.88, P=0.003), airway bleeding (aOR 4.53, 95% CI 1.85-11.13, P=0.001) and age over 30 years (aOR 2.69, 95% CI 1.08-6.68, P=0.033). A personal history of furuncles appeared to be protective (OR 0.11, 95% CI 0.01-0.96, P=0.046). Conclusion S. aureus-necrotizing pneumonia is still an extremely severe disease in patients with severe leukopenia. Some factors could distinguish these patients, allowing better initial identification to initiate adapted, rapid

  20. Expression of Streptococcus pneumoniae Bacteriocins Is Induced by Antibiotics via Regulatory Interplay with the Competence System

    PubMed Central

    Slager, Jelle; Lake, Frank B.; Gericke, Oliver; Roberts, Ian S.; Rozen, Daniel E.; Veening, Jan-Willem

    2016-01-01

    Pneumococcal bacteriocins (pneumocins) are antibacterial toxins that mediate intra-species competition within the human host. However, the triggers of pneumocin expression are poorly understood. Using RNA-sequencing, we mapped the regulon of the pneumocin cluster (blp) of Streptococcus pneumoniae D39. Furthermore, by analogy with pneumococcal competence, we show that several antibiotics activate the blp-genes. Using real-time gene expression measurements we show that while the promoter driving expression of the two-component regulatory system blpR/H is constitutive, the remaining blp-promoters that control pneumocin expression, immunity and the inducer peptide BlpC, are pH-dependent and induced in the late exponential phase. Intriguingly, competence for genetic transformation, mediated by the paralogous ComD/E two-component quorum system, is induced by the same environmental cues. To test for interplay between these regulatory systems, we quantified the regulatory response to the addition of synthetic BlpC and competence-stimulating peptide (CSP). Supporting the idea of such interplay, we found that immediately upon addition of CSP, the blp-promoters were activated in a comD/E-dependent manner. After a delay, blp-expression was highly induced and was strictly dependent on blpRH and blpC. This raised the question of the mechanism of BlpC export, since bioinformatic analysis showed that the genes encoding the putative exporter for BlpC, blpAB, are not intact in strain D39 and most other strains. By contrast, all sequenced pneumococcal strains contain intact comAB genes, encoding the transport system for CSP. Consistent with the idea that comAB mediate BlpC export, we finally show that high-level expression of the blp-genes requires comAB. Together, our results demonstrate that regulation of pneumocin expression is intertwined with competence, explaining why certain antibiotics induce blp-expression. Antibiotic-induced pneumocin expression might therefore have

  1. Antibiotic Usage Prior and During Hospitalization for Clinical Severe Pneumonia in Children under Five Years of Age in Rabat, Morocco

    PubMed Central

    Jroundi, Imane; Benmessaoud, Rachid; Mahraoui, Chafiq; Moraleda, Cinta; Tligui, Houssain; Seffar, Myriam; Benjelloun, Badr Sououd; Vila, Jordi; Ruiz, Joaquim; Alonso, Pedro L.; Bassat, Quique

    2013-01-01

    Scarce and limited epidemiological, clinical and microbiological data are available regarding pediatric respiratory tract infections in the Kingdom of Morocco, a middle-income country in Northwestern Africa. Data on antibiotic usage for such infections are also scarce. A good understanding of pre-admission and intra-hospital usage of antibiotics in children with respiratory infections linked with an adequate surveillance of the antibiotic susceptibility from circulating pathogens could help policy makers improve their recommendations on management of respiratory infections. We hereby present data on antibiotic usage prior and during admission and antibiotic susceptibility of major circulating respiratory pathogens in children under five years of age admitted to the Hôpital d’Enfants de Rabat, Morocco, with a diagnosis of clinical severe pneumonia (using World Health Organization (WHO) standardized case definitions) during a period of 14 months (November 2010–December 2011), as part of a larger hospital-based surveillance study designed to understand the etiology and epidemiology of severe pneumonia cases among children. PMID:27029313

  2. Cytomegalovirus Colitis in a Critically Ill Patient Following Severe Legionella Pneumonia with Multiple Organ Failure.

    PubMed

    Nakashima, Kei; Aoshima, Masahiro; Suzuki, Fumi; Watanabe, Junko; Otsuka, Yoshihito

    2016-01-01

    A 68-year-old man visited an emergency department complaining of dyspnea. He was diagnosed to have Legionella pneumonia with multiple organ failure. Although his multiple organ failure improved, he suffered from persistent abdominal pain and diarrhea with continuous minor bleeding. Colonoscopy revealed a longitudinal ulcer of the rectum, below the peritoneal reflection. He was diagnosed with cytomegalovirus (CMV) colitis. Antiviral therapy with ganciclovir was initiated. He finally underwent a colostomy after a bowel stricture caused an intestinal outlet obstruction, which made oral intake impossible. Based on the present case, we believe that CMV colitis must be considered as one of the differential diagnoses when critically ill patients develop continuous diarrhea and abdominal pain. PMID:26935377

  3. Lung and chest wall mechanics in patients with acquired immunodeficiency syndrome and severe Pneumocystis carinii pneumonia.

    PubMed

    D'Angelo, E; Calderini, E; Robatto, F M; Puccio, P; Milic-Emili, J

    1997-10-01

    The aim of this study was to assess the mechanical characteristics of the respiratory system in patients with acquired immune deficiency syndrome (AIDS) and acute respiratory distress syndrome (ARDS) caused by Pneumocystis carinii pneumonia (PCP). In 12 mechanically ventilated patients, total respiratory system mechanics was assessed using the technique of rapid airway occlusion during constant flow inflation, and was partitioned into lung and chest wall components using the oesophageal balloon technique. We measured interrupter resistance (Rint), which mainly reflects airway resistance, additional resistance (deltaR) due to viscoelastic behaviour and time constant inequalities, and static elastance (Est). In addition, the static inflation volume-pressure (V-P) curve was assessed. In eight patients, computed tomography scans were performed within 2 days of the assessment of respiratory mechanics. Compared to values reported in the literature for normal subjects, Est and deltaR were markedly increased in AIDS patients with PCP, whilst Rint exhibited a relatively smaller increase. These changes, which involved only the lung and airways, were mainly due to the reduction of ventilated lung units, but additional factors were involved to cause independent modifications of lung stiffness, airway calibre, and viscoelastic properties. The changes in Rint, deltaR, and Est were similar to those observed in other studies on patients with ARDS of different aetiologies. At variance with common observations in the latter patients, none of the AIDS patients with PCP exhibited an inflection point on the static inflation V-P curve, suggesting little or no alveolar recruitment during lung inflation. This finding could be related to the distinctive histopathology of Pneumocystis carinii pneumonia. Indeed, computed tomography revealed homogeneous diffuse interstitial and alveolar infiltration rather than the dense, dependent opacities observed in other studies on acute respiratory

  4. Zinc as an adjunct to antibiotics for the treatment of severe pneumonia in children <5 years: a meta-analysis of randomised-controlled trials.

    PubMed

    Tie, Hong-Tao; Tan, Qi; Luo, Ming-Zhu; Li, Qiang; Yu, Jia-Lin; Wu, Qing-Chen

    2016-03-14

    The effect of Zn, as an adjunct to antibiotics, on the treatment of severe pneumonia in young children is still under debate; therefore, we performed a meta-analysis to evaluate the therapeutic role of Zn for severe pneumonia in children younger than 5 years. PubMed, Cochrane library and Embase databases were systematically searched from inception until October 2015 for randomised-controlled trials (RCT) that assessed the effect of Zn as an adjunct to antibiotics for severe pneumonia. Random-effects model was used for calculating the pooled estimates, and intention-to-treat principle was also applied. Nine RCT involving 2926 children were included. Overall, the pooled results showed that adjunct treatment with Zn failed to reduce the time to recovery from severe pneumonia (hazard ratios (HR)=1·04; 95% CI 0·90, 1·19; I(2)=39%; P=0·58), hospital length of stay (HR=1·04; 95% CI 0·83, 1·33; I(2)=57%; P=0·74), treatment failure (relative risk (RR)=0·95; 95% CI 0·79, 1·14; I(2)=20%; P=0·58) or change of antibiotics (RR=1·07; 95% CI 0·79, 1·45; I(2)=44%; P=0·67). In addition, continuous outcomes were consistent while meta-analysed with standard mean difference, and all outcomes remained stable in intention-to-treat analysis. No significant differences were observed in the two groups between death rate, adverse events or recovery times of severe pneumonia indicators. Our results suggested that adjunct treatment with Zn failed to benefit young children in the treatment of severe pneumonia. Considering the clinical heterogeneity, baseline characteristics of children, definition of severe pneumonia and Zn supplement way should be taken into consideration in future research. This study was registered at PRESPERO as CRD42015019798. PMID:26811108

  5. Thiopentone induced coma after severe birth asphyxia.

    PubMed Central

    Eyre, J A; Wilkinson, A R

    1986-01-01

    The aim of this study was to determine the feasibility of inducing a prolonged coma in severely asphyxiated newborn babies by the infusion of high dose thiopentone. In six severely asphyxiated babies the electroencephalograph (EEG) and blood pressure were monitored continuously. Thiopentone was infused at a rate sufficient to suppress completely the EEG providing the mean blood pressure remained above 35 mm Hg; it was continued until there was no evidence of cerebral oedema for 24 hours. In two the infusion was stopped prematurely because of hypotension that was unresponsive to treatment. In the other four a deep coma was maintained for a median duration of 127 hours. All developed pharmacodynamic tolerance to the thiopentone and showed non-linear elimination kinetics. Three babies died; the three survivors have moderate to severe handicap. It was concluded that with full intensive care it is possible to induce a deep coma; the outcome does not seem to be improved, however, and the incidence of complications was high. PMID:3789788

  6. Pneumocystis jiroveci pneumonia

    MedlinePlus

    Pneumocystis pneumonia can be life threatening, causing respiratory failure that can lead to death. People with this condition need early and effective treatment. For moderate to severe pneumocystis pneumonia in people with ...

  7. Analysis of Phase 3 telavancin nosocomial pneumonia data excluding patients with severe renal impairment and acute renal failure

    PubMed Central

    Torres, A.; Rubinstein, E.; Corey, G. R.; Stryjewski, M. E.; Barriere, S. L.

    2014-01-01

    Objectives Telavancin is approved in Europe for the treatment of nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus when other alternatives are not suitable. The approved European prescribing information contraindicates the use of telavancin in patients with severe renal impairment (creatinine clearance <30 mL/min, including patients on haemodialysis) and pre-existing acute renal failure owing to the higher observed mortality in these patients. Data from the ATTAIN studies were reanalysed, excluding patients with these contraindicating conditions at baseline. (At the time of submission of this article, the European marketing authorization of telavancin for the treatment of nosocomial pneumonia was suspended pending evidence of a new European Medicines Agency-approved supplier. Clinigen Healthcare Ltd, Theravance's commercialization partner for telavancin in Europe, is in the process of seeking approval of a new manufacturing source.) Methods A post hoc analysis of data from two Phase 3 ATTAIN trials of telavancin for the treatment of Gram-positive nosocomial pneumonia assessing clinical outcomes and safety. Results The all-treated population for this analysis represented 84.2% (1266/1503) of the ATTAIN all-treated population. The cure rates in the clinically evaluable population were similar in the telavancin (82.5%, 231/280) and vancomycin (81.3%, 243/299) groups [treatment difference (95% CI): 1.3% (−5.0% to 7.6%)], and were consistent with the overall ATTAIN study results. The cure rate was higher in the telavancin than the vancomycin treatment group in microbiologically evaluable patients with only Gram-positive pathogens isolated at baseline [85.0% (130/153) versus 75.2% (109/145), respectively; treatment difference (95% CI): 9.7% (0.6%–18.8%)]. The incidences of adverse events were similar between treatment groups and consistent with the overall findings of the ATTAIN study. Conclusions This analysis demonstrated that in the subset

  8. Heme oxygenase inhibition enhances neutrophil migration into the bronchoalveolar spaces and improves the outcome of murine pneumonia-induced sepsis.

    PubMed

    Czaikoski, Paula Giselle; Nascimento, Daniele Carvalho; Sônego, Fabiane; de Freitas, Andressa; Turato, Walter Miguel; de Carvalho, Michel A; Santos, Raquel Souza; de Oliveira, Gisele Pena; dos Santos Samary, Cynthia; Tefe-Silva, Cristiane; Alves-Filho, José C; Ferreira, Sérgio Henrique; Rossi, Marcos Antonio; Rocco, Patricia Rieken Macedo; Spiller, Fernando; Cunha, Fernando Queiroz

    2013-04-01

    A reduction of the neutrophil migration into the site of infection during cecal ligation and puncture-induced sepsis increases host mortality. Inhibition of heme oxygenase (HO) prevents this neutrophil paralysis and improves host survival in the cecal ligation and puncture model. Taking into account that almost 50% of all sepsis cases are a consequence of pneumonia, we designed the present study to determine the role of HO in an experimental model of pneumonia-induced sepsis. The objective of this study was to evaluate whether the inhibition of HO improves the outcome and pathophysiologic changes of sepsis induced by an intratracheal instillation of Klebsiella pneumoniae. The pretreatment of mice subjected to pneumonia-induced sepsis with ZnDPBG (zinc deuteroporphyrin 2,4-bis glycol), a nonspecific HO inhibitor, increased the number of neutrophils in the bronchoalveolar spaces, reduced the bacterial load at the site of infection, and prevented the upregulation of CD11b and the downregulation of CXCR2 on blood neutrophils. Moreover, the pretreatment with ZnDPBG decreased alveolar collapse, attenuating the deleterious changes in pulmonary mechanics and gas exchanges and, as a consequence, improved the survival rate of mice from 0% to ∼20%. These results show that heme oxygenase is involved in the pathophysiology of pneumonia-induced sepsis and suggest that HO inhibitors could be helpful for the management of this disease. PMID:23481491

  9. Pazopanib-Induced Severe Acute Pancreatitis.

    PubMed

    Kawakubo, Kazumichi; Hata, Hiroo; Kawakami, Hiroshi; Kuwatani, Masaki; Kawahata, Shuhei; Kubo, Kimitoshi; Imafuku, Keisuke; Kitamura, Shinya; Sakamoto, Naoya

    2015-01-01

    Pazopanib is an oral angiogenesis inhibitor targeting vascular endothelial growth factor receptors, platelet-derived growth factor receptors, and c-Kit approved for the treatment of renal cell carcinoma and soft tissue sarcoma. Nonselective kinase inhibitors, such as sunitinib and sorafenib, are known to be associated with acute pancreatitis. There are few case reports of severe acute pancreatitis induced by pazopanib treatment. We present a case of severe acute pancreatitis caused by pazopanib treatment for cutaneous angiosarcoma. The patient was an 82-year-old female diagnosed with cutaneous angiosarcoma. She had been refractory to docetaxel treatment and began pazopanib therapy. Three months after pazopanib treatment, CT imaging of the abdomen showed the swelling of the pancreas and surrounding soft tissue inflammation without abdominal pain. After she continued pazopanib treatment for 2 months, she presented with nausea and appetite loss. Abdominal CT showed the worsening of the surrounding soft tissue inflammation of the pancreas. Serum amylase and lipase levels were 296 and 177 IU/l, respectively. She was diagnosed with acute pancreatitis induced by pazopanib treatment and was managed conservatively with discontinuation of pazopanib, but the symptoms did not improve. Subsequently, an abdominal CT scan demonstrated the appearance of a pancreatic pseudocyst. She underwent endoscopic ultrasound-guided pseudocyst drainage using a flared-end fully covered self-expandable metallic stent. Then, the symptoms resolved without recurrence. Due to the remarkable progress of molecular targeted therapy, the oncologist should know that acute pancreatitis was recognized as a potential adverse event of pazopanib treatment and could proceed to severe acute pancreatitis. PMID:26464570

  10. Pathogenesis of influenza virus-induced pneumonia: involvement of both nitric oxide and oxygen radicals.

    PubMed Central

    Akaike, T; Noguchi, Y; Ijiri, S; Setoguchi, K; Suga, M; Zheng, Y M; Dietzschold, B; Maeda, H

    1996-01-01

    The role of nitric oxide (NO) in the pathogenesis of influenza virus-induced pneumonia in mice was investigated. Experimental influenza virus pneumonia was produced with influenza virus A/Kumamoto/Y5/67(H2N2). Both the enzyme activity of NO synthase (NOS) and mRNA expression of the inducible NOS were greatly increased in the mouse lungs; increases were mediated by interferon gamma. Excessive production of NO in the virus-infected lung was studied further by using electron spin resonance (ESR) spectroscopy. In vivo spin trapping with dithiocarbamate-iron complexes indicated that a significant amount of NO was generated in the virus-infected lung. Furthermore, an NO-hemoglobin ESR signal appeared in the virus-infected lung, and formation of NO-hemoglobin was significantly increased by treatment with superoxide dismutase and was inhibited by N(omega)-monomethyl-L-arginine (L-NMMA) administration. Immunohistochemistry with a specific anti-nitrotyrosine antibody showed intense staining of alveolar phagocytic cells such as macrophages and neutrophils and of intraalveolar exudate in the virus-infected lung. These results strongly suggest formation of peroxynitrite in the lung through the reaction of NO with O2-, which is generated by alveolar phagocytic cells and xanthine oxidase. In addition, administration of L-NMMA resulted in significant improvement in the survival rate of virus-infected mice without appreciable suppression of their antiviral defenses. On the basis of these data, we conclude that NO together with O2- which forms more reactive peroxynitrite may be the most important pathogenic factors in influenza virus-induced pneumonia in mice. Images Fig. 1 Fig. 5 PMID:8637894

  11. Amoxicillin plus temocillin as an alternative empiric therapy for the treatment of severe hospital-acquired pneumonia: results from a retrospective audit.

    PubMed

    Habayeb, H; Sajin, B; Patel, K; Grundy, C; Al-Dujaili, A; Van de Velde, S

    2015-08-01

    A formulary decision was made at a large provider of acute hospital services in Surrey to replace piperacillin/tazobactam with amoxicillin+temocillin for the empiric treatment of severe hospital-acquired pneumonia. This decision was made because the use of broad-spectrum-β-lactam antibiotics is a known risk factor for Clostridium difficile infection (CDI) and for the selection of resistance. After the antibiotic formulary was changed, a retrospective audit was conducted to assess the effect of this change. Data from patients hospitalised between January 2011 and July 2012 for severe hospital-acquired pneumonia and treated empirically with piperacillin/tazobactam or amoxicillin+temocillin were reviewed retrospectively. Clinical characteristics of patients, data related to the episode of pneumonia, clinical success and incidence of significant diarrhoea and CDI were analysed. One hundred ninety-two episodes of severe hospital-acquired pneumonia in 188 patients were identified from hospital records. Ninety-eight patients received piperacillin/tazobactam and 94 amoxicillin+temocillin. At baseline, the two treatment groups were comparable, except that more patients with renal insufficiency were treated with piperacillin/tazobactam. Clinical success was comparable (80 versus 82 %; P = 0.86), but differences were observed between piperacillin/tazobactam and amoxicillin+temocillin for the rates of significant diarrhoea (34 versus 4 %, respectively; P < 0.0001) and for CDI (7 versus 0 %, respectively; P < 0.0028). This preliminary study suggests that the combination amoxicillin+temocillin is a viable alternative to piperacillin/tazobactam for the treatment of severe hospital-acquired pneumonia. This combination appears to be associated with fewer gastrointestinal adverse events. Further studies are needed to evaluate the place of amoxicillin+temocillin as empiric treatment of severe hospital-acquired pneumonia. PMID:25987247

  12. Chlamydia pneumoniae infection induced allergic airway sensitization is controlled by regulatory T-cells and plasmacytoid dendritic cells.

    PubMed

    Crother, Timothy R; Schröder, Nicolas W J; Karlin, Justin; Chen, Shuang; Shimada, Kenichi; Slepenkin, Anatoly; Alsabeh, Randa; Peterson, Ellena; Arditi, Moshe

    2011-01-01

    Chlamydia pneumoniae (CP) is associated with induction and exacerbation of asthma. CP infection can induce allergic airway sensitization in mice in a dose- and time-dependent manner. Allergen exposure 5 days after a low dose (mild-moderate), but not a high dose (severe) CP infection induces antigen sensitization in mice. Innate immune signals play a critical role in controlling CP infection induced allergic airway sensitization, however these mechanisms have not been fully elucidated. Wild-type, TLR2-/-, and TLR4-/- mice were infected intranasally (i.n.) with a low dose of CP, followed by i.n. exposure to human serum albumin (HSA) and challenged with HSA 2 weeks later. Airway inflammation, immunoglobulins, eosinophils, and goblet cells were measured. Low dose CP infection induced allergic sensitization in TLR2-/- mice, but not in TLR4-/- mice, due to differential Treg responses in these genotypes. TLR2-/- mice had reduced numbers of Tregs in the lung during CP infection while TLR4-/- mice had increased numbers. High dose CP infection resulted in an increase in Tregs and pDCs in lungs, which prevented antigen sensitization in WT mice. Depletion of Tregs or pDCs resulted in allergic airway sensitization. We conclude that Tregs and pDCs are critical determinants regulating CP infection-induced allergic sensitization. Furthermore, TLR2 and TLR4 signaling during CP infection may play a regulatory role through the modulation of Tregs. PMID:21695198

  13. Mycoplasma ovipneumoniae--a primary cause of severe pneumonia epizootics in the Norwegian Muskox (Ovibos moschatus) population.

    PubMed

    Handeland, Kjell; Tengs, Torstein; Kokotovic, Branko; Vikøren, Turid; Ayling, Roger D; Bergsjø, Bjarne; Sigurðardóttir, Olöf G; Bretten, Tord

    2014-01-01

    The Norwegian muskox (Ovibos moschatus) population lives on the high mountain plateau of Dovre and originates from animals introduced from Greenland. In the late summers of 2006 and 2012, severe outbreaks of pneumonia with mortality rates of 25-30% occurred. During the 2012 epidemic high quality samples from culled sick animals were obtained for microbiological and pathological examinations. High throughput sequencing (pyrosequencing) of pneumonic lung tissue revealed high concentrations of Mycoplasma ovipneumoniae in all six animals examined by this method and Pasteurella multocida subsp. multocida in four animals, whereas no virus sequences could be identified. Mycoplasma ovipneumoniae and P. multocida multocida were also isolated by culture. Using real time PCR on lung swabs, M. ovipneumoniae was detected in all of the 19 pneumonic lungs examined. Gross pathological examination revealed heavy consolidations primarily in the cranial parts of the lungs and it also identified one case of otitis media. Histologically, lung lesions were characterized as acute to subacute mixed exudative and moderately proliferative bronchoalveolar pneumonia. Immunohistochemical (IHC) examination revealed high load of M. ovipneumoniae antigens within lung lesions, with particularly intensive staining in the neutrophils. Similar IHC finding were observed in archived lung tissue blocks from animals examined during the 2006 epidemic. An M. ovipneumoniae specific ELISA was applied on bio-banked muskox sera from stray muskoxen killed in the period 2004-2013 and sick muskoxen culled, as well as sera from wild reindeer (Rangifer tarandus tarandus) on Dovre and muskoxen from Greenland. Serology and mycoplasma culturing was also carried out on sheep that had been on pasture in the muskox area during the outbreak in 2012. Our findings indicated separate introductions of M. ovipneumoniae infection in 2006 and 2012 from infected co-grazing sheep. Salt licks shared by the two species were a

  14. Clinical Risk Factors of Death From Pneumonia in Children with Severe Acute Malnutrition in an Urban Critical Care Ward of Bangladesh

    PubMed Central

    Chisti, Mohammod Jobayer; Salam, Mohammed Abdus; Ashraf, Hasan; Faruque, Abu S. G.; Bardhan, Pradip Kumar; Hossain, Md Iqbal; Shahid, Abu S. M. S. B.; Shahunja, K. M.; Das, Sumon Kumar; Imran, Gazi; Ahmed, Tahmeed

    2013-01-01

    Background Risks of death are high when children with pneumonia also have severe acute malnutrition (SAM) as a co-morbidity. However, there is limited published information on risk factors of death from pneumonia in SAM children. We evaluated clinically identifiable factors associated with death in under-five children who were hospitalized for the management of pneumonia and SAM. Methods For this unmatched case-control design, SAM children of either sex, aged 0–59 months, admitted to the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) during April 2011 to July 2012 with radiological pneumonia were studied. The SAM children with pneumonia who had fatal outcome constituted the cases (n = 35), and randomly selected SAM children with pneumonia who survived constituted controls (n = 105). Results The median (inter-quartile range) age (months) was comparable among the cases and the controls [8.0 (4.9, 11.0) vs. 9.7 (5.0, 18.0); p = 0.210)]. In logistic regression analysis, after adjusting for potential confounders, such as vomiting, abnormal mental status, and systolic hypotension (<70 mm of Hg) in absence of dehydration, fatal cases of severely malnourished under-five children with pneumonia were more often hypoxemic (OR = 23.15, 95% CI = 4.38–122.42), had clinical dehydration (some/severe) (OR = 9.48, 95% CI = 2.42–37.19), abdominal distension at admission (OR = 4.41, 95% CI = 1.12–16.52), and received blood transfusion (OR = 5.50, 95% CI = 1.21–24.99) for the management of crystalloid resistant systolic hypotension. Conclusion and Significance We identified hypoxemia, clinical dehydration, and abdominal distension as the independent predictors of death in SAM children with pneumonia. SAM children with pneumonia who required blood transfusion for the management of crystalloid resistant systolic hypotension were also at risk for death. Thus, early identification and

  15. DAS181 Treatment of Severe Parainfluenza Virus 3 Pneumonia in Allogeneic Hematopoietic Stem Cell Transplant Recipients Requiring Mechanical Ventilation

    PubMed Central

    Dhakal, B.; D'Souza, A.; Pasquini, M.; Saber, W.; Fenske, T. S.; Moss, R. B.; Drobyski, W. R.; Hari, P.; Abidi, M. Z.

    2016-01-01

    Parainfluenza virus (PIV) may cause life-threatening pneumonia in allogeneic hematopoietic stem cell transplant (HSCT) recipients. Currently, there are no proven effective therapies. We report the use of inhaled DAS181, a novel sialidase fusion protein, for treatment of PIV type 3 pneumonia in two allogeneic hematopoietic SCT recipients with respiratory failure. PMID:26941799

  16. Aspiration pneumonia

    MedlinePlus

    Anaerobic pneumonia; Aspiration of vomitus; Necrotizing pneumonia; Aspiration pneumonitis ... The type of bacteria that caused the pneumonia depends on: Your ... facility, for example) Whether you were recently hospitalized ...

  17. Vaccination with Klebsiella pneumoniae-derived extracellular vesicles protects against bacteria-induced lethality via both humoral and cellular immunity.

    PubMed

    Lee, Won-Hee; Choi, Hyun-Il; Hong, Sung-Wook; Kim, Kwang-Sun; Gho, Yong Song; Jeon, Seong Gyu

    2015-01-01

    The emergence of multidrug-resistant Klebsiella pneumoniae highlights the need to develop preventive measures to ameliorate Klebsiella infections. Bacteria-derived extracellular vesicles (EVs) are spherical nanometer-sized proteolipids enriched with outer membrane proteins. Gram-negative bacteria-derived EVs have gained interest for use as nonliving complex vaccines. In the present study, we evaluated whether K. pneumoniae-derived EVs confer protection against bacteria-induced lethality. K. pneumoniae-derived EVs isolated from in vitro bacterial culture supernatants induced innate immunity, including the upregulation of co-stimulatory molecule expression and proinflammatory mediator production. EV vaccination via the intraperitoneal route elicited EV-reactive antibodies and interferon-gamma-producing T-cell responses. Three vaccinations with the EVs prevented bacteria-induced lethality. As verified by sera and splenocytes adoptive transfer, the protective effect of EV vaccination was dependent on both humoral and cellular immunity. Taken together, these findings suggest that K. pneumoniae-derived EVs are a novel vaccine candidate against K. pneumoniae infections. PMID:26358222

  18. Vaccination with Klebsiella pneumoniae-derived extracellular vesicles protects against bacteria-induced lethality via both humoral and cellular immunity

    PubMed Central

    Lee, Won-Hee; Choi, Hyun-Il; Hong, Sung-Wook; Kim, Kwang-sun; Gho, Yong Song; Jeon, Seong Gyu

    2015-01-01

    The emergence of multidrug-resistant Klebsiella pneumoniae highlights the need to develop preventive measures to ameliorate Klebsiella infections. Bacteria-derived extracellular vesicles (EVs) are spherical nanometer-sized proteolipids enriched with outer membrane proteins. Gram-negative bacteria-derived EVs have gained interest for use as nonliving complex vaccines. In the present study, we evaluated whether K. pneumoniae-derived EVs confer protection against bacteria-induced lethality. K. pneumoniae-derived EVs isolated from in vitro bacterial culture supernatants induced innate immunity, including the upregulation of co-stimulatory molecule expression and proinflammatory mediator production. EV vaccination via the intraperitoneal route elicited EV-reactive antibodies and interferon-gamma-producing T-cell responses. Three vaccinations with the EVs prevented bacteria-induced lethality. As verified by sera and splenocytes adoptive transfer, the protective effect of EV vaccination was dependent on both humoral and cellular immunity. Taken together, these findings suggest that K. pneumoniae-derived EVs are a novel vaccine candidate against K. pneumoniae infections. PMID:26358222

  19. Clinical severity of Mycoplasma pneumoniae (MP) infection is associated with bacterial load in oropharyngeal secretions but not with MP genotype

    PubMed Central

    2010-01-01

    Background Disease severity in Mycoplasma pneumoniae (MP) infection could potentially be related to bacterial factors such as MP genotype (MP1 or MP2; distinguished by different adhesions proteins) or bacterial load in airway secretions. We have compared these parameters in patients who were hospitalized for MP pneumonia, with outpatients with mild MP disease. Methods MP bacterial load was measured by real-time PCR in 45 in- and outpatients ("clinical study group") in whom MP DNA had been detected in oropharyngeal secretions by PCR. In addition, genotype and phylogenetic relationships were determined. The phylogenetical assessment was done by partial DNA sequencing of the P1 gene on isolates from 33 patients in the clinical study-group where sufficient DNA was available. The assessment was further extended to isolates from 13 MP-positive family members and 37 unselected MP positive patients from the two subsequent years and two different geographical locations. In total 83 strains were molecular characterized. Results Mean MP loads were significantly higher in 24 hospitalized patients than in 21 outpatients (1600 vs. 170 genomic equivalents/μL, p = 0.009). This difference remained significant after adjustment for age and days between disease onset and sampling. Hospitalized patients also had higher C-reactive protein levels. Mean levels were 188 vs 20 mg/L (p = 0,001). The genotype assessment showed MP genotype 1 in 17 of the 33 sequenced strains from the clinical study-group, and type 2 in 16 of these patients. Within each genotype, sequence differences were minimal. No association between disease severity and MP genotype was observed. In the extended genotype assessment, MP1 was found in similar proportions. In family contacts it was found in 53% and among patients from the two subsequent years 53% and 40%. Conclusions A higher MP bacterial load in throat secretions at diagnosis was associated with more advanced respiratory disease in patients, but MP genotype

  20. The impact of Staphylococcus aureus-associated molecular patterns on staphylococcal superantigen-induced toxic shock syndrome and pneumonia.

    PubMed

    Tilahun, Ashenafi Y; Karau, Melissa; Ballard, Alessandro; Gunaratna, Miluka P; Thapa, Anusa; David, Chella S; Patel, Robin; Rajagopalan, Govindarajan

    2014-01-01

    Staphylococcus aureus is capable of causing a spectrum of human illnesses. During serious S. aureus infections, the staphylococcal pathogen-associated molecular patterns (PAMPs) such as peptidoglycan, lipoteichoic acid, and lipoproteins and even intact S. aureus, are believed to act in conjunction with the staphylococcal superantigens (SSAg) to activate the innate and adaptive immune system, respectively, and cause immunopathology. However, recent studies have shown that staphylococcal PAMPs could suppress inflammation by several mechanisms and protect from staphylococcal toxic shock syndrome, a life-threatening systemic disease caused by toxigenic S. aureus. Given the contradictory pro- and anti-inflammatory roles of staphylococcal PAMPs, we examined the effects of S. aureus-derived molecular patterns on immune responses driven by SSAg in vivo using HLA-DR3 and HLA-DQ8 transgenic mice. Our study showed that neither S. aureus-derived peptidoglycans (PGN), lipoteichoic acid (LTA), nor heat-killed Staphylococcus aureus (HKSA) inhibited SSAg-induced T cell proliferation in vitro. They failed to antagonize the immunostimulatory effects of SSAg in vivo as determined by their inability to attenuate systemic cytokine/chemokine response and reduce SSAg-induced T cell expansion. These staphylococcal PAMPs also failed to protect HLA-DR3 as well as HLA-DQ8 transgenic mice from either SSAg-induced toxic shock or pneumonia induced by a SSAg-producing strain of S. aureus. PMID:25024509

  1. Elevated Plasma Stromal-Cell-Derived Factor-1 Protein Levels Correlate with Severity in Patients with Community-Acquired Pneumonia

    PubMed Central

    Tsai, Ping-Kun; Hsieh, Ming-Ju; Wang, Hsiang-Ling; Chou, Ming-Chih; Yang, Shun-Fa

    2014-01-01

    Background. The aim of this study was to investigate differential changes in plasma levels of stromal-cell-derived factor-1 (SDF-1) before and after antibiotic treatment in patients with community-acquired pneumonia (CAP) and observe the association between the severity of CAP and the plasma SDF-1 level. Methods. We gathered blood specimens from 61 adult CAP patients before and after antibiotic treatment and from 60 healthy controls to measure the plasma concentrations of SDF-1 by using an enzyme-linked immunosorbent assay. Results. The plasma SDF-1 concentration was elevated significantly in patients with CAP before receiving treatment compared with the controls and decreased significantly after the patients received treatment. Leukocyte (WBC) and neutrophil counts and C-reactive protein (CRP) levels decreased significantly after antibiotic treatment. Moreover, differences in the plasma concentration of SDF-1 were significantly correlated with PSI, CURB-65, and APACHE II scores (r = 0.389, P = 0.002, and n = 61; r = 0.449, P < 0.001, and n = 61; and r = 0.363, P = 0.004, and n = 61, resp.). Conclusions. An elevated plasma SDF-1 concentration can be used as a biological marker for the early diagnosis of CAP and for the early detection of its severity. PMID:25371597

  2. Integrated Clinical, Pathologic, Virologic, and Transcriptomic Analysis of H5N1 Influenza Virus-Induced Viral Pneumonia in the Rhesus Macaque

    PubMed Central

    Shinya, Kyoko; Gao, Yuwei; Cilloniz, Cristian; Suzuki, Yasuhiro; Fujie, Masahiro; Deng, Guohua; Zhu, Qiyun; Fan, Shufang; Makino, Akiko; Muramoto, Yukiko; Fukuyama, Satoshi; Tamura, Daisuke; Noda, Takeshi; Eisfeld, Amie J.; Katze, Michael G.

    2012-01-01

    Viral pneumonia has been frequently reported during early stages of influenza virus pandemics and in many human cases of highly pathogenic avian influenza (HPAI) H5N1 virus infection. To better understand the pathogenesis of this disease, we produced nonlethal viral pneumonia in rhesus macaques by using an HPAI H5N1 virus (A/Anhui/2/2005; referred to as Anhui/2). Infected macaques were monitored for 14 days, and tissue samples were collected at 6 time points for virologic, histopathologic, and transcriptomic analyses. Anhui/2 efficiently replicated in the lung from 12 h to 3 days postinfection (p.i.) and caused temporal but severe pneumonia that began to resolve by day 14. Lung transcriptional changes were first observed at 6 h, and increased expression of vascular permeability regulators and neutrophil chemoattractants correlated with increased serum leakage and neutrophil infiltration in situ. Additional inflammatory, antiviral, and apoptotic genes were upregulated from 12 h, concurrent with viral antigen detection and increasing immune cell populations. A shift toward upregulation of acquired immunity was apparent after day 6. Expression levels of established immune cell molecular markers revealed remarkable similarity with pathological findings, indicating early and robust neutrophil infiltration, a slight delay in macrophage accumulation, and abundant late populations of T lymphocytes. We also characterized the putative mechanisms regulating a unique, pneumonia-associated biphasic fever pattern. Thus, this study is the first to use a comprehensive and integrative approach to delineate specific molecular mechanisms regulating influenza virus-induced pneumonia in nonhuman primates, an important first step toward better management of human influenza virus disease. PMID:22491448

  3. Characteristics associated with severe pneumonia in under-five children admitted to emergency units of two teaching hospitals in Khartoum, Sudan

    PubMed Central

    Salih, Karim Eldin M. A.; Salih, Ali; El Samani, El Fatih Z. E.; Hussien, Kamal Eldin; Ibrahim, Salah A.

    2011-01-01

    Pneumonia, defined as infection of lung parenchyma, is associated with severe complications especially in the very young and old patients. It is the world’s leading cause of childhood mortality. The World Health Organization (WHO) classification and guidelines are commonly used in Sudan in the diagnosis and management of pneumonia patients. A group of 224 patients at Gaafar Ibn Oaf Children’s Hospital and Omdurman Children’s Hospital were assessed and managed for severe presentation of pneumonia. The data collected showed that most of the patients were of low socioeconomic class families. The vast majority (99%) of patients had chronic exposure to tobacco smoke at home. Female patients (52.7%) were more than males, with 42% of the presenting patients in the less than 12 months age group. Pneumonia is a dangerous childhood menace that is associated with severe presentations. Public health community outreach programs should be put in place to raise awareness. The case fatality rate during the study period was 4%.

  4. Effects of early physiotherapy with respect to severity of pneumonia of elderly patients admitted to an intensive care unit: a single center study in Japan

    PubMed Central

    Chigira, Yusuke; Takai, Tomoko; Igusa, Hironobu; Dobashi, Kunio

    2015-01-01

    [Purpose] We performed early physiotherapy for elderly patients with pneumonia admitted to an intensive care unit (ICU), and examined the effects of this early physiotherapy on the severity of pneumonia. [Subjects and Methods] Patients for whom physiotherapy was started the day after admission to the ICU (acute phase) were assigned to the early intervention group and compared with patients in the standard intervention group. All patients were divided into three groups (Groups I, II, and III) based on the severity of pneumonia. We evaluated the ICU admission period, hospitalization period, and activities of daily living (ADL) before and after admission. [Results] With respect to the severity of pneumonia, Group II showed significant differences in the ICU admission period and rates of change in the operating range, cognitive domain, and Functional Independence Measure (FIM). Group III showed significant differences in the ICU admission period and rate of change in the cognitive domain (FIM item). The results were more favorable in the early intervention group than in the standard intervention group. [Conclusion] The ICU admission period was shorter and a reduction in the ADL level was prevented in Groups II, and III compared to Group I. This may have occurred because of the early rehabilitation. PMID:26311924

  5. Effects of early physiotherapy with respect to severity of pneumonia of elderly patients admitted to an intensive care unit: a single center study in Japan.

    PubMed

    Chigira, Yusuke; Takai, Tomoko; Igusa, Hironobu; Dobashi, Kunio

    2015-07-01

    [Purpose] We performed early physiotherapy for elderly patients with pneumonia admitted to an intensive care unit (ICU), and examined the effects of this early physiotherapy on the severity of pneumonia. [Subjects and Methods] Patients for whom physiotherapy was started the day after admission to the ICU (acute phase) were assigned to the early intervention group and compared with patients in the standard intervention group. All patients were divided into three groups (Groups I, II, and III) based on the severity of pneumonia. We evaluated the ICU admission period, hospitalization period, and activities of daily living (ADL) before and after admission. [Results] With respect to the severity of pneumonia, Group II showed significant differences in the ICU admission period and rates of change in the operating range, cognitive domain, and Functional Independence Measure (FIM). Group III showed significant differences in the ICU admission period and rate of change in the cognitive domain (FIM item). The results were more favorable in the early intervention group than in the standard intervention group. [Conclusion] The ICU admission period was shorter and a reduction in the ADL level was prevented in Groups II, and III compared to Group I. This may have occurred because of the early rehabilitation. PMID:26311924

  6. Uptake of extracellular DNA: Competence induced pili in natural transformation of Streptococcus pneumoniae

    PubMed Central

    Muschiol, Sandra; Balaban, Murat; Normark, Staffan; Henriques-Normark, Birgitta

    2015-01-01

    Transport of DNA across bacterial membranes involves complex DNA uptake systems. In Gram-positive bacteria, the DNA uptake machinery shares fundamental similarities with type IV pili and type II secretion systems. Although dedicated pilus structures, such as type IV pili in Gram-negative bacteria, are necessary for efficient DNA uptake, the role of similar structures in Gram-positive bacteria is just beginning to emerge. Recently two essentially very different pilus structures composed of the same major pilin protein ComGC were proposed to be involved in transformation of the Gram-positive bacterium Streptococcus pneumoniae – one is a long, thin, type IV pilus-like fiber with DNA binding capacity and the other one is a pilus structure that was thicker, much shorter and not able to bind DNA. Here we discuss how competence induced pili, either by pilus retraction or by a transient pilus-related opening in the cell wall, may mediate DNA uptake in S. pneumoniae. PMID:25640084

  7. Meningococcal pneumonia.

    PubMed

    Vossen, Matthias; Mitteregger, Dieter; Steininger, Christoph

    2016-08-17

    Neisseria meningitidis remains the most important cause of bacterial meningitis worldwide, particularly in children and young adults. The second most common and a potentially severe end-organ manifestation of invasive meningococcal disease (excluding systemic sepsis) is meningococcal pneumonia. It occurs in between 5% and 15% of all patients with invasive meningococcal disease and is thus the second most common non-systemic end-organ manifestation. To establish the diagnosis requires a high level of clinical awareness - the incidence is therefore very likely underreported and underestimated. This review of 344 meningococcal pneumonia cases reported in the Americas, Europe, Australia, and Asia between 1906 and 2015 presents risk factors, pathogenesis, clinical manifestations, diagnostic approaches, treatment, and prognosis of meningococcal pneumonia. PMID:27443594

  8. IκBζ Regulates Human Monocyte Pro-Inflammatory Responses Induced by Streptococcus pneumoniae.

    PubMed

    Sundaram, Kruthika; Rahman, Mohd Akhlakur; Mitra, Srabani; Knoell, Daren L; Woodiga, Shireen A; King, Samantha J; Wewers, Mark D

    2016-01-01

    Pneumococcal lung infections represent a major cause of death worldwide. Single nucleotide polymorphisms (SNPs) in the NFKBIZ gene, encoding the transcription factor IκBζ, are associated with increased susceptibility to invasive pneumococcal disease. We hence analyzed how IκBζ might regulate inflammatory responses to pneumococcal infection. We first demonstrate that IκBζ is expressed in human blood monocytes but not in bronchial epithelial cells, in response to wild type pneumococcal strain D39. D39 transiently induced IκBζ in a dose dependent manner, with subsequent induction of downstream molecules involved in host defense. Of these molecules, IκBζ knockdown reduced the expression of IL-6 and GMCSF. Furthermore, IκBζ overexpression increased the activity of IL-6 and GMCSF promoters, supporting the knockdown findings. Pneumococci lacking either pneumolysin or capsule still induced IκBζ. While inhibition of TLR1/TLR2 blocked D39 induced IκBζ expression, TLR4 inhibition did not. Blockade of p38 MAP kinase and NFκB suppressed D39 induced IκBζ. Overall, our data demonstrates that IκBζ regulates monocyte inflammatory responses to Streptococcus pneumoniae by promoting the production of IL-6 and GMCSF. PMID:27597997

  9. Vitamin D deficiency in community-acquired pneumonia: low levels of 1,25(OH)2 D are associated with disease severity

    PubMed Central

    2014-01-01

    Objectives We aimed to explore the association between vitamin D levels and the severity, mortality and microbiological etiology of community-acquired pneumonia. Methods Vitamin D levels (both, the reservoir form 25-OH and the activated form 1,25-OH2) of 300 randomly selected patients with community-acquired pneumonia due to pre-specified pathogens included in the German competence network (CAPNETZ) study were measured. Prior to statistical analysis, values of 25-OH and 1,25-OH2 were power-transformed to achieve parametric distribution. All further analyses were performed with seasonally and age adjusted values. Results There was only a modest (Spearman Coefficient 0.38) positive correlation between 25-OH and 1,25-OH2. For 1,25-OH2 but not 25-OH, the general linear model revealed a significant inverse correlation between serum concentration and CURB score (p = 0.011). Liver and respiratory co-morbidity were associated with significantly lower 25-OH values and renal co-morbidity with significantly lower 1,25-OH2 values. No significant differences of 1,25-OH2 or 25-OH between different pathogens (influenza virus, Legionella spp., Streptococcus pneumoniae) were detected. Conclusion For 1,25-OH2, we found a significant and independent (controlled for age, season and pathogen) negative correlation to pneumonia severity. Therefore, supplementation of non-activated vitamin D to protect from pneumonia may be non-sufficient in patients that have a decreased capacity to hydroxylate 25-OH to 1,25-OH2. PMID:24766747

  10. Severe Hypertriglyceridemia Induced Pancreatitis in Pregnancy

    PubMed Central

    Ahmed, Seema; Shaffer, Lemuel; Cavens, Paula; Blankstein, Josef

    2014-01-01

    Acute pancreatitis caused by severe gestational hypertriglyceridemia is a rare complication of pregnancy. Acute pancreatitis has been well associated with gallstone disease, alcoholism, or drug abuse but rarely seen in association with severe hypertriglyceridemia. Hypertriglyceridemia may occur in pregnancy due to normal physiological changes leading to abnormalities in lipid metabolism. We report a case of severe gestational hypertriglyceridemia that caused acute pancreatitis at full term and was successfully treated with postpartum therapeutic plasma exchange. Patient also developed several other complications related to her substantial hypertriglyceridemia including preeclampsia, chylous ascites, retinal detachment, pleural effusion, and chronic pericarditis. This patient had no previous family or personal history of lipid abnormality and had four successful prior pregnancies without developing gestational hypertriglyceridemia. Such a severe hypertriglyceridemia is usually seen in patients with familial chylomicronemia syndromes where hypertriglyceridemia is exacerbated by the pregnancy, leading to fatal complications such as acute pancreatitis. PMID:24995138

  11. Risk factors for severe outcomes among members of the United States military hospitalized with pneumonia and influenza, 2000–2012

    PubMed Central

    Van Kerkhove, Maria D; Cooper, Michael J.; Eick-Cost, Angelia A.; Sanchez, Jose L.; Riley, Steven

    2016-01-01

    Background The progression from hospitalization for a respiratory infection to requiring substantial supportive therapy is a key stage of the influenza severity pyramid. Respiratory infections are responsible for 300,000 to 400,000 medical encounters each year among US military personnel, some of which progress to severe acute respiratory infections. Methods We obtained data on 11,086 hospitalizations for pneumonia and influenza (P&I) among non-recruit US military service members during the period of 1 January 2000 through 31 December 2012. From these, we identified 512 P&I hospitalizations that progressed to severe episodes using standard case definitions. We evaluated the effect of demographic and occupational characteristics, comorbid conditions, and history of influenza vaccination on the risk of a hospitalized P&I case becoming a severe case. We also evaluated the risk of a severe outcome and the length of time since influenza vaccination (within 180, 60 and 30 days). Results The median age of subjects at the time of the P&I episode was 32 years (range, 28–40) and subjects were predominantly male (89.5%). In a univariate analysis, demographic risk factors for a severe episode included service in the US Air Force (RR=1.6 relative to US Army, 95%CI 1.3-2.1), US Coast Guard (RR=2.1, 1.2-3.7) or US Navy (RR=1.4, 1.1-1.8). Being born in the US and recent influenza vaccination (within 180 days of episode) were protective against developing severe disease. Among comorbid conditions, univariate risk factors for severe disease included chronic renal or liver disease (RR=4.98, 95%CI 4.1-6.1), diseases of the circulatory system (RR=3.1, 95%CI 2.6-3.7), diabetes mellitus (RR=2.3, 95%CI 1.5-3.6), obesity (RR=1.6, 95%CI 1.2-2.1), cancer (RR=1.6, 95%CI 1.3-2.0) and chronic obstructive pulmonary disease (RR=1.4, 95%CI 1.1-1.7). Although many of the risk factors found to be significant in univariate analysis were no longer significant under a multivariate analysis, receipt

  12. Pleural and pericardial effusions combined with ascites in a patient with severe sunitinib-induced hypothyroidism.

    PubMed

    Kust, Davor; Kruljac, Ivan; Peternac, Ana Šverko; Ostojić, Jelena; Prpić, Marin; Čaržavec, Dubravka; Gaćina, Petar

    2016-06-01

    To best of our knowledge, this is the first reported case of pericardial and pleural effusions combined with ascites, precipitated with severe sunitinib-induced hypothyroidism. A 58-year-old man presented in our emergency department due to dyspnoea and dry cough. Sixteen months earlier, the patient underwent left nephrectomy due to metastatic renal cell adenocarcinoma (RCC), and therapy with sunitinib was initiated postoperatively. Thyroid function was not assessed during the therapy. On admission, all laboratory findings were within normal range. Computed tomography of the chest detected voluminous bilateral pleural effusions and mild pericardial effusion, and echocardiography revealed pericardial effusion. Thoracocentesis was carried out three times, and cytological examination showed no signs of malignant cells. After assessment of the thyroid function, neglected hypothyroidism was registered. Substitution therapy with levothyroxine was initiated, and thyroid function normalised 2 weeks later. Few days after the last thoracocentesis, his condition suddenly got worse. Thoracocentesis was repeated, and microbiological analysis of the exudate came positive for Klebsiella pneumoniae and Streptococcus pneumoniae. Despite the implemented therapeutic measures, his clinical condition progressively deteriorated. The patient died 27 days after the admission, hospital-acquired pneumonia was identified as the cause of death. Our case emphasises the necessity of careful monitoring and management of side-effects in patients who receive sunitinib. Hypothyroidism is a known cause of pleural, pericardial and abdominal effusions, as reported in several case reports. Timely initiation of substitution levothyroxine therapy can decrease unnecessary pauses in the therapy with sunitinib, as well as prevent development of severe symptoms. PMID:26319226

  13. Disease-specific dynamic biomarkers selected by integrating inflammatory mediators with clinical informatics in ARDS patients with severe pneumonia.

    PubMed

    Chen, Chengshui; Shi, Lin; Li, Yuping; Wang, Xiangdong; Yang, Shuanying

    2016-06-01

    Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome that occurs as a result of various risk factors, including either direct or indirect lung injury, and systemic inflammation triggered also by severe pneumonia (SP). SP-ARDS-associated morbidity and mortality remains high also due to the lack of disease-specific biomarkers. The present study aimed at identifying disease-specific biomarkers in SP or SP-ARDS by integrating proteomic profiles of inflammatory mediators with clinical informatics. Plasma was sampled from the healthy as controls or patients with SP infected with bacteria or infection-associated SP-ARDS on the day of admission, day 3, and day 7. About 15 or 52 cytokines showed significant difference between SP and SP-ARDS patients with controls or 13 between SP-ARDS with SP alone and controls, including bone morphogenetic protein-15 (BMP-15), chemokine (C-X-C motif) ligand 16 (CXCL16), chemokine (C-X-C motif) receptor 3 (CXCR3), interleukin-6 (IL-6), protein NOV homolog (NOV/CCN3), glypican 3, insulin-like growth factor binding protein 4 (IGFBP-4), IL-5, IL-5 R alpha, IL-22 BP, leptin, MIP-1d, and orexin B with a significant correlation with Digital Evaluation Score System (DESS) scores. ARDS patients with overexpressed IL-6, CXCL16, or IGFBP-4 had significantly longer hospital stay and higher incidence of secondary infection. We also found higher levels of those mediators were associated with poor survival rates in patients with lung cancer and involved in the process of the epithelial mesenchymal transition of alveolar epithelial cells. Our preliminary study suggested that integration of proteomic profiles with clinical informatics as part of clinical bioinformatics is important to validate and optimize disease-specific and disease-staged biomarkers. PMID:27095254

  14. Peripheral Ovine Progressive Pneumonia Provirus Levels Correlate with and Predict Histological Tissue Lesion Severity in Naturally Infected Sheep

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Studies were undertaken to determine whether host immune responses in the form of serum anti-ovine progressive pneumonia virus (OPPV) antibody responses or virus replication in the form of peripheral OPP provirus levels associate with the degree of histological tissue lesions in naturally OPPV infec...

  15. Predictors and Implications of Early Clinical Stability in Patients Hospitalized for Moderately Severe Community-Acquired Pneumonia

    PubMed Central

    Felix, Garance; Chuard, Christian; Genné, Daniel; Carballo, Sebastian; Hugli, Olivier; Lamy, Olivier; Marti, Christophe; Nendaz, Mathieu; Rutschmann, Olivier; Harbarth, Stephan; Perrier, Arnaud

    2016-01-01

    Background Assessment of early response to treatment is crucial for the management of community-acquired pneumonia (CAP). Objective To describe the predictors and the outcomes of early clinical stability Methods We did a secondary analysis of a multicentre randomized controlled trial on CAP treatment in which 580 patients hospitalized for moderately severe CAP were included. The association between demographic, clinical and biological variables available at inclusion and early clinical stability (stabilization of vital signs within 72 hours with predetermined cut-offs) was assessed by multivariate logistic regression. The association between early clinical stability and mortality, severe adverse events, and length of stay was also tested. Results Younger age (OR 0.98, 95% CI 0.96–0.99), lower platelet count (OR per 10 G/L increment 0.96, 95% CI 0.94–0.98), lower respiratory rate (OR 0.94, 95% CI 0.90–0.97), absence of hypoxemia (OR 0.58, 95% CI 0.40–0.85), lower numbers of co-morbid conditions (OR 0.82, 95% CI 0.69–0.98) and signs or symptoms (OR 0.78, 95% CI 0.68–0.90) were significantly associated with early clinical stability. Patients with early clinical stability had lower 90-days mortality (3.4% vs. 11.9%, p<0.001), fewer admissions to the intensive care unit (2.7% vs. 8.0%, p = 0.005) and a shorter length of stay (6.0 days, IQR 4.0–10.0 vs. 10.0 days, IQR 7.0–15.0, p<0.001). Conclusions Patients with younger age, less co-morbidity, fewer signs or symptoms, less respiratory compromise, and a lower platelet count are more likely to reach early clinical stability. Patients without early clinical stability have a worse prognosis and warrant close scrutiny. PMID:27305046

  16. Pneumonia - weakened immune system

    MedlinePlus

    ... immunocompromised host." Related conditions include: Hospital-acquired pneumonia Pneumocystis jirovecii (previously called Pneumocystis carinii) pneumonia Pneumonia - cytomegalovirus Pneumonia ...

  17. Cluster Randomized Trial of Community Case Management of Severe Pneumonia with Oral Amoxicillin in Children 2-59 Months of Age in Haripur District, Pakistan

    PubMed Central

    Bari, Abdul; Sadruddin, Salim; Khan, Attaullah; Khan, Ibad ul Haque; Ullah, Aman; Lehri, Iqbal A.; Macleod, William B.; Fox, Matthew P.; Thea, Donald M; Qazi, Shamim A.

    2013-01-01

    Background First dose oral cotrimoxazole and referral is the recommended treatment for WHO-defined severe pneumonia. Difficulties with referral compliance are reported from many low resource settings resulting in low access to appropriate treatment. Methods In a cluster-randomized equivalence trial in Haripur District, Pakistan 28 clusters were randomized equally to intervention and control clusters. In 14 intervention clusters children 2-59 months of age with severe pneumonia were treated with oral amoxicillin by community-based Lady Health Workers (LHW). In 14 control clusters LHWs gave first dose of oral cotrimoxazole and referred to a health facility for appropriate treatment, which was standard of care. The objective was to determine whether community case-management (CCM) of severe pneumonia by LHW using oral amoxicillin was equivalent to current standard of care. Primary outcome was treatment failure on day 6 of treatment. Participants, care givers, and assessors were not blinded to study therapy. Per-protocol analysis was conducted adjusting for clustering within arms using generalized estimating equations. Findings 1995 children were randomized to intervention and 1477 to control clusters. We analysed 1857 children randomized to intervention and 1354 randomized to control clusters. They were similar in sex, age, and clinical characteristics. Treatment failure was 8·9% (165/1857) in intervention and 17·8% (241/1354) in control clusters. Cluster adjusted failure rates, the primary outcome, were significantly reduced in intervention clusters (risk difference (RD) -8·9%; 95% CI:-12.4% to -5.4%) by day 6. Further adjusting for baseline covariates made little difference (RD: -7·3%, CI: -10·1% to -4·5%). Three deaths occurred, only one in the intervention arm. Two deaths were before day 6, while one occurred between day 6 and 14. Most reduction in risk was in fever and lower chest indrawing on day 3 (RD -6·38%; 95% CI: -8·3% to -4·5%). Age, gender and

  18. [Chest radiograph of atypical pneumonia: comparison among Chlamydia pneumoniae. Pneumonia, ornithosis, and Mycoplasma pneumoniae pneumonia].

    PubMed

    Itoh, I; Ishida, T; Hashimoto, T; Arita, M; Osawa, M; Tachibana, H; Nishiyama, H; Takakura, S; Bando, K; Nishizawa, Y; Amitani, R; Onishi, H; Taguchi, Y

    2000-11-01

    No report has been found comparing Chlamydia pneumoniae (C. pneumoniae) pneumonia radiographically with other atypical pneumonias, Chlamydia psittaci (C. psittaci) pneumonia and Mycoplasma pneumoniae (M. pneumoniae) pneumonia. We described the chest radiographs of three kinds of pneumonia cases: 46 cases of C. pneumoniae pneumonia, 39 cases of C. psittaci pneumonia, and 131 cases of M. pneumoniae pneumonia. Radiographic shadows were categorized into main shadows and sub-shadows. The main shadows are classified from the viewpoint of the characteristics; air space consolidation(AS), ground-glass opacity(GG), reticular shadow(RS), bronchopneumonia(BP), and small nodular shadows (SN). The size, the site, and the number of the main shadows were also analyzed. In comparison among the three pneumonias, BP was the most frequent in M. pneumoniae pneumonia (0.40/case). AS predominated in C. pneumoniae pneumonia (0.67/case), and GG in C. psittaci pneumonia (0.62/case). The number of main shadows was equal, about 1.4/case in three pneumonias. Large shadows were less frequent in M. pneumoniae pneumonia than C. pneumoniae pneumonia (p = 0.02) and C. psittaci pneumonia (p = 0.01). Main shadows were more frequent in the outer zone in M. pneumoniae pneumonia than C. psittaci pneumonia (p = 0.01), and in the middle zone in C. psittaci pneumonia than in M. pneumoniae pneumonia (p = 0.02). Cases with bilateral main shadows were less common in M. pneumoniae pneumonia (9%) than C. pneumoniae pneumonia(33%, p = 0.001) and C. psittaci pneumonia(30%, p = 0.005). Thickening of bronchovascular bundles as a sub-shadow was most frequently noted in M. pneumoniae pneumonia. Some differences among the three atypical pneumonias were seen in the chest radiograph. However, no specific findings of C. pneumoniae pneumonia were shown radiographically in this study. PMID:11140079

  19. Chloramphenicol versus ampicillin plus gentamicin for community acquired very severe pneumonia among children aged 2-59 months in low resource settings: multicentre randomised controlled trial (SPEAR study)

    PubMed Central

    2008-01-01

    Objective To evaluate whether five days’ treatment with injectable ampicillin plus gentamicin compared with chloramphenicol reduces treatment failure in children aged 2-59 months with community acquired very severe pneumonia in low resource settings. Design Open label randomised controlled trial. Setting Inpatient wards within tertiary care hospitals in Bangladesh, Ecuador, India, Mexico, Pakistan, Yemen, and Zambia. Participants Children aged 2-59 months with WHO defined very severe pneumonia. Intervention Chloramphenicol versus a combination of ampicillin plus gentamicin. Main outcome measures Primary outcome measure was treatment failure at five days. Secondary outcomes were treatment failure defined similarly among all participants evaluated at 48 hours and at 10 and 21 days. Results More children failed treatment with chloramphenicol at day 5 (16% v 11%; relative risk 1.43, 95% confidence interval 1.03 to 1.97) and also by days 10 and 21. Overall, 112 bacterial isolates were obtained from blood and lung aspirates in 110 children (11.5%), with the most common organisms being Staphylococcus aureus (n=47) and Streptococcus pneumoniae (n=22). In subgroup analysis, bacteraemia with any organism increased the risk of treatment failure at 21 days in the chloramphenicol group (2.09, 1.41 to 3.10) but not in the ampicillin plus gentamicin group (1.12, 0.59 to 2.13). Similarly, isolation of S pneumoniae increased the risk of treatment failure at day 21 (4.06, 2.73 to 6.03) and death (5.80, 2.62 to 12.85) in the chloramphenicol group but not in the ampicillin plus gentamicin group. No difference was found in treatment failure for children with S aureus bacteraemia in the two groups, but the power to detect a difference in this subgroup analysis was low. Independent predictors of treatment failure by multivariate analysis were hypoxaemia (oxygen saturation <90%), receiving chloramphenicol, being female, and poor immunisation status. Conclusion Injectable ampicillin plus

  20. [A case of interstitial pneumonia exacerbated by kampo-induced pneumonitis].

    PubMed

    Suzuki, Kazuo; Kinebuchi, Shinichi; Sugiyama, Kentaro; Satoh, Hiroshi; Tango, Masuo; Moriyama, Hirochi; Terada, Masaki; Ooi, Hidemi; Hasegawa, Takashi; Igarashi, Kenichi; Satoh, Makoto; Suzuki, Eiichi; Gejyo, Fumitake

    2002-07-01

    A 65-year-old woman who had complained of non-productive cough since May 1998 visited our hospital on November 5, 2000. She had been treated at another hospital with Kampo (Chinese herbal medicine), including Moku-boui-to, Bakumon-do-to, and Saiko-keishi-kankyo-to for chronic non-productive cough. Chest radiographs and CT films showed the reticular shadows that had been present in 1998, in both lower lung fields, and also demonstrated new reticular shadows in the right upper lung field and left lingular segment. Laboratory data revealed hypoxemia and pulmonary function tests revealed restrictive ventilatory disturbance, so she was admitted to our hospital on November 9, 2000. After the cessation of Kampo treatment, her symptoms disappeared, and the hypoxemia, restrictive disturbance, and reticular shadows in the chest radiograph gradually improved. Video-assisted lung biopsy specimens showed thickened alveolar walls with lymphocyte and eosinophil infiltration. A leukocyte migration test was positive for Moku-boui-to, Bakumon-do-to, and weakly positive for Saiko-keishi-kankyo-to. Although no challenge test for Kampo was performed, we diagnosed this case as interstitial pneumonia exacerbated Kampo-induced pneumonitis based on these clinical, laboratory and histological findings. PMID:12382427

  1. Neutrophil elastase modulates cytokine expression: contribution to host defense against Pseudomonas aeruginosa-induced pneumonia.

    PubMed

    Benabid, Rym; Wartelle, Julien; Malleret, Laurette; Guyot, Nicolas; Gangloff, Sophie; Lebargy, François; Belaaouaj, Azzaq

    2012-10-12

    There is accumulating evidence that following bacterial infection, the massive recruitment and activation of the phagocytes, neutrophils, is accompanied with the extracellular release of active neutrophil elastase (NE), a potent serine protease. Using NE-deficient mice in a clinically relevant model of Pseudomonas aeruginosa-induced pneumonia, we provide compelling in vivo evidence that the absence of NE was associated with decreased protein and transcript levels of the proinflammatory cytokines TNF-α, MIP-2, and IL-6 in the lungs, coinciding with increased mortality of mutant mice to infection. The implication of NE in the induction of cytokine expression involved at least in part Toll-like receptor 4 (TLR-4). These findings were further confirmed following exposure of cultured macrophages to purified NE. Together, our data suggest strongly for the first time that NE not only plays a direct antibacterial role as it has been previously reported, but released active enzyme can also modulate cytokine expression, which contributes to host protection against P. aeruginosa. In light of our findings, the long held view that considers NE as a prime suspect in P. aeruginosa-associated diseases will need to be carefully reassessed. Also, therapeutic strategies aiming at NE inhibition should take into account the physiologic roles of the enzyme. PMID:22927440

  2. Chlamydia pneumoniae Augments the Oxidized Low-Density Lipoprotein-Induced Death of Mouse Macrophages by a Caspase-Independent Pathway

    PubMed Central

    Yaraei, Kambiz; Campbell, Lee Ann; Zhu, Xiaodong; Liles, W. Conrad; Kuo, Cho-chou; Rosenfeld, Michael E.

    2005-01-01

    Chlamydia pneumoniae is a common respiratory pathogen that is associated with an increased risk of cardiovascular disease. However, the mechanisms by which C. pneumoniae contributes to cardiovascular disease have not been determined yet. C. pneumoniae infection may accelerate the death of cells within atherosclerotic lesions and contribute to the formation of unstable lesions. To test this hypothesis, the impact of C. pneumoniae infection on the death of lipid-loaded mouse macrophages was investigated. It was observed that RAW 264.7 cells are highly susceptible to the toxic effects of oxidized low-density lipoprotein (LDL) and exhibit markers of cell death within 24 h of treatment with as little as 5 μg/ml oxidized LDL. Subsequent infection with either live C. pneumoniae or heat-killed or UV-inactivated C. pneumoniae at a low multiplicity of infection for 24 to 72 h stimulated both additional binding of annexin V and the uptake of propidium iodide. Thus, C. pneumoniae augments the effects of oxidized LDL on cell death independent of a sustained infection. However, unlike oxidized LDL, C. pneumoniae infection does not activate caspase 3 or induce formation of the mitochondrial transition pore or the fragmentation of DNA, all of which are classical markers of apoptosis. Furthermore, primary bone marrow macrophages isolated from mice deficient in Toll-like receptor 2 (TLR-2) but not TLR-4 are resistant to C. pneumoniae-induced death. These data suggest that C. pneumoniae kills cells by a caspase-independent pathway and that the process is potentially mediated by activation of TLR-2. PMID:15972525

  3. The protective effects of Ambroxol in Pseudomonas aeruginosa-induced pneumonia in rats

    PubMed Central

    Gao, Xiwen; Huang, Yi; Han, Yipin; Bai, Chun-xue; Wang, Guifang

    2011-01-01

    Introduction To evaluate the effect of Ambroxol on the pulmonary surfactant (PS) in rat pneumonia induced by Pseudomonas aeruginosa (PA). Material and methods The pneumonic rats were obtained by injecting ATCC27853 intratracheally. One hundred and twenty SD rats were randomized into four groups: normal saline and Ambroxol was injected intraperitoneally following PA challenge in the PA/NS and PA/AM group; the other two groups were NS/AM and NS/NS. The wet/dry weight ratio (W/D), and pathological changes were assayed. Total proteins (TP), total phospholipid (TPL), and dipalmitoylphosphatidylcholine (DPPC) in bronchial alveolar lavage fluid (BALF) were analysed. Some BALF was cultured for colony counts. Ultrastructural change of the lung was observed by electron microscopy. Results The W/D ratio in the PA/AM group was lower than that in the PA/NS group; both were higher than that in the NS/NS group (p < 0.05). There were more neutrophils in the PA/NS group than in the PA/AM group (p < 0.05), and more in the PA/AM group than in the NS/NS group (p < 0.05). The ratio of DSPC/TPL and DSPC/TP in the BALF in PA/NS group was lower than that in the PA/AM group; DSPC/TPL and DSPC/TP ratios also increased in the NS/AM group. The PA colony numbers in the PA/AM group were lower than in the PA/NS group (p > 0.05). In the PA/NS group, vacuolation occurred in the lamellar body of alveolar type 2 cells (AT2) and the PS layer was rough and broken in some areas. In the PA/AM group, the degree of vacuolation of the lamellar body was less than in the PA/NS group. Conclusions Ambroxol could protect rats from pneumonia by improving the level of endogenous PS, especially DPPC. PMID:22312374

  4. Allergic lung inflammation alters neither susceptibility to Streptococcus pneumoniae infection nor inducibility of innate resistance in mice

    PubMed Central

    Clement, Cecilia G; Tuvim, Michael J; Evans, Christopher M; Tuvin, Daniel M; Dickey, Burton F; Evans, Scott E

    2009-01-01

    Background Protective host responses to respiratory pathogens are typically characterized by inflammation. However, lung inflammation is not always protective and it may even become deleterious to the host. We have recently reported substantial protection against Streptococcus pneumoniae (pneumococcal) pneumonia by induction of a robust inflammatory innate immune response to an inhaled bacterial lysate. Conversely, the allergic inflammation associated with asthma has been proposed to promote susceptibility to pneumococcal disease. This study sought to determine whether preexisting allergic lung inflammation influences the progression of pneumococcal pneumonia or reduces the inducibilty of protective innate immunity against bacteria. Methods To compare the effect of different inflammatory and secretory stimuli on defense against pneumonia, intraperitoneally ovalbumin-sensitized mice were challenged with inhaled pneumococci following exposure to various inhaled combinations of ovalbumin, ATP, and/or a bacterial lysate. Thus, allergic inflammation, mucin degranulation and/or stimulated innate resistance were induced prior to the infectious challenge. Pathogen killing was evaluated by assessing bacterial CFUs of lung homogenates immediately after infection, the inflammatory response to the different conditions was evaluated by measurement of cell counts of bronchoalveolar lavage fluid 18 hours after challenge, and mouse survival was assessed after seven days. Results We found no differences in survival of mice with and without allergic inflammation, nor did the induction of mucin degranulation alter survival. As we have found previously, mice treated with the bacterial lysate demonstrated substantially increased survival at seven days, and this was not altered by the presence of allergic inflammation or mucin degranulation. Allergic inflammation was associated with predominantly eosinophilic infiltration, whereas the lysate-induced response was primarily neutrophilic

  5. Ethanol-Induced Alcohol Dehydrogenase E (AdhE) Potentiates Pneumolysin in Streptococcus pneumoniae

    PubMed Central

    Luong, Truc Thanh; Kim, Eun-Hye; Bak, Jong Phil; Nguyen, Cuong Thach; Choi, Sangdun; Briles, David E.; Pyo, Suhkneung

    2014-01-01

    Alcohol impairs the host immune system, rendering the host more vulnerable to infection. Therefore, alcoholics are at increased risk of acquiring serious bacterial infections caused by Streptococcus pneumoniae, including pneumonia. Nevertheless, how alcohol affects pneumococcal virulence remains unclear. Here, we showed that the S. pneumoniae type 2 D39 strain is ethanol tolerant and that alcohol upregulates alcohol dehydrogenase E (AdhE) and potentiates pneumolysin (Ply). Hemolytic activity, colonization, and virulence of S. pneumoniae, as well as host cell myeloperoxidase activity, proinflammatory cytokine secretion, and inflammation, were significantly attenuated in adhE mutant bacteria (ΔadhE strain) compared to D39 wild-type bacteria. Therefore, AdhE might act as a pneumococcal virulence factor. Moreover, in the presence of ethanol, S. pneumoniae AdhE produced acetaldehyde and NADH, which subsequently led Rex (redox-sensing transcriptional repressor) to dissociate from the adhE promoter. An increase in AdhE level under the ethanol condition conferred an increase in Ply and H2O2 levels. Consistently, S. pneumoniae D39 caused higher cytotoxicity to RAW 264.7 cells than the ΔadhE strain under the ethanol stress condition, and ethanol-fed mice (alcoholic mice) were more susceptible to infection with the D39 wild-type bacteria than with the ΔadhE strain. Taken together, these data indicate that AdhE increases Ply under the ethanol stress condition, thus potentiating pneumococcal virulence. PMID:25312953

  6. Observational Follow-up Study on a Cohort of Children with Severe Pneumonia after Discharge from a Day-care Clinic in Dhaka, Bangladesh

    PubMed Central

    Alam, Nur H.; Chisti, Mohammod J.; Salam, Mohammed A.; Ahmed, Tahmeed; Gyr, Niklaus

    2014-01-01

    ABSTRACT Compliance, morbidity, mortality, and hospitalization during fortnightly follow-up were evaluated by an observational study on a cohort of children with severe and very severe pneumonia after day-care treatment at an urban clinic. The primary outcome measures were proportions of success (compliance) and failure (non-compliance) of follow-up visits at the day-care clinic. In total, 251 children were followed up, with median (IQR) age of 5.0 (3.0-9.0) months, and their compliance dropped from 92% at the first to 85% at the sixth visit. Cough (28%), fever (20%), and rapid breathing (13%) were common morbidities. Successful follow-up visits were possible in 180 (95.2%) and 56 (90.3%) of the children with severe and very severe pneumonia respectively. Eleven (4.4%) needed hospitalization, and four (1.6%) died. Majority (≈90%) of the children could be successfully followed up; some failed to attend their scheduled follow-up visits due to hospitalization and death. The common morbidities indicate the importance of follow-up for detecting medical problems and early treatment, thus reducing risk of death. PMID:25076656

  7. Mycoplasma pneumoniae Pneumonia Associated With Methemoglobinemia and Anemia: An Overlooked Association?

    PubMed Central

    Khoury, Tawfik; Abu Rmeileh, Ayman; Kornspan, Jonathan David; Abel, Roy; Mizrahi, Meir; Nir-Paz, Ran

    2015-01-01

    We report a case of acute methemoglobinemia and anemia in a patient with Mycoplasma pneumoniae pneumonia. We suggest that M. pneumoniae secretes a putative protein that can induce methemoglobin in red blood cells. Thus, Mycoplasma pneumoniae may induce methemoglobinemia in patients who have low oxygen saturation and anemia. PMID:26034771

  8. Failure of standard antimicrobial therapy in children aged 3-59 months with mild or asymptomatic HIV infection and severe pneumonia.

    PubMed Central

    Jeena, Prakash; Thea, Donald M.; MacLeod, William B.; Chisaka, Noel; Fox, Matthew P.; Coovadia, H. M.; Qazi, Shamim

    2006-01-01

    OBJECTIVE: To determine whether children aged 3-59 months with mild or non-symptomatic human immunodeficiency virus (HIV) infection and WHO-defined severe pneumonia have a higher failure rate than do HIV-uninfected children when treated with the standard WHO treatment of parenteral penicillin or oral amoxicillin. METHODS: This study was a planned sub-analysis of a randomized trial of 3-59-month-old children presenting with WHO-defined severe pneumonia (the APPIS study). We included two sites with high HIV prevalence in Durban, South Africa and Ndola, Zambia. Primary outcome measures were clinical treatment failure at day 2 and day 14. CLINICALTRIALS.GOV IDENTIFIER: CT00227331http://www.clinicaltrialsgov/show/NCT00227331). FINDINGS: Of the 523 children enrolled, HIV status was known for 464 participants; 106 (23%) of these were infected with HIV. By day 2, 57 (12.3%) children had failed treatment and 110 (23.7%) failed by day 14. Twenty (18.9%) HIV-infected children failed by day 2 compared with 37 (10.3%) uninfected children (adjusted odds ratio (OR) 2.07; 95% confidence interval (CI): 1.07-4.00). Thirty-four (32.1%) HIV-infected children failed treatment by day 14 compared with 76 (21.2%) uninfected children (adjusted OR 1.88; 95% CI: 1.11-3.17). Analysis stratified by age showed that the greatest differential in treatment failure at day 2 and day 14 occurred in the children aged 3-5 months. CONCLUSIONS: HIV-infected children with severe pneumonia fail WHO-standard treatment with parenteral penicillin or amoxicillin at day 2 and day 14 more often than do HIV-uninfected children, especially young infants. Standard case management of acute respiratory infection (ARI) using WHO treatment guidelines is inadequate in areas of high HIV prevalence and reappraisal of empiric antimicrobial therapy is urgently needed for severe pneumonia associated with HIV-1. PMID:16628299

  9. A Case of Pneumocystis jirovecii Pneumonia in a Severely Malnourished, HIV-Negative Patient: A Role for Malnutrition in Opportunistic Infections?

    PubMed

    Attalla El Halabieh, Nadia; Petrillo, Enrico; Laviano, Alessandro; Delfino, Massimo; Rossi Fanelli, Filippo

    2016-07-01

    Malnutrition increases the risk of infections in patients receiving medical and surgical procedures, but it is not clear whether it may facilitate also the development of opportunistic infections in human immunodeficiency virus (HIV)-negative patients not receiving immunosuppressive therapies. Here we report the first case of a non-HIV, severely malnourished woman who developed Pneumocystis jirovecii pneumonia. This report highlights the clinical relevance of malnutrition as a determinant of immune suppression, which in turn may also favor opportunistic infections. Therefore, routine nutrition screening and assessment, as well as timely start of nutrition therapy, should be prioritized in daily clinical practice to reduce complications and improve outcome. PMID:25172049

  10. Overview of Community-Acquired Pneumonia and the Role of Inflammatory Mechanisms in the Immunopathogenesis of Severe Pneumococcal Disease

    PubMed Central

    Steel, Helen C.; Anderson, Ronald; Feldman, Charles

    2013-01-01

    Community-acquired pneumonia (CAP) remains a leading cause of morbidity and mortality among the infectious diseases. Despite the implementation of national pneumococcal polyvalent vaccine-based immunisation strategies targeted at high-risk groups, Streptococcus pneumoniae (the pneumococcus) remains the most common cause of CAP. Notwithstanding the HIV pandemic, major challenges confronting the control of CAP include the range of bacterial and viral pathogens causing this condition, the ever-increasing problem of antibiotic resistance worldwide, and increased vulnerability associated with steadily aging populations in developed countries. These and other risk factors, as well as diagnostic strategies, are covered in the first section of this review. Thereafter, the review is focused on the pneumococcus, specifically the major virulence factors of this microbial pathogen and their role in triggering overexuberant inflammatory responses which contribute to the immunopathogenesis of invasive disease. The final section of the review is devoted to a consideration of pharmacological, anti-inflammatory strategies with adjunctive potential in the antimicrobial chemotherapy of CAP. This is focused on macrolides, corticosteroids, and statins with respect to their modes of anti-inflammatory action, current status, and limitations. PMID:24453422

  11. A Histologically Distinctive Interstitial Pneumonia Induced by Overexpression of the Interleukin 6, Transforming Growth Factor β1, or Platelet-Derived Growth Factor B Gene

    NASA Astrophysics Data System (ADS)

    Yoshida, Mitsuhiro; Sakuma, Junko; Hayashi, Seiji; Abe, Kin'ya; Saito, Izumu; Harada, Shizuko; Sakatani, Mitsunoir; Yamamoto, Satoru; Matsumoto, Norinao; Kaneda, Yasufumi; Kishmoto, Tadamitsu

    1995-10-01

    Interstitial pneumonia is characterized by alveolitis with resulting fibrosis of the interstitium. To determine the relevance of humoral factors in the pathogenesis of interstitial pneumonia, we introduced expression vectors into Wistar rats via the trachea to locally overexpress humoral factors in the lungs. Human interleukin (IL) 6 and IL-6 receptor genes induced lymphocytic alveolitis without marked fibroblast proliferation. In contrast, overexpression of human transforming growth factor β1 or human platelet-derived growth factor B gene induced only mild or apparent cellular infiltration in the alveoli, respectively. However, both factors induced significant proliferation of fibroblasts and deposition of collagen fibrils. These histopathologic changes induced by the transforming growth factor β1 and platelet-derived growth factor B gene are partly akin to those changes seen in lung tissues from patients with pulmonary fibrosis and markedly contrast with the changes induced by overexpression of the IL-6 and IL-6 receptor genes that mimics lymphocytic interstitial pneumonia.

  12. Severe Q fever community-acquired pneumonia (CAP) mimicking Legionnaires' disease: Clinical significance of cold agglutinins, anti-smooth muscle antibodies and thrombocytosis.

    PubMed

    Cunha, Burke A; Nausheen, Sara; Busch, Lori

    2009-01-01

    Atypical community-acquired pneumonia (CAP) may be caused by zoonotic or nonpulmonary pathogens. However, atypical pathogens are systemic infectious disease accompanied by pneumonia in contrast with typical bacterial pathogens with infection limited to the lungs and absent extrapulmonary findings. Clinically and radiologically, the atypical CAP pathogens that most closely resemble each other are psittacosis, Q fever, and Legionnaires' disease. Psittacosis can usually be readily suspected or eliminated on the basis of a recent psittacine bird contact history. The 2 atypical pneumonias that most closely resemble each other clinically are Q fever and Legionnaires' disease. The epidemiology of Q fever is related to livestock, and sporadic cases are related to contact to parturient cats. In nonendemic areas, Q fever CAP mimics Legionnaires' disease most closely. Both Q fever and Legionella CAP have several clinical and laboratory features in common. However, there are subtle but important differences that allow the astute clinician to differentiate between these 2 disorders on the basis of clinical and nonspecific laboratory findings before definitive diagnostic tests results are reported. We report a case of severe Q fever CAP mimicking Legionnaires' disease in a young adult normal host. Her initial zoonotic contact history was negative, and her clinical presentation suggested Legionnaires' disease as the most likely diagnosis. Against the diagnosis of Legionnaires' disease was the patient's age and occurrence of the disease in spring time. In contrast, Legionnaires' disease is usually an infection of older individuals and occurs in late summer/fall. Although the patient did not have splenomegaly, a common finding in Q fever CAP, she did have mild hepatomegaly. Hepatomegaly is a uncommon in Q fever CAP but is not a feature of Legionnaires' disease. In the absence of a positive zoonotic contact history, the cardinal findings pointing to the diagnosis of Q fever in this

  13. Radiation-induced organizing pneumonia after stereotactic body radiotherapy for lung tumor

    PubMed Central

    Ochiai, Satoru; Nomoto, Yoshihito; Yamashita, Yasufumi; Murashima, Shuuichi; Hasegawa, Daisuke; Kurobe, Yusuke; Toyomasu, Yutaka; Kawamura, Tomoko; Takada, Akinori; II, Noriko

    2015-01-01

    The aim of this retrospective study was to investigate characteristics of organizing pneumonia (OP) after stereotactic body radiotherapy (SBRT) for lung tumor. Between September 2010 and June 2014, patients who were diagnosed as Stage I lung cancer and treated with SBRT at our institution were included in this study. A total of 78 patients (47 males with a median age of 80 years) were analyzed. The median follow-up period was 23 months. Five patients (6.4%) developed OP at 6–18 months after SBRT. The cumulative incidence of OP was 4.3% (95% confidence interval [CI], 1.1–11.0) and 8.2% (95% CI, 2.9–17.0) at 1 and 2 years, respectively. Tumor location (superior and middle lobe vs inferior lobe) was shown to be a borderline significant factor for the occurrence of OP (P = 0.069). In the subgroup analysis of patients with a radiographic follow-up period at least 6 months, or who died within 6 months after SBRT, 7 of 72 patients (9.7%) developed Grade 2 or 3 radiation pneumonitis (G2/3 RP) at 2–4 months after SBRT. A statistically significant association between G2/3 RP in the subacute phase and OP was shown (P = 0.040). In two of the five patients who developed OP, the symptoms and radiographic change were improved rapidly by corticosteroid administration. One patient had relapsed OP after suspending the treatment and re-administration was required. Three patients with minor symptoms were managed without corticosteroid administration and OP resolved without any relapse. The radiation-induced OP should be considered as one of the late lung injuries after SBRT for lung tumors. PMID:26338993

  14. Acute and subacute idiopathic interstitial pneumonias.

    PubMed

    Taniguchi, Hiroyuki; Kondoh, Yasuhiro

    2016-07-01

    Idiopathic interstitial pneumonias (IIPs) may have an acute or subacute presentation, or acute exacerbation may occur in a previously subclinical or unrecognized chronic IIP. Acute or subacute IIPs include acute interstitial pneumonia (AIP), cryptogenic organizing pneumonia (COP), nonspecific interstitial pneumonia (NSIP), acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) and AE-NSIP. Interstitial lung diseases (ILDs) including connective tissue disease (CTD) associated ILD, hypersensitivity pneumonitis, acute eosinophilic pneumonia, drug-induced lung disease and diffuse alveolar haemorrhage need to be differentiated from acute and subacute IIPs. Despite the severe lack of randomized controlled trials for the treatment of acute and subacute IIPs, the mainstream treatment remains corticosteroid therapy. Other potential therapies reported in the literature include corticosteroids and immunosuppression, antibiotics, anticoagulants, neutrophil elastase inhibitor, autoantibody-targeted treatment, antifibrotics and hemoperfusion therapy. With regard to mechanical ventilation, patients in recent studies with acute and subacute IIPs have shown better survival than those in previous studies. Therefore, a careful value-laden decision about the indications for endotracheal intubation should be made for each patient. Noninvasive ventilation may be beneficial to reduce ventilator associated pneumonia. PMID:27123874

  15. Pneumonia (image)

    MedlinePlus

    Pneumonia is an inflammation of the lungs caused by an infection. Many different organisms can cause it, including bacteria, viruses, and fungi. Pneumonia is a common illness that affects millions of ...

  16. Mycoplasma pneumonia

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/000082.htm Mycoplasma pneumonia To use the sharing features on this page, please enable JavaScript. Mycoplasma pneumonia is an infection of the lungs by the ...

  17. Quinupristin/dalfopristin and voriconazole controlled Staphylococcus epidermidis pneumonia and chronic necrotizing aspergillosis in a patient with severe lung degradation consequent to multiple treatments for Hodgkin's lymphoma.

    PubMed

    Muto, Hideharu; Kaneko, Shin; Machino, Takayuki; Okoshi, Yasushi; Mukai, Harumi Y; Suzukawa, Kazumi; Hasegawa, Yuichi; Imagawa, Shigehiko; Kojima, Hiroshi; Ishii, Yukio; Hitomi, Shigemi; Nagasawa, Toshiro

    2006-12-01

    We report here a 34-year-old woman with complicated severe opportunistic pulmonary infection, who was treated with the newly developed antibiotics quinupristin/dalfopristin (QPR/DPR) and voriconazole. She had received repeated chemotherapy, irradiation of the left lung, autologous and allogeneic bone marrow transplantation (BMT), and segmentectomy of the base of the left lung as treatments for Hodgkin's lymphoma. Although she had been in complete remission (CR), the structure of the left lung was severely degraded. Four years after achieving CR, she developed complicated life-threatening pulmonary infections with methicillin-resistant Staphylococcus epidermidis and Aspergillus niger during outpatient care. Chemotherapies with QPR/DPR for S. epidermidis pneumonia and voriconazole for chronic necrotizing pulmonary aspergillosis (CNPA) improved her symptoms rapidly without any major complications. QPR/DPR and voriconazole are considered effective for patients with life-threatening opportunistic pulmonary infections who have previously been treated with intensive regimens including radiotherapies to the lung. PMID:17235646

  18. [Sensitivity surveillance of Streptococcus pneumoniae isolates for several antibacterial agents in Gifu and Aichi prefectures (2011-2012)].

    PubMed

    Funatsu, Tori; Mizunaga, Shingo; Fukuda, Yoshiko; Nomura, Nobuhiko; Hashido, Hikonori; Mitsuyama, Junichi; Hatano, Masakazu; Yamaoka, Kazukiyo; Watanabe, Kunitomo; Asano, Yuko; Suematsu, Hiroyuki; Sawamura, Haruki; Matsukawa, Yoko; Ohta, Hirotoshi; Yamagishi, Yuka; Mikamo, Hiroshige; Matsubara, Shigenori; Shibata, Naohiro

    2015-08-01

    We investigated the susceptibility to antibacterial agents, genotype of penicillin-binding protein (PBP) genes and macrolide resistant genes, and the serotypes against 270 strains of Streptococcus pneumoniae isolated from medical facilities in Gifu and Aichi prefectures between October 2011 and April 2012. These results were compared with those against S. pneumoniae isolated in 2008-2009 and 2010-2011. The number of gPSSP with 3 normal PBP genes, gPISP with 1 or 2 normal PBP genes and gPRSP with 3 abnormal genes isolated in 2011-2012 was 15 (5.6%), 162 (60.0%) and 93 (34.4%) strains, respectively. Compared with those isolated in 2008-2009 and 2010-2011, the numbers of gPRSP were decreasing. On the other hand, the isolates with no macrolide-resistant gene, only mefA, only ermB, and both mefA and ermB were 16 (5.9%), 75 (27.8%), 153 (56.7%) and 26 (9.6%). Compared with those isolated in 2008-2009 and 2010-2011, the numbers of isolates with ermB, which was usually associated with high-level resistance, were increasing. The prevalent pneumococcal serotypes in children were type 3 (14.4%), following by type 15 and 19F (9.3%). The coverages of 7-valent pneumococcal conjugate vaccine (PCV7) and 13-valent pneumococcal conjugate vaccine (PCV13) were calculated as 22.9% and 49.2%, respectively. The coverages of PCV7 and PCV13 in gPRSP isolated from children were 47.7% (21/44 strains) and 72.7% (32/44 strains). The MIC90 of each antibacterial agent was as follows; 0.125pg/mL for imipenem, panipenem and garenoxacin, 0.25 μg/mL for meropenem and doripenem, 0.5 μg/mL for cefditoren, moxifloxacin and tosufloxacin, 1 μg/mL for amoxicillin, clavulanic acid/amoxicillin, cefteram, cefcapene and ceftriaxone, 2 μg/mL for benzylpenicillin, ampicillin, sulbactam/ampicillin, piperacillin, tazobactam/piperacillin and levofloxacin, 4 μg/mL for cefdinir, flomoxef and pazufloxacin, 16 μg/mL for minocycline, > 64 μg/mL for clarithromycin and azithromycin, and these MIC90s were about the

  19. In Vitro Streptococcus pneumoniae Biofilm Formation and In Vivo Middle Ear Mucosal Biofilm in a Rat Model of Acute Otitis Induced by S. pneumoniae

    PubMed Central

    Yadav, Mukesh Kumar; Chae, Sung-Won

    2012-01-01

    Objectives Streptococcus pneumoniae is one of the most common pathogens of otitis media (OM) that exists in biofilm, which enhances the resistance of bacteria against antibiotic killing and diagnosis, compared to the free-floating (planktonic) form. This study evaluated biofilm formation by S. pneumoniae on an abiotic surface and in the middle ear cavity in a rat model of OM. Methods In vitro biofilm formation was evaluated by inoculation of a 1:100 diluted S. pneumoniae cell suspension in a 96-well microplate. Adherent cells were quantified spectrophotometrically following staining with crystal violet by measurement of optical density at 570 nm. The ultrastructure of pneumococcal biofilm was assessed by scanning electron microscopy (SEM). For in vitro biofilm study, S. pneumoniae cell suspensions containing 1×107 colony forming units were injected through transtympanic membrane into the middle ear cavity of Sprague Dawley rats. The ultrastructure of middle ear mucus was observed by SEM 1 and 2 weeks post-inoculation. Results The in vitro study revealed robust biofilm formation by S. pneumoniae after 12-18 hours of incubation in high glucose medium, independent of exogenously supplied competence stimulating peptide and medium replacement. Adherent cells formed three-dimensional structures approximately 20-30 µm thick. The in vivo study revealed that ciliated epithelium was relatively resistant to biofilm formation and that biofilm formation occurred mainly on non-ciliated epithelium of the middle ear cavity. One week after inoculation, biofilm formation was high in 50% of the treated rats and low in 25% of the rats. After 2 weeks, biofilm formation was high and low in 25% and 37.5% of rats, respectively. Conclusion The results imply that glucose level is important for the S. pneumoniae biofilm formation and S. pneumoniae biofilm formation may play important role in the pathophysiology of OM. PMID:22977710

  20. IFN-τ inhibits S. aureus-induced inflammation by suppressing the activation of NF-κB and MAPKs in RAW 264.7 cells and mice with pneumonia.

    PubMed

    Zhao, Gan; Wu, Haichong; Jiang, Kangfeng; Rui, Guangze; Zhu, Zhe; Qiu, Changwei; Guo, Mengyao; Deng, Ganzhen

    2016-06-01

    Staphylococcus aureus (S. aureus), a significant cause of pneumonia, leads to severe inflammation. Few effective treatments or drugs have been reported for S. aureus infection. Interferon tau (IFN-τ) is a type I interferon with low cellular toxicity even at high doses. Previous studies have reported that IFN-τ could significantly mitigate tissue inflammation; however, IFN-τ treatment in S. aureus-induced pneumonia has not been well reported. Thus, the aim of this study was to identify the anti-inflammatory mechanism of IFN-τ in S. aureus-induced pneumonia in mice. A S. aureus-induced pneumonia model and RAW 264.7 cells were used in this research. The histopathological as well as lung wet to dry ratio (W/D) and myeloperoxidase (MPO) activity results showed that IFN-τ could protect the lung from S. aureus damage. In addition, ELISA and qPCR revealed that IFN-τ treatment led to a decreased expression of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in both the cells and mouse model, but IL-10 was increased. TLR2, which is involved in the response during S. aureus infection, was also down-regulated by IFN-τ treatment and directly affected NF-κB and MAPK pathway activation. Then, we examined the phosphorylation of IκBα, NF-κB p65 and MAPKs by western blotting, and the results displayed that the phosphorylation of IκBα, NF-κB p65 and MAPKs was inhibited upon IFN-τ treatment in both the cells and mouse model. These findings indicate that IFN-τ has anti-inflammatory properties in vitro and in vivo through the inhibition of NF-κB and MAPK activation, suggesting that IFN-τ may have potential as a therapeutic agent against S. aureus-induced inflammatory diseases. PMID:27025553

  1. Elevated Plasma Matrix Metalloproteinase-9 and Its Correlations with Severity of Disease in Patients with Ventilator-Associated Pneumonia

    PubMed Central

    Li, Yia-Ting; Wang, Yao-Chen; Lee, Hsiang-Lin; Lu, Min-Chi; Yang, Shun-Fa

    2016-01-01

    Ventilator-associated pneumonia (VAP) increases patient mortality and medical expenditure, and a real-time and reliable method for the rapid diagnosis of VAP may help reduce fatal complications. Matrix metalloproteinases-9 (MMP-9) is considered significant in the pathogenesis of lung inflammation and infection. Therefore, we examined its relationship with the clinical course of VAP. This retrospective observational study recruited 30 healthy volunteers, 12 patients who used mechanical ventilation without the development of VAP (hereafter, patients without VAP), and 30 patients with a clinical diagnosis of VAP (hereafter, patients with VAP). The activity and level of plasma MMP-9 were determined through a gelatin zymography assay and ELISA. Our results report that both plasma MMP-9 activity and concentration were significantly elevated in the acute stage of patients with VAP when compared with control group and patients without VAP (p < 0.001). Subsequently, the plasma MMP-9 of patients with VAP decreased significantly after antibiotic treatment. Furthermore, plasma MMP-9 concentration was positively correlated with the clinical pulmonary infection score (r = 0.409, p = 0.007), WBCs (r = 0.620, p < 0.001), and neutrophils counts (r = 0.335, p = 0.035). In addition, plasma MMP-9 is an excellent tool for recognizing VAP when the cutoff level is set to 92.62 ng/mL (AUC = 0.863, 95% CI = 0.761 to 0.932). In conclusions, we concluded that MMP-9 levels play a role in the development of VAP and might have the potential to be applied in the development of VAP therapies. PMID:27499696

  2. Laser therapy for severe radiation-induced rectal bleeding

    SciTech Connect

    Ahlquist, D.A.; Gostout, C.J.; Viggiano, T.R.; Pemberton, J.H.

    1986-12-01

    Four patients with chronic hematochezia and transfusion-dependent anemia from postradiation rectal vascular lesions were successfully managed by endoscopic laser coagulation. In all four patients, symptomatic, hematologic, and endoscopic improvement was evident. Laser therapy for severe radiation-induced rectal bleeding seems to be safe and efficacious and should be considered before surgical intervention.

  3. TLR2, TLR4 AND MyD88 Mediate Allergic Airway Disease (AAD) and Streptococcus pneumoniae-Induced Suppression of AAD

    PubMed Central

    Thorburn, Alison N.; Tseng, Hsin-Yi; Donovan, Chantal; Hansbro, Nicole G.; Jarnicki, Andrew G.; Foster, Paul S.; Gibson, Peter G.; Hansbro, Philip M.

    2016-01-01

    Background Exposure to non-pathogenic Streptococcus pneumoniae and vaccination are inversely associated with asthma. Studies in animal models demonstrate that airway administration of S. pneumoniae (live or killed), or its vaccines or components, suppresses the characteristic features of asthma in mouse models of allergic airway disease (AAD). These components could be developed into immunoregulatory therapies. S. pneumoniae components are recognized by Toll-like receptors (TLR) 2 and TLR4, and both induce inflammatory cell responses through the adaptor protein myeloid differentiation primary response gene 88 (MyD88). The involvement of TLR2, TLR4 and MyD88 in the pathogenesis of AAD and asthma is incompletely understood, and has not been studied in S. pneumoniae-mediated suppression of AAD. We investigated the role of TLR2, TLR4 and MyD88 in the development of AAD and S. pneumoniae-mediated suppression of AAD. Methods and Findings OVA-induced AAD and killed S. pneumoniae-mediated suppression of AAD were assessed in wild-type, TLR2-/-, TLR4-/-, TLR2/4-/- and MyD88-/- BALB/c mice. During OVA-induced AAD, TLR2, TLR4 and MyD88 were variously involved in promoting eosinophil accumulation in bronchoalveolar lavage fluid and blood, and T-helper type (Th)2 cytokine release from mediastinal lymph node T cells and splenocytes. However, all were required for the induction of airways hyperresponsiveness (AHR). In S. pneumoniae-mediated suppression of AAD, TLR2, TLR4 and MyD88 were variously involved in the suppression of eosinophilic and splenocyte Th2 responses but all were required for the reduction in AHR. Conclusions These results highlight important but complex roles for TLR2, TLR4 and MyD88 in promoting the development of OVA-induced AAD, but conversely in the S. pneumoniae-mediated suppression of AAD, with consistent and major contributions in both the induction and suppression of AHR. Thus, TLR signaling is likely required for both the development of asthma and the

  4. Granulomatous interstitial pneumonia induced by the intake of rice bran pickles: a rare subtype of pulmonary manifestation associated with food allergy.

    PubMed

    Kinoshita, Yoshiaki; Sakamoto, Atsuhiko; Aishima, Shinichi; Hidaka, Kouko

    2015-01-01

    Pulmonary manifestations associated with food allergy are rich in variety. We report the first case of food-induced granulomatous interstitial pneumonia mimicking hypersensitivity pneumonitis (HP). A 77-year-old woman with respiratory symptoms was referred to our hospital. We performed a surgical lung biopsy, which showed the features of granulomatous interstitial pneumonia. Her clinical history resembled those observed in HP. However, avoidance of exposure to the causative antigens did not improve her symptoms. Moreover, the patient had some features inconsistent with HP, such as elevated serum IgE levels, blood eosinophilia, intrathoracic lymphadenopathies and pleural effusion. Therefore, we pursued another extrinsic non-inhaled antigen as the cause of pulmonary involvements. We noted that she had been eating homemade rice bran pickles, and pulmonary involvements were induced by an ingestion challenge test. We suggest that granulomatous interstitial pneumonia may be a rare subtype of the pulmonary manifestations associated with food allergy. PMID:25858927

  5. A Case of Severe Ganciclovir-Induced Encephalopathy

    PubMed Central

    Sakamoto, Hikaru; Hirano, Makito; Nose, Kazuhiro; Ueno, Shuichi; Oki, Takashi; Sugimoto, Koichi; Nishioka, Tsukasa; Kusunoki, Susumu; Nakamura, Yusaku

    2013-01-01

    Background Ganciclovir, a drug against cytomegalovirus (CMV) infection, is generally well tolerated, but can cause neurotoxicity such as encephalopathy. Although ganciclovir-induced encephalopathy has been described in several reports, a literature search revealed that ganciclovir concentrations in the blood or cerebrospinal fluid were previously measured in only 3 patients with encephalopathy. Symptoms usually include confusion and disturbed consciousness, which mimic CMV encephalitis. Prompt and accurate diagnosis is thus sometimes difficult, and is derived solely from accumulated clinical information of definite cases, since ganciclovir concentrations, not routinely measured, become available after several days or a few weeks. Case Presentation Here, we summarize clinical information of all patients with definite ganciclovir-induced encephalopathy including our own patient, who had severe symptoms, with the highest reported trough concentration of ganciclovir in the blood, and underwent therapeutic dialysis with complete recovery. Conclusion Our summary of patients with definite encephalopathy could lead to prompt and accurate diagnoses. PMID:24403897

  6. Phenytoin-induced severe gingival overgrowth in a child

    PubMed Central

    Kumar, Rakesh; Singh, Rajeev Kumar; Verma, Nidhi; Verma, Umesh Pratap

    2014-01-01

    Gingival enlargement or overgrowth (GO) is a common complication of the anticonvulsant drug phenytoin (PHT). GO is evident in almost half of the patients receiving PHT therapy. PHT-induced gingival overgrowth (PGO) is more common in children than in adults and affects both males and females equally. PGO may vary from mild to severe and does not seem to be dose dependant. It is supposed that PHT and its metabolites cause a direct effect on the periodontal tissues; however, poor oral hygiene may contribute to the severity of gingival inflammation in patients with PGO. Management of PGO includes meticulous oral hygiene practice to reduce inflammation and surgical excision of the overgrown tissue, known as gingivectomy. We present a case of PHT-induced severe GO in a 10-year-old boy and discuss the clinical features, aetiology, pathogenesis and management of PGO. PMID:25053668

  7. Prevalence and correlates of treatment failure among Kenyan children hospitalised with severe community-acquired pneumonia: a prospective study of the clinical effectiveness of WHO pneumonia case management guidelines

    PubMed Central

    Agweyu, Ambrose; Kibore, Minnie; Digolo, Lina; Kosgei, Caroline; Maina, Virginia; Mugane, Samson; Muma, Sarah; Wachira, John; Waiyego, Mary; Maleche-Obimbo, Elizabeth

    2014-01-01

    Objective To determine the extent and pattern of treatment failure (TF) among children hospitalised with community-acquired pneumonia at a large tertiary hospital in Kenya. Methods We followed up children aged 2–59 months with WHO-defined severe pneumonia (SP) and very severe pneumonia (VSP) for up to 5 days for TF using two definitions: (i) documentation of pre-defined clinical signs resulting in change of treatment (ii) primary clinician's decision to change treatment with or without documentation of the same pre-defined clinical signs. Results We enrolled 385 children. The risk of TF varied between 1.8% (95% CI 0.4–5.1) and 12.4% (95% CI 7.9–18.4) for SP and 21.4% (95% CI 15.9–27) and 39.3% (95% CI 32.5–46.4) for VSP depending on the definition applied. Higher rates were associated with early changes in therapy by clinician in the absence of an obvious clinical rationale. Non-adherence to treatment guidelines was observed for 70/169 (41.4%) and 67/201 (33.3%) of children with SP and VSP, respectively. Among children with SP, adherence to treatment guidelines was associated with the presence of wheeze on initial assessment (P = 0.02), while clinician non-adherence to guideline-recommended treatments for VSP tended to occur in children with altered consciousness (P < 0.001). Using propensity score matching to account for imbalance in the distribution of baseline clinical characteristics among children with VSP revealed no difference in TF between those treated with the guideline-recommended regimen vs. more costly broad-spectrum alternatives [risk difference 0.37 (95% CI −0.84 to 0.51)]. Conclusion Before revising current pneumonia case management guidelines, standardised definitions of TF and appropriate studies of treatment effectiveness of alternative regimens are required. Objectif Déterminer l'ampleur et les caractéristiques de l’échec du traitement (ET) chez les enfants hospitalisés avec une pneumonie acquise dans la communauté dans

  8. Bilateral spontaneous pneumothorax secondary to aspiration pneumonia induced by a wristwatch lodged at the pharyngoesophageal junction.

    PubMed

    Kawai, Chihiro; Miyao, Masashi; Kotani, Hirokazu; Tamaki, Keiji

    2015-06-01

    Bilateral spontaneous pneumothorax secondary to disease is rare and seldom encountered in forensic autopsies; however, traumatic bilateral pneumothorax occurs often. Herein, we present a forensic case involving a 50-year-old woman who died 4 days after ingesting a wristwatch. Postmortem computed tomography and autopsy findings demonstrated that the wristwatch was lodged at the pharyngoesophageal junction, that she had a bilateral pneumothorax unaccompanied by any thoracic wound, and that macular hemorrhagic lesions on the lung surfaces were responsible for the pneumothorax. A histological examination of the macular lesions revealed that they were aspiration pneumonia foci with many birefringent foreign materials. Furthermore, a necrotic process secondary to aspiration pneumonia with a one way check-valve hyperinflation caused by foreign materials in the bronchioles was the most probable pathogenesis of her pneumothorax. To our knowledge, this is the first reported case of a bilateral secondary spontaneous pneumothorax caused by a large foreign body at the pharyngoesophageal junction leading to death. PMID:25724839

  9. A case of montelukast induced hypercholesterolemia, severe hypertriglyceridemia and pancreatitis

    PubMed Central

    Das, Saibal; Mondal, Somnath; Dey, Jayanta Kumar; Bandyopadhyay, Sanjib; Saha, Indranil; Tripathi, Santanu Kumar

    2013-01-01

    Montelukast sodium is a leukotriene inhibitor, and competitively antagonizes cys-LT1 receptor and used widely and effectively in treating allergic rhinitis, bronchial asthma and allied respiratory conditions. This case report outlines a rare case of montelukast induced hypercholesterolemia, severe hypertriglyceridemia and acute pancreatitis in a 22 years old male patient. The patient was taking 10 mg oral montelukast daily for allergic rhinitis. Although his symptoms improved considerably, after 2 months of therapy, he experienced unusual weight gain and got admitted with severe pain abdomen. Clinical and other relevant investigation findings revealed the presence of acute pancreatitis with associated hypercholesterolemia and severe hypertriglyceridemia. There were no evidences of any other possible hereditary, surgical, metabolic, infective, organic or other pathologic causes giving rise to these conditions. De-challenge was done and the patient was treated conservatively resulting in reversal of the diseased state. Naranjo adverse drug reaction probability scale suggested that it was 'probable' that oral administration of montelukast was responsible for the acute pancreatitis associated with hypercholesterolemia and severe hypertriglyceridemia. There is only a singular and confirmed reported case of montelukast induced hypertriglyceridemia from India. For patients taking montelukast for a long duration, routine lipid profile monitoring should be done, and if these patients present with symptoms of epigastric and periumbilical pain with vomiting, provisions for screening acute pancreatitis might be warranted. PMID:24023457

  10. Plasma IL-6/IL-10 Ratio and IL-8, LDH, and HBDH Level Predict the Severity and the Risk of Death in AIDS Patients with Pneumocystis Pneumonia.

    PubMed

    Sun, Jia; Su, Junwei; Xie, Yirui; Yin, Michael T; Huang, Ying; Xu, Lijun; Zhou, Qihui; Zhu, Biao

    2016-01-01

    Objective. To identify blood biomarkers to predict severity and mortality in AIDS PCP patients. Methods. Biomarkers including clinical parameters and plasma inflammatory cytokines were assessed in 32 HIV-infected patients with Pneumocystis pneumonia (PCP) at time of admission. Predictive value of the biomarkers for clinical severity and in-hospital mortality was evaluated by corresponding ROC curve. Results. Levels of CRP, WBC, LDH, HBDH, and Ferritin were significantly higher in the severe and nonsurvivor AIDS PCP patients. These important biochemical indicators have inverse correlation with oxygenation index, especially levels of LDH (P = 0.008, R (2) = 0.258), HBDH (P = 0.001, R (2) = 0.335), and Ferritin (P = 0.005, R (2) = 0.237). Plasma IL-8 and IL-6 levels were significantly higher in patients with PaO2/FiO2 ≤ 200 mmHg and nonsurvivors than in those with PaO2/FiO2 > 200 mmHg and survivors. Severe and nonsurvival groups showed higher ratio of mean IL-6/IL-10 level (1.78 ± 1.56, P < 0.001; 1.11 ± 0.72, P = 0.043), larger AUC (95% CI 0.781-1.000, P < 0.001; 95% CI 0.592-0.917, P = 0.043), and more significantly inverse correlation with the oxygenation index. Conclusion. Plasma IL-8, LDH, and HBDH levels and IL-6/IL-10 ratio could be helpful for early evaluation of the severity and predicting fatal outcomes in AIDS PCP patients. PMID:27579328

  11. Plasma IL-6/IL-10 Ratio and IL-8, LDH, and HBDH Level Predict the Severity and the Risk of Death in AIDS Patients with Pneumocystis Pneumonia

    PubMed Central

    Sun, Jia; Su, Junwei; Xie, Yirui; Yin, Michael T.; Huang, Ying; Xu, Lijun; Zhou, Qihui

    2016-01-01

    Objective. To identify blood biomarkers to predict severity and mortality in AIDS PCP patients. Methods. Biomarkers including clinical parameters and plasma inflammatory cytokines were assessed in 32 HIV-infected patients with Pneumocystis pneumonia (PCP) at time of admission. Predictive value of the biomarkers for clinical severity and in-hospital mortality was evaluated by corresponding ROC curve. Results. Levels of CRP, WBC, LDH, HBDH, and Ferritin were significantly higher in the severe and nonsurvivor AIDS PCP patients. These important biochemical indicators have inverse correlation with oxygenation index, especially levels of LDH (P = 0.008, R2 = 0.258), HBDH (P = 0.001, R2 = 0.335), and Ferritin (P = 0.005, R2 = 0.237). Plasma IL-8 and IL-6 levels were significantly higher in patients with PaO2/FiO2 ≤ 200 mmHg and nonsurvivors than in those with PaO2/FiO2 > 200 mmHg and survivors. Severe and nonsurvival groups showed higher ratio of mean IL-6/IL-10 level (1.78 ± 1.56, P < 0.001; 1.11 ± 0.72, P = 0.043), larger AUC (95% CI 0.781–1.000, P < 0.001; 95% CI 0.592–0.917, P = 0.043), and more significantly inverse correlation with the oxygenation index. Conclusion. Plasma IL-8, LDH, and HBDH levels and IL-6/IL-10 ratio could be helpful for early evaluation of the severity and predicting fatal outcomes in AIDS PCP patients. PMID:27579328

  12. Restoring Functional Status: A Long-Term Case Report of Severe Lung and Ventilatory Muscle Pump Dysfunction Involving Recurrent Bacterial Pneumonias

    PubMed Central

    Sobush, Dennis C.; Laatsch, Linda; Lipchik, Randolph J.

    2012-01-01

    Background and Purpose Prolonged mechanical ventilation contributes to immobility and deconditioning making efforts to safely discontinue ventilator support desirable. This case report documents how implementing physical therapy treatment interventions, based on the Guide to Physical Therapist Practice, can help to restore a person's functional status even after multiple years of mechanical ventilation dependency. Case Description A patient (female; aged 63 years) with severe restrictive and obstructive ventilatory impairment has survived 34 recurrent pneumonias involving 6 bacterial pathogens while being mechanically ventilated at home. A 3-year study was approved and informed consent obtained for a home exercise program of resistive extremity and inspiratory muscle training along with exercise reconditioning. Tolerable distances walked, maximal inspiratory and expiratory pressures, hours spent on versus off mechanical ventilation, activities performed within and around her home, and community excursions taken were charted. Outcomes Daily time tolerated off the ventilator improved from less than one to 12 hours, distance walked in 6 minutes increased 33%, and maximal inspiratory and expiratory pressures improved 62% and 9.6% respectively. These improvements made out-of-home social excursions possible. Discussion and Conclusions This patient's functional status improved following multiple physical therapy interventions dictated by the evaluation of initial physical therapy examination findings according to the Guide to Physical Therapist Practice. Long term mechanical ventilator dependency in the home environment did not exclude this patient from achieving clinically significant gains in functional status even when having severe restrictive and obstructive ventilator impairment. PMID:22833704

  13. Chronic mould exposure as a risk factor for severe community acquired pneumonia in a patient requiring extra corporeal membrane oxygenation.

    PubMed

    Thomas, Stephanie; Hassan, Ibrahim; Barker, Julian; Ashworth, Alan; Barnes, Anita; Fedor, Igor; Feddy, Lee; Hayes, Tim; Malagon, Ignacio; Stirling, Sarah; Szentgyorgyi, Lajos; Mutton, Ken; Richardson, Malcolm

    2015-01-01

    A previously fit and well man developed acute respiratory failure due to environmental mould exposure from living in damp rental accommodation. Despite aggressive intensive care management he rapidly deteriorated and required respiratory and cardiac Extracorporeal Membrane Oxygenation. We hypothesize that poor domiciliary conditions may make an underestimated contribution to community respiratory disease. These conditions may present as acute and severe illness with non-typical pathogens identified. PMID:26236598

  14. Chronic mould exposure as a risk factor for severe community acquired pneumonia in a patient requiring extra corporeal membrane oxygenation

    PubMed Central

    Thomas, Stephanie; Hassan, Ibrahim; Barker, Julian; Ashworth, Alan; Barnes, Anita; Fedor, Igor; Feddy, Lee; Hayes, Tim; Malagon, Ignacio; Stirling, Sarah; Szentgyorgyi, Lajos; Mutton, Ken; Richardson, Malcolm

    2015-01-01

    A previously fit and well man developed acute respiratory failure due to environmental mould exposure from living in damp rental accommodation. Despite aggressive intensive care management he rapidly deteriorated and required respiratory and cardiac Extracorporeal Membrane Oxygenation. We hypothesize that poor domiciliary conditions may make an underestimated contribution to community respiratory disease. These conditions may present as acute and severe illness with non-typical pathogens identified. PMID:26236598

  15. Viral pneumonia

    MedlinePlus

    ... Names Pneumonia - viral; "Walking pneumonia" - viral Images Lungs Respiratory system References Lee FE, Treanor J. Viral infections. In: Mason RJ, VC Broaddus, Martin TR, et al, eds. Murray and Nadel’s Textbook of Respiratory Medicine . 5th ed. Philadelphia, PA: Saunders Elsevier; 2010: ...

  16. Vancomycin-induced thrombocytopaenia in a patient with severe pancreatitis.

    PubMed

    Rowland, Simon P; Rankin, Iain; Sheth, Hemant

    2013-01-01

    Vancomycin-induced thrombocytopenia is a rare side effect of a commonly used drug that may cause life-threatening disease. A 51-year-old man was treated for an episode of acute severe alcohol-induced pancreatitis complicated by development of a peripancreatic fluid collection. He developed fever of unknown origin and was treated with intravenous vancomycin and piperacillin with tazobactam. On day 6 of vancomycin therapy his platelet count dropped to 46×10(9)/L (237×10(9)/L on day 1 of treatment) and by day 8 of therapy platelets had fallen to a nadir of 9×10(9)/L. The patient at this stage displayed a florid purpuric rash and haematoma formation on attempted intravenous cannulation. A clinical diagnosis of vancomycin-induced thrombocytopaenia was made and the drug withdrawn. After 3 days a significant improvement in the platelet count was noted, rising to 56 × 10(9)/L. Immunofluorescence testing (PIFT) ruled out teicoplanin and heparin as causes of drug-induced thrombocytopenia. PMID:24132444

  17. Cell morphology variations of Klebsiella pneumoniae induced by acetate stress using biomimetic vesicle assay.

    PubMed

    Lu, Shengguo; Han, Yuwang; Duan, Xujia; Luo, Fang; Zhu, Lingyan; Li, Shuang; Huang, He

    2013-10-01

    Supplementation with acetate under low levels was used as a novel approach to control the morphological development of Klebsiella pneumoniae aimed to improve 1,3-propanediol (1,3-PD) production. A full range of morphological types formed from rod shape to oval shape even round shape in response to different concentrations of acetate. The cell growth and 1,3-PD productions in the shake flasks with 0.5 g/L acetate addition were improved by 9.4 and 28.37%, respectively, as compared to the control, while the cell became shorter and began to lose its original shape. The cell membrane penetration by acetate was investigated by the biomimetic vesicles, while higher concentration of acetate led to more moderate colorimetric transitions. Moreover, the percentage composition of unsaturated fatty acid (UFA) was increased as well as the increased concentrations of acetate, whereas higher UFA percentage, higher fluidity of bacterial cell membrane. PMID:23892619

  18. Severe Hemoperitoneum after Patient Self-Induced Fecal Evacuation

    PubMed Central

    Gianesini, S.; Lanzara, S.; Stano, R.; Santini, S.; De Troia, A.; Gennari, S.; Vasquez, G.

    2011-01-01

    An increasing incidence of rectal injuries following patient self-induced harmful acts, aimed to sexual or laxatives porpouses, is a fact reported in literature (El-Ashaal et al., 2008). We herein report a case of severe hemoperitoneum related to a middle and upper rectal third seromuscolar tear caused by a self-induced fecal evacuation by means of an arrow with a covered cork tip. An urgent intestinal diversion by means of a Hartmann's operation was performed. The clinical case is presented in relation to the literature debate, regarding the issue of primary repair or resection and anastomosis versus fecal diversion for penetrating rectal injuries (Fabian, 2002; Cleary et al., 2006; Office of the Surgeon General, 1943; Busic et al., 2002). In conclusion, the importance of avoiding an anastomotic breakdown in a patient undergoing a hemorrhagic shock is highlighted. PMID:21876699

  19. Severe hemoperitoneum after patient self-induced fecal evacuation.

    PubMed

    Gianesini, S; Lanzara, S; Stano, R; Santini, S; De Troia, A; Gennari, S; Vasquez, G

    2011-01-01

    An increasing incidence of rectal injuries following patient self-induced harmful acts, aimed to sexual or laxatives porpouses, is a fact reported in literature (El-Ashaal et al., 2008). We herein report a case of severe hemoperitoneum related to a middle and upper rectal third seromuscolar tear caused by a self-induced fecal evacuation by means of an arrow with a covered cork tip. An urgent intestinal diversion by means of a Hartmann's operation was performed. The clinical case is presented in relation to the literature debate, regarding the issue of primary repair or resection and anastomosis versus fecal diversion for penetrating rectal injuries (Fabian, 2002; Cleary et al., 2006; Office of the Surgeon General, 1943; Busic et al., 2002). In conclusion, the importance of avoiding an anastomotic breakdown in a patient undergoing a hemorrhagic shock is highlighted. PMID:21876699

  20. Bacteriology and drug susceptibility analysis of pus from patients with severe intra-abdominal infection induced by abdominal trauma

    PubMed Central

    ZHANG, SHAOYI; REN, LELE; LI, YOUSHENG; WANG, JIAN; YU, WENKUI; LI, NING; LI, JIESHOU

    2014-01-01

    The aim of the present study was to retrospectively analyze the bacteriology and drug susceptibility of pus flora from abdominal trauma patients with severe intra-abdominal infection (SIAI). A total of 41 patients with SIAI induced by abdominal trauma were enrolled in the study, from which 123 abdominal pus samples were obtained. The results from laboratory microbiology and drug sensitivity were subjected to susceptibility analysis using WHONET software. A total of 297 strains were isolated in which Gram-negative bacteria, Gram-positive bacteria and fungi accounted for 53.5 (159/297), 44.1 (131/297) and 0.7% (2/297), respectively. Anaerobic bacteria accounted for 1.7%. The five predominant bacteria were Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), Klebsiella pneumoniae (K. pneumoniae), Enterococcus faecalis and Pseudomonas aeruginosa (P. aeruginosa). E. coli was highly susceptible to cefoperazone (91%) and imipenem (98%), while Gram-positive cocci were highly susceptible to teicoplanin (100%) and linezolid (100%). S. aureus was 100% susceptible to vancomycin and K. pneumoniae was highly susceptible to imipenem (100%) and amikacin (79%). P. aeruginosa was the most susceptible to ciprofloxacin (90%). Gram-negative bacterial infection was present in the majority of cases of SIAI. However, a large number of patients were infected by Gram-positive bacteria, particularly S. aureus that exhibited significant resistance to penicillin (100%), oxacillin (100%) and a third-generation cephalosporin antibiotic cefotaxime (95%). Amongst the pathogenic bacteria that cause SIAI, both Gram-negative and Gram-positive bacteria account for a high proportion, so high-level and broad-spectrum antibiotics should be initially used. PMID:24940451

  1. Severe cefepime-induced status epilepticus treated with haemofiltration.

    PubMed

    Suarez-de-la-Rica, A; Hernández-Gancedo, C; López-Tofiño, A; Maseda, E; Gilsanz, F

    2016-01-01

    Neurotoxicity caused by cefepime may occur predominantly in patients with impaired renal function. A case of a cefepime-induced non-convulsive status epilepticus (NCSE) is presented. A 65-year-old woman suffered a severe NCSE due to cefepime in the presence of acute renal failure, requiring coma induction with sodium thiopental. A serious interaction between valproic acid (VPA) and meropenem was also produced after changing cefepime to meropenem. Continuous veno-venous haemofiltration was employed to improve cefepime clearance, and the patient progressively regained her previous mental condition. In conclusion, the cefepime dose must be adjusted according to renal function in order to avoid toxicity in patients with renal failure. Electroencephalogram should be considered in cases of acute confusional state in patients receiving cefepime, to achieve early detection of NCSE. Continuous renal replacement therapy may be successfully employed in severe cases in order to accelerate cefepime removal. Likewise, meropenem should not be used concomitantly with VPA. PMID:26633605

  2. A Survey of Radiation-Induced Bronchiolitis Obliterans Organizing Pneumonia Syndrome After Breast-Conserving Therapy in Japan

    SciTech Connect

    Ogo, Etsuyo Komaki, Ritsuko; Fujimoto, Kiminori; Uchida, Masafumi; Abe, Toshi; Nakamura, Katsumasa; Mitsumori, Michihide; Sekiguchi, Kenji; Kaneyasu, Yuko; Hayabuchi, Naofumi

    2008-05-01

    Purpose: We observed a rare and unique occurrence of radiation-induced pulmonary injury outside the tangential field for early breast cancer treatment. The findings appeared to be idiopathic and were called radiation-induced bronchiolitis obliterans organizing pneumonia (BOOP) syndrome. We surveyed major hospitals in Japan to review their findings of radiation-induced BOOP, in particular the clinical and pictorial characteristics of the entity. Methods and Materials: We reviewed surveys completed and returned by 20 institutions. The survey responses were based on a total of 37 cases of BOOP syndrome. We also reviewed X-ray and computed tomography scans provided by these institutions. We discussed the information derived from the questionnaire and analyzed patients' characteristics, methods used in the treatment of BOOP syndrome, and prognosis. Results: The incidence of the radiation-induced BOOP syndrome was about 1.8% (37 of 2,056). We did not find a relationship between the characteristics of patients and the occurrence of radiation-induced BOOP syndrome. The pulmonary findings were classified into four patterns on chest computed tomography scans. Progression of the pulmonary lesions observed on chest X-ray was classified into three patterns. Pneumonitis appeared within 6 months after radiotherapy was completed and disappeared within 6-12 months after its onset. At 5-year follow-up, 2 patients had died, 1 of breast cancer and the other of interstitial pneumonitis, which seemed to be idiopathic and unrelated to the radiation-induced BOOP syndrome. Conclusions: Although the incidence of BOOP syndrome and its associated prognosis are not significant, the patients' clinical condition must be carefully followed.

  3. Mitochondrial ROS Induces Cardiac Inflammation via a Pathway through mtDNA Damage in a Pneumonia-Related Sepsis Model.

    PubMed

    Yao, Xiao; Carlson, Deborah; Sun, Yuxiao; Ma, Lisha; Wolf, Steven E; Minei, Joseph P; Zang, Qun S

    2015-01-01

    We have previously shown that mitochondria-targeted vitamin E (Mito-Vit-E), a mtROS specific antioxidant, improves cardiac performance and attenuates inflammation in a pneumonia-related sepsis model. In this study, we applied the same approaches to decipher the signaling pathway(s) of mtROS-dependent cardiac inflammation after sepsis. Sepsis was induced in Sprague Dawley rats by intratracheal injection of S. pneumoniae. Mito-Vit-E, vitamin E or vehicle was administered 30 minutes later. In myocardium 24 hours post-inoculation, Mito-Vit-E, but not vitamin E, significantly protected mtDNA integrity and decreased mtDNA damage. Mito-Vit-E alleviated sepsis-induced reduction in mitochondria-localized DNA repair enzymes including DNA polymerase γ, AP endonuclease, 8-oxoguanine glycosylase, and uracil-DNA glycosylase. Mito-Vit-E dramatically improved metabolism and membrane integrity in mitochondria, suppressed leakage of mtDNA into the cytoplasm, inhibited up-regulation of Toll-like receptor 9 (TLR9) pathway factors MYD88 and RAGE, and limited RAGE interaction with its ligand TFAM in septic hearts. Mito-Vit-E also deactivated NF-κB and caspase 1, reduced expression of the essential inflammasome component ASC, and decreased inflammatory cytokine IL-1β. In vitro, both Mito-Vit-E and TLR9 inhibitor OND-I suppressed LPS-induced up-regulation in MYD88, RAGE, ASC, active caspase 1, and IL-1β in cardiomyocytes. Since free mtDNA escaped from damaged mitochondria function as a type of DAMPs to stimulate inflammation through TLR9, these data together suggest that sepsis-induced cardiac inflammation is mediated, at least partially, through mtDNA-TLR9-RAGE. At last, Mito-Vit-E reduced the circulation of myocardial injury marker troponin-I, diminished apoptosis and amended morphology in septic hearts, suggesting that mitochondria-targeted antioxidants are a potential cardioprotective approach for sepsis. PMID:26448624

  4. Mitochondrial ROS Induces Cardiac Inflammation via a Pathway through mtDNA Damage in a Pneumonia-Related Sepsis Model

    PubMed Central

    Yao, Xiao; Carlson, Deborah; Sun, Yuxiao; Ma, Lisha; Wolf, Steven E.; Minei, Joseph P.; Zang, Qun S.

    2015-01-01

    We have previously shown that mitochondria-targeted vitamin E (Mito-Vit-E), a mtROS specific antioxidant, improves cardiac performance and attenuates inflammation in a pneumonia-related sepsis model. In this study, we applied the same approaches to decipher the signaling pathway(s) of mtROS-dependent cardiac inflammation after sepsis. Sepsis was induced in Sprague Dawley rats by intratracheal injection of S. pneumoniae. Mito-Vit-E, vitamin E or vehicle was administered 30 minutes later. In myocardium 24 hours post-inoculation, Mito-Vit-E, but not vitamin E, significantly protected mtDNA integrity and decreased mtDNA damage. Mito-Vit-E alleviated sepsis-induced reduction in mitochondria-localized DNA repair enzymes including DNA polymerase γ, AP endonuclease, 8-oxoguanine glycosylase, and uracil-DNA glycosylase. Mito-Vit-E dramatically improved metabolism and membrane integrity in mitochondria, suppressed leakage of mtDNA into the cytoplasm, inhibited up-regulation of Toll-like receptor 9 (TLR9) pathway factors MYD88 and RAGE, and limited RAGE interaction with its ligand TFAM in septic hearts. Mito-Vit-E also deactivated NF-κB and caspase 1, reduced expression of the essential inflammasome component ASC, and decreased inflammatory cytokine IL–1β. In vitro, both Mito-Vit-E and TLR9 inhibitor OND-I suppressed LPS-induced up-regulation in MYD88, RAGE, ASC, active caspase 1, and IL–1β in cardiomyocytes. Since free mtDNA escaped from damaged mitochondria function as a type of DAMPs to stimulate inflammation through TLR9, these data together suggest that sepsis-induced cardiac inflammation is mediated, at least partially, through mtDNA-TLR9-RAGE. At last, Mito-Vit-E reduced the circulation of myocardial injury marker troponin-I, diminished apoptosis and amended morphology in septic hearts, suggesting that mitochondria-targeted antioxidants are a potential cardioprotective approach for sepsis. PMID:26448624

  5. Sepsis Caused by Extended-Spectrum Beta-Lactamase (ESBL)-Positive K. pneumoniae and E. coli: Comparison of Severity of Sepsis, Delay of Anti-Infective Therapy and ESBL Genotype.

    PubMed

    Sakellariou, Christian; Gürntke, Stephan; Steinmetz, Ivo; Kohler, Christian; Pfeifer, Yvonne; Gastmeier, Petra; Schwab, Frank; Kola, Axel; Deja, Maria; Leistner, Rasmus

    2016-01-01

    Infections with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) are associated with increased mortality. Outcome differences due to various species of ESBL-E or ESBL genotypes are not well investigated. We conducted a cohort study to assess risk factors for mortality in cases of ESBL-E bacteremia (K. pneumoniae or E. coli) and the risk factors for sepsis with organ failure. All consecutive patients of our institution from 2008 to 2011 with bacteremia due to ESBL-E were included. Basic epidemiological data, underlying comorbidities, origin of bacteremia, severity of sepsis and delay of appropriate anti-infective treatment were collected. Isolates were PCR-screened for the presence of ESBL genes and plasmid-mediated AmpC β-lactamases. Cox proportional hazard regression on mortality and multivariable logistic regression on risk factors for sepsis with organ failure was conducted. 219 cases were included in the analysis: 73.1% due to E. coli, 26.9% due to K. pneumoniae. There was no significant difference in hospital mortality (ESBL-E. coli, 23.8% vs. ESBL-K. pneumoniae 27.1%, p = 0.724). However, the risk of sepsis with organ failure was associated in cases of K. pneumoniae bacteremia (OR 4.5, p<0.001) and patients with liver disease (OR 3.4, p = 0.004) or renal disease (OR 6.8, p<0.001). We found significant differences in clinical presentation of ESBL-E bacteremia due to K. pneumoniae compared to E. coli. As K. pneumoniae cases showed a more serious clinical presentation as E. coli cases and were associated with different risk factors, treatment and prevention strategies should be adjusted accordingly. PMID:27442425

  6. Sepsis Caused by Extended-Spectrum Beta-Lactamase (ESBL)-Positive K. pneumoniae and E. coli: Comparison of Severity of Sepsis, Delay of Anti-Infective Therapy and ESBL Genotype

    PubMed Central

    Steinmetz, Ivo; Kohler, Christian; Pfeifer, Yvonne; Gastmeier, Petra; Schwab, Frank; Kola, Axel; Deja, Maria; Leistner, Rasmus

    2016-01-01

    Infections with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) are associated with increased mortality. Outcome differences due to various species of ESBL-E or ESBL genotypes are not well investigated. We conducted a cohort study to assess risk factors for mortality in cases of ESBL-E bacteremia (K. pneumoniae or E. coli) and the risk factors for sepsis with organ failure. All consecutive patients of our institution from 2008 to 2011 with bacteremia due to ESBL-E were included. Basic epidemiological data, underlying comorbidities, origin of bacteremia, severity of sepsis and delay of appropriate anti-infective treatment were collected. Isolates were PCR-screened for the presence of ESBL genes and plasmid-mediated AmpC β-lactamases. Cox proportional hazard regression on mortality and multivariable logistic regression on risk factors for sepsis with organ failure was conducted. 219 cases were included in the analysis: 73.1% due to E. coli, 26.9% due to K. pneumoniae. There was no significant difference in hospital mortality (ESBL-E. coli, 23.8% vs. ESBL-K. pneumoniae 27.1%, p = 0.724). However, the risk of sepsis with organ failure was associated in cases of K. pneumoniae bacteremia (OR 4.5, p<0.001) and patients with liver disease (OR 3.4, p = 0.004) or renal disease (OR 6.8, p<0.001). We found significant differences in clinical presentation of ESBL-E bacteremia due to K. pneumoniae compared to E. coli. As K. pneumoniae cases showed a more serious clinical presentation as E. coli cases and were associated with different risk factors, treatment and prevention strategies should be adjusted accordingly. PMID:27442425

  7. CREBH Determines the Severity of Sulpyrine-Induced Fatal Shock

    PubMed Central

    Saiga, Hiroyuki; Ma, Ji Su; Ohshima, Jun; Machimura, Sakaaki; Sasai, Miwa; Kimura, Taishi; Ueda, Yoshiyasu; Kayama, Hisako; Takeda, Kiyoshi

    2013-01-01

    Although the pyrazolone derivative sulpyrine is widely used as an antipyretic analgesic drug, side effects, including fatal shock, have been reported. However, the molecular mechanism underlying such a severe side effect is largely unclear. Here, we report that the transcription factor CREBH that is highly expressed in the liver plays an important role in fatal shock induced by sulpyrine in mice. CREBH-deficient mice were resistant to experimental fatal sulpyrine shock. We found that sulpyrine-induced expression of cytochrome P450 2B (CYP2B) family genes, which are involved in sulpyrine metabolism, in the liver was severely impaired in CREBH-deficient mice. Moreover, introduction of CYP2B in CREBH-deficient liver restored susceptibility to sulpyrine. Furthermore, ectopic expression of CREBH up-regulated CYP2B10 promoter activity, and in vivo knockdown of CREBH in wild-type mice conferred a significant resistance to fatal sulpyrine shock. These data demonstrate that CREBH is a positive regulator of CYP2B in response to sulpyrine administration, which possibly results in fatal shock. PMID:23409047

  8. [Healthcare associated pneumonia].

    PubMed

    Ceccato, Adrián; González, Alejandra; Heres, Marcela; Peluffo, Graciela; Monteverde, Alfredo

    2014-01-01

    Healthcare associated pneumonia (HCAP) is a different entity from community-acquired pneumonia and nosocomial pneumonia. There exist several risk factors that lead to it. Different features, severity and pathogens are described and there is controversy about the initial empirical treatment. The aim of this work was to analyze the etiology, clinical characteristics and evolution of the HCAP. It is a prospective and observational study that includes 60 patients; 32 had previous hospitalization during the last 90 days, 9 were under hemodialysis, 12 residents in nursing homes and 7 received outpatient intravenous therapy. The mean age was 63 years and the severity index was high. The most frequent comorbidities were cardiac. The radiological compromise was more than one lobe in 42% of cases and 18% had pleural effusion. Germ isolation was obtained in 30% of patients where the most isolated germ was Streptococcus pneumoniae (9 cases). There was only one case of multidrug-resistance. The mean length hospital stay was 11 days, six patients had complications and mortality was 5%. Complications but not mortality were significantly higher in the group of patients on hemodialysis (p value = 0.011 and 0.056 respectively). The antibiotic-resistance found do not justify a change in the antibiotic treatment commonly used for community acquired pneumonia. PMID:24561835

  9. Acute Pneumonia.

    PubMed

    Arshad, Hammad; Fasanya, Adebayo; Cheema, Tariq; Singh, Anil C

    2016-01-01

    Acute pneumonia is an active infection of the lungs that results when an individual at risk gets exposed to a particular microbiological pathogen. Acute pneumonia is the leading cause of death in the United States that is attributable to an infection. The risk factors, pathogenesis, and microbiological organisms involved differ if the pneumonia develops in the community versus health care-associated environment. The development of concise and comprehensive guidelines has led to an improvement in the management of the problem. However, the emergence of multidrug-resistant organisms and the increase in the percentage of elderly population keep mortality risk very substantial. PMID:26919676

  10. A case of losartan-induced severe hyponatremia

    PubMed Central

    Das, Saibal; Bandyopadhyay, Sanjib; Ramasamy, Anand; Prabhu, V. Vinoth; Pachiappan, Sudhakar

    2015-01-01

    This case report outlines a very rare case of losartan-induced severe hyponatremia in a 73-year-old type 2 diabetic patient. The patient was initiated with 50 mg daily oral losartan monotherapy for newly diagnosed moderate hypertension. After 3.5 months of taking the drug, he presented to the emergency department in a drowsy state with severe generalized weakness and occasional palpitations. He was a known diabetic for the last 3 years and well controlled by oral metformin alone. On examination, his serum sodium level was found to be 123 meq/L. There were no evidences of any other possible metabolic, infective, organic or other pathologic causes giving rise to that condition, except losartan itself. De-challenge was done and he was treated vigorously resulting in reversal of the diseased state. Naranjo adverse drug reaction probability scale suggested that it was “probable” that oral losartan was responsible for the development of severe hyponatremia in this patient. PMID:26816476

  11. Pneumonia caused by Pittsburgh pneumonia agent: radiologic manifestations

    SciTech Connect

    Muder, R.R.; Reddy, S.C.; Yu, V.L.; Kroboth, F.J.

    1984-03-01

    Using an objective scoring system, chest radiographs were reviewed in 23 cases of pneumonia due to the Pittsburgh pneumonia agent (PPA, Tatlockia micdadei, Legionella micdadei), including six cases of pneumonia with simultaneous isolation of PPA and L pneumophila (Legionnaires' disease). Infiltrates were typically segmental to lobar; nodular infiltrates were noted in three cases. Spread to additional lobes after presentation occurred in four of 17 PPA infections. Pneumonia caused by both PPA and L pneumophila was unusually severe, with involvement of all lobes occurring in four of six cases, compared with one of 17 cases of PPA infection (p>0.02). Radiographic severity did not correlate with underlying disease, immune status, or outcome. The majority of patients receiving erythromycin demonstrated objective radiologic improvement. In a patients, population that included nonimmunosuppressed patient, nodule formation and rapid radiologic progression were not found to be characteristic of PPA pneumonia.

  12. Alcohol induced diabetic ketoacidosis exacerbated by an acute respiratory infection with Klebsiella pneumoniae.

    PubMed

    Distel, Caleb; Jacobson, Stephanie; Tille, Patricia M

    2013-01-01

    Ketoacidosis is a metabolic condition that occurs as a result of an insufficient amount of insulin. The lack of insulin results in an increased release of glucose from the liver and an excess of ketone bodies as a result of the breakdown of adipose tissue. This occurs when carbohydrates are unable to be properly processed for needed energy requirements during cellular metabolism. Ketoacidosis is commonly linked to diabetes mellitus. Diabetes mellitus is a condition where the body is unable to produce the proper amount of insulin or is unable to effectively respond to insulin stimulation. Excessive alcohol use can damage the pancreas, reducing insulin secretion. Other conditions such as pneumonia or urinary tract infections can trigger the release of counter-regulatory hormones that may contribute to the decrease in insulin's activity and secretion. Symptoms of diabetic ketoacidosis often include nausea and vomiting, increased thirst and urine production, hyperglycemia, abdominal pain, shortness of breath, confusion, headache, general weakness, fatigue and increased heart rate. If left untreated, diabetic ketoacidosis can lead to more serious complications including circulatory collapse, decreased blood potassium levels, infection and cerebral edema. The following case study presents a complex condition of ketoacidosis associated with a bacterial infection compounded by the patient's history of alcohol abuse. PMID:23772471

  13. Hydrocarbon pneumonia

    MedlinePlus

    Pneumonia - hydrocarbon ... Coughing Fever Shortness of breath Smell of a hydrocarbon product on the breath Stupor (decreased level of ... Most children who drink or inhale hydrocarbon products and develop ... hydrocarbons may lead to rapid respiratory failure and death.

  14. Viral pneumonia

    MedlinePlus

    More serious infections can result in respiratory failure, liver failure, and heart failure. Sometimes, bacterial infections occur during or just after viral pneumonia, which may lead to more serious forms ...

  15. Comorbidities and Disease Severity as Risk Factors for Carbapenem-Resistant Klebsiella pneumoniae Colonization: Report of an Experience in an Internal Medicine Unit

    PubMed Central

    Nouvenne, Antonio; Ticinesi, Andrea; Lauretani, Fulvio; Maggio, Marcello; Lippi, Giuseppe; Guida, Loredana; Morelli, Ilaria; Ridolo, Erminia; Borghi, Loris; Meschi, Tiziana

    2014-01-01

    Background Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an emerging multidrug-resistant nosocomial pathogen, spreading to hospitalized elderly patients. Risk factors in this setting are unclear. Our aims were to explore the contribution of multi-morbidity and disease severity in the onset of CRKP colonization/infection, and to describe changes in epidemiology after the institution of quarantine-ward managed by staff-cohorting. Methods and Findings With a case-control design, we evaluated 133 CRKP-positive patients (75 M, 58 F; mean age 79±10 years) and a control group of 400 CRKP-negative subjects (179 M, 221 F; mean age 79±12 years) admitted to Internal Medicine and Critical Subacute Care Unit of Parma University Hospital, Italy, during a 10-month period. Information about comorbidity type and severity, expressed through Cumulative Illness Rating Scale-CIRS, was collected in each patient. During an overall 5-month period, CRKP-positive patients were managed in an isolation ward with staff cohorting. A contact-bed isolation approach was established in the other 5 months. The effects of these strategies were evaluated with a cross-sectional study design. CRKP-positive subjects had higher CIRS comorbidity index (12.0±3.6 vs 9.1±3.5, p<0.0001) and CIRS severity index (3.2±0.4 vs 2.9±0.5, p<0.0001), along with higher cardiovascular, respiratory, renal and neurological disease burden than control group. CIRS severity index was associated with a higher risk for CRKP-colonization (OR 13.3, 95%CI6.88–25.93), independent of comorbidities. Isolation ward activation was associated with decreased monthly incidence of CRKP-positivity (from 16.9% to 1.2% of all admissions) and infection (from 36.6% to 22.5% of all positive cases; p = 0.04 derived by Wilcoxon signed-rank test). Mortality rate did not differ between cases and controls (21.8% vs 15.2%, p = 0.08). The main limitations of this study are observational design and lack of data about prior

  16. Analysis of Factors Associated With Radiation-Induced Bronchiolitis Obliterans Organizing Pneumonia Syndrome After Breast-Conserving Therapy

    SciTech Connect

    Katayama, Norihisa Sato, Shuhei; Katsui, Kuniaki; Takemoto, Mitsuhiro; Tsuda, Toshihide; Yoshida, Atsushi; Morito, Tsuneharu; Nakagawa, Tomio; Mizuta, Akifumi; Waki, Takahiro; Niiya, Harutaka; Kanazawa, Susumu

    2009-03-15

    Purpose: To evaluate factors associated with radiation-induced bronchiolitis obliterans organizing pneumonia (BOOP) syndrome after breast-conserving therapy. Methods and Materials: A total of 702 women with breast cancer who received radiotherapy after breast-conserving surgery at seven institutions between July 1995 and December 2006 were analyzed. In all patients, the whole breast was irradiated with two tangential photon beams. The criteria used for the diagnosis of radiation-induced BOOP syndrome were as follows: (1) radiotherapy to the breast within 12 months, (2) general and/or respiratory symptoms lasting for {>=}2 weeks, (3) radiographs showing lung infiltration outside the radiation port, and (4) no evidence of a specific cause. Results: Radiation-induced BOOP syndrome was seen in 16 patients (2.3%). Eleven patients (68.8%) were administered steroids. The duration of steroid administration ranged from 1 week to 3.7 years (median, 1.1 years). Multivariate analysis revealed that age ({>=}50 years; odds ratio [OR] 8.88; 95% confidence interval [CI] 1.16-67.76; p = 0.04) and concurrent endocrine therapy (OR 3.05; 95% CI 1.09-8.54; p = 0.03) were significantly associated with BOOP syndrome. Of the 161 patients whose age was {>=}50 years and who received concurrent endocrine therapy, 10 (6.2%) developed BOOP syndrome. Conclusions: Age ({>=}50 years) and concurrent endocrine therapy can promote the development of radiation-induced BOOP syndrome after breast-conserving therapy. Physicians should carefully follow patients who received breast-conserving therapy, especially those who are older than 50 years and received concurrent endocrine therapy during radiotherapy.

  17. Large Eddy Simulations of Severe Convection Induced Turbulence

    NASA Technical Reports Server (NTRS)

    Ahmad, Nash'at; Proctor, Fred

    2011-01-01

    Convective storms can pose a serious risk to aviation operations since they are often accompanied by turbulence, heavy rain, hail, icing, lightning, strong winds, and poor visibility. They can cause major delays in air traffic due to the re-routing of flights, and by disrupting operations at the airports in the vicinity of the storm system. In this study, the Terminal Area Simulation System is used to simulate five different convective events ranging from a mesoscale convective complex to isolated storms. The occurrence of convection induced turbulence is analyzed from these simulations. The validation of model results with the radar data and other observations is reported and an aircraft-centric turbulence hazard metric calculated for each case is discussed. The turbulence analysis showed that large pockets of significant turbulence hazard can be found in regions of low radar reflectivity. Moderate and severe turbulence was often found in building cumulus turrets and overshooting tops.

  18. A case of severe psychosis induced by novel recreational drugs

    PubMed Central

    Dragogna, Filippo; Oldani, Lucio; Buoli, Massimiliano; Altamura, A. Carlo

    2014-01-01

    Introduction:  The use of novel recreational drugs is becoming of public interest, especially after recent international alerts about their cardiovascular and neurological toxicity. Additionally, little is known about the psychiatric consequences of the long-term use of these compounds. Case presentation: We describe a case of severe psychotic episode likely induced by chronic use of a combination of new recreational drugs (methylenedioxypyrovalerone, mephedrone, butylone and alpha-pyrrolidinopentiophenone). The patient had no psychiatric history and showed poor response to conventional antipsychotic treatment (haloperidol). Conclusions: This case illustrates the potential negative effects of recreational drugs that cannot be limited to an acute psychotic episode but might determine a condition of prolonged paranoid psychosis. Although the use of these compounds is currently increasing, such molecules might often pass undetected in patients accessing the emergency room, leading to misdiagnosis (e.g. schizophrenic episode) and lack of appropriate treatment. PMID:25352977

  19. Treating leukemia at the risk of inducing severe anemia.

    PubMed

    Chen, Wendy S; Zhu, Helen He; Feng, Gen-Sheng

    2016-05-01

    Anemia is a frequently observed adverse effect in cancer patients who receive chemotherapy or drugs designed to block specific oncogenic signaling pathways, although the underlying mechanisms are poorly understood. An article first published online (Zhu HH, Luo X, Zhang K, et al. Proc Natl Acad Sci USA 2015;112:13342-13347) presented data indicating that cell type-specific pathway cross-talk is likely an important mechanism to consider. Shp2 and Pten, two master regulators of central cytoplasmic signaling pathways, oppose each other in myeloproliferation and leukemogenesis, but cooperate in promoting erythropoiesis. Thus, genetic ablation or pharmacologic inhibition of Shp2 suppresses the leukemogenic effect of Pten loss, yet simultaneously induces severe anemia in mice with Pten deficiency in blood cells. PMID:26826310

  20. Drebrin inhibits cofilin-induced severing of F-actin.

    PubMed

    Grintsevich, Elena E; Reisler, Emil

    2014-08-01

    Molecular cross-talk between neuronal drebrin A and cofilin is believed to be a part of the activity-dependent cytoskeleton-modulating pathway in dendritic spines. Impairments in this pathway are implicated also in synaptic dysfunction in Alzheimer's disease, Down syndrome, epilepsy, and normal aging. However, up to now the molecular interplay between cofilin and drebrin has not been elucidated. TIRF microscopy and solution experiments revealed that full length drebrin A or its actin binding core (Drb1-300) inhibits, but do not abolish cofilin-induced severing of actin filaments. Cosedimentation experiments showed that F-actin can be fully occupied with combination of these two proteins. The dependence of cofilin binding on fractional saturation of actin filaments with drebrin suggests direct competition between these two proteins for F-actin binding. This implies that cofilin and drebrin can either overcome or reverse the allosteric changes in F-actin induced by the competitor's binding. The ability of cofilin to displace drebrin from actin filaments is pH dependent and is facilitated at acidic pH (6.8). Pre-steady state kinetic experiments reveal that both binding and dissociation of drebrin to/from actin filaments is faster than that reported for cooperative binding of cofilin. We found, that drebrin displacement by cofilin is greatly inhibited when actin severing is abolished, which might be linked to the cooperativity of drebrin binding to actin filaments. Our results contribute to molecular understanding of the competitive interactions of drebrin and cofilin with actin filaments. PMID:25047716

  1. Animal models of polymicrobial pneumonia

    PubMed Central

    Hraiech, Sami; Papazian, Laurent; Rolain, Jean-Marc; Bregeon, Fabienne

    2015-01-01

    Pneumonia is one of the leading causes of severe and occasionally life-threatening infections. The physiopathology of pneumonia has been extensively studied, providing information for the development of new treatments for this condition. In addition to in vitro research, animal models have been largely used in the field of pneumonia. Several models have been described and have provided a better understanding of pneumonia under different settings and with various pathogens. However, the concept of one pathogen leading to one infection has been challenged, and recent flu epidemics suggest that some pathogens exhibit highly virulent potential. Although “two hits” animal models have been used to study infectious diseases, few of these models have been described in pneumonia. Therefore the aims of this review were to provide an overview of the available literature in this field, to describe well-studied and uncommon pathogen associations, and to summarize the major insights obtained from this information. PMID:26170617

  2. Expression of activation-induced cytidine deaminase enhances the clearance of pneumococcal pneumonia: evidence of a subpopulation of protective anti-pneumococcal B1a cells.

    PubMed

    Yamamoto, Natsuo; Kerfoot, Steven M; Hutchinson, Andrew T; Dela Cruz, Charles S; Nakazawa, Naomi; Szczepanik, Marian; Majewska-Szczepanik, Monika; Nazimek, Katarzyna; Ohana, Noboru; Bryniarski, Krzysztof; Mori, Tsutomu; Muramatsu, Masamichi; Kanemitsu, Keiji; Askenase, Philip W

    2016-01-01

    We describe a protective early acquired immune response to pneumococcal pneumonia that is mediated by a subset of B1a cells. Mice deficient in B1 cells (xid), or activation-induced cytidine deaminase (AID(-/-) ), or invariant natural killer T (iNKT) cells (Jα18(-/-) ), or interleukin-13 (IL-13(-/-) ) had impaired early clearance of pneumococci in the lung, compared with wild-type mice. In contrast, AID(-/-) mice adoptively transferred with AID(+/+) B1a cells, significantly cleared bacteria from the lungs as early as 3 days post infection. We show that this early bacterial clearance corresponds to an allergic contact sensitivity-like cutaneous response, probably due to a subpopulation of initiating B1a cells. In the pneumonia model, these B1a cells were found to secrete higher affinity antigen-specific IgM. In addition, as in contact sensitivity, iNKT cells were required for the anti-pneumococcal B1a cell initiating response, probably through early production of IL-13, given that IL-13(-/-) mice also failed to clear infection. Our study is the first to demonstrate the importance of AID in generating an appropriate B1a cell response to pathogenic bacteria. Given the antibody affinity and pneumonia resistance data, natural IgM produced by conventional B1a cells are not responsible for pneumonia clearance compared with the AID-dependent subset. PMID:26456931

  3. Toll-like receptor 4-positive macrophages protect mice from Pasteurella pneumotropica-induced pneumonia

    NASA Technical Reports Server (NTRS)

    Hart, Marcia L.; Mosier, Derek A.; Chapes, Stephen K.

    2003-01-01

    This study investigates Toll-like receptor 4 (TLR4)-positive macrophages in early recognition and clearance of pulmonary bacteria. TLR4 is a trans-membrane receptor that is the primary recognition molecule for lipopolysaccharide of gram-negative bacteria. The TLR4(Lps-del) mouse strains C57BL10/ScN (B10) and STOCK Abb(tm1) TLR4(Lps-del) Slc11a1(s)(B10 x C2D) are susceptible to pulmonary infections and develop pneumonia when naturally or experimentally infected by the opportunistic bacterium Pasteurella pneumotropica. Since these mice have the TLR4(Lps-del) genotype, we hypothesized that reconstitution of mice with TLR4-positive macrophages would provide resistance to this bacterium. A cultured macrophage cell line (C2D macrophages) and bone marrow cells from C2D mice were adoptively transferred to B10 and B10 x C2D mice by intraperitoneal injection. C2D macrophages increased B10 and B10 x C2D mouse resistance to P. pneumotropica. In C2D-recipient mice there was earlier transcription of tumor necrosis factor alpha and chemokines JE and macrophage inflammatory protein 2 (MIP-2) in the lungs of B10 and B10 x C2D mice, and there was earlier transcription of KC and MIP-1alpha in B10 x C2D mice. In addition, the course of inflammation following experimental Pasteurella challenge was altered in C2D recipients. C2D macrophages also protected B10 x C2D mice, which lack CD4(+) T cells. These data indicate that macrophages are critical for pulmonary immunity and can provide host resistance to P. pneumotropica. This study indicates that TLR4-positive macrophages are important for early recognition and clearance of pulmonary bacterial infections.

  4. Rattus model utilizing selective pulmonary ischemia induces bronchiolitis obliterans organizing pneumonia.

    PubMed

    Densmore, John C; Jeziorczak, Paul M; Clough, Anne V; Pritchard, Kirkwood A; Cummens, Breana; Medhora, Meetha; Rao, Arjun; Jacobs, Elizabeth R

    2013-03-01

    Bronchiolitis obliterans organizing pneumonia (BOOP), a morbid condition when associated with lung transplant and chronic lung disease, is believed to be a complication of ischemia. Our goal was to develop a simple and reliable model of lung ischemia in the Sprague-Dawley rat that would produce BOOP. Unilateral ischemia without airway occlusion was produced by an occlusive slipknot placed around the left main pulmonary artery. Studies were performed 7 days later. Relative pulmonary and systemic flow to each lung was measured by injection of technetium Tc 99m macroaggregated albumin. Histological sections were examined for structure and necrosis and scored for BOOP. Apoptosis was detected by immunohistochemistry with an antibody against cleaved caspase 3. Pulmonary artery blood flow to left lungs was less than 0.1% of the cardiac output, and bronchial artery circulation was ∼2% of aortic artery flow. Histological sections from ischemic left lungs consistently showed Masson bodies, inflammation, and young fibroblasts filling the distal airways and alveoli, consistent with BOOP. In quantitative evaluation of BOOP using epithelial changes, inflammation and fibrosis were higher in ischemic left lungs than right or sham-operated left lungs. Apoptosis was increased in areas exhibiting histological BOOP, but there was no histological evidence of necrosis. Toll-like receptor 4 expression was increased in ischemic left lungs over right. An occlusive slipknot around the main left pulmonary artery in rats produces BOOP, providing direct evidence that ischemia without immunomodulation or coinfection is sufficient to initiate this injury. It also affords an excellent model to study signaling and genetic mechanisms underlying BOOP. PMID:23364425

  5. Increased Serum LIGHT Levels Correlate with Disease Progression and Severity of Interstitial Pneumonia in Patients with Dermatomyositis: A Case Control Study

    PubMed Central

    Kotani, Takuya; Takeuchi, Tohru; Ishida, Takaaki; Masutani, Ryota; Isoda, Kentaro; Hata, Kenichiro; Yoshida, Shuzo; Makino, Shigeki; Hanafusa, Toshiaki

    2015-01-01

    Background Activated CD8+ T cells play an important role in the pathogenesis of dermatomyositis (DM) with interstitial pneumonia (IP). Serum CD8+ T-cell activator, LIGHT, and Th1/Th2/Th17 cytokines were measured in DM-IP patients and compared with clinical parameters to investigate their usefulness. Methods The correlations between the clinical findings and serum LIGHT and Th1/Th2/Th17 cytokine levels were investigated in 21 patients with DM-IP (14 with rapidly progressive IP [RPIP] and 7 with chronic IP [CIP], including 4 fatal cases of IP). Results The median serum LIGHT level was 119 (16–335.4) pg/ml, which was higher than that in healthy control subjects and DM patients without IP. The median serum IL–6 level was 14.7 (2.4–154.5) pg/ml (n = 13). The other cytokines were detected in only a few patients. The median serum LIGHT level in DM-RPIP patients (156 [49.6–335.4] pg/ml) was significantly higher than that in DM-CIP patients (94.3 [16–164.2] pg/ml) (P = 0.02). The serum IL–6 level did not correlate with either progression or outcome of DM-IP. ROC curve analysis determined a serum LIGHT level of ≥120 pg/ml to be the cut-off value for the rapid progression of DM-IP. Serum LIGHT levels correlated significantly with %DLco (R = 0.55, P = 0.04) and total ground-glass opacity scores (R = 0.72, P = 0.0002). The serum LIGHT level significantly decreased to 100.5 (12.4–259.3) pg/ml 4 weeks after treatment initiation (P = 0.04). Conclusions The serum LIGHT level may be a promising marker of disease progression and severity in patients with DM-IP. PMID:26448572

  6. How Is Pneumonia Treated?

    MedlinePlus

    ... page from the NHLBI on Twitter. How Is Pneumonia Treated? Treatment for pneumonia depends on the type ... can go back to their normal routines. Bacterial Pneumonia Bacterial pneumonia is treated with medicines called antibiotics. ...

  7. Cutaneous Vasculitis, Interstitial Pneumonia with Crazy-Paving Appearance, and Positive pANCA in a Patient with Severe Crohn's Disease

    PubMed Central

    Chen, Guang-liang; Wang, Juan; Li, Li-mei; Mo, Han-you; Ye, Shuang

    2014-01-01

    Cutaneous vasculitis, interstitial pneumonia with crazy-paving appearance on high-resolution computed tomography, and repeated positive perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) are rarely found together in patients with inflammatory bowel disease in the existing literature. We report the case of a Chinese patient previously diagnosed with cutaneous vasculitis and interstitial pneumonia, who presented with acute pain and mass in his right lower quadrant a couple of years later. The terminal ileum biopsy and postoperative pathology confirmed Crohn's disease (CD). PMID:25371834

  8. Coagulopathy induced by acidosis, hypothermia and hypocalcaemia in severe bleeding.

    PubMed

    De Robertis, E; Kozek-Langenecker, S A; Tufano, R; Romano, G M; Piazza, O; Zito Marinosci, G

    2015-01-01

    Acidosis, hypothermia and hypocalcaemia are determinants for morbidity and mortality during massive hemorrhages. However, precise pathological mechanisms of these environmental factors and their potential additive or synergistic anticoagulant and/or antiplatelet effects are not fully elucidated and are at least in part controversial. Best available evidences from experimental trials indicate that acidosis and hypothermia progressively impair platelet aggregability and clot formation. Considering the cell-based model of coagulation physiology, hypothermia predominantly prolongs the initiation phase, while acidosis prolongs the propagation phase of thrombin generation. Acidosis increases fibrinogen breakdown while hypothermia impairs its synthesis. Acidosis and hypothermia have additive effects. The effect of hypocalcaemia on coagulopathy is less investigated but it appears that below the cut-off of 0.9 mmol/L, several enzymatic steps in the plasmatic coagulation system are blocked while above that cut-off effects remain without clinical sequalae. The impact of environmental factor on hemostasis is underestimated in clinical practice due to our current practice of using routine coagulation laboratory tests such as partial thromboplastin time or prothrombin time, which are performed at standardized test temperature, after pH correction, and upon recalcification. Temperature-adjustments are feasible in viscoelastic point-of-care tests such as thrombelastography and thromboelastometry which may permit quantification of hypothermia-induced coagulopathy. Rewarming hypothermic bleeding patients is highly recommended because it improves patient outcome. Despite the absence of high-quality evidence, calcium supplementation is clinical routine in bleeding management. Buffer administration may not reverse acidosis-induced coagulopathy but may be essential for the efficacy of coagulation factor concentrates such as recombinant activated factor VII. PMID:24608516

  9. Pulse pressure variation does not reflect stroke volume variation in mechanically ventilated rats with lipopolysaccharide-induced pneumonia.

    PubMed

    Cherpanath, Thomas G V; Smeding, Lonneke; Lagrand, Wim K; Hirsch, Alexander; Schultz, Marcus J; Groeneveld, Johan A B

    2014-01-01

    1. The present study examined the relationship between centrally measured stroke volume variation (SVV) and peripherally derived pulse pressure variation (PPV) in the setting of increased total arterial compliance (CA rt ). 2. Ten male Wistar rats were anaesthetized, paralysed and mechanically ventilated before being randomized to receive intrapulmonary lipopolysaccharide (LPS) or no LPS. Pulse pressure (PP) was derived from the left carotid artery, whereas stroke volume (SV) was measured directly in the left ventricle. Values of SVV and PPV were calculated over three breaths. Balloon inflation of a catheter positioned in the inferior vena cava was used, for a maximum of 30 s, to decrease preload while the SVV and PPV measurements were repeated. Values of CA rt were calculated as SV/PP. 3. Intrapulmonary LPS increased CA rt and SV. Values of SVV and PPV increased in both LPS-treated and untreated rats during balloon inflation. There was a correlation between SVV and PPV in untreated rats before (r = 0.55; P = 0.005) and during (r = 0.69; P < 0.001) occlusion of the vena cava. There was no such correlation in LPS-treated rats either before (r = -0.08; P = 0.70) or during (r = 0.36; P = 0.08) vena cava occlusion. 4. In conclusion, under normovolaemic and hypovolaemic conditions, PPV does not reflect SVV during an increase in CA rt following LPS-induced pneumonia in mechanically ventilated rats. Our data caution against their interchangeability in human sepsis. PMID:24372424

  10. Efficacy of high doses of oral penicillin versus amoxicillin in the treatment of adults with non-severe pneumonia attended in the community: study protocol for a randomised controlled trial

    PubMed Central

    2013-01-01

    other antimicrobial treatment will be necessary. Any clinical result other than the anterior will be considered as treatment failure. A total of 210 patients will be recruited to detect a non-inferiority margin of 15% between the two treatments with a minimum power of 80% considering an alpha error of 2.5% for a unilateral hypothesis and maximum possible losses of 15%. Discussion This pragmatic trial addresses the long-standing hypothesis that the administration of high doses of a narrow-spectrum antibiotic (penicillin V) in patients with non-severe pneumonia attended in the community is not less effective than high doses of amoxicillin (treatment currently recommended) in patients under the age of 65 years. Trial registration EudraCT number 2012-003511-63. PMID:23594463

  11. Chlamydia pneumoniae (TWAR).

    PubMed Central

    Kuo, C C; Jackson, L A; Campbell, L A; Grayston, J T

    1995-01-01

    Chlamydia pneumoniae (TWAR) is a recently recognized third species of the genus Chlamydia that causes acute respiratory disease. It is distinct from the other two chlamydial species that infect humans, C. trachomatis and C. psittaci, in elementary body morphology and shares less than 10% of the DNA homology with those species. The organism has a global distribution, with infection most common among children between the ages of 5 and 14 years. In children, TWAR infection is usually mild or asymptomatic, but it may be more severe in adults. Pneumonia and bronchitis are the most common clinical manifestations of infection, and TWAR is responsible for approximately 10% of cases of pneumonia and 5% of cases of bronchitis in the United States. The microimmunofluorescence serologic assay is specific for TWAR and can distinguish between recent and past infections. The organism can be isolated in cell culture; however, PCR techniques have recently facilitated its detection in tissues and clinical specimens. PMID:8665464

  12. Extracorporeal Treatment in Severe Hypertriglyceridemia-Induced Pancreatitis.

    PubMed

    Zeitler, Heike; Balta, Zeynep; Klein, Burkhard; Strassburg, Christian P

    2015-08-01

    Plasmapheresis is a well-accepted treatment option in severe hypertriglyceridemia-induced pancreatitis (HTGP). The rationale behind this approach is the depletion of triglycerides and the reduction of inflammatory cytokines. The time span between onset of clinical symptoms and start of plasmapheresis might have an important impact on mortality. Hyperviscosity of patients' plasma represents another special challenge for the applied separation technology. The procedures can be performed either by centrifugal device (CFD) or membrane based (MBS) units. The present study reports the outcome of 10 patients suffering from HTG. The expected mortality of the collective was 25%. Plasmapheresis was started after an average 16.3 h (SD ± 6.7 h) after onset of symptoms. No mortality occurred. Apheresis was statistically equally effective with both devices. A median of 3 sessions reduced the TG level to normal and correlated with patients' improvement. During follow up, three patients developed a pancreatic pseudocyst requiring surgical intervention without further complication. PMID:25851561

  13. Vinpocetine inhibits Streptococcus pneumoniae-induced upregulation of mucin MUC5AC expression via induction of MKP-1 phosphatase in the pathogenesis of otitis media.

    PubMed

    Lee, Ji-Yun; Komatsu, Kensei; Lee, Byung-Cheol; Miyata, Masanori; O'Neill Bohn, Ashley; Xu, Haidong; Yan, Chen; Li, Jian-Dong

    2015-06-15

    Mucin overproduction is a hallmark of otitis media (OM). Streptococcus pneumoniae is one of the most common bacterial pathogens causing OM. Mucin MUC5AC plays an important role in mucociliary clearance of bacterial pathogens. However, if uncontrolled, excessive mucus contributes significantly to conductive hearing loss. Currently, there is a lack of effective therapeutic agents that suppress mucus overproduction. In this study, we show that a currently existing antistroke drug, vinpocetine, a derivative of the alkaloid vincamine, inhibited S. pneumoniae-induced mucin MUC5AC upregulation in cultured middle ear epithelial cells and in the middle ear of mice. Moreover, vinpocetine inhibited MUC5AC upregulation by inhibiting the MAPK ERK pathway in an MKP-1-dependent manner. Importantly, ototopical administration of vinpocetine postinfection inhibited MUC5AC expression and middle ear inflammation induced by S. pneumoniae and reduced hearing loss and pneumococcal loads in a well-established mouse model of OM. Thus, these studies identified vinpocetine as a potential therapeutic agent for inhibiting mucus production in the pathogenesis of OM. PMID:25972475

  14. Natural Antioxidant Betanin Protects Rats from Paraquat-Induced Acute Lung Injury Interstitial Pneumonia

    PubMed Central

    Ma, Deshun; Zhang, Miao; Yang, Xuelian; Tan, Dehong

    2015-01-01

    The effect of betanin on a rat paraquat-induced acute lung injury (ALI) model was investigated. Paraquat was injected intraperitoneally at a single dose of 20 mg/kg body weight, and betanin (25 and 100 mg/kg/d) was orally administered 3 days before and 2 days after paraquat administration. Rats were sacrificed 24 hours after the last betanin dosage, and lung tissue and bronchoalveolar lavage fluid (BALF) were collected. In rats treated only with paraquat, extensive lung injury characteristic of ALI was observed, including histological changes, elevation of lung : body weight ratio, increased lung permeability, increased lung neutrophilia infiltration, increased malondialdehyde (MDA) and myeloperoxidase (MPO) activity, reduced superoxide dismutase (SOD) activity, reduced claudin-4 and zonula occluden-1 protein levels, increased BALF interleukin (IL-1) and tumor necrosis factor (TNF)-α levels, reduced BALF IL-10 levels, and increased lung nuclear factor kappa (NF-κB) activity. In rats treated with betanin, paraquat-induced ALI was attenuated in a dose-dependent manner. In conclusion, our results indicate that betanin attenuates paraquat-induced ALI possibly via antioxidant and anti-inflammatory mechanisms. Thus, the potential for using betanin as an auxilliary therapy for ALI should be explored further. PMID:25861636

  15. Granzyme A impairs host defense during Streptococcus pneumoniae pneumonia.

    PubMed

    van den Boogaard, Florry E; van Gisbergen, Klaas P J M; Vernooy, Juanita H; Medema, Jan P; Roelofs, Joris J T H; van Zoelen, Marieke A D; Endeman, Henrik; Biesma, Douwe H; Boon, Louis; Van't Veer, Cornelis; de Vos, Alex F; van der Poll, Tom

    2016-08-01

    Streptococcus pneumoniae is the most common causative pathogen in community-acquired pneumonia (CAP). Granzyme A (GzmA) is a serine protease produced by a variety of cell types involved in the immune response. We sought to determine the role of GzmA on the host response during pneumococcal pneumonia. GzmA was measured in bronchoalveolar lavage fluid (BALF) harvested from CAP patients from the infected and contralateral uninfected side and in lung tissue slides from CAP patients and controls. In CAP patients, GzmA levels were increased in BALF obtained from the infected lung. Human lungs showed constitutive GzmA expression by both parenchymal and nonparenchymal cells. In an experimental setting, pneumonia was induced in wild-type (WT) and GzmA-deficient (GzmA(-/-)) mice by intranasal inoculation of S. pneumoniae In separate experiments, WT and GzmA(-/-) mice were treated with natural killer (NK) cell depleting antibodies. Upon infection with S. pneumoniae, GzmA(-/-) mice showed a better survival and lower bacterial counts in BALF and distant body sites compared with WT mice. Although NK cells showed strong GzmA expression, NK cell depletion did not influence bacterial loads in either WT or GzmA(-/-) mice. These results implicate that GzmA plays an unfavorable role in host defense during pneumococcal pneumonia by a mechanism that does not depend on NK cells. PMID:27343190

  16. [Aspiration pneumonia].

    PubMed

    Almirall, Jordi; Cabré, Mateu; Clavé, Pere

    2007-09-29

    The incidence and the prevalence of aspiration pneumonia (AP) in the community is poorly defined. It increases in direct relation with age and underlying diseases. The pathogenesis of AP presumes the contribution of risk factors that alter swallowing funtion and predispose the orofaringe and gastric region to bacterial colonization. The microbial etiology of AP involves Staphylococcus aureus, Haemophilus influenzae and Streptococcus pneumoniae for community-acquired aspiration pneumonia and Gram-negative aerobic bacilli in nosocomial pneumonia. It is worth bearing in mind the relative unimportance of anaerobic bacterias in AP. When we choose the empirical antibiotic treatmentant we have to consider some pathogens identified in orofaríngea flora. Empirical treatment with antianaerobics should only be used in certain patients. Videofluoroscopic swallowing studies should be used to determine the nature and extent of any swallow disorder and to rule out silent aspiration. Assessment of swallowing disorders is cost-effective and results in a significant reduction in overall morbidity and mortality. PMID:17927938

  17. CMV pneumonia

    MedlinePlus

    ... help prevent CMV pneumonia in certain people: Using organ transplant donors who don't have CMV Using CMV-negative blood products for transfusion Using CMV-immune globulin in certain ... that can occur in people who have a weakened immune system.

  18. Streptococcus pneumoniae Infection of Host Epithelial Cells via Polymeric Immunoglobulin Receptor Transiently Induces Calcium Release from Intracellular Stores*

    PubMed Central

    Asmat, Tauseef M.; Agarwal, Vaibhav; Räth, Susann; Hildebrandt, Jan-Peter; Hammerschmidt, Sven

    2011-01-01

    The pneumococcal surface protein C (PspC) is a major adhesin of Streptococcus pneumoniae (pneumococci) that interacts in a human-specific manner with the ectodomain of the human polymeric immunoglobulin receptor (pIgR) produced by respiratory epithelial cells. This interaction promotes bacterial colonization and bacterial internalization by initiating host signal transduction cascades. Here, we examined alterations of intracellular calcium ([Ca2+]i) levels in epithelial cells during host cell infections with pneumococci via the PspC-hpIgR mechanism. The release of [Ca2+]i from intracellular stores in host cells was significantly increased by wild-type pneumococci but not by PspC-deficient pneumococci. The increase in [Ca2+]i was dependent on phospholipase C as pretreatment of cells with a phospholipase C-specific inhibitor U73122 abolished the increase in [Ca2+]i. In addition, we demonstrated the effect of [Ca2+]i on pneumococcal internalization by epithelial cells. Uptake of pneumococci was significantly increased after pretreatment of epithelial cells with the cell-permeable calcium chelator 1,2-bis-(o-aminophenoxy)-ethane-N,N,N′,N′-tetraacetic acid-tetraacetoxymethyl ester or use of EGTA as an extracellular Ca2+-chelating agent. In contrast, thapsigargin, an inhibitor of endoplasmic reticulum Ca2+ATPase, which increases [Ca2+]i in a sustained fashion, significantly reduced pIgR-mediated pneumococcal invasion. Importantly, pneumococcal adherence to pIgR-expressing cells was not altered in the presence of inhibitors as demonstrated by immunofluorescence microscopy. In conclusion, these results demonstrate that pneumococcal infections induce mobilization of [Ca2+]i from intracellular stores. This may constitute a defense response of host cells as the experimental reduction of intracellular calcium levels facilitates pneumococcal internalization by pIgR-expressing cells, whereas elevated calcium levels diminished bacterial internalization by host epithelial

  19. Efficacy of single-dose ceftriaxone in experimental otitis media induced by penicillin- and cephalosporin-resistant Streptococcus pneumoniae.

    PubMed Central

    Barry, B; Muffat-Joly, M; Bauchet, J; Faurisson, F; Gehanno, P; Pocidalo, J J; Carbon, C

    1996-01-01

    We used a gerbil model of otitis media to assess the efficacy of single-dose ceftriaxone against three Streptococcus pneumoniae strains highly resistant to penicillin (MICs, 4 to 8 micrograms/ml) and with various susceptibilities to ceftriaxone (MICs, 0.5, 4, and 8 micrograms/ml). Middle ear infection was induced by bilateral transbullar challenge with 10(7) bacteria per ear. Antibiotic treatment was administered subcutaneously at 2 h postinfection. Infection status was checked 2 days later by counting the bacteria in middle ear and cerebrospinal fluid samples. With the cefriaxone-susceptible strain (MIC, 0.5 microgram/ml), we tested doses of 5 to 100 mg/kg of body weight. With a dose of 50 mg/kg, treatment outcome was equivalent to that with amoxicillin, which was used as a reference (25 mg/kg, two injections); no bacteria were recovered from 82% of the middle ear samples, and the rate of cerebrospinal fluid culture positivity was significantly reduced to 6%, relative to 59% for the untreated controls. Similar efficacy was obtained with a dose of 100 mg/kg against the two ceftriaxone-resistant strains. Pharmacokinetic study indicates that the values of the parameters in plasma after the administration of a dose of 100 mg/kg (peak level of total drug, 268 +/- 33 micrograms/ml; elimination half-life, 0.8 h; area under concentration-time curve, 488 micrograms.h.ml-1) were still suboptimal compared with the values of the parameters measured in pediatric patients after intravenous or intramuscular administration of a dose of 50 mg/kg. Our results indicate the efficacy of ceftriaxone against experimental cephalosporin-resistant pneumococcal otitis and provide a basis for the clinical use of single-dose ceftriaxone against pneumococcal otitis media. PMID:8878566

  20. Extracorporeal membrane oxygenation and toilet bronchoscopy as a bridge to pneumonectomy in severe community-acquired methicillin-resistant Staphylococcus aureus pneumonia

    PubMed Central

    Panchabhai, Tanmay S.; Khabbaza, Joseph E.; Raja, Siva; Mehta, Atul C.; Hatipoğlu, Umur

    2015-01-01

    Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) pneumonia is associated with very high mortality. Though surgical evacuation of necrotic tissue is desirable in patients unresponsive to antimicrobial therapy, most patients are acutely ill precluding surgical intervention. We utilized a combination of extracorporeal membrane oxygenation (ECMO) with frequent toilet bronchoscopies to salvage an unaffected right lung from spillage of necrotic pus from left lung cavitary CA-MRSA pneumonia in a 22-year-old patient. Our patient while on ECMO and after decannulation was positioned with the right lung up at all times with 1-2 toilet bronchoscopies every day for almost 30 days. This time was utilized for ventilator weaning and optimizing the nutritional status prior to extrapleural left pneumonectomy. Prevention of soilage of the unaffected right lung and mitigating volutrauma with ECMO support combined with the subsequent surgical evacuation of necrotic left lung tissue led to a favorable outcome in this case. This strategy could be of value in similar presentations of unilateral suppurative pneumonia, where the progressive disease occurs despite optimal medical therapy. PMID:26664570

  1. The role of the PM2.5-associated metals in pathogenesis of child Mycoplasma Pneumoniae infections: a systematic review.

    PubMed

    Hou, Wei; Xu, Xijin; Lei, Yongge; Cao, Junjun; Zhang, Yu; Chen, Liang; Huo, Xia

    2016-06-01

    The peak occurrence of Mycoplasma pneumoniae (M. pneumoniae) infections in childhood and haze episodes is concurrent. Together, the prevalence of macrolide-resistant M. pneumoniae varies among countries might also be related to the concentration of ambient fine particulate mass (aerodynamic diameter ≤2.5 μm, PM2.5). Numerous cohort studies have identified consistent associations between ambient PM2.5 and cardiorespiratory morbidity and mortality. PM2.5 is a carrier of the heavy metals. The relationship between PM2.5-associated metals and M. pneumoniae infections in childhood has been increasingly drawing public attention. First, we reviewed original articles and review papers in Pubmed and Web of Science regarding M. pneumoniae and PM2.5-associated metal and analyzed the structural basis of PM2.5-associated metal interaction with M. pneumoniae. Then, the possible mechanisms of action between them were conjectured. Mechanisms of oxidative stress induction and modulation of the host immune system and inflammatory responses via Toll-like receptors (TLRs) and/or the nuclear factor-kappa B (NF-κB) pathway are postulated to be the result of PM2.5-associated metal complex interaction with M. pneumoniae. In addition, a heavy metal effect on M. pneumoniae-expressed community-acquired respiratory distress syndrome (CARDS) toxin, and activation of the aryl hydrocarbon receptor (AhR) and TLRs to induce the differentiation of T helper (Th) cells are also regarded as important reasons for the influence of the heavy metals on the severity of M. pneumoniae pneumonia and the initial onset and exacerbation of M. pneumoniae associated asthma. PM2.5-associated metals via complex mechanisms can exert a great impact on the host through interaction with M. pneumoniae. PMID:27040534

  2. [Nosocomial pneumonia].

    PubMed

    Díaz, Emili; Martín-Loeches, Ignacio; Vallés, Jordi

    2013-12-01

    The hospital acquired pneumonia (HAP) is one of the most common infections acquired among hospitalised patients. Within the HAP, the ventilator-associated pneumonia (VAP) is the most common nosocomial infection complication among patients with acute respiratory failure. The VAP and HAP are associated with increased mortality and increased hospital costs. The rise in HAP due to antibiotic-resistant bacteria also causes an increase in the incidence of inappropriate empirical antibiotic therapy, with an associated increased risk of hospital mortality. It is very important to know the most common organisms responsible for these infections in each hospital and each Intensive Care Unit, as well as their antimicrobial susceptibility patterns, in order to reduce the incidence of inappropriate antibiotic therapy and improve the prognosis of patients. Additionally, clinical strategies aimed at the prevention of HAP and VAP should be employed in hospital settings caring for patients at risk for these infections. PMID:23827827

  3. A population-based nested case control study on recurrent pneumonias in children with severe generalized cerebral palsy: ethical considerations of the design and representativeness of the study sample

    PubMed Central

    Veugelers, Rebekka; Calis, Elsbeth AC; Penning, Corine; Verhagen, Arianne; Bernsen, Roos; Bouquet, Jan; Benninga, Marc A; Merkus, Peter JFM; Arets, Hubertus GM; Tibboel, Dick; Evenhuis, Heleen M

    2005-01-01

    Background In children with severe generalized cerebral palsy, pneumonias are a major health issue. Malnutrition, dysphagia, gastro-oesophageal reflux, impaired respiratory function and constipation are hypothesized risk factors. Still, no data are available on the relative contribution of these possible risk factors in the described population. This paper describes the initiation of a study in 194 children with severe generalized cerebral palsy, on the prevalence and on the impact of these hypothesized risk factors of recurrent pneumonias. Methods/Design A nested case-control design with 18 months follow-up was chosen. Dysphagia, respiratory function and constipation will be assessed at baseline, malnutrition and gastro-oesophageal reflux at the end of the follow-up. The study population consists of a representative population sample of children with severe generalized cerebral palsy. Inclusion was done through care-centres in a predefined geographical area and not through hospitals. All measurements will be done on-site which sets high demands on all measurements. If these demands were not met in "gold standard" methods, other methods were chosen. Although the inclusion period was prolonged, the desired sample size of 300 children was not met. With a consent rate of 33%, nearly 10% of all eligible children in the Netherlands are included (n = 194). The study population is subtly different from the non-participants with regard to severity of dysphagia and prevalence rates of pneumonias and gastro-oesophageal reflux. Discussion Ethical issues complicated the study design. Assessment of malnutrition and gastro-oesophageal reflux at baseline was considered unethical, since these conditions can be easily treated. Therefore, we postponed these diagnostics until the end of the follow-up. In order to include a representative sample, all eligible children in a predefined geographical area had to be contacted. To increase the consent rate, on-site measurements are of first

  4. Ampicillin plus mecillinam vs. cefotaxime/cefadroxil treatment of patients with severe pneumonia or pyelonephritis: a double-blind multicentre study evaluated by intention-to-treat analysis.

    PubMed

    Cronberg, S; Banke, S; Bruno, A M; Carlsson, M; Elmrud, H; Elowsson, S; Josefsson, K; Lindholm, A C; Montelius, H; Neringer, R

    1995-01-01

    In this double-blind multicentre study, using the intention-to-treat approach, a total of 293 patients with fever (> or = 38.5 degrees C), symptoms of sepsis and signs of pneumonia or pyelonephritis were randomly assigned to treatment with ampicillin and mecillinam (A+M) or cefotaxime followed by cefadroxil. In the febrile phase, treatment was given intravenously twice daily, either with 1,200 mg ampicillin together with 600 mg mecillinam or with 2 g cefotaxime alone. When the patients stayed afebrile, the intravenous administration was replaced by oral treatment twice daily for 14 days, either with 500 mg pivampicillin and 400 mg pivmecillinam or 1 g cefadroxil. In the A+M group, 33% (48/144) of the patients did not complete the full course of treatment as compared with 32% (47/149) in the cephalosporin group, the reasons being treatment failure in 27 and 29, respectively, or adverse effects (n = 16 in both groups). The median duration of fever was 47 h in the A + M group and 50 h in the cephalosporin group. Of 135 patients with pneumonia, 68% were completely cured in the A + M group, and 65% in the cephalosporin group, the main reasons for treatment failure being Mycoplasma pneumonia or ornithosis. Of 136 patients with pyelonephritis, 63% were cured in each group. The main reason for failure was bacteriological relapse. Side-effects were reported by 32 patients (22%) of the A+M group, as compared with 41 (28%) of the cephalosporin group. Epigastric complaints were equally frequent in both groups, but there was a tendency for a higher frequency of exanthema in the A+M group, and for antibiotic-associated diarrhoea and fungal superinfections in the cephalosporin group. PMID:8588136

  5. How Is Pneumonia Diagnosed?

    MedlinePlus

    ... page from the NHLBI on Twitter. How Is Pneumonia Diagnosed? Pneumonia can be hard to diagnose because it may ... than these other conditions. Your doctor will diagnose pneumonia based on your medical history, a physical exam, ...

  6. What Is Pneumonia?

    MedlinePlus

    ... page from the NHLBI on Twitter. What Is Pneumonia? Pneumonia (nu-MO-ne-ah) is an infection in ... such as bacteria, viruses, and fungi—can cause pneumonia. The infection inflames your lungs' air sacs, which ...

  7. Pneumonia (For Parents)

    MedlinePlus

    ... kids under 6 years old. Take your child's temperature at least once each morning and each evening, ... Respiratory System Croup Fever and Taking Your Child's Temperature Influenza (Flu) Walking Pneumonia Word! Pneumonia Pneumonia Hib ...

  8. Klebsiella pneumoniae Bloodstream Infection

    PubMed Central

    Girometti, Nicolò; Lewis, Russell E.; Giannella, Maddalena; Ambretti, Simone; Bartoletti, Michele; Tedeschi, Sara; Tumietto, Fabio; Cristini, Francesco; Trapani, Filippo; Gaibani, Paolo; Viale, Pierluigi

    2014-01-01

    Abstract Multidrug resistance associated with extended-spectrum beta-lactamase (ESBL) and Klebsiella pneumoniae carbapenemase (KPC) among K. pneumoniae is endemic in southern Europe. We retrospectively analyzed the impact of resistance on the appropriateness of empirical therapy and treatment outcomes of K. pneumoniae bloodstream infections (BSIs) during a 2-year period at a 1420-bed tertiary-care teaching hospital in northern Italy. We identified 217 unique patient BSIs, including 92 (42%) KPC-positive, 49 (23%) ESBL-positive, and 1 (0.5%) metallo-beta-lactamase-positive isolates. Adequate empirical therapy was administered in 74% of infections caused by non-ESBL non-KPC strains, versus 33% of ESBL and 23% of KPC cases (p < 0.0001). To clarify the impact of resistance on BSI treatment outcomes, we compared several different models comprised of non-antibiotic treatment-related factors predictive of patients’ 30-day survival status. Acute Physiology and Chronic Health Evaluation (APACHE) II score determined at the time of positive blood culture was superior to other investigated models, correctly predicting survival status in 83% of the study cohort. In multivariate analysis accounting for APACHE II, receipt of inadequate empirical therapy was associated with nearly a twofold higher rate of death (adjusted hazard ratio 1.9, 95% confidence interval 1.1–3.4; p = 0.02). Multidrug-resistant K. pneumoniae accounted for two-thirds of all K. pneumoniae BSIs, high rates of inappropriate empirical therapy, and twofold higher rates of patient death irrespective of underlying illness. PMID:25398065

  9. Acinetobacter Pneumonia: A Review

    PubMed Central

    Hartzell, Joshua D.; Kim, Andrew S.; Kortepeter, Mark G.; Moran, Kimberly A.

    2007-01-01

    Acinetobacter species are becoming a major cause of nosocomial infections, including hospital-acquired and ventilator-associated pneumonia. Acinetobacter species have become increasingly resistant to antibiotics over the past several years and currently present a significant challenge in treating these infections. Physicians now rely on older agents, such as polymyxins (colistin), for treatment. This paper reviews the epidemiology, treatment, and prevention of this emerging pathogen. PMID:18092011

  10. Pathology of Idiopathic Interstitial Pneumonias

    PubMed Central

    Hashisako, Mikiko; Fukuoka, Junya

    2015-01-01

    The updated classification of idiopathic interstitial pneumonias (IIPs) in 2013 by American Thoracic Society/European Respiratory Society included several important revisions to the categories described in the 2002 classification. In the updated classification, lymphoid interstitial pneumonia (LIP) was moved from major to rare IIPs, pleuroparenchymal fibroelastosis (PPFE) was newly included in the rare IIPs, acute fibrinous and organizing pneumonia (AFOP) and interstitial pneumonias with a bronchiolocentric distribution are recognized as rare histologic patterns, and unclassifiable IIP (UCIP) was classified as an IIP. However, recent reports indicate the areas of concern that may require further evaluation. Here, we describe the histopathologic features of the updated IIPs and their rare histologic patterns and also point out some of the issues to be considered in this context. PMID:26949346

  11. Inhibition of host cell catalase by Mycoplasma pneumoniae: a possible mechanism for cell injury.

    PubMed Central

    Almagor, M; Yatziv, S; Kahane, I

    1983-01-01

    This study demonstrates that viable Mycoplasma pneumoniae cells inhibit catalase activity in several types of intact human cells as well as in solution. Human erythrocyte catalase was inhibited up to 72%, and the inhibition of catalase in human cultured skin fibroblasts, lung carcinoma epithelial cells, and ciliated epithelial cells from human nasal polyps ranged between 75 and 80%. UV light-killed mycoplasmas failed to inhibit catalase activity both in intact cells and in vitro. After M. pneumoniae infection of human cultured skin fibroblasts, the level of malonyldialdehyde, an indicator for membrane lipid peroxidation, was 3.5 times higher than in control fibroblasts. Virulent M. pneumoniae completely inhibited catalase activity in solution, whereas the nonvirulent strains had a lesser ability to inhibit catalase activity. These findings suggest that as a result of host cell catalase inhibition by M. pneumoniae, the toxicity of the hydrogen peroxide generated by the microorganism and the affected cell is enhanced, thereby inducing host cell damage. PMID:6407999

  12. Healthcare-associated Pneumonia and Aspiration Pneumonia

    PubMed Central

    Komiya, Kosaku; Ishii, Hiroshi; Kadota, Jun-ichi

    2015-01-01

    Healthcare-associated pneumonia (HCAP) is a new concept of pneumonia proposed by the American Thoracic Society/Infectious Diseases Society of America in 2005. This category is located between community-acquired pneumonia and hospital-acquired pneumonia with respect to the characteristics of the causative pathogens and mortality, and primarily targets elderly patients in healthcare facilities. Aspiration among such patients is recognized to be a primary mechanism for the development of pneumonia, particularly since the HCAP guidelines were published. However, it is difficult to manage patients with aspiration pneumonia because the definition of the condition is unclear, and the treatment is associated with ethical aspects. This review focused on the definition, prevalence and role of aspiration pneumonia as a prognostic factor in published studies of HCAP and attempted to identify problems associated with the concept of aspiration pneumonia. PMID:25657850

  13. Quinine-induced arrhythmia in a patient with severe malaria.

    PubMed

    Gunawan, Carta A; Harijanto, Paul N; Nugroho, Agung

    2007-01-01

    It was reported that there was a case of severe malaria patient with jaundice who presented with arrhythmia (premature ventricular contraction) while getting quinine infusion was reported. A man, 25 years old, was admitted to hospital with high fever, chill, vomiting, jaundice. The patient was fully conscious, blood pressure 120/80 mmHg, pulse rate 100 x/minute, regular. On admission, laboratory examination showed Plasmodium falciparum (++++), total bilirubin 8.25 mg/dL, conjugated bilirubin 4.36 mg/dL, unconjugated bilirubin 3.89 mg/dL, potassium 3.52 meq/L Patient was diagnosed as severe malaria with jaundice and got quinine infusion in dextrose 5% 500 mg/8 hour. On the second day the patient had vomitus, diarrhea, tinnitus, loss of hearing. After 30 hours of quinine infusion the patient felt palpitation and electrocardiography (ECG) recording showed premature ventricular contraction (PVC) > 5 x/minute, trigemini, constant type--sinoatrial block, positive U wave. He was treated with lidocaine 50 mg intravenously followed by infusion 1500 mg in dextrose 5%/24 hour and potassium aspartate tablet. Quinine infusion was discontinued and changed with sulfate quinine tablets. Three hours later the patient felt better, the frequency of PVC reduced to 4 - 5 x/minute and on the third day ECG was normal, potassium level was 3.34 meq/L. He was discharged on 7th day in good condition. Quinine, like quinidine, is a chincona alkaloid that has anti-arrhythmic property, although it also pro-arrhythmic that can cause various arrhythmias, including severe arrhythmia such as multiple PVC. Administration of parenteral quinine must be done carefully and with good observation because of its pro-arrhythmic effect, especially in older patients who have heart diseases or patients with electrolyte disorder (hypokalemia) which frequently occurs due to vomiting and or diarrhea in malaria cases. PMID:17297207

  14. Baking soda induced severe metabolic alkalosis in a haemodialysis patient.

    PubMed

    Solak, Yalcin; Turkmen, Kultigin; Atalay, Huseyin; Turk, Suleyman

    2009-08-01

    Metabolic alkalosis is a rare occurence in hemodialysis population compared to metabolic acidosis unless some precipitating factors such as nasogastric suction, vomiting and alkali ingestion or infusion are present. When metabolic alkalosis develops, it may cause serious clinical consequences among them are sleep apnea, resistent hypertension, dysrhythmia and seizures. Here, we present a 54-year-old female hemodialysis patient who developed a severe metabolic alkalosis due to baking soda ingestion to relieve dyspepsia. She had sleep apnea, volume overload and uncontrolled hypertension due to metabolic alkalosis. Metabolic alkalosis was corrected and the patient's clinical condition was relieved with negative-bicarbonate hemodialysis. PMID:25984015

  15. Trimethoprim/Sulfamethoxazole-Induced Severe Lactic Acidosis: A Case Report and Review of the Literature.

    PubMed

    Bulathsinghala, Marie; Keefer, Kimberly; Van de Louw, Andry

    2016-04-01

    Propylene glycol (PG) is used as a solvent in numerous medications, including trimethoprim/sulfamethoxazole (TMP/SMX) and lorazepam, and is metabolized in the liver to lactic acid. Cases of lactic acidosis related to PG toxicity have been described and always involved large doses of benzodiazepines and PG. We present the first case of severe lactic acidosis after a 3-day course of TMP/SMX alone, involving allegedly safe amounts of PG.A 31-year-old female with neurofibromatosis and pilocytic astrocytoma, receiving temozolomide and steroids, was admitted to the intensive care unit for pneumonia and acute respiratory failure requiring intubation. Her initial hemodynamic and acid-base statuses were normal. She was treated with intravenous TMP/SMX for possible Pneumocystis jirovecii pneumonia and was successfully extubated on day 2. On day 3, she developed tachypnea and arterial blood gas analysis revealed a severe metabolic acidosis (pH 7.2, PCO2 19 mm Hg, bicarbonates 8 mEq/L) with anion gap of 25 mEq/L and lactate of 12.1 mmol/L. TMP/SMX was discontinued and the lactate decreased to 2.9 mmol/L within 24 hours while her plasma bicarbonates normalized, without additional intervention. The patient never developed hypotension or severe hypoxia, and her renal and liver functions were normal. No other cause for lactic acidosis was identified and it resolved after TMP/SMX cessation alone, suggesting PG toxicity.Although PG-related lactic acidosis is well recognized after large doses of lorazepam, clinicians should bear in mind that TMP/SMX contains PG as well and should suspect PG toxicity in patients developing unexplained metabolic acidosis while receiving TMP/SMX. PMID:27124045

  16. A Case Report on the Successful Treatment of Streptococcus pneumoniae-Induced Infectious Abdominal Aortic Aneurysm Initially Presenting with Meningitis

    PubMed Central

    Kawatani, Yohei; Nakamura, Yoshitsugu; Hayashi, Yujiro; Taneichi, Tetsuyoshi; Ito, Yujiro; Kurobe, Hirotsugu; Suda, Yuji; Hori, Takaki

    2015-01-01

    Infectious abdominal aortic aneurysms often present with abdominal and lower back pain, but prolonged fever may be the only symptom. Infectious abdominal aortic aneurysms initially presenting with meningitis are extremely rare; there are no reports of their successful treatment. Cases with Streptococcus pneumoniae as the causative bacteria are even rarer with a higher mortality rate than those caused by other bacteria. We present the case of a 65-year-old man with lower limb weakness and back pain. Examination revealed fever and neck stiffness. Cerebrospinal fluid showed leukocytosis and low glucose levels. The patient was diagnosed with meningitis and bacteremia caused by Streptococcus pneumoniae and treated with antibiotics. Fever, inflammatory response, and neurologic findings showed improvement. However, abdominal computed tomography revealed an aneurysm not present on admission. Antibiotics were continued, and a rifampicin soaked artificial vascular graft was implanted. Tissue cultures showed no bacteria, and histological findings indicated inflammation with high leukocyte levels. There were no postoperative complications or neurologic abnormalities. Physical examination, blood tests, and computed tomography confirmed there was no relapse over the following 13 months. This is the first reported case of survival of a patient with an infectious abdominal aortic aneurysm initially presenting with meningitis caused by Streptococcus pneumoniae. PMID:26779361

  17. Pericardiectomy for Pleuropericardial Effusion Complicating Bacterial Pneumonia

    PubMed Central

    Quarti, Andrea; de Benedictis, Fernando Maria; Soura, Elli; Pozzi, Marco

    2010-01-01

    Severe pericardial effusion is a rare complication of bacterial pneumonia and it usually disappears under medical treatment. Herein we report a case of a girl with a congenital immunodeficient syndrome and bacterial pneumonia, who developed recurrent and life-threatening pericardial effusion refractory to medical treatment. She was finally treated with pericardiectomy. PMID:20585369

  18. Coxiella burnetii pneumonia.

    PubMed

    Marrie, T J

    2003-04-01

    This report reviews the pulmonary and extrapulmonary manifestation of infections due to Coxiella burnetii. Q fever, a zoonosis, is due to infection with C. burnetii. This spore-forming microorganism is a small gram-negative coccobacillus that is an obligate intracellular parasite. The most common animal reservoirs are goats, cattle, sheep, cats, and occasionally dogs. The organism reaches high concentrations in the placenta of infected animals. Aerosolisation occurs at the time of parturition and infection follows inhalation of this aerosol. There are three distinct clinical syndromes of the acute form of the illness: nonspecific febrile illness, pneumonia, and hepatitis. The chronic form of Q fever is almost always endocarditis, but occasionally it is manifest as hepatitis, osteomyelitis or endovascular infection. The pneumonic form of the illness can range from very mild-to-severe pneumonia requiring assisted ventilation. Multiple round opacities are a common finding on chest radiography. Treatment with doxycycline or a fluoroquinolone is preferred. Susceptibility to macrolides is variable. In conclusion, Coxiella burnetii pneumonia should be considered when there is a suitable exposure history and when outbreaks of a pneumonic illness are being investigated. PMID:12762362

  19. [Travel-associated pneumonias].

    PubMed

    Geerdes-Fenge, H F

    2014-10-01

    Respiratory infections are responsible for up to 11% of febrile infections in travellers or immigrants from tropical and subtropical regions. The main pathogens are the same as in temperate climate zones: Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Chlamydophila pneumoniae, influenza viruses, Legionella pneumophila. However, some pulmonary diseases can be attributed to bacterial, parasitic, viral or fungal pathogens that are endemic in tropical and subtropical regions. The most commonly imported infections are malaria, dengue, and tuberculosis. Pulmonary symptoms and eosinophilia in returning travellers and migrants may be caused by several parasitic infections such as Katayama syndrome, Loeffler syndrome, tropical pulmonary eosinophilia, amebiasis, paragonimiasis, echinococcosis, and toxocariasis. In Asia, Tsutsugamushi fever is transmitted by chiggers, spotted fever rickettsiae are transmitted by ticks. Transmission of zoonotic diseases occurs mainly via contact with infected animals or their excretions, human-to-human transmission is generally rare: MERS-CoA (dromedary camels), pulmonary hantavirus infection (rodents), tularemia (rabbits and hares), leptospirosis (rats), Q-fever (sheep and goats), very rarely anthrax (hides of ruminants) and pest (infected rats and wildlife). Inhalation of contaminated dust can cause infections with dimorphic fungi: histoplasmosis (bat guano) and coccidioidomycosis in America and parts of Africa, blastomycosis in America. Some infections can cause symptoms years after a stay in tropical or subtropical regions (melioidosis, tuberculosis, histoplasmosis, schistosomiasis-associated pulmonary hypertension). Noninfectious respiratory diseases caused by inhalation of high amounts of air pollution or toxic dusts may also be considered. PMID:25290923

  20. Differential susceptibility of transgenic mice expressing human surfactant protein B genetic variants to Pseudomonas aeruginosa induced pneumonia.

    PubMed

    Ge, Lin; Liu, Xinyu; Chen, Rimei; Xu, Yongan; Zuo, Yi Y; Cooney, Robert N; Wang, Guirong

    2016-01-01

    Surfactant protein B (SP-B) is essential for lung function. Previous studies have indicated that a SP-B 1580C/T polymorphism (SNP rs1130866) was associated with lung diseases including pneumonia. The SNP causes an altered N-linked glycosylation modification at Asn129 of proSP-B, e.g. the C allele with this glycosylation site but not in the T allele. This study aimed to generate humanized SP-B transgenic mice carrying either SP-B C or T allele without a mouse SP-B background and then examine functional susceptibility to bacterial pneumonia in vivo. A total of 18 transgenic mouse founders were generated by the DNA microinjection method. These founders were back-crossed with SP-B KO mice to eliminate mouse SP-B background. Four founder lines expressing similar SP-B levels to human lung were chosen for further investigation. After intratracheal infection with 50 μl of Pseudomonas aeruginosa solution (1 × 10(6) CFU/mouse) or saline in SP-B-C, SP-B-T mice the mice were sacrificed 24 h post-infection and tissues were harvested. Analysis of surfactant activity revealed differential susceptibility between SP-B-C and SP-B-T mice to bacterial infection, e.g. higher minimum surface tension in infected SP-B-C versus infected SP-B-T mice. These results demonstrate for the first time that human SP-B C allele is more susceptible to bacterial pneumonia than SP-B T allele in vivo. PMID:26620227

  1. Vaccine-Induced Human Antibodies to PspA Augment Complement C3 Deposition on Streptococcus pneumoniae

    PubMed Central

    Ochs, Martina M.; Bartlett, William; Briles, David E.; Hicks, Bryony; Jurkuvenas, Audra; Lau, Peggy; Ren, Bing; Millar, Amanda

    2008-01-01

    Pneumococcal surface protein (PspA) is a virulence factor expressed by all clinical isolates of Streptococcus pneumoniae. PspAs are variable in structure and have been grouped into clades and cross-reacting families based on sequence similarities and immunologic cross-reactivity. At least 98 percent of PspAs are found in PspA families 1 or 2. PspA has been shown to interfere with complement deposition on pneumococci, thus reducing opsonization and clearance of bacteria by the host immune system. Prior studies using pooled human sera have shown that PspA interferes with C3 deposition on a single strain of S. pneumoniae, WU2, and that mouse antibody to PspA can enhance the deposition of C3 on WU2. The present studies have demonstrated that these previous findings are representative of most normal human sera and each of 7 different strains of S. pneumoniae. It was observed that PspAs of PspA families 1 and 2 could inhibit C3 deposition in the presence of immunoglobulin present in all but 3 of 22 normal human sera. These studies have also demonstrated that rabbit and human antibody to PspA can enhance the deposition of C3 on pneumococci expressing either family 1 or 2 PspAs and either capsular types 2, 3, or 11. A vaccine candidate that can elicit immunity that neutralizes or compensates for S. pneumoniae’s ability to thwart host immunity would be of value. PMID:18006268

  2. [An Elderly Patient with Metastatic Breast Cancer Who Developed Severe Adverse Events such as Stomatitis and Interstitial Pneumonia after Everolimus plus Exemestane Treatment].

    PubMed

    Sakiyama, Kana; Yoshida, Takashi; Goto, Yoshinari; Kimura, Morihiko

    2016-06-01

    An 80-year-old woman was diagnosed with right breast cancer with clinical Stage IIIA 6 years previously. She underwent mastectomy and axillary lymph node dissection. The pathological diagnosis was invasive micropapillary carcinoma with lymph node involvement. Immunohistochemically, the tumor was positive for estrogen receptor and progesterone receptor, and negative for HER2. Postoperatively, the patient was treated with adjuvant chemotherapy consisting of cyclophosphamide, epirubicin, 5-fluorouracil, and paclitaxel, followed by endocrine therapy with letrozole. Four years after surgery, she experienced a recurrence of breast cancer in the thoracic wall, and was treated with exemestane, toremifene, and fulvestrant for 1 year and 5 months. However, she developed carcinomatous pleurisy and was treated with eribulin. This last treatment was ineffective. Subsequently, she received combination therapy with everolimus and exemestane. Although the pleural effusion reduced markedly after 5 weeks, stomatitis, diarrhea, melena, and interstitial pneumonia occurred as adverse events. The symptoms improved after drug discontinuation and steroid therapy. The combination therapy with everolimus and exemestane is a prospective therapy for hormone-resistant recurrent breast cancer, but the management of adverse events is very important. PMID:27306814

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

    PubMed

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

    2002-07-01

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

  4. Impaired acquired resistance of mice to Klebsiella pneumoniae infection induced by acute NO/sub 2/ exposure

    SciTech Connect

    Bouley, G.; Azoulay-Dupuis, E.; Gaudebout, C.

    1985-12-01

    The natural resistance of nonimmunized C57B1/6 mice to an intraperitoneal Klebsiella pneumoniae challenge was not significantly affected by prior continuous exposure to 20 ppm NO/sub 2/ for 4 days. In contrast, the acquired resistance of mice immunized just before and infected just after NO/sub 2/ exposure was seriously impaired. This could not be explained by the loss of appetite (about 30%) observed in NO/sub 2/ treated mice, for neither the natural nor acquired resistance of control air exposure mice given approximately 70% ad libitum food and water were significantly modified.

  5. Rare extrapulmonary complications of Mycoplasma pneumoniae infection.

    PubMed

    Dhaliwal, Kiran; Enright, Kevin

    2016-01-01

    Stevens-Johnsons syndrome (SJS) is a rare extra-pulmonary complication of Mycoplasma pneumoniae infection. We present the case of a 26-year-old man with fever, cough, extensive oral mucosal ulceration and a widespread truncal rash. He was diagnosed with M. pneumoniae-induced SJS. He responded well to antibiotics and steroids initially, but went on to develop pseudomembranous conjunctivitis requiring bilateral amniotic membrane grafting. SJS is most commonly drug-induced, however, M. pneumoniae is the commonest infectious cause and should be considered in the differential diagnosis. It is also important to get specialist care involved early to minimise the long-term effects of any complications. PMID:26837942

  6. Classification of Extrapulmonary Manifestations Due to Mycoplasma pneumoniae Infection on the Basis of Possible Pathogenesis.

    PubMed

    Narita, Mitsuo

    2016-01-01

    The list of extrapulmonary manifestations due to Mycoplasma pneumoniae infection can be classified according to the following three possible mechanisms derived from the established biological activity of M. pneumoniae; (1) a direct type in which the bacterium is present at the site of inflammation and local inflammatory cytokines induced by the bacterium play an important role (2) an indirect type in which the bacterium is not present at the site of inflammation and immune modulations, such as autoimmunity or formation of immune complexes, play an important role, and (3) a vascular occlusion type in which obstruction of blood flow induced either directly or indirectly by the bacterium plays an important role. Recent studies concerning extrapulmonary manifestations have prompted the author to upgrade the list, including cardiac and aortic thrombi as cardiovascular manifestations; erythema nodosum, cutaneous leukocytoclastic vasculitis, and subcorneal pustular dermatosis as dermatological manifestations; acute cerebellar ataxia, opsoclonus-myoclonus syndrome, and thalamic necrosis as neurological manifestations; pulmonary embolism as a respiratory system manifestation; and renal artery embolism as a urogenital tract manifestation. Continuing nosological confusion on M. pneumoniae-induced mucositis (without skin lesions), which may be called M. pneumoniae-associated mucositis or M. pneumoniae-induced rash and mucositis separately from Stevens-Johnson syndrome, is argued in the dermatological manifestations. Serological methods are recommended for diagnosis because pneumonia or respiratory symptoms are often minimal or even absent in extrapulmonary manifestations due to M. pneumoniae infection. Concomitant use of immunomodulators, such as corticosteroids or immunoglobulins with antibiotics effective against M. pneumoniae, can be considered as treatment modalities for most severe cases, such as encephalitis. Further studies would be necessary to construct a

  7. Inhibition of Phosphodiesterase-4 during Pneumococcal Pneumonia Reduces Inflammation and Lung Injury in Mice.

    PubMed

    Tavares, Luciana P; Garcia, Cristiana C; Vago, Juliana P; Queiroz-Junior, Celso M; Galvão, Izabela; David, Bruna A; Rachid, Milene A; Silva, Patrícia M R; Russo, Remo C; Teixeira, Mauro M; Sousa, Lirlândia P

    2016-07-01

    Pneumococcal pneumonia is a leading cause of mortality worldwide. The inflammatory response to bacteria is necessary to control infection, but it may also contribute to tissue damage. Phosphodiesterase-4 inhibitors, such as rolipram (ROL), effectively reduce inflammation. Here, we examined the impact of ROL in a pneumococcal pneumonia murine model. Mice were infected intranasally with 10(5)-10(6) CFU of Streptococcus pneumoniae, treated with ROL in a prophylactic or therapeutic schedule in combination, or not, with the antibiotic ceftriaxone. Inflammation and bacteria counts were assessed, and ex vivo phagocytosis assays were performed. ROL treatment during S. pneumoniae infection decreased neutrophil recruitment into lungs and airways and reduced lung injury. Prophylactic ROL treatment also decreased cytokine levels in the airways. Although modulation of inflammation by ROL ameliorated pneumonia, bacteria burden was not reduced. On the other hand, antibiotic therapy reduced bacteria without reducing neutrophil infiltration, cytokine level, or lung injury. Combined ROL and ceftriaxone treatment decreased lethality rates and was more efficient in reducing inflammation, by increasing proresolving protein annexin A1 (AnxA1) expression, and bacterial burden by enhancing phagocytosis. Lack of AnxA1 increased inflammation and lethality induced by pneumococcal infection. These data show that immunomodulatory effects of phosphodiesterase-4 inhibitors are useful during severe pneumococcal pneumonia and suggest their potential benefit as adjunctive therapy during infectious diseases. PMID:26677751

  8. Bacterial Pneumonia in Older Adults.

    PubMed

    Marrie, Thomas J; File, Thomas M

    2016-08-01

    Community-acquired pneumonia is common in the elderly person; its presentation in this population is often confounded by multiple comorbid illnesses, including those that result in confusion. Although severity-of-illness scoring systems might aid decision-making, clinical judgment following a careful assessment is key in deciding on the site of care and appropriate therapy. PMID:27394017

  9. Polyradiculoneuritis and Mycoplasma pneumoniae infection.

    PubMed

    Holt, S; Khan, M M; Charles, R G; Epstein, E J

    1977-07-01

    A patient with severe Mycoplasma pneumonia developed polyradiculoneuritis and respiratory failure. The acute phase of the illness was complicated by a myocarditis, and recovery of neurological function was slow. Residual left hemidiaphragmatic paralysis was present 1 year after onset of the illness. PMID:882485

  10. Modulation of paired immunoglobulin-like type 2 receptor signaling alters the host response to Staphylococcus aureus-induced pneumonia.

    PubMed

    Banerjee, Antara; Stevenaert, Frederik; Pande, Kalyan; Haghjoo, Erik; Antonenko, Svetlana; Gorman, Dan M; Sathe, Manjiri; McClanahan, Terrill K; Pierce, Robert; Turner, Scott P; Bigler, Michael E; Phillips, Joseph H; Heyworth, Paul G

    2010-03-01

    Paired immunoglobulin-like type 2 receptors (PILRs) inhibitory PILRalpha and activating PILRbeta are predominantly expressed on myeloid cells. Their functions in host defense and inflammation are largely unknown, and in this study, we evaluated their roles in an acute Staphylococcus aureus pneumonia model. Compared to their respective controls, Pilrb(-/-) mice or mice in which PILRalpha was activated with an agonistic antibody showed improved clearance of pulmonary staphylococci and improved survival. These mice had reduced serum or bronchoalveolar lavage fluid levels of interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), and IL-6 and elevated levels of gamma interferon (IFN-gamma), IL-12, and IL-10. In contrast, mice in which PILRbeta was activated had increased lung bacterial burdens and higher mortality coupled with an intense proinflammatory response with highly elevated levels of IL-1beta, TNF-alpha, and IL-6. Treatment groups with reduced bacterial burdens had higher levels of Keratinocyte-derived chemokine (KC), macrophage inflammatory protein 2 (MIP-2), and MIP-1alpha in bronchoalveolar lavage fluid and an increased influx of neutrophils and macrophages to the lungs. Consistent with our in vivo findings, bone marrow-derived macrophages from Pilrb(-/-) mice released significantly less IL-1beta and TNF-alpha and more IFN-gamma and IL-12 than did the wild-type macrophages when directly stimulated with heat-killed S. aureus. To our knowledge, this is the first evidence that S. aureus directly interacts with PILRbeta. It provides a mechanism by which manipulating the balance in favor of an inhibitory PILR signal, by activation of PILRalpha or deletion of PILRbeta, helps to control acute S. aureus-mediated pneumonia and attenuate the inflammatory response. These results highlight the importance of PILRs in innate immunity and the control of inflammation. PMID:20065029

  11. Hospital-acquired pneumonia

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000146.htm Hospital-acquired pneumonia To use the sharing features on this page, please enable JavaScript. Hospital-acquired pneumonia is an infection of the lungs ...

  12. Pneumonia - weakened immune system

    MedlinePlus

    ... medlineplus.gov/ency/article/000093.htm Pneumonia - weakened immune system To use the sharing features on this page, ... fighting off infection because of problems with the immune system. This type of disease is called "pneumonia in ...

  13. Pneumonia - adults - discharge

    MedlinePlus

    You have pneumonia, which is an infection in your lungs. In the hospital, your doctors and nurses helped you breathe better. ... body get rid of the germs that cause pneumonia. They also made sure you got enough liquids ...

  14. Pneumonia - children - discharge

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000011.htm Pneumonia in children - discharge To use the sharing features ... this page, please enable JavaScript. Your child has pneumonia, which is an infection in the lungs. In ...

  15. Pneumonia - adults - discharge

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000017.htm Pneumonia in adults - discharge To use the sharing features on this page, please enable JavaScript. You have pneumonia, which is an infection in your lungs. In ...

  16. A mouse model of Acinetobacter baumannii-associated pneumonia using a clinically isolated hypervirulent strain.

    PubMed

    Harris, Greg; Kuo Lee, Rhonda; Lam, Christopher K; Kanzaki, Gregory; Patel, Girishchandra B; Xu, H Howard; Chen, Wangxue

    2013-08-01

    Acinetobacter baumannii is an important emerging pathogen in health care-acquired infections and is responsible for severe nosocomial and community-acquired pneumonia. Currently available mouse models of A. baumannii pneumonia show poor colonization with little to no extrapulmonary dissemination. Here, we describe a mouse model of A. baumannii pneumonia using a clinical isolate (LAC-4 strain) that reliably reproduces the most relevant features of human pulmonary A. baumannii infection and pathology. Using this model, we have shown that LAC-4 infection induced rapid bacterial replication in the lungs, significant extrapulmonary dissemination, and severe bacteremia by 24 h postintranasal inoculation. Infected mice showed severe bronchopneumonia and dilatation and inflammatory cell infiltration in the perivascular space. More significantly, 100% of C57BL/6 and BALB/c mice succumbed to 10(8) CFU of LAC-4 inoculation within 48 h. When this model was used to assess the efficacy of antimicrobials, all mice treated with imipenem and tigecycline survived a lethal intranasal challenge, with minimal clinical signs and body weight loss. Moreover, intranasal immunization of mice with formalin-fixed LAC-4 protected 40% of mice from a lethal (100× 100% lethal dose) intraperitoneal challenge. Thus, this model offers a reproducible acute course of A. baumannii pneumonia without requiring additional manipulation of host immune status, which will facilitate the development of therapeutic agents and vaccines against A. baumannii pneumonia in humans. PMID:23689726

  17. Presence of the Panton-Valentine Leukocidin Genes in Methicillin-Resistant Staphylococcus aureus Is Associated with Severity and Clinical Outcome of Hospital-Acquired Pneumonia in a Single Center Study in China

    PubMed Central

    Zhang, Chuanling; Guo, Liang; Chu, Xu; Shen, Limeng; Guo, Yuanyu; Dong, Huali; Mao, Jianfeng; van der Veen, Stijn

    2016-01-01

    The Panton-Valentine leukocidin (PVL) genes of methicillin-resistant Staphylococcus aureus (MRSA) have previously been associated with severe infections. Here, the impact of the PVL genes on severity of disease and clinical outcome of patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP) due to MRSA was investigated in a single center observational study in a hospital in China. HAP due to MRSA was diagnosed in 100 patients and 13 of the patients were PVL positive, while VAP was diagnosed in 5 patients and 2 were PVL positive. The PVL positive patient group showed a significantly higher Acute Physiology and Chronic Health Evaluation (APACHE) II score (14.3 ±7.8 vs. 10.1 ±4.7, P = 0.005) and significantly more patients with CRP levels >80 mg/L (8/15 vs. 12/90, P = 0.006) or WBC counts >15x109/L (7/15 vs. 12/90, P = 0.006), indicating that the severity of disease is affected by the presence of the PVL genes. The outcome of the study was defined by 30-day mortality. Four (27%) of the PVL positive patients and four (4%) of the PVL negative patients died within 30 days (P = 0.01, Fisher exact test). Kaplan-Meier survival curves were generated for the PVL positive and PVL negative patient groups, which differed significantly (P = 0.003). Among the patients that died, the mean interval between diagnosis and death was shorter for the PVL positive patients (9.3 ±5.6 vs. 40.8 ±6.6 days, P = 0.013). Further analysis within the HAP and VAP patient groups showed that the presence of PVL in MRSA impacted the severity of disease and clinical outcome of HAP, but for VAP the number of patients included in the study was too low. In conclusion, in this single center study in a Chinese hospital the presence of the PVL genes in MRSA impacted the severity of disease and clinical outcome in patients with HAP due to MRSA. PMID:27249225

  18. Presence of the Panton-Valentine Leukocidin Genes in Methicillin-Resistant Staphylococcus aureus Is Associated with Severity and Clinical Outcome of Hospital-Acquired Pneumonia in a Single Center Study in China.

    PubMed

    Zhang, Chuanling; Guo, Liang; Chu, Xu; Shen, Limeng; Guo, Yuanyu; Dong, Huali; Mao, Jianfeng; van der Veen, Stijn

    2016-01-01

    The Panton-Valentine leukocidin (PVL) genes of methicillin-resistant Staphylococcus aureus (MRSA) have previously been associated with severe infections. Here, the impact of the PVL genes on severity of disease and clinical outcome of patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP) due to MRSA was investigated in a single center observational study in a hospital in China. HAP due to MRSA was diagnosed in 100 patients and 13 of the patients were PVL positive, while VAP was diagnosed in 5 patients and 2 were PVL positive. The PVL positive patient group showed a significantly higher Acute Physiology and Chronic Health Evaluation (APACHE) II score (14.3 ±7.8 vs. 10.1 ±4.7, P = 0.005) and significantly more patients with CRP levels >80 mg/L (8/15 vs. 12/90, P = 0.006) or WBC counts >15x109/L (7/15 vs. 12/90, P = 0.006), indicating that the severity of disease is affected by the presence of the PVL genes. The outcome of the study was defined by 30-day mortality. Four (27%) of the PVL positive patients and four (4%) of the PVL negative patients died within 30 days (P = 0.01, Fisher exact test). Kaplan-Meier survival curves were generated for the PVL positive and PVL negative patient groups, which differed significantly (P = 0.003). Among the patients that died, the mean interval between diagnosis and death was shorter for the PVL positive patients (9.3 ±5.6 vs. 40.8 ±6.6 days, P = 0.013). Further analysis within the HAP and VAP patient groups showed that the presence of PVL in MRSA impacted the severity of disease and clinical outcome of HAP, but for VAP the number of patients included in the study was too low. In conclusion, in this single center study in a Chinese hospital the presence of the PVL genes in MRSA impacted the severity of disease and clinical outcome in patients with HAP due to MRSA. PMID:27249225

  19. [Exogenous lipoid pneumonia].

    PubMed

    Castañeda-Ramos, S A; Ramos-Solano, F

    1989-09-01

    We report 30 patients with exogenous lipoid pneumonia due to vegetal oil. This was employed in most of the cases during the first month of life for digestive tube symptomatology; clinical manifestations began three months following administrations, as a pneumonia or bronchopneumonia with a respiratory distress syndrome of variable severity. 60% of the thorax x-ray studies were abnormal, the main finding was opacity. One patient has alterations of the mechanics of deglutition; seven had gastroesophageal reflux. Arterial gasometry showed hypoxaemia and increase of alveolo-arterial gradient of oxygen in all. Ten patients died and all the survivors were reevaluated in september, 1988; 18 had normal physical findings. Thorax x-ray studies in 13 patients had right reticulate infiltration and 6 right apical opacity; ECG showed right ventricular hypertrophy in 3. Perfusion pulmonary gamagram with technetium 99 was abnormal in 5. Gastroesophageal reflux was evident in 2. Five were under treatment for several causes. Diagnosis and treatment is discussed. PMID:2604874

  20. Pneumocystis Pneumonia (For Parents)

    MedlinePlus

    ... 5 Things to Know About Zika & Pregnancy Pneumocystis Pneumonia KidsHealth > For Parents > Pneumocystis Pneumonia Print A A A Text Size What's in ... article? About PCP Diagnosing PCP Treating PCP Pneumocystis pneumonia (PCP) is an infection caused by Pneumocystis jiroveci , ...

  1. H1N1 influenza pneumonia and bacterial coinfection.

    PubMed

    Calbo, Esther; Robles, Alejandro; Sangil, Anna; Benet, Susana; Viladot, Maria Eugenia; Pascual, Vanesa; Barreiro, Bienvenido

    2011-12-01

    The model described by Bewick et al seems to be able to distinguish between H1N1 influenza-related pneumonia and non-H1N1 community acquired pneumonia (CAP) based on five criteria. However, bacterial infection in the influenza group has not been accurately excluded. Therefore, this model could misidentify these patients and lead to an inappropriate treatment. We conducted a prospective observational study to compare mixed pneumonia vs viral pneumonia. In the mixed pneumonia group patients were older, had higher levels of procalcitonine and higher scores of severity. In our cohort the model proposed by Bewick et al would not identify patients with coinfection. PMID:21994246

  2. Recurrent Moderate Hypoglycemia Ameliorates Brain Damage and Cognitive Dysfunction Induced by Severe Hypoglycemia

    PubMed Central

    Puente, Erwin C.; Silverstein, Julie; Bree, Adam J.; Musikantow, Daniel R.; Wozniak, David F.; Maloney, Susan; Daphna-Iken, Dorit; Fisher, Simon J.

    2010-01-01

    OBJECTIVE Although intensive glycemic control achieved with insulin therapy increases the incidence of both moderate and severe hypoglycemia, clinical reports of cognitive impairment due to severe hypoglycemia have been highly variable. It was hypothesized that recurrent moderate hypoglycemia preconditions the brain and protects against damage caused by severe hypoglycemia. RESEARCH DESIGN AND METHODS Nine-week-old male Sprague-Dawley rats were subjected to either 3 consecutive days of recurrent moderate (25–40 mg/dl) hypoglycemia (RH) or saline injections. On the fourth day, rats were subjected to a hyperinsulinemic (0.2 units · kg−1 · min−1) severe hypoglycemic (∼11 mg/dl) clamp for 60 or 90 min. Neuronal damage was subsequently assessed by hematoxylin-eosin and Fluoro-Jade B staining. The functional significance of severe hypoglycemia–induced brain damage was evaluated by motor and cognitive testing. RESULTS Severe hypoglycemia induced brain damage and striking deficits in spatial learning and memory. Rats subjected to recurrent moderate hypoglycemia had 62–74% less brain cell death and were protected from most of these cognitive disturbances. CONCLUSIONS Antecedent recurrent moderate hypoglycemia preconditioned the brain and markedly limited both the extent of severe hypoglycemia–induced neuronal damage and associated cognitive impairment. In conclusion, changes brought about by recurrent moderate hypoglycemia can be viewed, paradoxically, as providing a beneficial adaptive response in that there is mitigation against severe hypoglycemia–induced brain damage and cognitive dysfunction. PMID:20086229

  3. Life-threatening hemorrhagic pneumonia caused by Stenotrophomonas maltophilia in the treatment of hematologic diseases.

    PubMed

    Mori, Minako; Tsunemine, Hiroko; Imada, Kazunori; Ito, Kiminari; Kodaka, Taiichi; Takahashi, Takayuki

    2014-06-01

    Since the late 1990s, Stenotrophomonas maltophilia (S. maltophilia) has become one of the most common nonfermenting Gram-negative bacilli that cause opportunistic infection. Patients with hematologic diseases are the most risky candidate for S. maltophilia pneumonia or sepsis because of chemotherapy-induced neutropenia or immunodeficiency. Frequent exposure to broad-spectrum antibiotics and prolonged insertion of central venous catheter further enhance the risk of S. maltophilia infection. One of the most severe S. maltophilia infections is hemorrhagic pneumonia. This type of infection is mostly fatal because of pulmonary alveolar hemorrhage that leads to acute respiratory failure. Furthermore, S. maltophilia exhibits a high-level intrinsic resistance to conventional antibiotics such as β-lactams and aminoglycosides and, more recently, the increasing acquired resistance to co-trimoxazole and quinolones. According to our experienced and previously reported cases, all of the patients with hemorrhagic pneumonia caused by S. maltophilia had a fatal course within a few days after the onset of the pneumonia. In this article, we perform a systematic review on a total 30 cases of hemorrhagic pneumonia induced by S. maltophilia from our institutions and the literature, and we describe its early diagnosis, prophylaxis, and recommended therapeutic strategy for the infection in the treatment of hematologic disease. PMID:24535696

  4. Ultrasound in Rheumatologic Interstitial Lung Disease: A Case Report of Nonspecific Interstitial Pneumonia in Rheumatoid Arthritis.

    PubMed

    Laria, A; Lurati, A; Scarpellini, M

    2015-01-01

    According to the American Thoracic Society (ATS)/European Respiratory Society consensus classification, idiopathic interstitial pneumonias (IIPs) include several clinic-radiologic-pathologic entities: idiopathic pulmonary fibrosis (IPF), usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), cryptogenic organizing pneumonia, acute interstitial pneumonia, respiratory bronchiolitis-associated ILD, desquamative interstitial pneumonia, and lymphoid interstitial pneumonia. Ultrasound Lung Comets (ULCs) are an echographic chest-sonography hallmark of pulmonary interstitial fibrosis. We describe the ultrasound (US) findings in the follow-up of a NSIP's case in rheumatoid arthritis (RA). PMID:26240772

  5. Influenza-induced type I interferon enhances susceptibility to gram-negative and gram-positive bacterial pneumonia in mice

    PubMed Central

    Lee, Benjamin; Robinson, Keven M.; McHugh, Kevin J.; Scheller, Erich V.; Mandalapu, Sivanarayana; Chen, Chen; Di, Y. Peter; Clay, Michelle E.; Enelow, Richard I.; Dubin, Patricia J.

    2015-01-01

    Suppression of type 17 immunity by type I interferon (IFN) during influenza A infection has been shown to enhance susceptibility to secondary bacterial pneumonia. Although this mechanism has been described in coinfection with gram-positive bacteria, it is unclear whether similar mechanisms may impair lung defense against gram-negative infections. Furthermore, precise delineation of the duration of type I IFN-associated susceptibility to bacterial infection remains underexplored. Therefore, we investigated the effects of preceding influenza A virus infection on subsequent challenge with the gram-negative bacteria Escherichia coli or Pseudomonas aeruginosa and the temporal association between IFN expression with susceptibility to Staphylococcus aureus challenge in a mouse model of influenza and bacterial coinfection. Here we demonstrate that preceding influenza A virus led to increased lung E. coli and P. aeruginosa bacterial burden, which was associated with suppression of type 17 immunity and attenuation of antimicrobial peptide expression. Enhanced susceptibility to S. aureus coinfection ceased at day 14 of influenza infection, when influenza-associated type I IFN levels had returned to baseline levels, further suggesting a key role for type I IFN in coinfection pathogenesis. These findings further implicate type I IFN-associated suppression of type 17 immunity and antimicrobial peptide production as a conserved mechanism for enhanced susceptibility to both gram-positive and gram-negative bacterial coinfection during influenza infection. PMID:26001778

  6. Fever-triggered Brugada syndrome in an adult patient presenting with hemophagocytic syndrome induced by Chlamydophila pneumoniae.

    PubMed

    Vieira, Miguel Bigotte; Gaibino, Nuno; Pignatelli, Alexandra; Oliveira, Anabela

    2015-01-01

    A previously healthy 29-year-old man was admitted to our hospital, with a 4-day history of fever (>39°C), rigours, diaphoresis, fatigue and retro-orbital headache. On examination, he was febrile (37.8°C) and tachycardic (110 bpm). Laboratory work up revealed bicytopenia (white cell count 1.37×10(9)/L, platelets 60×10(9)/L) and an increase in C reactive protein (9 mg/dL). The ECG showed ST segment elevation in V1, V2 and V3 leads. The patient was admitted and investigation was initiated revealing prolonged fever (>7 days), pancytopenia, hepatosplenomegaly, hyperferritinemia, hypertriglyceridemia, hypofibrinogenemia, elevated soluble CD25 and hemophagocytosis in bone marrow. Therefore, the patient presented 7 of the 8 diagnostic criteria of hemophagocytic syndrome. Laboratorial investigation for infectious causes was negative, except for IgA and IgG Chlamydophila pneumoniae. ECG re-evaluation on the day of discharge showed no ST segment elevation and no other abnormalities. Genetic testing for known mutations associated with hemophagocytic syndrome and Brugada syndrome did not show any mutations in these genes. PMID:26452737

  7. Nanogel-based pneumococcal surface protein A nasal vaccine induces microRNA-associated Th17 cell responses with neutralizing antibodies against Streptococcus pneumoniae in macaques.

    PubMed

    Fukuyama, Y; Yuki, Y; Katakai, Y; Harada, N; Takahashi, H; Takeda, S; Mejima, M; Joo, S; Kurokawa, S; Sawada, S; Shibata, H; Park, E J; Fujihashi, K; Briles, D E; Yasutomi, Y; Tsukada, H; Akiyoshi, K; Kiyono, H

    2015-09-01

    We previously established a nanosized nasal vaccine delivery system by using a cationic cholesteryl group-bearing pullulan nanogel (cCHP nanogel), which is a universal protein-based antigen-delivery vehicle for adjuvant-free nasal vaccination. In the present study, we examined the central nervous system safety and efficacy of nasal vaccination with our developed cCHP nanogel containing pneumococcal surface protein A (PspA-nanogel) against pneumococcal infection in nonhuman primates. When [(18)F]-labeled PspA-nanogel was nasally administered to a rhesus macaque (Macaca mulatta), longer-term retention of PspA was noted in the nasal cavity when compared with administration of PspA alone. Of importance, no deposition of [(18)F]-PspA was seen in the olfactory bulbs or brain. Nasal PspA-nanogel vaccination effectively induced PspA-specific serum IgG with protective activity and mucosal secretory IgA (SIgA) Ab responses in cynomolgus macaques (Macaca fascicularis). Nasal PspA-nanogel-induced immune responses were mediated through T-helper (Th) 2 and Th17 cytokine responses concomitantly with marked increases in the levels of miR-181a and miR-326 in the serum and respiratory tract tissues, respectively, of the macaques. These results demonstrate that nasal PspA-nanogel vaccination is a safe and effective strategy for the development of a nasal vaccine for the prevention of pneumonia in humans. PMID:25669148

  8. Nanogel-based pneumococcal surface protein A nasal vaccine induces microRNA-associated Th17 cell responses with neutralizing antibodies against Streptococcus pneumoniae in macaques

    PubMed Central

    Fukuyama, Y; Yuki, Y; Katakai, Y; Harada, N; Takahashi, H; Takeda, S; Mejima, M; Joo, S; Kurokawa, S; Sawada, S; Shibata, H; Park, E J; Fujihashi, K; Briles, D E; Yasutomi, Y; Tsukada, H; Akiyoshi, K; Kiyono, H

    2015-01-01

    We previously established a nanosized nasal vaccine delivery system by using a cationic cholesteryl group-bearing pullulan nanogel (cCHP nanogel), which is a universal protein-based antigen-delivery vehicle for adjuvant-free nasal vaccination. In the present study, we examined the central nervous system safety and efficacy of nasal vaccination with our developed cCHP nanogel containing pneumococcal surface protein A (PspA-nanogel) against pneumococcal infection in nonhuman primates. When [18F]-labeled PspA-nanogel was nasally administered to a rhesus macaque (Macaca mulatta), longer-term retention of PspA was noted in the nasal cavity when compared with administration of PspA alone. Of importance, no deposition of [18F]-PspA was seen in the olfactory bulbs or brain. Nasal PspA-nanogel vaccination effectively induced PspA-specific serum IgG with protective activity and mucosal secretory IgA (SIgA) Ab responses in cynomolgus macaques (Macaca fascicularis). Nasal PspA-nanogel-induced immune responses were mediated through T-helper (Th) 2 and Th17 cytokine responses concomitantly with marked increases in the levels of miR-181a and miR-326 in the serum and respiratory tract tissues, respectively, of the macaques. These results demonstrate that nasal PspA-nanogel vaccination is a safe and effective strategy for the development of a nasal vaccine for the prevention of pneumonia in humans. PMID:25669148

  9. Classification of Extrapulmonary Manifestations Due to Mycoplasma pneumoniae Infection on the Basis of Possible Pathogenesis

    PubMed Central

    Narita, Mitsuo

    2016-01-01

    The list of extrapulmonary manifestations due to Mycoplasma pneumoniae infection can be classified according to the following three possible mechanisms derived from the established biological activity of M. pneumoniae; (1) a direct type in which the bacterium is present at the site of inflammation and local inflammatory cytokines induced by the bacterium play an important role (2) an indirect type in which the bacterium is not present at the site of inflammation and immune modulations, such as autoimmunity or formation of immune complexes, play an important role, and (3) a vascular occlusion type in which obstruction of blood flow induced either directly or indirectly by the bacterium plays an important role. Recent studies concerning extrapulmonary manifestations have prompted the author to upgrade the list, including cardiac and aortic thrombi as cardiovascular manifestations; erythema nodosum, cutaneous leukocytoclastic vasculitis, and subcorneal pustular dermatosis as dermatological manifestations; acute cerebellar ataxia, opsoclonus-myoclonus syndrome, and thalamic necrosis as neurological manifestations; pulmonary embolism as a respiratory system manifestation; and renal artery embolism as a urogenital tract manifestation. Continuing nosological confusion on M. pneumoniae–induced mucositis (without skin lesions), which may be called M. pneumoniae-associated mucositis or M. pneumoniae-induced rash and mucositis separately from Stevens-Johnson syndrome, is argued in the dermatological manifestations. Serological methods are recommended for diagnosis because pneumonia or respiratory symptoms are often minimal or even absent in extrapulmonary manifestations due to M. pneumoniae infection. Concomitant use of immunomodulators, such as corticosteroids or immunoglobulins with antibiotics effective against M. pneumoniae, can be considered as treatment modalities for most severe cases, such as encephalitis. Further studies would be necessary to construct a

  10. Bronchoscopic diagnosis of pneumonia.

    PubMed Central

    Baselski, V S; Wunderink, R G

    1994-01-01

    Lower respiratory tract infections are characterized by significant morbidity and mortality but also by a relative inability to establish a specific etiologic agent on clinical grounds alone. With the recognized shortcomings of expectorated or aspirated secretions toward establishing an etiologic diagnosis, clinicians have increasingly used bronchoscopy to obtain diagnostic samples. A variety of specimen types may be obtained, including bronchial washes or brushes, protected specimen brushings, bronchoalveolar lavage, and transbronchial biopsies. Bronchoscopy has been applied in three primary clinical settings, including the immunocompromised host, especially human immunodeficiency virus-infected and organ transplant patients; ventilator-associated pneumonia; and severe, nonresolving community- or hospital-acquired pneumonia in nonventilated patients. In each clinical setting, and for each specimen type, specific laboratory protocols are required to provide maximal information. These protocols should provide for the use of a variety of rapid microscopic and quantitative culture techniques and the use of a variety of specific stains and selective culture to detect unusual organism groups. PMID:7834604

  11. Chitinases in Pneumocystis carinii pneumonia

    PubMed Central

    Villegas, Leah R.; Kottom, Theodore J.

    2014-01-01

    Pneumocystis pneumonia remains an important complication of immune suppression. The cell wall of Pneumocystis has been demonstrated to potently stimulate host inflammatory responses, with most studies focusing on β-glucan components of the Pneumocystis cell wall. In the current study, we have elaborated the potential role of chitins and chitinases in Pneumocystis pneumonia. We demonstrated differential host mammalian chitinase expression during Pneumocystis pneumonia. We further characterized a chitin synthase gene in Pneumocystis carinii termed Pcchs5, a gene with considerable homolog to the fungal chitin biosynthesis protein Chs5. We also observed the impact of chitinase digestion on Pneumocystis-induced host inflammatory responses by measuring TNFα release and mammalian chitinase expression by cultured lung epithelial and macrophage cells stimulated with Pneumocystis cell wall isolates in the presence and absence of exogenous chitinase digestion. These findings provide evidence supporting a chitin biosynthetic pathway in Pneumocystis organisms and that chitinases modulate inflammatory responses in lung cells. We further demonstrate lung expression of chitinase molecules during Pneumocystis pneumonia. PMID:22535444

  12. Statins in pneumonia--magic versus science?

    PubMed

    Kruger, Peter S; Thomas, Robert M

    2012-01-01

    Several studies have investigated the use of statins as an adjunct in the treatment of pneumonia, some with conflicting conclusions. The most recent of these large observational studies again suggests statin use is associated with an improved outcome for patients with pneumonia. How best to incorporate these findings into current practice is of great interest. Hidden confounders plague database interrogation and so cast doubt on the real or causal nature of observed associations. Data from large, observational studies must be complemented by smaller biological studies and randomised controlled trials in an effort to complete missing pieces in the biological puzzle of the use of statins in patients with pneumonia. PMID:23025797

  13. Risk Factors and Clinical Impact of Klebsiella pneumoniae Carbapenemase–Producing K. pneumoniae

    PubMed Central

    Gasink, Leanne B.; Edelstein, Paul H.; Lautenbach, Ebbing; Synnestvedt, Marie; Fishman, Neil O.

    2010-01-01

    BACKGROUND Klebsiella pneumoniae carbapenemase (KPC)–producing K. pneumoniae is an emerging pathogen with serious clinical and infection control implications. To our knowledge, no study has specifically examined risk factors for KPC-producing K. pneumoniae or its impact on mortality. METHODS To identify risk factors for infection or colonization with KPC-producing K. pneumoniae, a case-control study was performed. Case patients with KPC-producing K. pneumoniae were compared with control subjects with carbapenem-susceptible K. pneumoniae. A cohort study evaluated the association between KPC-producing K. pneumoniae and in-hospital mortality. RESULTS Fifty-six case patients and 863 control subjects were identified. In multivariable analysis, independent risk factors for KPC-producing K. pneumoniae were (1) severe illness (adjusted odds ratio [AOR], 4.31; 95% confidence interval [CI], 2.25–8.25), (2) prior fluoroquinolone use (AOR, 3.39; 95% CI, 1.50, 7.66), and (3) prior extended-spectrum cephalosporin use (AOR, 2.55; 95% CI, 1.18, 5.52). Compared with samples from other anatomic locations, K. pneumoniae isolates from blood samples were less likely to harbor KPC (AOR, 0.33; 95% CI, 0.12, 0.86). KPC-producing K. pneumoniae was independently associated with in-hospital mortality (AOR, 3.60; 95% CI, 1.87–6.91). CONCLUSIONS KPC-producing K. pneumoniae is an emerging pathogen associated with significant mortality. Our findings highlight the urgent need to develop strategies for prevention and infection control. Limiting use of certain antimicrobials, specifically fluoroquinolones and cephalosporins, use may be effective strategies. PMID:19860564

  14. Pathophysiological Changes Induced by Pseudomonas aeruginosa Infection Are Involved in MMP-12 and MMP-13 Upregulation in Human Carcinoma Epithelial Cells and a Pneumonia Mouse Model

    PubMed Central

    Park, Ji-Won; Shin, In-Sik; Ha, Un-Hwan; Oh, Sei-Ryang

    2015-01-01

    Pseudomonas aeruginosa infections persist in patients with cystic fibrosis (CF) and drive lung disease progression. P. aeruginosa potently activates the innate immune system mostly through the recognition of pathogen-associated molecular patterns, such as flagellin. Matrix metalloproteinases 12 and 13 (MMP-12 and MMP-13, respectively) exacerbate chronic lung infection and inflammation by promoting uncontrolled tissue rearrangements and fibrosis, yet the underlying molecular mechanisms by which this occurs remain largely unknown. In this study, we used quantitative bacteriology, histological examination, and proinflammatory cytokine levels to evaluate the effects of MMP-12 and MMP-13 on P. aeruginosa strain K-induced infection and pneumonia in H292 epithelial cells and mice, respectively. Under inflammatory stimulation, mRNA and protein expression levels of proinflammatory mediators were higher in strain K-infected mice and cells than in uninfected counterparts, in which MMP-12 and MMP-13 expression reached levels similar to those observed in epithelial cells. Moreover, we also found that the NF-κB pathway might be involved in the induction of cytokines in response to strain K infection. Taken together, these data suggest that MMP-12 and MMP-13 alter strain K infection in mice and play a role in inflammatory regulation by modulating cytokine levels. PMID:26438797

  15. Paneth cell ablation in the presence of Klebsiella pneumoniae induces necrotizing enterocolitis (NEC)-like injury in the small intestine of immature mice

    PubMed Central

    Zhang, Chunxian; Sherman, Michael P.; Prince, Lawrence S.; Bader, David; Weitkamp, Jörn-Hendrik; Slaughter, James C.; McElroy, Steven J.

    2012-01-01

    SUMMARY Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in premature infants. During NEC pathogenesis, bacteria are able to penetrate innate immune defenses and invade the intestinal epithelial layer, causing subsequent inflammation and tissue necrosis. Normally, Paneth cells appear in the intestinal crypts during the first trimester of human pregnancy. Paneth cells constitute a major component of the innate immune system by producing multiple antimicrobial peptides and proinflammatory mediators. To better understand the possible role of Paneth cell disruption in NEC, we quantified the number of Paneth cells present in infants with NEC and found that they were significantly decreased compared with age-matched controls. We were able to model this loss in the intestine of postnatal day (P)14-P16 (immature) mice by treating them with the zinc chelator dithizone. Intestines from dithizone-treated animals retained approximately half the number of Paneth cells compared with controls. Furthermore, by combining dithizone treatment with exposure to Klebsiella pneumoniae, we were able to induce intestinal injury and inflammatory induction that resembles human NEC. Additionally, this novel Paneth cell ablation model produces NEC-like pathology that is consistent with other currently used animal models, but this technique is simpler to use, can be used in older animals that have been dam fed, and represents a novel line of investigation to study NEC pathogenesis and treatment. PMID:22328592

  16. The Pneumonia Etiology Research for Child Health Project: A 21st Century Childhood Pneumonia Etiology Study

    PubMed Central

    O’Brien, Katherine L.; Deloria-Knoll, Maria; Murdoch, David R.; Feikin, Daniel R.; DeLuca, Andrea N.; Driscoll, Amanda J.; Baggett, Henry C.; Brooks, W. Abdullah; Howie, Stephen R. C.; Kotloff, Karen L.; Madhi, Shabir A.; Maloney, Susan A.; Sow, Samba; Thea, Donald M.; Scott, J. Anthony

    2012-01-01

    The Pneumonia Etiology Research for Child Health (PERCH) project is a 7-country, standardized, comprehensive evaluation of the etiologic agents causing severe pneumonia in children from developing countries. During previous etiology studies, between one-quarter and one-third of patients failed to yield an obvious etiology; PERCH will employ and evaluate previously unavailable innovative, more sensitive diagnostic techniques. Innovative and rigorous epidemiologic and analytic methods will be used to establish the causal association between presence of potential pathogens and pneumonia. By strategic selection of study sites that are broadly representative of regions with the greatest burden of childhood pneumonia, PERCH aims to provide data that reflect the epidemiologic situation in developing countries in 2015, using pneumococcal and Haemophilus influenzae type b vaccines. PERCH will also address differences in host, environmental, and/or geographic factors that might determine pneumonia etiology and, by preserving specimens, will generate a resource for future research and pathogen discovery. PMID:22403238

  17. Clopidogrel-Induced Severe Hepatitis: A Case Report and Literature Review

    PubMed Central

    Keshmiri, Hesam; Behal, Anuj; Shroff, Shawn

    2016-01-01

    Clopidogrel is a commonly prescribed antiplatelet agent that carries a rare risk of hepatotoxicity. We describe a case of severe clopidogrel-induced hepatitis with liver biopsy assessment. Prompt recognition and withdrawal of the offending agent are imperative to prevent progression and potentially fatal liver injury. PMID:27429813

  18. Role of plasma exchange in autoimmune hyperthyroidism complicated by severe tiamazol-induced cholestatic jaundice.

    PubMed

    Miljić, D; Stojanović, M; Ješić, R; Bogadnović, G; Popović, V

    2013-10-01

    Therapeutic plasma exchange (TPE) is an alternative treatment for hyperthyroidism, resulting in a rapid decline in plasma thyroid hormones and anti-thyroid antibodies. TPE has also been used both in primary liver disease and in drug-induced cholestasis. Data on thyrotoxic patients with severe hepatic complications are scarce. Cholestasis induced by imidazol-derived anti-thyroid drugs is extremely rare. The use of TPE for treating this complication was not previously reported. We report the experience of one such patient with a favorable response to TPE. A 45-year-old male patient with Graves' disease, presented with severe jaundice and extremely high serum bilirubin levels due to hepatotoxicity induced by tiamazol. Through extensive investigation primary liver disease, including viral, metabolic, neoplastic and autoimmune disease, as a cause of cholestasis were all ruled out. The patient underwent total of 6 TPEs which in combination with low dose of glucocorticoids and standard supportive measures, resulted in normalization of thyroid hormones and normal liver function tests. TPE provided a safe, rapid and effective treatment of severe drug-induced cholestasis and auto immune hyperthyroidism. From this case we conclude that TPE should be considered as a valuable alternative therapeutic option in thyrotoxic patients with severe complications. Guidelines and indication criteria for TPE treatment in patients with hyperthyroidism are still lacking. PMID:23756266

  19. Severe pegfilgrastim-induced bone pain completely alleviated with loratadine: A case report.

    PubMed

    Romeo, Cristina; Li, Quan; Copeland, Larry

    2015-08-01

    Febrile neutropenia is an oncologic emergency that can result in serious consequences. Granulocyte colony stimulating factors (G-CSFs) are often used as prophylaxis for febrile neutropenia. Bone pain is the most notorious adverse effect caused by G-CSFs. Specifically, with pegfilgrastim (Neulasta(®)), the incidence of bone pain is higher in practice than was observed during clinical trials. Traditional analgesics, such as non-steroidal anti-inflammatory drugs (NSAIDs) and opioids, can be ineffective in severe pegfilgrastim-induced bone pain. With the high frequency of this adverse effect, it is clear that health practitioners need additional treatment options for patients who experience severe pegfilgrastim-induced bone pain. The mechanisms of bone pain secondary to G-CSFs are not fully known, but research has shown that histamine release is involved in the inflammatory process. There is scant previous clinical data on antihistamine use in the management of G-CSF-induced pain. We present the first case report in which loratadine prophylaxis completely alleviated NSAID-resistant severe pain secondary to pegfilgrastim. The result showed that loratadine may be a promising option for severe, resistant pegfilgrastim-induced bone pain. Further clinical studies are warranted and ongoing. PMID:24664474

  20. How Can Pneumonia Be Prevented?

    MedlinePlus

    ... page from the NHLBI on Twitter. How Can Pneumonia Be Prevented? Pneumonia can be very serious and ... t last as long Fewer serious complications Pneumococcal Pneumonia Vaccine A vaccine is available to prevent pneumococcal ...

  1. Microparticle-Induced Coagulation Relates to Coronary Artery Atherosclerosis in Severe Aortic Valve Stenosis

    PubMed Central

    Horn, Patrick; Erkilet, Gülsüm; Veulemans, Verena; Kröpil, Patric; Schurgers, Leon; Zeus, Tobias; Heiss, Christian; Kelm, Malte; Westenfeld, Ralf

    2016-01-01

    Background Circulating microparticles (MPs) derived from endothelial cells and blood cells bear procoagulant activity and promote thrombin generation. Thrombin exerts proinflammatory effects mediating the progression of atherosclerosis. Aortic valve stenosis may represent an atherosclerosis-like process involving both the aortic valve and the vascular system. The aim of this study was to investigate whether MP-induced thrombin generation is related to coronary atherosclerosis and aortic valve calcification. Methods In a cross-sectional study of 55 patients with severe aortic valve stenosis, we assessed the coronary calcification score (CAC) as indicator of total coronary atherosclerosis burden, and aortic valve calcification (AVC) by computed tomography. Thrombin-antithrombin complex (TATc) levels were measured as a marker for thrombin formation. Circulating MPs were characterized by flow cytometry according to the expression of established surface antigens and by measuring MP-induced thrombin generation. Results Patients with CAC score below the median were classified as patients with low CAC, patients with CAC Score above the median as high CAC. In patients with high CAC compared to patients with low CAC we detected higher levels of TATc, platelet-derived MPs (PMPs), endothelial-derived MPs (EMPs) and MP-induced thrombin generation. Increased level of PMPs and MP-induced thrombin generation were independent predictors for the severity of CAC. In contrast, AVC Score did not differ between patients with high and low CAC and did neither correlate with MPs levels nor with MP-induced thrombin generation. Conclusion In patients with severe aortic valve stenosis MP-induced thrombin generation was independently associated with the severity of CAC but not AVC indicating different pathomechanisms involved in coronary artery and aortic valve calcification. PMID:27010400

  2. HIV Associated Opportunistic Pneumonias.

    PubMed

    Ismail, T; Lee, C

    2011-03-01

    Opportunistic pneumonias are major causes of morbidity and mortality in HIV infected individuals. The majority of new HIV infections in Malaysia are adults aged 20 to 39 years old and many are unaware of their HIV status until they present with an opportunistic infection. HIV associated opportunistic pneumonias can progress rapidly without appropriate therapy. Therefore a proper diagnostic evaluation is vital and prompt empiric treatment of the suspected diagnosis should be commenced while waiting for the results of the diagnostic studies. Tuberculosis, Pneumocystis pneumonia (PCP) and recurrent bacterial pneumonias are common causes of AIDS-defining diseases and are discussed in this article. PMID:23765154

  3. Comparison of Passively Transferred Antibodies in Bighorn and Domestic Lambs Reveals One Factor in Differential Susceptibility of These Species to Mannheimia haemolytica-Induced Pneumonia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mannheimia haemolytica consistently causes fatal bronchopneumonia in bighorn sheep (BHS; Ovis canadensis) under natural and experimental conditions. Leukotoxin is the primary virulence factor of this organism. BHS are more susceptible to developing fatal pneumonia than the related species Ovis aries...

  4. IL-17A is proatherogenic in high-fat diet-induced and Chlamydia pneumoniae-infection accelerated atherosclerosis in mice

    PubMed Central

    Chen, Shuang; Shimada, Kenichi; Zhang, Wenxuan; Huang, Ganghua; Crother, Timothy R.; Arditi, Moshe

    2011-01-01

    The role of IL-17 in atherogenesis remains controversial. We previously reported that the TLR/MyD88 signaling pathway plays an important role in high–fat diet, as well as Chlamydophila pneumoniae (Cpn) infection-mediated acceleration of atherosclerosis in ApoE deficient mice. Here we investigated the role of the IL-17A in high-fat diet and Cpn-induced acceleration of atherosclerosis. The aortic sinus plaque and aortic lesion size and lipid composition as well as macrophage accumulation in the lesions were significantly diminished in IL-17A−/− mice fed high-fat diet compared to wild-type C57Bl/6 control mice. As expected, Cpn infection led to a significant increase in size and lipid content of the atherosclerotic lesions in wild-type mice. However, IL-17A−/− mice developed significantly less acceleration of lesion size following Cpn infection compared to wild-type control despite similar levels of blood cholesterol levels. Furthermore, Cpn infection in wild-type but not in IL-17A−/− mice was associated with significant increases in serum concentrations of IL-12p40, CCL2, INFγ and numbers of macrophages in their plaques. Additionally, in vitro studies suggest that IL-17A activates vascular endothelial cells, which secrete cytokines that in turn enhance foam cell formation in bone marrow macrophages. Taken together, our data suggest that IL-17A is pro-atherogenic and that it plays an important role in both diet-induced atherosclerotic lesion development, and Cpn infection-mediated acceleration of atherosclerotic lesions in the presence of high fat diet. PMID:20935201

  5. A Detailed Characterization of the Dysfunctional Immunity and Abnormal Myelopoiesis Induced by Severe Shock and Trauma in the Aged.

    PubMed

    Nacionales, Dina C; Szpila, Benjamin; Ungaro, Ricardo; Lopez, M Cecilia; Zhang, Jianyi; Gentile, Lori F; Cuenca, Angela L; Vanzant, Erin; Mathias, Brittany; Jyot, Jeevan; Westerveld, Donevan; Bihorac, Azra; Joseph, Anna; Mohr, Alicia; Duckworth, Lizette V; Moore, Frederick A; Baker, Henry V; Leeuwenburgh, Christiaan; Moldawer, Lyle L; Brakenridge, Scott; Efron, Philip A

    2015-09-01

    The elderly are particularly susceptible to trauma, and their outcomes are frequently dismal. Such patients often have complicated clinical courses and ultimately die of infection and sepsis. Recent research has revealed that although elderly subjects have increased baseline inflammation as compared with their younger counterparts, the elderly do not respond to severe infection or injury with an exaggerated inflammatory response. Initial retrospective analysis of clinical data from the Glue Grant trauma database demonstrated that despite a similar frequency, elderly trauma patients have worse outcomes to pneumonia than younger subjects do. Subsequent analysis with a murine trauma model also demonstrated that elderly mice had increased mortality after posttrauma Pseudomonas pneumonia. Blood, bone marrow, and bronchoalveolar lavage sample analyses from juvenile and 20-24-mo-old mice showed that increased mortality to trauma combined with secondary infection in the aged are not due to an exaggerated inflammatory response. Rather, they are due to a failure of bone marrow progenitors, blood neutrophils, and bronchoalveolar lavage cells to initiate and complete an emergency myelopoietic response, engendering myeloid cells that fail to clear secondary infection. In addition, elderly people appeared unable to resolve their inflammatory response to severe injury effectively. PMID:26246141

  6. Dysphagia, dystussia, and aspiration pneumonia in elderly people

    PubMed Central

    Sekiya, Hideki; Miyagi, Midori; Ebihara, Takae; Okazaki, Tatsuma

    2016-01-01

    Despite the development and wide distribution of guidelines for pneumonia, death from pneumonia is increasing due to population aging. Conventionally, aspiration pneumonia was mainly thought to be one of the infectious diseases. However, we have proven that chronic repeated aspiration of a small amount of sterile material can cause the usual type of aspiration pneumonia in mouse lung. Moreover, chronic repeated aspiration of small amounts induced chronic inflammation in both frail elderly people and mouse lung. These observations suggest the need for a paradigm shift of the treatment for pneumonia in the elderly. Since aspiration pneumonia is fundamentally based on dysphagia, we should shift the therapy for aspiration pneumonia from pathogen-oriented therapy to function-oriented therapy. Function-oriented therapy in aspiration pneumonia means therapy focusing on slowing or reversing the functional decline that occurs as part of the aging process, such as “dementia → dysphagia → dystussia → atussia → silent aspiration”. Atussia is ultimate dysfunction of cough physiology, and aspiration with atussia is called silent aspiration, which leads to the development of life-threatening aspiration pneumonia. Research pursuing effective strategies to restore function in the elderly is warranted in order to decrease pneumonia deaths in elderly people. PMID:27076964

  7. Clozapine-induced hypersalivation: an estimate of prevalence, severity and impact on quality of life

    PubMed Central

    Maher, Senan; Cunningham, Aoife; O’Callaghan, Niamh; Byrne, Fintan; Mc Donald, Colm; McInerney, Shane; Hallahan, Brian

    2016-01-01

    Objectives: The objective of this study was to evaluate the prevalence and severity of clozapine-induced hypersalivation, and assess the impact hypersalivation has on global functioning. Methods: Participants attending a dedicated clozapine clinic were invited to undertake a structured interview regarding their experiences of clozapine-induced hypersalivation. Two psychometric instruments to measure hypersalivation, the Nocturnal Hypersalivation Rating Scale and the Drooling Severity and Frequency Scale were used. Results: Clozapine-induced hypersalivation was experienced by 92% of participants, with nocturnal hypersalivation more prevalent compared to daytime hypersalivation (85% versus 48%). Daytime drooling was severe in 18% of cases and was present on a frequent or constant basis for 20% of individuals. Hypersalivation had at least a moderate impact on the quality of life of 15% of study participants. Conclusions: Clozapine-induced hypersalivation is the most prevalent adverse effect experienced by patients treated with clozapine and negatively impacts on quality of life, particularly if daytime drooling is present. The development of further strategies to ameliorate this adverse effect is required given the demonstrated lack of success to date in managing this condition. PMID:27354906

  8. Incidence, severity and factors related to drug-induced keratoepitheliopathy with glaucoma medications

    PubMed Central

    Fukuchi, Takeo; Wakai, Kimiko; Suda, Kieko; Nakatsue, Tomoko; Sawada, Hideko; Hara, Hiroaki; Ueda, Jun; Tanaka, Takayuki; Yamada, Akiko; Abe, Haruki

    2010-01-01

    Purpose To evaluate the incidence, severity, and factors related to drug-induced keratoepitheliopathy in eyes using antiglaucoma eye drops. Patients and methods In a cross-sectional study, 749 eyes from 427 patients who had used one or more antiglaucoma eye drops were examined at Niigata University Medical and Dental Hospital or related facilities. The incidence and severity of superficial punctate keratitis (SPK), patient gender and age, type of glaucoma, and type of eye drops were recorded. SPK was graded according to the AD (A, area; D, density) classification. The severity score (SS) was calculated from A × D. Results SPK was observed in 382 (51.0%) of 749 eyes that had received any type of antiglaucoma eye drops. While 254 eyes (33.9%) were classified as A1D1 (SS 1), 34 eyes (4.6%) had severe SPK with SS 4 or more. The number of eye drops and the total dosing frequency per day were significantly greater in SPK-positive eyes than in eyes without SPK. The number of eye drops was proportional to the frequency and severity of SPK. Among eyes that were treated with three or more eye drops, SPK was more severe and more frequent in older patients (≥71 years). In addition, a considerable difference was detected for each type of glaucoma. Conclusion Drug-induced keratoepitheliopathy is often observed in eyes that have received recent antiglaucoma eye drops. The number of eye drops, the total dose frequency per day, patient age, and type of glaucoma may affect this condition. We have to consider not only the effects on intraocular pressure but also the incidence and severity of drug-induced keratoepitheliopathy as a frequent side effect of glaucoma medications. PMID:20463785

  9. Is 13-Valent Pneumococcal Conjugate Vaccine (PCV13) Combined With 23-Valent Pneumococcal Polysaccharide Vaccine (PPSV23) Superior to PPSV23 Alone for Reducing Incidence or Severity of Pneumonia in Older Adults? A Clin-IQ

    PubMed Central

    Hayward, Starla; Thompson, Lou Ann; McEachern, Andrea

    2016-01-01

    Pneumonia infection is a significant cause of morbidity and mortality worldwide. In addition to the public health concerns, pneumonia also accounts for a significant cost to the health care system. Currently there are two leading vaccines targeted against S. pneumoniae: 23-valent pneumococcal polysaccharide vaccine (PPSV23) and 13-valent pneumococcal conjugate vaccine (PCV13). Until recently the recommendation for adult pneumonia vaccination has been a single dose of PPSV23 for all adults 65 years and older. However, concerns were raised regarding the vaccine’s efficacy due to the persistent burden of pneumococcal disease in the elderly population. This paper focuses on two trials which evaluate the safety and efficacy of PCV13 in the adult population. The first study reveals improved immune response with the addition of PCV13 to PPSV23, while the second shows PCV13 was effective in the prevention of vaccine-type community-acquired pneumonia. The two studies observed adequate safety profiles for PCV13 in series with PPSV23 and with PCV13 compared to placebo. PMID:27376105

  10. Persistent Pneumonia in an Infant

    PubMed Central

    Padilla, Kristen; Logan, Latania; Codispoti, Christopher; Jones, Carolyn

    2015-01-01

    A 4-month-old boy with past medical history of eczema presented with fever and cough; a chest radiograph showed lung consolidation, and he was initially treated with amoxicillin for presumed community-acquired pneumonia. After several days, his fever persisted. He was also profoundly anemic. Antibiotic coverage was broadened because of the concern for resistant organisms; he began to improve and was discharged from the hospital. However, at 5 months of age, his fever returned, and he continued to demonstrate lung consolidation on chest radiograph. Additionally, he had lost weight and continued to be anemic. Splenic cysts were noted on abdominal ultrasound. He was diagnosed with an unusual etiology for his pneumonia and improved with the appropriate therapy. An underlying immunodeficiency was suspected, but initial testing was nondiagnostic. At 12 months of age, he presented with another infection, and the final diagnosis was made. PMID:26122810

  11. Acute fibrinous and organizing pneumonia: A rare form of nonbacterial pneumonia.

    PubMed

    Saxena, Prashant; Kumar, Kuldeep; Mittal, Sarita; Goyal, Nidhi; Trikha, Sahil; Vashisth, Arti

    2016-04-01

    Acute fibrinous and organizing pneumonia (AFOP) is a rare disease characterized by bilateral basilar infiltrates and histological findings of organizing pneumonia and intra-alveolar fibrin in the form of "fibrin balls." Here, we report a 43-year-old female with complaints of fever, dry cough, and shortness of breath with hypoxemia. High-resolution computed tomography thorax revealed diffuse confluent consolidation in bilateral lung zones. Bronchoscopy and transbronchial biopsy revealed features of AFOP. With prednisolone treatment, there was an improvement in her condition. AFOP is a rare disease and should be taken into consideration and differential diagnosis of severe acute pneumonias with no significant comorbidities. PMID:27303141

  12. Acute fibrinous and organizing pneumonia: A rare form of nonbacterial pneumonia

    PubMed Central

    Saxena, Prashant; Kumar, Kuldeep; Mittal, Sarita; Goyal, Nidhi; Trikha, Sahil; Vashisth, Arti

    2016-01-01

    Acute fibrinous and organizing pneumonia (AFOP) is a rare disease characterized by bilateral basilar infiltrates and histological findings of organizing pneumonia and intra-alveolar fibrin in the form of “fibrin balls.” Here, we report a 43-year-old female with complaints of fever, dry cough, and shortness of breath with hypoxemia. High-resolution computed tomography thorax revealed diffuse confluent consolidation in bilateral lung zones. Bronchoscopy and transbronchial biopsy revealed features of AFOP. With prednisolone treatment, there was an improvement in her condition. AFOP is a rare disease and should be taken into consideration and differential diagnosis of severe acute pneumonias with no significant comorbidities. PMID:27303141

  13. Valproic Acid-Induced Severe Acute Pancreatitis with Pseudocyst Formation: Report of a Case.

    PubMed

    Ray, Sukanta; Khamrui, Sujan; Kataria, Mohnish; Biswas, Jayanta; Saha, Suman

    2015-08-01

    Valproic acid is the most widely used anti-epilep-tic drug in children, and it is probably the most frequent cause of drug-induced acute pancreatitis. Outcomes for patients with valproic acid-associated pancreatitis vary from full recovery after discontinuation of the drug to severe acute pancreatitis and death. Here, we present a case of valproic acid-induced severe acute pancreatitis with pseudocyst formation in a 10-year-old girl with cerebral palsy and generalized tonic-clonic seizure. There was no resolution of the pseudocyst after discontinuation of valproic acid. The patient became symptomatic with a progressive increase in the size of the pseudocyst. She was successfully treated with cystogastrostomy and was well at 12-month follow-up. PMID:26366333

  14. Valproic Acid-Induced Severe Acute Pancreatitis with Pseudocyst Formation: Report of a Case

    PubMed Central

    Khamrui, Sujan; Kataria, Mohnish; Biswas, Jayanta; Saha, Suman

    2015-01-01

    Valproic acid is the most widely used anti-epilep­tic drug in children, and it is probably the most frequent cause of drug-induced acute pancreatitis. Outcomes for patients with valproic acid-associated pancreatitis vary from full recovery after discontinuation of the drug to severe acute pancreatitis and death. Here, we present a case of valproic acid-induced severe acute pancreatitis with pseudocyst formation in a 10-year-old girl with cerebral palsy and generalized tonic-clonic seizure. There was no resolution of the pseudocyst after discontinuation of valproic acid. The patient became symptomatic with a progressive increase in the size of the pseudocyst. She was successfully treated with cystogastrostomy and was well at 12-month follow-up. PMID:26366333

  15. Cyclophosphamide-induced symptomatic hyponatremia, a rare but severe side effect: a case report.

    PubMed

    Elazzazy, Shereen; Mohamed, Asmaa Elhassan; Gulied, Amaal

    2014-01-01

    Cyclophosphamide is commonly used in the treatment of malignant diseases. Symptomatic severe hyponatremia induced by low-dose cyclophosphamide is very uncommon worldwide. We report a case of severe symptomatic hyponatremia that developed in a female breast cancer patient following the first cycle of chemotherapy containing low-dose cyclophosphamide. Her laboratory test showed serum Na of 112 mmol/L. Her hyponatremia was initially treated with sodium bicarbonate. She completely recovered without neurological deficits after slow correction of the serum Na concentration. Although hyponatremia is a rare toxicity it should always be considered during the usage of cyclophosphamide, even if the dosage is low, especially with concurrent use of other medications that impair water excretion, like chlorthalidone. This report describes the first reported case of cyclophosphamide-induced hyponatremia in Qatar. PMID:25336968

  16. Hyperactivity induced by prenatal BrdU exposure across several experimental conditions.

    PubMed

    Kuwagata, Makiko; Ogawa, Tetsuo; Muneoka, Katsumasa; Shioda, Seiji

    2011-12-01

    Behavioral results are sometimes not reproducible even in the positive controls of developmental neurotoxicity (DNT) tests. Effects of several factors on the results should be considered. In the present paper, we examined the effects of strain-, gender-, and test-condition differences on BrdU-induced hyperactivity. The results showed that BrdU-induced hyperactivity was reproducible in two rat strains (SD and F344 rats), rodent species (rat and mouse), and both sexes. When the level of background sound in a test room was increased, the hyperactivity was persistent, resulting in no effect of background sound on BrdU-induced hyperactivity. Thus, we have demonstrated that the BrdU-animal model is a useful positive control via prenatal exposure to validate the entire DNT test process. PMID:22103457

  17. Protective Effect of Tetrandrine on Sodium Taurocholate-Induced Severe Acute Pancreatitis

    PubMed Central

    Wu, Xian-lin; Li, Jie-xing; Li, Zhen-dong; Liu, Da-sheng; Lu, Su-hong; Liu, Kang-li; Duan, Hong-yan; Luo, Yu-hong

    2015-01-01

    Tet is a type of alkaloid extracted from Stephania tetrandra, and it has recently been demonstrated that Tet can protect against inflammation and free radical injury and inhibit the release of inflammatory mediators. The present study was designed to observe the protective effect of Tet on sodium taurocholate-induced severe acute pancreatitis (SAP). The rat model of SAP was induced by retrograde bile duct injection of sodium taurocholate and then treated with Verapamil and Tet. The results showed that Tet can reduce NF-κB activation in pancreas issue, inhibit the SAP cascade, and improve SAP through inducing pancreas acinar cell apoptosis and stabilizing intracellular calcium in the pancreas, thus mitigating the damage to the pancreas. Our study revealed that Tet may reduce systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndromes (MODS) to protect against damage, and these roles may be mediated through the NF-κB pathway to improve the proinflammatory/anti-inflammatory imbalance. PMID:26557854

  18. Protective Effect of Tetrandrine on Sodium Taurocholate-Induced Severe Acute Pancreatitis.

    PubMed

    Wu, Xian-Lin; Li, Jie-Xing; Li, Zhen-Dong; Liu, Da-Sheng; Lu, Su-Hong; Liu, Kang-Li; Duan, Hong-Yan; Luo, Yu-Hong

    2015-01-01

    Tet is a type of alkaloid extracted from Stephania tetrandra, and it has recently been demonstrated that Tet can protect against inflammation and free radical injury and inhibit the release of inflammatory mediators. The present study was designed to observe the protective effect of Tet on sodium taurocholate-induced severe acute pancreatitis (SAP). The rat model of SAP was induced by retrograde bile duct injection of sodium taurocholate and then treated with Verapamil and Tet. The results showed that Tet can reduce NF-κB activation in pancreas issue, inhibit the SAP cascade, and improve SAP through inducing pancreas acinar cell apoptosis and stabilizing intracellular calcium in the pancreas, thus mitigating the damage to the pancreas. Our study revealed that Tet may reduce systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndromes (MODS) to protect against damage, and these roles may be mediated through the NF-κB pathway to improve the proinflammatory/anti-inflammatory imbalance. PMID:26557854

  19. Investigation on the conA binding properties of Klebsiella pneumoniae.

    PubMed

    Anuar, A S S; Tay, S T

    2014-12-01

    Klebsiella pneumoniae is a healthcare-associated bacterial pathogen which causes severe diseases in immunocompromised individuals. Concanavalin A (conA), a lectin which recognizes proteins with mannose or glucose residues, has been reported to agglutinate K. pneumoniae and hence, is postulated to have therapeutical potential for K. pneumoniae-induced liver infection. This study investigated the conA binding properties of a large collection of clinical isolates of K. pneumoniae. ConA agglutination reaction was demonstrated by 94 (51.4%) of 183 K. pneumoniae isolates using a microtiter plate assay. The conA agglutination reactions were inhibited in the presence of 2.5 mg/ml D-mannose and 2.5 mg/ml glucose, and following pretreatment of the bacterial suspension with protease and heating at 80ºC. Majority of the positive isolates originated from respiratory specimens. Isolation of conA-binding proteins from K. pneumoniae ATCC 700603 strain was performed using conA affinity column and the conA binding property of the eluted proteins was confirmed by western blotting analysis using conA-HRP conjugates. Proteins with molecular weights ranging from 35 to 60 kDa were eluted from the conA affinity column, of which four were identified as outer membrane protein precursor A (37 kDa), outer membrane protein precursor C (40 kDa), enolase (45 kDa) and chaperonin (60 kDa) using mass spectrometry analysis. Several conA binding proteins (including 45 and 60 kDa) were found to be immunogenic when reacted with rabbit anti-Klebsiella antibody. The function and interplay of the conA binding proteins in bacterium-host cell relationship merits further investigation. PMID:25776607

  20. Allergic airway inflammation disrupts interleukin-17 mediated host defense against streptococcus pneumoniae infection.

    PubMed

    Guo, Sheng; Wu, Liang-Xia; Jones, Can-Xin; Chen, Ling; Hao, Chun-Li; He, Li; Zhang, Jian-Hua

    2016-02-01

    Despite decreasing rates of invasive pneumococcal disease caused by vaccine serotypes, the prevalence of invasive pneumococcal pneumonia in asthmatic patients remains high. However, little is known about the mechanisms underlying the susceptibility of the asthmatic airway to bacterial infections. In this study, we used a combined model of allergic airway inflammation and Streptococcus pneumoniae lung infection to investigate the association between persistent allergic inflammation in the airway and antibacterial host defenses against S. pneumoniae. When challenged with S. pneumoniae, allergic mice exhibited higher airway bacterial burdens, greater eosinophil infiltration, lower neutrophil infiltration, and more severe structural damage than non-allergic mice. In sensitized mice, S. pneumoniae infection elicited higher IL-4 but lower IFN-γ, IL-17 and defensin-β2 expression than in control mice. These results indicate that persistent allergic inflammation impaired airway host defense against S. pneumoniae is associated with the insufficient IL-17 responses. To elicit IL-17 induced-anti-bacterial immune responses, mice were intranasally immunized with rIL-17. Immunized mice exhibited fewer bacterial colonies in the respiratory tract and less severe lung pathology than unimmunized mice. rIL-17 contributed to airway host defense enhancement and innate immune response promotion, which was associated with increased IL-23, MIP-2 and defensin-β2 expression. Administration of exogenous IL-17 (2μg/mouse) suppressed eosinophil-related immune responses. The results demonstrate IL-17 plays a key role in host defenses against bacterial infection in allergic airways and suggest that exogenous IL-17 administration promotes the anti-becterial immune responses and attenuates the existed allergic inflammation. PMID:26699848

  1. Severe arrhythmia induced by orally disintegrating aripiprazole tablets (Bosiqing(®)): a case report.

    PubMed

    Shao, Qing; Quan, Wei; Jia, Xiaoni; Chen, Jianbo; Ma, Shanbo; Zhang, Xiaohong

    2015-01-01

    Psychotropic medications have been known to cause cardiac conduction disturbances. Not much is known about the cardiovascular side effects of newer atypical antipsychotics such as aripiprazole. A case of a 13-year-old girl with schizophrenia is presented. An analysis of the presented patient's clinical history indicates the need for a detailed analysis of the severe arrhythmia induced by aripiprazole. This presented case report contains valuable guidelines that can be of assistance in the treatment of patients with aripiprazole. PMID:26677328

  2. Glutamate carboxypeptidase inhibition reduces the severity of chemotherapy-induced peripheral neurotoxicity in rat.

    PubMed

    Carozzi, Valentina A; Chiorazzi, Alessia; Canta, Annalisa; Lapidus, Rena G; Slusher, Barbara S; Wozniak, Krystyna M; Cavaletti, Guido

    2010-05-01

    Chemotherapy is the most common method to treat cancer. The use of certain antineoplastic drugs, however, is associated with the development of peripheral neuropathy that can be dose-limiting. Excitotoxic glutamate release, leading to excessive glutamatergic neurotransmission and activation of N-methyl-D-aspartate (NMDA) receptors, is associated with neuronal damage and death in several nervous system disorders. N-Acetyl-aspartyl-glutamate (NAAG) is an abundant neuropeptide widely distributed in the central and peripheral nervous system which is physiologically hydrolyzed by the enzyme glutamate carboxypeptidase into N-Acetyl-aspartyl (NAA) and glutamate. Pharmacological inhibition of glutamate carboxypeptidase results in decreased glutamate and increased endogenous NAAG and has been shown to provide neuroprotection in several preclinical models. Here, we report the neuroprotective effect of an orally available glutamate carboxypeptidase inhibitor on three well-established animal models of chemotherapy (cisplatin, paclitaxel, bortezomib)-induced peripheral neuropathy. In all cases, glutamate carboxypeptidase inhibition significantly improved the chemotherapy-induced nerve conduction velocity deficits. In addition, morphological and morphometrical alterations induced by cisplatin and bortezomib in dorsal root ganglia (DRG) were improved by glutamate carboxypeptidase inhibition. Our data support a novel approach for the treatment of chemotherapy-induced peripheral neuropathy. PMID:19763734

  3. Mycoplasma pneumoniae infection and Tourette's syndrome.

    PubMed

    Müller, Norbert; Riedel, Michael; Blendinger, Christa; Oberle, Karin; Jacobs, Enno; Abele-Horn, Marianne

    2004-12-15

    An association between infection and Tourette's syndrome (TS) has been described repeatedly. A role for streptococcal infection (PANDAS) has been established for several years, but the involvement of other infectious agents such as Borrelia Burgdorferi or Mycoplasma pneumoniae has only been described in single case reports. We examined antibody titers against M. pneumoniae and various types of antibodies by immunoblot in patients and in a sex- and age-matched comparison group. Participants comprised 29 TS patients and 29 controls. Antibody titers against M. pneumoniae were determined by microparticle agglutination (MAG) assay and confirmed by immunoblot. Elevated titers were found in significantly more TS patients than controls (17 vs. 1). Additionally, the number of IgA positive patients was significantly higher in the TS group than in the control group (9 vs. 1). A higher proportion of increased serum titers and especially of IgA antibodies suggests a role for M. pneumoniae in a subgroup of patients with TS and supports the finding of case reports implicating an acute or chronic infection with M. pneumoniae as one etiological agent for tics. An autoimmune reaction, however, has to be taken into account. In predisposed persons, infection with various agents including M. pneumoniae should be considered as at least an aggravating factor in TS. PMID:15590039

  4. Pathogenesis of Mycoplasma pneumoniae: An update.

    PubMed

    Chaudhry, R; Ghosh, A; Chandolia, A

    2016-01-01

    Genus Mycoplasma, belonging to the class Mollicutes, encompasses unique lifeforms comprising of a small genome of 8,00,000 base pairs and the inability to produce a cell wall under any circumstances. Mycoplasma pneumoniae is the most common pathogenic species infecting humans. It is an atypical respiratory bacteria causing community acquired pneumonia (CAP) in children and adults of all ages. Although atypical pneumonia caused by M. pneumoniae can be managed in outpatient settings, complications affecting multiple organ systems can lead to hospitalization in vulnerable population. M. pneumoniae infection has also been associated with chronic lung disease and bronchial asthma. With the advent of molecular methods of diagnosis and genetic, immunological and ultrastructural assays that study infectious disease pathogenesis at subcellular level, newer virulence factors of M. pneumoniae have been recognized by researchers. Structure of the attachment organelle of the organism, that mediates the crucial initial step of cytadherence to respiratory tract epithelium through complex interaction between different adhesins and accessory adhesion proteins, has been decoded. Several subsequent virulence mechanisms like intracellular localization, direct cytotoxicity and activation of the inflammatory cascade through toll-like receptors (TLRs) leading to inflammatory cytokine mediated tissue injury, have also been demonstrated to play an essential role in pathogenesis. The most significant update in the knowledge of pathogenesis has been the discovery of Community-Acquired Respiratory Distress Syndrome toxin (CARDS toxin) of M. pneumoniae and its ability of adenosine diphosphate (ADP) ribosylation and inflammosome activation, thus initiating airway inflammation. Advances have also been made in terms of the different pathways behind the genesis of extrapulmonary complications. This article aims to comprehensively review the recent advances in the knowledge of pathogenesis of this

  5. Premedication with Clarithromycin Is Effective against Secondary Bacterial Pneumonia during Influenza Virus Infection in a Pulmonary Emphysema Mouse Model.

    PubMed

    Harada, Tatsuhiko; Ishimatsu, Yuji; Hara, Atsuko; Morita, Towako; Nakashima, Shota; Kakugawa, Tomoyuki; Sakamoto, Noriho; Kosai, Kosuke; Izumikawa, Koichi; Yanagihara, Katsunori; Mukae, Hiroshi; Kohno, Shigeru

    2016-09-01

    Secondary bacterial pneumonia (SBP) during influenza increases the severity of chronic obstructive pulmonary disease (COPD) and its associated mortality. Macrolide antibiotics, including clarithromycin (CAM), are potential treatments for a variety of chronic respiratory diseases owing to their pharmacological activities, in addition to antimicrobial action. We examined the efficacy of CAM for the treatment of SBP after influenza infection in COPD. Specifically, we evaluated the effect of CAM in elastase-induced emphysema mice that were inoculated with influenza virus (strain A/PR8/34) and subsequently infected with macrolide-resistant Streptococcus pneumoniae CAM was administered to the emphysema mice 4 days prior to influenza virus inoculation. Premedication with CAM improved pathologic responses and bacterial load 2 days after S. pneumoniae inoculation. Survival rates were higher in emphysema mice than control mice. While CAM premedication did not affect viral titers or exert antibacterial activity against S. pneumoniae in the lungs, it enhanced host defense and reduced inflammation, as evidenced by the significant reductions in total cell and neutrophil counts and interferon (IFN)-γ levels in bronchoalveolar lavage fluid and lung homogenates. These results suggest that CAM protects against SBP during influenza in elastase-induced emphysema mice by reducing IFN-γ production, thus enhancing immunity to SBP, and by decreasing neutrophil infiltration into the lung to prevent injury. Accordingly, CAM may be an effective strategy to prevent secondary bacterial pneumonia in COPD patients in areas in which vaccines are inaccessible or limited. PMID:27489022

  6. Assessing the effects of severe rainstorm-induced mixing on a subtropical, subalpine lake.

    PubMed

    Kimura, Nobuaki; Liu, Wen-Cheng; Chiu, Chih-Yu; Kratz, T K

    2014-05-01

    Severe rainstorms cause vertical mixing that modifies the internal dynamics (e.g., internal seiche, thermal structure, and velocity filed) in warm polymictic lakes. Yuan Yang Lake (YYL), a subtropical, subalpine, and seasonally stratified small lake in the north-central region of Taiwan, is normally affected by typhoons accompanied with strong wind and heavy rainfall during the summer and fall. In this study, we used the field data, statistical analysis, spectral analysis, and numerical modeling to investigate severe rainstorm-induced mixing in the lake. Statistical determination of the key meteorological and environmental conditions underlying the observed vertical mixing suggests that the vertical mixing, caused by heat loss during severe rainstorms, was likely larger than wind-induced mixing and that high inflow discharge strongly increased heat loss through advection heat. Spectral analysis revealed that internal seiches at the basin scale occurred under non-rainstorm meteorological conditions and that the internal seiches under the rainstorm were modified on the increase of the internal seiche frequencies. Based upon observed frequencies of the internal seiches, a two-dimensional model was simulated and then appropriate velocity patterns of the internal seiches were determined under non-rainstorm conditions. Moreover, the model implemented with inflow boundary condition was conducted for rainstorm events. The model results showed that the severe rainstorms promoted thermal destratification and changed vertical circulation of the basin-scale, internal seiche motion into riverine flow. PMID:24415132

  7. Infection with and Carriage of Mycoplasma pneumoniae in Children

    PubMed Central

    Meyer Sauteur, Patrick M.; Unger, Wendy W. J.; Nadal, David; Berger, Christoph; Vink, Cornelis; van Rossum, Annemarie M. C.

    2016-01-01

    “Atypical” pneumonia was described as a distinct and mild form of community-acquired pneumonia (CAP) already before Mycoplasma pneumoniae had been discovered and recognized as its cause. M. pneumoniae is detected in CAP patients most frequently among school-aged children from 5 to 15 years of age, with a decline after adolescence and tapering off in adulthood. Detection rates by polymerase chain reaction (PCR) or serology in children with CAP admitted to the hospital amount 4–39%. Although the infection is generally mild and self-limiting, patients of every age can develop severe or extrapulmonary disease. Recent studies indicate that high rates of healthy children carry M. pneumoniae in the upper respiratory tract and that current diagnostic PCR or serology cannot discriminate between M. pneumoniae infection and carriage. Further, symptoms and radiologic features are not specific for M. pneumoniae infection. Thus, patients may be unnecessarily treated with antimicrobials against M. pneumoniae. Macrolides are the first-line antibiotics for this entity in children younger than 8 years of age. Overall macrolides are extensively used worldwide, and this has led to the emergence of macrolide-resistant M. pneumoniae, which may be associated with severe clinical features and more extrapulmonary complications. This review focuses on the characteristics of M. pneumoniae infections in children, and exemplifies that simple clinical decision rules may help identifying children at high risk for CAP due to M. pneumoniae. This may aid physicians in prescribing appropriate first-line antibiotics, since current diagnostic tests for M. pneumoniae infection are not reliably predictive. PMID:27047456

  8. Several domains from VAR2CSA can induce Plasmodium falciparum adhesion-blocking antibodies

    PubMed Central

    2010-01-01

    Background Malaria caused by Plasmodium falciparum can result in several different syndromes with severe clinical consequences for the about 200 million individuals infected each year. During pregnancy, women living in endemic areas become susceptible to malaria due to lack of antibodies against a unique P. falciparum membrane protein, named VAR2CSA. This antigen is not expressed in childhood infections, since it binds chondroitin sulphate A (CSA) expressed on the intervillous space in the placenta. A vaccine appears possible because women acquire protective antibodies hindering sequestration in the placenta as a function of parity. A challenge for vaccine development is to design small constructs of this large antigen, which can induce broadly protective antibodies. It has previously been shown that one domain of VAR2CSA, DBL4-FCR3, induces parasite adhesion-blocking antibodies. In this study, it is demonstrated that other domains of VAR2CSA also can induce antibodies with inhibitory activity. Methods All VAR2CSA domains from the 3D7 and HB3 parasites were produced in Baculovirus-transfected insect cells. Groups of three rats per protein were immunized and anti-sera were tested for surface reactivity against infected erythrocytes expressing FCR3 VAR2CSA and for the ability to inhibit FCR3CSA parasite adhesion to CSA. The fine specificity of the immune sera was analysed by VAR2CSA peptide arrays. Results Inhibitory antibodies were induced by immunization with DBL3-HB3 T1 and DBL1-3D7. However, unlike the previously characterised DBL4-FCR3 response the inhibitory response against DBL1-3D7 and DBL3-HB3 T1 was poorly reproduced in the second rounds of immunizations. Conclusion It is possible to induce parasite adhesion-blocking antibodies when immunizing with a number of different VAR2CSA domains. This indicates that the CSA binding site in VAR2CSA is comprised of epitopes from different domains. PMID:20064234

  9. Diagnosis of nosocomial pneumonia.

    PubMed

    Bamberger, D M

    1988-06-01

    Nosocomial pneumonia occurs in 0.6% of hospitalized patients. The usual causative agents are gram-negative bacilli, Staphylococcus aureus, Streptococcus pneumoniae, and anaerobic bacteria. In immunocompromised hosts, the differential diagnosis also includes fungi, mycobacteria, viruses, Nocardia, and Pneumocystis carinii. Important risk factors for the development of nosocomial pneumonia include prolonged mechanical ventilation, thoracic or upper abdominal surgery, altered mental status, underlying immunosuppression, chronic obstructive pulmonary disease, and the use of antacids or histamine type 2 blockers. Colonization of the oropharynx and tracheal secretions with gram-negative aerobic bacteria is common in hospitalized patients with or without pneumonia. The diagnosis of nosocomial pneumonia is usually based on the clinical features of dyspnea, cough, fever, purulent sputum production, new pulmonary infiltrates, hypoxemia, and leukocytosis. However, the clinician must recognize that the presence of these features is neither sensitive nor specific in the diagnosis of nosocomial pneumonia. Microbiologic diagnosis is also difficult because blood cultures are usually negative, and cultures of tracheal secretions, although usually sensitive, are not specific. Invasive procedures may prove useful, but most have yet to be studied in large groups of patients with nosocomial pneumonia. PMID:3041515

  10. A reliable, practical, and economical protocol for inducing diarrhea and severe dehydration in the neonatal calf.

    PubMed Central

    Walker, P G; Constable, P D; Morin, D E; Drackley, J K; Foreman, J H; Thurmon, J C

    1998-01-01

    Fifteen healthy, colostrum-fed, male dairy calves, aged 2 to 7 d were used in a study to develop a diarrhea protocol for neonatal calves that is reliable, practical, and economical. After instrumentation and recording baseline data, diarrhea and dehydration were induced by administering milk replacer [16.5 mL/kg of body weight (BW), PO], sucrose (2 g/kg in a 20% aqueous solution, p.o.), spironolactone and hydrochlorothiazide (1 mg/kg, PO) every 8 h, and furosemide (2 mg/kg, i.m., q6h). Calves were administered sucrose and diuretic agents for 48 h to induce diarrhea and severe dehydration. Clinical changes after 48 h were severe watery diarrhea, severe depression, and marked dehydration (mean, 14% BW loss). Cardiac output, stroke volume, mean central venous pressure, plasma volume, thiocyanate space, blood pH and bicarbonate concentration, base excess, serum chloride concentration, and fetlock temperature were decreased. Plasma lactate concentration, hematocrit, and serum potassium, creatinine, phosphorus, total protein and albumin concentrations were increased. This non-infectious calf diarrhea protocol has a 100% response rate, while providing a consistent and predictable hypovolemic state with diarrhea that reflects most of the clinicopathologic changes observed in osmotic/maldigestive diarrhea caused by infection with rotavirus, coronavirus or cryptosporidia. Limitations of the protocol, when compared to infectious diarrhea models, include failure to induce a severe metabolic acidosis, absence of hyponatremia, renal instead of enteric loss of chloride, renal as well as enteric loss of free water, absence of profound clinical depression and suspected differences in the morphologic and functional effect on intestinal epithelium. Despite these differences, the sucrose/diuretic protocol should be useful in the initial screening of new treatment modalities for calf diarrhea. To confirm their efficacy, the most effective treatment methods should then be examined in

  11. Community-acquired pneumonia.

    PubMed

    Falguera, M; Ramírez, M F

    2015-11-01

    This article not only reviews the essential aspects of community-acquired pneumonia for daily clinical practice, but also highlights the controversial issues and provides the newest available information. Community-acquired pneumonia is considered in a broad sense, without excluding certain variants that, in recent years, a number of authors have managed to delineate, such as healthcare-associated pneumonia. The latter form is nothing more than the same disease that affects more frail patients, with a greater number of risk factors, both sharing an overall common approach. PMID:26186969

  12. Helminth-induced arginase-1 exacerbates lung inflammation and disease severity in tuberculosis

    PubMed Central

    Monin, Leticia; Griffiths, Kristin L.; Lam, Wing Y.; Gopal, Radha; Kang, Dongwan D.; Ahmed, Mushtaq; Rajamanickam, Anuradha; Cruz-Lagunas, Alfredo; Zúñiga, Joaquín; Babu, Subash; Kolls, Jay K.; Mitreva, Makedonka; Rosa, Bruce A.; Ramos-Payan, Rosalio; Morrison, Thomas E.; Murray, Peter J.; Rangel-Moreno, Javier; Pearce, Edward J.; Khader, Shabaana A.

    2015-01-01

    Parasitic helminth worms, such as Schistosoma mansoni, are endemic in regions with a high prevalence of tuberculosis (TB) among the population. Human studies suggest that helminth coinfections contribute to increased TB susceptibility and increased rates of TB reactivation. Prevailing models suggest that T helper type 2 (Th2) responses induced by helminth infection impair Th1 immune responses and thereby limit Mycobacterium tuberculosis (Mtb) control. Using a pulmonary mouse model of Mtb infection, we demonstrated that S. mansoni coinfection or immunization with S. mansoni egg antigens can reversibly impair Mtb-specific T cell responses without affecting macrophage-mediated Mtb control. Instead, S. mansoni infection resulted in accumulation of high arginase-1–expressing macrophages in the lung, which formed type 2 granulomas and exacerbated inflammation in Mtb-infected mice. Treatment of coinfected animals with an antihelminthic improved Mtb-specific Th1 responses and reduced disease severity. In a genetically diverse mouse population infected with Mtb, enhanced arginase-1 activity was associated with increased lung inflammation. Moreover, in patients with pulmonary TB, lung damage correlated with increased serum activity of arginase-1, which was elevated in TB patients coinfected with helminths. Together, our data indicate that helminth coinfection induces arginase-1–expressing type 2 granulomas, thereby increasing inflammation and TB disease severity. These results also provide insight into the mechanisms by which helminth coinfections drive increased susceptibility, disease progression, and severity in TB. PMID:26571397

  13. Glutamine in Alleviation of Radiation-Induced Severe Oral Mucositis: A Meta-Analysis.

    PubMed

    Leung, Henry W C; Chan, Agnes L F

    2016-07-01

    The aim of this meta-analysis was to assess the effectiveness of glutamine to treat severe mucositis induced by radiation therapy in patients with head and neck cancer. We undertook electronic searches of PubMed (1990 to January 2015), Embase (1990 to January 2015), and the Cochrane Library (2013, Issue 2) to identify relevant studies. We included randomized controlled trials of glutamine to alleviate oral mucositis (OM) in patients with head and neck cancer who received radiotherapy. Information regarding methods, patients, results, and risk of bias was independently extracted by two authors. Statistical analyses were conducted to calculate the odds ratio and 95% confidence intervals (95%CIs) using fixed-effect models. We identified five clinical studies that included 234 patients with head and neck cancer. All studies were assessed as being at low risk of bias in most items of six domains. In this meta-analysis, glutamine treatment showed a statistically significant benefit with respect to reducing the risk and severity of OM induced by radiotherapy compared to either placebo or no treatment (risk ratio 0.17, 95%CI 0.06-0.47). Overall, glutamine significantly reduces the risk and severity of OM during radiotherapy or chemotherapy. Further prospective and large trials are required to support the findings. PMID:27045857

  14. Pneumonia treated in the internal medicine department: focus on healthcare-associated pneumonia.

    PubMed

    Giannella, M; Pinilla, B; Capdevila, J A; Martínez Alarcón, J; Muñoz, P; López Álvarez, J; Bouza, E

    2012-08-01

    Patients with pneumonia treated in the internal medicine department (IMD) are often at risk of healthcare-associated pneumonia (HCAP). The importance of HCAP is controversial. We invited physicians from 72 IMDs to report on all patients with pneumonia hospitalized in their department during 2 weeks (one each in January and June 2010) to compare HCAP with community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP). We analysed 1002 episodes of pneumonia: 58.9% were CAP, 30.6% were HCAP and 10.4% were HAP. A comparison between CAP, HCAP and HAP showed that HCAP patients were older (77, 83 and 80.5 years; p < 0.001), had poorer functional status (Barthel 100, 30 and 65; p < 0.001) and had more risk factors for aspiration pneumonia (18, 50 and 34%; p < 0.001). The frequency of testing to establish an aetiological diagnosis was lower among HCAP patients (87, 72 and 79; p < 0.001), as was adherence to the therapeutic recommendations of guidelines (70, 23 and 56%; p < 0.001). In-hospital mortality increased progressively between CAP, HCAP and HAP (8, 19 and 27%; p < 0.001). Streptococcus pneumoniae was the main pathogen in CAP and HCAP. Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) caused 17 and 12.3% of HCAP. In patients with a confirmed aetiological diagnosis, the independent risk factors for pneumonia due do difficult-to-treat microorganisms (Enterobacteriaceae, P. aeruginosa or MRSA) were HCAP, chronic obstructive pulmonary diseases and higher Port Severity Index. Our data confirm the importance of maintaining high awareness of HCAP among patients treated in IMDs, because of the different aetiologies, therapy requirements and prognosis of this population. PMID:22284436

  15. Vitamin D Deficiency Is Associated With the Severity of Radiation-Induced Proctitis in Cancer Patients

    SciTech Connect

    Ghorbanzadeh-Moghaddam, Amir; Gholamrezaei, Ali; Hemati, Simin

    2015-07-01

    Purpose: Radiation-induced injury to normal tissues is a common complication of radiation therapy in cancer patients. Considering the role of vitamin D in mucosal barrier hemostasis and inflammatory responses, we investigated whether vitamin D deficiency is associated with the severity of radiation-induced acute proctitis in cancer patients. Methods and Materials: This prospective observational study was conducted in cancer patients referred for pelvic radiation therapy. Serum concentration of 25-hydroxyvitamin D was measured before radiation therapy. Vitamin D deficiency was defined as 25-hydroxyvitamin D concentrations of <35 nmol/L and <40 nmol/L in male and female patients, respectively, based on available normative data. Acute proctitis was assessed after 5 weeks of radiation therapy (total received radiation dose of 50 Gy) and graded from 0 to 4 using Radiation Therapy Oncology Group (RTOG) criteria. Results: Ninety-eight patients (57.1% male) with a mean age of 62.8 ± 9.1 years were studied. Vitamin D deficiency was found in 57 patients (58.1%). Symptoms of acute proctitis occurred in 72 patients (73.4%) after radiation therapy. RTOG grade was significantly higher in patients with vitamin D deficiency than in normal cases (median [interquartile range] of 2 [0.5-3] vs 1 [0-2], P=.037). Vitamin D deficiency was associated with RTOG grade of ≥2, independent of possible confounding factors; odds ratio (95% confidence interval) = 3.07 (1.27-7.50), P=.013. Conclusions: Vitamin D deficiency is associated with increased severity of radiation-induced acute proctitis. Investigating the underlying mechanisms of this association and evaluating the effectiveness of vitamin D therapy in preventing radiation-induced acute proctitis is warranted.

  16. Complement resistance mechanisms of Klebsiella pneumoniae.

    PubMed

    Doorduijn, Dennis J; Rooijakkers, Suzan H M; van Schaik, Willem; Bardoel, Bart W

    2016-10-01

    The current emergence of antibiotic-resistant bacteria causes major problems in hospitals worldwide. To survive within the host, bacterial pathogens exploit several escape mechanisms to prevent detection and killing by the immune system. As a major player in immune defense, the complement system recognizes and destroys bacteria via different effector mechanisms. The complement system can label bacteria for phagocytosis or directly kill Gram-negative bacteria via insertion of a pore-forming complex in the bacterial membrane. The multi-drug resistant pathogen Klebsiella pneumoniae exploits several mechanisms to resist complement. In this review, we present an overview of strategies used by K. pneumoniae to prevent recognition and killing by the complement system. Understanding these complement evasion strategies is crucial for the development of innovative strategies to combat K. pneumoniae. PMID:27364766

  17. Pneumonia - adults (community acquired)

    MedlinePlus

    Ellison RT, Donowitz GR. Acute pneumonia. In: Bennett JE, Dolin R, Blaser MJ, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases . 8th ed. Philadelphia, PA: Elsevier Saunders; 2015: ...

  18. Hospital-acquired pneumonia

    MedlinePlus

    ... tends to be more serious than other lung infections because: People in the hospital are often very sick and cannot fight off ... prevent pneumonia. Most hospitals have programs to prevent hospital-acquired infections.

  19. Pneumonia - adults (community acquired)

    MedlinePlus

    ... Fever , which may be mild or high Shaking chills Shortness of breath (may only occur when you ... or unexplained weight loss Shortness of breath, shaking chills, or persistent fevers Signs of pneumonia and a ...

  20. Carcinoma of the lung complicating lipoid pneumonia

    SciTech Connect

    Felson, B.; Ralaisomay, G.

    1983-11-01

    The authors have encountered four cases of oil aspiration pneumonia complicated by carcinoma. Each had a clear-cut history of chronic intake of an oily substance, radiographic changes, and histologically documented oil aspiration pneumonia. Lung cancer later appeared in the involved area. A small number of similar cases also have been reported. The implication is that oil aspiration pneumonitis may induce bronchogenic carcinoma, particularly either the alveolar cell or the squamous cell variety. The radiographic diagnosis of the malignant transformation is difficult, and consequently the prognosis is poor.

  1. Risk assessment of severe accident-induced steam generator tube rupture

    SciTech Connect

    1998-03-01

    This report describes the basis, results, and related risk implications of an analysis performed by an ad hoc working group of the U.S. Nuclear Regulatory Commission (NRC) to assess the containment bypass potential attributable to steam generator tube rupture (SGTR) induced by severe accident conditions. The SGTR Severe Accident Working Group, comprised of staff members from the NRC`s Offices of Nuclear Reactor Regulation (NRR) and Nuclear Regulatory Research (RES), undertook the analysis beginning in December 1995 to support a proposed steam generator integrity rule. The work drew upon previous risk and thermal-hydraulic analyses of core damage sequences, with a focus on the Surry plant as a representative example. This analysis yielded new results, however, derived by predicting thermal-hydraulic conditions of selected severe accident scenarios using the SCDAP/RELAP5 computer code, flawed tube failure modeling, and tube failure probability estimates. These results, in terms of containment bypass probability, form the basis for the findings presented in this report. The representative calculation using Surry plant data indicates that some existing plants could be vulnerable to containment bypass resulting from tube failure during severe accidents. To specifically identify the population of plants that may pose a significant bypass risk would require more definitive analysis considering uncertainties in some assumptions and plant- and design-specific variables. 46 refs., 62 figs., 37 tabs.

  2. Severe hyponatremia caused by nab-paclitaxel-induced syndrome of inappropriate antidiuretic hormone secretion

    PubMed Central

    Neuzillet, Cindy; Babai, Samy; Kempf, Emmanuelle; Pujol, Géraldine; Rousseau, Benoît; Le-Louët, Hervé; Christophe Tournigand

    2016-01-01

    Abstract Incidence of pancreatic ductal adenocarcinoma (PDAC) is increasing. Most patients have advanced disease at diagnosis and therapeutic options in this setting are limited. Gemcitabine plus nab-paclitaxel regimen was demonstrated to increase survival compared with gemcitabine monotherapy and is therefore indicated as first-line therapy in patients with metastatic PDAC and performance status Eastern Cooperative Oncology Group (ECOG) 0-2. The safety profile of gemcitabine and nab-paclitaxel combination includes neutropenia, fatigue, and neuropathy as most common adverse events of grade 3 or higher. No case of severe hyponatremia associated with the use of nab-paclitaxel for the treatment of PDAC has been reported to date. We report the case of a 72-year-old Caucasian man with a metastatic PDAC treated with gemcitabine and nab-paclitaxel regimen, who presented with a severe hyponatremia (grade 4) caused by a documented syndrome of inappropriate antidiuretic hormone secretion (SIADH). This SIADH was attributed to nab-paclitaxel after a rigorous imputability analysis, including a rechallenge procedure with dose reduction. After dose and schedule adjustment, nab-paclitaxel was pursued without recurrence of severe hyponatremia and with maintained efficacy. Hyponatremia is a rare but potentially severe complication of nab-paclitaxel therapy that medical oncologists and gastroenterologists should be aware of. Nab-paclitaxel-induced hyponatremia is manageable upon dose and schedule adaptation, and should not contraindicate careful nab-paclitaxel reintroduction. This is of particular interest for a disease in which the therapeutic options are limited. PMID:27368013

  3. Severe dopaminergic neuron loss in rhesus monkey brain impairs morphine-induced conditioned place preference

    PubMed Central

    Yan, Ting; Rizak, Joshua Dominic; Wang, Jianhong; Yang, Shangchuan; Ma, Yuanye; Hu, Xintian

    2015-01-01

    It is well known that dopamine (DA) is critical for reward, but the precise role of DA in reward remains uncertain. The aim of this study was to determine what percentage of dopaminergic neurons in the primate brain is required for the expression of conditioned reward by measuring the performance of DA-deficient rhesus monkeys in a morphine-induced conditioned place preference (CPP) paradigm. Animals with mild Parkinsonian symptoms successfully developed and retained a morphine preference that was equivalent to control monkeys. However, these monkeys could not maintain the preference as well as controls when they retained severe Parkinsonian symptoms. On the other hand, monkeys initially in a severe Parkinsonian state developed a preference for morphine, but this preference was weaker than that of the controls. Histological results showed that the loss of dopaminergic neurons in monkeys that had severe Parkinsonian symptoms was about 80% in comparison to the control monkeys. All these data suggest that a severely impaired DA system alters rewarding-seeking behavior in non-human primates. PMID:26528155

  4. Chronic Klebsiella pneumonia: a rare manifestation of Klebsiella pneumonia

    PubMed Central

    Thungtitigul, Poungrat; Suwatanapongched, Thitiporn

    2015-01-01

    K. pneumoniae can present as two forms of community-acquired pneumonia, acute and chronic. Although acute pneumonia may turn into necrotizing pneumonia, which results in a prolonged clinical course, it often has a rapidly progressive clinical course. In contrast, chronic Klebsiella pneumonia runs a protracted indolent course that mimics other chronic pulmonary infections and malignancies. Herein, we present two cases of chronic Klebsiella pneumonia. The diagnosis was made by microorganism identification, as well as absence of other potential causes. Clinical and radiographic findings improved after a prolonged course of antibiotic therapy. PMID:26543615

  5. Enzootic pneumonia in feeder pigs: Observations on causal factors

    PubMed Central

    DiFranco, Enrico; Marois, Paul; Descôteaux, Jean-Paul; Lacroix, Martial; Flipot, Paul

    1989-01-01

    A number of factors were studied in eight feeder pig herds, affected with severe or mild enzootic pneumonia, in order to identify those associated with this disease. Piggeries with poor facilities and management and where procurement of piglets was from sales barns were more severely affected with enzootic pneumonia than were those with good facilities and where pigs originated directly from breeding units. Serological tests and virus isolation revealed that all herds had been exposed to Mycoplasma hyopneumoniae and to many viruses; transmissible gastroenteritis virus infection was the only viral infection that was apparently associated with the severity of enzootic pneumonia and the performance observed in the herds. PMID:17423261

  6. [Differential diagnosis of pulmonary tuberculosis and community-acquired pneumonia].

    PubMed

    Deĭkina, O N; Mishin, V Iu; Demikhova, O V

    2007-01-01

    The purpose of this investigation was to enhance the efficiency of differential diagnosis of pneumonia and pulmonary tuberculosis. A hundred and fifty-nine adult patients were examined. These included 78 patients with pulmonary tuberculosis and 81 with community-acquired p neumonia. The clinical features of infiltrative pulmonary tuberculosis (n = 48) and mild community-acquired pneumonia (n = 51) were compared. The course of caseous pneumonia (n = 30) was compared with that of moderate and severe community-acquired pneumonia (n = 30). Significant differences in the manifestations of the intoxication and bronchopulmonary syndrome were not found in patients with community-acquired pneumonia and infiltrative pulmonary tuberculosis. Physical studies showed that in patients with community-acquired pneumonia, moist rale (54.9%) and crepitation (11.8%) were prevalent, but in those with infiltrative tuberculosis rale was absent in 60.4% of cases and the pattern of respiration was unchanged in 79.2%. Chest X-ray studies indicated that in patients with community-acquired pneumonia, lower lobar inflammatory changes were predominant in 62.8% of cases whereas in those with infiltrative pulmonary tuberculosis the process was mainly bilateral (43.8%) with the presence of destructive changes (83.3%) and bronchogenic dissemination (66.7%). In patients with caseous pneumonia, the intoxication syndrome was more significant than in those with severe community-acquired pneumonia. Chest X-ray studies demonstrated that in patients with caseous pneumonia, specific changes were bilateral with the involvement of 2 lobes or more, with destruction and bronchogenic dissemination while in those with community-acquired pneumonia, the pulmonary processes were predominantly bilateral (76.6%) at the lower lobar site (36.7%). PMID:17338353

  7. Aluminizing a Ni sheet through severe plastic deformation induced by ball collisions

    NASA Astrophysics Data System (ADS)

    Romankov, S.; Shchetinin, I. V.; Park, Y. C.

    2015-07-01

    Aluminizing a Ni sheet was performed through severe plastic deformation induced by ball collisions. The Ni sheet was fixed in the center of a mechanically vibrated vial between two connected parts. The balls were loaded into the vial on both sides of the Ni disk. Al disks, which were fixed on the top and the bottom of the vial, served as the sources of Al contamination. During processing, the Ni sheet was subject to intense ball collisions. The Al fragments were transferred and alloyed to the surface of the Ni sheet by these collisions. The combined effects of deformation-induced plastic flow, mechanical intermixing, and grain refinement resulted in the formation of a dense, continuous nanostructured Al layer on the Ni surface on both sides of the sheet. The Al layer consisted of Al grains with an average size of about 40 nm. The Al layer was reinforced with nano-sized Ni flakes that were introduced from the Ni surface during processing. The local amorphization at the Ni/Al interface revealed that the bonding between Ni and Al was formed by mechanical intermixing of atomic layers at the interface. The hardness of the fabricated Al layer was 10 times that of the initial Al plate. The ball collisions destroyed the initial rolling texture of the Ni sheet and induced the formation of the mixed [1 0 0] + [1 1 1] fiber texture. The laminar rolling structure of the Ni was transformed into an ultrafine grain structure.

  8. [Rifampicin-induced severe thrombocytopenia in a patient with miliary tuberculosis].

    PubMed

    Onoda, Tetsuya; Murakami, Kazuo; Eda, Ryousuke; Hiraki, Akio; Makihata, Kiyoshi; Takao, Kazushi; Aoe, Keisuke; Maeda, Tadashi; Takeyama, Hiroyasu

    2003-07-01

    A 74-year-old female visited a local clinic complaining of fever on January 21, 2002. A chest X-ray and a chest computed tomography (CT) showed diffuse micronodules in all lung fields, which strongly suggested miliary tuberculosis. On January 23, she was referred to our hospital for further examinations. Though sputum was negative on smear, culture, and polymerase chain reaction (PCR) for M. tuberculosis, bone marrow aspirate examined on admission revealed epithelioid granuloma. Therefore we diagnosed her as a miliary tuberculosis, and she was treated with 300 mg of Isoniazid (INH), 450 mg of Rifampicin, and 750 mg of Streptomycin (SM) daily. Five days later, severe thrombocytopenia (platelet count 0.3 x 10(4)/microliter) was observed. We immediately discontinued all antituberculous drugs and administered concentrated platelets and immune globulin. Platelet-associated IgG was detected, and megakaryocytes were slightly increased in moderately hypocellular marrow on the bone marrow aspirate examined again after the appearance of thrombocytopenia. Eleven days after discontinuing all antituberculous drugs, platelet count recovered to 10.2 x 10(4)/microliter. INH, SM, Levofloxacin (LV) were administered afterward, and these drugs did not induce thrombocytopenia. Though challenge administration of RFP was not performed, we concluded that the thrombocytopenia was immunologically induced by RFP. We should keep in mind that RFP-induced thromobocytopenia could appear in the first week after the initiation of therapy. PMID:12931647

  9. Severe hypoxia induces chemo-resistance in clinical cervical tumors through MVP over-expression

    PubMed Central

    Lara, Pedro C; Lloret, Marta; Clavo, Bernardino; Apolinario, Rosa M; Henríquez-Hernández, Luis Alberto; Bordón, Elisa; Fontes, Fausto; Rey, Agustín

    2009-01-01

    Oxygen molecule modulates tumour response to radiotherapy. Higher radiation doses are required under hypoxic conditions to induce cell death. Hypoxia may inhibit the non-homologous end-joining DNA repair through down regulating Ku70/80 expression. Hypoxia induces drug resistance in clinical tumours, although the mechanism is not clearly elucidated. Vaults are ribonucleoprotein particles with a hollow barrel-like structure composed of three proteins: major vault protein (MVP), vault poly(ADP-ribose) polymerase, and telomerase associated protein-1 and small untranslated RNA. Over-expression of MVP has been associated with chemotherapy resistance. Also, it has been related to poor outcome in patients treated with radiotherapy alone. The aim of the present study was to assess the relation of Major Vault Protein expression and tumor hypoxia in clinical cervical tumors. MVP, p53 and angiogenesis, together with tumor oxygenation, were determined in forty-three consecutive patients suffering from localized cervix carcinoma. High MVP expression was related to severe hypoxia compared to low MVP expressing tumors (p = 0.022). Tumors over-expressing MVP also showed increased angiogenesis (p = 0.003). Besides it, in this study we show for the first time that severe tumor hypoxia is associated with high MVP expression in clinical cervical tumors. Up-regulation of MVP by hypoxia is of critical relevance as chemotherapy is currently a standard treatment for those patients. From our results it could be suggested that hypoxia not only induces increased genetic instability, oncogenic properties and metastatization, but through the correlation observed with MVP expression, another pathway of chemo and radiation resistance could be developed. PMID:19660100

  10. Hydrogen-rich saline ameliorates the severity of L-arginine-induced acute pancreatitis in rats

    SciTech Connect

    Chen, Han; Sun, Yan Ping; Li, Yang; Liu, Wen Wu; Xiang, Hong Gang; Fan, Lie Ying; Sun, Qiang; Xu, Xin Yun; Cai, Jian Mei; Ruan, Can Ping; Su, Ning; Yan, Rong Lin; Sun, Xue Jun; Wang, Qiang

    2010-03-05

    Molecular hydrogen, which reacts with the hydroxyl radical, has been considered as a novel antioxidant. Here, we evaluated the protective effects of hydrogen-rich saline on the L-arginine (L-Arg)-induced acute pancreatitis (AP). AP was induced in Sprague-Dawley rats by giving two intraperitoneal injections of L-Arg, each at concentrations of 250 mg/100 g body weight, with an interval of 1 h. Hydrogen-rich saline (>0.6 mM, 6 ml/kg) or saline (6 ml/kg) was administered, respectively, via tail vein 15 min after each L-Arg administration. Severity of AP was assessed by analysis of serum amylase activity, pancreatic water content and histology. Samples of pancreas were taken for measuring malondialdehyde and myeloperoxidase. Apoptosis in pancreatic acinar cell was determined with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling technique (TUNEL). Expression of proliferating cell nuclear antigen (PCNA) and nuclear factor kappa B (NF-{kappa}B) were detected with immunohistochemistry. Hydrogen-rich saline treatment significantly attenuated the severity of L-Arg-induced AP by ameliorating the increased serum amylase activity, inhibiting neutrophil infiltration, lipid oxidation and pancreatic tissue edema. Moreover, hydrogen-rich saline treatment could promote acinar cell proliferation, inhibit apoptosis and NF-{kappa}B activation. These results indicate that hydrogen treatment has a protective effect against AP, and the effect is possibly due to its ability to inhibit oxidative stress, apoptosis, NF-{kappa}B activation and to promote acinar cell proliferation.

  11. Severe hypoxia induces chemo-resistance in clinical cervical tumors through MVP over-expression.

    PubMed

    Lara, Pedro C; Lloret, Marta; Clavo, Bernardino; Apolinario, Rosa M; Henríquez-Hernández, Luis Alberto; Bordón, Elisa; Fontes, Fausto; Rey, Agustín

    2009-01-01

    Oxygen molecule modulates tumour response to radiotherapy. Higher radiation doses are required under hypoxic conditions to induce cell death. Hypoxia may inhibit the non-homologous end-joining DNA repair through down regulating Ku70/80 expression. Hypoxia induces drug resistance in clinical tumours, although the mechanism is not clearly elucidated. Vaults are ribonucleoprotein particles with a hollow barrel-like structure composed of three proteins: major vault protein (MVP), vault poly(ADP-ribose) polymerase, and telomerase associated protein-1 and small untranslated RNA. Over-expression of MVP has been associated with chemotherapy resistance. Also, it has been related to poor outcome in patients treated with radiotherapy alone. The aim of the present study was to assess the relation of Major Vault Protein expression and tumor hypoxia in clinical cervical tumors. MVP, p53 and angiogenesis, together with tumor oxygenation, were determined in forty-three consecutive patients suffering from localized cervix carcinoma. High MVP expression was related to severe hypoxia compared to low MVP expressing tumors (p = 0.022). Tumors over-expressing MVP also showed increased angiogenesis (p = 0.003). Besides it, in this study we show for the first time that severe tumor hypoxia is associated with high MVP expression in clinical cervical tumors. Up-regulation of MVP by hypoxia is of critical relevance as chemotherapy is currently a standard treatment for those patients. From our results it could be suggested that hypoxia not only induces increased genetic instability, oncogenic properties and metastatization, but through the correlation observed with MVP expression, another pathway of chemo and radiation resistance could be developed. PMID:19660100

  12. Role of the Mycoplasma pneumoniae/Interleukin-8/Neutrophil Axis in the Pathogenesis of Pneumonia

    PubMed Central

    Zhang, Xinxing; Wang, Yuqing; Zhu, Canhong; Hao, Chuangli; Fan, Mingyue; Ji, Wei; Yan, Yongdong

    2016-01-01

    Neutrophil infiltration is the characteristic pathological feature of M. pneumoniae pneumonia (MPP). This study aimed to explore the associations among neutrophil activity, clinical presentation, and role of the M. pneumoniae/interleukin-8 (IL-8)/neutrophil axis in the pathogenesis of MPP. A total of 42 patients with MPP were prospectively enrolled in the study. Neutrophil activity, including matrix metalloproteinase-9 (MMP-9), myeloperoxidase (MPO), and neutrophil elastase (NE), were measured. Clinical information was collected for all patients and control group. In vitro, IL-8 production was measured at different time points after M. pneumoniae infection of bronchial epithelial cells, and neutrophil activity was analyzed after IL-8 stimulation. The percentage of neutrophil in the bronchoalveolar lavage fluid was higher in the group of patients with high levels of M. pneumoniae DNA than in those with low levels of M. pneumoniae DNA (P < 0.05). IL-8, MMP-9, and NE in patients with MPP significantly increased compared with controls and decreased after treatment (P < 0.05). MPO and MMP-9 were associated with duration of fever (r = 0.332, P < 0.05) and length of stay (r = 0.342, P < 0.05), respectively. In vitro, M. pneumoniae induced IL-8 production by bronchial epithelial cells in a time dependent manner. MPO, MMP-9 and NE production by neutrophils significantly increased compared with medium controls after IL-8 stimulation. In summary, the M. pneumoniae/IL-8/neutrophil axis likely plays a vital role in the pathogenesis of MPP. PMID:26752656

  13. HLA-B*1502 and carbamazepine-induced severe cutaneous adverse drug reactions in Vietnamese

    PubMed Central

    Chu, Hieu Chi; Nguyen, Doan Van; Phan, Minh Hong; Craig, Timothy; Baumgart, Karl; van Nunen, Sheryl

    2015-01-01

    Background In Vietnam, we observed a high incidence of carbamazepine (CBZ)-induced severe cutaneous adverse drug reactions (SCARs)-Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), and drug-induced hypersensitivity rash with eosinophilia and systemic symptoms (DRESS). In other Asian countries, HLA-B*1502 is an established risk factor for SCARs. Objective The aim of our study was to determine the frequency of HLA-B*1502 in SCARs patients at a large University Medical Center in Hanoi, Vietnam. Methods Thirty-eight cases of SCARs caused by CBZ and 25 patients with epilepsy tolerating CBZ were enrolled in a case-controlled study. Clinical manifestations and laboratory findings were recorded for each subject. Genomic DNA was isolated using the QIAamp DNA purification system. The combination of polymerase chain reaction and sequence specific oligonucleotide probes with the Luminex 100×MAP flow cytometry dual laser system was then used to quantitate fluorescently labelled oligonucleotides attached to colour-coded microbeads. Results Cases comprised 20 SJS (52.6%), 7 TEN (18.4%), 8 overlap syndrome (21.1%), and 3 DRESS patients (7.9%). A strong association between HLA B*1502 and bullous skin reactions such as SJS/TEN and overlap was confirmed with an odds ratio (OR) of 33.78 (95% confidence interval [CI], 7.55-151.03), p < 0.0001, Sensitivity 91.4%, Specificity 76.0%, positive predictive value 84.2%, and negative predictive value 86.4%. We did not, however, observe any correlation between the presence of this allele and CBZ-induced nonbullous skin reactions (DRESS) (OR, 6.33; 95% CI, 0.48-82.74; p = 0.1592). Conclusion Our results indicate the presence of HLA-B*1502 in Vietnamese is a pharmacogenetic risk factor for developing CBZ-induced SJS/TEN. PMID:25938071

  14. L-Dopa induced dyskinesias in Parkinsonian mice: Disease severity or L-Dopa history.

    PubMed

    Shan, Lufei; Diaz, Oscar; Zhang, Yajun; Ladenheim, Bruce; Cadet, Jean-Lud; Chiang, Yung-Hsiao; Olson, Lars; Hoffer, Barry J; Bäckman, Cristina M

    2015-08-27

    In Parkinson's disease, the efficacy of l-Dopa treatment changes over time, as dyskinesias emerge with previously beneficial doses. Using MitoPark mice, that models mitochondrial failure in dopamine (DA) neurons and mimics the progressive loss of dopamine observed in Parkinson's disease, we found that the severity of DA denervation and associated adaptations in striatal neurotransmission at the time of initiation of l-Dopa treatment determines development of l-Dopa induced dyskinesias. We treated 20-week, and 28-week old MitoPark mice with l-Dopa (10mg/kg i.p. twice a day) and found locomotor responses to be significantly different. While all MitoPark mice developed sensitization to l-Dopa treatment over time, 28-week old MitoPark mice with extensive striatal DA denervation developed abnormal involuntary movements rapidly and severely after starting l-Dopa treatment, as compared to a more gradual escalation of movements in 20-week old animals that started treatment at earlier stages of degeneration. Our data support that it is the extent of loss of DA innervation that determines how soon motor complications develop with l-Dopa treatment. Gene array studies of striatal neurotransmitter receptors revealed changes in mRNA expression levels for DA, serotonin, glutamate and GABA receptors in striatum of 28-week old MitoPark mice. Our results support that delaying l-Dopa treatment until Parkinson's disease symptoms become more severe does not delay the development of l-Dopa-induced dyskinesias. MitoPark mice model genetic alterations known to impair mitochondrial function in a subgroup of Parkinson patients and provide a platform in which to study treatments to minimize the development of dyskinesia. PMID:26086365

  15. Severe Burn–Induced Endoplasmic Reticulum Stress and Hepatic Damage in Mice

    PubMed Central

    Song, Juquan; Finnerty, Celeste C; Herndon, David N; Boehning, Darren; Jeschke, Marc G

    2009-01-01

    Severe burn injury results in liver dysfunction and damage, with subsequent metabolic derangements contributing to patient morbidity and mortality. On a cellular level, significant postburn hepatocyte apoptosis occurs and likely contributes to liver dysfunction. However, the underlying mechanisms of hepatocyte apoptosis are poorly understood. The endoplasmic reticulum (ER) stress response/unfolded protein response (UPR) pathway can lead to hepatocyte apoptosis under conditions of liver dysfunction. Thus, we hypothesized that ER stress/UPR may mediate hepatic dysfunction in response to burn injury. We investigated the temporal activation of hepatic ER stress in mice after a severe burn injury. Mice received a scald burn over 35% of their body surface and were killed at 1, 7, 14, and 21 d postburn. We found that severe burn induces hepatocyte apoptosis as indicated by increased caspase-3 activity (P < 0.05). Serum albumin levels decreased postburn and remained lowered for up to 21 d, indicating that constitutive secretory protein synthesis was reduced. Significantly, upregulation of the ER stress markers glucose-related protein 78 (GRP78)/BIP, protein disulfide isomerase (PDI), p–protein kinase R–like endoplasmic reticulum kinase (p-PERK), and inositol-requiring enzyme 1α (IRE-1α) were found beginning 1 d postburn (P < 0.05) and persisted up to 21 d postburn (P < 0.05). Hepatic ER stress induced by burn injury was associated with compensatory upregulation of the calcium chaperone/storage proteins calnexin and calreticulin (P < 0.05), suggesting that ER calcium store depletion was the primary trigger for induction of the ER stress response. In summary, thermal injury in mice causes long-term adaptive and deleterious hepatic function alterations characterized by significant upregulation of the ER stress response. PMID:19603103

  16. Severe burn-induced endoplasmic reticulum stress and hepatic damage in mice.

    PubMed

    Song, Juquan; Finnerty, Celeste C; Herndon, David N; Boehning, Darren; Jeschke, Marc G

    2009-01-01

    Severe burn injury results in liver dysfunction and damage, with subsequent metabolic derangements contributing to patient morbidity and mortality. On a cellular level, significant postburn hepatocyte apoptosis occurs and likely contributes to liver dysfunction. However, the underlying mechanisms of hepatocyte apoptosis are poorly understood. The endoplasmic reticulum (ER) stress response/unfolded protein response (UPR) pathway can lead to hepatocyte apoptosis under conditions of liver dysfunction. Thus, we hypothesized that ER stress/UPR may mediate hepatic dysfunction in response to burn injury. We investigated the temporal activation of hepatic ER stress in mice after a severe burn injury. Mice received a scald burn over 35% of their body surface and were killed at 1, 7, 14, and 21 d postburn. We found that severe burn induces hepatocyte apoptosis as indicated by increased caspase-3 activity (P < 0.05). Serum albumin levels decreased postburn and remained lowered for up to 21 d, indicating that constitutive secretory protein synthesis was reduced. Significantly, upregulation of the ER stress markers glucose-related protein 78 (GRP78)/BIP, protein disulfide isomerase (PDI), p-protein kinase R-like endoplasmic reticulum kinase (p-PERK), and inositol-requiring enzyme 1alpha (IRE-1alpha) were found beginning 1 d postburn (P < 0.05) and persisted up to 21 d postburn (P < 0.05). Hepatic ER stress induced by burn injury was associated with compensatory upregulation of the calcium chaperone/storage proteins calnexin and calreticulin (P < 0.05), suggesting that ER calcium store depletion was the primary trigger for induction of the ER stress response. In summary, thermal injury in mice causes long-term adaptive and deleterious hepatic function alterations characterized by significant upregulation of the ER stress response. PMID:19603103

  17. Pneumonectomy combined with SU5416 induces severe pulmonary hypertension in rats.

    PubMed

    Happé, C M; de Raaf, M A; Rol, N; Schalij, I; Vonk-Noordegraaf, A; Westerhof, N; Voelkel, N F; de Man, F S; Bogaard, H J

    2016-06-01

    The SU5416 + hypoxia (SuHx) rat model is a commonly used model of severe pulmonary arterial hypertension. While it is known that exposure to hypoxia can be replaced by another type of hit (e.g., ovalbumin sensitization) it is unknown whether abnormal pulmonary blood flow (PBF), which has long been known to invoke pathological changes in the pulmonary vasculature, can replace the hypoxic exposure. Here we studied if a combination of SU5416 administration combined with pneumonectomy (PNx), to induce abnormal PBF in the contralateral lung, is sufficient to induce severe pulmonary arterial hypertension (PAH) in rats. Sprague Dawley rats were subjected to SuPNx protocol (SU5416 + combined with left pneumonectomy) or standard SuHx protocol, and comparisons between models were made at week 2 and 6 postinitiation. Both SuHx and SuPNx models displayed extensive obliterative vascular remodeling leading to an increased right ventricular systolic pressure at week 6 Similar inflammatory response in the lung vasculature of both models was observed alongside increased endothelial cell proliferation and apoptosis. This study describes the SuPNx model, which features severe PAH at 6 wk and could serve as an alternative to the SuHx model. Our study, together with previous studies on experimental models of pulmonary hypertension, shows that the typical histopathological findings of PAH, including obliterative lesions, inflammation, increased cell turnover, and ongoing apoptosis, represent a final common pathway of a disease that can evolve as a consequence of a variety of insults to the lung vasculature. PMID:27036867

  18. Substance P Mediates Reduced Pneumonia Rates After Traumatic Brain Injury

    PubMed Central

    Yang, Sung; Stepien, David; Hanseman, Dennis; Robinson, Bryce; Goodman, Michael D.; Pritts, Timothy A.; Caldwell, Charles C.; Remick, Daniel G.; Lentsch, Alex B.

    2014-01-01

    brain injury have lower rates of pneumonia compared to non–head-injured trauma patients and suggest that the mechanism of this effect occurs through traumatic brain injury–induced release of substance P, which improves innate immunity to decrease pneumonia. PMID:25014065

  19. SEVERE AMIODARONE-INDUCED BRADICARDIA CONCEALES SICK SINUS SYNDROME: CASE REPORT.

    PubMed

    Crăcană, Irina; Vasilcu, T F; Mardare, Alexandra; Alexa, Ioana Dana; Marcu, D T M

    2016-01-01

    Sinus node dysfunction is one of the most common arrhythmias in elderly patients; it is usually associated with intermittent and variable symptoms, thus making it difficult to diagnose. We present the case of an elderly female patient with a personal history of atrial fibrillation treated for the last three years with amiodarone; she was admitted to the Geriatric Clinic for non-specific symptoms with onset two months previously for which she had already sought care in different medical services. Clinical examination showed severe bradycardia; ECG and Holter ECG on admission confirmed severe bradycardia, with a heart rate between 29 and 50 beats/min (bpm). Given her long-term treatment with amiodarone we looked for and found hyperthyroidism; the endocrine examination led to the diagnosis of mixed type Amiodarone-induced thyrotoxicosis and initiation of corticosteroid and antithyroid treatment. The evolution of cardiac arrhythmia was monitored with the help of several Holter ECGs performed after amiodarone washout and return to the euthyroid state, which revealed a tachycardia-bradycardia syndrome initially masked by the side effects of the unsupervised therapy with amiodarone, and properly treated by the implantation of a pacemaker. PMID:27125081

  20. Severe Food Protein-Induced Enterocolitis Syndrome to Cow’s Milk in Infants

    PubMed Central

    Yang, Min; Geng, Lanlan; Xu, Zhaohui; Chen, Peiyu; Friesen, Craig A.; Gong, Sitang; Li, Ding-You

    2015-01-01

    Cow’s milk is the most common cause of food-protein-induced enterocolitis syndrome (FPIES). The aim of this study was to examine the clinical features and treatment outcomes of infants with severe FPIES to cow’s milk. We reviewed all infants ≤12 months of age who were hospitalized and diagnosed with severe FPIES to cow’s milk between 1 January 2011 and 31 August 2014 in a tertiary Children’s Medical Center in China. Patients’ clinical features, feeding patterns, laboratory tests, and treatment outcomes were reviewed. A total of 12 infants met the inclusion criteria. All infants presented with diarrhea, edema, and hypoalbuminemia. Other main clinical manifestations included regurgitation/vomiting, skin rashes, low-grade fever, bloody and/or mucous stools, abdominal distention, and failure to thrive. They had clinical remission with resolution of diarrhea and significant increase of serum albumin after elimination of cow’s milk protein (CMP) from the diet. The majority of infants developed tolerance to the CMP challenge test after 12 months of avoidance. In conclusion, we reported the clinical experience of 12 infants with severe FPIES to cow’s milk, which resulted in malnutrition, hypoproteinemia, and failure to thrive. Prompt treatment with CMP-free formula is effective and leads to clinical remission of FPIES in infants. PMID:26703722

  1. Severe Food Protein-Induced Enterocolitis Syndrome to Cow's Milk in Infants.

    PubMed

    Yang, Min; Geng, Lanlan; Xu, Zhaohui; Chen, Peiyu; Friesen, Craig A; Gong, Sitang; Li, Ding-You

    2016-01-01

    Cow's milk is the most common cause of food-protein-induced enterocolitis syndrome (FPIES). The aim of this study was to examine the clinical features and treatment outcomes of infants with severe FPIES to cow's milk. We reviewed all infants ≤ 12 months of age who were hospitalized and diagnosed with severe FPIES to cow's milk between 1 January 2011 and 31 August 2014 in a tertiary Children's Medical Center in China. Patients' clinical features, feeding patterns, laboratory tests, and treatment outcomes were reviewed. A total of 12 infants met the inclusion criteria. All infants presented with diarrhea, edema, and hypoalbuminemia. Other main clinical manifestations included regurgitation/vomiting, skin rashes, low-grade fever, bloody and/or mucous stools, abdominal distention, and failure to thrive. They had clinical remission with resolution of diarrhea and significant increase of serum albumin after elimination of cow's milk protein (CMP) from the diet. The majority of infants developed tolerance to the CMP challenge test after 12 months of avoidance. In conclusion, we reported the clinical experience of 12 infants with severe FPIES to cow's milk, which resulted in malnutrition, hypoproteinemia, and failure to thrive. Prompt treatment with CMP-free formula is effective and leads to clinical remission of FPIES in infants. PMID:26703722

  2. [Treatment of pneumonia in childhood (author's transl)].

    PubMed

    Weippl, G

    1976-01-01

    It is necessary to start with antibiotic treatment in infections of the lower respiratory system, especially pneumonias. The finding of the infectious agent is difficult and without security. With simple investigations, as sedimentation rate, white blood cell count and cell differentiation there is a possibility of 80% to get a diagnosis of bacterial infection. In 25 patients aged 1 1/2 to 9 years with x-ray diagnosis of pneumonia the results of treatment with cephacetril (100 mg/kg/d) are given. Clinical symptoms disappeared after 5 days, the average time of illness was 12 days. One patient got a severe pleural effusion. PMID:934680

  3. [Community-acquired pneumonia in the elderly].

    PubMed

    Füri, Julia; Oestmann, Andreas; Repond, Fernand

    2016-04-13

    We report the case of a 88 years old patient with cough and new onset confusion. Delirium was caused by a necrotizing Methicillin-sensible staphylococcus aureus pneumonia with bacteremia. Despite antibiotic therapy for several weeks and fall of inflammatory markers the patient died from consequences of delirium. PMID:27078731

  4. Pneumonia in the immunocompetent patient

    PubMed Central

    Reynolds, J H; Mcdonald, G; Alton, H; Gordon, S B

    2010-01-01

    Pneumonia is an acute inflammation of the lower respiratory tract. Lower respiratory tract infection is a major cause of mortality worldwide. Pneumonia is most common at the extremes of life. Predisposing factors in children include an under-developed immune system together with other factors, such as malnutrition and over-crowding. In adults, tobacco smoking is the single most important preventable risk factor. The commonest infecting organisms in children are respiratory viruses and Streptoccocus pneumoniae. In adults, pneumonia can be broadly classified, on the basis of chest radiographic appearance, into lobar pneumonia, bronchopneumonia and pneumonia producing an interstitial pattern. Lobar pneumonia is most commonly associated with community acquired pneumonia, bronchopneumonia with hospital acquired infection and an interstitial pattern with the so called atypical pneumonias, which can be caused by viruses or organisms such as Mycoplasma pneumoniae. Most cases of pneumonia can be managed with chest radiographs as the only form of imaging, but CT can detect pneumonia not visible on the chest radiograph and may be of value, particularly in the hospital setting. Complications of pneumonia include pleural effusion, empyema and lung abscess. The chest radiograph may initially indicate an effusion but ultrasound is more sensitive, allows characterisation in some cases and can guide catheter placement for drainage. CT can also be used to characterise and estimate the extent of pleural disease. Most lung abscesses respond to medical therapy, with surgery and image guided catheter drainage serving as options for those cases who do not respond. PMID:21088086

  5. Pneumonia in the immunocompetent patient.

    PubMed

    Reynolds, J H; McDonald, G; Alton, H; Gordon, S B

    2010-12-01

    Pneumonia is an acute inflammation of the lower respiratory tract. Lower respiratory tract infection is a major cause of mortality worldwide. Pneumonia is most common at the extremes of life. Predisposing factors in children include an under-developed immune system together with other factors, such as malnutrition and over-crowding. In adults, tobacco smoking is the single most important preventable risk factor. The commonest infecting organisms in children are respiratory viruses and Streptoccocus pneumoniae. In adults, pneumonia can be broadly classified, on the basis of chest radiographic appearance, into lobar pneumonia, bronchopneumonia and pneumonia producing an interstitial pattern. Lobar pneumonia is most commonly associated with community acquired pneumonia, bronchopneumonia with hospital acquired infection and an interstitial pattern with the so called atypical pneumonias, which can be caused by viruses or organisms such as Mycoplasma pneumoniae. Most cases of pneumonia can be managed with chest radiographs as the only form of imaging, but CT can detect pneumonia not visible on the chest radiograph and may be of value, particularly in the hospital setting. Complications of pneumonia include pleural effusion, empyema and lung abscess. The chest radiograph may initially indicate an effusion but ultrasound is more sensitive, allows characterisation in some cases and can guide catheter placement for drainage. CT can also be used to characterise and estimate the extent of pleural disease. Most lung abscesses respond to medical therapy, with surgery and image guided catheter drainage serving as options for those cases who do not respond. PMID:21088086

  6. Severe noise-induced deafness--a 10-year review of cases.

    PubMed

    Tay, P

    1996-08-01

    Noise Induced Deafness (NID) is the leading occupational disease in Singapore. Every year, over 500 new cases of NID are detected by the Department of Industrial Health (DIH). Severe NID is a disabling disease which is compensable under the law. A retrospective study was conducted to elicit the profile of workers with severe, disabling NID. From 1 January 1985 to 31 December 1994, the DIH confirmed 127 of such cases. Of these, 57 (44.9%) were involved in the building and repair of ships and boats, 30 (23.6%) with the basic steel industries, manufacture and fabrication of metal products and storage batteries, 9 (7.2%) with the transport and allied support industries, 7 (5.5%) in granite quarrying, 7 (5.5%) in the manufacture of food and drinks, 5 (3.9%) in the manufacture of wooden furniture and 7 (5.5%) in other industries such as manufacture of glass, electricity generation, construction, textiles, printing and so on. The mean age of these workers upon diagnosis of severe NID was 48 years (SD 8.07). The mean duration of exposure to noise was 24 years (SD 9.11). The mean of the average hearing thresholds at 1, 2 and 3 kHz for these workers was found to be 61.5 dBA (SD 4.26). The main jobs at risk were grit blasters, steel workers, fitters, boiler fabricators, panel beaters and carpenters. Noise dosimetry was performed on 46 of the cases and the mean time-weighted exposure level was 90 dBA (SD 10.00). Finally, 82.7% of cases already had audiometric evidence of severe deafness at the time of notification. PMID:8993132

  7. Severe inflammatory reaction induced by peritoneal trauma is the key driving mechanism of postoperative adhesion formation

    PubMed Central

    2011-01-01

    Background Many factors have been put forward as a driving mechanism of surgery-triggered adhesion formation (AF). In this study, we underline the key role of specific surgical trauma related with open surgery (OS) and laparoscopic (LS) conditions in postoperative AF and we aimed to study peritoneal tissue inflammatory reaction (TIR), remodelling specific complications of open surgery (OS) versus LS and subsequently evaluating AF induced by these conditions. Methods A prospective randomized study was done in 80 anaesthetised female Wistar rats divided equally into 2 groups. Specific traumatic OS conditions were induced by midline incision line (MIL) extension and tissue drying and specific LS conditions were remodelled by intraperitoneal CO2 insufflation at the 10 cm of water. TIR was evaluated at the 24th, 72nd, 120th and 168th hour by scoring scale. Statistical analysis was performed by the non-parametric t test and two-way ANOVA using Bonferroni post-tests. Results More pronounced residual TIR was registered after OS than after LS. There were no significant TIR interactions though highly significant differences were observed between the OS and LS groups (p < 0.0001) with regard to surgical and time factors. The TIR change differences between the OS and LS groups were pronounced with postoperative time p < 0.05 at the 24th and 72nd; p < 0.01 - 120th and p < 0.001 - 168th hrs. Adhesion free wounds were observed in 20.0 and 31.0% of cases after creation of OS and LS conditions respectively; with no significant differences between these values (p > 0.05). However larger adhesion size (41.67 ± 33.63) was observed after OS in comparison with LS (20.31 ± 16.38). The upper-lower 95% confidential limits ranged from 60.29 to 23.04 and from 29.04 to 11.59 respectively after OS and LS groups with significant differences (p = 0.03). Analogous changes were observed in adhesion severity values. Subsequently, severe TIR parameters were followed by larger sizes of severe

  8. Suckdown, fountain lift, and pressures induced on several tandem jet V/STOL configurations

    NASA Technical Reports Server (NTRS)

    Bellavia, David C.; Wardwell, Douglas A.; Corsiglia, Victor R.; Kuhn, Richard E.

    1991-01-01

    As part of a program to improve the methods for predicting the suckdown and hot gas ingestion for jet V/STOL aircraft in ground effect, a data base is being created that provides a systematic variation of parameters so that a new empirical prediction procedure can be developed. The first series of tests in this program was completed. Suckdown, fountain lift, and pressures induced on several two-jet V/STOL configurations are described. It is one of three reports that present the data obtained from tests conducted at Lockheed Aeronautical Systems-Rye Canyon Facility and in the High Bay area of the 40 by 80 foot wind tunnel complex at NASA Ames Research Center.

  9. Inhibition of SOCs Attenuates Acute Lung Injury Induced by Severe Acute Pancreatitis in Rats and PMVECs Injury Induced by Lipopolysaccharide.

    PubMed

    Wang, Guanyu; Zhang, Jingwen; Xu, Caiming; Han, Xiao; Gao, Yanyan; Chen, Hailong

    2016-06-01

    Acute lung injury (ALI) is a critical complication of the severe acute pancreatitis (SAP), characterized by increased pulmonary permeability with high mortality. Pulmonary microvascular endothelial cells (PMVECs) injury and apoptosis play a key role in ALI. Previous studies indicated that store-operated calcium entry (SOCE) could regulate a variety of cellular processes. The present study was to investigate the effects of SOCE inhibition on ALI induced by SAP in Sprague-Dawley rats, and PMVECs injury induced by lipopolysaccharide (LPS). Rat model of SAP-associated ALI were established by the retrograde infusion of sodium deoxycholate. Serum levels of amylase, TNF-α, and IL-6, histological changes, water content of the lung, oxygenation index, and ultrastructural changes of PMVECs were examined in ALI rats with or without store-operated Ca(2+) channels (SOCs) pharmacological inhibitor (2-aminoethoxydiphenyl borate, 2-APB) pretreatment. For in vitro studies, PMVECs were transiently transfected with or without small interfering RNA (siRNA) against calcium release-activated calcium channel protein1 (Orai1) and stromal interaction molecule1 (STIM1), the two main molecular constituents of SOCs, then exposed to LPS. The viability of PMVECs was determined. The expression of STIM1, Orai1, Bax, and caspase3, both in lung tissue and in PMVECs, were assessed by quantitative real-time PCR and western blot. Administration of sodium deoxycholate upregulated the expression of SOCs proteins in lung tissue. Similarly, the SOCs proteins were increased in PMVECs induced by LPS. 2-APB reduced the serum levels of amylase, TNF-α, and IL-6, and attenuated lung water content and histological findings. In addition, the decreased oxygenation index and ultrastructural damage in PMVECs associated with SAP were ameliorated after administration of 2-APB. Knockdown of STIM1 and Orai1 inhibited LPS-induced PMVECs death. Furthermore, blockade of SOCE significantly suppressed Orai1, STIM1, Bax

  10. Severe Burn Injury Induces Thermogenically Functional Mitochondria in Murine White Adipose Tissue.

    PubMed

    Porter, Craig; Herndon, David N; Bhattarai, Nisha; Ogunbileje, John O; Szczesny, Bartosz; Szabo, Csaba; Toliver-Kinsky, Tracy; Sidossis, Labros S

    2015-09-01

    Chronic cold exposure induces functionally thermogenic mitochondria in the inguinal white adipose tissue (iWAT) of mice. Whether this response occurs in pathophysiological states remains unclear. The purpose of this study was to determine the impact of severe burn trauma on iWAT mitochondrial function in mice. Male BALB/c mice (10-12 weeks) received full-thickness scald burns to ∼30% of the body surface area. Inguinal white adipose tissue was harvested from mice at 1, 4, 10, 20, and 40 days postinjury. Total and uncoupling protein 1 (UCP1)-dependent mitochondrial thermogenesis were determined in iWAT. Citrate synthase activity was determined as a proxy of mitochondrial abundance. Immunohistochemistry was performed to assess iWAT morphology and UCP1 expression. Uncoupling protein 1-dependent respiration was significantly greater at 4 and 10 days after burn compared with sham, peaking at 20 days after burn (P < 0.001). Citrate synthase activity was threefold greater at 4, 10, 20, and 40 days after burn versus sham (P < 0.05). Per mitochondrion, UCP1 function increased after burn trauma (P < 0.05). After burn trauma, iWAT exhibited numerous multilocular lipid droplets that stained positive for UCP1. The current findings demonstrate the induction of thermogenically competent mitochondria within rodent iWAT in a model of severe burn trauma. These data identify a specific pathology that induces the browning of white adipose tissue in vivo and may offer a mechanistic explanation for the chronic hypermetabolism observed in burn victims. PMID:26009824

  11. LPS-induced systemic inflammation is more severe in P2Y12 null mice.

    PubMed

    Liverani, Elisabetta; Rico, Mario C; Yaratha, Laxmikausthubha; Tsygankov, Alexander Y; Kilpatrick, Laurie E; Kunapuli, Satya P

    2014-02-01

    Thienopyridines are a class of antiplatelet drugs that are metabolized in the liver to several metabolites, of which only one active metabolite can irreversibly antagonize the platelet P2Y12 receptor. Possible effects of these drugs and the role of activated platelets in inflammatory responses have also been investigated in a variety of animal models, demonstrating that thienopyridines could alter inflammation. However, it is not clear whether it is caused only by the P2Y12 antagonism or whether off-target effects of other metabolites also intervene. To address this question, we investigated P2Y12 KO mice during a LPS-induced model of systemic inflammation, and we treated these KO mice with a thienopyridine drug (clopidogrel). Contrary to the reported effects of clopidogrel, numbers of circulating WBCs and plasma levels of cytokines were increased in LPS-exposed KO mice compared with WT in this inflammation model. Moreover, both spleen and bone marrow show an increase in cell content, suggesting a role for P2Y12 in regulation of bone marrow and spleen cellular composition. Finally, the injury was more severe in the lungs of KO mice compared with WT. Interestingly, clopidogrel treatments also exerted protective effects in KO mice, suggesting off-target effects for this drug. In conclusion, the P2Y12 receptor plays an important role during LPS-induced inflammation, and this signaling pathway may be involved in regulating cell content in spleen and bone marrow during LPS systemic inflammation. Furthermore, clopidogrel may have effects that are independent of P2Y12 receptor blockade. PMID:24142066

  12. The Role of Intestinal Microbiota in the Development and Severity of Chemotherapy-Induced Mucositis

    PubMed Central

    van Vliet, Michel J.; Harmsen, Hermie J. M.; de Bont, Eveline S. J. M.; Tissing, Wim J. E.

    2010-01-01

    Mucositis, also referred to as mucosal barrier injury, is one of the most debilitating side effects of radiotherapy and chemotherapy treatment. Clinically, mucositis is associated with pain, bacteremia, and malnutrition. Furthermore, mucositis is a frequent reason to postpone chemotherapy treatment, ultimately leading towards a higher mortality in cancer patients. According to the model introduced by Sonis, both inflammation and apoptosis of the mucosal barrier result in its discontinuity, thereby promoting bacterial translocation. According to this five-phase model, the intestinal microbiota plays no role in the pathophysiology of mucositis. However, research has implicated a prominent role for the commensal intestinal microbiota in the development of several inflammatory diseases like inflammatory bowel disease, pouchitis, and radiotherapy-induced diarrhea. Furthermore, chemotherapeutics have a detrimental effect on the intestinal microbial composition (strongly decreasing the numbers of anaerobic bacteria), coinciding in time with the development of chemotherapy-induced mucositis. We hypothesize that the commensal intestinal microbiota might play a pivotal role in chemotherapy-induced mucositis. In this review, we propose and discuss five pathways in the development of mucositis that are potentially influenced by the commensal intestinal microbiota: 1) the inflammatory process and oxidative stress, 2) intestinal permeability, 3) the composition of the mucus layer, 4) the resistance to harmful stimuli and epithelial repair mechanisms, and 5) the activation and release of immune effector molecules. Via these pathways, the commensal intestinal microbiota might influence all phases in the Sonis model of the pathogenesis of mucositis. Further research is needed to show the clinical relevance of restoring dysbiosis, thereby possibly decreasing the degree of intestinal mucositis. PMID:20523891

  13. Polaprezinc reduces the severity of radiation-induced mucositis in head and neck cancer patients

    PubMed Central

    DOI, HIROSHI; FUJIWARA, MASAYUKI; SUZUKI, HITOMI; NIWA, YASUE; NAKAYAMA, MASAHIRO; SHIKATA, TOSHIYUKI; ODAWARA, SOICHI; TAKADA, YASUHIRO; KIMURA, TAKESHI; KAMIKONYA, NORIHIKO; HIROTA, SHOZO

    2015-01-01

    Polaprezinc (PZ), an antiulcer drug, has been reported to have antioxidant properties. The aim of the present study was to assess the feasibility and efficacy of administering PZ for radiation-induced mucositis in head and neck cancer patients. Patients with newly diagnosed head and neck cancer were enrolled in this prospective study. PZ was prepared as an oral rinse. The PZ oral rinse was used four times per day during the course of radiotherapy. Sequential changes in radiation mucositis were assessed during and after radiotherapy according to the Common Terminology Criteria for Adverse Events, version 3.0. Furthermore, a retrospective comparison analysis was performed to assess the efficacy of PZ for radiation-induced mucositis. A total of 32 patients were enrolled in the prospective study of the PZ oral rinse. Radiotherapy was performed up to a total dose of 60–66 Gy using a conventional schedule combined with chemotherapy. Of the 32 patients, 30 (93.8%) reported no complaints due to the PZ oral rinse. In addition, PZ was not associated with severe adverse effects. Among the patients who received PZ, grade 3 mucositis was observed in 29.0% based on the mucosal findings and in 39.3% based on the symptoms. In the patients who did not receive PZ, the incidence of grade 3 mucositis was 40.0% based on the mucosal findings and 60.7% based on the symptoms. Moreover, PZ promoted the recovery from mucositis caused by chemoradiotherapy and was not associated with reduced tumor response to radiotherapy. Therefore, the PZ oral rinse was well tolerated and proved to be efficient for the treatment of radiotherapy-induced oral mucositis. PMID:25798271

  14. Severe hypoxia induces complete antifolate resistance in carcinoma cells due to cell cycle arrest

    PubMed Central

    Raz, S; Sheban, D; Gonen, N; Stark, M; Berman, B; Assaraf, Y G

    2014-01-01

    Antifolates have a crucial role in the treatment of various cancers by inhibiting key enzymes in purine and thymidylate biosynthesis. However, the frequent emergence of inherent and acquired antifolate resistance in solid tumors calls for the development of novel therapeutic strategies to overcome this chemoresistance. The core of solid tumors is highly hypoxic due to poor blood circulation, and this hypoxia is considered to be a major contributor to drug resistance. However, the cytotoxic activity of antifolates under hypoxia is poorly characterized. Here we show that under severe hypoxia, gene expression of ubiquitously expressed key enzymes and transporters in folate metabolism and nucleoside homeostasis is downregulated. We further demonstrate that carcinoma cells become completely refractory, even at sub-millimolar concentrations, to all hydrophilic and lipophilic antifolates tested. Moreover, tumor cells retained sensitivity to the proteasome inhibitor bortezomib and the topoisomerase II inhibitor doxorubicin, which are independent of cell cycle. We provide evidence that this antifolate resistance, associated with repression of folate metabolism, is a result of the inability of antifolates to induce DNA damage under hypoxia, and is attributable to a hypoxia-induced cell cycle arrest, rather than a general anti-apoptotic mechanism. Our findings suggest that solid tumors harboring a hypoxic core of cell cycle-arrested cells may display antifolate resistance while retaining sensitivity to the chemotherapeutics bortezomib and doxorubicin. This study bears important implications for the molecular basis underlying antifolate resistance under hypoxia and its rational overcoming in solid tumors. PMID:24556682

  15. Fatal pneumonia due to Serratia proteamaculans subsp. quinovora.

    PubMed Central

    Bollet, C; Grimont, P; Gainnier, M; Geissler, A; Sainty, J M; De Micco, P

    1993-01-01

    Serratia proteamaculans subsp. quinovora was isolated from several samples (blood cultures, tracheal aspirates, pleural effusion) from a patient with pneumonia. This is the first clinical isolate and the first documented human infection caused by this organism. PMID:8432835

  16. A Compendium for Mycoplasma pneumoniae.

    PubMed

    Parrott, Gretchen L; Kinjo, Takeshi; Fujita, Jiro

    2016-01-01

    Historically, atypical pneumonia was a term used to describe an unusual presentation of pneumonia. Currently, it is used to describe the multitude of symptoms juxtaposing the classic symptoms found in cases of pneumococcal pneumonia. Specifically, atypical pneumonia is a syndrome resulting from a relatively common group of pathogens including Chlamydophila sp., and Mycoplasma pneumoniae. The incidence of M. pneumoniae pneumonia in adults is less than the burden experienced by children. Transmission rates among families indicate children may act as a reservoir and maintain contagiousness over a long period of time ranging from months to years. In adults, M. pneumoniae typically produces a mild, "walking" pneumonia and is considered to be one of the causes of persistent cough in patients. M. pneumoniae has also been shown to trigger the exacerbation of other lung diseases. It has been repeatedly detected in patients with bronchitis, asthma, chronic obstructive pulmonary disorder, and cystic fibrosis. Recent advances in technology allow for the rapid diagnosis of M. pneumoniae through the use of polymerase chain reaction or rapid antigen tests. With this, more effort has been afforded to identify the causative etiologic agent in all cases of pneumonia. However, previous practices, including the overprescribing of macrolide treatment in China and Japan, have created increased incidence of macrolide-resistant M. pneumoniae. Reports from these countries indicate that >85% of M. pneumoniae pneumonia pediatric cases are macrolide-resistant. Despite its extensively studied past, the smallest bacterial species still inspires some of the largest questions. The developments in microbiology, diagnostic features and techniques, epidemiology, treatment and vaccines, and upper respiratory conditions associated with M. pneumoniae in adult populations are included within this review. PMID:27148202

  17. A Compendium for Mycoplasma pneumoniae

    PubMed Central

    Parrott, Gretchen L.; Kinjo, Takeshi; Fujita, Jiro

    2016-01-01

    Historically, atypical pneumonia was a term used to describe an unusual presentation of pneumonia. Currently, it is used to describe the multitude of symptoms juxtaposing the classic symptoms found in cases of pneumococcal pneumonia. Specifically, atypical pneumonia is a syndrome resulting from a relatively common group of pathogens including Chlamydophila sp., and Mycoplasma pneumoniae. The incidence of M. pneumoniae pneumonia in adults is less than the burden experienced by children. Transmission rates among families indicate children may act as a reservoir and maintain contagiousness over a long period of time ranging from months to years. In adults, M. pneumoniae typically produces a mild, “walking” pneumonia and is considered to be one of the causes of persistent cough in patients. M. pneumoniae has also been shown to trigger the exacerbation of other lung diseases. It has been repeatedly detected in patients with bronchitis, asthma, chronic obstructive pulmonary disorder, and cystic fibrosis. Recent advances in technology allow for the rapid diagnosis of M. pneumoniae through the use of polymerase chain reaction or rapid antigen tests. With this, more effort has been afforded to identify the causative etiologic agent in all cases of pneumonia. However, previous practices, including the overprescribing of macrolide treatment in China and Japan, have created increased incidence of macrolide-resistant M. pneumoniae. Reports from these countries indicate that >85% of M. pneumoniae pneumonia pediatric cases are macrolide-resistant. Despite its extensively studied past, the smallest bacterial species still inspires some of the largest questions. The developments in microbiology, diagnostic features and techniques, epidemiology, treatment and vaccines, and upper respiratory conditions associated with M. pneumoniae in adult populations are included within this review. PMID:27148202

  18. Dopamine Disposition in the Presynaptic Process Regulates the Severity of Methamphetamine-induced Neurotoxicity

    PubMed Central

    KUHN, DONALD M.; FRANCESCUTTI-VERBEEM, DINA M.; THOMAS, DAVID M.

    2008-01-01

    Methamphetamine (METH) is well-known for its ability to cause damage to dopamine (DA) nerve endings of the striatum. The mechanisms by which METH causes neurotoxicity are not fully understood but likely candidates are increased oxidative and nitrosative stress and mitochondrial dysfunction. Microglial activation is also emerging as an important element of the METH neurotoxic cascade and it appears that extensive crosstalk between these cells and DA nerve endings is an early event in this process. It may seem paradoxical, but DA itself is also thought to be an essential factor in the neuronal damaging effects of METH, but issues relating to its precise role in this regard remain unanswered. We present in this overview a summary of studies that tested how alterations in the disposition of presynaptic DA (injections of reserpine, L-DOPA, or clorgyline) modulate METH neurotoxicity. In all cases, these drugs significantly increased the magnitude of microglial activation as well as the severity of damage to striatal DA nerve endings caused by METH. The enhancement of METH effects in striatum by reserpine, L-DOPA, and clorgyline persisted for 14 days and showed no evidence of recovery. These data establish that subtle shifts in the newly-synthesized pool of DA can cause substantial changes in the severity of METH-induced neurotoxicity. DA released into the synapse by METH is very likely the source of downstream reactants that provoke microglial activation and the ensuing damage to DA nerve endings. PMID:18991856

  19. Influence of injection timing on severity of cadmium-induced testicular toxicity in mice.

    PubMed

    Ohtani, Katsumi; Yanagiba, Yukie; Ashimori, Atsushige; Takeuchi, Asuka; Takada, Naoko; Togawa, Masako; Hasegawa, Tatsuya; Ikeda, Masayuki; Miura, Nobuhiko

    2013-02-01

    Cadmium (Cd) is one of the endocrine disrupter and is a well-known testicular toxicant. Recently, we reported that Cd-induced mortality was markedly different by injection timing. In this report, we investigated whether severity of testicular toxicity was affected by injection timing of Cd. C57BL/6J mice (male, 7 w) were received single intraperitoneal injection of CdCl(2) (4.5 mg/kg) at zeitgeber time 6 (ZT6) or ZT18; these injection timings showed highest (ZT6) or lowest (ZT18) mortality in our previous study (Miura, 2012). After one week of the injection, several parameters for testicular toxicity such as epididymal sperm motility and numbers of sperm head both in cauda epididymidis and testis were measured. At ZT6 injection group, all parameters examined were significantly reduced compared to the control group. However, very interestingly, no significant changes were observed at ZT18 injection group. We obtained similar results by another experiment in which mice were received single subcutaneous injection of CdCl(2) (4 or 6 mg/kg) followed by measuring the parameters ten days after the injection. This diurnal variation was not contradictory to the result of the lethal toxicity which we showed earlier. Therefore, our results indicate that the testicular toxicity of Cd is also influenced by the injection timing. PMID:23358149

  20. Patterns and severity of vincristine-induced peripheral neuropathy in children with acute lymphoblastic leukemia

    PubMed Central

    Smith, Ellen M. Lavoie; Li, Lang; Chiang, ChienWei; Thomas, Karin; Hutchinson, Raymond J.; Wells, Elizabeth M.; Ho, Richard H.; Skiles, Jodi; Chakraborty, Arindom; Bridges, Celia M.; Renbarger, Jamie

    2015-01-01

    Vincristine, a critical component of combination chemotherapy treatment for pediatric acute lymphoblastic leukemia (ALL), can lead to vincristine-induced peripheral neuropathy (VIPN). Longitudinal VIPN assessments were obtained over 12 months from newly diagnosed children with ALL (N = 128) aged 1–18 years who received vincristine at one of four academic children’s hospitals. VIPN assessments were obtained using the Total Neuropathy Score-Pediatric Vincristine (TNS©-PV), National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE©), Balis© grading scale, and Pediatric Neuropathic Pain Scale©–Five (PNPS©-5). Of children who provided a full TNS©-PV score, 85/109 (78%) developed VIPN (TNS©-PV ≥4). Mean TNS©-PV, grading scale, and pain scores were low. CTCAE©-derived grades 3 and 4 sensory and motor VIPN occurred in 1.6%/0%, and 1.9%/0% of subjects, respectively. VIPN did not resolve in months 8–12 despite decreasing dose density. VIPN was worse in older children. Partition cluster analysis revealed 2–3 patient clusters; one cluster (n = 14) experienced severe VIPN. In this population, VIPN occurs more commonly than previous research suggests, persists throughout the first year of treatment, and can be severe. PMID:25977177

  1. Respiratory heat/water loss alone does not determine the severity of exercise-induced asthma.

    PubMed

    Noviski, N; Bar-Yishay, E; Gur, I; Godfrey, S

    1988-03-01

    Respiratory heat loss (RHL) or water loss (RWL) have been proposed as possible triggering factors in exercise and hyperventilation-induced asthma (EIA and HIA). It has recently been demonstrated that exercise intensity and climatic factors are both important in determining the severity of EIA. Eight young asthmatics performed both exercise and isocapnic hyperventilation (IHV) manoeuvres under identical climatic conditions, as part of our investigation of these interactive factors which determine the severity of the asthmatic response. It was found that, when challenged at low ventilatory levels, exercise produced a significantly attenuated asthmatic response compared to IHV. The fall in forced expired volume in 1 sec (delta FEV1) following exercise was 15 +/- 4% as compared with 27 +/- 3% after IHV (p less than 0.002). It is concluded that while the hypernoea in exercise may serve as a trigger, exercise per se introduces an additional factor which serves to limit the full response seen with IHV. This attenuated response is revealed at low ventilatory levels but is masked at high levels. PMID:3384078

  2. Porphyromonas gingivalis oral infection exacerbates the development and severity of collagen-induced arthritis

    PubMed Central

    2013-01-01

    Introduction Clinical studies suggest a direct influence of periodontal disease (PD) on serum inflammatory markers and disease assessment of patients with established rheumatoid arthritis (RA). However, the influence of PD on arthritis development remains unclear. This investigation was undertaken to determine the contribution of chronic PD to immune activation and development of joint inflammation using the collagen-induced arthritis (CIA) model. Methods DBA1/J mice orally infected with Porphyromonas gingivalis were administered with collagen II (CII) emulsified in complete Freund’s adjuvant (CFA) or incomplete Freund’s adjuvant (IFA) to induce arthritis. Arthritis development was assessed by visual scoring of paw swelling, caliper measurement of the paws, mRNA expression, paw micro-computed tomography (micro-CT) analysis, histology, and tartrate resistant acid phosphatase for osteoclast detection (TRAP)-positive immunohistochemistry. Serum and reactivated splenocytes were evaluated for cytokine expression. Results Mice induced for PD and/or arthritis developed periodontal disease, shown by decreased alveolar bone and alteration of mRNA expression in gingival tissues and submandibular lymph nodes compared to vehicle. P. gingivalis oral infection increased paw swelling and osteoclast numbers in mice immunized with CFA/CII. Arthritis incidence and severity were increased by P. gingivalis in mice that received IFA/CII immunizations. Increased synovitis, bone erosions, and osteoclast numbers in the paws were observed following IFA/CII immunizations in mice infected with P gingivalis. Furthermore, cytokine analysis showed a trend toward increased serum Th17/Th1 ratios when P. gingivalis infection was present in mice receiving either CFA/CII or IFA/CII immunizations. Significant cytokine increases induced by P. gingivalis oral infection were mostly associated to Th17-related cytokines of reactivated splenic cells, including IL-1β, IL-6, and IL-22 in the CFA

  3. Protective efficacy of the chimeric Staphylococcus aureus vaccine candidate IC in sepsis and pneumonia models

    PubMed Central

    Yang, Liuyang; Cai, Changzhi; Feng, Qiang; Shi, Yun; Zuo, Qianfei; Yang, Huijie; Jing, Haiming; Wei, Chao; Zhuang, Yuan; Zou, Quanming; Zeng, Hao

    2016-01-01

    Staphylococcus aureus causes serious sepsis and necrotic pneumonia worldwide. Due to the spread of multidrug-resistant strains, developing an effective vaccine is the most promising method for combating S. aureus infection. In this study, based on the immune-dominant areas of the iron surface determinant B (IsdB) and clumping factor A (ClfA), we designed the novel chimeric vaccine IsdB151-277ClfA33-213 (IC). IC formulated with the AlPO4 adjuvant induced higher protection in an S. aureus sepsis model compared with the single components alone and showed broad immune protection against several clinical S. aureus isolates. Immunisation with IC induced strong antibody responses. The protective effect of antibodies was demonstrated through the opsonophagocytic assay (OPA) and passive immunisation experiment. Moreover, this new chimeric vaccine induced Th1/Th17-skewed cellular immune responses based on cytokine profiles and CD4+ T cell stimulation tests. Neutralisation of IL-17A alone (but not IFN-γ) resulted in a significant decrease in vaccine immune protection. Finally, we found that IC showed protective efficacy in a pneumonia model. Taken together, these data provide evidence that IC is a potentially promising vaccine candidate for combating S. aureus sepsis and pneumonia. PMID:26865417

  4. Mycoplasma-induced minimally conscious state.

    PubMed

    Horvath, Thomas; Fischer, Urs; Müller, Lionel; Ott, Sebastian; Bassetti, Claudio L; Wiest, Roland; Sendi, Parham; Schefold, Joerg C

    2016-01-01

    Mycoplasma pneumoniae (M. pneumoniae) frequently causes community-acquired respiratory tract infection and often presents as atypical pneumonia. Following airborne infection and a long incubation period, affected patients mostly suffer from mild or even asymptomatic and self-limiting disease. In particular in school-aged children, M. pneumoniae is associated with a wide range of extrapulmonary manifestations including central nervous system (CNS) disease. In contrast to children, severe CNS manifestations are rarely observed in adults. We report a case of a 37 year-old previously healthy immunocompetent adult with fulminant M. pneumoniae-induced progressive encephalomyelitis who was initially able to walk to the emergency department. A few hours later, she required controlled mechanical ventilation for ascending transverse spinal cord syndrome, including complete lower extremity paraplegia. Severe M. pneumoniae-induced encephalomyelitis was postulated, and antimicrobial, anti-inflammatory and immunosuppressive therapy was applied on the intensive care unit. Despite early and targeted therapy using four different immunosuppressive strategies, clinical success was limited. In our patient, locked-in syndrome developed followed by persistent minimally conscious state. The neurological status was unchanged until day 230 of follow-up. Our case underlines that severe M. pneumoniae- related encephalomyelitis must not only be considered in children, but also in adults. Moreover, it can be fulminant and fatal in adults. Our case enhances the debate for an optimal antimicrobial agent with activity beyond the blood-brain barrier. Furthermore, it may underline the difficulty in clinical decision making regarding early antimicrobial treatment in M. pneumoniae disease, which is commonly self-limited. PMID:27026840

  5. [Ceftaroline fosamil in community-acquired and nosocomial pneumonia].

    PubMed

    Calbo, Esther; Zaragoza, Rafael

    2014-03-01

    Community-acquired pneumonia (CAP) is a common infection in developed countries and causes a large number of hospital admissions and deaths. In recent years, the incidence of this disease has increased, caused by progressive population aging. Following the introduction of the conjugate vaccine against Streptococcus pneumoniae, there have been significant epidemiological changes that require close monitoring because of the possible emergence of new patterns of resistance. This article aims to review the role of ceftaroline fosamil, a new parenteral cephalosporin with antibacterial activity against Gram-negative and Gram-positive pathogens, in the treatment of pneumonia. Several in vitro and in vivo studies have shown the efficacy of ceftaroline fosamil against penicillin-resistant S. pneumoniae and methicillin-resistant Staphylococcus aureus (MRSA). Additionally, ceftaroline has shown similar efficacy and safety to ceftriaxone in the treatment of community-acquired pneumonia with severe prognosis (prognostic severity index III and IV) in two phase III clinical trials. Although a non-inferiority design was used for these clinical trials, some data suggest a superior efficacy of ceftaroline, with earlier clinical response and higher cure rate in infections caused by S. pneumoniae, making this drug particularly interesting for critically-ill patients admitted to the intensive care unit. Ceftaroline may also be considered for empirical and directed treatment of MRSA pneumonia. PMID:24702978

  6. Chlamydia pneumoniae infection-related hemophagocytic lymphohistiocytosis and acute encephalitis and poliomyelitis-like flaccid paralysis.

    PubMed

    Yagi, Kanae; Kano, Gen; Shibata, Mayumi; Sakamoto, Izumi; Matsui, Hirofumi; Imashuku, Shinsaku

    2011-05-01

    A 3-year-old male presented with Chlamydia pneumoniae infection-related hemophagocytic lymphohistiocytosis (HLH). The patient developed an episode of HLH with severe skin eruption following C. pneumoniae pneumonia. Symptoms responded to steroid/cyclosporine A therapy, but the patient slowly lost consciousness and developed systemic flaccid paralysis. He was diagnosed with encephalitis/myelitis by brain and spinal MRI. Neurological symptoms and signs gradually resolved. We thought that the immune response to C. pneumoniae infection triggered the development of HLH, associated with unusual neurological complications. This report describes a novel case of C. pneumoniae-associated HLH and with poliomyelitis like flaccid paralysis. PMID:21370423

  7. Delineation of immunodominant and cytadherence segment(s) of Mycoplasma pneumoniae P1 gene

    PubMed Central

    2014-01-01

    Background Adhesion of Mycoplasma pneumoniae (M. pneumoniae) to host epithelial cells requires several adhesin proteins like P1, P30 and P116. Among these proteins, P1 protein has been inedited as one of the major adhesin and immunogenic protein present on the attachment organelle of M. pneumoniae. In the present study, we scanned the entire sequence of M. pneumoniae P1 protein to identify the immunodominant and cytadherence region(s). M. pneumoniae P1 gene was synthesized in four segments replacing all the UGA codons to UGG codons. Each of the four purified P1 protein fragment was analyzed for its immunogenicity with anti-M. pneumoniae M129 antibodies (Pab M129) and sera of M. pneumoniae infected patients by western blotting and ELISA. Antibodies were produced against all the P1 protein fragments and these antibodies were used for M. pneumoniae adhesion, M. pneumoniae adhesion inhibition and M. pneumoniae surface exposure assays using HEp-2 cells lines. Results Our results show that the immunodominant regions are distributed throughout the entire length of P1 protein, while only the N- and C- terminal region(s) of P1 protein are surface exposed and block cytadhesion to HEp-2 cells, while antibodies to two middle fragments failed to block cytadhesion. Conclusions These results have important implications in designing strategies to block the attachment of M. pneumoniae to epithelial cells, thus preventing the development of atypical pneumonia. PMID:24774062

  8. Lung dendritic cells facilitate extrapulmonary bacterial dissemination during pneumococcal pneumonia

    PubMed Central

    Rosendahl, Alva; Bergmann, Simone; Hammerschmidt, Sven; Goldmann, Oliver; Medina, Eva

    2013-01-01

    Streptococcus pneumoniae is a leading cause of bacterial pneumonia worldwide. Given the critical role of dendritic cells (DCs) in regulating and modulating the immune response to pathogens, we investigated here the role of DCs in S. pneumoniae lung infections. Using a well-established transgenic mouse line which allows the conditional transient depletion of DCs, we showed that ablation of DCs resulted in enhanced resistance to intranasal challenge with S. pneumoniae. DCs-depleted mice exhibited delayed bacterial systemic dissemination, significantly reduced bacterial loads in the infected organs and lower levels of serum inflammatory mediators than non-depleted animals. The increased resistance of DCs-depleted mice to S. pneumoniae was associated with a better capacity to restrict pneumococci extrapulmonary dissemination. Furthermore, we demonstrated that S. pneumoniae disseminated from the lungs into the regional lymph nodes in a cell-independent manner and that this direct way of dissemination was much more efficient in the presence of DCs. We also provide evidence that S. pneumoniae induces expression and activation of matrix metalloproteinase-9 (MMP-9) in cultured bone marrow-derived DCs. MMP-9 is a protease involved in the breakdown of extracellular matrix proteins and is critical for DC trafficking across extracellular matrix and basement membranes during the migration from the periphery to the lymph nodes. MMP-9 was also significantly up-regulated in the lungs of mice after intranasal infection with S. pneumoniae. Notably, the expression levels of MMP-9 in the infected lungs were significantly decreased after depletion of DCs suggesting the involvement of DCs in MMP-9 production during pneumococcal pneumonia. Thus, we propose that S. pneumoniae can exploit the DC-derived proteolysis to open tissue barriers thereby facilitating its own dissemination from the local site of infection. PMID:23802100

  9. Loss of Bace1 in Mice Does Not Alter the Severity of Caerulein Induced Pancreatitis

    PubMed Central

    Heindl, Mario; Tuennemann, Jan; Sommerer, Ines; Mössner, Joachim; Hoffmeister, Albrecht

    2015-01-01

    Context Beta-site alpha-amyloid protein cleaving enzyme1 (BACE1) plays a key role in the pathogenesis of Alzheimer’s disease. Additional to its moderate expression in the brain, high levels of BACE1 mRNA were found in the pancreas. Murine Bace1 has been immunohistochemicaly detected at the apical pole of acinar cells within the exocrine pancreas of mice and Bace1 activity was observed in pancreatic juice. In vitro experiments revealed enteropeptidase as a putative substrate for Bace1 suggesting a role in acute pancreatitis. Objective The aim of this study was to address a protective mechanism of Bace1 in acute experimental pancreatitis in mice. Methods Acute experimental pancreatitis was induced by intraperitoneal injection of caerulein in homozygote Bace1-/- mice and wild type mice. Serum and tissue analyses were carried out after 4 h, 8 h and 24 h. Measurement of plasma amylase and lipase was performed to confirm pancreatitis induction. In order to assess the severity of pancreatitis H&E stained pancreatic sections were examined regarding edema, inflammation and apoptosis. Immunohistochemical detection of myeloperoxidase (MPO) positive cells was carried out to further quantify the extent of inflammation. Expression of Bace2 within the pancreas was analyzed by immunohistochemistry and RT-qPCR. Results We demonstrate that total loss of Bace1 in mice leads to no alterations in the course of acute experimental caerulein-pancreatitis. Bace1-/- mice develop a moderate pancreatitis that is comparable in histomorphological and serological features with those seen in wild type mice. Discussion We discuss the results in the context of the applied caerulein induced edematous pancreatitis model and possible compensatory mechanisms via Bace2 that might be responsible for the observed results. PMID:25961820

  10. MAG-EPA reduces severity of DSS-induced colitis in rats.

    PubMed

    Morin, Caroline; Blier, Pierre U; Fortin, Samuel

    2016-05-15

    Ulcerative colitis (UC) is a chronic disease characterized by diffuse inflammation of the intestinal mucosa of the large bowel. Omega-3 (ω3) fatty acid supplementation has been associated with a decreased production of inflammatory cytokines involved in UC pathogenesis. The aim of this study was to determine the preventive and therapeutic potential of eicosapentaenoic acid monoglyceride (MAG-EPA) in an in vivo rats model of UC induced by dextran sulfate sodium (DSS). DSS rats were untreated or treated per os with MAG-EPA. Morphological, histological, and biochemical analyses were performed following MAG-EPA administrations. Morphological and histological analyses revealed that MAG-EPA pretreatment (12 days pre-DSS) and treatment (6 days post-DSS) exhibited strong activity in reducing severity of disease in DSS rats. Following MAG-EPA administrations, tissue levels of the proinflammatory cytokines TNF-α, IL-1β, and IL-6 were markedly lower compared with rats treated only with DSS. MAG-EPA per os administration decrease neutrophil infiltration in colon tissues, as depicted by myelohyperoxidase activity. Results also revealed a reduced activation of NF-κB pathways correlated with a decreased expression of COX-2 in colon homogenates derived from MAG-EPA-pretreated and treated rats. Tension measurements performed on colon tissues revealed that contractile responses to methacholine and relaxing effect induced by sodium nitroprusside were largely increased following MAG-EPA treatment. The combined treatment of MAG-EPA and vitamin E displayed an antagonistic effect on anti-inflammatory properties of MAG-EPA in DSS rats. PMID:27012773

  11. Epidemiology of pneumonia in a burn care unit: the influence of inhalation trauma on pneumonia and of pneumonia on burn mortality

    PubMed Central

    Liodaki, E.; Kalousis, K.; Mauss, K.L.; Kisch, T.; Mailaender, P.; Stang, F.

    2015-01-01

    Summary The aim of this study is to determine the epidemiological characteristics of burn patients developing pneumonia, as well as the predisposing factors and the mortality of these patients. Infectious complications present serious problems in severely burned patients. Pneumonia, in particular, is a major cause of morbidity and mortality in burn patients. Patients with inhalation injuries are exposed to a greater risk due to the possible development of infectious complications in the lower respiratory tract. During their stay in our Burn Care Unit, 22.9% of our burn patients developed pneumonia and 10.9 % of these patients died. Risk factors for the development of pneumonia in burn patients were found to be inhalation trauma, high ABSI score, the Baux and modified Baux index, and high ASA score (p<0.01). Age and gender showed no significant correlation to the incidence of pneumonia. In this study we were able to determine the incidence of pneumonia in burn patients, their mortality and the strong correlation of the presence of inhalation injury with the development of pneumonia.

  12. Continuous plasma filtration adsorption in treatment of severe infection-induced multiple organ dysfunction syndrome.

    PubMed

    Yin, S L; Lan, C; Pei, H; Zu, Z Q

    2016-01-01

    Multiple organ dysfunction syndrome (MODS), a high-risk disease, has a fatality rate of 70%. To improve treatment of this disease, in recent years many scholars have explored the pathological and physiological changes of MODS. To observe the curative effect of continuous plasma filtration adsorption (CPFA) in the treatment of MODS, we selected 96 patients who were diagnosed with severe infection-induced MODS and were treated in the First Affiliated Hospital of Zhengzhou University between February 2012 and October 2014 and divided them into an observation group and a control group. Besides conventional treatment, the observation group was also given CFPA in combination with high volume hemofiltration (HVHF), while the control group only received HVHF. Changes of blood routine index, balance of electrolyte and acid-base as well as vital signs were observed before and after treatment. Also, blood, kidney and blood gas were examined. For all patients, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and C-reactive protein (CRP) were recorded at the start of treatment (0 h), and 5 h and 10 h after treatment. It was found that both therapies could lower blood urea nitrogen (BUN) and creatinine levels and maintain balance of electrolyte and acid-base, but had no obvious influence on leukocyte, blood platelet and hematocrit. In the observation group, PaO2/FiO2 and mean arterial pressure (MAP) were significantly improved after surgery (P less than 0.05), while Acute Physiology and Chronic Health Evaluation (APACHE) II score had an obvious decrease (P less than 0.05). In contrast, the control group was observed with insignificantly changed PaO2/FiO2, MAP and APACHE II score (P>0.05). TNF-α, IL-6 and CRP levels of the two groups had no statistically significant difference at the start of treatment (P>0.05), but TNF-α, IL-6 and CRP levels of the observation group became remarkably lower than those of the control group 5 h and 10 h after treatment (P less than 0

  13. A prebiotic galactooligosaccharide mixture reduces severity of hyperpnoea-induced bronchoconstriction and markers of airway inflammation.

    PubMed

    Williams, Neil C; Johnson, Michael A; Shaw, Dominick E; Spendlove, Ian; Vulevic, Jelena; Sharpe, Graham R; Hunter, Kirsty A

    2016-09-01

    Gut microbes have a substantial influence on systemic immune function and allergic sensitisation. Manipulation of the gut microbiome through prebiotics may provide a potential strategy to influence the immunopathology of asthma. This study investigated the effects of prebiotic Bimuno-galactooligosaccharide (B-GOS) supplementation on hyperpnoea-induced bronchoconstriction (HIB), a surrogate for exercise-induced bronchoconstriction, and airway inflammation. A total of ten adults with asthma and HIB and eight controls without asthma were randomised to receive 5·5 g/d of either B-GOS or placebo for 3 weeks separated by a 2-week washout period. The peak fall in forced expiratory volume in 1 s (FEV1) following eucapnic voluntary hyperpnoea (EVH) defined HIB severity. Markers of airway inflammation were measured at baseline and after EVH. Pulmonary function remained unchanged in the control group. In the HIB group, the peak post-EVH fall in FEV1 at day 0 (-880 (sd 480) ml) was unchanged after placebo, but was attenuated by 40 % (-940 (sd 460) v. -570 (sd 310) ml, P=0·004) after B-GOS. In the HIB group, B-GOS reduced baseline chemokine CC ligand 17 (399 (sd 140) v. 323 (sd 144) pg/ml, P=0·005) and TNF-α (2·68 (sd 0·98) v. 2·18 (sd 0·59) pg/ml, P=0·040) and abolished the EVH-induced 29 % increase in TNF-α. Baseline C-reactive protein was reduced following B-GOS in HIB (2·46 (sd 1·14) v. 1·44 (sd 0·41) mg/l, P=0·015) and control (2·16 (sd 1·02) v. 1·47 (sd 0·33) mg/l, P=0·050) groups. Chemokine CC ligand 11 and fraction of exhaled nitric oxide remained unchanged. B-GOS supplementation attenuated airway hyper-responsiveness with concomitant reductions in markers of airway inflammation associated with HIB. PMID:27523186

  14. Effects of resveratrol on the treatment of inflammatory response induced by severe burn.

    PubMed

    Tao, Ke; Bai, Xiaozhi; Jia, Wenbin; Liu, Yang; Zhu, Xiongxiang; Han, Juntao; Dong, Maolong; Li, Jun; Chen, Dongdong; Hu, Dahai

    2015-01-01

    The aim of this study was to preliminarily investigate the effects of resveratrol on the treatment of systemic inflammatory response induced by severe burn wounding. Through the simulation experiment in vivo on burned mice and simulative experiment in vitro on mice macrophage respectively, differences of the related pro-inflammatory cytokines and SIRT1 expression levels between the resveratrol-treated group and the untreated control group were detected and analyzed. The results of the simulation experiment in vivo on burned mice manifested that the survival rate of the mice in the resveratrol-treated group was markedly higher than that of controls (p<0.05). Resveratrol could significantly reduce the levels of pro-inflammatory factors TNF-α, IL-1β, and IL-6 in serum (p<0.01) and greatly elevate the expression level of SIRT1 (p<0.01). The results of the simulative experiment in vitro on mice macrophage showed no significant difference in TNF-α, IL-1β, or IL-6 contents among three groups (C, mice macrophage control group; R, resveratrol-treated macrophage group; I, SIRT1-inhibitor-treated macrophage group). Whereas, after lipopolysaccharide (LPS) activation (L group), macrophage TNF-α, IL-1β, and IL-6 levels were significantly increased in L group, dramatically higher than those in L+R group (LPS and resveratrol treatment group) (p<0.01). After adding SITR1 inhibitor, three pro-inflammatory cytokines in L+R+I group all showed significant increases compared with those in L+R group (p<0.01). LPS activated macrophages were able to promote the expression of pro-inflammatory cytokines. By upregulating the expression levels of SIRT1, resveratrol could effectively inhibit the inflammation cascade reaction and increase the survival rate of severe burn with bacterial infections in a large extent. PMID:25586484

  15. Intermittent severe hypoxia induces plasticity within serotonergic and catecholaminergic neurons in the neonatal rat ventrolateral medulla.

    PubMed

    Givan, Scott A; Cummings, Kevin J

    2016-06-01

    5-HT neurons contribute to autoresuscitation and survival during intermittent severe hypoxia (IsH). In adults, catecholaminergic neurons in the ventrolateral medulla (VLM) contribute to the autonomic response to hypoxia. We hypothesized that 1) catecholaminergic neurons in the neonatal VLM are activated following IsH, 2) this activation is compromised following an acute loss of brain stem 5-HT, and 3) IsH induces cellular and/or transcriptomic plasticity within catecholaminergic and serotonergic neurons that are within or project to the VLM, respectively. To test these hypotheses, we treated rat pups with 6-fluorotryptophan, a tryptophan hydroxylase (TPH) inhibitor, and then exposed treated and vehicle controls to IsH or air. Along with immunohistochemistry to detect tyrosine hydroxylase (TH)- or Fos-positive neurons, we used RNA sequencing to resolve the effects of IsH and 5-HT deficiency on the expression of serotonergic and catecholaminergic system genes in the VLM. 5-HT deficiency compromised autoresuscitation and survival. IsH significantly increased the number of identifiable TH-positive VLM neurons, an effect enhanced by 5-HT deficiency (P = 0.003). Contrary to our hypothesis, 5-HT-deficient pups had significantly more Fos-positive neurons following IsH (P = 0.008) and more activated TH-positive neurons following IsH or air (P = 0.04). In both groups the expression of the 5-HT transporter and TPH2 was increased following IsH. In 5-HT-deficient pups, the expression of the inhibitory 5-HT1A receptor was decreased following IsH, while the expression of DOPA decarboxylase was increased. These data show that the serotonergic and catecholaminergic systems in the VLM of the neonatal rat are dynamically upregulated by IsH, potentially adapting cardiorespiratory responses to severe hypoxia. PMID:26968026

  16. Antipsychotic withdrawal-induced relapse predicts future relapses in institutionalized adults with severe intellectual disability.

    PubMed

    Janowsky, David S; Barnhill, L Jarrett; Khalid, Abdul S; Davis, John M

    2008-08-01

    Severe intellectual and developmental disabilities are frequently associated with aggression toward self and others, destruction of property, and disruption. Antipsychotic medications are a mainstay of treatment of such behaviors. National and state guidelines suggest stopping these medications or decreasing their dosages when possible if patients have maintained stability. The current study evaluated the likelihood of future antipsychotic drug withdrawal-induced relapses in those individuals where such a relapse had occurred previously. Subjects were 57 institutionalized adults with severe or profound intellectual disability. Between 1990 and 2000, each had experienced an initial activation of maladaptive aggressive behaviors after an attempt at antipsychotic drug withdrawal and/or termination. Quarterly behavioral reports were evaluated to determine whether subsequent antipsychotic drug withdrawal attempts were also associated with future relapses. Initial relapse was followed by subsequent antipsychotic drug withdrawal attempts in 49 of the 57 individuals. Between 1990 and 2005, 28.6% of these 49 subjects had experienced 1, 38.7% had 2, 20.4% had 3, and 8.2% had 4 additional relapses. Two (4.1%) had not relapsed. Eight individuals remained on antipsychotic agents without a subsequent withdrawal attempt. By the end of 2005, only 4 (7%) of the 57 individuals had become antipsychotic drug free, 22.8% were receiving first-generation antipsychotic agents alone, 45.6% were receiving second-generation antipsychotic agents alone, and 24.6% were receiving a combination of first- and second-generation antipsychotic agents. Thus, if relapse occurs after an antipsychotic drug withdrawal attempt, subsequent attempts at withdrawal are also very likely to lead to further relapses. PMID:18626266

  17. Vaccinating welders against pneumonia

    PubMed Central

    Palmer, Keith T; Cosgrove, Martin P

    2013-01-01

    Background In 2011 the Department of Health in England recommended that welders should each receive a single dose of the 23-valent pneumococcal vaccine (PPV23). This review assesses the evidence behind the advice and its practical implications. Method The review was informed by a systematic search in Medline, which related pneumonia to welding and/or exposure to metal fume, and was supplemented using the personal libraries of the authors. Findings There is consistent evidence that welders die more often of pneumonia, especially lobar pneumonia, are hospitalised more often with lobar and pneumococcal pneumonia, and more often develop invasive pneumococcal disease (IPD). It is estimated that one case of IPD may be prevented over a 10-year period by vaccinating 588 welders against pneumococcal infection. Conclusions A good case exists that employers should offer PPV23 vaccination to welders and other employees exposed to metal fume. Additionally, reasonable measures must be taken to minimise exposure to welding fume and welders should be encouraged not to smoke. PMID:22764269

  18. Lipoid pneumonia: an overview.

    PubMed

    Hadda, Vijay; Khilnani, Gopi C

    2010-12-01

    Lipoid pneumonia is an uncommon disease caused by the presence of lipid in the alveoli. It is classified into two major groups, depending on whether the lipid/oil in the respiratory tract is from an exogenous (exogenous lipoid pneumonia) or endogenous/idiopathic (endogenous lipoid pneumonia) source. The usual presentation occurs with insidious onset and nonspecific respiratory symptoms such as dyspnea and/or cough. The main radiological findings include airspace consolidations, ground-glass attenuation, airspace nodules and 'crazy-paving' pattern. However, the radiological appearance of the disorder can mimic many other lung diseases, including carcinoma. Owing to the nonspecific clinical presentation and radiological features, the diagnosis is often missed or delayed. Pathologically, lipoid pneumonia is a chronic foreign body reaction to fat, characterized by lipid-laden macrophages. Diagnosis of this disease requires a high index of suspicion and can be confirmed by demonstration of lipid-laden macrophages in respiratory samples such as sputum, bronchoalveolar lavage fluid or fine-needle aspiration cytology/biopsy from lung lesions. Treatment protocols for this illness are poorly defined. PMID:21128754

  19. Pathophysiology of pneumonia.

    PubMed

    Alcón, Amalia; Fàbregas, Neus; Torres, Antoni

    2005-03-01

    The development of pneumonia requires that a pathogen reach the alveoli and that the host defenses are overwhelmed by microorganism virulence or by the inoculum size. The endogenous sources of microorganisms are nasal carriers, sinusitis, oropharynx, gastric, or tracheal colonization, and hematogenous spread. Other external sources of contamination, such as intensive care unit workers, aerosols, or fibrobronchoscopy, must be considered as accidental. PMID:15802164

  20. Pneumonia - children - discharge

    MedlinePlus

    ... have some symptoms of pneumonia after leaving the hospital. Coughing will slowly get better over 7 to 14 days. Sleeping and eating may take up to a week to return to normal. You may need to take time off work to care for your child.

  1. Severe Global DNA Hypomethylation Blocks Differentiation and Induces Histone Hyperacetylation in Embryonic Stem Cells

    PubMed Central

    Jackson, Melany; Krassowska, Anna; Gilbert, Nick; Chevassut, Timothy; Forrester, Lesley; Ansell, John; Ramsahoye, Bernard

    2004-01-01

    It has been reported that DNA methyltransferase 1-deficient (Dnmt1−/−) embryonic stem (ES) cells are hypomethylated (20% CpG methylation) and die through apoptosis when induced to differentiate. Here, we show that Dnmt[3a−/−,3b−/−] ES cells with just 0.6% of their CpG dinucleotides behave differently: the majority of cells within the culture are partially or completely blocked in their ability to initiate differentiation, remaining viable while retaining the stem cell characteristics of alkaline phosphatase and Oct4 expression. Restoration of DNA methylation levels rescues these defects. Severely hypomethylated Dnmt[3a−/−,3b−/−] ES cells have increased histone acetylation levels, and those cells that can differentiate aberrantly express extraembryonic markers of differentiation. Dnmt[3a−/−,3b−/−] ES cells with >10% CpG methylation are able to terminally differentiate, whereas Dnmt1−/− ES cells with 20% of the CpG methylated cannot differentiate. This demonstrates that successful terminal differentiation is not dependent simply on adequate methylation levels. There is an absolute requirement that the methylation be delivered by the maintenance enzyme Dnmt1. PMID:15456861

  2. Chronic nitrate enrichment decreases severity and induces protection against an infectious disease.

    PubMed

    Smallbone, Willow; Cable, Jo; Maceda-Veiga, Alberto

    2016-05-01

    Excessive fertilisation is one of the most pernicious forms of global change resulting in eutrophication. It has major implications for disease control and the conservation of biodiversity. Yet, the direct link between nutrient enrichment and disease remains largely unexplored. Here, we present the first experimental evidence that chronic nitrate enrichment decreases severity and induces protection against an infectious disease. Specifically, this study shows that nitrate concentrations ranging between 50 and 250mgNO3(-)/l reduce Gyrodactylus turnbulli infection intensity in two populations of Trinidadian guppies Poecilia reticulata, and that the highest nitrate concentration can even clean the parasites from the fish. This added to the fact that host nitrate pre-exposure altered the fish epidermal structure and reduced parasite intensity, suggests that nitrate protected the host against the disease. Nitrate treatments also caused fish mortality. As we used ecologically-relevant nitrate concentrations, and guppies are top-consumers widely used for mosquito bio-control in tropical and often nutrient-enriched waters, our results can have major ecological and social implications. In conclusion, this study advocates reducing nitrate level including the legislative threshold to protect the aquatic biota, even though this may control an ectoparasitic disease. PMID:26995268

  3. Severe global DNA hypomethylation blocks differentiation and induces histone hyperacetylation in embryonic stem cells.

    PubMed

    Jackson, Melany; Krassowska, Anna; Gilbert, Nick; Chevassut, Timothy; Forrester, Lesley; Ansell, John; Ramsahoye, Bernard

    2004-10-01

    It has been reported that DNA methyltransferase 1-deficient (Dnmt1-/-) embryonic stem (ES) cells are hypomethylated (20% CpG methylation) and die through apoptosis when induced to differentiate. Here, we show that Dnmt[3a-/-,3b-/-] ES cells with just 0.6% of their CpG dinucleotides behave differently: the majority of cells within the culture are partially or completely blocked in their ability to initiate differentiation, remaining viable while retaining the stem cell characteristics of alkaline phosphatase and Oct4 expression. Restoration of DNA methylation levels rescues these defects. Severely hypomethylated Dnmt[3a-/-,3b-/-] ES cells have increased histone acetylation levels, and those cells that can differentiate aberrantly express extraembryonic markers of differentiation. Dnmt[3a-/-,3b-/-] ES cells with >10% CpG methylation are able to terminally differentiate, whereas Dnmt1-/- ES cells with 20% of the CpG methylated cannot differentiate. This demonstrates that successful terminal differentiation is not dependent simply on adequate methylation levels. There is an absolute requirement that the methylation be delivered by the maintenance enzyme Dnmt1. PMID:15456861

  4. Warming-induced upslope advance of subalpine forest is severely limited by geomorphic processes.

    PubMed

    Macias-Fauria, Marc; Johnson, Edward A

    2013-05-14

    Forests are expected to expand into alpine areas because of climate warming, causing land-cover change and fragmentation of alpine habitats. However, this expansion will only occur if the present upper treeline is limited by low-growing season temperatures that reduce plant growth. This temperature limitation has not been quantified at a landscape scale. Here, we show that temperature alone cannot realistically explain high-elevation tree cover over a >100-km(2) area in the Canadian Rockies and that geologic/geomorphic processes are fundamental to understanding the heterogeneous landscape distribution of trees. Furthermore, upslope tree advance in a warmer scenario will be severely limited by availability of sites with adequate geomorphic/topographic characteristics. Our results imply that landscape-to-regional scale projections of warming-induced, high-elevation forest advance into alpine areas should not be based solely on temperature-sensitive, site-specific upper-treeline studies but also on geomorphic processes that control tree occurrence at long (centuries/millennia) timescales. PMID:23569221

  5. Pathogenesis of ELANE-mutant severe neutropenia revealed by induced pluripotent stem cells.

    PubMed

    Nayak, Ramesh C; Trump, Lisa R; Aronow, Bruce J; Myers, Kasiani; Mehta, Parinda; Kalfa, Theodosia; Wellendorf, Ashley M; Valencia, C Alexander; Paddison, Patrick J; Horwitz, Marshall S; Grimes, H Leighton; Lutzko, Carolyn; Cancelas, Jose A

    2015-08-01

    Severe congenital neutropenia (SCN) is often associated with inherited heterozygous point mutations in ELANE, which encodes neutrophil elastase (NE). However, a lack of appropriate models to recapitulate SCN has substantially hampered the understanding of the genetic etiology and pathobiology of this disease. To this end, we generated both normal and SCN patient-derived induced pluripotent stem cells (iPSCs), and performed genome editing and differentiation protocols that recapitulate the major features of granulopoiesis. Pathogenesis of ELANE point mutations was the result of promyelocyte death and differentiation arrest, and was associated with NE mislocalization and activation of the unfolded protein response/ER stress (UPR/ER stress). Similarly, high-dose G-CSF (or downstream signaling through AKT/BCL2) rescues the dysgranulopoietic defect in SCN patient-derived iPSCs through C/EBPβ-dependent emergency granulopoiesis. In contrast, sivelestat, an NE-specific small-molecule inhibitor, corrected dysgranulopoiesis by restoring normal intracellular NE localization in primary granules; ameliorating UPR/ER stress; increasing expression of CEBPA, but not CEBPB; and promoting promyelocyte survival and differentiation. Together, these data suggest that SCN disease pathogenesis includes NE mislocalization, which in turn triggers dysfunctional survival signaling and UPR/ER stress. This paradigm has the potential to be clinically exploited to achieve therapeutic responses using lower doses of G-CSF combined with targeting to correct NE mislocalization. PMID:26193632

  6. An unusual autopsy case of lethal hypothermia exacerbated by body lice-induced severe anemia.

    PubMed

    Nara, Akina; Nagai, Hisashi; Yamaguchi, Rutsuko; Makino, Yohsuke; Chiba, Fumiko; Yoshida, Ken-ichi; Yajima, Daisuke; Iwase, Hirotaro

    2016-05-01

    Pediculus humanus humanus (known as body lice) are commonly found in the folds of clothes, and can cause skin disorders when they feed on human blood, resulting in an itching sensation. Body lice are known as vectors of infectious diseases, including typhus, recurrent fever, and trench fever. An infestation with blood-sucking body lice induces severe cutaneous pruritus, and this skin disorder is known as "vagabond's disease." A body lice infestation is sometimes complicated with iron deficiency anemia. In the present case, a man in his late 70s died of lethal hypothermia in the outdoors during the winter season. The case history and autopsy findings revealed that the cause of the lethal hypothermia was iron deficiency anemia, which was associated with a prolonged infestation of blood-sucking body lice. Also, he had vagabond's disease because the skin on his body was abnormal and highly pigmented. This is an unusual autopsy case since the body lice contributed to the cause of the death. PMID:26384507

  7. Dengue NS1 antigen contributes to disease severity by inducing interleukin (IL)-10 by monocytes.

    PubMed

    Adikari, T N; Gomes, L; Wickramasinghe, N; Salimi, M; Wijesiriwardana, N; Kamaladasa, A; Shyamali, N L A; Ogg, G S; Malavige, G N

    2016-04-01

    Both dengue NS1 antigen and serum interleukin (IL)-10 levels have been shown to associate with severe clinical disease in acute dengue infection, and IL-10 has also been shown to suppress dengue-specific T cell responses. Therefore, we proceeded to investigate the mechanisms by which dengue NS1 contributes to disease pathogenesis and if it is associated with altered IL-10 production. Serum IL-10 and dengue NS1 antigen levels were assessed serially in 36 adult Sri Lankan individuals with acute dengue infection. We found that the serum IL-10 levels correlated positively with dengue NS1 antigen levels (Spearman's r = 0·47, P < 0·0001), and NS1 also correlated with annexin V expression by T cells in acute dengue (Spearman's r = 0·63, P = 0·001). However, NS1 levels did not associate with the functionality of T cell responses or with expression of co-stimulatory molecules. Therefore, we further assessed the effect of dengue NS1 on monocytes and T cells by co-culturing primary monocytes and peripheral blood mononuclear cells (PBMC), with varying concentrations of NS1 for up to 96 h. Monocytes co-cultured with NS1 produced high levels of IL-10, with the highest levels seen at 24 h, and then declined gradually. Therefore, our data show that dengue NS1 appears to contribute to pathogenesis of dengue infection by inducing IL-10 production by monocytes. PMID:26621477

  8. Streptococcus pneumoniae infections in western Nepal.

    PubMed

    Easow, Joshy Maducolil; Joseph, Noyal Mariya; Shankar, Pathiyil Ravi; Rajamony, Asish Purushothaman; Dhungel, Banodita Acharya; Shivananda, P G

    2011-07-01

    We conducted a study to determine the prevalence of antibiotic resistance among clinical isolates of S. pneumoniae. This study was conducted from January 2000 to August 2007 at a tertiary care teaching hospital in Nepal. The isolates were identified based on standard bacteriological techniques. Antibiotic susceptibility testing used the Kirby-Bauer disc diffusion method; penicillin resistance was confirmed by agar dilution method. During the study period, there were 312 S. pneumoniae isolates. Penicillin, trimethoprim-sulfamethoxazole, erythromycin, tetracycline and chloramphenicol resistance were observed in 5, 34.3, 7.4, 11.1 and 0.4% of isolates, respectively. Resistance to all tested antibiotics declined with time except for penicillin, in which resistance increased. Penicillin-resistant S. pneumoniae were significantly co-resistant to erythromycin. Co-resistance to tetracycline and erythromycin were observed in trimethoprim-sulfamethoxazole resistant isolates. Penicillin resistance is increasing; therefore, measures to ensure judicious use of beta-lactams and macrolides (inducers of penicillin resistance) should be advocated to control the development of penicillin-resistant S. pneumoniae. PMID:22299473

  9. Early Additional Immune-Modulators for Mycoplasma pneumoniae Pneumonia in Children: An Observation Study

    PubMed Central

    Lee, Sung-Churl; Rhim, Jung-Woo; Shin, Myung-Seok; Kang, Jin-Han

    2014-01-01

    Background Mycoplasma pneumoniae (MP) pneumonia is a self-limiting disease, but some patients complain of progressive pneumonia, despite of appropriate antibiotic treatment. We aimed to introduce the role of immune-modulators (corticosteroid and/or intravenous immunoglobulin, IVIG) treatment for childhood MP pneumonia based on previous our experiences. Materials and Methods A retrospective case series analysis for 183 children with MP pneumonia was performed. MP pneumonia patients were diagnosed by two Immunoglobulin M (IgM) tests: the micro-particle agglutination method (≥1:40) and the cold agglutination test (≥1:4), and were examined twice at the initial admission and at discharge. Among 183 MP pneumonia patients, 90 patients with persistent fever for over 48 hours after admission or those with severe respiratory symptoms and signs received additional prednisolone (82 patients, 1 mg/kg/day) or intravenous methylprednisolone (8 patients, 5-10 mg/kg/day) with antibiotics. Four patients with aggravated clinical symptoms and chest radiographic findings after corticosteroid treatment received IVIG (1 g/kg/day, 1-2 doses). Results Mean age of 183 patients was 5.5 ± 3.2 years (6 months-15 years), and the male: female ratio was 1.1:1 (96:87). Fifty-seven patients (31%) were seroconverters and 126 seropositive patients showed increased diagnostic IgM antibody titres during admission (over 4 folds). The majority of the patients who received corticosteroids (86/90 cases) showed rapid defervescence within 48 hours with improved clinical symptoms, regardless of the used antibiotics. Also, 4 patients who received additional IVIG improved both clinically and radiographically within 2 days without adverse reaction. Conclusions In the era of macrolide-resistant MP strains, early additional immune-modulator therapy with antibiotics might prevent from the disease progression and reduce the disease morbidity without adverse reaction. PMID:25566403

  10. Chronic Infection and Severe Asthma.

    PubMed

    Carr, Tara F; Kraft, Monica

    2016-08-01

    Chronic bacterial infection is implicated in both the development and severity of asthma. The atypical bacteria Mycoplasma pneumoniae and Chlamydophila pneumoniae have been identified in the airways of asthmatics and correlated with clinical features such as adult onset, exacerbation risks, steroid sensitivity, and symptom control. Asthmatic patients with evidence of bacterial infection may benefit from antibiotic treatment directed towards these atypical organisms. Examination of the airway microbiome may identify microbial communities that confer risk for or protection from severe asthma. PMID:27401621

  11. Septic shock, necrotizing pneumonitis, and meningoencephalitis caused by Mycoplasma pneumoniae in a child: a case report.

    PubMed

    Barreira, Eliane R; Souza, Daniela C; Góes, Patricia F; Bousso, Albert

    2009-04-01

    Mycoplasma pneumoniae is an important causative agent of respiratory infection in childhood. Although the infection caused by M. pneumoniae is classically described as benign, severe and life-threatening pulmonary and extrapulmonary complications can occur. This study describes the first case of septic shock related to M. pneumoniae in a child with necrotizing pneumonitis, severe encephalitis, and multiple organs involvement, with a favorable outcome after lobectomy and systemic corticosteroids. PMID:19023109

  12. Mothers' Perception and Healthcare Seeking Behavior of Pneumonia Children in Rural Bangladesh

    PubMed Central

    Ferdous, Farzana; Dil Farzana, Fahmida; Ahmed, Shahnawaz; Das, Sumon Kumar; Malek, Mohammad Abdul; Das, Jui; Faruque, Abu Syed Golam; Chisti, Mohammod Jobayer

    2014-01-01

    We describe mothers' perception about signs and symptoms, causes of the illness, and healthcare seeking behaviors related to pneumonia and express the major modifiable barriers to seeking timely treatment when their under-5 children had pneumonia in rural Bangladesh. Using focus group discussion, we understood mothers' perception and healthcare seeking behavior of childhood pneumonia. Although mothers described pneumonia as a serious life threatening disease in young children but most of the mothers (n = 24) could not diagnose whether their child had pneumonia or not. Environmental factors such as dust particles, spread from coughing mother, and drinking cold water or playing with water were perceived as the causes for pneumonia. Three common barriers noted were as follows: illness was not perceived as serious enough or distance from healthcare facility or lack of money at household for seeking treatment outside. Most of the rural mothers did not have knowledge about severity of childhood pneumonia. PMID:24967328

  13. Uncomplicated pneumonia in healthy Canadian children and youth: Practice points for management

    PubMed Central

    Le Saux, Nicole; Robinson, Joan L

    2015-01-01

    Although immunization has decreased the incidence of bacterial pneumonia in vaccinated children, pneumonia remains common in healthy children. Symptoms of bacterial pneumonia frequently overlap those present with viral infections or reactive airway disease. Optimally, the diagnosis of bacterial pneumonia should be supported by a chest radiograph before starting antimicrobials. Factors such as age, vital signs and other measures of illness severity are critical when deciding whether to admit a patient to hospital. Because Streptococcus pneumoniae continues to be the most common cause of bacterial pneumonia in children, prescribing amoxicillin or ampicillin for seven to 10 days remains the mainstay of empirical therapy for nonsevere pneumonia. If improvement does not occur, consideration should be given to searching for complications (empyema or lung abscess). Routine chest radiographs at the end of therapy are not recommended unless clinically indicated. PMID:26744558

  14. The Ratio KL-6 to SLX in Serum for Prediction of the Occurrence of Drug-Induced Interstitial Lung Disease in Lung Cancer Patients with Idiopathic Interstitial Pneumonias Receiving Chemotherapy.

    PubMed

    Kashiwabara, Kosuke; Semba, Hiroshi; Fujii, Shinji; Tsumura, Shinsuke; Aoki, Ryota

    2015-01-01

    We retrospectively evaluated whether the ratio KL-6 to SLX in serum (K/S ratio) before chemotherapy was a predictor for the occurrence of drug-induced interstitial lung disease (D-ILD) in lung cancer patients with idiopathic interstitial pneumonias (IIPs). D-ILD occurred in 8 of 20 IIPs-positive cases and in 14 of 100 IIPs-negative cases (40 vs. 14%, p = .015). In IIPs-positive cases, the high K/S ratio (>20) before first-line chemotherapy had a tendency to increase the risk of D-ILD (p = .085). Serum K/S ratio may be a useful predictor for the occurrence of D-ILD in lung cancer patients with IIPs. PMID:26305851

  15. In situ molecular hybridization for detection of Aleutian mink disease parvovirus DNA by using strand-specific probes: identification of target cells for viral replication in cell cultures and in mink kits with virus-induced interstitial pneumonia.

    PubMed Central

    Alexandersen, S; Bloom, M E; Wolfinbarger, J; Race, R E

    1987-01-01

    Strand-specific hybridization probes were utilized in in situ molecular hybridization specifically to localize replicative form DNA of Aleutian mink disease parvovirus (ADV). Throughout in vitro infection, duplex replicative form DNA of ADV was located in the cell nuclei. Single-stranded virion DNA and capsid proteins were present in the nuclei early in infection, but were later translocated to the cytoplasm. In neonatal mink, ADV causes acute interstitial pneumonia, and replicative forms of viral DNA were found predominantly in alveolar type II cells of the lung. Viral DNA was also found in other organs, but strand-specific probes made it possible to show that most of this DNA represented virus sequestration. In addition, glomerular immune complexes containing intact virions were detected, suggesting that ADV virions may have a role in the genesis of ADV-induced glomerulonephritis. Images PMID:3037104

  16. Modelling staphylococcal pneumonia in a human 3D lung tissue model system delineates toxin-mediated pathology

    PubMed Central

    Mairpady Shambat, Srikanth; Chen, Puran; Nguyen Hoang, Anh Thu; Bergsten, Helena; Vandenesch, Francois; Siemens, Nikolai; Lina, Gerard; Monk, Ian R.; Foster, Timothy J.; Arakere, Gayathri; Svensson, Mattias; Norrby-Teglund, Anna

    2015-01-01

    ABSTRACT Staphylococcus aureus necrotizing pneumonia is recognized as a toxin-mediated disease, yet the tissue-destructive events remain elusive, partly as a result of lack of mechanistic studies in human lung tissue. In this study, a three-dimensional (3D) tissue model composed of human lung epithelial cells and fibroblasts was used to delineate the role of specific staphylococcal exotoxins in tissue pathology associated with severe pneumonia. To this end, the models were exposed to the mixture of exotoxins produced by S. aureus strains isolated from patients with varying severity of lung infection, namely necrotizing pneumonia or lung empyema, or to purified toxins. The necrotizing pneumonia strains secreted high levels of α-toxin and Panton-Valentine leukocidin (PVL), and triggered high cytotoxicity, inflammation, necrosis and loss of E-cadherin from the lung epithelium. In contrast, the lung empyema strain produced moderate levels of PVL, but negligible amounts of α-toxin, and triggered limited tissue damage. α-toxin had a direct damaging effect on the epithelium, as verified using toxin-deficient mutants and pure α-toxin. Moreover, PVL contributed to pathology through the lysis of neutrophils. A combination of α-toxin and PVL resulted in the most severe epithelial injury. In addition, toxin-induced release of pro-inflammatory mediators from lung tissue models resulted in enhanced neutrophil migration. Using a collection of 31 strains from patients with staphylococcal pneumonia revealed that strains producing high levels of α-toxin and PVL were cytotoxic and associated with fatal outcome. Also, the strains that produced the highest toxin levels induced significantly greater epithelial disruption. Of importance, toxin-mediated lung epithelium destruction could be inhibited by polyspecific intravenous immunoglobulin containing antibodies against α-toxin and PVL. This study introduces a novel model system for study of staphylococcal pneumonia in a human

  17. Impact of Stress-Induced Diabetes on Outcomes in Severely Burned Children

    PubMed Central

    Finnerty, Celeste C.; Ali, Arham; McClean, Josef; Benjamin, Nicole; Clayton, Robert P.; Andersen, Clark R.; Mlcak, Ronald P.; Suman, Oscar E.; Meyer, Walter; Herndon, David N.

    2014-01-01

    Background Post-burn hyperglycemia leads to graft failure, multiple organ failure, and death. A hyperinsulinemic-euglycemic clamp is used to keep serum glucose between 60-110mg/dL. Because of frequent hypoglycemic episodes, a less stringent sliding scale insulin protocol is used to maintain serum glucose levels between 80-160mg/dL following elevations above 180mg/dL. Study Design We randomized pediatric patients with massive burns into two groups – patients receiving sliding scale insulin to lower blood glucose levels (n=145) and those receiving no insulin (n = 98) to determine the differences in morbidity and mortality. Patients 0-18 years old with burns covering ≥30% of the total body surface area and not randomized to receive anabolic agents were included in this study. Endpoints included glucose levels, infections, resting energy expenditure (REE), lean body mass, bone mineral content (BMC), fat mass, muscle strength, and serum inflammatory cytokines, hormones, and liver enzymes. Results Maximal glucose levels occurred within 6 days of burn injury. Blood glucose levels were age dependent with older children requiring more insulin, p<0.05. Daily maximum and daily minimum, but not 6am,glucose levels were significantly different based on treatment group, p<0.05. Insulin significantly increased REE and improved BMC, p<0.05. Each additional wound infection increased incidence of hyperglycemia, p=0.004. There was no mortality in patients not receiving insulin, only in patients who received insulin (p<0.004). Muscle strength was increased in patients receiving insulin (p<0.05). Conclusions A subset of severely burned children develops burn-induced hyperglycemia. Length of stay was reduced in the no insulin group, and there were no deaths in this group. Administration of insulin positively impacted BMC and muscle strength, but increased REE, hypoglycemic episodes, and mortality. New glucose-lowering strategies may be needed. PMID:24655871

  18. [Thousand faces of Streptococcus pneumonia (pneumococcus) infections].

    PubMed

    Szabó, Bálint Gergely; Lénárt, Katalin Szidónia; Kádár, Béla; Gombos, Andrea; Dezsényi, Balázs; Szanka, Judit; Bobek, Ilona; Prinz, Gyula

    2015-11-01

    Incidence and mortality rates of infections caused by Streptococcus pneumoniae (pneumococcus) are high worldwide and in Hungary among paediatric as well as adult populations. Pneumococci account for 35-40% of community acquired adult pneumonias requiring hospitalization, while 25-30% of Streptococcus pneumoniae pneumonias are accompanied by bacteraemia. 5-7% of all infections are fatal but this rate is exponentially higher in high risk patients and elderly people. Mortality could reach 20% among patients with severe invasive pneumococcal infections. Complications may develop despite administration of adequate antibiotics. The authors summarize the epidemiology of pneumococcal infections, pathogenesis of non-invasive and invasive disease and present basic clinical aspects through demonstration of four cases. Early risk stratification, sampling of hemocultures, administration of antibiotics and wider application of active immunization could reduce the mortality of invasive disease. Anti-pneumococcal vaccination is advisable for adults of ≥50 years and high risk patients of ≥18 years who are susceptible to pneumococcal disease. PMID:26498896

  19. Exogenous lipoid pneumonia. Clinical and radiological manifestations.

    PubMed

    Marchiori, Edson; Zanetti, Gláucia; Mano, Claudia Mauro; Hochhegger, Bruno

    2011-05-01

    Lipoid pneumonia results from the pulmonary accumulation of endogenous or exogenous lipids. Host tissue reactions to the inhaled substances differ according to their chemical characteristics. Symptoms can vary significantly among individuals, ranging from asymptomatic to severe, life-threatening disease. Acute, sometimes fatal, cases can occur, but the disease is usually indolent. Possible complications include superinfection by nontuberculous mycobacteria, pulmonary fibrosis, respiratory insufficiency, cor pulmonale, and hypercalcemia. The radiological findings are nonspecific, and the disease presents with variable patterns and distribution. For this reason, lipoid pneumonia may mimic many other diseases. The diagnosis of exogenous lipoid pneumonia is based on a history of exposure to oil, characteristic radiological findings, and the presence of lipid-laden macrophages on sputum or BAL analysis. High-resolution computed tomography (HRCT) is the best imaging modality for the diagnosis of lipoid pneumonia. The most characteristic CT finding in LP is the presence of negative attenuation values within areas of consolidation. There are currently no studies in the literature that define the best therapeutic option. However, there is a consensus that the key measure is identifying and discontinuing exposure to the offending agent. Treatment in patients without clinical symptoms remains controversial, but in patients with diffuse pulmonary damage, aggressive therapies have been reported. They include whole lung lavage, systemic corticosteroids, and thoracoscopy with surgical debridement. PMID:21185165

  20. Survival of a cat with pneumonia due to cowpox virus and feline herpesvirus infection.

    PubMed

    Johnson, M S; Martin, M; Stone, B; Hetzel, U; Kipar, A

    2009-09-01

    Cowpox virus infection in cats is rare and usually leads to cutaneous lesions alone. Pulmonary infection and pneumonia have been documented occasionally but all such cases described to date have been fatal. Although usually affecting the upper respiratory tract, feline herpesvirus can also induce pneumonia. The present report describes the case of a cat that recovered from a pneumonia in which both poxvirus and feline herpesvirus were demonstrated. PMID:19769672

  1. Impact of bacterial coinfection on clinical outcomes in pneumococcal pneumonia.

    PubMed

    Kumagai, S; Ishida, T; Tachibana, H; Ito, Y; Ito, A; Hashimoto, T

    2015-09-01

    The aim of this study was to investigate the influence of bacterial coinfection on patients with pneumococcal pneumonia. We retrospectively analyzed the incidence, clinical features, microbial distributions, and outcomes of patients with bacterial coinfection in a cohort of 433 hospitalized patients with pneumococcal pneumonia. Eighty-five patients (19.6 %) were diagnosed with bacterial coinfection; the most frequent pathogens were Haemophilus influenzae (25 patients, 33.3 %), methicillin-susceptible Staphylococcus aureus (MSSA) (15 patients, 20.0 %), and Moraxella catarrhalis (13 patients, 17.3 %). The CURB-65 score and pneumonia severity index (PSI) were significantly higher in patients with bacterial coinfection (both P < 0.001). In addition, the proportion of patients with bacterial coinfection who met the Infectious Disease Society of America (IDSA)/American Thoracic Society (ATS) severe pneumonia criteria was significantly higher (P < 0.001). Multivariate logistic regression analysis identified three risk factors for bacterial coinfection in patients with pneumococcal pneumonia: alcoholism (odds ratio [OR], 5.12; 95 % confidence interval (95 % CI), 1.60-16.4; P = 0.006), hospitalization for 2 days or more within 90 days preceding admission (OR, 2.02; 95 % CI, 1.03-3.98; P = 0.041), and residence in a nursing home or extended care facility (OR, 3.22; 95 % CI, 1.48-6.97; P = 0.003). Multivariate analysis for 30-day mortality showed that bacterial coinfection was a significant adverse prognostic factor (OR, 2.50; 95 % CI, 1.13-5.53; P = 0.023), independent of IDSA/ATS severe pneumonia, PSI, or healthcare-associated pneumonia. In conclusion, bacterial coinfection may have an adverse impact on severity and outcomes of pneumococcal pneumonia. PMID:26059041

  2. [Impact of vaccination on the epidemiology of childhood pneumonia].

    PubMed

    Crisinel, Pierre-Alex

    2016-02-17

    The impact of vaccination on non-bacteremic Haemophilus influenza pneumonia is difficult to appreciate, in the absence of proper microbiological documentation. It has certainly been largely underestimated. Vaccination has reduced the incidence of pneumococcal pneumonia. However, the increase of incidence of empyema due to nonvaccine serotypes was observed in several countries. The replacement of Prevenar 7 by Prevenar 13 portends a decrease in the occurrence of these infections, but, unfortunately, without eliminating them completely. PMID:27039460

  3. Community-acquired pneumonia.

    PubMed

    Polverino, E; Torres Marti, A

    2011-02-01

    Despite the remarkable advances in antibiotic therapies, diagnostic tools, prevention campaigns and intensive care, community-acquired pneumonia (CAP) is still among the primary causes of death worldwide, and there have been no significant changes in mortality in the last decades. The clinical and economic burden of CAP makes it a major public health problem, particularly for children and the elderly. This issue provides a clinical overview of CAP, focusing on epidemiology, economic burden, diagnosis, risk stratification, treatment, clinical management, and prevention. Particular attention is given to some aspects related to the clinical management of CAP, such as the microbial etiology and the available tools to achieve it, the usefulness of new and old biomarkers, and antimicrobial and other non-antibiotic adjunctive therapies. Possible scenarios in which pneumonia does not respond to treatment are also analyzed to improve clinical outcomes of CAP. PMID:21242952

  4. Klebsiella pneumoniae Flocculation Dynamics

    PubMed Central

    Jackson, T. L.; Taylor, K. A.; Thompson, A. P.; Younger, J. G.

    2011-01-01

    The bacterial pathogen Klebsiella pneumoniae is a cause of community- and hospital-acquired lung, urinary tract, and blood stream infections. A common contaminant of indwelling catheters, it is theorized that a common infection pathway for this organism is via shedding of aggregates off of biofilm colonies. In an effort to better understand bacterial proliferation in the host bloodstream, we develop a PDE model for the flocculation dynamics of Klebsiella pneumoniae in suspension. Existence and uniqueness results are provided, as well as a brief description of the numerical approximation scheme. We generate artificial data and illustrate the requirements to accurately identify proliferation, aggregation, and fragmentation of flocs in the experimental domain of interest. PMID:18071828

  5. Four infants presenting with severe vomiting in solid food protein-induced enterocolitis syndrome: a case series

    PubMed Central

    2012-01-01

    Introduction Several different foods have been implicated in inducing the delayed and very significant vomiting and sometimes diarrhea that occurs in food protein-induced enterocolitis syndrome. While immunoglobulin E is not involved, the mechanism(s) that result in the food-induced gastrointestinal symptoms are unclear, although T cell activation has been considered. We report four cases of food protein-induced enterocolitis syndrome caused by different solid foods and without concomitant immunoglobulin E sensitization to milk and soya. Clinical and laboratory evidence of type I immunoglobulin E mediated food reactivity and food-induced T cell activation was absent in each case. Case presentations Case 1 concerned a 20-month-old South Asian boy who had experienced four episodes of severe vomiting with flaccidity since four months of age and two hours after consuming rice. Case 2 involved a nine-month-old Caucasian boy who had suffered three episodes of severe vomiting with flaccidity since six months of age and three hours after consuming wheat. The child in Case 3 was a 16-month-old Caucasian boy who had suffered three episodes of severe vomiting with flaccidity since nine months of age and two hours after consuming cod. Case 4 involved a 15-month-old South Asian boy who had suffered three episodes of severe vomiting since eight months of age and two hours after consuming chicken. Conclusion In children with recurrent marked delayed vomiting after the ingestion of specific foods and in whom bronchospasm, skin rash and angioedema are absent, food protein-induced enterocolitis syndrome should be considered. Skin prick testing and specific immunoglobulin E antibodies are negative and the mechanism of the vomiting is unclear. We speculate whether food protein-induced oligoclonal T cell activation may be present. This has similarities to various animal models and improvement may involve deletion of these T cells. PMID:22734807

  6. Fungal diagnostics in pneumonia.

    PubMed

    Lease, Erika D; Alexander, Barbara D

    2011-12-01

    Fungal pneumonia is increasingly common, particularly in highly immunosuppressed patients, such as solid organ or hematopoietic stem cell transplant recipients, and the diagnosis is evolving. Although standard techniques such as microscopy and culture remain the mainstays of diagnosis, relatively recent advances in serological and molecular testing are important additions to the field. This article reviews the laboratory tools used to diagnose fungal respiratory disease. PMID:22167394

  7. Fungal Diagnostics in Pneumonia

    PubMed Central

    Lease, Erika D.; Alexander, Barbara D.

    2014-01-01

    Fungal pneumonia is increasingly common, particularly in highly immunosuppressed patients, such as solid organ or hematopoietic stem cell transplant recipients, and the diagnosis is evolving. While standard techniques such as microscopy and culture remain the mainstay of diagnosis, relatively recent advances in serologic and molecular testing are important additions to the field. This chapter will review the laboratory tools used to diagnose fungal respiratory disease. PMID:22167394

  8. mPneumonia: Development of an Innovative mHealth Application for Diagnosing and Treating Childhood Pneumonia and Other Childhood Illnesses in Low-Resource Settings

    PubMed Central

    Ginsburg, Amy Sarah; Delarosa, Jaclyn; Brunette, Waylon; Levari, Shahar; Sundt, Mitch; Larson, Clarice; Tawiah Agyemang, Charlotte; Newton, Sam; Borriello, Gaetano; Anderson, Richard

    2015-01-01

    Pneumonia is the leading infectious cause of death in children worldwide. Each year, pneumonia kills an estimated 935,000 children under five years of age, with most of these deaths occurring in developing countries. The current approach for pneumonia diagnosis in low-resource settings—using the World Health Organization Integrated Management of Childhood Illness (IMCI) paper-based protocols and relying on a health care provider’s ability to manually count respiratory rate—has proven inadequate. Furthermore, hypoxemia—a diagnostic indicator of the presence and severity of pneumonia often associated with an increased risk of death—is not assessed because pulse oximetry is frequently not available in low-resource settings. In an effort to address childhood pneumonia mortality and improve frontline health care providers’ ability to diagnose, classify, and manage pneumonia and other childhood illnesses, PATH collaborated with the University of Washington to develop “mPneumonia,” an innovative mobile health application using an Android tablet. mPneumonia integrates a digital version of the IMCI algorithm with a software-based breath counter and a pediatric pulse oximeter. We conducted a design-stage usability field test of mPneumonia in Ghana, with the goal of creating a user-friendly diagnostic and management tool for childhood pneumonia and other childhood illnesses that would improve diagnostic accuracy and facilitate adherence by health care providers to established guidelines in low-resource settings. The results of the field test provided valuable information for understanding the usability and acceptability of mPneumonia among health care providers, and identifying approaches to iterate and improve. This critical feedback helped ascertain the common failure modes related to the user interface design, navigation, and accessibility of mPneumonia and the modifications required to improve user experience and create a tool aimed at decreasing mortality

  9. mPneumonia: Development of an Innovative mHealth Application for Diagnosing and Treating Childhood Pneumonia and Other Childhood Illnesses in Low-Resource Settings.

    PubMed

    Ginsburg, Amy Sarah; Delarosa, Jaclyn; Brunette, Waylon; Levari, Shahar; Sundt, Mitch; Larson, Clarice; Tawiah Agyemang, Charlotte; Newton, Sam; Borriello, Gaetano; Anderson, Richard

    2015-01-01

    Pneumonia is the leading infectious cause of death in children worldwide. Each year, pneumonia kills an estimated 935,000 children under five years of age, with most of these deaths occurring in developing countries. The current approach for pneumonia diagnosis in low-resource settings--using the World Health Organization Integrated Management of Childhood Illness (IMCI) paper-based protocols and relying on a health care provider's ability to manually count respiratory rate--has proven inadequate. Furthermore, hypoxemia--a diagnostic indicator of the presence and severity of pneumonia often associated with an increased risk of death--is not assessed because pulse oximetry is frequently not available in low-resource settings. In an effort to address childhood pneumonia mortality and improve frontline health care providers' ability to diagnose, classify, and manage pneumonia and other childhood illnesses, PATH collaborated with the University of Washington to develop "mPneumonia," an innovative mobile health application using an Android tablet. mPneumonia integrates a digital version of the IMCI algorithm with a software-based breath counter and a pediatric pulse oximeter. We conducted a design-stage usability field test of mPneumonia in Ghana, with the goal of creating a user-friendly diagnostic and management tool for childhood pneumonia and other childhood illnesses that would improve diagnostic accuracy and facilitate adherence by health care providers to established guidelines in low-resource settings. The results of the field test provided valuable information for understanding the usability and acceptability of mPneumonia among health care providers, and identifying approaches to iterate and improve. This critical feedback helped ascertain the common failure modes related to the user interface design, navigation, and accessibility of mPneumonia and the modifications required to improve user experience and create a tool aimed at decreasing mortality from

  10. Prioritized Expression of BTN2 of Saccharomyces cerevisiae under Pronounced Translation Repression Induced by Severe Ethanol Stress

    PubMed Central

    Yamauchi, Yukina; Izawa, Shingo

    2016-01-01

    Severe ethanol stress (>9% ethanol, v/v) as well as glucose deprivation rapidly induces a pronounced repression of overall protein synthesis in budding yeast Saccharomyces cerevisiae. Therefore, transcriptional activation in yeast cells under severe ethanol stress does not always indicate the production of expected protein levels. Messenger RNAs of genes containing heat shock elements can be intensively translated under glucose deprivation, suggesting that some mRNAs are preferentially translated even under severe ethanol stress. In the present study, we tried to identify the mRNA that can be preferentially translated under severe ethanol stress. BTN2 encodes a v-SNARE binding protein, and its null mutant shows hypersensitivity to ethanol. We found that BTN2 mRNA was efficiently translated under severe ethanol stress but not under mild ethanol stress. Moreover, the increased Btn2 protein levels caused by severe ethanol stress were smoothly decreased with the elimination of ethanol stress. These findings suggested that severe ethanol stress extensively induced BTN2 expression. Further, the BTN2 promoter induced protein synthesis of non-native genes such as CUR1, GIC2, and YUR1 in the presence of high ethanol concentrations, indicating that this promoter overcame severe ethanol stress-induced translation repression. Thus, our findings provide an important clue about yeast response to severe ethanol stress and suggest that the BTN2 promoter can be used to improve the efficiency of ethanol production and stress tolerance of yeast cells by modifying gene expression in the presence of high ethanol concentration. PMID:27602028

  11. Prioritized Expression of BTN2 of Saccharomyces cerevisiae under Pronounced Translation Repression Induced by Severe Ethanol Stress.

    PubMed

    Yamauchi, Yukina; Izawa, Shingo

    2016-01-01

    Severe ethanol stress (>9% ethanol, v/v) as well as glucose deprivation rapidly induces a pronounced repression of overall protein synthesis in budding yeast Saccharomyces cerevisiae. Therefore, transcriptional activation in yeast cells under severe ethanol stress does not always indicate the production of expected protein levels. Messenger RNAs of genes containing heat shock elements can be intensively translated under glucose deprivation, suggesting that some mRNAs are preferentially translated even under severe ethanol stress. In the present study, we tried to identify the mRNA that can be preferentially translated under severe ethanol stress. BTN2 encodes a v-SNARE binding protein, and its null mutant shows hypersensitivity to ethanol. We found that BTN2 mRNA was efficiently translated under severe ethanol stress but not under mild ethanol stress. Moreover, the increased Btn2 protein levels caused by severe ethanol stress were smoothly decreased with the elimination of ethanol stress. These findings suggested that severe ethanol stress extensively induced BTN2 expression. Further, the BTN2 promoter induced protein synthesis of non-native genes such as CUR1, GIC2, and YUR1 in the presence of high ethanol concentrations, indicating that this promoter overcame severe ethanol stress-induced translation repression. Thus, our findings provide an important clue about yeast response to severe ethanol stress and suggest that the BTN2 promoter can be used to improve the efficiency of ethanol production and stress tolerance of yeast cells by modifying gene expression in the presence of high ethanol concentration. PMID:27602028

  12. The role of influenza in the epidemiology of pneumonia.

    PubMed

    Shrestha, Sourya; Foxman, Betsy; Berus, Joshua; van Panhuis, Willem G; Steiner, Claudia; Viboud, Cécile; Rohani, Pejman

    2015-01-01

    Interactions arising from sequential viral and bacterial infections play important roles in the epidemiological outcome of many respiratory pathogens. Influenza virus has been implicated in the pathogenesis of several respiratory bacterial pathogens commonly associated with pneumonia. Though clinical evidence supporting this interaction is unambiguous, its population-level effects-magnitude, epidemiological impact and variation during pandemic and seasonal outbreaks-remain unclear. To address these unknowns, we used longitudinal influenza and pneumonia incidence data, at different spatial resolutions and across different epidemiological periods, to infer the nature, timing and the intensity of influenza-pneumonia interaction. We used a mechanistic transmission model within a likelihood-based inference framework to carry out formal hypothesis testing. Irrespective of the source of data examined, we found that influenza infection increases the risk of pneumonia by ~100-fold. We found no support for enhanced transmission or severity impact of the interaction. For model-validation, we challenged our fitted model to make out-of-sample pneumonia predictions during pandemic and non-pandemic periods. The consistency in our inference tests carried out on several distinct datasets, and the predictive skill of our model increase confidence in our overall conclusion that influenza infection substantially enhances the risk of pneumonia, though only for a short period. PMID:26486591

  13. The role of influenza in the epidemiology of pneumonia

    PubMed Central

    Shrestha, Sourya; Foxman, Betsy; Berus, Joshua; van Panhuis, Willem G.; Steiner, Claudia; Viboud, Cécile; Rohani, Pejman

    2015-01-01

    Interactions arising from sequential viral and bacterial infections play important roles in the epidemiological outcome of many respiratory pathogens. Influenza virus has been implicated in the pathogenesis of several respiratory bacterial pathogens commonly associated with pneumonia. Though clinical evidence supporting this interaction is unambiguous, its population-level effects—magnitude, epidemiological impact and variation during pandemic and seasonal outbreaks—remain unclear. To address these unknowns, we used longitudinal influenza and pneumonia incidence data, at different spatial resolutions and across different epidemiological periods, to infer the nature, timing and the intensity of influenza-pneumonia interaction. We used a mechanistic transmission model within a likelihood-based inference framework to carry out formal hypothesis testing. Irrespective of the source of data examined, we found that influenza infection increases the risk of pneumonia by ~100-fold. We found no support for enhanced transmission or severity impact of the interaction. For model-validation, we challenged our fitted model to make out-of-sample pneumonia predictions during pandemic and non-pandemic periods. The consistency in our inference tests carried out on several distinct datasets, and the predictive skill of our model increase confidence in our overall conclusion that influenza infection substantially enhances the risk of pneumonia, though only for a short period. PMID:26486591

  14. Motility of Mycoplasma pneumoniae.

    PubMed Central

    Radestock, U; Bredt, W

    1977-01-01

    Cell of Mycoplasma pneumoniae FH gliding on a glass surface in liquid medium were examined by microscopic observation and quantitatively by microcinematography (30 frames per min). Comparisons were made only within the individual experiments. The cells moved in an irregular pattern with numerous narrow bends and circles. They never changed their leading end. The average speed (without pauses) was relatively constant between o.2 and 0.5 mum/s. The maximum speed was about 1.5 to 2.0 mum/s. The movements were interrupted by resting periods of different lengths and frequency. Temperature, viscosity, pH, and the presence of yeast extract in the medium influenced the motility significantly; changes in glucose, calcium ions, and serum content were less effective. The movements were affected by iodoacetate, p-mercuribenzoate, and mitomycin C at inhibitory or subinhibitory concentrations. Sodium fluoride, sodium cyanide, dinitrophenol, chloramphenicol, puromycin, cholchicin, and cytochalasin B at minimal inhibitory concentrations did not affect motility. The movements were effectively inhibited by anti-M. pneumoniae antiserum. Studies with absorbed antiserum suggested that the surface components involved in motility are heat labile. The gliding of M. pneumoniae cells required an intact energy metabolism and the proteins involved seemed to have a low turnover. Images PMID:14925

  15. Hypervirulent (hypermucoviscous) Klebsiella pneumoniae

    PubMed Central

    Shon, Alyssa S.; Bajwa, Rajinder P.S.; Russo, Thomas A.

    2013-01-01

    A new hypervirulent (hypermucoviscous) variant of Klebsiella pneumoniae has emerged. First described in the Asian Pacific Rim, it now increasingly recognized in Western countries. Defining clinical features are the ability to cause serious, life-threatening community-acquired infection in younger healthy hosts, including liver abscess, pneumonia, meningitis and endophthalmitis and the ability to metastatically spread, an unusual feature for enteric Gram-negative bacilli in the non-immunocompromised. Despite infecting a healthier population, significant morbidity and mortality occurs. Although epidemiologic features are still being defined, colonization, particularly intestinal colonization, appears to be a critical step leading to infection. However the route of entry remains unclear. The majority of cases described to date are in Asians, raising the issue of a genetic predisposition vs. geospecific strain acquisition. The traits that enhance its virulence when compared with “classical” K. pneumoniae are the ability to more efficiently acquire iron and perhaps an increase in capsule production, which confers the hypermucoviscous phenotype. An objective diagnostic test suitable for routine use in the clinical microbiology laboratory is needed. If/when these strains become increasingly resistant to antimicrobials, we will be faced with a frightening clinical scenario. PMID:23302790

  16. Modulation of Paired Immunoglobulin-Like Type 2 Receptor Signaling Alters the Host Response to Staphylococcus aureus-Induced Pneumonia ▿ †

    PubMed Central

    Banerjee, Antara; Stevenaert, Frederik; Pande, Kalyan; Haghjoo, Erik; Antonenko, Svetlana; Gorman, Dan M.; Sathe, Manjiri; McClanahan, Terrill K.; Pierce, Robert; Turner, Scott P.; Bigler, Michael E.; Phillips, Joseph H.; Heyworth, Paul G.

    2010-01-01

    Paired immunoglobulin-like type 2 receptors (PILRs) inhibitory PILRα and activating PILRβ are predominantly expressed on myeloid cells. Their functions in host defense and inflammation are largely unknown, and in this study, we evaluated their roles in an acute Staphylococcus aureus pneumonia model. Compared to their respective controls, Pilrb−/− mice or mice in which PILRα was activated with an agonistic antibody showed improved clearance of pulmonary staphylococci and improved survival. These mice had reduced serum or bronchoalveolar lavage fluid levels of interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), and IL-6 and elevated levels of gamma interferon (IFN-γ), IL-12, and IL-10. In contrast, mice in which PILRβ was activated had increased lung bacterial burdens and higher mortality coupled with an intense proinflammatory response with highly elevated levels of IL-1β, TNF-α, and IL-6. Treatment groups with reduced bacterial burdens had higher levels of Keratinocyte-derived chemokine (KC), macrophage inflammatory protein 2 (MIP-2), and MIP-1α in bronchoalveolar lavage fluid and an increased influx of neutrophils and macrophages to the lungs. Consistent with our in vivo findings, bone marrow-derived macrophages from Pilrb−/− mice released significantly less IL-1β and TNF-α and more IFN-γ and IL-12 than did the wild-type macrophages when directly stimulated with heat-killed S. aureus. To our knowledge, this is the first evidence that S. aureus directly interacts with PILRβ. It provides a mechanism by which manipulating the balance in favor of an inhibitory PILR signal, by activation of PILRα or deletion of PILRβ, helps to control acute S. aureus-mediated pneumonia and attenuate the inflammatory response. These results highlight the importance of PILRs in innate immunity and the control of inflammation. PMID:20065029

  17. Pulmonary Vein Stenosis Mimicking Nonspecific Interstitial Pneumonia

    PubMed Central

    Linga, Karthika R.; Khoor, Andras; Phelan, Jonathan A.; Mira-Avendano, Isabel

    2015-01-01

    Pulmonary vein stenosis (PVS) is a known complication after catheter ablation of arrhythmias. Surprisingly, little information is available on its manifestations in the lung. We describe the case of a 39-year-old woman who presented from an outside hospital with worsening shortness of breath after catheter ablation of pulmonary veins for atrial fibrillation. After an initial diagnosis of pneumonia and its nonimprovement with antibiotics, a surgical lung biopsy was done and interpreted as nonspecific interstitial pneumonia (NSIP) with vascular changes consistent with pulmonary arterial hypertension. Later, she was admitted to our institution where a transthoracic echocardiogram (TTE) and subsequent computed tomography (CT) angiogram of the heart showed severe stenosis of all four pulmonary veins. The previous lung biopsy was rereviewed and reinterpreted as severe parenchymal congestion mimicking NSIP. Our case demonstrates that PVS is an underrecognized complication of catheter ablation, and increased awareness among both clinicians and pathologists is necessary to avoid misdiagnosis. PMID:26779359

  18. Streptococcus pneumoniae-associated pneumonia complicated by purulent pericarditis: case series *

    PubMed Central

    Cillóniz, Catia; Rangel, Ernesto; Barlascini, Cornelius; Piroddi, Ines Maria Grazia; Torres, Antoni; Nicolini, Antonello

    2015-01-01

    Abstract Objective: In the antibiotic era, purulent pericarditis is a rare entity. However, there are still reports of cases of the disease, which is associated with high mortality, and most such cases are attributed to delayed diagnosis. Approximately 40-50% of all cases of purulent pericarditis are caused by Gram-positive bacteria, Streptococcus pneumoniae in particular. Methods: We report four cases of pneumococcal pneumonia complicated by pericarditis, with different clinical features and levels of severity. Results: In three of the four cases, the main complication was cardiac tamponade. Microbiological screening (urinary antigen testing and pleural fluid culture) confirmed the diagnosis of severe pneumococcal pneumonia complicated by purulent pericarditis. Conclusions: In cases of pneumococcal pneumonia complicated by pericarditis, early diagnosis is of paramount importance to avoid severe hemodynamic compromise. The complications of acute pericarditis appear early in the clinical course of the infection. The most serious complications are cardiac tamponade and its consequences. Antibiotic therapy combined with pericardiocentesis drastically reduces the mortality associated with purulent pericarditis. PMID:26398760

  19. A cohort study of bacteremic pneumonia

    PubMed Central

    Guillamet, Cristina Vazquez; Vazquez, Rodrigo; Noe, Jonas; Micek, Scott T.; Kollef, Marin H.

    2016-01-01

    Abstract Bacteremic pneumonia is usually associated with greater mortality. However, risk factors associated with hospital mortality in bacteremic pneumonia are inadequately described. The study was a retrospective cohort study, conducted in Barnes-Jewish Hospital (2008–2015). For purposes of this investigation, antibiotic susceptibility was determined according to ceftriaxone susceptibility, as ceftriaxone represents the antimicrobial agent most frequently recommended for hospitalized patients with community-acquired pneumonia as opposed to nosocomial pneumonia. Two multivariable analyses were planned: the first model included resistance to ceftriaxone as a variable, whereas the second model included the various antibiotic-resistant species (methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Enterobacteriaceae). In all, 1031 consecutive patients with bacteremic pneumonia (mortality 37.1%) were included. The most common pathogens associated with infection were S aureus (34.1%; methicillin resistance 54.0%), Enterobacteriaceae (28.0%), P aeruginosa (10.6%), anaerobic bacteria (7.3%), and Streptococcus pneumoniae (5.6%). Compared with ceftriaxone-susceptible pathogens (46.8%), ceftriaxone-resistant pathogens (53.2%) were significantly more likely to receive inappropriate initial antibiotic treatment (IIAT) (27.9% vs 7.1%; P < 0.001) and to die during hospitalization (41.5% vs 32.0%; P = 0.001). The first logistic regression analysis identified IIAT with the greatest odds ratio (OR) for mortality (OR 2.2, 95% confidence interval [CI] 1.5–3.2, P < 0.001). Other independent predictors of mortality included age, mechanical ventilation, immune suppression, prior hospitalization, prior antibiotic administration, septic shock, comorbid conditions, and severity of illness. In the second multivariable analysis that included the antibiotic-resistant species, IIAT was still associated with excess mortality, and P aeruginosa infection was

  20. Traditional Chinese medicine, Qing Ying Tang, ameliorates the severity of acute lung injury induced by severe acute pancreatitis in rats via the upregulation of aquaporin-1

    PubMed Central

    GAO, ZHENMING; XU, JUNFENG; SUN, DEGUANG; ZHANG, RIXIN; LIANG, RUI; WANG, LIMING; FAN, RONG

    2014-01-01

    Aquaporin-1 (AQP-1) is expressed in lung endothelial cells and regulates water transport; thus, AQP-1 plays an important role in a number of edema-associated lung diseases. Qing Yin Tang (QYT), a traditional Chinese medicine, has been shown to effectively reduce the mortality rate of acute lung injury (ALI) induced by severe acute pancreatitis (SAP). The current study aimed to investigate the detailed mechanisms underlying the effects of QYT on ALI induced by SAP, particularly the effects on the expression levels of AQP-1 in the lung tissue. ALI was established in Wister rats who were subsequently divided into four groups: SHAM, ALI, dexamethasone (DEX) and QYT groups (n=8 per group). In the QYT group, 20 ml/kg QYT was administered by gavage immediately following the induction of SAP. Blood and lung tissues were collected 8 h following the induction of pancreatitis. The lung wet/dry ratio, as well as the levels of blood gases, serum amylase and tumor necrosis factor-α (TNF-α), were measured at 4, 8 and 12 h following SAP-associated ALI induction surgery. The expression levels of AQP-1 in the lung tissue were detected by quantitative polymerase chain reaction, immunohistochemistry and western blot analysis. No statistically significant differences were observed with regard to the levels of serum amylase, wet/dry ratio, partial pressure of oxygen, serum TNF-α and pathological changes in the pulmonary tissue between the QYT and DEX groups; however, a statistically significant difference was observed when compared with the ALI group. The expression levels of AQP-1 significantly increased (P<0.05) and lung edema was alleviated in the QYT and DEX groups, when compared with ALI group. Therefore, the expression level of AQP-1 is associated with pulmonary edema. QYT protects the lungs from injury induced by SAP via the upregulation of AQP-1, which suppresses TNF-α expression. PMID:25371738

  1. Traditional Chinese medicine, Qing Ying Tang, ameliorates the severity of acute lung injury induced by severe acute pancreatitis in rats via the upregulation of aquaporin-1.

    PubMed

    Gao, Zhenming; Xu, Junfeng; Sun, Deguang; Zhang, Rixin; Liang, Rui; Wang, Liming; Fan, Rong

    2014-12-01

    Aquaporin-1 (AQP-1) is expressed in lung endothelial cells and regulates water transport; thus, AQP-1 plays an important role in a number of edema-associated lung diseases. Qing Yin Tang (QYT), a traditional Chinese medicine, has been shown to effectively reduce the mortality rate of acute lung injury (ALI) induced by severe acute pancreatitis (SAP). The current study aimed to investigate the detailed mechanisms underlying the effects of QYT on ALI induced by SAP, particularly the effects on the expression levels of AQP-1 in the lung tissue. ALI was established in Wister rats who were subsequently divided into four groups: SHAM, ALI, dexamethasone (DEX) and QYT groups (n=8 per group). In the QYT group, 20 ml/kg QYT was administered by gavage immediately following the induction of SAP. Blood and lung tissues were collected 8 h following the induction of pancreatitis. The lung wet/dry ratio, as well as the levels of blood gases, serum amylase and tumor necrosis factor-α (TNF-α), were measured at 4, 8 and 12 h following SAP-associated ALI induction surgery. The expression levels of AQP-1 in the lung tissue were detected by quantitative polymerase chain reaction, immunohistochemistry and western blot analysis. No statistically significant differences were observed with regard to the levels of serum amylase, wet/dry ratio, partial pressure of oxygen, serum TNF-α and pathological changes in the pulmonary tissue between the QYT and DEX groups; however, a statistically significant difference was observed when compared with the ALI group. The expression levels of AQP-1 significantly increased (P<0.05) and lung edema was alleviated in the QYT and DEX groups, when compared with ALI group. Therefore, the expression level of AQP-1 is associated with pulmonary edema. QYT protects the lungs from injury induced by SAP via the upregulation of AQP-1, which suppresses TNF-α expression. PMID:25371738

  2. DO ACUTE PHASE PROTEINS REFLECT SEVERITY OF INFLAMMATION IN RAT MODELS OF POLLUTANT-INDUCED LUNG INJURY?

    EPA Science Inventory

    Title: DO ACUTE PHASE PROTEINS REFLECT THE SEVERITY OF INFLAMMATION IN RAT MODELS OF POLLUTANT-INDUCED LUNG INJURY?

    M. C. Schladweiler, BS 1, P. S. Gilmour, PhD 2, D. L. Andrews, BS 1, D. L. Costa, ScD 1, A. D. Ledbetter, BS 1, K. E. Pinkerton, PhD 3 and U. P. Kodavanti, ...

  3. The Clinical Characteristics and Predictors of Refractory Mycoplasma pneumoniae Pneumonia in Children

    PubMed Central

    Zhang, Yuanyuan; Zhou, Yunlian; Li, Shuxian; Yang, Dehua; Wu, Xiling; Chen, Zhimin

    2016-01-01

    Objective To analyze the clinical characteristics of refracory Mycoplasma pneumoniae pneumonia (RMPP), and explore the related factors predicting RMPP. Methods Retrospective analysis was performed on 634 children with Mycoplasma pneumoniae pneumonia (MPP) hospitalized in our hospital between January 1, 2011 and December 31, 2014. The clinical features, laboratory data, radiological findings between the RMPP group and the general Mycoplasma pneumoniae pneumonia (GMPP) group were compared and the predictive values of related factors were analyzed. Results The median age of the RMPP patients (n = 145) was much older than that of the GMPP patients (n = 489) (P<0.01). We also found more severe presentations, higher incidence of extra-pulmonary complications and more serious radiological findings in RMPP group, which needed oxygen more often, longer antibiotics administration and intensive care (P<0.05). Meanwhile, the levels of C-reactive protein (CRP), lactic dehydrogenase (LDH), immunoglobulin A (IgM), interleukin (IL)-6, IL-10, interferon gamma (IFN-γ) and the percentage of neutrophils, CD8+ in RMPP group were significantly higher than those in GMPP group (P<0.05); while the levels of prealbumin (PAB) were lower than that in GMPP group (P<0.01). In ROC curve analysis, the percentage of neutrophil, CRP, LDH, PAB, IL-6, IL-10 and IFN-γ were useful for differentiating patients with RMPP from those with GMPP. Multiple logistic regression analysis showed that the CRP≥16.5mg/L, LDH ≥417IU/L and IL-6 ≥14.75pg/ml were significant predictors regarding to RMPP. Conclusions CRP≥16.5mg/L, LDH ≥417IU/L and IL-6 ≥14.75pg/ml might be the significant predictors of RMPP in children, which can aid in early recognition of RMPP. PMID:27227519

  4. Neuroprotective effects of bloodletting at Jing points combined with mild induced hypothermia in acute severe traumatic brain injury

    PubMed Central

    Tu, Yue; Miao, Xiao-mei; Yi, Tai-long; Chen, Xu-yi; Sun, Hong-tao; Cheng, Shi-xiang; Zhang, Sai

    2016-01-01

    Bloodletting at Jing points has been used to treat coma in traditional Chinese medicine. Mild induced hypothermia has also been shown to have neuroprotective effects. However, the therapeutic effects of bloodletting at Jing points and mild induced hypothermia alone are limited. Therefore, we investigated whether combined treatment might have clinical effectiveness for the treatment of acute severe traumatic brain injury. Using a rat model of traumatic brain injury, combined treatment substantially alleviated cerebral edema and blood-brain barrier dysfunction. Furthermore, neurological function was ameliorated, and cellular necrosis and the inflammatory response were lessened. These findings suggest that the combined effects of bloodletting at Jing points (20 μL, twice a day, for 2 days) and mild induced hypothermia (6 hours) are better than their individual effects alone. Their combined application may have marked neuroprotective effects in the clinical treatment of acute severe traumatic brain injury. PMID:27482221

  5. Examining Severe Drought-Induced Vegetation Change and its Influence on Water Resources

    NASA Astrophysics Data System (ADS)

    White, A. B.; Springer, E. P.; Vivoni, E. R.

    2007-12-01

    A "global-change-type" drought that occurred in the southwestern U.S. from 2000 to 2003, accompanied by increased temperatures and bark beetle infestations, induced large-scale woodland overstory mortality, the consequent redistribution of water, radiation, and nutrients, as well as modification of the ecosystem phenology. Our objectives in this research are to examine these vegetation changes in detail and to determine whether they translated to changes in hydrological processes. We chose the Rio Ojo Caliente, a subbasin of the Rio Grande, as a study site since a significant portion of the woodland ecosystem (piñon-juniper) was affected. Examining a remotely-sensed vegetation index (1-km AVHRR NDVI from 1989 to 2006), there is an increasing trend in the mean NDVI from 1989 to 1998 (pre-drought period), a decreasing trend from 1999 to 2003 (drought period), and a dramatic increasing trend from 2004 to 2006 (post-drought period) in which the mean NDVI rebounds to pre- drought magnitudes. Streamflow records from 1932 to 2006 show the watershed to be primarily spring snowmelt-driven, although monsoonal summer precipitation also plays a significant role. We compare the temporal variability in the streamflow to the NDVI, including the mean, anomalies from the mean, and seasonally- based duration curves, and find significant correlations (correlation coefficient ρ = -0.61) between the streamflow and NDVI at approximately a three-month lag (NDVI lagging streamflow). In analyzing the three phases of the drought, the correlation is slightly stronger during the pre-drought (ρ = -0.64) and drought (ρ = -0.65) periods, yet markedly stronger during the post-drought period (ρ = -0.74). This suggests that the coupling between vegetation water use and streamflow is tighter after the drought. This may be attributable to the reduction in the less-responsive overstory (pinñon mortality) and increase in the more-responsive understory (grasses and shrubs exploiting newly

  6. Lipoid pneumonia--a case of refractory pneumonia in a child treated with ketogenic diet.

    PubMed

    Buda, Piotr; Wieteska-Klimczak, Anna; Własienko, Anna; Mazur, Agnieszka; Ziołkowski, Jerzy; Jaworska, Joanna; Kościesza, Andrzej; Dunin-Wąsowicz, Dorota; Książyk, Janusz

    2013-01-01

    Lipoid pneumonia (LP) is a chronic inflammation of the lung parenchyma with interstitial involvement due to the accumulation of endogenous or exogenous lipids. Exogenous LP (ELP) is associated with the aspiration or inhalation of oil present in food, oil-based medications or radiographic contrast media. The clinical manifestations of LP range from asymptomatic cases to severe pulmonary involvement, with respiratory failure and death, according to the quantity and duration of the aspiration. The diagnosis of exogenous lipoid pneumonia is based on a history of exposure to oil and the presence of lipid-laden macrophages on sputum or bronchoalveolar lavage (BAL) analysis. High-resolution computed tomography (HRCT) is the imaging technique of choice for evaluation of patients with suspected LP. The best therapeutic strategy is to remove the oil as early as possible through bronchoscopy with multiple BALs and interruption in the use of mineral oil. Steroid therapy remains controversial, and should be reserved for severe cases. We describe a case of LP due to oil aspiration in 3-year-old girl with intractable epilepsy on ketogenic diet. Diagnostic problems were due to non-specific symptoms that were mimicking serious infectious pneumonia. A high index of suspicion and precise medical history is required in cases of refractory pneumonia and fever unresponsive to conventional therapy. Gastroesophageal reflux and a risk of aspiration may be regarded as relative contraindications to the ketogenic diet. Conservative treatment, based on the use of oral steroids, proved to be an efficient therapeutic approach in this case. PMID:23996884

  7. A review of factors influencing the incidence and severity of plaque-induced gingivitis.

    PubMed

    Trombelli, L; Farina, R

    2013-06-01

    An individual variation in the gingival inflammatory response to the dental biofilm has been demonstrated. This variability can be observed between individuals with neither quantitative nor qualitative differences in plaque accumulation. The reported significant differences in gingival inflammatory response under quantitatively and/or qualitatively almost identical bacterial challenge suggest that the gingival response to plaque accumulation may be an individual trait, possibly genetic in origin. The most recent classification of periodontal diseases acknowledges that the clinical expression of plaque-induced gingival inflammation can be substantially modified by systemic factors, either inherent to the host or related to environmental influences. The aim of the present literature review is to describe (i) the factors influencing the development of plaque-induced gingivitis as well as (ii) those metabolic, environmental and systemic factors which have a direct impact on the etiopathogenetic pathway of plaque-induced gingivitis, thus altering the nature or course of the gingival inflammatory response to dental biofilm. PMID:23828258

  8. ACE2 Decreases Formation and Severity of Angiotensin II-induced Abdominal Aortic Aneurysms

    PubMed Central

    Thatcher, Sean E.; Zhang, Xuan; Howatt, Deborah A.; Yiannikouris, Frederique; Gurley, Susan B.; Ennis, Terri; Curci, John A.; Daugherty, Alan; Cassis, Lisa A.

    2014-01-01

    Objective Angiotensin converting enzyme 2 (ACE2) cleaves angiotensin II (AngII) to form angiotensin-(1-7) (Ang-(1-7)), which generally opposes effects of AngII. AngII infusion into hypercholesterolemic male mice induces formation of abdominal aortic aneurysms (AAAs). This study tests the hypothesis that deficiency of ACE2 promotes AngII-induced AAAs, while ACE2 activation suppresses aneurysm formation. Approach and Results ACE2 protein was detectable by immunostaining in mice and human AAAs. Whole body deficiency of ACE2 significantly increased aortic lumen diameters and external diameters of suprarenal aortas from AngII-infused mice. Conversely, ACE2 deficiency in bone marrow-derived cells had no effect on AngII-induced AAAs. In contrast to AngII-induced AAAs, ACE2 deficiency had no significant effect on external aortic diameters of elastase-induced AAAs. Since ACE2 deficiency promoted AAA formation in AngII-infused mice, we determined if ACE2 activation suppressed AAAs. ACE2 activation by administration of diminazine aceturate (DIZE, 30 mg/kg/day) to Ldlr−/− mice increased kidney ACE2 mRNA abundance and activity and elevated plasma Ang-(1-7) concentrations. Unexpectedly, administration of DIZE significantly reduced total sera cholesterol and VLDL-cholesterol concentrations. Notably, DIZE significantly decreased aortic lumen diameters and aortic external diameters of AngII-infused mice resulting in a marked reduction in AAA incidence (from 73 to 29%). None of these effects of DIZE were observed in the Ace2−/y mice. Conclusions These results demonstrate that ACE2 exerts a modulatory role in AngII-induced AAA formation, and that therapeutic stimulation of ACE2 could be a benefit to reduce AAA expansion and rupture in patients with an activated renin-angiotensin system. PMID:25301841

  9. Community-acquired pneumonia related to intracellular pathogens.

    PubMed

    Cillóniz, Catia; Torres, Antoni; Niederman, Michael; van der Eerden, Menno; Chalmers, James; Welte, Tobias; Blasi, Francesco

    2016-09-01

    Community-acquired pneumonia (CAP) is associated with high rates of morbidity and mortality worldwide; the annual incidence of CAP among adults in Europe has ranged from 1.5 to 1.7 per 1000 population. Intracellular bacteria are common causes of CAP. However, there is considerable variation in the reported incidence between countries and change over time. The intracellular pathogens that are well established as causes of pneumonia are Legionella pneumophila, Mycoplasma pneumoniae, Chlamydophila pneumoniae, Chlamydophila psittaci, and Coxiella burnetii. Since it is known that antibiotic treatment for severe CAP is empiric and includes coverage of typical and atypical pathogens, microbiological diagnosis bears an important relationship to prognosis of pneumonia. Factors such as adequacy of initial antibiotic or early de-escalation of therapy are important variables associated with outcomes, especially in severe cases. Intracellular pathogens sometimes appear to cause more severe disease with respiratory failure and multisystem dysfunction associated with fatal outcomes. The clinical relevance of intracellular pathogens in severe CAP has not been specifically investigated. We review the prevalence, general characteristics, and outcomes of severe CAP cases caused by intracellular pathogens. PMID:27276986

  10. Spatio-temporal dynamics of pneumonia in bighorn sheep

    USGS Publications Warehouse

    Cassirer, E. Frances; Plowright, Raina K.; Manlove, Kezia R.; Cross, Paul C.; Dobson, Andrew P.; Potter, Kathleen A.; Hudson, Peter J.

    2013-01-01

    Bighorn sheep mortality related to pneumonia is a primary factor limiting population recovery across western North America, but management has been constrained by an incomplete understanding of the disease. We analysed patterns of pneumonia-caused mortality over 14 years in 16 interconnected bighorn sheep populations to gain insights into underlying disease processes. 2. We observed four age-structured classes of annual pneumonia mortality patterns: all-age, lamb-only, secondary all-age and adult-only. Although there was considerable variability within classes, overall they differed in persistence within and impact on populations. Years with pneumonia-induced mortality occurring simultaneously across age classes (i.e. all-age) appeared to be a consequence of pathogen invasion into a naïve population and resulted in immediate population declines. Subsequently, low recruitment due to frequent high mortality outbreaks in lambs, probably due to association with chronically infected ewes, posed a significant obstacle to population recovery. Secondary all-age events occurred in previously exposed populations when outbreaks in lambs were followed by lower rates of pneumonia-induced mortality in adults. Infrequent pneumonia events restricted to adults were usually of short duration with low mortality. 3. Acute pneumonia-induced mortality in adults was concentrated in fall and early winter around the breeding season when rams are more mobile and the sexes commingle. In contrast, mortality restricted to lambs peaked in summer when ewes and lambs were concentrated in nursery groups. 4. We detected weak synchrony in adult pneumonia between adjacent populations, but found no evidence for landscape-scale extrinsic variables as drivers of disease. 5. We demonstrate that there was a >60% probability of a disease event each year following pneumonia invasion into bighorn sheep populations. Healthy years also occurred periodically, and understanding the factors driving these

  11. Severe morbidities associated with induced abortions among misoprostol users and non-users in a tertiary public hospital in Ghana

    PubMed Central

    2014-01-01

    Background Misoprostol has become a popular over the counter self-administered abortifacient in Ghana. This study aimed to compare the socio-demographic characteristics and clinical complications associated with misoprostol and non-misoprostol induced