Science.gov

Sample records for pneumonia induced severe

  1. [Severe haemolysis caused by Mycoplasma pneumoniae].

    PubMed

    Bohr, Anne Lisbeth; Aagaard, Thomas Granum; Birgens, Henrik; Søborg, Christian

    2015-10-01

    Mycoplasma pneumoniae is naturally resistant to betalactamase antibiotics but is sensitive to macrolides. Occasionally, infections with M. pneumoniae can lead to severe anaemia due to its ability to cause haemolysis when cold agglutination occurs. Increasing bacterial resistance to macrolid antibiotics is a growing concern worldwide. We present two cases where infection with M. pneumoniae caused severe haemolysis, one of which was macrolide-resistant.

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

    PubMed

    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 results

  4. [Severe community-acquired pneumonia in adults].

    PubMed

    Arancibia H, Francisco; Díaz P, Orlando

    2005-01-01

    Patients with severe community acquired pneumonia (CAP) need continuous surveillance and monitoring at intensive care units (ICU), where they can receive specialized support as mechanical ventilation and/or hemodynamic support. Patients that require ICU admittance represent 10 to 30% of all patients interned because a pneumonia. In this category, high complication rate, prolonged hospital stay and high mortality rate are the rule. The American Thoracic Society (ATS) criteria for severe pneumonia establishes the following main criteria: necessity of mechanical ventilation and presence of septic shock; minor criteria: systolic blood pressure < 90 mmHg, radiological multilobar involvement and PaO2/FiO2 < 250 mmHg. British Thoracic Society (BTS) criteria for severe CAP are: respiratory rate over 30 breaths/min, diastolic blood pressure under 60 mmHg, BUN > 20 mg/dl and mental confusion. In all patients with CAP it is recommended the evaluation of its severity at admission. This evaluation should be done in conjunction with an experienced physician, and if criteria for poor prognosis are met, an early admission to ICU is recommended. ATS and BTS modified criteria (CURB) are useful in this procedure. In severely ill patients with CAP it is recommended to perform the following microbiological analysis: sputum Gram stain and culture, blood culture, pleural fluid Gram stain and culture, if present and tapped, Legionella pneumophila urine antigen test, influenza A and B antigen detection tests (epidemic period: autumn and winter), and serology for atypical bacteria (Mycoplasma pneumoniae and Chlamydia pneumoniae).

  5. Eosinophilic pneumonia induced by daptomycin.

    PubMed

    Hayes, Don; Anstead, Michael I; Kuhn, Robert J

    2007-04-01

    We present a case of drug-induced eosinophilic pneumonia resulting from intravenous daptomycin being used as therapy for recurrent methicillin-sensitive Staphlococcus aureus endocarditis. The patient developed hypoxic respiratory failure requiring intubation and mechanical ventilation. Daptomycin therapy was discontinued immediately, and the patient improved significantly after the administration of intravenous corticosteroids allowing for extubation 3 days later.

  6. 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

  7. Barium sulfate aspiration: Severe chemical pneumonia induced by a massive reflux of contrast medium during small bowel barium enema.

    PubMed

    Zhang, Lin; Yang, Yi; Zhang, Ji; Zhou, Xiaowei; Dong, Hongmei; Zhou, Yiwu

    2015-08-01

    Barium contrast radiography is a conventional procedure aimed at revealing lesions of the alimentary tract using barium sulfate on X-ray irradiation. Although it is widely used in clinics, adverse effects and complications are observed, such as anaphylaxis, granuloma, fecalithes, abdomen-leaking, embolism, bacterial contamination, and aspiration. We report a case of death due to a massive barium sulfate aspiration resulted from an air-barium double contrast enema radiography. A 25-year-old female patient was hospitalized with symptoms of abdominal distention, nausea, vomiting and diarrhea for three days. A progressive respiratory distress presented only 1h after a small bowel air-barium double contrast enema. The patient died 11h later. The result of autopsy revealed the cause of death to be severe chemical pneumonitis induced by gastric fluid which was aspirated into her lungs. Barium sulfate is generally recognized to be chemically inert for the respiratory system, but a mixture of barium sulfate with gastric contents is fatal. Here we intend to suggest that, when determining the potential cause of death, medical examiners should consider a patient's status quo as well as the possible adverse effects and complications caused by the barium sulfate preparation during gastrointestinal radiography.

  8. Inhibition of pulmonary nuclear factor kappa-B decreases the severity of acute Escherichia coli pneumonia but worsens prolonged pneumonia

    PubMed Central

    2013-01-01

    Introduction Nuclear factor (NF)-κB is central to the pathogenesis of inflammation in acute lung injury, but also to inflammation resolution and repair. We wished to determine whether overexpression of the NF-κB inhibitor IκBα could modulate the severity of acute and prolonged pneumonia-induced lung injury in a series of prospective randomized animal studies. Methods Adult male Sprague-Dawley rats were randomized to undergo intratracheal instillation of (a) 5 × 109 adenoassociated virus (AAV) vectors encoding the IκBα transgene (5 × 109 AAV-IκBα); (b) 1 × 1010 AAV-IκBα; (c) 5 × 1010 AAV-IκBα; or (d) vehicle alone. After intratracheal inoculation with Escherichia coli, the severity of the lung injury was measured in one series over a 4-hour period (acute pneumonia), and in a second series after 72 hours (prolonged pneumonia). Additional experiments examined the effects of IκBα and null-gene overexpression on E. coli-induced and sham pneumonia. Results In acute pneumonia, IκBα dose-dependently decreased lung injury, improving arterial oxygenation and lung static compliance, reducing alveolar protein leak and histologic injury, and decreasing alveolar IL-1β concentrations. Benefit was maximal at the intermediate (1 × 1010) IκBα vector dose; however, efficacy was diminished at the higher (5 × 1010) IκBα vector dose. In contrast, IκBα worsened prolonged pneumonia-induced lung injury, increased lung bacterial load, decreased lung compliance, and delayed resolution of the acute inflammatory response. Conclusions Inhibition of pulmonary NF-κB activity reduces early pneumonia-induced injury, but worsens injury and bacterial load during prolonged pneumonia. PMID:23622108

  9. Towards a sensible comprehension of severe community-acquired pneumonia.

    PubMed

    Ewig, Santiago; Woodhead, Mark; Torres, Antoni

    2011-02-01

    Four different rules have been suggested and validated for intensive care unit (ICU) admission for community-acquired pneumonia: modified American Thoracic Society (ATS) rule, Infectious Diseases Society of America (IDSA)/ATS rule, España rule, and SMART-COP. Their performance varies, with sensitivity of around 70% and specificity of around 80-90%. Only negative predictive values are consistently high. Critical methodological issues include the appropriate reference for derivation, the populations studied, the variables included, and the time course of pneumonia. Severe community-acquired pneumonia (SCAP) may evolve because of acute respiratory failure or/and severe sepsis/septic shock. Pneumonia-related complications and decompensated comorbidities may be additional or independent reasons for a severe course. All variables included in predictive rules relate to the two principal reasons for SCAP. However, taken as major criteria, they are of little value for clinical assessment. Instead, a limited set of minor criteria reflecting severity seems appropriate. However, predictive rules may not meet principal needs of severity assessment because of failure in sensitivity, ignorance of the potential contribution of complications or decompensated comorbidity to pneumonia severity, and poor sensitivity for the lower extreme in the spectrum of severe pneumonia, i.e., patients at risk of SCAP. We therefore advocate an approach that refers to the evaluation of the need for intensified treatment rather than ICU, based on a set of minor criteria and sensitive to the dynamic nature of pneumonia. Intensified treatment such as monitoring and treatment of acute respiratory failure or/and severe sepsis/septic shock is thought to improve management and possibly outcomes by setting the focus on both patients with severity criteria at admission and those at risk for SCAP.

  10. [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.

  11. 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

  12. Setting a standard for the initiation of steroid therapy in refractory or severe Mycoplasma pneumoniae pneumonia in adolescents and adults.

    PubMed

    Miyashita, Naoyuki; Kawai, Yasuhiro; Inamura, Norikazu; Tanaka, Takaaki; Akaike, Hiroto; Teranishi, Hideto; Wakabayashi, Tokio; Nakano, Takashi; Ouchi, Kazunobu; Okimoto, Niro

    2015-03-01

    Serum interleukin (IL)-18 level was thought to be a useful as a predictor of refractory or severe Mycoplasma pneumoniae pneumonia, and steroid administration is reported to be effective in this situation. The serum levels of IL-18 correlated significantly with those of lactate dehydrogenase (LDH). The purpose of this study was to set a standard for the initiation of steroid therapy in M. pneumoniae pneumonia using a simple serum marker. We analyzed 41 adolescent and adult patients with refractory or severe M. pneumoniae pneumonia who received steroid therapy, and compared them with 108 patients with M. pneumoniae pneumonia who responded to treatment promptly (control group). Serum LDH levels were significantly higher in the refractory and severe group than in the control group at the initiation of steroid therapy (723 vs 210 IU/L, respectively; p < 0.0001). From receiver operating characteristic curve analysis, we calculated serum LDH cut-off levels of 364 IU/L at initiation of steroid therapy and 302 IU/L at 1-3 days before the initiation of steroid therapy. The administration of steroids to patients in the refractory and severe group resulted in the rapid improvement of symptoms and a decrease in serum LDH levels in all patients. Serum LDH level can be used as a useful parameter to determine the initiation of steroid therapy in refractory or severe M. pneumoniae pneumonia. A serum LDH level of 302-364 IU/L seems to be an appropriate criterion for the initiation of steroid therapy.

  13. 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 ...

  14. Resveratrol ameliorates Serratia marcescens-induced acute pneumonia in rats.

    PubMed

    Lu, Chia-Chen; Lai, Hsin-Chih; Hsieh, Shang-Chen; Chen, Jan-Kan

    2008-04-01

    Serratia marcescens is an important nosocomial pathogen, which has been especially problematic as a cause of hospital-acquired pneumonia in the past two decades. Treatment of S. marcescens-related infections has been limited by emergence of multiple drug-resistant strains. Thus, the development of alternative agents for the prevention and treatment of Serratia infection is urgently needed. Resveratrol (RSV) is a compound with diverse biological effects including anti-cancer, anti-inflammation, anti-diabetes, and cancer chemoprevention. Whether RSV has in vivo prophylactic or therapeutic potential against infection remains uncharacterized. In the present study, we used a murine acute pneumonia model initiated by intratracheal application of S. marcescens to evaluate whether RSV possesses anti-infection properties. We showed that pretreatment with RSV for 3 days markedly increased alveolar macrophage infiltration, elevated NK cell activity, and decreased bacterial burden in the infected lung with a subsequent decrease in mortality. These effects were associated with significantly less-severe inflammatory phenotypes in lung tissue and bronchoalveolar lavage fluid, including reduced neutrophil infiltration of the lungs, reduced phagocytosis activity, and reduced secretion of cytokines such as TNF-alpha, IL-1beta, and IL-6. To further characterize the underlying mechanism responsible for these effects of RSV, LPS derived from S. marcescens was used to induce acute pneumonia in rats, with or without RSV pretreatment. RSV was shown to ameliorate acute pneumonia via inhibition of the NF-kappaB signaling pathway, including inhibition of IkappaBalpha phosphorylation and subsequent NF-kappaB activation. These findings suggest that RSV might be beneficial as a prophylactic treatment in patients at risk of an episode of S. marcescens-induced acute pneumonia.

  15. Household costs for treatment of severe pneumonia in Pakistan.

    PubMed

    Sadruddin, Salim; Shehzad, Shafqat; Bari, Abdul; Khan, Attaullah; Ibad-ul-Haque; Khan, Amanullah; Qazi, Shamim

    2012-11-01

    Current World Health Organization (WHO) guidelines for severe pneumonia treatment of under-5 children recommend hospital referral. However, high treatment cost is a major barrier for communities. We compared household costs for referred cases with management by lady health workers (LHWs) using oral antibiotics. This study was nested within a cluster randomized trial in Haripur, Pakistan. Data on direct and indirect costs were collected through interviews and record reviews in the 14 intervention and 14 control clusters. The average household cost/case for a LHW managed case was $1.46 compared with $7.60 for referred cases. When the cost of antibiotics provided by the LHW program was excluded from the estimates, the cost/case came to $0.25 and $7.51 for the community managed and referred cases, respectively, a 30-fold difference. Expanding severe pneumonia treatment with oral amoxicillin to community level could significantly reduce household costs and improve access to the underprivileged population, preventing many child deaths.

  16. Antimicrobial and immunologic activities of clarithromycin in a murine model of Mycoplasma pneumoniae-induced pneumonia.

    PubMed

    Hardy, Robert D; Rios, Ana Maria; Chavez-Bueno, Susana; Jafri, Hasan S; Hatfield, Jeanine; Rogers, Beverly B; McCracken, George H; Ramilo, Octavio

    2003-05-01

    Because macrolide antibiotics are hypothesized to possess immunomodulatory activity independent of their antimicrobial activity, we evaluated the immunomodulatory effect of clarithromycin in a murine model of lung inflammation induced by either live or UV-killed Mycoplasma pneumoniae. BALB/c mice were intranasally inoculated once with live or UV-killed M. pneumoniae. Clarithromycin (25 mg/kg of body weight) or placebo was subcutaneously administered once daily in both groups of mice. In mice infected with live M. pneumoniae, clarithromycin treatment significantly reduced quantitative M. pneumoniae bronchoalveolar lavage (BAL) culture, pulmonary histopathologic scores (HPS), and airway resistance-obstruction (as measured by plethysmography) compared with placebo. Concentrations of tumor necrosis factor alpha, gamma interferon, interleukin-6 (IL-6), mouse KC (functional IL-8), JE/MCP-1, and MIP-1alpha in BAL fluid were also significantly decreased in mice infected with live M. pneumoniae given clarithromycin. In contrast, mice inoculated with UV-killed M. pneumoniae had no significant reduction in HPS, airway resistance-obstruction, or BAL cytokine or chemokine concentrations in response to clarithromycin administration. Clarithromycin therapy demonstrated beneficial effects (microbiologic, histologic, respiratory, and immunologic) on pneumonia in the mice infected with live M. pneumoniae; this was not observed in the mice inoculated with UV-killed M. pneumoniae.

  17. Klebsiella pneumoniae Siderophores Induce Inflammation, Bacterial Dissemination, and HIF-1α Stabilization during Pneumonia

    PubMed Central

    Holden, Victoria I.; Breen, Paul; Houle, Sébastien; Dozois, Charles M.

    2016-01-01

    ABSTRACT Klebsiella pneumoniae is a Gram-negative pathogen responsible for a wide range of infections, including pneumonia and bacteremia, and is rapidly acquiring antibiotic resistance. K. pneumoniae requires secretion of siderophores, low-molecular-weight, high-affinity iron chelators, for bacterial replication and full virulence. The specific combination of siderophores secreted by K. pneumoniae during infection can impact tissue localization, systemic dissemination, and host survival. However, the effect of these potent iron chelators on the host during infection is unknown. In vitro, siderophores deplete epithelial cell iron, induce cytokine secretion, and activate the master transcription factor hypoxia inducible factor-1α (HIF-1α) protein that controls vascular permeability and inflammatory gene expression. Therefore, we hypothesized that siderophore secretion by K. pneumoniae directly contributes to inflammation and bacterial dissemination during pneumonia. To examine the effects of siderophore secretion independently of bacterial growth, we performed infections with tonB mutants that persist in vivo but are deficient in siderophore import. Using a murine model of pneumonia, we found that siderophore secretion by K. pneumoniae induces the secretion of interleukin-6 (IL-6), CXCL1, and CXCL2, as well as bacterial dissemination to the spleen, compared to siderophore-negative mutants at an equivalent bacterial number. Furthermore, we determined that siderophore-secreting K. pneumoniae stabilized HIF-1α in vivo and that bacterial dissemination to the spleen required alveolar epithelial HIF-1α. Our results indicate that siderophores act directly on the host to induce inflammatory cytokines and bacterial dissemination and that HIF-1α is a susceptibility factor for bacterial invasion during pneumonia. PMID:27624128

  18. 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

  19. 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

  20. Preliminary investigation of a mice model of Klebsiella pneumoniae subsp. ozaenae induced pneumonia.

    PubMed

    Renois, Fanny; Jacques, Jérôme; Guillard, Thomas; Moret, Hélène; Pluot, Michel; Andreoletti, Laurent; de Champs, Christophe

    2011-11-01

    In the present study, we comparatively assessed the pathophysiological mechanisms developed during lung infection of BALB/C female mice infected by an original wild type Klebsiella pneumoniae subsp. ozaenae strain (CH137) or by a referent subspecies K. pneumoniae. subsp. pneumoniae strain (ATCC10031). The mice infected with 2.10⁶ CFU K. p. subsp. pneumoniae (n = 10) showed transient signs of infection and all of them recovered. All of those infected with 1.10⁶ CFU K. p. subsp. ozaenae (n = 10) developed pneumonia within 24 h and died between 48 and 72 h. Few macrophages, numerous polymorphonuclear cells and lymphocytes were observed in their lungs in opposite to K. p. subsp. pneumoniae. In bronchoalveolar lavage, a significant increase in MIP-2, IL-6, KC and MCP-1 levels was only observed in K. p. subsp. ozaenae infected mice whereas high levels of TNF-α were evidenced with the two subspecies. Our findings indicated a lethal effect of a wild type K. p. subsp. ozaenae strain by acute pneumonia reflecting an insufficient alveolar macrophage response. This model might be of a major interest to comparatively explore the pathogenicity of K. p. subsp ozaenae strains and to further explore the physiopathological mechanisms of gram-negative bacteria induced human pneumonia.

  1. 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

  2. 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

  3. 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

  4. Severe pulmonary hypertension in idiopathic nonspecific interstitial pneumonia

    PubMed Central

    Hallowell, Robert W.; Reed, Robert M.; Fraig, Mostafa; Horton, Maureen R.; Girgis, Reda E.

    2012-01-01

    Pulmonary hypertension (PH) is a common complication of interstitial lung disease (ILD), particularly in idiopathic pulmonary fibrosis (IPF) and ILD associated with connective tissue disease, where the underlying pathology is often a nonspecific interstitial pneumonia (NSIP) pattern. The degree of PH in ILD is typically mild to moderate and radiographic changes of ILD are usually prominent. We describe four patients with idiopathic NSIP and severe PH (mPAP > 40 mmHg). The average mean pulmonary artery pressure was 51±7 mmHg and pulmonary vascular resistance was 13±4 Wood's units. Pulmonary function was characterized by mild restriction (total lung capacity 63–94% predicted) and profound reductions in DLCO (19–53% predicted). Computed tomographic imaging revealed minimal to moderate interstitial thickening without honeycombing. In two of the cases, an initial clinical diagnosis of idiopathic pulmonary arterial hypertension was made. Both were treated with intravenous epoprostenol, which was associated with worsening of hypoxemia. All four patients died or underwent lung transplant within 4 years of PH diagnonsis. Lung pathology in all four demonstrated fibrotic NSIP with medial thickening of the small and medium pulmonary arteries, and proliferative intimal lesions that stained negative for endothelial markers (CD31 and CD34) and positive for smooth muscle actin. There were no plexiform lesions. Severe pulmonary hypertension can therefore occur in idiopathic NSIP, even in the absence of advanced radiographic changes. Clinicians should suspect underlying ILD as the basis for PH when DLCO is severely reduced or gas exchange deteriorates with pulmonary vasodilator therapy. PMID:22558525

  5. 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.

  6. 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.

  7. 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) ...

  8. 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

  9. 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

  10. 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

  11. Impact of management guidelines on the outcome of severe community acquired pneumonia

    PubMed Central

    Hirani, N. A.; Macfarlane, J. T.

    1997-01-01

    BACKGROUND: Ten years ago we published a study of 50 adults with severe community acquired pneumonia admitted to our intensive care unit and subsequently introduced guidelines for the management of severe community acquired pneumonia which are largely in accordance with those of the British Thoracic Society. The results of a follow up study are now reported in order to assess their impact on the outcome of this disease. METHODS: Fifty seven cases of severe community acquired pneumonia admitted to our ICU between 1984 and 1993 were studied. Causal pathogens, clinical and laboratory features of severity, antibiotic therapy and mortality were studied and, where possible, compared with results from the previous study. RESULTS: Streptococcus pneumoniae, Legionella pneumophila and Staphylococcus aureus were the most frequent causes of severe community acquired pneumonia, as in the previous study. The intensity of microbial investigation has increased, particularly with regard to pneumococcal and Legionella antigen testing, the latter allowing earlier diagnosis of Legionella infection than previously. In spite of this, no pathogen was identified in 33% of cases compared with 18% previously. Indices of severity of illness were widely recognised, and a decrease in unplanned transfers to the ICU following "unexpected" cardiorespiratory arrest from 25% to 7% (p < 0.02) was found. Antibiotic therapy largely reflected guideline recommendations with 98% receiving a beta-lactam agent and 91% erythromycin. The overall mortality was 58% compared with 54% previously. CONCLUSIONS: Management guidelines for severe community acquired pneumonia have been widely adopted but without a reduction in mortality in our hospital. Factors other than early diagnosis, appropriate antibiotics, or prompt ICU transfer may influence the outcome in severe community acquired pneumonia. 


 PMID:9039234

  12. Pneumonia

    MedlinePlus

    ... better than treating it. Vaccines are available to prevent pneumococcal pneumonia and the flu. Other preventive measures include washing your hands frequently and not smoking. NIH: National Heart, Lung, and Blood Institute

  13. 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

  14. 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

  15. Risk factors for the severity and mortality of pneumococcal pneumonia: Importance of premorbid patients' performance status.

    PubMed

    Ishiguro, Takashi; Kagiyama, Naho; Uozumi, Ryuji; Odashima, Kyuto; Kurashima, Kazuyoshi; Morita, Satoshi; Takayanagi, Noboru

    2016-10-01

    Comorbidity is known to be associated with the severity and mortality of pneumonia. The severity of each underlying disease varies, and performance status, which is known to be a prognostic factor of malignant diseases, reflects the overall patient condition as affected by his/her comorbidity and underlying diseases of various severity. We investigated whether premorbid patients' performance status is associated with the severity and mortality of pneumococcal pneumonia. This retrospective study assessed these factors in hospitalized patients suffering from pneumococcal pneumonia from 2002 to 2015. We included 424 patients aged 68.9 ± 14.1 years in the study, of which 68.9% were men. A multivariate analysis found that advanced age (≥65 years), diabetes mellitus, and poor performance status were independent factors associated with severity, whereas old pulmonary tuberculosis, poor performance status, pneumococcal bacteremia, and severe pneumonia were independent factors that were associated with non-survival. Poor performance status was associated with the severity and mortality of pneumococcal pneumonia. PMID:27593263

  16. [Serrapeptase-induced lung injury manifesting as acute eosiniphilic pneumonia].

    PubMed

    Sasaki, S; Kawanami, R; Motizuki, Y; Nakahara, Y; Kawamura, T; Tanaka, A; Watanabe, S

    2000-07-01

    An 84-year-old man was referred to our hospital because of fever, cough, and hemoptysis. The patient had acute respiratory failure (PaO2 < 40 mmHg) on admission, with diffuse interstitial infiltration and bilateral pleural effusion. The bronchoalveolar lavage fluid was bloody, and contained a high percentage of eosinophils (32%). A diagnosis of acute eosinophilic pneumonia was established, and the patient made a rapid recovery after corticosteroids were administered. When the DLST (drug lymphocyte stimulation test) was performed after the corticosteroid therapy was stopped, it was positive for serrapeptase, which had been prescribed for chronic cystitis for 3 months before the onset of the pneumonia. This was a case of drug (serrapeptase)-induced pneumonitis manifesting as acute eosinophilic pneumonia.

  17. 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

  18. 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

  19. [Case of multiple pulmonary arteriovenous fistulas detected during treatment for severe pneumonia].

    PubMed

    Kyoraku, Yuka; Ashitani, Jun-Ichi; Imazu, Yoshifumi; Fukuyama, Chikara; Miyoshi, Kahori; Kodama, Tsuyoshi; Yanagi, Shigehisa; Matsumoto, Nobuhiro; Nakazato, Masamitsu

    2008-09-01

    A 55-year-old woman who developed severe hypoxemia associated with severe pneumonia was admitted to our hospital for mechanical ventilation. She was treated with antibiotics under a diagnosis of mycoplasma pneumonia. Although most clinical findings improved, hypoxemia remained. As a chest CT film showed multiple nodules and an enhanced CT film revealed arterial filling in the nodules, multiple pulmonary arteriovenous fistulas (PAVFs) were considered to be an underlying cause of hypoxemia. Transcatheter coil embolization for 5 PAVFs, significantly ameliorated hypoxemia in the patient. PAVF is a congenital desease, and in many cases, is asymptomatic. Therefore, it was rare for PAVFs to be detected in a middle-aged patient with prolonged hypoxemia associated with pneumonia. PMID:18939419

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

    PubMed

    Gupta, Arjun; Sen, Shiraj; Naina, Harris

    2016-04-06

    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.

  1. 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

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. Clinical and temporal patterns of severe pneumonia causing critical illness during Hajj

    PubMed Central

    2012-01-01

    Background Pneumonia is a leading cause of hospitalization during Hajj and susceptibility and transmission may be exacerbated by extreme spatial and temporal crowding. We describe the number and temporal onset, co–morbidities, and outcomes of severe pneumonia causing critical illness among pilgrims. Method A cohort study of all critically ill Hajj patients, of over 40 nationalities, admitted to 15 hospitals in 2 cities in 2009 and 2010. Demographic, clinical, and laboratory data, and variables necessary for calculation of the Acute Physiology and Chronic Health Evaluation IV scores were collected. Results There were 452 patients (64.6% male) who developed critical illness. Pneumonia was the primary cause of critical illness in 123 (27.2%) of all intensive care unit (ICU) admissions during Hajj. Pneumonia was community (Hajj)–acquired in 66.7%, aspiration–related in 25.2%, nosocomial in 3.3%, and tuberculous in 4.9%. Pneumonia occurred most commonly in the second week of Hajj, 95 (77.2%) occurred between days 5–15 of Hajj, corresponding to the period of most extreme pilgrim density. Mechanical ventilation was performed in 69.1%. Median duration of ICU stay was 4 (interquartile range [IQR] 1–8) days and duration of ventilation 4 (IQR 3–6) days. Commonest preexisting co–morbidities included smoking (22.8%), diabetes (32.5%), and COPD (17.1%). Short–term mortality (during the 3–week period of Hajj) was 19.5%. Conclusion Pneumonia is a major cause of critical illness during Hajj and occurs amidst substantial crowding and pilgrim density. Increased efforts at prevention for at risk pilgrim prior to Hajj and further attention to spatial and physical crowding during Hajj may attenuate this risk. PMID:22591189

  8. 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

  9. 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

  10. Streptococcus pneumoniae Coinfection Is Correlated with the Severity of H1N1 Pandemic Influenza

    PubMed Central

    Cisterna, Daniel; Savji, Nazir; Bussetti, Ana Valeria; Kapoor, Vishal; Hui, Jeffrey; Tokarz, Rafal; Briese, Thomas; Baumeister, Elsa; Lipkin, W. Ian

    2009-01-01

    Background Initial reports in May 2009 of the novel influenza strain H1N1pdm estimated a case fatality rate (CFR) of 0.6%, similar to that of seasonal influenza. In July 2009, however, Argentina reported 3056 cases with 137 deaths, representing a CFR of 4.5%. Potential explanations for increased CFR included virus reassortment or genetic drift, or infection of a more vulnerable population. Virus genomic sequencing of 26 Argentinian samples representing both severe and mild disease indicated no evidence of reassortment, mutations associated with resistance to antiviral drugs, or genetic drift that might contribute to virulence. Furthermore, no evidence was found for increased frequency of risk factors for H1N1pdm disease. Methods/Principal Findings We examined nasopharyngeal swab samples (NPS) from 199 cases of H1N1pdm infection from Argentina with MassTag PCR, testing for 33 additional microbial agents. The study population consisted of 199 H1N1pdm-infected subjects sampled between 23 June and 4 July 2009. Thirty-nine had severe disease defined as death (n = 20) or hospitalization (n = 19); 160 had mild disease. At least one additional agent of potential pathogenic importance was identified in 152 samples (76%), including Streptococcus pneumoniae (n = 62); Haemophilus influenzae (n = 104); human respiratory syncytial virus A (n = 11) and B (n = 1); human rhinovirus A (n = 1) and B (n = 4); human coronaviruses 229E (n = 1) and OC43 (n = 2); Klebsiella pneumoniae (n = 2); Acinetobacter baumannii (n = 2); Serratia marcescens (n = 1); and Staphylococcus aureus (n = 35) and methicillin-resistant S. aureus (MRSA, n = 6). The presence of S. pneumoniae was strongly correlated with severe disease. S. pneumoniae was present in 56.4% of severe cases versus 25% of mild cases; more than one-third of H1N1pdm NPS with S. pneumoniae were from subjects with severe disease (22 of 62 S. pneumoniae-positive NPS, p = 0

  11. Severe parainfluenza pneumonia in a case of transient hypogammalobulinemia of infancy

    PubMed Central

    Cotugno, Nicola; Manno, Emma Concetta; Stoppa, Francesca; Sinibaldi, Serena; Saffirio, Claudia; D'Argenio, Parizia; Marano, Marco; Nardo, Matteo Di; Palma, Paolo

    2013-01-01

    Human parainfluenza viruses (HPIVs) infection, largely known to cause self-limiting bronchiolitis and pneumonia in immune competent patients, can lead to severe to fatal pulmonary disease in immune disorders, such as primary or acquired-immune deficiencies. We report the case of a 1-year-old child who developed an acute respiratory distress syndrome. Because of a progressive respiratory failure unresponsive to conventional treatment extracorporeal membrane oxygenation (ECMO) was rapidly started. HPIV-3 infection was diagnosed on the rhinopharyngeal fluid and immunological examinations revealed a hypogammaglobulinemia. A combination therapy with ribavirin, intravenous immunoglobulin (IVIG) and steroid under ECMO support was started with considerable improvement. Subsequent analysis and more specific immunological assessment resulted normal confirming the diagnosis of transient hypogammaglobulinemia of infancy (THI). This case highlights the importance of prompt therapy with early ECMO support in combination with ribavirin, IVIG and steroids in patients affected by severe HPIV-3 pneumonia and THI. PMID:23814123

  12. 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.

  13. 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

  14. Aerobic exercise attenuates pulmonary inflammation induced by Streptococcus pneumoniae.

    PubMed

    Olivo, Clarice R; Miyaji, Eliane N; Oliveira, Maria Leonor S; Almeida, Francine M; Lourenço, Juliana D; Abreu, Rodrigo M; Arantes, Petra M M; Lopes, Fernanda Dtqs; Martins, Milton A

    2014-11-01

    Aerobic exercise has been recognized as a stimulator of the immune system, but its effect on bacterial infection has not been extensively evaluated. We studied whether moderate aerobic exercise training prior to Streptococcus pneumoniae infection influences pulmonary inflammatory responses. BALB/c mice were divided into four groups: Sedentary Untreated (sedentary without infection); Sedentary Infected (sedentary with infection); Trained Untreated (aerobic training without infection); and Trained Infected (aerobic training with infection). Animals underwent aerobic training for 4 wk, and 72 h after last exercise training, animals received a challenge with S. pneumoniae and were evaluated either 12 h or 10 days after instillation. In acute phase, Sedentary Infected group had an increase in respiratory system resistance and elastance; number of neutrophils, lymphocytes, and macrophages in bronchoalveolar lavage fluid (BAL); polymorphonuclear cells in lung parenchyma; and levels of keratinocyte-derived chemokine (KC), tumor necrosis factor-α (TNF-α), and interleukin (IL)-1β (IL-1β) in lung homogenates. Exercise training significantly attenuated the increase in all of these parameters and induced an increase in expression of antioxidant enzymes (CuZnSOD and MnSOD) in lungs. Trained Infected mice had a significant decrease in the number of colony-forming units of pneumococci in the lungs compared with Sedentary Infected animals. Ten days after infection, Trained Infected group exhibited lower numbers of macrophages in BAL, polymorphonuclear cells in lung parenchyma and IL-6 in lung homogenates compared with Sedentary Infected group. Our results suggest a protective effect of moderate exercise training against respiratory infection with S. pneumoniae. This effect is most likely secondary to an effect of exercise on oxidant-antioxidant balance.

  15. 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

  16. 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

  17. Association between pneumococcal load and disease severity in adults with pneumonia.

    PubMed

    Werno, Anja M; Anderson, Trevor P; Murdoch, David R

    2012-08-01

    Determination of pneumococcal load by quantitative PCR may be useful for diagnostic and prognostic purposes. We hypothesized that higher pneumococcal load would be associated with increased pneumonia severity. Therefore, we tested serum, sputum and urine specimens from 304 adults with community-acquired pneumonia by using a quantitative lytA pneumococcal real-time PCR assay. The association between pneumococcal load and disease severity was assessed using several markers of severity: CURBage score, PSI risk class, intensive care unit admission, in-hospital death and admission duration. For PCR-positive specimens, the bacterial loads were higher in sputum specimens [median 8.55×10(5) copies ml(-1); interquartile range (IQR) 4.70×10(4)-4.69×10(6) copies ml(-1)] than either serum (median 180 copies ml(-1); IQR 165-8970 copies ml(-1)) or urine (median 623 copies ml(-1); IQR 510-650 copies ml(-1)). Detection of pneumococcal DNA in serum was associated with severe disease, and there was evidence of a dose-response effect with increased bacterial load being associated with increased severity. The same observations were not observed for other specimen types. This study adds to an increasing body of evidence suggesting that determination of pneumococcal load has a clinical utility. Further work is needed to determine whether measuring pneumococcal load in respiratory specimens from adults will differentiate colonization from coincidental carriage.

  18. Age Alterations in Extent and Severity of Experimental Intranasal Infection with Chlamydophila pneumoniae in BALB/c Mice

    PubMed Central

    Little, C. Scott; Bowe, Andrew; Lin, Richard; Litsky, Jason; Fogel, Robert M.; Balin, Brian J.; Fresa-Dillon, Kerin L.

    2005-01-01

    The intracellular bacterium Chlamydophila (“Chlamydia”) pneumoniae is a pathogen for several respiratory diseases and may be a factor in the pathogenesis of chronic diseases of aging including atherosclerosis and Alzheimer's disease. We assessed whether aging is coupled with increased burden of infection in BALB/c mice after intranasal infection by C. pneumoniae. Six- and twenty-month-old BALB/c mice were infected intranasally with 5 × 104 inclusion forming units (IFU) or 5 × 105 IFU of C. pneumoniae. Lung, brain, and heart tissue were analyzed for infectious C. pneumoniae and for Chlamydophila antigen by immunohistochemistry. At both doses, aging was associated with a decreased proportion of animals that cleared infection from the lung and greater burden of infectious organism within the lung. We observed dose-dependent spread to the heart/ascending aorta in animals infected with C. pneumoniae. In mice given 5 × 104 IFU, spread to the heart by day 14 was only observed in old mice. By day 28, all animals inoculated with 5 × 104 IFU showed evidence of spread to the heart, although higher C. pneumoniae titers were observed in the hearts from old mice. In mice inoculated with 5 × 105 IFU, spread of C. pneumoniae to the heart was evident by day 14, with no discernible age effect. C. pneumoniae was also recovered from the central nervous system (brain and olfactory bulb) of all mice by day 28 postinfection, with higher C. pneumoniae titers in old animals than in young animals. Our results suggest that infection with C. pneumoniae may be more severe in old animals. PMID:15731073

  19. The effect of Haemophilus influenzae type b and pneumococcal conjugate vaccines on childhood pneumonia incidence, severe morbidity and mortality

    PubMed Central

    Jhass, Arnoupe; Madhi, Shabir A; Clark, Andrew; Boschi-Pinto, Cynthia; Bhopal, Sunil; Rudan, Igor; Campbell, Harry

    2010-01-01

    Background With the aim of populating the Lives Saved Tool (LiST) with parameters of effectiveness of existing interventions, we conducted a systematic review of the literature assessing the effect of Haemophilus influenzae type b (Hib) and pneumococcal (PC) conjugate vaccines on incidence, severe morbidity and mortality from childhood pneumonia. Methods We summarized cluster randomized controlled trials (cRCTs) and case–control studies of Hib conjugate vaccines and RCTs of 9- and 11-valent PC conjugate vaccines conducted in developing countries across outcome measures using standard meta-analysis methods. We used a set of standardized rules developed for the purpose of populating the LiST tool with required parameters to promote comparability across reviews of interventions against the major causes of childhood mortality. The estimates could be adjusted further to account for factors such as PC vaccine serotype content, PC serotype distribution and human immunodeficiency virus prevalence but this was not included as part of the LiST model approach. Results The available evidence from published data points to a summary effect of the Hib conjugate vaccine on clinical pneumonia of 4%, on clinical severe pneumonia of 6% and on radiologically confirmed pneumonia of 18%. Respective effectiveness estimates for PC vaccines (all valent) on clinical pneumonia is 7%, clinical severe pneumonia is 7% and radiologically confirmed pneumonia is 26%. Conclusions The findings indicated that radiologically confirmed pneumonia, as a severe morbidity proxy for mortality, provided better estimates for the LiST model of effect of interventions on mortality reduction than did other outcomes evaluated. The LiST model will use this to estimate the pneumonia mortality reduction which might be observed when scaling up Hib and PC conjugate vaccination in the context of an overall package of child health interventions. PMID:20348119

  20. Multidisciplinary Comprehensive Care for Early Recommencement of Oral Intake in Older Adults With Severe Pneumonia.

    PubMed

    Koyama, Tamami; Shamoto, Hiroshi; Anzai, Hideaki; Koganei, Yutaka; Maeda, Keisuke; Wakabayashi, Hidetaka

    2016-10-01

    HOW TO OBTAIN CONTACT HOURS BY READING THIS ARTICLE INSTRUCTIONS 1.3 contact hours will be awarded by Villanova University College of Nursing upon successful completion of this activity. A contact hour is a unit of measurement that denotes 60 minutes of an organized learning activity. This is a learner-based activity. Villanova University College of Nursing does not require submission of your answers to the quiz. A contact hour certificate will be awarded once you register, pay the registration fee, and complete the evaluation form online at http://goo.gl/gMfXaf. To obtain contact hours you must: 1. Read the article, "Multidisciplinary Comprehensive Care for Early Recommencement of Oral Intake in Older Adults With Severe Pneumonia" found on pages 21-29, carefully noting any tables and other illustrative materials that are included to enhance your knowledge and understanding of the content. Be sure to keep track of the amount of time (number of minutes) you spend reading the article and completing the quiz. 2. Read and answer each question on the quiz. After completing all of the questions, compare your answers to those provided within this issue. If you have incorrect answers, return to the article for further study. 3. Go to the Villanova website listed above to register for contact hour credit. You will be asked to provide your name; contact information; and a VISA, MasterCard, or Discover card number for payment of the $20.00 fee. Once you complete the online evaluation, a certificate will be automatically generated. This activity is valid for continuing education credit until September 30, 2019. CONTACT HOURS This activity is co-provided by Villanova University College of Nursing and SLACK Incorporated. Villanova University College of Nursing is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation. ACTIVITY OBJECTIVES 1. Describe the effect of multidisciplinary comprehensive care

  1. Multidisciplinary Comprehensive Care for Early Recommencement of Oral Intake in Older Adults With Severe Pneumonia.

    PubMed

    Koyama, Tamami; Shamoto, Hiroshi; Anzai, Hideaki; Koganei, Yutaka; Maeda, Keisuke; Wakabayashi, Hidetaka

    2016-10-01

    HOW TO OBTAIN CONTACT HOURS BY READING THIS ARTICLE INSTRUCTIONS 1.3 contact hours will be awarded by Villanova University College of Nursing upon successful completion of this activity. A contact hour is a unit of measurement that denotes 60 minutes of an organized learning activity. This is a learner-based activity. Villanova University College of Nursing does not require submission of your answers to the quiz. A contact hour certificate will be awarded once you register, pay the registration fee, and complete the evaluation form online at http://goo.gl/gMfXaf. To obtain contact hours you must: 1. Read the article, "Multidisciplinary Comprehensive Care for Early Recommencement of Oral Intake in Older Adults With Severe Pneumonia" found on pages 21-29, carefully noting any tables and other illustrative materials that are included to enhance your knowledge and understanding of the content. Be sure to keep track of the amount of time (number of minutes) you spend reading the article and completing the quiz. 2. Read and answer each question on the quiz. After completing all of the questions, compare your answers to those provided within this issue. If you have incorrect answers, return to the article for further study. 3. Go to the Villanova website listed above to register for contact hour credit. You will be asked to provide your name; contact information; and a VISA, MasterCard, or Discover card number for payment of the $20.00 fee. Once you complete the online evaluation, a certificate will be automatically generated. This activity is valid for continuing education credit until September 30, 2019. CONTACT HOURS This activity is co-provided by Villanova University College of Nursing and SLACK Incorporated. Villanova University College of Nursing is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation. ACTIVITY OBJECTIVES 1. Describe the effect of multidisciplinary comprehensive care

  2. 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

  3. Propolis-induced descending necrotizing mediastinitis and aspiration pneumonia.

    PubMed

    Wu, Jeng-Yuan; Hsu, Nan-Yung

    2013-04-01

    Propolis is a resinous substance collected by bees as a sealant for their hives. It is also used in traditional medicine as an antioxidant and antiinflammatory agent to treat ulcers, superficial burns, and microbial diseases. In this report, a 40-year-old woman who took liquid propolis for relief of her common cold experienced severe sore throat, dysphagia, and easy choking followed by fever and chills. Descending necrotizing mediastinitis and concomitant aspiration pneumonia were evident on the image studies. We performed video-assisted thoracoscopic surgery to achieve immediate and adequate drainage, and the patient resumed normal deglutition 2 months later. Early diagnosis and prompt video-assisted thoracoscopic surgery intervention are paramount to manage this life-threatening situation.

  4. Influenza A/H1N1 Severe Pneumonia: Novel Morphocytological Findings in Bronchoalveolar Lavage

    PubMed Central

    Faverio, Paola; Messinesi, Grazia; Brenna, Ambrogio; Pesci, Alberto

    2014-01-01

    We present the results of bronchoalveolar lavage (BAL) performed in three patients with severe influenza A/H1N1 pneumonia complicated by acute respiratory distress syndrome (ARDS). Light microscopy analysis of BAL cytocentrifugates showed the presence of characteristic large, mononuclear, plasmoblastic/plasmocytoid-like cells never described before. Via transmission electron microscopy, these cells were classified as atypical type II pneumocytes and some of them showed cytoplasmic vesicles and inclusions. We concluded that plasmoblastic/plasmocytoid-like type II pneumocytes might represent a morphologic marker of A/H1N1 influenza virus infection as well as reparative cellular activation after diffuse alveolar damage. PMID:25383078

  5. 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.

  6. Severe pneumonia associated with pandemic (H1N1) 2009 outbreak, San Luis Potosí, Mexico.

    PubMed

    Gómez-Gómez, Alejandro; Magaña-Aquino, Martin; Garcia-Sepúlveda, Christian; Ochoa-Pérez, Uciel R; Falcón-Escobedo, Reynaldo; Comas-García, Andreu; Aranda-Romo, Saray; Contreras-Treviño, Hugo I; Jimenéz-Rico, Paulina V; Banda-Barbosa, Mario A; Dominguez-Paulin, Félix; Bernal-Blanco, J Mario; Peréz-González, Luis F; Noyola, Daniel E

    2010-01-01

    We describe the clinical characteristics and outcomes of adults hospitalized with pneumonia during the pandemic (H1N1) 2009 outbreak. Patients admitted to a general hospital in San Luis Potosí, Mexico, from April 10 through May 11, 2009, suspected to have influenza virus-associated pneumonia were evaluated. We identified 50 patients with suspected influenza pneumonia; the presence of influenza virus was confirmed in 18: 11 with pandemic (H1N1) 2009 virus, 5 with unsubtypeable influenza A virus, 1 with seasonal influenza A virus (H3N2), and 1 in whom assay results for seasonal and pandemic (H1N1) 2009 viruses were positive. Eighteen patients were treated in the intensive care unit, and 10 died. During the pandemic (H1N1) 2009 outbreak, severe pneumonia developed in young adults who had no identifiable risk factors; early diagnosis and treatment of influenza virus infections may have a determinant role in outcome.

  7. 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

  8. Aerosolized clindamycin is superior to aerosolized dexamethasone or clindamycin-dexamethasone combination in the treatment of severe Porphyromonas gingivalis aspiration pneumonia in an experimental murine model.

    PubMed

    Nemec, Ana; Pavlica, Zlatko; Nemec-Svete, Alenka; Eržen, Damijan; Milutinović, Aleksandra; Petelin, Milan

    2012-02-01

    Adjunctive corticosteroid treatment to reduce excessive local inflammatory response in pneumonia is controversial. To study the effects of an early local adjunct dexamethasone treatment on the course of pneumonia and inflammatory/cytokine response, mice were intratracheally inoculated with live Porphyromonas gingivalis and treated with either clindamycin (C), dexamethasone (D), C+D combination, or were not treated (Pg). Six mice from each group were euthanized at 6, 24, 72, and 168 hours after inoculation. Levels of tumor necrosis factor (TNF)-α, soluble TNF-α receptors (sTNFR1 and sTNFR2), interleukin (IL)-1β, and IL-6 in the serum and lung-homogenate supernatant were determined. Lung samples were histopathologically assessed and all findings compared to those found in 24 sham-inoculated mice (phosphate-buffered saline [PBS]). Severe P. gingivalis-induced bronchopneumonia progressed from 24 hours, peaked at 72 hours, and resolved after 168 hours with changes in local and systemic cytokine levels. Clindamycin-treated mice developed only mild bronchopneumonia that resolved fast (72 hours) with an early (6-24 hours) normalization of local and systemic cytokine levels. Similar course of pneumonia and cytokine level changes were observed in mice treated with C+D, but later. Early (6-24 hours) local elevation of sTNFRs was observed in C and C+D groups of mice, whereas nontreated (Pg) mice had increased systemic sTNFRs. Severe bronchopneumonia with delayed resolution was observed in D-group mice, with an early local and systemic decrease in sTNFR1 and persistent elevation of local TNF-α. Clindamycin or a clindamycin-dexamethasone combination treatment significantly improves the course of P. gingivalis-aspiration pneumonia, but more so if clindamycin alone is used. A favorable course of pneumonia seems to be associated with an early elevation of sTNFRs and normalization of TNF-α.

  9. 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.

  10. 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

  11. Admission Chest Radiographs Predict Illness Severity for Children Hospitalized with Pneumonia

    PubMed Central

    McClain, Lauren; Hall, Matthew; Shah, Samir S.; Tieder, Joel S.; Myers, Angela L.; Auger, Katherine; Statile, Angela M.; Jerardi, Karen; Queen, Mary Ann; Fieldston, Evan; Williams, Derek J.

    2014-01-01

    Objective To assess whether radiographic findings predict outcomes among children hospitalized with pneumonia. Methods This retrospective study included children <18 years of age from 4 children's hospitals admitted in 2010 with clinical and radiographic evidence of pneumonia. Admission radiographs were categorized as single lobar, unilateral or bilateral multilobar, or interstitial. Pleural effusions were classified as absent, small, or moderate/large. Propensity scoring was used to adjust for potential confounders, including need for supplemental oxygen, intensive care, and mechanical ventilation, as well as hospital length of stay and duration of supplemental oxygen. Results There were 406 children (median age, 3 years). Infiltrate patterns included: single lobar, 61%; multilobar unilateral, 13%; multilobar bilateral, 16%; and interstitial, 10%. Pleural effusion was present in 21%. Overall, 63% required supplemental oxygen (median duration 31.5 hours), 8% required intensive care, and 3% required mechanical ventilation. Median length of stay was 51.5 hours. Compared with single lobar infiltrate, all other infiltrate patterns were associated with need for intensive care; only bilateral multilobar infiltrate was associated with need for mechanical ventilation (adjusted odds ratio [aOR] 3.0, 95% confidence interval 1.2, 7.9). Presence of effusion was associated with increased length of stay and duration of supplemental oxygen; only moderate/large effusion was associated with need for intensive care (aOR 3.2 [1.1, 8.9]) and mechanical ventilation (aOR 14.8 [9.8, 22.4]). Conclusions Admission radiographic findings are associated with important hospital outcomes and care processes and may help predict disease severity. PMID:24942619

  12. 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

  13. 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

  14. 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.

  15. Plasma-derived human C1-esterase inhibitor does not prevent mechanical ventilation-induced pulmonary complement activation in a rat model of Streptococcus pneumoniae pneumonia.

    PubMed

    de Beer, F M; Aslami, H; Hoeksma, J; van Mierlo, G; Wouters, D; Zeerleder, S; Roelofs, J J T H; Juffermans, N P; Schultz, M J; Lagrand, W K

    2014-11-01

    Mechanical ventilation has the potential to cause lung injury, and the role of complement activation herein is uncertain. We hypothesized that inhibition of the complement cascade by administration of plasma-derived human C1-esterase inhibitor (C1-INH) prevents ventilation-induced pulmonary complement activation, and as such attenuates lung inflammation and lung injury in a rat model of Streptococcus pneumoniae pneumonia. Forty hours after intratracheal challenge with S. pneumoniae causing pneumonia rats were subjected to ventilation with lower tidal volumes and positive end-expiratory pressure (PEEP) or high tidal volumes without PEEP, after an intravenous bolus of C1-INH (200 U/kg) or placebo (saline). After 4 h of ventilation blood, broncho-alveolar lavage fluid and lung tissue were collected. Non-ventilated rats with S. pneumoniae pneumonia served as controls. While ventilation with lower tidal volumes and PEEP slightly amplified pneumonia-induced complement activation in the lungs, ventilation with higher tidal volumes without PEEP augmented local complement activation more strongly. Systemic pre-treatment with C1-INH, however, failed to alter ventilation-induced complement activation with both ventilation strategies. In accordance, lung inflammation and lung injury were not affected by pre-treatment with C1-INH, neither in rats ventilated with lower tidal volumes and PEEP, nor rats ventilated with high tidal volumes without PEEP. Ventilation augments pulmonary complement activation in a rat model of S. pneumoniae pneumonia. Systemic administration of C1-INH, however, does not attenuate ventilation-induced complement activation, lung inflammation, and lung injury. PMID:24760631

  16. A distinct influenza infection signature in the blood transcriptome of patients with severe community-acquired pneumonia

    PubMed Central

    2012-01-01

    Introduction Diagnosis of severe influenza pneumonia remains challenging because of a lack of correlation between the presence of influenza virus and clinical status. We conducted gene-expression profiling in the whole blood of critically ill patients to identify a gene signature that would allow clinicians to distinguish influenza infection from other causes of severe respiratory failure, such as bacterial pneumonia, and noninfective systemic inflammatory response syndrome. Methods Whole-blood samples were collected from critically ill individuals and assayed on Illumina HT-12 gene-expression beadarrays. Differentially expressed genes were determined by linear mixed-model analysis and overrepresented biological pathways determined by using GeneGo MetaCore. Results The gene-expression profile of H1N1 influenza A pneumonia was distinctly different from those of bacterial pneumonia and systemic inflammatory response syndrome. The influenza gene-expression profile is characterized by upregulation of genes from cell-cycle regulation, apoptosis, and DNA-damage-response pathways. In contrast, no distinctive gene-expression signature was found in patients with bacterial pneumonia or systemic inflammatory response syndrome. The gene-expression profile of influenza infection persisted through 5 days of follow-up. Furthermore, in patients with primary H1N1 influenza A infection in whom bacterial co-infection subsequently developed, the influenza gene-expression signature remained unaltered, despite the presence of a superimposed bacterial infection. Conclusions The whole-blood expression-profiling data indicate that the host response to influenza pneumonia is distinctly different from that caused by bacterial pathogens. This information may speed the identification of the cause of infection in patients presenting with severe respiratory failure, allowing appropriate patient care to be undertaken more rapidly. PMID:22898401

  17. Characterisation of bovine viral diarrhoea virus (BVDV) isolates from an outbreak with haemorrhagic enteritis and severe pneumonia.

    PubMed

    Yeşilbağ, Kadir; Förster, Christine; Ozyiğit, M Ozgür; Alpay, Gizem; Tuncer, Pelin; Thiel, Heinz-Jürgen; König, Matthias

    2014-02-21

    During 2007 a disease outbreak occurred in cattle in the Marmara region of western Turkey characterised by severe pneumonia and haemorrhagic enteritis in calves. Cases from three farms at different locations were examined and bovine viral diarrhoea virus (BVDV) isolated in all cases. Phylogenetic characterisation of the virus isolates allocated them in a new cluster tentatively named as BVDV-1r.

  18. 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

  19. 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

  20. 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

  1. Emergency treatment and nursing of children with severe pneumonia complicated by heart failure and respiratory failure: 10 case reports

    PubMed Central

    Li, Wanli; An, Xinjiang; Fu, Mingyu; Li, Chunli

    2016-01-01

    Pneumonia refers to lung inflammation caused by different pathogens or other factors, and is a common pediatric disease occurring in infants and young children. It is closely related to the anatomical and physiological characteristics of infants and young children and is more frequent during winter and spring, or sudden changes in temperature. Pneumonia is a serious disease that poses a threat to children's health and its morbidity and mortality rank first, accounting for 24.5–65.2% of pediatric inpatients. Due to juvenile age, severe illness and rapid changes, children often suffer acute heart failure, respiratory failure and even toxic encephalopathy at the same time. The concurrence in different stages of the process of emergency treatment tends to relapse, which directly places the lives of these children at risk. Severe pneumonia constitutes one of the main causes of infant mortality. In the process of nursing children with severe pneumonia, intensive care was provided, including condition assessment and diagnosis, close observation of disease, keeping the airway unblocked, rational oxygen therapy, prevention and treatment of respiratory and circulatory failure, support of vital organs, complications, and health education. The inflammatory response was proactively controlled, to prevent suffocation and reduce mortality. In summary, positive and effective nursing can promote the rehabilitation of children patients, which can be reinforced with adequate communication with the parents and/or caretakers. PMID:27698703

  2. Emergency treatment and nursing of children with severe pneumonia complicated by heart failure and respiratory failure: 10 case reports

    PubMed Central

    Li, Wanli; An, Xinjiang; Fu, Mingyu; Li, Chunli

    2016-01-01

    Pneumonia refers to lung inflammation caused by different pathogens or other factors, and is a common pediatric disease occurring in infants and young children. It is closely related to the anatomical and physiological characteristics of infants and young children and is more frequent during winter and spring, or sudden changes in temperature. Pneumonia is a serious disease that poses a threat to children's health and its morbidity and mortality rank first, accounting for 24.5–65.2% of pediatric inpatients. Due to juvenile age, severe illness and rapid changes, children often suffer acute heart failure, respiratory failure and even toxic encephalopathy at the same time. The concurrence in different stages of the process of emergency treatment tends to relapse, which directly places the lives of these children at risk. Severe pneumonia constitutes one of the main causes of infant mortality. In the process of nursing children with severe pneumonia, intensive care was provided, including condition assessment and diagnosis, close observation of disease, keeping the airway unblocked, rational oxygen therapy, prevention and treatment of respiratory and circulatory failure, support of vital organs, complications, and health education. The inflammatory response was proactively controlled, to prevent suffocation and reduce mortality. In summary, positive and effective nursing can promote the rehabilitation of children patients, which can be reinforced with adequate communication with the parents and/or caretakers.

  3. 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

  4. 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

  5. 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

  6. 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

  7. Klebsiella pneumoniae alleviates influenza-induced acute lung injury via limiting NK cell expansion.

    PubMed

    Wang, Jian; Li, Fengqi; Sun, Rui; Gao, Xiang; Wei, Haiming; Tian, Zhigang

    2014-08-01

    A protective effect induced by bacterial preinfection upon a subsequent lethal influenza virus infection has been observed, but the underlying immune mechanisms have not yet been fully elucidated. In this study, we used a mouse model of Klebsiella pneumoniae preinfection to gain insight into how bacterial preinfection influences the subsequent lethal influenza virus infection. We found that K. pneumoniae preinfection significantly attenuated lung immune injury and decreased mortality during influenza virus infection, but K. pneumoniae-specific immunity was not involved in this cross-protection against influenza virus. K. pneumoniae preinfection limited NK cell expansion, which was involved in influenza-induced immune injury and death. Furthermore, K. pneumoniae preinfection could not control NK cell expansion and death during influenza virus infection in Rag1(-/-) mice, but adoptive transfer of T cells from wild-type mice was able to restore this protective effect. Our data suggest that the adaptive immune response activated by bacterial infection limits the excessive innate immune response induced by a subsequent influenza infection, ultimately protecting mice from death.

  8. Phenotyping community-acquired pneumonia according to the presence of acute respiratory failure and severe sepsis

    PubMed Central

    2014-01-01

    Background Acute respiratory failure (ARF) and severe sepsis (SS) are possible complications in patients with community-acquired pneumonia (CAP). The aim of the study was to evaluate prevalence, characteristics, risk factors and impact on mortality of hospitalized patients with CAP according to the presence of ARF and SS on admission. Methods This was a multicenter, observational, prospective study of consecutive CAP patients admitted to three hospitals in Italy, Spain, and Scotland between 2008 and 2010. Three groups of patients were identified: those with neither ARF nor SS (Group A), those with only ARF (Group B) and those with both ARF and SS (Group C) on admission. Results Among the 2,145 patients enrolled, 45% belonged to Group A, 36% to Group B and 20% to Group C. Patients in Group C were more severe than patients in Group B. Isolated ARF was correlated with age (p < 0.001), COPD (p < 0.001) and multilobar infiltrates (p < 0.001). The contemporary occurrence of ARF and SS was associated with age (p = 0.002), residency in nursing home (p = 0.007), COPD (p < 0.001), multilobar involvement (p < 0.001) and renal disease (p < 0.001). 4.2% of patients in Group A died, 9.3% in Group B and 26% in Group C, p < 0.001. After adjustment, the presence of only ARF had an OR for in-hospital mortality of 1.85 (p = 0.011) and the presence of both ARF and SS had an OR of 6.32 (p < 0.001). Conclusions The identification of ARF and SS on hospital admission can help physicians in classifying CAP patients into three different clinical phenotypes. PMID:24593040

  9. 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

  10. Myopathy and eosinophilic pneumonia coincidentally induced by treatment with daptomycin.

    PubMed

    Hagiya, Hideharu; Hasegawa, Kou; Asano, Kikuko; Terasaka, Tomohiro; Kimura, Kosuke; Nada, Takahiro; Nakamura, Eri; Waseda, Koichi; Hanayama, Yoshihisa; Otsuka, Fumio

    2015-01-01

    A 34-year-old man with 22q11.2 deletion syndrome (DiGeorge syndrome) concurrently suffered from myopathy and eosinophilic pneumonia shortly after receiving daptomycin (DAP) for right-sided infective endocarditis. The simultaneous occurrence of these phenomena in relation to DAP therapy has not been previously well described. An allergic reaction was suspected as a possible etiology of these DAP-related complications. This case highlights the need for close observation in order to detect both musculoskeletal and respiratory disorders from the start of DAP therapy. Physicians should pay more attention to this new drug, which is expected to be frequently used in various clinical settings. PMID:25758082

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. 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…

  16. Nebulized anticoagulants limit coagulopathy but not inflammation in pseudomonas aeruginosa-induced pneumonia in rats.

    PubMed

    Cornet, Alexander D; Hofstra, Jorrit J; Vlaar, Alexander P; van den Boogaard, Floor E; Roelofs, Joris J; van der Poll, Tom; Levi, Marcel; Groeneveld, A B Johan; Schultz, Marcus J

    2011-10-01

    Disturbed alveolar fibrin turnover is a characteristic feature of pneumonia. Inhibitors of coagulation could exert lung-protective effects via anticoagulant (inhibiting fibrin deposition) and possibly anti-inflammatory pathways, but could also affect host defense. In this randomized controlled in vivo laboratory study, rats were challenged intratracheally with Pseudomonas aeruginosa, inducing pneumonia, and randomized to local treatment with normal saline (placebo), recombinant human activated protein C (rh-APC), plasma-derived antithrombin (AT), heparin, or danaparoid. Induction of P. aeruginosa pneumonia resulted in activation of pulmonary coagulation and inhibition of pulmonary fibrinolysis, as reflected by increased pulmonary levels of thrombin-AT complexes and fibrin degradation products and decreased pulmonary levels plasminogen activator activity. Pseudomonas aeruginosa pneumonia was accompanied by systemic coagulopathy, since systemic levels of thrombin-AT complexes increased, and systemic levels of plasminogen activator activity decreased. Although rh-APC and plasma-derived AT potently limited pulmonary coagulopathy, neither heparin nor danaparoid affected net pulmonary fibrin turnover. Recombinant human APC also displayed systemic anticoagulant effects. Neither bacterial clearance nor pulmonary inflammation was affected by anticoagulant therapy. Nebulization of rh-APC or plasma-derived AT attenuated pulmonary coagulopathy, but not bacterial clearance or inflammation, in a rat model of P. aeruginosa pneumonia. PMID:21897338

  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

    2016-01-06

    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.

  19. TNF-related apoptosis-inducing ligand (TRAIL) exerts therapeutic efficacy for the treatment of pneumococcal pneumonia in mice.

    PubMed

    Steinwede, Kathrin; Henken, Stefanie; Bohling, Jennifer; Maus, Regina; Ueberberg, Bianca; Brumshagen, Christina; Brincks, Erik L; Griffith, Thomas S; Welte, Tobias; Maus, Ulrich A

    2012-10-22

    Apoptotic death of alveolar macrophages observed during lung infection with Streptococcus pneumoniae is thought to limit overwhelming lung inflammation in response to bacterial challenge. However, the underlying apoptotic death mechanism has not been defined. Here, we examined the role of the TNF superfamily member TNF-related apoptosis-inducing ligand (TRAIL) in S. pneumoniae-induced macrophage apoptosis, and investigated the potential benefit of TRAIL-based therapy during pneumococcal pneumonia in mice. Compared with WT mice, Trail(-/-) mice demonstrated significantly decreased lung bacterial clearance and survival in response to S. pneumoniae, which was accompanied by significantly reduced apoptosis and caspase 3 cleavage but rather increased necrosis in alveolar macrophages. In WT mice, neutrophils were identified as a major source of intraalveolar released TRAIL, and their depletion led to a shift from apoptosis toward necrosis as the dominant mechanism of alveolar macrophage cell death in pneumococcal pneumonia. Therapeutic application of TRAIL or agonistic anti-DR5 mAb (MD5-1) dramatically improved survival of S. pneumoniae-infected WT mice. Most importantly, neutropenic mice lacking neutrophil-derived TRAIL were protected from lethal pneumonia by MD5-1 therapy. We have identified a previously unrecognized mechanism by which neutrophil-derived TRAIL induces apoptosis of DR5-expressing macrophages, thus promoting early bacterial killing in pneumococcal pneumonia. TRAIL-based therapy in neutropenic hosts may represent a novel antibacterial treatment option.

  20. Severe and recurrent episodes of bronchiolitis obliterans organising pneumonia associated with indolent CD4+ CD8+ T-cell leukaemia.

    PubMed

    Martinez-Gallo, M; Puy, C; Ruiz-Hernandez, R; Rodriguez-Arias, J M; Bofill, M; Nomdedeu, J F; Cigudosa, J C; Rodriguez-Sanchez, J L; de la Calle-Martin, O

    2008-06-01

    The present study describes an adult male who has had recurrent episodes of pulmonary infiltrates with severe acute respiratory failure over a period of 10 yrs. Clinical and pathological characteristics revealed bronchiolitis obliterans with organising pneumonia (BOOP) that responded dramatically to prednisone. BOOP is characterised by inflammation of the bronchioles and surrounding tissue in the lungs. It can mimic infectious pneumonia but diagnosis is suspected when there is no response to multiple antibiotic treatment, and blood and sputum cultures are negative for microorganisms. A high proportion of double-positive (DP)-T-cells was detected in peripheral blood and in bronchoalveolar lavage, expressing CD4 and CD8alphabeta heterodimer with memory phenotype. These DP-T-lymphocytes expressed specific homing molecules that could explain their tropism to lung tissue, giving rise to the clinical symptoms. The patient did not present organomegaly, lymphadenopathy, lymphocytosis or other features of malignancy. However, T-cell receptor Vbeta chain analysis indicated clonal rearrangement, and cytogenetic studies displayed chromosomic alterations that were similar to clonal proliferation observed in ataxia-telangiectasia and T-prolymphocytic leukaemia. The findings suggest a smouldering form of lymphoproliferation, the first sign of which was bronchiolitis obliterans organising pneumonia requiring constant corticoid treatment.

  1. 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

  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. 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

  4. 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.

  5. 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

  6. 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

  7. 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

  8. Mycoplasma pneumoniae modulates STAT3-STAT6/EGFR-FOXA2 signaling to induce overexpression of airway mucins.

    PubMed

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

    2014-12-01

    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

  9. Viral pneumonia.

    PubMed

    Greenberg, S B

    1991-09-01

    Viral pneumonias are common in infants and young children but rare in adults. Respiratory syncytial virus (RSV) and para-influenza viruses are the most frequent viral pathogens in infants and children. Influenza virus types A and B account for over one half of viral pneumonias in adults. Immunocompromised hosts are susceptible to pneumonias caused by cytomegalovirus (CMV) and other herpesviruses, as well as rubeola and adenovirus. Diagnosis of viral pneumonia depends on appropriate viral cultures and acute and convalescent sera for specific antibodies. Superinfection with bacteria is common in adults. Anti-viral therapy is available for several respiratory viruses. Ribavirin, amantadine/rimantadine, interferon alpha, and acyclovir are antiviral drugs that may be of benefit in treatment and prophylaxis. Prevention of viral pneumonia will depend upon improved viral immunization practices.

  10. 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.

  11. Sorafenib-induced acute interstitial pneumonia in patients with advanced hepatocellular carcinoma: report of three cases.

    PubMed

    Takeda, Haruhiko; Nishikawa, Hiroki; Iguchi, Eriko; Matsuda, Fumihiro; Kita, Ryuichi; Kimura, Toru; Osaki, Yukio

    2012-01-01

    Little is known about acute interstitial pneumonia (AIP) induced by sorafenib therapy in patients with advanced hepatocellular carcinoma (HCC). Here, we present three patients with advanced HCC who developed AIP during sorafenib therapy, with fatal complications in two cases. Case 1 was a 76-year-old man who developed dyspnea. Chest CT showed interstitial pneumonia. Sorafenib was discontinued immediately, and prednisolone was started. His pneumonia resolved. A drug-induced lymphocyte stimulation test for sorafenib was positive. Case 2 was a 75-year-old man and case 3 was a 77-year-old man, both of whom developed high-grade fever and hypoxemia during sorafenib therapy, and were diagnosed with AIP. In spite of high-dose steroid therapy, their respiratory failure worsened and both patients died. In all three cases, serum KL-6 or surfactant protein D concentrations were elevated, and blood and sputum cultures did not grow pathogens. All three patients were smokers with restrictive lung disease on preoperative respiratory function testing, but did not have respiratory symptoms before sorafenib therapy. The clinical features of these three cases suggest that male gender, older age, smoking history, and lung disease are associated with acute sorafenib-induced AIP in patients with advanced HCC.

  12. Bacteriophage-loaded nanostructured lipid carrier: improved pharmacokinetics mediates effective resolution of Klebsiella pneumoniae-induced lobar pneumonia.

    PubMed

    Singla, Saloni; Harjai, Kusum; Katare, Om Prakash; Chhibber, Sanjay

    2015-07-15

    This study examined the therapeutic and prophylactic potential of bacteriophages in a mouse model of Klebsiella pneumoniae lobar pneumonia. Phages were administered intraperitoneally. Liposome-entrapped phages (LP) were effective in treating infection, even when therapy was delayed by 3 days after the induction of pneumonia. In contrast, nonliposomal phages provided protection when administered 24 hours after infection. Administration of nonliposomal phages 6 hours prior to intranasal bacterial challenge resulted in complete protection, compared with LP, which was effective even when administered 48 hours prior to infection. Increased reduction and a greater increment in the levels of proinflammatory and antiinflammatory cytokines, respectively, in homogenates of lung from LP-treated mice were suggestive of increased efficacy of LP in the treatment of pneumonia. This is the first study to assess liposomes as a delivery vehicle for phage, and the results confirm the superiority of LP for both therapeutic and prophylactic applications.

  13. Clopidogrel treatment on the incidence and severity of community acquired pneumonia in a cohort study and meta-analysis of antiplatelet therapy in pneumonia and critical illness

    PubMed Central

    Gross, A. Kendall; Dunn, Steven P.; Feola, David J.; Martin, Craig A.; Charnigo, Richard; Li, Zhenyu; Abdel-Latif, Ahmed; Smyth, Susan S.

    2013-01-01

    Background Platelet activation results in the release and upregulation of mediators responsible for immune cell activation and recruitment, suggesting that platelets play an active role in immunity. Animal models and retrospective data have demonstrated benefit of antiplatelet therapy on inflammatory mediator expression and clinical outcomes. This study sought to characterize effects of clopidogrel on the incidence and severity of community-acquired pneumonia (CAP). Methods A retrospective cohort study was conducted of Kentucky Medicaid patients (2001-2005). The exposed cohort consisted of patients receiving at least six consecutive clopidogrel prescriptions; the non-exposed cohort was comprised of patients not prescribed clopidogrel. Primary endpoints included incidence of CAP and inpatient treatment. Secondary severity endpoints included mortality, intensive care unit admission, mechanical ventilation, sepsis, and acute respiratory distress syndrome/acute lung injury. Results CAP incidence was significantly greater in the exposed cohort (OR 3.39, 95% CI 3.27-3.51, p < 0.0001) that remained after adjustment (OR 1.48, 95% CI 1.41-1.55, p < 0.0001). Inpatient treatment was more common in the exposed cohort (OR 1.96, 95% CI 1.85-2.07, p < 0.0001), but no significant difference remained after adjustment. Trends favoring the exposed cohort were found for the secondary severity endpoints of mechanical ventilation (p = 0.07) and mortality (p = 0.10). Pooled analysis of published studies supports these findings. Conclusions While clopidogrel use may be associated with increased CAP incidence, clopidogrel does not appear to increase – and may reduce – its severity among inpatients. Because this study was retrospective and could not quantify all variables (e.g., aspirin use), these findings should be explored prospectively. PMID:23124575

  14. Respiratory viruses associated with severe pneumonia in children under 2 years old in a rural community in Pakistan.

    PubMed

    Ali, Asad; Akhund, Tauseef; Warraich, Gohar Javed; Aziz, Fatima; Rahman, Najeeb; Umrani, Fayyaz Ahmed; Qureshi, Shahida; Petri, William A; Bhutta, Zulfiqar; Zaidi, Anita K M; Hughes, Molly A

    2016-11-01

    The objective of this study was to determine the incidence of respiratory viruses associated with severe pneumonia among children less than 2 years of age in the rural district of Matiari in Sindh, Pakistan. This study was a community-based prospective cohort active surveillance of infants enrolled at birth and followed for 2 years. Cases were identified using the World Health Organization's Integrated Management of Childhood Illnesses' definition of severe pneumonia. Nasopharyngeal swabs were obtained for assessment by multiplex RT-PCR for eight viruses and their subtypes, including RSV, influenza virus, human metapneumovirus, enterovirus/rhinovirus, coronavirus, parainfluenza virus, adenovirus, and human bocavirus. Blood cultures were collected from febrile participants. A total of 817 newborns were enrolled and followed with fortnightly surveillance for 2 years, accounting for a total of 1,501 child-years of follow-up. Of the nasopharyngeal swabs collected, 77.8% (179/230) were positive for one or more of the above mentioned respiratory viruses. The incidence of laboratory confirmed viral-associated pneumonia was 11.9 per 100 child-years of follow-up. Enterovirus/rhinovirus was detected in 51.7% patients, followed by parainfluenza virus type III (8.3%), and RSV (5.7%). Of the uncontaminated blood cultures, 1.4% (5/356) were positive. Respiratory viruses are frequently detected during acute respiratory infection episodes in children under 2 years old in a rural community in Pakistan. However, causal association is yet to be established and the concomitant role of bacteria as a co-infection or super-infection needs further investigation. J. Med. Virol. 88:1882-1890, 2016. © 2016 Wiley Periodicals, Inc.

  15. 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.

  16. 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

  17. 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

  18. 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

  19. 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.

  20. Development of interstitial pneumonia in a patient with rheumatoid arthritis induced by isoniazid for tuberculosis chemoprophylaxis.

    PubMed

    Migita, Kiyoshi; Umeno, Tetsuya; Miyagawa, Kana; Izumi, Yasumori; Sasaki, Eisuke; Kakugawa, Tomoyuki; Ito, Masahiro; Kinoshita, Akitoshi; Miyashita, Taichiro

    2012-05-01

    Here, we report a 56-year-old patient with rheumatoid arthritis (RA) who had been treated with methotrexate and sulfuasalazine, but the disease activity remained high. Therefore, we planned TNF-blocker treatment for this patient. A tuberculin skin test was positive, we started anti-tuberculosis (TB) chemoprophylaxis with isoniazid (INH). However, liver dysfunction was appeared after 2 weeks from the start of INH. Therefore, we discontinued INH transiently and tried the desensitization of INH. However, interstitial pneumonia was developed 2 weeks after the re-start of INH, we decided to stop the INH prophylaxis. Interstitial pneumonia was improved by corticosteroid treatments. This case report shows that INH-induced IP can be occurred during the course of anti-TB chemoprophylaxis in patients with RA.

  1. Aerosolized recombinant human lysozyme ameliorates Pseudomonas aeruginosa-induced pneumonia in hamsters.

    PubMed

    Bhavsar, Tapan; Liu, Ming; Hardej, Diane; Liu, Xingjian; Cantor, Jerome

    2010-03-01

    As an alternative to conventional antibiotics, aerosolized recombinant human lysozyme (rhLZ) was used to treat experimentally induced pneumonia. Syrian hamsters were inoculated intratracheally with a nonmucoid strain of Pseudomonas aeruginosa (PA), then exposed to a 1.0% solution of rhLZ in water for 2 hours per day for 3 consecutive days (controls were treated with aerosolized water alone). Compared to controls, the rhLZ-treated group showed statistically significant reductions in the following parameters: (1) lung histopathological changes, (2) bacterial colony-forming units in whole lung and bronchoalveolar lavage fluid (BALF), (3) total BALF leukocytes, (4) percent BALF neutrophils, and (5) alveolar septal apoptosis. Exposure to aerosolized rhLZ also resulted in a large increase in BALF lysozyme activity. These findings indicate that aerosolized rhLZ may be potentially useful in reducing the level of bacterial colonization and inflammation in the lungs of patients with PA pneumonia.

  2. Successful treatment of steroid-resistant methotrexate-induced interstitial pneumonia with peripherally administered ulinastatin.

    PubMed

    Yamazaki, Hayato; Nagasaka, Kenji

    2011-02-01

    A 76-year-old woman with rheumatoid arthritis who had been taking methotrexate (MTX) for 9 months was admitted because of acute respiratory failure. A chest radiograph revealed diffuse ground-glass attenuation. MTX-induced interstitial pneumonia (IP) was strongly suspected. Her respiratory failure worsened in spite of steroid pulse therapy. Intravenous administration of ulinastatin, however, dramatically improved her clinical condition. The second ulinastatin treatment was also effective. This case suggests that peripherally administered ulinastatin may be effective for steroid-resistant MTX-induced IP.

  3. Eosinophilic Pneumonias

    PubMed Central

    Akuthota, Praveen

    2012-01-01

    Summary: This review starts with discussions of several infectious causes of eosinophilic pneumonia, which are almost exclusively parasitic in nature. Pulmonary infections due specifically to Ascaris, hookworms, Strongyloides, Paragonimus, filariasis, and Toxocara are considered in detail. The discussion then moves to noninfectious causes of eosinophilic pulmonary infiltration, including allergic sensitization to Aspergillus, acute and chronic eosinophilic pneumonias, Churg-Strauss syndrome, hypereosinophilic syndromes, and pulmonary eosinophilia due to exposure to specific medications or toxins. PMID:23034324

  4. [Survival by a young woman with malnutrition due to alcoholism and eating disorders and with acute respiratory distress syndrome due to severe pneumonia who showed increased serum neutrophil elastase activity].

    PubMed

    Nakajima, Hirokazu; Sawaguchi, Hirochiyo; Nakajima, Shigenori

    2006-11-01

    A 30-year-old woman with malnutrition due to alcoholism and eating disorders was found to have acute respiratory distress syndrome (ARDS) and sepsis due to severe Streptococcus pneumoniae pneumonia. S. pneumoniae was detected by an in vitro rapid immunochromatographic assay for S. pneumoniae antigen in urine on the day of admission and by blood culture 2 days after admission. Symptoms and laboratory findings improved after treatment with sivelestat sodium hydrate, antibiotics, and mechanical ventilation. Treatment with sivelestat sodium hydrate also decreased serum neutrophil elastase activity. This case demonstrates the usefulness of early treatment with sivelestat sodium hydrate in ARDS due to severe pneumonia.

  5. Severe pneumonia caused by combined infection with Pneumocystis jiroveci, parainfluenza virus type 3, cytomegalovirus, and Aspergillus fumigatus in a patient with Stevens-Johnson syndrome/toxic epidermal necrolysis.

    PubMed

    Lee, Taehoon; Bae, Yun-Jeong; Park, Soo-Kyung; Park, Hyun Jung; Kim, Sung-Han; Cho, You Sook; Moon, Hee-Bom; Lee, Sang-Oh; Kim, Tae-Bum

    2010-11-01

    Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe adverse cutaneous reactions to drugs. We report here the first case of severe pneumonia caused by an unusual combined infection with Pneumocystis carinii (jiroveci), parainfluenza virus type 3, cytomegalovirus and Aspergillus fumigatus in a 63-year-old female patient with allopurinol-induced SJS/TEN overlap syndrome. Following treatment with high-dose systemic corticosteroids and intravenous immunoglobulin for SJS/TEN, her mucocutaneous lesions improved and she was due to be discharged. However, 15 days after cessation of corticosteroids, she developed pneumonia. Broncho-alveolar lavage revealed that the cause of infection was Pneumocystis carinii (jiroveci), parainfluenza virus type 3, cytomegalovirus and Aspergillus. These findings indicate that patients with SJS/TEN, particularly those treated with systemic corticosteroids, may be susceptible to infection with combinations of pathological agents resulting from damage to the bronchial epithelia. PMID:21057748

  6. Drug induced acute pancreatitis: incidence and severity.

    PubMed Central

    Lankisch, P G; Dröge, M; Gottesleben, F

    1995-01-01

    To determine the incidence and severity of drug induced acute pancreatitis, data from 45 German centres of gastroenterology were evaluated. Among 1613 patients treated for acute pancreatitis in 1993, drug induced acute pancreatitis was diagnosed in 22 patients (incidence 1.4%). Drugs held responsible were azathioprine, mesalazine/sulfasalazine, 2',3'-dideoxyinosine (ddI), oestrogens, frusemide, hydrochlorothiazide, and rifampicin. Pancreatic necrosis not exceeding 33% of the organ was found on ultrasonography or computed tomography, or both, in three patients (14%). Pancreatic pseudocysts did not occur. A decrease of arterial PO2 reflecting respiratory insufficiency, and an increase of serum creatinine, reflecting renal insufficiency as complications of acute pancreatitis were seen in two (9%) and four (18%) patients, respectively. Artificial ventilation was not needed, and dialysis was necessary in only one (5%) case. Two patients (9%) died of AIDS and tuberculosis, respectively; pancreatitis did not seem to have contributed materially to their death. In conclusion, drugs rarely cause acute pancreatitis, and drug induced acute pancreatitis usually runs a benign course. PMID:7489946

  7. 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

  8. Clinical Usefulness of Urinary Fatty Acid Binding Proteins in Assessing the Severity and Predicting Treatment Response of Pneumonia in Critically Ill Patients

    PubMed Central

    Tsao, Tsung-Cheng; Tsai, Han-Chen; Chang, Shi-Chuan

    2016-01-01

    assessing the pneumonia severity and in predicting treatment response, respectively. Further studies with larger populations are needed to verify these issues. PMID:27175705

  9. 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

  10. 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

  11. 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

  12. Childhood very severe pneumonia and meningitis-related hospitalization and death in Yemen, before and after introduction of H. influenzae type b (Hib) vaccine.

    PubMed

    Banajeh, S M; Ashoor, O; Al-Magramy, A S

    2014-07-08

    Haemophilus influenzae type b (Hib) vaccine was included in the Yemen immunization programme in 2005. This study compared the rates of very severe pneumonia and all-cause meningitis hospitalization and death, before and after introduction of conjugate Hib vaccine, and reports the results of the 2010 bacterial meningitis surveillance. A retrospective analysis was made of data collected for 2000-2010 for all children aged 2-60 months in the main children's hospital in Sana'a. Compared with the pre-Hib vaccination period, the post-Hib period showed significant and impressive reductions in the rates of hospitalization and death for all-cause meningitis. However, hospitalization and death for very severe pneumonia improved only modestly, and there was evidence of a decreasing but non-significant trend indicting that very severe pneumonia was a non-specific endpoint with multi-etiologies (both viral and bacterial). Very severe pneumonia remains the leading cause of severe morbidity and death for young children, particularly those aged < 12 months.

  13. 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

  14. 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

  15. 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 ...

  16. The management of severe community acquired pneumonia in the intensive care unit.

    PubMed

    Liapikou, Adamantia; Rosales-Mayor, Edmundo; Torres, Antoni

    2014-06-01

    Severe CAP (SCAP), accounting for 6% of admissions to intensive care units (ICUs) needs early diagnosis and aggressive interventions at the most proximal point of disease presentation. The prognostic scores as the ATS/IDSA rule, the systolic blood pressure, multilobar infiltrates, albumin, respiratory rate, tachycardia, confusion, oxygen and pH or SCAP system are appropriate in early identification of eligible patients requiring admission to ICU. Then the recommended initial resuscitation in SCAP in the ICU consists of fluid volume intake titrated to specific goals after a fluid challenge and hemodynamic optimization. The first selection of antimicrobial therapy should be started in the first hour and would be broad enough to cover all likely pathogens. Combination therapy may be useful in patients with non refractory septic shock and severe sepsis pneumococcal bacteremia as well. After 6 hours the patient would be reevaluated in terms of hemodynamic stability and antibiotic and therapy. Future developments will focus on sepsis biomarkers, molecular diagnostic techniques and the development of novel therapeutic immunomodulaty agents.

  17. 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

  18. Value of bronchoalveolar lavage in the management of severe acute pneumonia and interstitial pneumonitis in the immunocompromised child.

    PubMed Central

    de Blic, J; McKelvie, P; Le Bourgeois, M; Blanche, S; Benoist, M R; Scheinmann, P

    1987-01-01

    The diagnostic value of 73 bronchoalveolar lavages was assessed in 67 immunocompromised children (aged 3 months to 16 years) with pulmonary infiltrates. Thirty one children had primary and 19 secondary immune deficiency, 14 acquired immunodeficiency syndrome (AIDS), and three AIDS related complex. Bronchoalveolar lavage was performed during fibreoptic bronchoscopy, under local anaesthesia in all but two. One or more infective agents was found in eight of 11 patients with severe acute pneumonia and in 26 of 62 patients with interstitial pneumonitis. In interstitial pneumonitis, the most frequently encountered agents were Pneumocystis carinii (12), cytomegalovirus (8), and Aspergillus fumigatus (3). The yield was related to the severity of interstitial pneumonitis. The mean cellular count and cytological profile in lavage returns from patients with varying infective agents or underlying pathological conditions showed no significant difference, except in those children with AIDS and AIDS related complex who had appreciable lymphocytosis (mean percentage of lymphocytes 28 (SD 17]. In children with AIDS and chronic interstitial pneumonitis lymphocytosis without pneumocystis infection was observed in eight of nine bronchoalveolar lavage returns and was suggestive of pulmonary lymphoid hyperplasia. Finally, bronchoalveolar lavage produced a specific diagnosis from the microbiological or cytological findings in 44 instances (60%). Transient exacerbation of tachypnoea was observed in the most severely ill children but there was no case of respiratory decompensation attributable to the bronchoscopy. Bronchoalveolar lavage is a safe and rapid examination for the investigation of pulmonary infiltrates in immunocompromised children. It should be performed as a first line investigation and should reduce the use of open lung biopsy techniques. PMID:2827334

  19. Berberine inhibits Chlamydia pneumoniae infection-induced vascular smooth muscle cell migration through downregulating MMP3 and MMP9 via PI3K.

    PubMed

    Ma, Lu; Zhang, Lijun; Wang, Beibei; Wei, Junyan; Liu, Jingya; Zhang, Lijun

    2015-05-15

    The mechanisms by which Chlamydia pneumoniae infection promote vascular smooth muscle cell (VSMC) migration required in the development of atherosclerosis have not yet been fully clarified. Matrix metalloproteinases (MMPs) have important roles in VSMC migration. However, it is still unknown whether MMPs are involved in C. pneumoniae infection-induced VSMC migration. In addition, whether berberine can exert its inhibitory effects on the infection-induced VSMC migration also remains unclear. Accordingly, we investigated the effects of berberine on C. pneumoniae infection-induced VSMC migration and explored the possible mechanisms involved in this process. Herein, we found that C. pneumoniae infection could induce VSMC migration through Matrigel-coated membrane (P<0.05), which can be significantly inhibited by the broad-spectrum MMP inhibitor GM6001 (P<0.05). Our results also showed that C. pneumoniae infection upregulated both mRNA and protein expressions of MMP3 and MMP9 (P<0.05). The specific phosphoinositide 3-kinase (PI3K) inhibitor LY294002 significantly suppressed the increases in MMP3 and MMP9 protein expressions induced by C. pneumoniae infection (P<0.05). Further experiments showed that berberine significantly attenuated C. pneumoniae infection-induced VSMC migration (P<0.05). Moreover, berberine suppressed the protein expressions of MMP3 and MMP9 caused by C. pneumoniae infection in a dose-dependent manner (P<0.05). C. pneumoniae infection-induced increase in the phosphorylation level of Akt at Ser473 was inhibited by the treatment with berberine (P<0.05). Taken together, our data suggest that berberine inhibits C. pneumoniae infection-induced VSMC migration by downregulating the expressions of MMP3 and MMP9 via PI3K.

  20. Carbamazepine-Induced Incomplete Stevens-Johnson Syndrome: Report of a Case in Children without Mycoplasma pneumoniae Infection.

    PubMed

    Techasatian, Leelawadee; Panombualert, Sunee; Uppala, Rattapon; Jetsrisuparb, Charoon

    2015-08-01

    Incomplete Stevens-Johnson syndrome (SJS) is a rare reactive skin condition. Most cases are occurred in children and all are associated with Mycoplasma pneumoniae (M. pneumoniae) infection. We reported an unusual case of a 6-year-old boy who developed the presentation of isolated mucosal erosion with a lack of skin findings, which indicated incomplete SJS after two weeks of carbamazepine (CBZ) administration. Findings of positive HLA-B*1502 allele supported a possible causative influence of carbamazepine inducing SJS. Interestingly, this patient was tested negatively for M. pneumoniae. This is a significant finding since there is no previous report of incomplete SJS without M. pneumoniae infection. Discontinuation of CBZ and administration of systemic corticosteroids were accomplished to treat SJS, which resulted in complete recovery. Our interesting findings highlighted the manifestation of incomplete SJS, which can present with other causes rather than M. pneumoniae infection. Early manifestation of mucosal change without typical skin lesions should not be neglected in the diagnosis of incomplete SJS. PMID:26742396

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

    PubMed Central

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

    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

  2. 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

  3. 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

  4. 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

  5. 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

  6. Calf pneumonia.

    PubMed

    Bryson, D G

    1985-07-01

    Infectious calf pneumonia is a high-mortality pneumonia of housed dairy-type calves. Viruses are important etiologic agents and infection with bovine respiratory syncytial virus (RSV) and parainfluenza type 3 virus (PI-3 virus) may result in extensive, and sometimes fatal, lung damage. Respiratory viral infections are frequently followed by mycoplasmal and secondary bacterial invasion of the lower respiratory tract, which increases the extent and severity of lung damage. Bad housing, particularly bad ventilation, will increase the severity of pneumonia outbreaks. Although the source of respiratory viral infections is not always obvious, it is likely that a proportion of calves acquired infection from their dams early in life. The possibility of cross-infections from other domestic animals and from humans must also be considered. Diagnosis of respiratory virus infections necessitates submission of suitable respiratory tract specimens that are taken at an early stage in the outbreak together with paired sera. Various therapeutic and prophylactic regimens for the control of calf pneumonia are described. PMID:3907774

  7. 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

  8. Severe acute respiratory failure secondary to acute fibrinous and organizing pneumonia requiring mechanical ventilation: a case report and literature review.

    PubMed

    López-Cuenca, Sonia; Morales-García, Silvia; Martín-Hita, Ana; Frutos-Vivar, Fernando; Fernández-Segoviano, Pilar; Esteban, Andrés

    2012-08-01

    A 27-year-old woman was admitted to our ICU with acute hypoxemic respiratory failure and criteria for ARDS. Despite an F(IO(2)) of 1.0 and a lung protective strategy, the patient died on day 15 without any improvement. The relatives gave consent for post-mortem analysis. The histopathologic study of the lung showed findings typical of an acute fibrinous and organizing pneumonia. Apropos of this case we performed a PubMed search. We found 13 articles, including a total of 29 patients. Acute fibrinous and organizing pneumonia is an unusual cause of acute lung injury. The diagnostic criterion is histopathologic. There is little information regarding the pathophysiology of this illness. Important questions remain regarding this disease, including predisposing factors and management. Patients who require mechanical ventilation have poor outcomes.

  9. 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

  10. [Acute community-acquired pneumonia of moderate and grave severity investigated by bronchoscopy. Analysis of 193 cases hospitalized in a general hospital].

    PubMed

    Vivès, L; Biel, P; Maler, G; Labonne, F; Lecoules, N; Dufour, M; Marignol, G; Vanche, J

    1996-01-01

    Between February 1989 and June 1994 193 cases of acute community acquired pneumonia (PAC) which were of intermediate or great severity were admitted to two hospitals in the South West of France. These patients were explored using bronchofibroscopy (FB) with a protected brush (BP) and alveolar microlavage (MLBA) and quantitative cultures were performed, also there were other specimens taken in a regular fashion. The percentage of positive examinations was 60% for brushings (BP), 59% for MLBA and 21% for blood cultures and 16% for serological tests. An aetiology was determined in 137 cases (70.9%). The organisms recovered were Streptococcus pneumoniae (49.6%), gram negative bacilli (17.4%), Haemophilus influenzae (11.7%), Mycoplasma pneumoniae (4.4%), Mycobacterium tuberculosis (4.4%), Staphylococcus aureus (3.6%), Chlamydia pneumoniae (2.2%), Legionella pneumophila (0.7%), and various 5.8%. The overall mortality was 15% despite immediate antibiotics based on the likely organism in 88% of cases. The study of prognostic factors confirmed the Fine score system (determined a posteriori) which constitutes a useful and practical index determining the management of PAC. On the other hand the role of bacteriological documentation in improving the vital prognosis remains to be confirmed. If bronchofibroscopy has appeared to us as a safe and useful means of investigation, the management of these disease remains to specified. We suggest that its use is reserved for subjects with life threatening disease (a Fine score equal to or greater than 3) or for those patients who are likely to have unusual germs: failure of previous antibiotics, diabetes, malnourishment, cancer, airflow obstruction and inhalation. PMID:8711237

  11. 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

  12. Ethanol-induced alcohol dehydrogenase E (AdhE) potentiates pneumolysin in Streptococcus pneumoniae.

    PubMed

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

    2015-01-01

    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.

  13. Aspiration-related organizing pneumonia complicating laparoscopic adjustable gastric banding: A lung cancer mimicker

    PubMed Central

    Aljohaney, Ahmed A.; Ajlan, Amr M.; Alghamdi, Fahad A.

    2016-01-01

    There are several described pulmonary complications due to laparoscopic adjustable gastric banding. We report a rare case of a 32-year-old male who presented with pulmonary symptoms and a solitary lung mass 12 years after laparoscopic adjustable gastric banding. A bronchoscopic lung biopsy showed organizing pneumonia that was induced by aspiration pneumonia. The atypical radiological appearance of the aspiration pneumonia may pose a diagnostic challenge, and clinicians' awareness regarding such an entity is needed to avoid unnecessary intervention. PMID:27803757

  14. 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

  15. 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.

  16. Correspondence between hospital admission and the pneumonia severity index (PSI), CURB-65 criteria and comparison of their predictive value in mortality and hospital stay.

    PubMed

    Varshochi, Mojtaba; Kianmehr, Parisa; Naghavi-Behzad, Mohammad; Bayat-Makoo, Zhinous

    2013-06-01

    Pneumonia severity assessment systems, such as the pneumonia severity index (PSI) and CURB-65, were designed to guide physicians to admit the patients involved to appropriate wards of hospitals. This study evaluated concordance rate of decisions leading to patients' hospitalization in accordance with PSI and CURB-65 criteria and comparison of the two systems' P-values in evaluating mortality and the hospitalization period of the patients in question. A total of 134 hospitalized patients with community-acquired pneumonia (CAP) were evaluated. Patients were classified on the basis of risk factors implicated in the PSI and CURB-65 systems. Prognostic P-values and indication measures of hospitalization for the two systems were then compared. Eighty-seven males (64.9%) and 47 females (35.1%) with a mean age of 64.23±19.82 (15-103) years were enrolled in the study. Based on the results of both systems, hospitalization was indicated in 112 cases (83.6%) and there was total agreement between the two systems in 61 cases (45.5%). There was no significant association between hospitalization duration in the two systems. However, both systems significantly predicted mortality within the hospitalization period with rather equal accuracies. Patients expired more frequently in the group with indication of hospitalization based on the PSI classes. However, there was no significant difference in the mortality between the two groups with and without admission indication according to the CURB-65 system. A considerable portion of our hospitalizations met the related criteria of the PSI/CURB-65. The two evaluation systems have near equal sensitivity and specificity for predicting mortality among hospitalized patients with CAP when the PSI class IV-V and CURB-65 score ≥ 2.

  17. 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

  18. 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.

  19. 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 ...

  20. 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.

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

    PubMed

    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. 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

  3. Antibody responses of Chlamydophila pneumoniae pneumonia: Why is the diagnosis of C. pneumoniae pneumonia difficult?

    PubMed

    Miyashita, Naoyuki; Kawai, Yasuhiro; Tanaka, Takaaki; Akaike, Hiroto; Teranishi, Hideto; Wakabayashi, Tokio; Nakano, Takashi; Ouchi, Kazunobu; Okimoto, Niro

    2015-07-01

    The ELNAS Plate Chlamydophila pneumoniae commercial test kit for the detection of anti-C. pneumoniae-specific immunoglobulin M (IgM), IgA and IgG antibodies has become available in Japan recently. To determine the optimum serum collection point for the ELNAS plate in the diagnosis of C. pneumoniae pneumonia, we analyzed the kinetics of the antibody response in patients with laboratory-confirmed C. pneumoniae pneumonia. We enrolled five C. pneumoniae pneumonia cases and collected sera from patients for several months. The kinetics of the IgM and IgG antibody responses were similar among the five patients. Significant increases in IgM and IgG antibody titer between paired sera were observed in all patients. IgM antibodies appeared approximately 2-3 weeks after the onset of illness, reached a peak after 4-5 weeks, and were generally undetectable after 3-5 months. IgG antibodies developed slowly for the first 30 days and reached a plateau approximately 3-4 months after the onset of illness. The kinetics of IgA antibody responses were different among the five patients, and significant increases in IgA antibody titer between paired sera were observed in only two patients. Although the sample size was small, the best serum collection time seemed to be approximately 3-6 weeks after onset of illness when using a single serum sample for the detection of IgM antibodies. Paired sera samples should be obtained at least 4 weeks apart. IgA antibody analysis using ELNAS may not be a useful marker for acute C. pneumoniae pneumonia.

  4. 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

  5. Cylindromatosis (CYLD) inhibits Streptococcus pneumonia-induced plasminogen activator inhibitor-1 expression via interacting with TRAF-6.

    PubMed

    Wu, Jing; Zhao, Jing; Yu, Jie; Zhang, Wenhong; Huang, Yuxian

    2015-08-01

    Streptococcus pneumoniae (S. p) remains one of the foremost causes of community-acquired pneumonia. Recent studies have shown that S. p lung infection is associated with plasminogen activator inhibitor-1 (PAI-1) expression, which inhibits acute lung injury. Such effects by S. p were negatively regulated by cylindromatosis (CYLD). The current study explored the underlying mechanisms. We showed that S. p-induced PAI-1 expression requires tumor necrosis factor receptor-associated factor 6 (TRAF-6) signaling. Si-RNA-mediated knockdown of TRAF-6 remarkably inhibited S. p-induced PAI-1 expression. Reversely, over-expression of wild type (wt-) TRAF-6 further potentiated PAI-1 expression in S. p-treated cells. We provided evidences to support that CYLD-mediated anti-PAI-1 activity might be through direct regulation of TRAF-6. Our results from co-immunoprecipitation (co-IP) and confocal microscopy assays confirmed a direct association between the CYLD and TRAF-6 in A549 cells. Over-expression of wt-CYLD remarkably inhibited TRAF-6 ubiquitination and subsequent PAI-1 expression. Introducing a mutated CYLD, on the other hand, enhanced TRAF-6 ubiquitination and PAI-1 expression. Together, these results indicate that TRAF-6 mediates S. p-induced PAI-1 expression, and CYLD inhibits PAI-1 expression probably through deubiquitinating TRAF-6. The current study provided molecular insights of CYLD-mediated activities in S. p-induced PAI-1 expression and possible acute lung injury.

  6. Hospital Acquired Pneumonia is an Independent Predictor of Poor Global Outcome in Severe Traumatic Brain Injury up to 5 Years after Discharge

    PubMed Central

    Kesinger, Matthew R.; Kumar, Raj G.; Wagner, Amy K.; Puyana, Juan C.; Peitzman, Andrew P.; Billiar, Timothy R.; Sperry, Jason L.

    2016-01-01

    Objectives Long-term outcomes following traumatic brain injury (TBI) correlate with initial head injury severity and other acute factors. Hospital-acquired pneumonia (HAP) is a common complication in TBI. Little information exists regarding the significance of infectious complications on long-term outcomes post-TBI. We sought to characterize risks associated with HAP on outcomes 5 years post-TBI. Methods Ddata from the merger of an institutional trauma registry and the TBI Model Systems outcome data. Individuals with severe head injuries (Abbreviated Injury Scale≥4), who survived to rehabilitation were analyzed. Primary outcome was Glasgow Outcome Scaled-Extended (GOSE) at 1, 2, and 5 years. GOSE was dichotomized into LOW (GOSE<6) and HIGH (GOSE≥6). Logistic regression was utilized to determine adjusted odds of LOW-GOSE associated with HAP after controlling for age, sex, head and overall injury severity, cranial surgery, Glasgow Coma Scale (GCS), ventilation days, and other important confounders. A general estimating equation (GEE) model was used to analyze all outcome observations simultaneously while controlling for within-patient correlation. Results A total of 141 individuals met inclusion criteria, with a 30% incidence of HAP. Individuals with and without HAP had similar demographic profiles, presenting vitals, head injury severity, and prevalence of cranial surgery. Individuals with HAP had lower presenting GCS. Logistic regression demonstrated that HAP was independently associated with LOW-GOSE scores at follow-up (1year: OR=6.39, 95%CI: 1.76-23.14, p=0.005; 2-years: OR=7.30, 95%CI 1.87-27.89, p=0.004; 5-years: OR=6.89, 95%CI: 1.42-33.39, p=0.017). Stratifying by GCS≤8 and early intubation, HAP remained a significant independent predictor of LOW-GOSE in all strata. In the GEE model, HAP continued to be an independent predictor of LOW-GOSE (OR: 4.59; 95%CI: 1.82-11.60′ p=0.001). Conclusion HAP is independently associated with poor outcomes in severe

  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. Differential expression of cytokine genes and inducible nitric oxide synthase induced by opacity phenotype variants of Streptococcus pneumoniae during acute otitis media in the rat.

    PubMed

    Long, J P; Tong, H H; Shannon, P A; DeMaria, T F

    2003-10-01

    Phase variation in the colonial opacity phenotype of Streptococcus pneumoniae has been implicated as a factor in bacterial adherence, colonization, and invasion in the pathogenesis of pneumococcal otitis media (OM). The purpose of this study was to determine whether S. pneumoniae opacity variants influence the induction of gene expression for proinflammatory mediators in vivo using the rat model of OM. Both the opaque and transparent phenotype variants induced a significant up-regulation in gene expression for interleukin-1alpha (IL-1alpha), IL-1beta, IL-6, IL-10, tumor necrosis factor alpha, and inducible nitric oxide synthase (iNOS) compared to saline sham-inoculated controls at both 4 and 24 h postinoculation (P < 0.05 in all cases). Furthermore, whereas a significant difference in gene expression was evident for only IL-6 (greater following challenge with the opaque variant) and IL-1beta (greater following challenge with the transparent variant) at 4 h, by 24 h the opaque variant cohort demonstrated a significant increase in gene expression for IL-1alpha, IL-1beta, IL-6, IL-10, and iNOS relative to animals inoculated with the transparent phenotype variant (P < 0.05 in all cases). Enzyme-linked immunosorbent assay results confirmed the gene expression data as determined by real-time PCR. Moreover, the concentrations of the opaque variant in the middle ear lavage fluid were a full log higher than those of the transparent variant. The aforementioned results indicate that the opaque phenotype variant is more efficient at survival and multiplication within the middle ear space, resulting in the accumulation of more inflammatory cells and the enhanced expression and production of inflammatory mediators. However, when the data were normalized to account for differences in middle ear bacterial titers, it became apparent that the transparent variant of S. pneumoniae is a more potent inducer of inflammation, triggering the accumulation of more inflammatory cells and

  9. [Chronic eosinophilic pneumonia].

    PubMed

    Vivero, F; Ciocchini, C; Gandini, M J; Wehbe, L

    2012-03-01

    Chronic eosinophilic pneumonia. The chronic eosinophilic pneumonia is part of Pulmonary Eosinophilic Syndroms. It is presented a 33-years old man, Asmathic, with dry cough, fever, night sweats and fatigue of several weeks. The chest X-ray showed opacity in the right hemithorax. He was treated with antibiotics without response. A chest TC showed multifocal involvement. The patient refused bronchoalveolar lavage (BAL) so treatment antituberculostatic was started. Despite treatment the symptoms worsened. The Chest X-ray showed migration of the infiltrates and the blood smear marked eosinophilia. Finally, bronchoalveolar lavage was carried out and it showed a high percentage of eosinophils (over 50%). The patient was treated with inmmunosuppresive doses of corticosteroids with excellent response. The blood smear in Nonresolving pneumonia is key to consider eosinophilic pneumonia, an uncommon pathology but amenable to treatment.

  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 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

  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

    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

  12. Severe valproate induced hyperammonemic encephalopathy successfully managed with peritoneal dialysis.

    PubMed

    Kumar, Amandeep; Suri, Ashish; Sharma, Bhawani S

    2014-07-01

    Valproic acid (VPA) is a commonly used drug for epilepsy, psychiatric disorders and migraine and is frequently used in neurosurgical intensive care units. Though most of its side-effects are mild and transient, certain idiosyncratic side-effects have been attributed to VPA. Valproate induced hyperammonemia (VIH) is one such side-effect. VIH can produce symptoms of encephalopathy known as valproate induced hyperammonemic encephalopathy (VHE). VIH and VHE usually respond to withdrawal of VPA. However, in some cases VHE can be unresponsive to supportive measures and severe enough to be life-threatening. In such cases, dialysis can be used to rapidly reverse hyperammonemia and VHE and can prove to be a lifesaving measure. We report such a case of VIH and life-threatening VHE in a postoperative neurosurgical patient that was managed successfully with peritoneal dialysis.

  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. 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.

  17. 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.

  18. 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

  19. Therapeutic strategy for pandrug-resistant Klebsiella pneumoniae severe infections: short-course treatment with colistin increases the in vivo and in vitro activity of double carbapenem regimen.

    PubMed

    Oliva, Alessandra; Mascellino, Maria T; Cipolla, Alessia; D'Abramo, Alessandra; De Rosa, Annalisa; Savinelli, Stefano; Ciardi, Maria Rosa; Mastroianni, Claudio M; Vullo, Vincenzo

    2015-04-01

    Infections due to carbapenemase-producing Klebsiella pneumoniae represent an emerging threat due to the high mortality rate and lack of valid antimicrobial combinations, especially when the strain is colistin-resistant. We report a case of bloodstream infection due to pandrug-resistant K. pneumoniae treated successfully with an innovative regimen comprising a combination of colistin plus double carbapenem, along with an in vitro analysis showing the synergistic and bactericidal effect.

  20. Programmed Death Ligand 1 Promotes Early-Life Chlamydia Respiratory Infection-Induced Severe Allergic Airway Disease.

    PubMed

    Starkey, Malcolm R; Nguyen, Duc H; Brown, Alexandra C; Essilfie, Ama-Tawiah; Kim, Richard Y; Yagita, Hideo; Horvat, Jay C; Hansbro, Philip M

    2016-04-01

    Chlamydia infections are frequent causes of respiratory illness, particularly pneumonia in infants, and are linked to permanent reductions in lung function and the induction of asthma. However, the immune responses that protect against early-life infection and the mechanisms that lead to chronic lung disease are incompletely understood. In the current study, we investigated the role of programmed death (PD)-1 and its ligands PD-L1 and PD-L2 in promoting early-life Chlamydia respiratory infection, and infection-induced airway hyperresponsiveness (AHR) and severe allergic airway disease in later life. Infection increased PD-1 and PD-L1, but not PD-L2, mRNA expression in the lung. Flow cytometric analysis of whole lung homogenates identified monocytes, dendritic cells, CD4(+), and CD8(+) T cells as major sources of PD-1 and PD-L1. Inhibition of PD-1 and PD-L1, but not PD-L2, during infection ablated infection-induced AHR in later life. Given that PD-L1 was the most highly up-regulated and its targeting prevented infection-induced AHR, subsequent analyses focused on this ligand. Inhibition of PD-L1 had no effect on Chlamydia load but suppressed infection-induced pulmonary inflammation. Infection decreased the levels of the IL-13 decoy receptor in the lung, which were restored to baseline levels by inhibition of PD-L1. Finally, inhibition of PD-L1 during infection prevented subsequent infection-induced severe allergic airways disease in later life by decreasing IL-13 levels, Gob-5 expression, mucus production, and AHR. Thus, early-life Chlamydia respiratory infection-induced PD-L1 promotes severe inflammation during infection, permanent reductions in lung function, and the development of more severe allergic airway disease in later life.

  1. 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

  2. B7 homolog 3 aggravates brain injury in a murine model of Streptococcus pneumoniae-induced meningitis

    PubMed Central

    CHEN, XUQIN; WANG, YANPING; WANG, ZHEDONG; YAN, RUHONG; LIU, JIE; MENG, XIANGYING; LI, YAN; WANG, JIANGHUAI; WANG, JIAN

    2015-01-01

    Despite the application of antibiotics, Streptococcus pneumoniae (SP)-induced meningitis continues to be a life-threatening disease with a high fatality rate and an elevated risk of serious neurological sequelae, particularly in developing countries. In this study, the contribution of the co-stimulatory molecule B7 homolog 3 (B7-H3) to the pathogenesis of experimental SP-induced meningitis was investigated. Mice were challenged with the intracerebroventricular injection of serotype 3 SP with or without B7-H3. The clinical status of mice with SP-induced meningitis was examined by body weight loss and spontaneous motor activity with neurological scoring. Coronal brain sections were analyzed by counting Nissl-positive neurons and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells. Protein expression of neuron-specific enolase (NSE) and S100B in brain tissues was examined with immunohistochemical staining. All experiments were performed in a randomized and blinded setting. By the intracerebroventricular injection of SP suspension, a murine model of pneumococcal meningitis was successfully established. In this SP-induced meningitis model, B7-H3 deteriorated the clinical status, as manifested by a decreased neurological score and increased body weight loss. Following the B7-H3 challenge, the number of Nissl-positive cells decreased and TUNEL-stained positive cells increased in the brain tissues of mice with SP meningitis, which demonstrates the enhancement of neuronal necrosis and apoptosis, respectively. Protein expression of NSE was decreased, while that of S100B was increased. These in vivo findings indicate that B7-H3 aggravates brain injury during the pathological process of experimental SP-induced meningitis. PMID:26136926

  3. A case of losartan-induced severe hyponatremia.

    PubMed

    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

  4. 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.

  5. 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

  6. Drebrin Inhibits Cofilin-Induced Severing of F-Actin

    PubMed Central

    Grintsevich, Elena E.; Reisler, Emil

    2015-01-01

    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

  7. 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.

  8. 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.

  9. 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.

  10. The effects of danofloxacin and tilmicosin on neutrophil function and lung consolidation in beef heifer calves with induced Pasteurella (Mannheimia) haemolytica pneumonia.

    PubMed

    Fajt, V R; Apley, M D; Roth, J A; Frank, D E; Brogden, K A; Skogerboe, T L; Shostrom, V K; Chin, Y-L

    2003-06-01

    Pneumonia caused by Pasteurella (Mannheimia) haemolytica was induced in weaned beef heifer calves, approximately 6 months of age. Calves were treated at 20 h after challenge with therapeutic doses of danofloxacin or tilmicosin. Peripheral blood neutrophils were collected at 3, 24 and 48 h after treatment. The ex vivo effects on neutrophil function, neutrophil apoptosis, and hematological parameters were examined, as was the effect on percentage lung consolidation. Neutrophil function assays included random migration under agarose, cytochrome C reduction, iodination, Staphylococcus aureus ingestion, chemotaxis, and antibody-dependent and antibody-independent cell-mediated cytotoxicity. Apoptosis was determined using a cell death detection kit. Killing was performed at 72 h after treatment. Statistical comparisons were made among the three groups of challenged-treated animals: saline, danofloxacin, and tilmicosin. Comparisons were also made between nonchallenged nontreated animals (NCH) and challenged saline-treated animals. There were no significant differences for any of the neutrophil function assays or neutrophil apoptosis among the challenged-treated groups. This suggests that danofloxacin and tilmicosin have no clinically significant effects on neutrophil function or apoptosis. There were also no significant differences in percentage lung consolidation among the challenged-treated groups. Significant differences were found between the NCH calves and the challenged saline-treated calves in several neutrophil assays, which were attributed to effects of P. haemolytica infection.

  11. 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.

  12. 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

  13. 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

  14. 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. ...

  15. Targeting galectin-1-induced angiogenesis mitigates the severity of endometriosis.

    PubMed

    Bastón, Juan I; Barañao, Rosa I; Ricci, Analía G; Bilotas, Mariela A; Olivares, Carla N; Singla, José J; Gonzalez, Alejandro M; Stupirski, Juan C; Croci, Diego O; Rabinovich, Gabriel A; Meresman, Gabriela F

    2014-11-01

    Endometriosis is characterized by the presence of endometrial tissue outside the uterus that causes severe pelvic pain and infertility in women of reproductive age. Although not completely understood, the pathophysiology of the disease involves chronic dysregulation of inflammatory and vascular signalling. In the quest for novel therapeutic targets, we investigated the involvement of galectin-1 (Gal-1), an endogenous glycan-binding protein endowed with both immunosuppressive and pro-angiogenic activities, in the pathophysiology of endometriotic lesions. Here we show that Gal-1 is selectively expressed in stromal and endothelial cells of human endometriotic lesions. Using an experimental endometriosis model induced in wild-type and Gal-1-deficient (Lgals1(-/-) ) mice, we showed that this lectin orchestrates the formation of vascular networks in endometriotic lesions in vivo, facilitating their ectopic growth independently of vascular endothelial growth factor (VEGF) and the keratinocyte-derived CXC-motif (CXC-KC) chemokine. Targeting Gal-1 using a specific neutralizing mAb reduced the size and vascularized area of endometriotic lesions within the peritoneal compartment. These results underline the essential role of Gal-1 during endometriosis and validate this lectin as a possible target for the treatment of disease.

  16. 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

  17. 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

  18. 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

  19. Natural antioxidant betanin protects rats from paraquat-induced acute lung injury interstitial pneumonia.

    PubMed

    Han, Junyan; 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.

  20. 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

  1. Evaluation of Curetis Unyvero, a multiplex PCR-based testing system, for rapid detection of bacteria and antibiotic resistance and impact of the assay on management of severe nosocomial pneumonia.

    PubMed

    Jamal, Wafaa; Al Roomi, Ebtehal; AbdulAziz, Lubna R; Rotimi, Vincent O

    2014-07-01

    Health care-associated pneumonia due to multidrug-resistant organisms represents a major therapeutic challenge. Unfortunately, treatment is dependent on empirical therapy, which often leads to improper and inadequate antimicrobial therapy. A rapid multiplex PCR-based Unyvero pneumonia application (UPA) assay that assists in timely decision-making has recently become available. In this study, we evaluated the performance of UPA in detecting etiological pathogens and resistance markers in patients with nosocomial pneumonia (NP). The impact of this assay on the management of severe nosocomial pneumonia was also assessed. Appropriate specimens were processed by UPA according to the manufacturer's protocol in parallel with conventional culture methods. Of the 56 patients recruited into the study, 49 (87.5%) were evaluable. Of these, 27 (55.1%) and 4 (8.2%) harbored multiple bacteria by the PCR assay and conventional culture, respectively. A single pathogen was detected in 8 (16.3%) and 4 (8.2%) patients, respectively. Thirteen different genes were detected from 38 patients, including the ermB gene (40.8%), the blaOXA-51-like gene (28.6%), the sul1 (28.6%) and int1 (20.4%) integrase genes, and the mecA and blaCTX-M genes (12.3% each). The time from sample testing to results was 4 h versus 48 to 96 h by UPA and culture, respectively. Initial empirical treatment was changed within 5 to 6 h in 33 (67.3%) patients based on the availability of UPA results. Thirty (62.2%) of the patients improved clinically. A total of 3 (6.1%) patients died, mainly from their comorbidities. These data demonstrate the potential of a multiplex PCR-based assay for accurate and timely detection of etiological agents of NP, multidrug-resistant (MDR) organisms, and resistance markers, which can guide clinicians in making early antibiotic adjustments.

  2. Early plasmapheresis in patients with severe hypertriglyceridemia induced acute pancreatitis.

    PubMed

    Nasa, Prashant; Alexander, George; Kulkarni, Amitabh; Juneja, Deven; Sehra, Sudhish; Agarwal, Rajesh; Koul, Kandy

    2015-08-01

    Hypertriglyceridemia can cause severe diseases such as acute pancreatitis (AP) and coronary artery disease. The routine management of hypertriglyceridemia is dietary restriction of fat and lipid-lowering medications to manage the secondary or precipitating causes of hypertriglyceridemia. However, in cases of AP with severe hypertriglyceridemia (SHTG) (triglycerides [TG] >1000 mg/dl) rapid reduction of TG levels to well below 1000 mg/dl can improve outcome and prevent further episodes of pancreatitis. Plasmapheresis is a therapeutic option in such medical emergencies. We discussed 2 cases of severe AP with SHTG where we used early plsmapheresis along with other supportive management. PMID:26321811

  3. [DRUG INDUCED EXANTHEMA AND SEVERE CUTANEOUS DRUG REACTIONS].

    PubMed

    Bensaïd, Benoît; Valeyrie-Allanore, Laurence; Lebrun-Vignes, Bénédicte; Nicolas, Jean-François

    2015-09-01

    Cutaneous adverse drug reactions (CADR) are delayed hypersensivities. Their clinical presentation and severity are very diverse ranging from the frequent and benign exanthemas to the rare but severe CADR involving deep organs in the case of drug reaction with eosinophilia and systemic symptoms (DRESS) or leading to skin bulla and epidermal detachment in toxic epidermal necrolysis. The main differential diagnoses are infections, especially viral ones, which could give clinical symptoms identical to those occurring in CADR.

  4. [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.

  5. [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

  6. 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

  7. Chlamydia pneumoniae and asthma

    PubMed Central

    Cook, P; Davies, P; Tunnicliffe, W; Ayres, J; Honeybourne, D; Wise, R

    1998-01-01

    BACKGROUND—This study was designed to test the association of Chlamydia pneumoniae infection with asthma in a multiracial population, after adjustments for several potential confounding variables.
METHODS—Antibodies to C pneumoniae were measured by microimmunofluorescence in 123 patients with acute asthma, 1518 control subjects admitted to the same hospital with various non-cardiovascular, non-pulmonary disorders, and 46 patients with severe chronic asthma, including some with "brittle" asthma. Acute infection or reinfection was defined by titres of IgG of ⩾512 or IgM ⩾8 or a fourfold rise in IgG, and previous infection by IgG 64-256 or IgA ⩾8. Logistic regression was used to control for likely confounders, including ethnic origin, age, sex, smoking habit, steroid medication, diabetes mellitus and social deprivation, on antibody levels.
RESULTS—Antibody titres consistent with acute C pneumoniae infection were found in 5.7% of patients with acute asthma and 5.7% of control patients, while 14.6% of patients with acute asthma and 12.7% of control patients had titres suggesting previous infection. These two groups did not differ significantly. However, titres suggesting previous infection were found in 34.8% of patients with severe chronic asthma: the difference between this group and the control group was statistically significant with an adjusted odds ratio of 3.99 (95% confidence interval 1.60 to 9.97).
CONCLUSIONS—These data raise important questions about the previously demonstrated association of C pneumoniae infection with asthma, and suggest that future studies of this association should give particular attention to the presence or absence of a history of severe chronic asthma.

 PMID:9741366

  8. 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, ...

  9. 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 ...

  10. 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 ...

  11. 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

  12. IVIG-mediated protection against necrotizing pneumonia caused by MRSA.

    PubMed

    Diep, Binh An; Le, Vien T M; Badiou, Cedric; Le, Hoan N; Pinheiro, Marcos Gabriel; Duong, Au H; Wang, Xing; Dip, Etyene Castro; Aguiar-Alves, Fábio; Basuino, Li; Marbach, Helene; Mai, Thuy T; Sarda, Marie N; Kajikawa, Osamu; Matute-Bello, Gustavo; Tkaczyk, Christine; Rasigade, Jean-Philippe; Sellman, Bret R; Chambers, Henry F; Lina, Gerard

    2016-09-21

    New therapeutic approaches are urgently needed to improve survival outcomes for patients with necrotizing pneumonia caused by Staphylococcus aureus One such approach is adjunctive treatment with intravenous immunoglobulin (IVIG), but clinical practice guidelines offer conflicting recommendations. In a preclinical rabbit model, prophylaxis with IVIG conferred protection against necrotizing pneumonia caused by five different epidemic strains of community-associated methicillin-resistant S. aureus (MRSA) as well as a widespread strain of hospital-associated MRSA. Treatment with IVIG, either alone or in combination with vancomycin or linezolid, improved survival outcomes in this rabbit model. Two specific IVIG antibodies that neutralized the toxic effects of α-hemolysin (Hla) and Panton-Valentine leukocidin (PVL) conferred protection against necrotizing pneumonia in the rabbit model. This mechanism of action of IVIG was uncovered by analyzing loss-of-function mutant bacterial strains containing deletions in 17 genes encoding staphylococcal exotoxins, which revealed only Hla and PVL as having an impact on necrotizing pneumonia. These results demonstrate the potential clinical utility of IVIG in the treatment of severe pneumonia induced by S. aureus. PMID:27655850

  13. Synoviolin inhibitor LS-102 reduces endoplasmic reticulum stress-induced collagen secretion in an in vitro model of stress-related interstitial pneumonia.

    PubMed

    Nakajima, Fukami; Aratani, Satoko; Fujita, Hidetoshi; Yagishita, Naoko; Ichinose, Shizuko; Makita, Koshi; Setoguchi, Yasuhiro; Nakajima, Toshihiro

    2015-01-01

    The deletion mutation of exon 4 in surfactant protein C (SP-C), a lung surfactant protein, has been identified in parent-child cases of familial interstitial pneumonia. It has been shown that this mutation induces endoplasmic reticulum (ER) stress. Synoviolin is an E3 ubiquitin ligase that is localized to the ER and is an important factor in the degradation of ER-related proteins. It has been demonstrated that synoviolin is involved in liver fibrosis. In the present study, we investigated the involvement of synoviolin in the pathogenesis of interstitial pneumonia caused by the exon 4 deletion in the SP-C gene. We transfected wild-type and exon 4-deleted SP-C genes into A549 human lung adenocarcinoma cells and measured the secretion of collagen, which is a representative extracellular matrix protein involved in fibrosis. Secreted collagen levels were increased in the culture medium in SP-C mutants compared to the wild-type cells. Furthermore, the transcription of mRNAs coding for factors associated with fibrosis was increased. Subsequently, to assess the involvement of synoviolin, we constructed plasmids with a luciferase gene under the control of the synoviolin promoter. The A549 cells were transfected with the construct along with the exon 4-deleted SP-C plasmid for use in the luciferase assay. We found a 1.6-fold increase in luciferase activity in the cells carrying exon 4 deleted SP-C, as well as an increase in intrinsic synoviolin expression at the mRNA and protein levels. Collagen secretion was decreased by the addition of LS-102, a synoviolin inhibitor, to the A549 culture medium following transfection with wild-type and exon 4-deleted SP-C. These results demonstrate that synoviolin is involved in the onset of interstitial pneumonia induced by exon 4-deleted SP-C, which suggests that synoviolin inhibitors may be used in the treatment of the disease.

  14. 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

  15. 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

  16. 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

  17. 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.

  18. Epidermal growth factor receptor tyrosine kinase inhibition up-regulates interleukin-6 in cancer cells and induces subsequent development of interstitial pneumonia.

    PubMed

    Ishiguro, Yukari; Ishiguro, Hitoshi; Miyamoto, Hiroshi

    2013-04-01

    Acute interstitial pneumonia is one of serious side effects of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatment, while it often has significant clinical benefit in cancer patients. Therefore, it is necessary to clarify underlying mechanisms for the development of the adverse effects by EGFR-TKI. In the present study, we attempted to determine how EGFR-TKI treatment in cancer cells induced interstitial pneumonia. The growth of tongue cancer HSC-3 and lung cancer A549 cell lines treated with EGFR-TKI was assessed by MTT assay. Cytokines and growth factors in conditioned medium (CM) obtained from EGFR-TKI-treated cancer cells were analyzed using cytokine membrane array and ELISA. Interleukin-6 (IL-6) promoter activity was measured by luciferase assay. We found that EGFR-TKI treatment significantly decreased the cell viability yet increased expression levels of IL-6 protein and mRNA, IL-6 secretion, and IL-6 transcriptional activity in these lines. In addition, using the co-culture model and IL-6 treatment was found to increase the expression of collagen and α-actin, which were markers for fibrosis, in lung fibroblast cells. These results suggest that up-regulated IL-6 plays an important role in the development of EGFR-TKI-induced interstitial fibroblastic proliferation. Therefore, blocking of IL-6 signaling could be beneficial to cancer patients undergoing EGFR-TKI treatment for reducing the risk of its unfavorable effects.

  19. Healthcare-associated Pneumonia and Aspiration Pneumonia.

    PubMed

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

    2015-02-01

    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.

  20. 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

  1. 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

  2. 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

  3. [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

  4. 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.

  5. 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.

  6. [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

  7. Severe hypoglycemia-induced lethal cardiac arrhythmias are mediated by sympathoadrenal activation.

    PubMed

    Reno, Candace M; Daphna-Iken, Dorit; Chen, Y Stefanie; VanderWeele, Jennifer; Jethi, Krishan; Fisher, Simon J

    2013-10-01

    For people with insulin-treated diabetes, severe hypoglycemia can be lethal, though potential mechanisms involved are poorly understood. To investigate how severe hypoglycemia can be fatal, hyperinsulinemic, severe hypoglycemic (10-15 mg/dL) clamps were performed in Sprague-Dawley rats with simultaneous electrocardiogram monitoring. With goals of reducing hypoglycemia-induced mortality, the hypotheses tested were that: 1) antecedent glycemic control impacts mortality associated with severe hypoglycemia; 2) with limitation of hypokalemia, potassium supplementation could limit hypoglycemia-associated deaths; 3) with prevention of central neuroglycopenia, brain glucose infusion could prevent hypoglycemia-associated arrhythmias and deaths; and 4) with limitation of sympathoadrenal activation, adrenergic blockers could prevent hypoglycemia-induced arrhythmic deaths. Severe hypoglycemia-induced mortality was noted to be worsened by diabetes, but recurrent antecedent hypoglycemia markedly improved the ability to survive an episode of severe hypoglycemia. Potassium supplementation tended to reduce mortality. Severe hypoglycemia caused numerous cardiac arrhythmias including premature ventricular contractions, tachycardia, and high-degree heart block. Intracerebroventricular glucose infusion reduced severe hypoglycemia-induced arrhythmias and overall mortality. β-Adrenergic blockade markedly reduced cardiac arrhythmias and completely abrogated deaths due to severe hypoglycemia. Under conditions studied, sudden deaths caused by insulin-induced severe hypoglycemia were mediated by lethal cardiac arrhythmias triggered by brain neuroglycopenia and the marked sympathoadrenal response.

  8. Granzymes A and B Regulate the Local Inflammatory Response during Klebsiella pneumoniae Pneumonia.

    PubMed

    García-Laorden, M Isabel; Stroo, Ingrid; Blok, Dana C; Florquin, Sandrine; Medema, Jan Paul; de Vos, Alex F; van der Poll, Tom

    2016-01-01

    Klebsiella pneumoniae is a common cause of hospital-acquired pneumonia. Granzymes (gzms), mainly found in cytotoxic lymphocytes, have been implicated as mediators of infection and inflammation. We here sought to investigate the role of gzmA and gzmB in the host response to K. pneumoniae-induced airway infection and sepsis. For this purpose, pneumonia was induced in wild-type (WT) and gzmA-deficient (gzmA-/-), gzmB-/- and gzmAxB-/- mice by intranasal infection with K. pneumoniae. In WT mice, gzmA and gzmB were mainly expressed by natural killer cells. Pneumonia was associated with reduced intracellular gzmA and increased intracellular gzmB levels. Gzm deficiency had little impact on antibacterial defence: gzmA-/- and gzmAxB-/- mice transiently showed modestly higher bacterial loads in the lungs but not in distant organs. GzmB-/- and, to a larger extent, gzmAxB-/- mice displayed transiently increased lung inflammation, reflected in the semi-quantitative histology scores and levels of pro-inflammatory cytokines and chemokines. Most differences between gzm-deficient and WT mice had disappeared during late-stage pneumonia. Gzm deficiency did not impact on distant organ injury or survival. These results suggest that gzmA and gzmB partly regulate local inflammation during early pneumonia but eventually play an insignificant role during pneumosepsis by the common human pathogen K. pneumoniae.

  9. 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

  10. 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.

  11. Pneumonia - weakened immune system

    MedlinePlus

    If you have a weakened immune system, you may receive daily antibiotics to prevent some types of pneumonia. Ask your provider if you should receive the influenza (flu) and pneumococcal (pneumonia) vaccines. Practice ...

  12. 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

  13. 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 , ...

  14. 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

  15. New aspirations: the debate on aspiration pneumonia treatment guidelines.

    PubMed

    Kwong, Jason C; Howden, Benjamin P; Charles, Patrick G P

    2011-10-01

    Aspiration pneumonia occurs most commonly in patients with a predisposition to aspiration (eg, those with neurological bulbar dysfunction). There is limited evidence regarding the involvement of anaerobes in most cases of aspiration pneumonia. Most patients respond to treatment for aspiration pneumonia without specific anti-anaerobic therapy such as metronidazole. Metronidazole has adverse side effects, and widespread use where not indicated can promote carriage of multiresistant intestinal flora such as vancomycin-resistant enterococci. Use of metronidazole may be appropriate in patients with aspiration pneumonia and evidence of a lung abscess, necrotising pneumonia, putrid sputum or severe periodontal disease.

  16. Facts and controversies in the classification of idiopathic interstitial pneumonias.

    PubMed

    Poletti, V; Kitaichi, M

    2000-10-01

    Idiopathic interstitial pneumonias are defined from the pathological point of view as non granulomatous intralobular inflammatory and fibrotic processes involving the alveolar walls. More than thirty years ago Liebow and Carrington pioneered the notion that morphological characteristics could be used with benefit in separating the different entities found in this group, which present with typical, but not pathognomonic clinical features. In the mid-1980s some entities, including giant cell interstitial pneumonia (GIP) and lymphocytic interstitial pneumonia (LIP), were removed from this group and considered as peculiar forms. In the early 90s the concept of cellular or nonspecific interstitial pneumonia was reconsidered, leading to an in depth revision of various types of interstitial pneumonia of unknown etiology. The histological pattern observed in patients with idiopathic pulmonary fibrosis is now referred to as usual interstitial pneumonia (UIP). Other entities that have been revised during the last ten years are desquamative interstitial pneumonia/alveolar macrophage pneumonia (DIP/AMP), respiratory bronchiolitis-interstitial lung disease (RB-ILD), acute interstitial pneumonia (AIP), cryptogenic organizing pneumonia (COP) and nonspecific interstitial pneumonia (NSIP). This paper provides a detailed description of pulmonary disorders which have been included in the new classification systems of idiopathic interstitial pneumonias. In the second part of the paper we will discuss several doubts and controversies that this new classification schemes leave unresolved.

  17. 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

  18. 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

  19. Novel aspects on the pathogenesis of Mycoplasma pneumoniae pneumonia and therapeutic implications

    PubMed Central

    Saraya, Takeshi; Kurai, Daisuke; Nakagaki, Kazuhide; Sasaki, Yoshiko; Niwa, Shoichi; Tsukagoshi, Hiroyuki; Nunokawa, Hiroki; Ohkuma, Kosuke; Tsujimoto, Naoki; Hirao, Susumu; Wada, Hiroo; Ishii, Haruyuki; Nakata, Koh; Kimura, Hirokazu; Kozawa, Kunihisa; Takizawa, Hajime; Goto, Hajime

    2014-01-01

    Mycoplasma pneumoniae (Mp) is a leading cause of community acquired pneumonia. Knowledge regarding Mp pneumonia obtained from animal models or human subjects has been discussed in many different reports. Accumulated expertise concerning this critical issue has been hard to apply clinically, and potential problems may remain undiscovered. Therefore, our multidisciplinary team extensively reviewed the literature regarding Mp pneumonia, and compared findings from animal models with those from human subjects. In human beings, the characteristic pathological features of Mp pneumonia have been reported as alveolar infiltration with neutrophils and lymphocytes and lymphocyte/plasma cell infiltrates in the peri-bronchovascular area. Herein, we demonstrated the novel aspects of Mp pneumonia that the severity of the Mp pneumonia seemed to depend on the host innate immunity to the Mp, which might be accelerated by antecedent Mp exposure (re-exposure or latent respiratory infection) through up-regulation of Toll-like receptor 2 expression on bronchial epithelial cells and alveolar macrophages. The macrolides therapy might be beneficial for the patients with macrolide-resistant Mp pneumonia via not bacteriological but immunomodulative effects. This exhaustive review focuses on pathogenesis and extends to some therapeutic implications such as clarithromycin, and discusses the various diverse aspects of Mp pneumonia. It is our hope that this might lead to new insights into this common respiratory disease. PMID:25157244

  20. 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

  1. 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

  2. From Moderately Severe to Severe Hypertriglyceridemia Induced Acute Pancreatitis: Circulating MiRNAs Play Role as Potential Biomarkers

    PubMed Central

    Xia, Min; Jiang, Lisha; Lu, Guoming; Huang, Mindan; Guo, Jizhong; Liu, Side

    2014-01-01

    The incidence of hypertriglyceridemia induced acute pancreatitis (HTAP) continues to rise in China. It has systemic complications and high mortality, making the early assessment of the severity of this disease even more important. Circulating microRNAs (miRNAs) could be novel, non-invasive biomarkers for disease progression judgment. This study aimed to identify the potential role of serum miRNAs as novel biomarkers of HTAP progression. HTAP patients were divided into two groups: moderately severe (HTMSAP) and severe (HTSAP), healthy people were used as control group. The serum miRNA expression profiles of these three groups were determined by microarray and verified by qRT-PCR. The functions and pathways of the targeted genes of deregulated miRNAs were predicted, using bioinformatics analysis; miRNA-mRNA network was generated. Moreover, the correlation between miR-181a-5p and pancreatitis metabolism related substances were studied and the serum concentration of inflammatory cytokines and miRNAs at different time points during the MSAP and SAP were investigated, respectively. Finally, the receiver operating characteristic (ROC) curve of miRNAs was studied. Significant changes in the serum concentration of the following miRNAs of HTAP patients (P<0.05) were discovered: miR24-3p, 361-5p, 1246, and 222-3p (constantly upregulated), and 181a-5p (constantly downregulated) (P<0.05). Bioinformatics analysis predicted that 13 GOs and 36 pathways regulated by overlap miRNAs were involved in glucose, fat, calcium (Ca++), and insulin metabolism (P<0.001). miRNA-mRNA network revealed that the overlap miRNAs targeted genes participating in pancreas metabolism and miR-181a-5p, the only downregulated miRNA, had good negative correlation with triglyceride (TG), total cholesterol (TC), and fast blood glucose (FBG), but a positive correlation with Ca++. When compared with inflammatory cytokines, the changes of all five overlap miRNAs were more stable. It was found that when used for

  3. Severe acute cholangitis after endoscopic sphincterotomy induced by barium examination: A case report.

    PubMed

    Zhang, Zhen-Hai; Wu, Ya-Guang; Qin, Cheng-Kun; Su, Zhong-Xue; Xu, Jian; Xian, Guo-Zhe; Wu, Shuo-Dong

    2012-10-21

    Endoscopic sphincterotomy (EST) is considered as a possible etiological factor for severe cholangitis. We herein report a case of severe cholangitis after endoscopic sphincterotomy induced by barium examination. An adult male patient presented with epigastric pain was diagnosed as having choledocholithiasis by ultrasonography. EST was performed and the stone was completely cleaned. Barium examination was done 3 d after EST and severe cholangitis appeared 4 h later. The patient was recovered after treated with tienam for 4 d. Barium examination may induce severe cholangitis in patients after EST, although rare, barium examination should be chosen cautiously. Cautions should be also used when EST is performed in patients younger than 50 years to avoid the damage to the sphincter of Oddi.

  4. A Thrombomodulin Mutation that Impairs Active Protein C Generation Is Detrimental in Severe Pneumonia-Derived Gram-Negative Sepsis (Melioidosis)

    PubMed Central

    Kager, Liesbeth M.; Wiersinga, W. Joost; Roelofs, Joris J. T. H.; de Boer, Onno J.; Weiler, Hartmut; van 't Veer, Cornelis; van der Poll, Tom

    2014-01-01

    Background During severe (pneumo)sepsis inflammatory and coagulation pathways become activated as part of the host immune response. Thrombomodulin (TM) is involved in a range of host defense mechanisms during infection and plays a pivotal role in activation of protein C (PC) into active protein C (APC). APC has both anticoagulant and anti-inflammatory properties. In this study we investigated the effects of impaired TM-mediated APC generation during melioidosis, a common form of community-acquired Gram-negative (pneumo)sepsis in South-East Asia caused by Burkholderia (B.) pseudomallei. Methodology/Principal Findings (WT) mice and mice with an impaired capacity to activate protein C due to a point mutation in their Thbd gene (TMpro/pro mice) were intranasally infected with B. pseudomallei and sacrificed after 24, 48 or 72 hours for analyses. Additionally, survival studies were performed. When compared to WT mice, TMpro/pro mice displayed a worse survival upon infection with B. pseudomallei, accompanied by increased coagulation activation, enhanced lung neutrophil influx and bronchoalveolar inflammation at late time points, together with increased hepatocellular injury. The TMpro/pro mutation had limited if any impact on bacterial growth and dissemination. Conclusion/Significance TM-mediated protein C activation contributes to protective immunity after infection with B. pseudomallei. These results add to a better understanding of the regulation of the inflammatory and procoagulant response during severe Gram-negative (pneumo)sepsis. PMID:24762740

  5. Lymphatic fluctuation in the parenchymal remodeling stage of acute interstitial pneumonia, organizing pneumonia, nonspecific interstitial pneumonia and idiopathic pulmonary fibrosis.

    PubMed

    Parra, E R; Araujo, C A L; Lombardi, J G; Ab'Saber, A M; Carvalho, C R R; Kairalla, R A; Capelozzi, V L

    2012-05-01

    Because the superficial lymphatics in the lungs are distributed in the subpleural, interlobular and peribroncovascular interstitium, lymphatic impairment may occur in the lungs of patients with idiopathic interstitial pneumonias (IIPs) and increase their severity. We investigated the distribution of lymphatics in different remodeling stages of IIPs by immunohistochemistry using the D2-40 antibody. Pulmonary tissue was obtained from 69 patients with acute interstitial pneumonia/diffuse alveolar damage (AIP/DAD, N = 24), cryptogenic organizing pneumonia/organizing pneumonia (COP/OP, N = 6), nonspecific interstitial pneumonia (NSIP/NSIP, N = 20), and idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP, N = 19). D2-40+ lymphatic in the lesions was quantitatively determined and associated with remodeling stage score. We observed an increase in the D2-40+ percent from DAD (6.66 ± 1.11) to UIP (23.45 ± 5.24, P = 0.008) with the advanced process of remodeling stage of the lesions. Kaplan-Meier survival curves showed a better survival for patients with higher lymphatic D2-40+ expression than 9.3%. Lymphatic impairment occurs in the lungs of IIPs and its severity increases according to remodeling stage. The results suggest that disruption of the superficial lymphatics may impair alveolar clearance, delay organ repair and cause severe disease progress mainly in patients with AIP/DAD. Therefore, lymphatic distribution may serve as a surrogate marker for the identification of patients at greatest risk for death due to IIPs.

  6. 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

  7. 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

  8. Low Levels of NDRG1 in Nerve Tissue Are Predictive of Severe Paclitaxel-Induced Neuropathy

    PubMed Central

    Sundar, Raghav; Jeyasekharan, Anand D.; Pang, Brendan; Soong, Richie Chuan Teck; Kumarakulasinghe, Nesaretnam Barr; Ow, Samuel Guan Wei; Ho, Jingshan; Lim, Joline Si Jing; Tan, David Shao Peng; Wilder-Smith, Einar P. V.; Bandla, Aishwarya; Tan, Stacey Sze Hui; Asuncion, Bernadette Reyna; Fazreen, Zul; Hoppe, Michal Marek; Putti, Thomas Choudary; Poh, Lay Mui; Goh, Boon Cher; Lee, Soo-Chin

    2016-01-01

    Introduction Sensory peripheral neuropathy caused by paclitaxel is a common and dose limiting toxicity, for which there are currently no validated predictive biomarkers. We investigated the relationship between the Charcot-Marie-Tooth protein NDRG1 and paclitaxel-induced neuropathy. Methods/Materials Archived mammary tissue specimen blocks of breast cancer patients who received weekly paclitaxel in a single centre were retrieved and NDRG1 immunohistochemistry was performed on normal nerve tissue found within the sample. The mean nerve NDRG1 score was defined by an algorithm based on intensity of staining and percentage of stained nerve bundles. NDRG1 scores were correlated with paclitaxel induced neuropathy Results 111 patients were studied. 17 of 111 (15%) developed severe paclitaxel-induced neuropathy. The mean nerve NDRG1 expression score was 5.4 in patients with severe neuropathy versus 7.7 in those without severe neuropathy (p = 0.0019). A Receiver operating characteristic (ROC) curve analysis of the mean nerve NDRG1 score revealed an area under the curve of 0.74 (p = 0.0013) for the identification of severe neuropathy, with a score of 7 being most discriminative. 13/54 (24%) subjects with an NDRG1 score < = 7 developed severe neuropathy, compared to only 4/57 (7%) in those with a score >7 (p = 0.017). Conclusion Low NDRG1 expression in nerve tissue present within samples of surgical resection may identify subjects at risk for severe paclitaxel-induced neuropathy. Since nerve biopsies are not routinely feasible for patients undergoing chemotherapy for early breast cancer, this promising biomarker strategy is compatible with current clinical workflow. PMID:27716814

  9. 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...

  10. A Detailed Characterization of the Dysfunctional Immunity and Abnormal Myelopoiesis Induced by Severe Shock and Trauma in the Aged

    PubMed Central

    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.

    2015-01-01

    The elderly are particularly susceptible to trauma, and their outcomes are frequently dismal. Such patients often have complicated clinical courses and ultimately die from infection and sepsis. Recent research has revealed that although elderly subjects have increased baseline inflammation as compared to their younger counterparts, the elderly do not respond to severe infection/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. Subsequent analysis with a murine trauma model also demonstrated that elderly mice had increased mortality after post-trauma Pseudomonas pneumonia. Blood, bone marrow, and bronchoalveolar lavage sample analyses from juvenile and 20–24 month 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, the elderly appeared unable to effectively resolve their inflammatory response to severe injury. PMID:26246141

  11. Immunoinformatics Approach in Designing Epitope-based Vaccine Against Meningitis-inducing Bacteria (Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae Type b)

    PubMed Central

    Zahroh, Hilyatuz; Ma’rup, Ahmad; Tambunan, Usman Sumo Friend; Parikesit, Arli Aditya

    2016-01-01

    Meningitis infection is one of the major threats during Hajj season in Mecca. Meningitis vaccines are available, but their uses are limited in some countries due to religious reasons. Furthermore, they only give protection to certain serogroups, not to all types of meningitis-inducing bacteria. Recently, research on epitope-based vaccines has been developed intensively. Such vaccines have potential advantages over conventional vaccines in that they are safer to use and well responded to the antibody. In this study, we developed epitope-based vaccine candidates against various meningitis-inducing bacteria, including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type b. The epitopes were selected from their protein of polysaccharide capsule. B-cell epitopes were predicted by using BCPred, while T-cell epitope for major histocompatibility complex (MHC) class I was predicted using PAProC, TAPPred, and Immune Epitope Database. Immune Epitope Database was also used to predict T-cell epitope for MHC class II. Population coverage and molecular docking simulation were predicted against previously generated epitope vaccine candidates. The best candidates for MHC class I- and class II-restricted T-cell epitopes were MQYGDKTTF, MKEQNTLEI, ECTEGEPDY, DLSIVVPIY, YPMAMMWRNASNRAI, TLQMTLLGIVPNLNK, ETSLHHIPGISNYFI, and SLLYILEKNAEMEFD, which showed 80% population coverage. The complexes of class I T-cell epitopes–HLA-C*03:03 and class II T-cell epitopes–HLA-DRB1*11:01 showed better affinity than standards as evaluated from their ΔGbinding value and the binding interaction between epitopes and HLA molecules. These peptide constructs may further be undergone in vitro and in vivo testings for the development of targeted vaccine against meningitis infection. PMID:27812281

  12. A novel initiation mechanism of death in Streptococcus pneumoniae induced by the human milk protein-lipid complex HAMLET and activated during physiological death.

    PubMed

    Clementi, Emily A; Marks, Laura R; Duffey, Michael E; Hakansson, Anders P

    2012-08-01

    To cause colonization or infection, most bacteria grow in biofilms where differentiation and death of subpopulations is critical for optimal survival of the whole population. However, little is known about initiation of bacterial death under physiological conditions. Membrane depolarization has been suggested, but never shown to be involved, due to the difficulty of performing such studies in bacteria and the paucity of information that exists regarding ion transport mechanisms in prokaryotes. In this study, we performed the first extensive investigation of ion transport and membrane depolarization in a bacterial system. We found that HAMLET, a human milk protein-lipid complex, kills Streptococcus pneumoniae (the pneumococcus) in a manner that shares features with activation of physiological death from starvation. Addition of HAMLET to pneumococci dissipated membrane polarity, but depolarization per se was not enough to trigger death. Rather, both HAMLET- and starvation-induced death of pneumococci specifically required a sodium-dependent calcium influx, as shown using calcium and sodium transport inhibitors. This mechanism was verified under low sodium conditions, and in the presence of ionomycin or monensin, which enhanced pneumococcal sensitivity to HAMLET- and starvation-induced death. Pneumococcal death was also inhibited by kinase inhibitors, and indicated the involvement of Ser/Thr kinases in these processes. The importance of this activation mechanism was made evident, as dysregulation and manipulation of physiological death was detrimental to biofilm formation, a hallmark of bacterial colonization. Overall, our findings provide novel information on the role of ion transport during bacterial death, with the potential to uncover future antimicrobial targets.

  13. A Novel Initiation Mechanism of Death in Streptococcus pneumoniae Induced by the Human Milk Protein-Lipid Complex HAMLET and Activated during Physiological Death*

    PubMed Central

    Clementi, Emily A.; Marks, Laura R.; Duffey, Michael E.; Hakansson, Anders P.

    2012-01-01

    To cause colonization or infection, most bacteria grow in biofilms where differentiation and death of subpopulations is critical for optimal survival of the whole population. However, little is known about initiation of bacterial death under physiological conditions. Membrane depolarization has been suggested, but never shown to be involved, due to the difficulty of performing such studies in bacteria and the paucity of information that exists regarding ion transport mechanisms in prokaryotes. In this study, we performed the first extensive investigation of ion transport and membrane depolarization in a bacterial system. We found that HAMLET, a human milk protein-lipid complex, kills Streptococcus pneumoniae (the pneumococcus) in a manner that shares features with activation of physiological death from starvation. Addition of HAMLET to pneumococci dissipated membrane polarity, but depolarization per se was not enough to trigger death. Rather, both HAMLET- and starvation-induced death of pneumococci specifically required a sodium-dependent calcium influx, as shown using calcium and sodium transport inhibitors. This mechanism was verified under low sodium conditions, and in the presence of ionomycin or monensin, which enhanced pneumococcal sensitivity to HAMLET- and starvation-induced death. Pneumococcal death was also inhibited by kinase inhibitors, and indicated the involvement of Ser/Thr kinases in these processes. The importance of this activation mechanism was made evident, as dysregulation and manipulation of physiological death was detrimental to biofilm formation, a hallmark of bacterial colonization. Overall, our findings provide novel information on the role of ion transport during bacterial death, with the potential to uncover future antimicrobial targets. PMID:22700972

  14. 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 ...

  15. 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

  16. Pharmacogenomics of severe cutaneous adverse reactions and drug-induced liver injury.

    PubMed

    Kaniwa, Nahoko; Saito, Yoshiro

    2013-06-01

    Rare but severe adverse drug reactions (ADRs) are an important issue in drug development and in the proper usage of drugs during the post-approval phase. The ability to predict patient susceptibility to severe ADRs would prevent drug administration to high-risk patients. This would save lives and ensure the quality of life for these patients, but occurrence of idiosyncratic severe ADRs had been very difficult to predict for a long time. However, in this decade, genetic markers have been found for several ADRs, especially for severe cutaneous adverse reactions (SCARs) and drug-induced liver injury (DILI). In this review, we summarize recent progress in identifying genetic markers for SCARS and DILI, and discuss issues that remain unresolved. As for SCARs, associations of HLA-B*15:02 or HLA-A*31:01 and HLA-B*58:01 have been revealed for carbamazepine- and allopurinol-related Stevens-Johnson syndrome and toxic epidermal neclolysis, respectively. HLA-B*57:01 is strongly associated with abacavir-induced hypersensitivity syndrome. Several HLA alleles also demonstrate drug-specific associations with DILI, such as HLA-A*33:03 for ticlopidine, HLA-B*57:01 for flucloxacillin and HLA-DQA1*02:01 for lapatinib. Efforts should be continued to find other genetic markers to achieve high predictability for ADRs, with the goal being development of genetic tests for use in clinical settings.

  17. Significant response to lacosamide in a patient with severe chemotherapy-induced peripheral neuropathy.

    PubMed

    Ibrahim, Samar A; Albany, Zhanna; Albany, Constantine

    2015-05-01

    Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting toxicity of potentially curative cancer therapy regimens. Cisplatin is the class of chemotherapy agent that has a broad spectrum of activity against several solid tumors, but it induces sensory neuropathy of upper and lower extremities. Cisplatin-induced peripheral neuropathy is usually in a "gloves and socks" distribution that can persist for months or years after completion of chemotherapy treatment. If the pain is severe, it affects the patient's long-term quality of life and can potentially result in chemotherapy dose reduction or treatment discontinuation. The mechanism of CIPN is not well understood, and a number of pathophysiological mechanisms have been proposed to explain the phenomenon. Although many therapies have been investigated for the prevention or treatment of CIPN, there is currently no accepted proven therapy. Here we report a case in which lacosamide alleviated painful CIPN symptoms. Lacosamide is an anticonvulsant drug that blocks the voltage-gated sodium channels in the neurons and may also be a promising novel candidate for the prevention and treatment of chemotherapy-induced peripheral neuropathy. Preclinical data support the role of lacosamide protective effect in a rat model of chemotherapy-induced neuropathy, randomized clinical trial is needed.

  18. 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

  19. Dysphagia, dystussia, and aspiration pneumonia in elderly people.

    PubMed

    Ebihara, Satoru; Sekiya, Hideki; Miyagi, Midori; Ebihara, Takae; Okazaki, Tatsuma

    2016-03-01

    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.

  20. 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

  1. Variable severity and Ia antigen expression in streptococcal-cell-wall-induced hepatic granulomas in rats.

    PubMed

    Allen, J B; Wilder, R L

    1987-03-01

    We have previously reported that a single intraperitoneal injection of an aqueous suspension of group A streptococcal cell wall (SCW) fragments induces extensive hepatic granulomas in LEW/N female rats, but not in F344/N female rats. To further understand the mechanisms underlying these differences, we compared granuloma development and class II major histocompatibility complex antigen (Ia) expression in histocompatible LEW/N, F344/N, and CAR/N female rats in response to SCW fragments of four different average molecular sizes. In LEW/N female rats, the smallest fragments (less than 5 megadaltons) induced the most severe hepatic inflammatory disease, with development of widespread granulomas composed of macrophages, lymphocytes, and a peripheral rim of fibroblasts. The largest fragments (greater than 500 megadaltons) induced equivocal disease. Fragments of intermediate size induced granulomas of intermediate severity. The extent of granuloma development, the intensity of Ia antigen expression, and the amount of SCW antigen deposited in the liver qualitatively paralleled each other. In contrast, injection of the most granulomagenic SCW fragments into F344/N and CAR/N rats did not induce granulomas. Although these rat strains are histocompatible with the LEW/N (i.e., RTL.1) strain, hepatic Ia antigen expression in these strains was not increased significantly above basal levels. The amount of SCW antigen in the livers of the resistant rat strains appeared similar to the amount in the susceptible LEW/N strain. These data indicate that granuloma development is dependent on the size of the SCW fragment and host genetic background and that Ia expression directly parallels the severity of the hepatic disease. In addition, the data suggest that non-major histocompatibility complex genetic loci play a major role in regulating the development of the hepatic disease.

  2. 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

  3. 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

  4. Tail pinch induces fos immunoreactivity within several regions of the male rat brain: effects of age.

    PubMed

    Smith, W J; Stewart, J; Pfaus, J G

    1997-05-01

    Brief, intermittent stressors, such as low-level foot shock or tail pinch, induce a general excitement and autonomic arousal in rats that increases their sensitivity to external incentives. Such stimulation can facilitate a variety of behaviors, including feeding, aggression, sexual activity, parental behavior, and drug taking if the appropriate stimuli exist in the environment. However, the ability of tail pinch to induce general arousal and incentive motivation appears to diminish with age. Here we report on the ability of tail pinch to induce Fos immunoreactivity within several brain regions as a function of age. Young (2-3 months) and middle-aged (12-13 months) male rats were administered either five tail pinches (one every 2 min), one tail pinch, or zero (sham) tail pinches (n = 4 per stimulation condition). Rats were sacrificed 75 min following the onset of stimulation, and their brains were prepared for immunocytochemical detection of Fos protein. Fos immunoreactivity was induced by one and five tail pinches in several brain regions, including the anterior medial preoptic area (mPOA), paraventricular nucleus of the hypothalamus (PVN), paraventricular nucleus of the thalamus (PV-Thal), medial amygdala (MEA), basolateral amygdala (BLA), lateral habenula (LHab), and ventral tegmental area (VTA), of young rats compared with those that received zero tail pinches. In contrast to young rats, middle-aged rats had significantly less Fos induced by one and five tail pinches in the mPOA, PVN, MEA, BLA, and VTA, but an equivalent amount induced in the LHab. Fos immunoreactivity was not found within the medial prefrontal cortex, nucleus accumbens, striatum, lateral septum, or locus coeruleus in either young or old rats. Tail pinch appears to activate regions of the brain known to be involved in behavioral responses to both incentive cues and stressors. The lower level of cellular reactivity to tail pinch in middle-aged rats suggests a diminished neural responsiveness to

  5. Cryptogenic organising pneumonia.

    PubMed

    Cordier, J-F

    2006-08-01

    Organising pneumonia is defined histopathologically by intra-alveolar buds of granulation tissue, consisting of intermixed myofibroblasts and connective tissue. Although nonspecific, this histopathological pattern, together with characteristic clinical and imaging features, defines cryptogenic organising pneumonia when no cause or peculiar underlying context is found. Rapid clinical and imaging improvement is obtained with corticosteroid treatment, but relapses are common after stopping treatment.

  6. [Pneumonia in the elderly].

    PubMed

    Catherinot, Emilie

    2012-01-01

    Pneumonia is a serious medical pathology frequent in elderly people. The physiological changes of the respiratory system linked with age reduce postural drainage capacities and increase the risk of acute respiratory failure. Associated with other comorbidities, chronic inhalation is a major risk factor of pneumonia in elderly people. Prevention is based on vaccination, nutrition, dental care and an adapted diet.

  7. 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

  8. Persistent Pneumonia in an Infant.

    PubMed

    Padilla, Kristen; Logan, Latania; Codispoti, Christopher; Jones, Carolyn; Van Opstal, Elizabeth

    2015-07-01

    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

  9. Comparative genomic analysis of human Chlamydia pneumoniae isolates from respiratory, brain and cardiac tissues.

    PubMed

    Roulis, Eileen; Bachmann, Nathan L; Myers, Garry S A; Huston, Wilhelmina; Summersgill, James; Hudson, Alan; Dreses-Werringloer, Ute; Polkinghorne, Adam; Timms, Peter

    2015-12-01

    Chlamydia pneumoniae is an obligate intracellular bacterium implicated in a wide range of human diseases including atherosclerosis and Alzheimer's disease. Efforts to understand the relationships between C. pneumoniae detected in these diseases have been hindered by the availability of sequence data for non-respiratory strains. In this study, we sequenced the whole genomes for C. pneumoniae isolates from atherosclerosis and Alzheimer's disease, and compared these to previously published C. pneumoniae genomes. Phylogenetic analyses of these new C. pneumoniae strains indicate two sub-groups within human C. pneumoniae, and suggest that both recombination and mutation events have driven the evolution of human C. pneumoniae. Further fine-detailed analyses of these new C. pneumoniae sequences show several genetically variable loci. This suggests that similar strains of C. pneumoniae are found in the brain, lungs and cardiovascular system and that only minor genetic differences may contribute to the adaptation of particular strains in human disease.

  10. Polymorphic membrane protein (PMP) 20 and PMP 21 of Chlamydia pneumoniae induce proinflammatory mediators in human endothelial cells in vitro by activation of the nuclear factor-kappaB pathway.

    PubMed

    Niessner, Alexander; Kaun, Christoph; Zorn, Gerlinde; Speidl, Walter; Türel, Zeynep; Christiansen, Gunna; Pedersen, Anna-Sofie; Birkelund, Svend; Simon, Susan; Georgopoulos, Apostolos; Graninger, Wolfgang; de Martin, Rainer; Lipp, Joachim; Binder, Bernd R; Maurer, Gerald; Huber, Kurt; Wojta, Johann

    2003-07-01

    We tested whether polymorphic membrane proteins (PMPs) of Chlamydia pneumoniae might play a role in triggering an inflammatory response in human endothelial cells. Of 15 purified, recombinant chlamydial PMPs tested, 2 (PMP 20 and PMP 21) dose-dependently increased the production of the inflammatory mediators interleukin (IL)-6 and monocyte chemoattractant protein-1 (MCP-1), in cultured human endothelial cells; production of IL-8 was also increased. When endothelial cells were infected by live C. pneumoniae, an increase in the production of IL-6, IL-8, and MCP-1 was seen. We used adenovirus-induced overexpression of IkappaBalpha-an inhibitor of nuclear factor (NF)-kappaB-to demonstrate that PMP 20 and PMP 21 increase the production of IL-6 and MCP-1 in human endothelial cells by activation of the NF-kappaB pathway, because, in cells overexpressing IkappaBalpha, treatment with the respective PMP did not result in increased production of IL-6 and MCP-1. Thus, C. pneumoniae could, by interactions of its PMPs with the endothelium, contribute to the process of vascular injury during the development and progression of atherosclerotic lesions.

  11. A reliable, practical, and economical protocol for inducing diarrhea and severe dehydration in the neonatal calf.

    PubMed

    Walker, P G; Constable, P D; Morin, D E; Drackley, J K; Foreman, J H; Thurmon, J C

    1998-07-01

    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

  12. 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

  13. 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.

  14. 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

  15. 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

  16. Ventilator-associated pneumonia caused by colistin-resistant KPC-producing Klebsiella pneumoniae: a case report and literature review.

    PubMed

    Viaggi, Bruno; Sbrana, Francesco; Malacarne, Paolo; Tascini, Carlo

    2015-05-01

    Klebsiella pneumoniae producing KPC-type carbapenemase causes severe nosocomial infection at a high mortality rate. Nosocomial pneumonia in particular is associated with high mortality, likely due to the unfavorable pulmonary pharmacokinetics of the antibiotics used against this agent. Therefore, early and accurate microbiological identification and susceptibility evaluation are crucial in order to optimize antibiotic therapy. We report a case of ventilator-associated pneumonia caused by colistin-resistant K. pneumoniae producing KPC-type carbapenemase treated using a carbapenem-sparing therapy and tailored according to the serum procalcitonin concentration in order to limit the duration of antibiotic therapy.

  17. Regeneration of toxigenic Pasteurella multocida induced severe turbinate atrophy in pigs detected by computed tomography

    PubMed Central

    2013-01-01

    Background Atrophic rhinitis is a widely prevalent infectious disease of swine caused by Bordetella bronchiseptica and Pasteurella multocida. The course of the disease is considered to be different depending on the principal aetiological agents distinguishing B. bronchiseptica induced non-progressive and toxigenic P. multocida produced progressive forms. In order to compare the pathological events of the two forms of the disease, the development of nasal lesions has longitudinally been studied in pigs infected by either B. bronchiseptica alone or B. bronchiseptica and toxigenic P. multocida together using computed tomography to visualise the nasal structures. Results B. bronchiseptica infection alone caused moderately severe nasal turbinate atrophy and these lesions completely regenerated by the time of slaughter. Unexpectedly, complete regeneration of the bony structures of the nasal cavity was also observed in pigs infected by B. bronchiseptica and toxigenic P. multocida together in spite of seeing severe turbinate atrophy in most of the infected animals around the age of six weeks. Conclusions B. bronchiseptica mono-infection has been confirmed to cause only mild to moderate and transient lesions, at least in high health status pigs. Even severe turbinate atrophy induced by B. bronchiseptica and toxigenic P. multocida combined infection is able to be reorganised to their normal anatomical structure. Computed tomography has further been verified to be a useful tool to examine the pathological events of atrophic rhinitis in a longitudinal manner. PMID:24171824

  18. 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

  19. Expression of the 1918 Influenza A Virus PB1-F2 Enhances the Pathogenesis of Viral and Secondary Bacterial Pneumonia

    PubMed Central

    McAuley, Julie L.; Hornung, Felicita; Boyd, Kelli L.; Smith, Amber M.; McKeon, Raelene; Bennink, Jack; Yewdell, Jonathan W.; McCullers, Jonathan A.

    2007-01-01

    Secondary bacterial pneumonia frequently claimed the lives of victims during the devastating 1918 influenza A virus pandemic. Little is known about the viral factors contributing to the lethality of the 1918 pandemic. Here we show that expression of the viral accessory protein PB1-F2 enhances inflammation during primary viral infection of mice and increases both the frequency and severity of secondary bacterial pneumonia. The priming effect of PB1-F2 on bacterial pneumonia could be recapitulated in mice by intranasal delivery of a synthetic peptide derived from the C-terminal portion of the PB1-F2. Relative to its isogenic parent, an influenza virus engineered to express a PB1-F2 with coding changes matching the 1918 pandemic strain was more virulent in mice, induced more pulmonary immunopathology, and led to more severe secondary bacterial pneumonia. These findings help explain both the unparalleled virulence of the 1918 strain and the high incidence of fatal pneumonia during the pandemic. PMID:18005742

  20. [A case of eosinophilic pneumonia due to Nicolase (serrapeptase) after recovery from acute eosinophilic pneumonia].

    PubMed

    Kai, Naoko; Shirai, Ryo; Hirata, Norio; Iwata, Atsuko; Umeki, Kenji; Ishii, Hiroshi; Kishi, Kenji; Tokimatsu, Issei; Hiramatsu, Kazufumi; Kadota, Jun-ichi

    2009-03-01

    A case of eosinophilic pneumonia due to Nicolase (serrapeptase) after recovery from acute eosinophilic pneumonia is described. A 32-year-old woman was previously admitted to another hospital because of acute onset of dyspnea accompanied by cough and fever. Chest X-ray films revealed diffuse infiltration in both lungs two days after her symptoms occurred. Her bronchoalveolar lavage fluid showed 13% eosinophils and transbronchial lung biopsy specimen also showed many eosinophils infiltrating in the lesions of the bronchial submucosa and alveolar septa. No infectious causes or related drugs were found. Acute eosinophilic pneumonia was diagnosed, and her condition improved gradually without steroid treatment. Because she recovered clinically and radiologically, she was discharged from hospital. Half a month later she was treated with Nicolase because of pharyngitis. She was admitted to the hospital again because of dyspnea, cough and fever three days after commencing to take Nicolase. Chest X-ray films also revealed diffuse infiltration in both lungs with pleural effusion, and her bronchoalveolar lavage fluid showed 37% eosinophils. When the drug lymphocyte stimulation test was performed, it was positive for Nicolase. Therefore drug-induced eosinophilic pneumonia was diagnosed. This is a very rare case of Nicolase (serrapeptase)-induced eosinophilic pneumonia after recovering from acute eosinophilic pneumonia.

  1. [Severe hypertriglyceridemia induced acute pancreatitis: a case report and review of the literature].

    PubMed

    Herrera Del Águila, Dwight Denis; Garavito Rentería, Jorge; Linarez Medina, Karen; Lizarzaburu Rodríguez, Víctor

    2015-01-01

    Hypertriglyceridemia-induced acute pancreatitis occurs in about 1-4% of the cases. It is the third leading cause of pancreatitis after biliary and alcoholic etiology. Hypertriglyceridemia can be caused by primary causes, lipid metabolism disorders and secondary causes. A 32 year old man, born in Huancayo, with a history of diabetes mellitus type 2, severe mixed dyslipidemia with primary hypertriglyceridemia, was admitted to emergency with 10 days of abdominal pain with moderate intensity in epigastrium and left hypochondrium spreading to dorsal region after intake of high-fat meal. 24 hours before admission, pain exacerbates increasing intensity and causing nausea and bilious vomits. Therefore, all laboratory examinations are carried out resulting in hypertriglyceridemia-induced acute pancreatitis. For that reason, an adequate clinical history physical examination associated with laboratory and image examinations are important to consider hypertriglyceridemia as part of the etiology of acute pancreatitis.

  2. 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.

  3. 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

  4. 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.

  5. Tribulus terrestris-induced severe nephrotoxicity in a young healthy male.

    PubMed

    Talasaz, Azita Hajhossein; Abbasi, Mohammad-Reza; Abkhiz, Saeed; Dashti-Khavidaki, Simin

    2010-11-01

    Herbal medications are being progressively utilized all over the world. Nevertheless, herbal remedies are not without hazards and several cases of adverse reactions have been described. Tribulus terrestris is traditionally used because of its aphrodisiac and antiurolithiatic activities with almost complete inhibition of stone formation. We report a case of T. terrestris-induced hepatotoxicity, nephrotoxicity and neurotoxicity in an Iranian male patient who used the plant's extract to prevent kidney stone formation. He presented with seizure and very high serum aminotransferases and creatinine after consuming herbal water for 2 days. Discontinuation of the herbal remedy resulted in improvement in symptoms and normalization of his liver enzymes.

  6. Mechanisms of Interferon-γ Production by Neutrophils and Its Function during Streptococcus pneumoniae Pneumonia

    PubMed Central

    Gomez, John C.; Yamada, Mitsuhiro; Martin, Jessica R.; Dang, Hong; Brickey, W. June; Bergmeier, Wolfgang; Dinauer, Mary C.

    2015-01-01

    Bacterial pneumonia is a common public health problem associated with significant mortality, morbidity, and cost. Neutrophils are usually the earliest leukocytes to respond to bacteria in the lungs. Neutrophils rapidly sequester in the pulmonary microvasculature and migrate into the lung parenchyma and alveolar spaces, where they perform numerous effector functions for host defense. Previous studies showed that migrated neutrophils produce IFN-γ early during pneumonia induced by Streptococcus pneumoniae and that early production of IFN-γ regulates bacterial clearance. IFN-γ production by neutrophils requires Rac2, Hck/Lyn/Fgr Src family tyrosine kinases, and NADPH oxidase. Our current studies examined the mechanisms that regulate IFN-γ production by lung neutrophils during acute S. pneumoniae pneumonia in mice and its function. We demonstrate that IFN-γ production by neutrophils is a tightly regulated process that does not require IL-12. The adaptor molecule MyD88 is critical for IFN-γ production by neutrophils. The guanine nucleotide exchange factor CalDAG-GEFI modulates IFN-γ production. The CD11/CD18 complex, CD44, Toll-like receptors 2 and 4, TRIF, and Nrf2 are not required for IFN-γ production by neutrophils. The recently described neutrophil–dendritic cell hybrid cell, identified by its expression of Ly6G and CD11c, is present at low numbers in pneumonic lungs and is not a source of IFN-γ. IFN-γ produced by neutrophils early during acute S. pneumoniae pneumonia induces transcription of target genes in the lungs, which are critical for host defense. These studies underline the complexity of the neutrophil responses during pneumonia in the acute inflammatory response and in subsequent resolution or initiation of immune responses. PMID:25100610

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. 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

  12. Childhood pneumonia - the Drakenstein Child Health Study.

    PubMed

    Zar, Heather Jessica; Barnett, Whitney; Myer, Landon; Nicol, Mark P

    2016-07-01

    Advances in immunisation, improvements in socioeconomic status and effective HIV prevention and treatment strategies have reduced the population burden of childhood pneumonia and severe disease. However, pneumonia remains the major single cause of death in children outside the neonatal period, causing approximately 1 million deaths annually, or 15% of an estimated 6.3 million deaths in children aged under 5 years. This burden is disproportionately high in low- and middle-income countries and in Africa, where almost 50% of deaths in children aged  under 5 years occur, despite African children comprising only 25% of live births globally. Pneumonia incidence and severity are highest in the first year of life, especially in the first 6 months. PMID:27384352

  13. 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.

  14. Pneumonia in adults - discharge

    MedlinePlus

    ... In: Bennett JE, Dolin R, Blaser MJ, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious ... ed. Philadelphia, PA: Elsevier Saunders; 2015:chap 69. Mandell LA. Streptococcus pneumoniae infections. In: Goldman L, Schafer ...

  15. Acute interstitial pneumonia.

    PubMed

    Bouros, D; Nicholson, A C; Polychronopoulos, V; du Bois, R M

    2000-02-01

    The term "acute interstitial pneumonia" (AIP) describes an idiopathic clinicopathological condition, characterized clinically by an interstitial lung disease causing rapid onset of respiratory failure, which is distinguishable from the other more chronic forms of interstitial pneumonia. It is synonymous with Hamman-Rich syndrome, occurring in patients without pre-existing lung disease. The histopathological findings are those of diffuse alveolar damage. AIP radiologically and physiologically resembles acute respiratory distress syndrome (ARDS) and is considered to represent the small subset of patients with idiopathic ARDS. It is frequently confused with other clinical entities characterized by rapidly progressive interstitial pneumonia, especially secondary acute interstitial pneumonia, acute exacerbations and accelerated forms of cryptogenic fibrosing alveolitis . Furthermore, many authors use the above terms, both erroneously and interchangeably. It has a grave prognosis with >70% mortality in 3 months, despite mechanical ventilation. This review aims to clarify the relative clinical and pathological issues and terminology.

  16. Community-acquired pneumonia.

    PubMed

    Prina, Elena; Ranzani, Otavio T; Torres, Antoni

    2015-09-12

    Community-acquired pneumonia causes great mortality and morbidity and high costs worldwide. Empirical selection of antibiotic treatment is the cornerstone of management of patients with pneumonia. To reduce the misuse of antibiotics, antibiotic resistance, and side-effects, an empirical, effective, and individualised antibiotic treatment is needed. Follow-up after the start of antibiotic treatment is also important, and management should include early shifts to oral antibiotics, stewardship according to the microbiological results, and short-duration antibiotic treatment that accounts for the clinical stability criteria. New approaches for fast clinical (lung ultrasound) and microbiological (molecular biology) diagnoses are promising. Community-acquired pneumonia is associated with early and late mortality and increased rates of cardiovascular events. Studies are needed that focus on the long-term management of pneumonia.

  17. 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.

  18. 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.

  19. 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.

  20. Vaccination Drives Changes in Metabolic and Virulence Profiles of Streptococcus pneumoniae.

    PubMed

    Watkins, Eleanor R; Penman, Bridget S; Lourenço, José; Buckee, Caroline O; Maiden, Martin C J; Gupta, Sunetra

    2015-07-01

    The bacterial pathogen, Streptococcus pneumoniae (the pneumococcus), is a leading cause of life-threatening illness and death worldwide. Available conjugate vaccines target only a small subset (up to 13) of >90 known capsular serotypes of S. pneumoniae and, since their introduction, increases in non-vaccine serotypes have been recorded in several countries: a phenomenon termed Vaccine Induced Serotype Replacement (VISR). Here, using a combination of mathematical modelling and whole genome analysis, we show that targeting particular serotypes through vaccination can also cause their metabolic and virulence-associated components to transfer through recombination to non-vaccine serotypes: a phenomenon we term Vaccine-Induced Metabolic Shift (VIMS). Our results provide a novel explanation for changes observed in the population structure of the pneumococcus following vaccination, and have important implications for strain-targeted vaccination in a range of infectious disease systems.

  1. Hospital study of adult community-acquired pneumonia.

    PubMed

    Macfarlane, J T; Finch, R G; Ward, M J; Macrae, A D

    1982-07-31

    The cause of primary pneumonia was diagnosed in 124 of 127 consecutive adult patients admitted to hospital with community-acquired illness. Pneumococcal infection was found in 96 (76%) patients and legionnaries' disease was the second commonest infection identified (15%). Other bacterial infections were uncommon. 11 patients had atypical pneumonia, including 7 with psittacosis. There were several mixed infections and most of the 11 patients with viral infections also had bacterial pneumonia. 19 patients died (15%) and mortality was associated with increasing age, the presence of coexisting disease, and the cause of the pneumonia. Recognition of the most likely causes of severe pneumonia allows logical initial antibiotic treatment for such patients admitted to hospital. PMID:6124681

  2. [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%).

  3. [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

  4. 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.

  5. 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

    2015-12-22

    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.

  6. 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

  7. 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

  8. Predictors of aspiration pneumonia: how important is dysphagia?

    PubMed

    Langmore, S E; Terpenning, M S; Schork, A; Chen, Y; Murray, J T; Lopatin, D; Loesche, W J

    1998-01-01

    Aspiration pneumonia is a major cause of morbidity and mortality among the elderly who are hospitalized or in nursing homes. Multiple risk factors for pneumonia have been identified, but no study has effectively compared the relative risk of factors in several different categories, including dysphagia. In this prospective outcomes study, 189 elderly subjects were recruited from the outpatient clinics, inpatient acute care wards, and the nursing home care center at the VA Medical Center in Ann Arbor, Michigan. They were given a variety of assessments to determine oropharyngeal and esophageal swallowing and feeding status, functional status, medical status, and oral/dental status. The subjects were followed for up to 4 years for an outcome of verified aspiration pneumonia. Bivariate analyses identified several factors as significantly associated with pneumonia. Logistic regression analyses then identified the significant predictors of aspiration pneumonia. The best predictors, in one or more groups of subjects, were dependent for feeding, dependent for oral care, number of decayed teeth, tube feeding, more than one medical diagnosis, number of medications, and smoking. The role that each of the significant predictors might play was described in relation to the pathogenesis of aspiration pneumonia. Dysphagia was concluded to be an important risk for aspiration pneumonia, but generally not sufficient to cause pneumonia unless other risk factors are present as well. A dependency upon others for feeding emerged as the dominant risk factor, with an odds ratio of 19.98 in a logistic regression model that excluded tube-fed patients.

  9. 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

  10. 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.

  11. 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.

  12. [Severe drug-induced skin reactions. Stevens-Johnson syndrome and toxic epidermal necrolysis].

    PubMed

    Mockenhaupt, M

    2014-05-01

    Stevens-Johnson syndrome (SJS) and Toxic epidermal necrolysis (TEN) are characterized by extensive blistering of the skin and mucosa; they are considered as one disease entity with varying severity. They are rare but potentially life-threatening and accompanied by high mortality. A clear clinical diagnosis is needed to direct specific therapy, but supportive therapy remains most important. In order to identify and withdraw the inducing drug, a very detailed and thorough medication history has to be obtained. Among the highly suspected (strongly associated) agents are allopurinol, antibacterial sulfonamides, non-steroidal anti-inflammatory drugs of the oxicam type, various anti-epileptics and nevaripine. Together they account for more than half of the cases of SJS/TEN. Although a drug is not always the cause, it is considered very like in approximately 75% of cases. Infections have also to be considered as etiologic factors. PMID:24820799

  13. 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.

  14. Drug-induced hypersensitivity syndrome due to minocycline complicated by severe myocarditis.

    PubMed

    Kanno, Kyoko; Sakai, Hiroyuki; Yamada, Yutaka; Iizuka, Hajime

    2014-02-01

    A 60-year-old woman presented with a 13-day history of a generalized erythematous rash accompanied by fever, periorbital edema and axillary lymphadenopathy. Prior to the appearance of the rash, the patient had been treated with intermittent courses of oral minocycline for cystitis. The patient was diagnosed with drug-induced hypersensitivity syndrome (DIHS) due to minocycline. During the admission, infectious endocarditis was suspected and the patient was treated with i.v. gammaglobulin (0.4 g/kg per day). The following day, the patient suffered from systemic deterioration and symptomatic low blood pressure that prompted repeat echocardiography which revealed an ejection fraction of 10%. DIHS-associated myocarditis was suspected and management with circulation assistance devices and steroid pulse therapy were started, resulting in satisfactory resolution. A rise in titer of human herpesvirus-6, cytomegalovirus and Herpes simplex virus-1 antibodies was detected. Although minocycline-induced myocarditis is rare, this severe drug reaction should be considered with DIHS.

  15. [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

  16. [Mycoplasma pneumoniae meningoencephalitis in a young adult].

    PubMed

    Del Castillo, Marcelo; D'Giano, Carlos; Goicoechea, María Teresa; Morello, Fernando; Salsamendi, Paz; Mora, Andrea

    2005-01-01

    Mycoplasma pneumoniae infections have extrapulmonary complications that involve the nervous system. The neurologic manifestations are diverse. Although the prognosis is usually favorable, the patients can undergo severe permanent sequelae. We present a young female adult with acute meningoencephalitis as a complication of a lower respiratory infection, which followed a benign course without neurologic sequelae.

  17. Therapeutic strategies in pneumonia: going beyond antibiotics.

    PubMed

    Müller-Redetzky, Holger; Lienau, Jasmin; Suttorp, Norbert; Witzenrath, Martin

    2015-09-01

    Dysregulation of the innate immune system drives lung injury and its systemic sequelae due to breakdown of vascular barrier function, harmful hyperinflammation and microcirculatory failure, which contribute to the unfavourable outcome of patients with severe pneumonia. A variety of promising therapeutic targets have been identified and numerous innovative therapeutic approaches demonstrated to improve lung injury in experimental preclinical studies. However, at present specific preventive or curative strategies for the treatment of lung failure in pneumonia in addition to antibiotics are still missing. The aim of this mini-review is to give a short overview of some, but not all, adjuvant therapeutic strategies for pneumonia and its most important complications, sepsis and acute respiratory distress syndrome, and briefly discuss future perspectives.

  18. 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

  19. Norepinephrine-induced nerve growth factor depletion causes cardiac sympathetic denervation in severe heart failure.

    PubMed

    Kimura, Kensuke; Kanazawa, Hideaki; Ieda, Masaki; Kawaguchi-Manabe, Haruko; Miyake, Yoshiko; Yagi, Takashi; Arai, Takahide; Sano, Motoaki; Fukuda, Keiichi

    2010-08-25

    In severe congestive heart failure (CHF), sympathetic overactivity correlates with the exacerbation of cardiac performance. To test the hypothesis that the cardiac sympathetic nerve density dramatically changes with the acceleration of circulating norepinephrine (NE) concentration, we investigated the temporal association of nerve growth factor (NGF) expression in the heart and cardiac sympathetic nerve density during the development of CHF in the continuous NE-infused rats. The animals were analyzed at 0-, 1-, 3-, 7-, 14-, and 28-day after implantation of osmotic pump at a rate of 0.05 mg/kg/hr. The cardiac performance was temporally facilitated in NE-exposed rats at 3-day in accordance with the sympathetic hyper-innervation induced by the augmentation of NGF mRNA expression in the heart. In NE-treated rats, left ventricular end-diastolic pressure was significantly increased after 7-day and marked left ventricular hypertrophy and systemic fluid retention were observed at 28-day. CHF-induced sympathetic overactivity further increased plasma NE concentration in NE-treated rats and finally reached to 16.1+/-5.6 ng/ml at 28-day (control level was 0.39+/-0.1 ng/ml, p<0.01). In the decompensated CHF rats at 28-day, the NGF mRNA expression was conspicuously reduced concomitant with the obvious nerve fiber loss confirmed by the immunostaining of nerve axonal marker, PGP9.5 and sympathetic neuron marker, tyrosine hydroxylase. This resulted in the attenuated tissue NE contents and the exacerbating cardiac performance. The cardiac sympathetic fiber loss was also confirmed in NE-exposed DBH (dopamine beta-hydroxylase)-Cre/Floxed-EGFP (enhanced green fluorescent protein) mice with severe CHF, in which sympathetic nerve could be traced by EGFP. Our results suggest that the cardiac sympathetic nerve density is strictly regulated by the NGF expression in the heart and long-exposure of high plasma NE concentration caused myocardial NGF reduction, following sympathetic fiber loss

  20. Epidemiology and Virulence of Klebsiella pneumoniae.

    PubMed

    Clegg, Steven; Murphy, Caitlin N

    2016-02-01

    Strains of Klebsiella pneumoniae are frequently opportunistic pathogens implicated in urinary tract and catheter-associated urinary-tract infections of hospitalized patients and compromised individuals. Infections are particularly difficult to treat since most clinical isolates exhibit resistance to several antibiotics leading to treatment failure and the possibility of systemic dissemination. Infections of medical devices such as urinary catheters is a major site of K. pneumoniae infections and has been suggested to involve the formation of biofilms on these surfaces. Over the last decade there has been an increase in research activity designed to investigate the pathogenesis of K. pneumoniae in the urinary tract. These investigations have begun to define the bacterial factors that contribute to growth and biofilm formation. Several virulence factors have been demonstrated to mediate K. pneumoniae infectivity and include, but are most likely not limited to, adherence factors, capsule production, lipopolysaccharide presence, and siderophore activity. The development of both in vitro and in vivo models of infection will lead to further elucidation of the molecular pathogenesis of K. pneumoniae. As for most opportunistic infections, the role of host factors as well as bacterial traits are crucial in determining the outcome of infections. In addition, multidrug-resistant strains of these bacteria have become a serious problem in the treatment of Klebsiella infections and novel strategies to prevent and inhibit bacterial growth need to be developed. Overall, the frequency, significance, and morbidity associated with K. pneumoniae urinary tract infections have increased over many years. The emergence of these bacteria as sources of antibiotic resistance and pathogens of the urinary tract present a challenging problem for the clinician in terms of management and treatment of individuals.

  1. 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

  2. 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

  3. 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

  4. Clinical features and outcomes of aspiration pneumonia compared with non-aspiration pneumonia: a retrospective cohort study.

    PubMed

    Hayashi, Makoto; Iwasaki, Takuya; Yamazaki, Yohei; Takayasu, Hiromi; Tateno, Hidetsugu; Tazawa, Sakiko; Kato, Eisuke; Wakabayashi, Aya; Yamaguchi, Fumihiro; Tsuchiya, Yutaka; Yamashita, Jun; Takeda, Norikazu; Matsukura, Satoshi; Kokubu, Fumio

    2014-07-01

    Pneumonia is a leading cause of death among elderly patients. Although aspiration pneumonia (AP) commonly occurs with aging, its clinical features and outcomes are still uncertain. The aims of this study were to describe the clinical features and outcomes of AP and to assess whether presence of AP affects clinical outcomes in patients with community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP). We retrospectively analyzed patients with CAP and HCAP hospitalized in our institution in Japan from October 2010 to March 2012. We compared clinical features and outcomes between AP and non-AP, and investigated risk factors for recurrence of pneumonia and death. Of 214 consecutive patients, 100 (46.7%) were diagnosed as having aspiration pneumonia. These patients were older and had lower body mass index, more comorbidities, and poorer Eastern Cooperative Oncology Group performance status (ECOG PS) than the patients with non-AP. Patients with AP had more severe disease, required longer hospital stays, and had a frequent recurrence rate of pneumonia and higher mortality. In multivariate analyses, AP, age, and ECOG PS were related to recurrence of pneumonia, and the prognostic factors were CURB-65 score and ECOG PS. AP was not a significant indicator for prognosis but was the strongest risk factor for recurrence of pneumonia. Clinical background and outcomes including recurrence and mortality of AP were obviously different from those of non-AP; therefore AP should be considered as a distinct subtype of pneumonia, and it is important to prevent the recurrence of pneumonia in the patients with AP.

  5. Viral-bacterial pneumonia in calves: duration of the interaction between bovine herpesvirus 1 and Pasteurella haemolytica.

    PubMed Central

    Yates, W D; Babiuk, L A; Jericho, K W

    1983-01-01

    Sixteen six to eight month old beef calves were exposed individually to a five minute aerosol of bovine herpesvirus 1, isolate 108. Aerosol exposure to Pasteurella haemolytica (biotype A, serotype 1) was administered individually for five minutes at either four, ten, 20 or 30 days after the virus. Fibrinous pneumonia and pleuritis occurred in all four groups but were most extensive and severe in those exposed to the virus and bacterium four days apart (the positive controls). Fibrinous pneumonia was associated with persistence of bovine herpesvirus 1 in the respiratory tract despite resolution of virus-induced necrotic lesions of the respiratory mucosa. The results presented here suggest that, although the severity of viral-bacterial synergism may be influenced by virus-induced morphological changes, the continued presence of viral antigens after the resolution of respiratory mucosal lesions may continue to exert some effect on host defenses and disease processes. Images Fig. 2. Fig. 3. Fig. 4. PMID:6315196

  6. 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

  7. 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.

  8. Diet-induced obesity severely impairs myelinated aortic baroreceptor reflex responses.

    PubMed

    McCully, Belinda H; Brooks, Virginia L; Andresen, Michael C

    2012-05-15

    Diet-induced obesity (DIO) attenuates the arterial cardiac baroreceptor reflex, but the mechanisms and sites of action are unknown. This study tested the hypothesis that DIO impairs central aortic baroreceptor pathways. Normal chow control (CON) and high-fat-chow obesity-resistant (OR) and obesity-prone (OP) rats were anesthetized (inactin, 120 mg/kg) and underwent sinoaortic denervation. The central end of the aortic depressor nerve (ADN) was electrically stimulated to generate frequency-dependent baroreflex curves (5-100 Hz) during selective activation of myelinated (A-fiber) or combined (A- and C-fiber) ADN baroreceptors. A mild stimulus (1 V) that activates only A-fiber ADN baroreceptors induced robust, frequency-dependent depressor and bradycardic responses in CON and OR rats, but these responses were completely abolished in OP rats. Maximal activation of A fibers (3 V) elicited frequency-dependent reflexes in all groups, but a dramatic deficit was still present in OP rats. Activation of all ADN baroreceptors (20 V) evoked even larger reflex responses. Depressor responses were nearly identical among groups, but OP rats still exhibited attenuated bradycardia. In separate groups of rats, the reduced heart rate (HR) response to maximal activation of ADN A fibers (3 V) persisted in OP rats following pharmacological blockade of β(1)-adrenergic or muscarinic receptors, suggesting deficits in both parasympathetic nervous system (PNS) and sympathetic nervous system (SNS) reflex pathways. However, the bradycardic responses to direct efferent vagal stimulation were similar among groups. Taken together, our data suggest that DIO severely impairs the central processing of myelinated aortic baroreceptor control of HR, including both PNS and SNS components.

  9. [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.

  10. [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

  11. Exogenous lipoid pneumonia.

    PubMed

    Cornacchia, D J; Snyder, C H; Dupont, D C; Yaron, N S

    1989-05-01

    Although a rare form of nonresolving pulmonary infiltrate, exogenous lipoid pneumonia is a great mimicker. It often is mistaken for bacterial pneumonia or cancer. Many cases have been diagnosed only by open lung biopsy or other invasive procedures. Depending on the type of lipid ingested and the degree of inflammation that occurs, damage to the lung can be little to none or can fulminate to necrosis and hemorrhage. Symptoms may range from none to respiratory failure. In the case presented, the patient was ingesting Vaseline Intensive Care Lotion and baby oil as laxatives. This information was elicited only after diagnosis was made by open lung biopsy.

  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, PaO(2)/FiO(2) 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 PaO(2)/FiO(2), 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

  13. 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, PaO(2)/FiO(2) 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 PaO(2)/FiO(2), 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

  14. 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.

  15. Muscarinic excitation of parvalbumin-positive interneurons contributes to the severity of pilocarpine-induced seizures

    PubMed Central

    Yi, Feng; DeCan, Evan; Stoll, Kurt; Marceau, Eric; Deisseroth, Karl; Lawrence, J. Josh

    2014-01-01

    SUMMARY Objective A common rodent model in epilepsy research employs the muscarinic acetylcholine receptor (mAChR) agonist pilocarpine, yet the mechanisms underlying the induction of pilocarpine-induced seizures (PISs) remain unclear. Global M1 mAChR (M1R) knockout mice are resistant to PISs, implying that M1R activation disrupts excitation/inhibition balance. Parvalbumin-positive (PV) inhibitory neurons express M1 mAChRs, participate in cholinergically-induced oscillations, and can enter a state of depolarization block (DB) during epileptiform activity. Here, we test the hypothesis that pilocarpine activation of M1Rs expressed on PV cells contributes to PISs. Methods CA1 PV cells in PV-CRE mice were visualized with a floxed YFP or hM3Dq-mCherry adeno-associated virus, or by crossing PV-CRE mice with the RosaYFP reporter line. To eliminate M1Rs from PV cells, we generated PV-M1KO mice by crossing PV-CRE and floxed M1 mice. Action potential (AP) frequency was monitored during application of pilocarpine (200 µM). In behavioral experiments, locomotion and seizure symptoms were recorded in WT or PV-M1KO mice during PISs. Results Pilocarpine significantly increased AP frequency in CA1 PV cells into the gamma range. In the continued presence of pilocarpine, a subset (5/7) of PV cells progressed to DB, which was mimicked by hM3Dq activation of Gq-receptor signaling. Pilocarpine-induced depolarization, AP firing at gamma frequency, and progression to DB were prevented in CA1 PV cells of PV-M1KO mice. Finally, compared to WT mice, PV-M1KO mice were associated with reduced severity of PISs. Significance Pilocarpine can directly depolarize PV+ cells via M1R activation but a subset of these cells progress to DB. Our electrophysiological and behavioral results suggest that this mechanism is active during PISs, contributing to a collapse of PV-mediated GABAergic inhibition, dysregulation of excitation/inhibition balance, and increased susceptibility to PISs. PMID:25495999

  16. 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

  17. 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

  18. Oral ruxolitinib induces hair regrowth in patients with moderate-to-severe alopecia areata

    PubMed Central

    Mackay-Wiggan, Julian; Nguyen, Nhan; Cerise, Jane E.; Clark, Charlotte; Ulerio, Grace; Furniss, Megan; Vaughan, Roger; Clynes, Raphael

    2016-01-01

    BACKGROUND. Alopecia areata (AA) is a common autoimmune disease with a lifetime risk of 1.7%; there are no FDA-approved treatments for AA. We previously identified a dominant IFN-γ transcriptional signature in cytotoxic T lymphocytes (CTLs) in human and mouse AA skin and showed that treatment with JAK inhibitors induced durable hair regrowth in mice by targeting this pathway. Here, we investigated the use of the oral JAK1/2 inhibitor ruxolitinib in the treatment of patients with moderate-to-severe AA. METHODS. We initiated an open-label clinical trial of 12 patients with moderate-to-severe AA, using oral ruxolitinib, 20 mg twice per day, for 3–6 months of treatment followed by 3 months follow-up off drug. The primary endpoint was the proportion of subjects with 50% or greater hair regrowth from baseline to end of treatment. RESULTS. Nine of twelve patients (75%) demonstrated a remarkable response to treatment, with average hair regrowth of 92% at the end of treatment. Safety parameters remained largely within normal limits, and no serious adverse effects were reported. Gene expression profiling revealed treatment-related downregulation of inflammatory markers, including signatures for CTLs and IFN response genes and upregulation of hair-specific markers. CONCLUSION. In this pilot study, 9 of 12 patients (75%) treated with ruxolitinib showed significant scalp hair regrowth and improvement of AA. Larger randomized controlled trials are needed to further assess the safety and efficacy of ruxolitinib in the treatment of AA. TRIAL REGISTRATION. Clinicaltrials.gov NCT01950780. FUNDING. Locks of Love Foundation, the Alopecia Areata Initiative, NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and the Irving Institute for Clinical and Translational Research/Columbia University Medical Center Clinical and Translational Science Award (CUMC CTSA). PMID:27699253

  19. Oral ruxolitinib induces hair regrowth in patients with moderate-to-severe alopecia areata

    PubMed Central

    Mackay-Wiggan, Julian; Nguyen, Nhan; Cerise, Jane E.; Clark, Charlotte; Ulerio, Grace; Furniss, Megan; Vaughan, Roger; Clynes, Raphael

    2016-01-01

    BACKGROUND. Alopecia areata (AA) is a common autoimmune disease with a lifetime risk of 1.7%; there are no FDA-approved treatments for AA. We previously identified a dominant IFN-γ transcriptional signature in cytotoxic T lymphocytes (CTLs) in human and mouse AA skin and showed that treatment with JAK inhibitors induced durable hair regrowth in mice by targeting this pathway. Here, we investigated the use of the oral JAK1/2 inhibitor ruxolitinib in the treatment of patients with moderate-to-severe AA. METHODS. We initiated an open-label clinical trial of 12 patients with moderate-to-severe AA, using oral ruxolitinib, 20 mg twice per day, for 3–6 months of treatment followed by 3 months follow-up off drug. The primary endpoint was the proportion of subjects with 50% or greater hair regrowth from baseline to end of treatment. RESULTS. Nine of twelve patients (75%) demonstrated a remarkable response to treatment, with average hair regrowth of 92% at the end of treatment. Safety parameters remained largely within normal limits, and no serious adverse effects were reported. Gene expression profiling revealed treatment-related downregulation of inflammatory markers, including signatures for CTLs and IFN response genes and upregulation of hair-specific markers. CONCLUSION. In this pilot study, 9 of 12 patients (75%) treated with ruxolitinib showed significant scalp hair regrowth and improvement of AA. Larger randomized controlled trials are needed to further assess the safety and efficacy of ruxolitinib in the treatment of AA. TRIAL REGISTRATION. Clinicaltrials.gov NCT01950780. FUNDING. Locks of Love Foundation, the Alopecia Areata Initiative, NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and the Irving Institute for Clinical and Translational Research/Columbia University Medical Center Clinical and Translational Science Award (CUMC CTSA).

  20. 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

  1. 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

  2. Violet diode laser-induced chlorophyll fluorescence: a tool for assessing mosaic disease severity in cassava (Manihot esculenta Crantz) cultivars.

    PubMed

    Anderson, Benjamin; Eghan, Moses J; Asare-Bediako, Elvis; Buah-Bassuah, Paul K

    2012-01-01

    Violet diode laser-induced chlorophyll fluorescence was used in agronomical assessment (disease severity and average yield per plant). Because cassava (Manihot esculenta Crantz) is of economic importance, improved cultivars with various levels of affinity for cassava mosaic disease were investigated. Fluorescence data correlated with cassava mosaic disease severity levels and with the average yield per plant.

  3. Warming-induced upslope advance of subalpine forest is severely limited by geomorphic processes

    PubMed Central

    Macias-Fauria, Marc; Johnson, Edward A.

    2013-01-01

    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-km2 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

  4. 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

  5. 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.

  6. 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

  7. [Pneumonia in wounded].

    PubMed

    Ovchinnikov, Iu V; Kharitonov, M A; Sadykov, R R; Shelukhin, V A; Gaĭduk, S V; Bogomolov, A B; Ivanov, V V; Dobrovol'skaia, L M

    2015-02-01

    Pneumonia is one of the common complications of wounds of any localization. Therapists are involved into the treatment of lung lesions in wounded in the ICU, in the surgical and if the patient arrives "on follow-up care,"--in the medical ward. The article analyzes the main statistical indicators reflecting the prevalence and clinical and pathogenetic characteristics of lung pathology in wounded during the Great Patriotic War, during the fighting Soviet troops in the Republic of Afghanistan, the 1st and 2nd Chechen campaign. Pneumonia as a manifestation of traumatic disease can occur in two ways. Primary pneumonia is in close connection with the pathogenetic traumatic injury. Secondary lung lesions complicate the injury at a later date and are due to the introduction of a nosocomial infection process flora. We describe the clinical picture of pneumonia in the affected, the basic pathogenesis, principles of therapy. Successful treatment of lung pathology in wounded depends on the performance of a complex of activities involving a wide range of doctors of various specialties. PMID:25920173

  8. Bovine Respiratory Syncytial Virus (BRSV) Pneumonia in Beef Calf Herds Despite Vaccination

    PubMed Central

    Larsen, LE; Tegtmeier, C; Pedersen, E

    2001-01-01

    The present report describes the clinical, pathological, serological and virological findings in calves from 2 larger Danish beef herds experiencing outbreaks of pneumonia. The calves had been vaccinated with an inactivated bovine respiratory syncytial virus (BRSV) vaccine 2 months prior to the outbreak. The clinical signs comprised nasal discharge, pyrexia, cough and increased respiratory rates. A total of 28 calves died in the 2 herds. The laboratory investigations revealed that BRSV was involved and probably initiated both outbreaks. Furthermore, the serological results suggested that the vaccine induced only sparse levels of antibodies probably due to the presence of maternally derived antibodies at the time of vaccination. Necropsy findings in 5 calves revealed changes typical for infectious pneumonia with involvment of BRSV. In conclusion, vaccination of calves against BRSV in 2 Danish beef herds failed to protect the calves against severe or even fatal BRSV mediated respiratory disease 2 months later. PMID:11455891

  9. Chlamydia pneumoniae and cardiovascular disease.

    PubMed Central

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

    1998-01-01

    Chlamydia pneumoniae is a ubiquitous pathogen that causes acute respiratory disease. The spectrum of C. pneumoniae infection has been extended to atherosclerosis and its clinical manifestations. Seroepidemiologic studies have associated C. pneumoniae antibody with coronary artery disease, myocardial infarction, carotid artery disease, and cerebrovascular disease. The association of C. pneumoniae with atherosclerosis is corroborated by the presence of the organism in atherosclerotic lesions throughout the arterial tree and the near absence of the organism in healthy arterial tissue. C. pneumoniae has also been isolated from coronary and carotid atheromatous plaques. To determine whether chronic infection plays a role in initiation or progression of disease, intervention studies in humans have been initiated, and animal models of C. pneumoniae infection have been developed. This review summarizes the evidence for the association and potential role of C. pneumoniae in cardiovascular disease. PMID:9866733

  10. Pneumonia caused by Aeromonas species in Taiwan, 2004-2011.

    PubMed

    Chao, C M; Lai, C C; Tsai, H Y; Wu, C J; Tang, H J; Ko, W C; Hsueh, P-R

    2013-08-01

    We investigated the clinical characteristics of patients with pneumonia caused by Aeromonas species. Patients with pneumonia caused by Aeromonas species during the period 2004 to 2011 were identified from a computerized database of a regional hospital in southern Taiwan. The medical records of these patients were retrospectively reviewed. Of the 84 patients with pneumonia due to Aeromonas species, possible Aeromonas pneumonia was diagnosed in 58 patients, probable Aeromonas pneumonia was diagnosed in 18 patients, and pneumonia due to Aeromonas was conclusively diagnosed in 8 patients. Most of the cases of Aeromonas pneumonia developed in men and in patients of advanced age. A. hydrophila (n = 50, 59.5 %) was the most common pathogen, followed by A. caviae (n = 24, 28.6 %), A. veronii biovar sobria (n = 7, 8.3 %), and A. veronii biovar veronii (n = 3, 3.6 %). Cancer (n = 37, 44.0 %) was the most common underlying disease, followed by diabetes mellitus (n = 27, 32.1 %). Drowning-associated pneumonia developed in 6 (7.1 %) patients. Of 47 patients who were admitted to the intensive care ward, 42 patients developed acute respiratory failure and 24 of those patients died. The overall in-hospital mortality rate was significantly associated with liver cirrhosis, cancer, initial presentation of shock, and usage of mechanical ventilation. In conclusion, Aeromonas species should be considered as one of the causative pathogens of severe pneumonia, especially in immunocompromised patients, and should be recognized as a cause of drowning-associated pneumonia. Cirrhosis, cancer, and shock as the initial presenting symptom are associated with poor outcome.

  11. Health care-associated Staphylococcus aureus pneumonia

    PubMed Central

    Webster, Duncan; Chui, Linda; Tyrrell, Gregory J; Marrie, Thomas J

    2007-01-01

    INTRODUCTION While Staphylococcus aureus is an uncommon but serious cause of traditional community-acquired pneumonia (CAP), it is a predominant cause of nosocomial pneumonia in addition to the unique clinical entity of health care-associated pneumonia (HCAP). A cohort of bacteremic S aureus pneumonia cases was reviewed to determine the role of HCAP among the cohort, and to assess for differences between CAP and HCAP. PATIENTS AND METHODS Bacteremic S aureus pneumonia cases were identified from a prospective study of all patients diagnosed with CAP who presented to hospitals in Edmonton, Alberta, between November 2000 and November 2002. These cases were subsequently reviewed retrospectively. Demographic, clinical and microbiological data were obtained, and patients were classified as having CAP or HCAP. Relatedness of isolates was determined by pulsed-field gel electrophoresis analysis in conjunction with epidemiological information. RESULTS There were 28 cases of bacteremic S aureus pneumonia identified. Fifty-seven per cent were reclassified as having HCAP, and 43% remained classified as having CAP. The CAP cohort was significantly younger than the HCAP cohort (mean age 49.0±23.7 years versus 67.8±18.6 years; P=0.035) with higher rates of intravenous drug use (50% versus 0%; P=0.002). Long-term care facility residence (44%) was common in the HCAP cohort. The HCAP cohort presented with more severe illness, having a higher mean pneumonia severity index score (143.1±41.1 versus 98.2±54.6; P=0.028), and despite fewer embolic complications, there was a trend toward a significantly higher mortality rate (31% versus 0%; P=0.052). Two community-acquired isolates cultured in the setting of intravenous drug use were methicillin-resistant, and no isolates were positive for Panton-Valentine leukocidin. There was evidence of relatedness involving 44% of the HCAP isolates by pulsed-field gel electrophoresis analysis. CONCLUSION HCAP accounts for a significant number of

  12. Haemoptysis as a primary manifestation of cryptogenic organizing pneumonia (COP).

    PubMed

    Chatzivasiloglou, Fotini; Katsenos, Stamatis; Psathakis, Konstantinos; Tsintiris, Konstantinos

    2015-01-01

    Cryptogenic organizing pneumonia (COP), previously called bronchiolitis obliterans organizing pneumonia (BOOP) is a clinicopathological disorder of unknown aetiology but increasingly reported. It usually presents with symptoms of dyspnea, cough, fever, weight loss accompanied by the presence of alveolar opacities on chest radiograph. Haemoptysis, described as blood streaking has only rarely been reported as primary presentation of COP. Herein, we report a case of COP in which submassive haemoptysis was the main clinical manifestation. The clinical, radiological, pathological, and therapeutic aspects of the disease are briefly discussed. Cryptogenic organizing pneumonia should be taken into consideration in the differential diagnosis of severe haemoptysis. PMID:27451594

  13. 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

    Alexandersen, S; Bloom, M E; Wolfinbarger, J; Race, R E

    1987-08-01

    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.

  14. 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

  15. Strength changes induced by extreme dieting and exercise in severely obese females.

    PubMed

    Pronk, N P; Donnelly, J E; Pronk, S J

    1992-04-01

    Strength changes, induced by very low-calorie diet (VLCD, 520 kcal/day) alone and in combination with exercise, were determined in 109 severely obese females (46.8 +/- 4.69% fat). Experimental treatments included VLCD alone (LC, n = 40), VLCD with endurance exercise (EE, n = 23), VLCD with endurance exercise and resistance strength training (EERST, n = 23), and VLCD with resistance strength training (RST, n = 23). All subjects participated in the study for 90 days while EE, EERST, and RST exercised four times/week according to specified schedules. Results indicated significant differences for the change scores (baseline to 90 days) for bench press, knee flexion, upper body and lower body composite strength scores between RST and all other groups. RST was the only treatment that increased upper and lower body strength. No differences between groups were found for body mass losses, decrease in percent fat and fat mass. In contrast, these variables showed significant change scores for all groups. Decreases in fat-free mass (FFM) were 5.18 +/- 3.40 kg, 4.79 +/- 4.15 kg (p = 0.001), 4.64 +/- 4.23 kg, and 3.26 +/- 2.67 kg for EE, LC, RST, and EERST, respectively. These data suggest that the combination of resistance strength training and VLCD increases strength despite a loss of FFM. However, endurance exercise and VLCD do not seem to affect body mass loss or FFM loss per se. Moreover, it seems that these increases in strength may represent a training effect which might imply improved central neuromuscular function rather than muscular hypertrophy since FFM decreased in all groups.

  16. Successful recovery of MERS CoV pneumonia in a patient with acquired immunodeficiency syndrome: a case report.

    PubMed

    Shalhoub, Sarah; AlZahrani, Abdulwahab; Simhairi, Raed; Mushtaq, Adnan

    2015-01-01

    Middle East Respiratory Syndrome Coronavirus (MERS CoV) may cause severe pneumonia with significant morbidity and mortality, particularly in patients with multiple comorbid condition. MERS CoV pneumonia has not been previously reported in patients with Human Immunodeficiency Virus (HIV). Herein, we report a case of MERS CoV pneumonia with a successful outcome in a patient recently diagnosed with HIV.

  17. 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

  18. Modelling staphylococcal pneumonia in a human 3D lung tissue model system delineates toxin-mediated pathology.

    PubMed

    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

    2015-11-01

    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 setting. The

  19. Modelling staphylococcal pneumonia in a human 3D lung tissue model system delineates toxin-mediated pathology.

    PubMed

    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

    2015-11-01

    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 setting. The

  20. 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

  1. Carboplatin-induced severe hypersensitivity reaction: role of IgE-dependent basophil activation and FcεRI.

    PubMed

    Iwamoto, Takuya; Hirai, Hiroyuki; Yamaguchi, Nozomi; Kobayashi, Natsuki; Sugimoto, Hiroko; Tabata, Tsutomu; Okuda, Masahiro

    2014-11-01

    Basophil activation was observed in patients with a history of carboplatin-induced severe hypersensitivity reaction (HR). However, the precise mechanism by which carboplatin induces basophil activation and the associated surrogate markers remains to be elucidated. To investigate whether IgE-dependent mechanisms, including the overexpression of FcεRI, participate in carboplatin-induced basophil activation, 13 ovarian cancer patients were enrolled: 5 with a history of carboplatin-induced severe hypersensitivity reaction within the past 2 years, and 8 with no such history. The expression levels of FcεRI, IgE, and CD203c on basophils were measured using a flow cytometer. Immunoglobulin E-dependent basophil activation was evaluated by testing for IgE passive sensitization using lactic acid, and by testing for phosphatidylinositol 3-kinase inhibition, using wortmannin. In three patients positive for carboplatin hypersensitivity, pretreatment with wortmannin almost completely inhibited carboplatin-induced basophil activation (P < 0.05). In a healthy control subject, whose own IgE showed no response to carboplatin, acquired reactivity to carboplatin when exposed to plasma from patients positive for carboplatin hypersensitivity. This did not occur when the same experiment was carried out using plasma from the patients negative for carboplatin hypersensitivity. Moreover, pretreatment with omalizumab, a monoclonal anti-IgE antibody, almost completely blocked carboplatin-induced basophil activation in the plasma of patients positive for carboplatin hypersensitivity. On further investigation, the HR-positive group had significantly higher levels of FcεRI compared with the negative group (P < 0.05). In conclusion, an IgE-dependent mechanism incorporating FcεRI overexpression participates in carboplatin-induced severe HR. These results establish the relevance of monitoring the pharmacodynamic changes of basophils to prevent carboplatin-induced severe HR.

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. [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.

  7. Vena-venous hemofiltration in treating severe injury-induced multiple organ dysfunction syndrome.

    PubMed

    Fang, Y; Zong, H L; Zhang, L; Wang, Z H; Sun, L M; Zhang, R F

    2016-01-01

    Severe multiple injury (SMI) can induce multiple organ dysfunction syndrome (MODS) and easily result in complications, as well as having a high mortality rate. To explore the curative effect of continuous vena-venous hemofiltration (CVVH) in treating MODS and its effect on serum tumor necrosis factor (TNF)-α interleukin (IL)-10 and nitric oxide (NO), we selected 200 patients who suffered from SMI and received treatment in the First Affiliated Hospital of Zhengzhou University between April 2012 and April 2014 as research subjects. All patients were treated with CVVH. Vital signs, blood oxygen pressure (PaO(2)) and oxygenation index (OI) of artery, electrolyte and acid-base balance were observed before and after treatment. Before treatment, 1 h and 12 h after the start of treatment, and at the end of treatment, TNF-α and IL-10 concentrations in serum and ultrafiltrate were tested using enzyme linked immunosorbent assay, and NO concentration in serum and ultrafiltrate was detected using nitrate reduction method. After treatment, heart rate and respiratory rate of patients had significant decline (P less than 0.05) and average arterial pressure rose remarkably (P less than 0.05); blood urea nitrogen and creatinine decreased (P less than 0.05 or 0.01); PaO(2) and OI were both significantly increased (P less than 0.01); hyperkalemia and acidosis were effectively corrected (P less than 0.01); but differences of Na+, Ca2+ and Cl- before and after treatment had no statistical significance (P>0.05). Serum IL-10 concentration had a significant increase after treatment, while TNF-α and NO concentrations had a significant decline after treatment. A small quantity of IL-10, but not of TNF-α, was detected from ultrafiltrate. Concentration of NO in ultrafiltrate was higher. It can be concluded that CVVH can effectively relieve clinical symptoms of MODS patients, improve function of organs, correct electrolyte disturbance and acid-base imbalance and eliminate TNF-α and NO in

  8. 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

  9. Streptococcus pneumoniae secretes hydrogen peroxide leading to DNA damage and apoptosis in lung cells

    PubMed Central

    Rai, Prashant; Parrish, Marcus; Tay, Ian Jun Jie; Li, Na; Ackerman, Shelley; He, Fang; Kwang, Jimmy; Chow, Vincent T.; Engelward, Bevin P.

    2015-01-01

    Streptococcus pneumoniae is a leading cause of pneumonia and one of the most common causes of death globally. The impact of S. pneumoniae on host molecular processes that lead to detrimental pulmonary consequences is not fully understood. Here, we show that S. pneumoniae induces toxic DNA double-strand breaks (DSBs) in human alveolar epithelial cells, as indicated by ataxia telangiectasia mutated kinase (ATM)-dependent phosphorylation of histone H2AX and colocalization with p53-binding protein (53BP1). Furthermore, results show that DNA damage occurs in a bacterial contact-independent fashion and that Streptococcus pyruvate oxidase (SpxB), which enables synthesis of H2O2, plays a critical role in inducing DSBs. The extent of DNA damage correlates with the extent of apoptosis, and DNA damage precedes apoptosis, which is consistent with the time required for execution of apoptosis. Furthermore, addition of catalase, which neutralizes H2O2, greatly suppresses S. pneumoniae-induced DNA damage and apoptosis. Importantly, S. pneumoniae induces DSBs in the lungs of animals with acute pneumonia, and H2O2 production by S. pneumoniae in vivo contributes to its genotoxicity and virulence. One of the major DSBs repair pathways is nonhomologous end joining for which Ku70/80 is essential for repair. We find that deficiency of Ku80 causes an increase in the levels of DSBs and apoptosis, underscoring the importance of DNA repair in preventing S. pneumoniae-induced genotoxicity. Taken together, this study shows that S. pneumoniae-induced damage to the host cell genome exacerbates its toxicity and pathogenesis, making DNA repair a potentially important susceptibility factor in people who suffer from pneumonia. PMID:26080406

  10. 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

  11. 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

  12. Prognostic score systems and community-acquired bacteraemic pneumococcal pneumonia.

    PubMed

    Spindler, C; Ortqvist, A

    2006-10-01

    The aim of this study was to evaluate the accuracy of three score systems: the pneumonia severity index (PSI); CURB-65 (confusion; urea >7 mM; respiratory rate > or =30 breaths x min(-1); blood pressure <90 mmHg systolic or < or =60 mmHg diastolic; aged > or =65 yrs old); and modified American Thoracic Society rule for predicting intensive care unit (ICU) need and mortality due to bacteraemic pneumococcal pneumonia. All adult patients (n = 114) with invasive pneumococcal pneumonia at the Karolinska University Hospital, Sweden, 1999-2000, were included in the study. Severity scores were calculated and the independent prognostic importance of different variables was analysed by multiple regression analyses. PSI > or = IV, CURB-65 > or = 2, and the presence of one major or more than one minor risk factor in mATS all had a high sensitivity, but somewhat lower specificity for predicting death and ICU need. The death rate was 12% (13 out of 114). Severity score and treatment in departments other than the Dept of Infectious Diseases were the only factors independently correlated to death. Patients treated in other departments more often had severe underlying illnesses and were more severely ill on admission. However, a significant difference in death rates remained after adjustment for severity between the two groups. In conclusion, all score systems were useful for predicting the need for intensive care unit treatment and death due to bacteremic pneumococcal pneumonia. The pneumonia severity index was the most sensitive, but CURB-65 was easier to use.

  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. 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

    2015-10-21

    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.

  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. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. STAT1 regulates IFN-alpha beta- and IFN-gamma-dependent control of infection with Chlamydia pneumoniae by nonhemopoietic cells.

    PubMed

    Rothfuchs, Antonio Gigliotti; Trumstedt, Christian; Mattei, Fabrizio; Schiavoni, Giovanna; Hidmark, Asa; Wigzell, Hans; Rottenberg, Martín E

    2006-06-01

    STAT1 mediates signaling in response to IFN-alpha, -beta, and -gamma, cytokines required for protective immunity against several viral, bacterial, and eukaryotic pathogens. The protective role of STAT1 in the control of intranasal infection with the obligate intracellular bacterium Chlamydia pneumoniae was analyzed. IFN-gamma-/- or IFN-gamma receptor (R)-/- mice were highly susceptible to infection with C. pneumoniae. We found that STAT1-/- mice were even more susceptible to C. pneumoniae than IFN-gamma-/- or IFN-gammaR-/- mice. Phosphorylation of STAT1 was detected in the lungs of C. pneumoniae-infected wild-type, IFN-gammaR-/-, and IFN-alphabetaR-/- mice, but not in mice lacking both IFN-alphabetaR and IFN-gammaR. In line with this, IFN-alphabetaR-/-/IFN-gammaR-/- mice showed increased susceptibility to infection compared with IFN-gammaR-/- mice. However, C. pneumoniae-infected IFN-alphabetaR-/- or IFN regulatory factor 3-/- mice showed no increased susceptibility and similar IFN-gamma expression compared with wild-type mice. CD4+ or CD8+ cells released IFN-gamma in vivo and conferred protection against C. pneumoniae in a STAT1-independent manner. In contrast, STAT1 mediated a nonredundant protective role of nonhemopoietic cells but not of hemopoietic cells. Nonhemopoietic cells accounted for the expression of STAT1-mediated indoleamine 2, 3-dioxygenase and the p47 GTPase LRG-47, but not inducible NO synthase mRNA. In summary, we demonstrate that STAT1 mediates a cooperative effect of IFN-alphabeta and IFN-gamma on nonhemopoietic cells, resulting in protection against C. pneumoniae. PMID:16709859

  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. 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

  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. 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.

  6. Severe Self-induced Beam Distortion in Laboratory Simulated Laser Propagation at 10.6 micro.

    PubMed

    Buser, R G; Rohde, R S

    1973-02-01

    Precision irradiance profiles have been determined for horizontally slewing high power laser beams through stationary absorbing gaseous media for the case of strong beam-medium interaction coupled with strong heating. Results are compared with the predictions of existing theoretical models concerning thermally induced lens effects in the presence of cross winds. Bending of the beam into the wind by beam slewing and intensification is found in reasonable agreement with the theory; for the observed overall beam spread, induced flow, turbulent tail, and concomitant beam breakup, no satisfactory theoretical treatment is available.

  7. Update on cryptogenic organising pneumonia (idiopathic bronchiolitis obliterans organising pneumonia).

    PubMed

    Cordier, Jean-François

    2002-11-23

    Organising pneumonia, defined by intraalveolar buds of connective tissue, may be a disorder secondary to a determined cause (infectious agents, drugs) or occurring in a specific context (as the connective tissue disorders). It may also be a cryptogenic interstitial pneumonia with characteristic clinical and imaging features and especially an excellent response to corticosteroids.

  8. Klebsiella pneumoniae FimK Promotes Virulence in Murine Pneumonia.

    PubMed

    Rosen, David A; Hilliard, Julia K; Tiemann, Kristin M; Todd, Elizabeth M; Morley, S Celeste; Hunstad, David A

    2016-02-15

    Klebsiella pneumoniae, a chief cause of nosocomial pneumonia, is a versatile and commonly multidrug-resistant human pathogen for which further insight into pathogenesis is needed. We show that the pilus regulatory gene fimK promotes the virulence of K. pneumoniae strain TOP52 in murine pneumonia. This contrasts with the attenuating effect of fimK on urinary tract virulence, illustrating that a single factor may exert opposing effects on pathogenesis in distinct host niches. Loss of fimK in TOP52 pneumonia was associated with diminished lung bacterial burden, limited innate responses within the lung, and improved host survival. FimK expression was shown to promote serum resistance, capsule production, and protection from phagocytosis by host immune cells. Finally, while the widely used K. pneumoniae model strain 43816 produces rapid dissemination and death in mice, TOP52 caused largely localized pneumonia with limited lethality, thereby providing an alternative tool for studying K. pneumoniae pathogenesis and control within the lung.

  9. Anthracyclines Induce DNA Damage Response-Mediated Protection against Severe Sepsis

    PubMed Central

    Figueiredo, Nuno; Chora, Angelo; Raquel, Helena; Pejanovic, Nadja; Pereira, Pedro; Hartleben, Björn; Neves-Costa, Ana; Moita, Catarina; Pedroso, Dora; Pinto, Andreia; Marques, Sofia; Faridi, Hafeez; Costa, Paulo; Gozzelino, Raffaella; Zhao, Jimmy L.; Soares, Miguel P.; Gama-Carvalho, Margarida; Martinez, Jennifer; Zhang, Qingshuo; Döring, Gerd; Grompe, Markus; Simas, J. Pedro; Huber, Tobias B.; Baltimore, David; Gupta, Vineet; Green, Douglas R.; Ferreira, João A.; Moita, Luis F.

    2014-01-01

    Summary Severe sepsis remains a poorly understood systemic inflammatory condition with high mortality rates and limited therapeutic options in addition to organ support measures. Here we show that the clinically approved group of anthracyclines acts therapeutically at a low dose regimen to confer robust protection against severe sepsis in mice. This salutary effect is strictly dependent on the activation of DNA damage response and autophagy pathways in the lung, as demonstrated by deletion of the ataxia telangiectasia mutated (Atm) or the autophagy-related protein 7 (Atg7) specifically in this organ. The protective effect of anthracyclines occurs irrespectively of pathogen burden, conferring disease tolerance to severe sepsis. These findings demonstrate that DNA damage responses, including the ATM and Fancony Anemia pathways, are important modulators of immune responses and might be exploited to confer protection to inflammation-driven conditions, including severe sepsis. PMID:24184056

  10. Successful steroid treatment of coma induced by severe spontaneous intracranial hypotension

    PubMed Central

    Goto, Shunsaku; Ohshima, Tomotaka; Yamamoto, Taiki; Shimato, Shinji; Nishizawa, Toshihisa; Kato, Kyozo

    2016-01-01

    ABSTRACT Spontaneous intracranial hypotension (SIH) is a syndrome characterized by low cerebrospinal fluid (CSF) pressure and postural headaches. It is a rare condition which may sometimes present with severe symptoms such as stupor or coma. The standard treatment protocol includes conservative measures such as bed rest, hydration, and steroids. However, severe cases may require invasive measures such as epidural blood patch (EBP), continuous epidural saline infusion, epidural fibrin glue, or surgical repair of the dural defect. In this report, we describe a case of severe SIH resulting in coma that exhibited dramatic improvement on intravenous administration of steroids. This is the first report of severe SIH causing coma that was treated non-invasively by steroids only. PMID:27303109

  11. Successful steroid treatment of coma induced by severe spontaneous intracranial hypotension.

    PubMed

    Goto, Shunsaku; Ohshima, Tomotaka; Yamamoto, Taiki; Shimato, Shinji; Nishizawa, Toshihisa; Kato, Kyozo

    2016-05-01

    Spontaneous intracranial hypotension (SIH) is a syndrome characterized by low cerebrospinal fluid (CSF) pressure and postural headaches. It is a rare condition which may sometimes present with severe symptoms such as stupor or coma. The standard treatment protocol includes conservative measures such as bed rest, hydration, and steroids. However, severe cases may require invasive measures such as epidural blood patch (EBP), continuous epidural saline infusion, epidural fibrin glue, or surgical repair of the dural defect. In this report, we describe a case of severe SIH resulting in coma that exhibited dramatic improvement on intravenous administration of steroids. This is the first report of severe SIH causing coma that was treated non-invasively by steroids only. PMID:27303109

  12. Prevention of lipid peroxidation induced by ochratoxin A in Vero cells in culture by several agents.

    PubMed

    Baudrimont, I; Ahouandjivo, R; Creppy, E E

    1997-04-18

    Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus ochraceus as well as other moulds. This mycotoxin contaminates animal feed and food and is nephrotoxic for all animal species studied so far. OTA is immunosuppressive, genotoxic, teratogenic and carcinogenic. It is a structural analogue of phenylalanine and contains a chlorinated dihydroisocoumarinic moiety. Ochratoxin A inhibits protein synthesis by competition with phenylalanine in the phenylalanine-tRNA aminoacylation reaction. Recently lipid peroxidation induced by OTA has been reported, indicating that the lesions induced by this toxin could also be related to oxidative damage. An attempt to prevent its toxic effect, mainly the lipid peroxidation, has been made using aspartame (L-aspartyl-L-phenylalanine methyl ester) a structural analogue of both OTA and phenylalanine, piroxicam, a non steroidal anti-inflammatory drug and superoxide dismutase+catalase (endogenous oxygen radical scavengers). Lipid peroxidation was assayed in monkey kidney cells (Vero cells) treated by increasing concentrations of OTA (5-50 microM). After 24 h incubation OTA induced lipid peroxidation in Vero cells in a concentration dependent manner, as measured by malonaldehyde (MDA) production. The MDA production, in Vero cells, was significantly increased by 50.5% from 694.1 +/- 21.0 to 1041.5 +/- 23.5 pmol/mg of protein. In the presence of superoxide dismutase (SOD)+catalase (25 micrograms/ml each) the MDA production induced by OTA was significantly decreased. At 50 microM of OTA concentration (optimal production of MDA) the MDA production decreased from 1041.5 +/- 23.5 to 827.5 +/- 21.3 pmol/mg of protein. SOD and catalase, when applied prior to the toxin, seemed to prevent lipid peroxidation more efficiently than piroxicam (at a ten-fold higher concentration than OTA) and aspartame (at equimolar concentration). These molecules also partially prevented the OTA-induced leakage of MDA in the culture medium. PMID:9158693

  13. Prevention of lipid peroxidation induced by ochratoxin A in Vero cells in culture by several agents.

    PubMed

    Baudrimont, I; Ahouandjivo, R; Creppy, E E

    1997-04-18

    Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus ochraceus as well as other moulds. This mycotoxin contaminates animal feed and food and is nephrotoxic for all animal species studied so far. OTA is immunosuppressive, genotoxic, teratogenic and carcinogenic. It is a structural analogue of phenylalanine and contains a chlorinated dihydroisocoumarinic moiety. Ochratoxin A inhibits protein synthesis by competition with phenylalanine in the phenylalanine-tRNA aminoacylation reaction. Recently lipid peroxidation induced by OTA has been reported, indicating that the lesions induced by this toxin could also be related to oxidative damage. An attempt to prevent its toxic effect, mainly the lipid peroxidation, has been made using aspartame (L-aspartyl-L-phenylalanine methyl ester) a structural analogue of both OTA and phenylalanine, piroxicam, a non steroidal anti-inflammatory drug and superoxide dismutase+catalase (endogenous oxygen radical scavengers). Lipid peroxidation was assayed in monkey kidney cells (Vero cells) treated by increasing concentrations of OTA (5-50 microM). After 24 h incubation OTA induced lipid peroxidation in Vero cells in a concentration dependent manner, as measured by malonaldehyde (MDA) production. The MDA production, in Vero cells, was significantly increased by 50.5% from 694.1 +/- 21.0 to 1041.5 +/- 23.5 pmol/mg of protein. In the presence of superoxide dismutase (SOD)+catalase (25 micrograms/ml each) the MDA production induced by OTA was significantly decreased. At 50 microM of OTA concentration (optimal production of MDA) the MDA production decreased from 1041.5 +/- 23.5 to 827.5 +/- 21.3 pmol/mg of protein. SOD and catalase, when applied prior to the toxin, seemed to prevent lipid peroxidation more efficiently than piroxicam (at a ten-fold higher concentration than OTA) and aspartame (at equimolar concentration). These molecules also partially prevented the OTA-induced leakage of MDA in the culture medium.

  14. 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

  15. A case of chronic hepatitis C patient of myocardial ischemia accompanied with interstitial pneumonia induced by pegylated interferon alpha-2a

    PubMed Central

    Qu, Caihong; Zheng, Zhenda; Liu, Weimin; Jiao, Ju; Zhu, Jieming

    2014-01-01

    After 3 months of combination treatment using interferon α-2a and Ribavirin, a case of 59-year-old female patient with chronic viral hepatitis C demonstrated symptoms such as headache, dizziness accompanied by nausea, vomiting, dry cough, breathing difficulty, and shortness of breath. Dynamic electrocardiogram showed occasional atrial premature beats, paroxysmal tachycardia, and abnormal ST-T (T wave inversion and prolongation of the QT interval). Ambulatory blood pressure indicated that mean blood pressure was elevated than before. Myocardial radionuclide scan showed focal myocardial ischemia in left ventricular inferior wall. Pulmonary function tests showed that pulmonary diffusion function was decreased, indicating the possibility of interstitial pneumonia. The patient had no history of coronary heart disease or chest X-ray abnormalities before medication, but had hypertensive medical history for 8 years with good blood pressure control. After withdrawal of antiviral drugs, symptoms such as dry cough, breathing difficulty and T wave inversion were gradually relieved. This case indicated that myocardial ischemia and pulmonary lesions were associated with the application of pegylated interferon α-2a. PMID:25197402

  16. A type III secretion negative clinical strain of Pseudomonas aeruginosa employs a two-partner secreted exolysin to induce hemorrhagic pneumonia.

    PubMed

    Elsen, Sylvie; Huber, Philippe; Bouillot, Stéphanie; Couté, Yohann; Fournier, Pierre; Dubois, Yohann; Timsit, Jean-François; Maurin, Max; Attrée, Ina

    2014-02-12

    Virulence of Pseudomonas aeruginosa is typically attributed to its type III secretion system (T3SS). A taxonomic outlier, the P. aeruginosa PA7 strain, lacks a T3SS locus, and no virulence phenotype is attributed to PA7. We characterized a PA7-related, T3SS-negative P. aeruginosa strain, CLJ1, isolated from a patient with fatal hemorrhagic pneumonia. CLJ1 is highly virulent in mice, leading to lung hemorrhage and septicemia. CLJ1-infected primary endothelial cells display characteristics of membrane damage and permeabilization. Proteomic analysis of CLJ1 culture supernatants identified a hemolysin/hemagglutinin family pore-forming toxin, Exolysin (ExlA), that is exported via ExlB, representing a putative two-partner secretion system. A recombinant P. aeruginosa PAO1ΔpscD::exlBA strain, deficient for T3SS but engineered to express ExlA, gained lytic capacity on endothelial cells and full virulence in mice, demonstrating that ExlA is necessary and sufficient for pathogenicity. This highlights clinically relevant T3SS-independent hypervirulence, isolates, and points to a broader P. aeruginosa pathogenic repertoire.

  17. 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

  18. The Regulation of Proresolving Lipid Mediator Profiles in Baboon Pneumonia by Inhaled Carbon Monoxide.

    PubMed

    Dalli, Jesmond; Kraft, Bryan D; Colas, Romain A; Shinohara, Masakazu; Fredenburgh, Laura E; Hess, Dean R; Chiang, Nan; Welty-Wolf, Karen; Choi, Augustine M; Piantadosi, Claude A; Serhan, Charles N

    2015-09-01

    Strategies for the treatment of bacterial pneumonia beyond traditional antimicrobial therapy have been limited. The recently discovered novel genus of lipid mediators, coined "specialized proresolving mediators" (SPMs), which orchestrate clearance of recruited leukocytes and restore epithelial barrier integrity, have offered new insight into the resolution of inflammation. We performed lipid mediator (LM) metabololipidomic profiling and identification of LMs on peripheral blood leukocytes and plasma from a baboon model of Streptococcus pneumoniae pneumonia. Leukocytes and plasma were isolated from whole blood of S. pneumoniae-infected (n = 5-6 per time point) and control, uninfected baboons (n = 4 per time point) at 0, 24, 48, and 168 hours. In a subset of baboons with pneumonia (n = 3), we administered inhaled carbon monoxide (CO) at 48 hours (200-300 ppm for 60-90 min). Unstimulated leukocytes from control animals produced a proresolving LM signature with elevated resolvins and lipoxins. In contrast, serum-treated, zymosan-stimulated leukocytes and leukocytes from baboons with S. pneumoniae pneumonia produced a proinflammatory LM signature profile with elevated leukotriene B4 and prostaglandins. Plasma from baboons with S. pneumoniae pneumonia also displayed significantly reduced LM-SPM levels, including eicosapentaenoic acid-derived E-series resolvins (RvE) and lipoxins. CO inhalation increased levels of plasma RvE and lipoxins relative to preexposure levels. These results establish the leukocyte and plasma LM profiles biosynthesized during S. pneumoniae pneumonia in baboons and provide evidence for pneumonia-induced dysregulation of these proresolution programs. Moreover, these SPM profiles are partially restored with inhaled low-dose CO and SPM, which may shorten the time to pneumonia resolution.

  19. A review of genetic methods and models for analysis of coronavirus-induced severe pneumonitis

    PubMed Central

    McGruder, Brenna

    2015-01-01

    Coronaviruses (CoVs) have been studied for over 60 years, but have only recently gained notoriety as deadly human pathogens with the emergence of severe respiratory syndrome CoV and Middle East respiratory syndrome virus. The rapid emergence of these viruses has demonstrated the need for good models to study severe CoV respiratory infection and pathogenesis. There are, currently, different methods and models for the study of CoV disease. The available genetic methods for the study and evaluation of CoV genetics are reviewed here. There are several animal models, both mouse and alternative animals, for the study of severe CoV respiratory disease that have been examined, each with different pros and cons relative to the actual pathogenesis of the disease in humans. A current limitation of these models is that no animal model perfectly recapitulates the disease seen in humans. Through the review and analysis of the available disease models, investigators can employ the most appropriate available model to study various aspects of CoV pathogenesis and evaluate possible antiviral treatments that may potentially be successful in future treatment and prevention of severe CoV respiratory infections. PMID:25252685

  20. Feedlot Acute Interstitial Pneumonia.

    PubMed

    Woolums, Amelia R

    2015-11-01

    Acute interstitial pneumonia (AIP) of feedlot cattle is a sporadically occurring respiratory condition that is often fatal. Affected cattle have a sudden onset of labored breathing. There is no confirmed effective treatment of feedlot AIP; however, administration of antibiotics effective against common bacterial respiratory pathogens and nonsteroidal anti-inflammatory drugs, especially aspirin, has been recommended. Protective strategies are not well defined, but efforts to limit dust exposure and heat stress; to ensure consistent formulation, mixing, and delivery of feed; and to identify and treat infectious respiratory disease in a timely manner may decrease rates of feedlot AIP.

  1. Lymphocytic Interstitial Pneumonia.

    PubMed

    Panchabhai, Tanmay S; Farver, Carol; Highland, Kristin B

    2016-09-01

    Lymphocytic interstitial pneumonia (LIP) is a rare lung disease on the spectrum of benign pulmonary lymphoproliferative disorders. LIP is frequently associated with connective tissue diseases or infections. Idiopathic LIP is rare; every attempt must be made to diagnose underlying conditions when LIP is diagnosed. Computed tomography of the chest in patients with LIP may reveal ground-glass opacities, centrilobular and subpleural nodules, and randomly distributed thin-walled cysts. Demonstrating polyclonality with immunohistochemistry is the key to differentiating LIP from lymphoma. The 5-year mortality remains between 33% and 50% and is likely to vary based on the underlying disease process. PMID:27514593

  2. Klebsiella pneumoniae splenic abscess.

    PubMed

    Gill, V; Marzocca, F J; Cunha, B A

    1994-01-01

    Splenic abscesses may be solitary or multiple and are unusual infections. Signs and symptoms are variable and do not always include left upper quadrant pain or tenderness, as the Case Report illustrate. Abscesses of the spleen may occur as a result of endocarditis or from hematogenous seeding from a distant focus of infection. Computed tomographic scan of the spleen is the diagnostic method of choice. We report a case of multiple splenic abscesses caused by Klebsiella pneumoniae that resulted from a Klebsiella urinary tract infection and was successfully managed with antibiotic therapy and splenectomy. PMID:8039997

  3. Enteral Tube Feeding and Pneumonia

    ERIC Educational Resources Information Center

    Gray, David Sheridan; Kimmel, David

    2006-01-01

    To determine the effects of enteral tube feeding on the incidence of pneumonia, we performed a retrospective review of all clients at our institution who had gastrostomy or jejunostomy tubes placed over a 10-year period. Ninety-three subjects had a history of pneumonia before feeding tube insertion. Eighty had gastrostomy and 13, jejunostomy…

  4. Vaccines to prevent severe acute respiratory syndrome coronavirus-induced disease

    PubMed Central

    Enjuanes, Luis; DeDiego, Marta L.; Álvarez, Enrique; Deming, Damon; Sheahan, Tim; Baric, Ralph

    2009-01-01

    An important effort has been performed after the emergence of severe acute respiratory syndrome (SARS) epidemic in 2003 to diagnose and prevent virus spreading. Several types of vaccines have been developed including inactivated viruses, subunit vaccines, virus-like particles (VLPs), DNA vaccines, heterologous expression systems, and vaccines derived from SARS-CoV genome by reverse genetics. This review describes several aspects essential to develop SARS-CoV vaccines, such as the correlates of protection, virus serotypes, vaccination side effects, and bio-safeguards that can be engineered into recombinant vaccine approaches based on the SARS-CoV genome. The production of effective and safe vaccines to prevent SARS has led to the development of promising vaccine candidates, in contrast to the design of vaccines for other coronaviruses, that in general has been less successful. After preclinical trials in animal models, efficacy and safety evaluation of the most promising vaccine candidates described has to be performed in humans. PMID:17416434

  5. Thrombocytopenia induces multiple intracranial hemorrhages in patients with severe burns: A review of 16 cases

    PubMed Central

    ZHOU, JIANDA; LIU, JINYAN; LUO, CHENGQUN; HU, FENG; LIU, RUI; CHEN, ZIZI; CHEN, YAO; XIONG, WU; XIE, JIANFEI; HE, QUANYONG; YIN, CHAOQI; WANG, SHAOHUA; ZHANG, YANWEN; ZENG, SAINAN

    2013-01-01

    The aim of this study was to explore the etiology and diagnosis of multiple intracranial hemorrhages (ICHs) following severe burns, with a retrospective review of 16 cases of severe burns further complicated by multiple ICHs. Using cranial CT scans of the brains, we identified that all patients presented with low platelet counts and coagulation abnormalities prior to intracranial hemorrhaging. Following conventional treatment and various supporting treatments, five cases succumbed following a progressive reduction in blood platelet levels and the ICHs were cured in 11 cases following the restoration of normal platelet levels. We conclude that low platelet counts and coagulation abnormalities may cause multiple ICHs following severe burns and early diagnosis and treatment is the key to successful treatment. PMID:23935750

  6. The role of respiratory viruses in the etiology of bacterial pneumonia: An ecological perspective.

    PubMed

    Lee, Kyu Han; Gordon, Aubree; Foxman, Betsy

    2016-01-01

    Pneumonia is the leading cause of death among children less than 5 years old worldwide. A wide range of viral, bacterial and fungal agents can cause pneumonia: although viruses are the most common etiologic agent, the severity of clinical symptoms associated with bacterial pneumonia and increasing antibiotic resistance makes bacterial pneumonia a major public health concern. Bacterial pneumonia can follow upper respiratory viral infection and complicate lower respiratory viral infection. Secondary bacterial pneumonia is a major cause of influenza-related deaths. In this review, we evaluate the following hypotheses: (i) respiratory viruses influence the etiology of pneumonia by altering bacterial community structure in the upper respiratory tract (URT) and (ii) respiratory viruses promote or inhibit colonization of the lower respiratory tract (LRT) by certain bacterial species residing in the URT. We conducted a systematic review of the literature to examine temporal associations between respiratory viruses and bacteria and a targeted review to identify potential mechanisms of interactions. We conclude that viruses both alter the bacterial community in the URT and promote bacterial colonization of the LRT. However, it is uncertain whether changes in the URT bacterial community play a substantial role in pneumonia etiology. The exception is Streptococcus pneumoniae where a strong link between viral co-infection, increased carriage and pneumococcal pneumonia has been established. PMID:26884414

  7. The role of respiratory viruses in the etiology of bacterial pneumonia

    PubMed Central

    Lee, Kyu Han; Gordon, Aubree; Foxman, Betsy

    2016-01-01

    Pneumonia is the leading cause of death among children less than 5 years old worldwide. A wide range of viral, bacterial and fungal agents can cause pneumonia: although viruses are the most common etiologic agent, the severity of clinical symptoms associated with bacterial pneumonia and increasing antibiotic resistance makes bacterial pneumonia a major public health concern. Bacterial pneumonia can follow upper respiratory viral infection and complicate lower respiratory viral infection. Secondary bacterial pneumonia is a major cause of influenza-related deaths. In this review, we evaluate the following hypotheses: (i) respiratory viruses influence the etiology of pneumonia by altering bacterial community structure in the upper respiratory tract (URT) and (ii) respiratory viruses promote or inhibit colonization of the lower respiratory tract (LRT) by certain bacterial species residing in the URT. We conducted a systematic review of the literature to examine temporal associations between respiratory viruses and bacteria and a targeted review to identify potential mechanisms of interactions. We conclude that viruses both alter the bacterial community in the URT and promote bacterial colonization of the LRT. However, it is uncertain whether changes in the URT bacterial community play a substantial role in pneumonia etiology. The exception is Streptococcus pneumoniae where a strong link between viral co-infection, increased carriage and pneumococcal pneumonia has been established. PMID:26884414

  8. Early detection of pneumonia as a risk factor for mortality in burn patients in Menoufiya University Hospitals, Egypt.

    PubMed

    Mgahed, M; El-Helbawy, R; Omar, A; El-Meselhy, H; Abd El-Halim, R

    2013-09-30

    Pneumonia is common among critically ill burn patients and is a major cause of morbidity and mortality among them. Prediction of mortality in patients with severe burns remains unreliable. The aim of this research is to study the incidence, early diagnosis and management of nosocomial pneumonia, and to discuss the relationship between pneumonia and death in burn patients. This prospective study was carried out on 80 burn patients (35 males and 45 females) admitted to Menoufiya University Hospital Burn Center and Chest Department, Egypt, from September 2011 to March 2012. Our findings showed an overall burn patient mortality rate of 26.25 % (21/80), 15% (12/80) incidence of pneumonia, and a 50% (6/12) mortality rate among patients with pneumonia compared to 22 % (15/68) for those without pneumonia. The incidence of pneumonia was twice as high in the subset of patients with inhalation injury as among those without inhalation injury (P< 0.001). It was found that the presence of pneumonia, inhalation injury, increased burn size, and advanced age were all associated with increased mortality (P< 0.001). In the late onset pneumonia, other associated factors also contributed to mortality. Severity of disease, severity of illness (APACHE score), organ failure, underlying co-morbidities, and VAP PIRO score all have significant correlations with mortality rate. Pneumonia was an important factor for predicting burn patient mortality. Early detection and management of pneumonia are absolutely essential. PMID:24563638

  9. A novel method for assessing the severity of levodopa-induced dyskinesia using wearable sensors.

    PubMed

    Lee, Sunghoon Ivan; Daneault, Jean-Francois; Golabchi, Fatemeh Noushin; Patel, Shyamal; Paganoni, Sabrina; Shih, Ludy; Bonato, Paolo

    2015-08-01

    Patients with Parkinson's disease often experience significant changes in the severity of dyskinesia when they undergo titration of their medications. Dyskinesia is marked by involuntary jerking movements that occur randomly in a burst-like fashion. The burst-like nature of such movements makes it difficult to estimate the clinical scores of severity of dyskinesia using wearable sensors. Clinical observations are generally made over intervals of 15-30 s. On the other hand, techniques designed to estimate the severity of dyskinesia based on the analysis of wearable sensor data typically use data segments of approximately 5 s. Consequently, some data segments might include dyskinetic movements, whereas others might not. Herein, we propose a novel method suitable to automatically select data segments from the training dataset that are marked by dyskinetic movements. The proposed method also aggregates results derived from the testing dataset using a machine learning algorithm to estimate the severity of dyskinesia from wearable sensor data. Results obtained from the analysis of sensor data collected from seven subjects with Parkinson's disease showed a marked improvement in the accuracy of the estimation of clinical scores of dyskinesia.

  10. Televised Models as Agents of Behavior Change: Inducing Pro-Social Interaction Among Severely Withdrawn Children.

    ERIC Educational Resources Information Center

    Kassier, Marjorie Rose

    The study examined the effectiveness of videotapes showing cooperative prosocial interaction between models on the behavior of 6 female and 14 male severely emotionally disturbed withdrawn children (aged between 9 and 14 years old). An introductory review of the literature considers general modeling theory, variables of the modeling act and their…

  11. Fixed-Time Schedules Attenuate Extinction-Induced Phenomena in the Treatment of Severe Aberrant Behavior.

    ERIC Educational Resources Information Center

    Vollmer, Timothy R.; Progar, Patrick R.; Lalli, Joseph S.; Van Camp, Carole M.; Sierp, Barbara J.; Wright, Carrie S.; Natasi, Julia; Eisenschink, Kevin J.

    1998-01-01

    A study compared the effects of extinction (EXT) and fixed-time (FT) schedules as treatment for the severe problem behaviors of three individuals with developmental disabilities. During EXT, the reinforcer maintaining problem behavior was withheld. During FT, the reinforcers were presented response independently at preset intervals. FT schedules…

  12. Mechanisms of Severe Acute Respiratory Syndrome Coronavirus-Induced Acute Lung Injury

    PubMed Central

    Gralinski, Lisa E.; Bankhead, Armand; Jeng, Sophia; Menachery, Vineet D.; Proll, Sean; Belisle, Sarah E.; Matzke, Melissa; Webb-Robertson, Bobbie-Jo M.; Luna, Maria L.; Shukla, Anil K.; Ferris, Martin T.; Bolles, Meagan; Chang, Jean; Aicher, Lauri; Waters, Katrina M.; Smith, Richard D.; Metz, Thomas O.; Law, G. Lynn; Katze, Michael G.; McWeeney, Shannon; Baric, Ralph S.

    2013-01-01

    ABSTRACT Systems biology offers considerable promise in uncovering novel pathways by which viruses and other microbial pathogens interact with host signaling and expression networks to mediate disease severity. In this study, we have developed an unbiased modeling approach to identify new pathways and network connections mediating acute lung injury, using severe acute respiratory syndrome coronavirus (SARS-CoV) as a model pathogen. We utilized a time course of matched virologic, pathological, and transcriptomic data within a novel methodological framework that can detect pathway enrichment among key highly connected network genes. This unbiased approach produced a high-priority list of 4 genes in one pathway out of over 3,500 genes that were differentially expressed following SARS-CoV infection. With these data, we predicted that the urokinase and other wound repair pathways would regulate lethal versus sublethal disease following SARS-CoV infection in mice. We validated the importance of the urokinase pathway for SARS-CoV disease severity using genetically defined knockout mice, proteomic correlates of pathway activation, and pathological disease severity. The results of these studies demonstrate that a fine balance exists between host coagulation and fibrinolysin pathways regulating pathological disease outcomes, including diffuse alveolar damage and acute lung injury, following infection with highly pathogenic respiratory viruses, such as SARS-CoV. PMID:23919993

  13. Differences in Severity and Outcomes Between Hypertriglyceridemia and Alcohol-Induced Pancreatitis

    PubMed Central

    Goyal, Hemant; Smith, Betsy; Bayer, Chelsey; Rutherford, Carla; Shelnut, Danielle

    2016-01-01

    Background: Alcohol and hypertriglyceridemia (HTG) are among the most common causes of acute pancreatitis (AP) after gallstones. However, differences in severity at the time of presentation and outcomes have not been well-studied. Objective: The aim of this study is to assess the differences between severity at presentation and outcomes of AP of hypertriglyceridemic and alcoholic origins. Materials and Methods: A retrospective review of 177 patients who were discharged with diagnosis of AP was performed. Severity at presentation was identified by the presence of systemic inflammatory response syndrome, bedside index for severity in AP (BISAP) score, and Balthazar index. Outcomes were measured by the length of stay, intensive care unit care, surgical intervention, and mortality. Results: We found 147 patients with alcoholic pancreatitis and 30 patients with hypertriglyceridemic pancreatitis. A larger percentage of hypertriglyceridemic pancreatitis patients (23.33%) had a BISAP score of ≥2 compared to the alcoholic group (12.24%). Only 32.65% of the patients with alcoholic pancreatitis but 60% of the patients with hypertriglyceridemic pancreatitis had the presence of systemic inflammatory response syndrome (SIRS) at admission (P = 0.0067). There were 73.34% hypertriglyceridemic pancreatits patients and only 40.28% alcoholic pancreatitis patients with Balthazar index C or greater, suggesting a higher disease burden at admission for hypertriglyceridemic pancreatitis patients (P = 0.0047). There was a statistically significant difference in the relative number of hypertriglyceridemic and alcoholic pancreatitis patients receiving intensive care (P = 0.00030) and in receiving surgical interventions related to pancreatitis (P = 0.016). Conclusion: Our study found that patients with hypertriglyceridemic pancreatitis have a greater severity of disease and they experience less favorable outcomes than patients with alcoholic pancreatitis. PMID:27042605

  14. Immunosuppressive therapy of cyclosporin A for severe benzene-induced haematopoietic disorders and a 6-month follow-up.

    PubMed

    Song, Yuguo; Du, Xuqin; Hao, Fentong; Gu, Xiaoxin; Zhang, Zhenghua; Zhang, Songquan; Li, Chunsheng; Li, Huiling; Ma, Jing

    2010-06-01

    Long-term exposure to benzene can potentially result in severe haematotoxicities, including pancytopaenia, aplastic anaemia and myelodysplastic syndrome, which are often accompanied by life-threatening symptoms and high mortality. Previous studies demonstrate that benzene-induced haematotoxicities are immune-mediated and that cyclosporin A is a prominent treatment in acquired aplastic anaemia. This study aims to evaluate the potential role of cyclosporin A immunosuppressive therapy for severe benzene-induced haematotoxicity. Between January 2002 and December 2008, 41 patients with severe benzene-induced haematopoietic disorders from five hospitals were enrolled in the study, 22 patients received cyclosporin A, supportive treatments and/or oral testosterone undecanoate, 19 patients were treated with supportive treatments and/or oral testosterone undecanoate as the control group, and a 6-month follow-up was conducted. The results showed that in the cyclosporin A group, 19 of 22 patients (86.36%) had responded to the treatments completely or partially with increased platelets, white blood cells and hemoglobulin counts by the fourth week (P=0.005), the sixth week (P=0.001) and the third month post-treatment (P=0.034), respectively. However, in the control group treated by supportive methods, only 5 of 19 patients (26.32%) responded to the treatments partially (P<0.001). Cyclosporin A in conjunction with supportive treatments may be an effective treatment modality for patients with severe benzene-induced haematopoietic disorders, which in turn implies that these haematotoxicities are immune-mediated. PMID:20381478

  15. [The changing epidemiology of extended spectrum β-lactamase-producing Klebsiella pneumoniae].

    PubMed

    Elhani, Dalèle; Bakir, Leila; Aouni, Mahjoub

    2011-01-01

    In the last two decades, Klebsiella pneumoniae demonstrated some characteristics of acquisition of plasmids coding extended spectrum β-lactamases (ESBL). The review data showed an increase in worldwide prevalence of ESBL and a temporal shift in the prevalence of ESBL types in K. pneumoniae during this last decade. CTX-M-15 seems to be the predominant ESBL type in K. pneumoniae in some parts of the world. The dissemination of several nosocomial CTX-M-15-producing K. pneumoniae clones was reported unlike the worldwide dissemination of a single virulent ST131 CTX-M-15 producing Escherichia coli clone. The diversity of plasmids carrying the bla(CTX-M-15) gene in K. pneumoniae suggested the frequent transfer of this gene between different replicons. The acquisition of the bla(CTX-M-15) gene by K. pneumoniae was probably occurred via horizontal transfer from E. coli.

  16. Pre-transplant gingival hyperplasia predicts severe cyclosporin-induced gingival overgrowth in renal transplant patients.

    PubMed

    Varga, E; Lennon, M A; Mair, L H

    1998-03-01

    The relationship between the pre-transplant periodontal status and the development of post-transplant gingival overgrowth was investigated in a longitudinal study. The periodontal condition of 35 patients was examined on 2 occasions while they were on the transplant waiting list and then at 4-6, 10-12, 16 and 20 weeks post-transplant. At each visit the plaque index, the bleeding index and a pocket index (CPITN) were measured. Dental impressions were taken of the pre- and post-transplant gingival condition and used to make stone models which were used to score the gingival overgrowth index (GOI). The patients divided into 3 distinct groups having severe (n=13), mild (n=16) or no post-transplant gingival overgrowth (n=6). Only 1 of the patients had taken cyclosporin prior to inclusion into the study. All the patients who developed severe overgrowth had evidence of gingival hyperplasia before the transplant. There was no difference in the serum cyclosporin levels between the three groups (chi2<2.28, p>0.319). Furthermore, there was no statistical difference for any of the periodontal indices. This study indicates that the hyperplastic gingival inflammatory response of some individuals appears to be potentiated by cyclosporin resulting in severe post-transplant overgrowth. In other patients the same reaction may allow the fibroblastic activity to occur to an extent where it produces a mild clinically apparent overgrowth.

  17. [National consensus for management of community acquired pneumonia in adults].

    PubMed

    Saldías P, Fernando; Pérez C, Carlos

    2005-01-01

    Community acquired pneumonia (CAP) is an acute respiratory infection that affects pulmonary parenchyma, and is caused by community acquired microorganisms. In Chile, pneumonia represents the main cause of death due to infectious diseases and is the third specific cause of mortality in adults. In 1999, an experts committee in representation of "Sociedad Chilena de Enfermedades Respiratorias", presented the first National Guidelines for the Treatment of Adult Community Acquired Pneumonia, mainly based in foreign experience and documents, and adapted it to our National Health System Organization. During the last decade, impressive epidemiological and technological changes have occurred, making the update of guidelines for treatment of NAC by several international scientific societies, necessary. These changes include: new respiratory pathogens that are being identified in CAP and affect adult patients (Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila); the increasing senescent adult population that carries multiple co-morbidities; the emergence of antimicrobial resistance among respiratory pathogens associated to massive antibiotic prescription; the development by the pharmaceutical industry of new drugs that are effective for pneumonia treatment (macrolides, ketolides and respiratory fluorquinolones); and the development of new diagnostic techniques for detection of antigens, antibodies, and bacterial DNA by molecular biology, useful in respiratory infections. Based on these antecedents, an Advisory Committee of "Sociedad Chilena de Enfermedades Respiratorias" and "Sociedad Chilena de Infectología" has reviewed the national and international evidence about CAP management in adults in order to update clinical recommendations for our country. PMID:16163422

  18. [National consensus for management of community acquired pneumonia in adults].

    PubMed

    Saldías P, Fernando; Pérez C, Carlos

    2005-01-01

    Community acquired pneumonia (CAP) is an acute respiratory infection that affects pulmonary parenchyma, and is caused by community acquired microorganisms. In Chile, pneumonia represents the main cause of death due to infectious diseases and is the third specific cause of mortality in adults. In 1999, an experts committee in representation of "Sociedad Chilena de Enfermedades Respiratorias", presented the first National Guidelines for the Treatment of Adult Community Acquired Pneumonia, mainly based in foreign experience and documents, and adapted it to our National Health System Organization. During the last decade, impressive epidemiological and technological changes have occurred, making the update of guidelines for treatment of NAC by several international scientific societies, necessary. These changes include: new respiratory pathogens that are being identified in CAP and affect adult patients (Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila); the increasing senescent adult population that carries multiple co-morbidities; the emergence of antimicrobial resistance among respiratory pathogens associated to massive antibiotic prescription; the development by the pharmaceutical industry of new drugs that are effective for pneumonia treatment (macrolides, ketolides and respiratory fluorquinolones); and the development of new diagnostic techniques for detection of antigens, antibodies, and bacterial DNA by molecular biology, useful in respiratory infections. Based on these antecedents, an Advisory Committee of "Sociedad Chilena de Enfermedades Respiratorias" and "Sociedad Chilena de Infectología" has reviewed the national and international evidence about CAP management in adults in order to update clinical recommendations for our country.

  19. Use of biperiden hydrochloride in a child with severe dyskinesia induced by phenytoin.

    PubMed

    Caksen, Hüseyin; Odabaş, Dursun; Anlar, Omer

    2003-07-01

    A 5-year-old girl was admitted with a 3-day history of speech disorder and gait abnormality. She had been diagnosed with idiopathic epilepsy and was given phenytoin 2 months before admission to our hospital. On physical examination, she had severe lingual-facial-buccal extrapyramidal movements, slurred speech, and ataxic gait. During examination, she was repetitively scratching her scalp with her right hand every 30 to 60 seconds. Serum phenytoin level was 10 microg/mL (normal 8-20 microg/mL). Electroencephalography showed diffuse slow waves. Magnetic resonance imaging of the brain was normal. During hospitalization, her abnormal findings were thought to be attributable to phenytoin; it was immediately discontinued, and biperiden was initiated. After biperiden was administered, her abnormal movements markedly decreased; later, they almost completely disappeared. In conclusion, we would like to emphasize that severe dyskinesia can be observed during phenytoin therapy and that biperiden can be successfully used in the treatment of this unpleasant condition.

  20. Investigation of severe UF membrane fouling induced by three marine algal species.

    PubMed

    Merle, Tony; Dramas, Laure; Gutierrez, Leonardo; Garcia-Molina, Veronica; Croué, Jean-Philippe

    2016-04-15

    Reducing membrane fouling caused by seawater algal bloom is a challenge for regions of the world where most of their freshwater is produced by seawater desalination. This study aims to compare ultrafiltration (UF) fouling potential of three ubiquitous marine algal species cultures (i.e., Skeletonema costatum-SKC, Tetraselmis sp.-TET, and Hymenomonas sp.-HYM) sampled at different phases of growth. Results showed that flux reduction and irreversible fouling were more severe during the decline phase as compared to the exponential phase, for all species. SKC and TET were responsible for substantial irreversible fouling but their impact was significantly lower than HYM. The development of a transparent gel layer surrounding the cell during the HYM growth and accumulating in water is certainly responsible for the more severe observed fouling. Chemical backwash with a standard chlorine solution did not recover any membrane permeability. For TET and HYM, the Hydraulically Irreversible Fouling Index (HIFI) was correlated to their biopolymer content but this correlation is specific for each species. Solution pre-filtration through a 1.2 μm membrane proved that cells and particulate algal organic matter (p-AOM) considerably contribute to fouling, especially for HYM for which the HIFI was reduced by a factor of 82.3.

  1. Investigation of severe UF membrane fouling induced by three marine algal species.

    PubMed

    Merle, Tony; Dramas, Laure; Gutierrez, Leonardo; Garcia-Molina, Veronica; Croué, Jean-Philippe

    2016-04-15

    Reducing membrane fouling caused by seawater algal bloom is a challenge for regions of the world where most of their freshwater is produced by seawater desalination. This study aims to compare ultrafiltration (UF) fouling potential of three ubiquitous marine algal species cultures (i.e., Skeletonema costatum-SKC, Tetraselmis sp.-TET, and Hymenomonas sp.-HYM) sampled at different phases of growth. Results showed that flux reduction and irreversible fouling were more severe during the decline phase as compared to the exponential phase, for all species. SKC and TET were responsible for substantial irreversible fouling but their impact was significantly lower than HYM. The development of a transparent gel layer surrounding the cell during the HYM growth and accumulating in water is certainly responsible for the more severe observed fouling. Chemical backwash with a standard chlorine solution did not recover any membrane permeability. For TET and HYM, the Hydraulically Irreversible Fouling Index (HIFI) was correlated to their biopolymer content but this correlation is specific for each species. Solution pre-filtration through a 1.2 μm membrane proved that cells and particulate algal organic matter (p-AOM) considerably contribute to fouling, especially for HYM for which the HIFI was reduced by a factor of 82.3. PMID:26874470

  2. Treatment of experimental pneumonia due to penicillin-resistant Streptococcus pneumoniae in immunocompetent rats.

    PubMed Central

    Gavaldà, J; Capdevila, J A; Almirante, B; Otero, J; Ruiz, I; Laguarda, M; Allende, H; Crespo, E; Pigrau, C; Pahissa, A

    1997-01-01

    A model of pneumonia due to Streptococcus pneumoniae resistant to penicillin was developed in immunocompetent Wistar rats and was used to evaluate the efficacies of different doses of penicillin, cefotaxime, cefpirome, and vancomycin. Adult Wistar rats were challenged by intratracheal inoculation with 3 x 10(9) CFU of one strain of S. pneumoniae resistant to penicillin (MICs of penicillin, cefotaxime, cefpirome, and vancomycin, 2, 1, 0.5, and 0.5 microg/ml, respectively) suspended in brain heart broth supplemented with 0.7% agar. The rats experienced a fatal pneumonia, dying within 5 days and with peak mortality (70 to 80%) occurring 48 to 72 h after infection, and the bacterial counts in the lungs persisted from 8.87 +/- 0.3 log10 CFU/g of lung at 24 h of the infection to 9.1 +/- 0.3 log10 CFU/g at 72 h. Four hours after infection the animals were randomized into the following treatment groups: (i) control without treatment, (ii) penicillin G at 100,000 IU/kg of body weight every 2 h, (iii) penicillin G at 250,000 IU/kg every 2 h, (iv) cefotaxime at 100 mg/kg every 2 h, (v) cefpirome at 200 mg/kg every 2 h, and (vi) vancomycin at 50 mg/kg every 8 h. Two different protocols were used for the therapeutic efficacy studies: four doses of beta-lactams and one dose of vancomycin or eight doses of beta-lactams and two doses of vancomycin. Results of the therapy for experimental pneumonia caused by penicillin-resistant S. pneumoniae showed that initially, all the antimicrobial agents tested had similar efficacies, but when we prolonged the treatment, higher doses of penicillin, cefotaxime, and cefpirome were more effective than penicillin at lower doses in decreasing the residual bacterial titers in the lungs. Also, when we extended the treatment, vancomycin was more efficacious than penicillin at lower doses but was less efficacious than higher doses of penicillin or cefpirome. The model that we have developed is simple and amenable for inducing pneumonia in

  3. Late increase of interleukin-18 levels in blood during Mycoplasma pneumoniae pneumonia.

    PubMed

    Narita, Mitsuo; Tanaka, Hiroshi

    2012-07-01

    To the Editor, we read with great interest the article by Chung et al. which appeared recently in the journal. In that paper the authors reported that the decreased IL-18 response in severe pneumonia group vs. non-severe group was observed regardless of asthma status of the patients, whose findings were somewhat different from ours on non-asthmatic patients which showed higher serum levels of IL-18 in severe cases of pneumonia than in mild cases in terms of both in children and in adults. In this point, the timing of venous sampling must be an important factor in explaining the discrepant results. Our previous results suggest that the level of IL-18 in blood as a marker of disease severity should cautiously be interpreted considering a timing of sampling; a value of IL-18 in a blood sample which is obtained at the first visit to the hospital does not always represent the highest level of IL-18 because of the fact that the time which elapsed from the onset of illness to the blood sampling may vary among patients. Analyses on sequential samples, therefore, must be necessary to fully understand the perplexing nature of cytokine activation during Mycoplasma pneumoniae infection.

  4. Identification of an atypical zinc metalloproteinase, ZmpC, from an epidemic conjunctivitis-causing strain of Streptococcus pneumoniae.

    PubMed

    Menon, Balaraj B; Govindarajan, Bharathi

    2013-03-01

    Streptococcus pneumoniae is a pathogen associated with a range of invasive and noninvasive infections. Despite the identification of the majority of virulence factors expressed by S. pneumoniae, knowledge of the strategies used by this bacterium to trigger infections, especially those originating at wet-surfaced epithelia, remains limited. In this regard, we recently reported a mechanism used by a nonencapsulated, epidemic conjunctivitis-causing strain of S. pneumoniae (strain SP168) to gain access into ocular surface epithelial cells. Mechanistically, strain SP168 secretes a zinc metalloproteinase, encoded by a truncated zmpC gene, to cleave off the ectodomain of a vital defense component - the membrane mucin MUC16 - from the apical glycocalyx barrier of ocular surface epithelial cells and, thereby invades underlying epithelial cells. Here, we compare the truncated SP168 ZmpC to its highly conserved archetype from S. pneumoniae serotype 4 (TIGR4), which has been linked to pneumococcal virulence in previous studies. Comparative nucleotide sequence analyses revealed that the zmpC gene corresponding to strain SP168 has two stretches of DNA deleted near its 5' end. A third 3 bp in-frame deletion, resulting in the elimination of an alanine residue, was found towards the middle segment of the SP168 zmpC. Closer examination of the primary structure revealed that the SP168 ZmpC lacks the canonical LPXTG motif - a signature typical of several surface proteins of gram-positive bacteria and of other pneumococcal zinc metalloproteinases. Surprisingly, in vitro assays performed using recombinant forms of ZmpC indicated that the truncated SP168 ZmpC induces more cleavage of the MUC16 ectodomain than its TIGR4 counterpart. This feature may help explain, in part, why S. pneumoniae strain SP168 is better equipped at abrogating the MUC16 glycocalyx barrier en route to causing epidemic conjunctivitis.

  5. Regulation of Matrix Metalloproteinase Expression in Endothelial Cells by Heat-Inactivated Streptococcus pneumoniae

    PubMed Central

    Michel, Uwe; Zobotke, Rita; Mäder, Michael; Nau, Roland

    2001-01-01

    Matrix metalloproteinases (MMPs) may contribute to an impaired endothelial layer in several diseases. We examined the effect of heat-inactivated Streptococcus pneumoniae R6 on MMP-2 and MMP-9 release by cultured aortic and brain capillary endothelial cells. Treatment with heat-inactivated S. pneumoniae caused an increased release of MMP-2 by both cell types. PMID:11179373

  6. The reduction of oxidative stress by nanocomposite Fullerol decreases mucositis severity and reverts leukopenia induced by Irinotecan.

    PubMed

    Arifa, Raquel Duque Nascimento; Paula, Talles Prosperi de; Madeira, Mila Fernandes Moreira; Lima, Renata Lacerda; Garcia, Zélia Menezes; Ávila, Thiago Vinícius; Pinho, Vanessa; Barcelos, Lucíola Silva; Pinheiro, Maurício Veloso Brant; Ladeira, Luiz Orlando; Krambrock, Klaus; Teixeira, Mauro Martins; Souza, Danielle Glória

    2016-05-01

    Irinotecan is a useful chemotherapeutic agent for the treatment of several solid tumors. However, this therapy is associated with side effects, including leukopenia and mucositis. Reactive oxygen species (ROS) activate inflammatory pathways and contribute to Irinotecan-induced mucositis. Fullerol is a nanocomposite with anti-oxidant properties that may reduce tissue damage after inflammatory stimuli. In this paper, the effects of Fullerol and mechanisms of protection were investigated in a model of Irinotecan-induced mucositis. Mucositis was induced by an injection of Irinotecan per 4 days in C57BL/6. Fullerol or a vehicle was injected every 12h. On day 7, the intestines were removed to evaluate histological changes, leukocyte influx, and the production of cytokines and ROS. Irinotecan therapy resulted in weight loss, an increased clinical score and intestinal injury. Treatment with Fullerol attenuated weight loss, decreased clinical score and intestinal damage. Irinotecan also induced increased ROS production in enterocytes, oxidative stress, IL-1β production, neutrophil and eosinophil influx in the ileum. Fullerol treatment decreased production of ROS in the enterocytes, oxidative stress, IL-1β production, neutrophil and eosinophil influx in the ileum. Irinotecan therapy also induced leukopenia in an ROS-dependent manner because leukopenia reverted in WT mice treated with Fullerol or Apocynin or in Gp91phox(-/-) mice. Mice treated with Irinotecan presented less melanoma tumor growth compared to the control group. Fullerol does not interfere in the anti-tumor action of Irinotecan. Fullerol has a great pharmacology potential to decreases the severity of mucositis and of leukopenia during chemotherapy treatment. PMID:26987941

  7. [Infectious aortitis caused by Streptococcus pneumoniae].

    PubMed

    Zizi, O; Jiber, H; Bouarhroum, A

    2016-02-01

    Infectious aortitis is a rare clinical entity that most often manifests itself by an aortic aneurysm. The syphilitic or tubercular forms can be subacute. When it is caused by Salmonella sp., Staphylococcus sp. or Streptococcus pneumoniae, the aortitis is acute with alarming symptoms. Germs found in most cases are Salmonella and Staphylococcus aureus. S. pneumoniae rarely causes infectious aortitis. We report the case of a 75-year-old patient seen in an emergency setting for sudden-onset abdominal pain with fever. An abdominal angio-computed tomography (CT) scan showed a sacciform infrarenal abdominal aortic aneurysm, with an inflammatory aspect and periaortic hematoma. Surgical cure was undertaken because of the impending rupture. An interposition aortic replacement graft was implanted. Blood cultures and bacteriological study of the aortic wall isolated a S. pneumoniae. The anatomical pathology study reported fibrin clot leukocyte remodeling of the aortic wall. An intravenous antibiotic regimen was started. Several organisms, including Streptococcus, can cause infectious aortitis. We found 36 cases described in the literature in addition to our patient. PMID:26775836

  8. Effects of several factors on the heat-shock-induced thermotolerance of Listeria monocytogenes.

    PubMed Central

    Pagán, R; Condón, S; Sala, F J

    1997-01-01

    The influence of the temperature at which Listeria monocytogenes had been grown (4 or 37 degrees C) on the response to heat shocks of different durations at different temperatures was investigated. For cells grown at 4 degrees C, the effect of storage, prior to and after heat shock, on the induced thermotolerance was also studied. Death kinetics of heat-shocked cells is also discussed. For L. monocytogenes grown at 37 degrees C, the greatest response to heat shock was a fourfold increase in thermotolerance. For L. monocytogenes grown at 4 degrees C, the greatest response to heat shock was a sevenfold increase in thermotolerance. The only survival curves of cells to have shoulders were those for cells that had been heat shocked. A 3% concentration of sodium chloride added to the recovery medium made these shoulders disappear and decreased decimal reduction times. The percentage of cells for which thermotolerance increased after a heat shock was smaller the milder the heat shock and the longer the prior storage. PMID:9251209

  9. Severe aggression in rats induced by mescaline but not other hallucinogens.

    PubMed

    Sbordone, R J; Wingard, J A; Gorelick, D A; Elliott, M L

    1979-01-01

    Pairs of male Sprague-Dawley rats were administered mescaline, lysergic acid diethylamide (LSD), psilocin, N,N-dimethyltryptamine (DMT), 3,4-dimethoxyphenylethylamine (DMPEA), or 5-hydroxydopamine (5-OHDA) IP prior to being placed in a shock-elicited aggression situation. When foot shock was delivered, controls struck each other with their forepaws, but never engaged in either biting or injurious fighting. Mescaline-treated rats (50 or 250 mg) rarely struck each other, but engaged in nearly lethal biting. While LSD (25--400 micrograms/kg), psilocin (2.0 mg/kg), and DMT (5 mg/kg) produced some biting, this did not significantly differ from controls and never resulted in injuries. At higher doses, psilocin, DMT, and DMPEA decreased the amount and intensity of fighting. Rats treated with 5-OHDA (8--200 mg/kg) or LSD (25--400 micrograms/kg) did not differ from controls. These results suggest that mescaline's ability to induce pathological aggression in rats exposed to foot shock is not shared by other hallucinogens or nonhallucinogenic mescaline analogues.

  10. Comparative studies of laser-induced damage of several single-layer optical films

    NASA Astrophysics Data System (ADS)

    Zu, X. T.; Chen, X. Q.; Zheng, W. G.; Jiang, X. D.; Yuan, X. D.; Li, X. P.; Xiang, X.

    2008-06-01

    Single-layer optical films, ZrO2, SiO2 and HfO2, were deposited on K9 glass substrates by ion beam sputtering deposit technique in order to study laser-induced damage threshold (LIDT) and damage mechanism. Impurities and defects will result in strong weak absorption coefficient and photothermal signal. Further LIDT is inverse proportional to the absorption coefficient of the films. AFM images of as-deposited films showed a similar roughness of 2-4 nm. Among the films, ZrO2 film has a pore structure, which results in the largest weak absorption, photothermal effect and smallest LIDT. HfO2 film has the largest LIDT (22.13 J/cm2) due to the smallest number and size of both defects and impurities on the surface. Different films have different damage morphology, which is related to the morphology of defects or impurities in the film before laser irradiation and the interface between films and substrates. In order to enhance LIDT, it is important to prepare high-quality film and passivate the defects in the films.

  11. Ice water submersion for rapid cooling in severe drug-induced hyperthermia

    PubMed Central

    Laskowski, Larissa K.; Landry, Adaira; Vassallo, Susi U.; Hoffman, Robert S.

    2015-01-01

    Context The optimal method of cooling hyperthermic patients is controversial. Although controlled data support ice water submersion, many authorities recommend a mist and fan technique. We report two patients with drug-induced hyperthermia, to demonstrate the rapid cooing rates of ice water submersion. Case details Case 1. A 27-year-old man presented with a sympathomimetic toxic syndrome and a core temperature of 41.4°C after ingesting 4-fluoroamphetamine. He was submerged in ice water and his core temperature fell to 38°C within 18 minutes (a mean cooling rate of 0.18°C/min). His vital signs stabilized, his mental status improved and he left on hospital day 2. Case 2. A 32-year-old man with a sympathomimetic toxic syndrome after cocaine use was transported in a body bag and arrived with a core temperature of 44.4°C. He was intubated, sedated with IV benzodiazepines, and submerged in ice water. After 20 minutes his temperature fell to 38.8°C (a cooling rate of 0.28°C/min). He was extubated the following day, and discharged on day 10. Discussion In these two cases, cooling rates exceeded those reported for mist and fan technique. Since the priority in hyperthermia is rapid cooling, clinical data need to be collected to reaffirm the optimal approach. PMID:25695144

  12. Gluten protein composition in several fractions obtained by shear induced separation of wheat flour.

    PubMed

    van der Zalm, Elizabeth E J; Grabowska, Katarzyna J; Strubel, Maurice; van der Goot, Atze J; Hamer, Rob J; Boom, Remko M

    2010-10-13

    Recently, it was found that applying curvilinear shear flow in a cone-cone shearing device to wheat flour dough induces separation, resulting in a gluten-enriched fraction in the apex of the cone and gluten-depleted fraction at the outer part. This article describes whether fractionation of the various proteineous components occurs during and after separation of Soissons wheat flour. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and size-exclusion high performance liquid chromatography (SE-HPLC) were found to be suitable techniques for this. It is concluded that all protein fractions migrate to the center of the cone as a result of which the composition of the gluten-enriched fraction remains rather similar to that in the original flour. However, the larger glutenin polymer fraction migrated faster, as a result of which the concentration of large polymers was increased with a factor 2.4 compared to that of Soissons flour. The concentration of monomers in the gluten-enriched fraction was decreased to 70% of the original concentration in the original wheat flour.

  13. Gastroprotective effects of several H2RAs on ibuprofen-induced gastric ulcer in rats.

    PubMed

    Liu, Jing; Sun, Dan; He, Jinfeng; Yang, Chengli; Hu, Tingting; Zhang, Lijing; Cao, Hua; Tong, Ai-Ping; Song, Xiangrong; Xie, Yongmei; He, Gu; Guo, Gang; Luo, Youfu; Cheng, Ping; Zheng, Yu

    2016-03-15

    Ibuprofen is the first line of treatment for osteoarthritis and arthritis. The main side effects of ibuprofen especially in long-term treatment include gastric ulcer, duodenal ulcer and indigestion etc. Therefore, screening drugs with effective gastric protective effects and low toxicity for combination therapy with ibuprofen is necessary. The mechanism of gastric damage induced by ibuprofen is still unclear, however, cell damage caused by reactive oxygen species (ROS) is considered as the main reason. Preliminary screening of literature with the criteria of low toxicity led to four histamine-2 receptor antagonists (H2RAs): nizatidine, famotidine, lafutidine, and roxatidine acetate, which were selected for further investigation. These drugs were evaluated systemically by examining the gastric ulcer index, lipid peroxidation (LPO), membrane permeability, toxicity to main organs, and the influence on the activity of antioxidant enzymes, and myeloperoxidase (MPO). Nizatidine was found to be the best gastric protective agent. It exhibited excellent protective effect by increasing antioxidant enzyme activity, decreasing MPO activity, reducing LPO, and membrane permeability. Combination treatment with nizatidine and ibuprofen did not show any significant toxicity. Nizatidine was considered as a good option for combination therapy with ibuprofen especially for diseases that require long-term treatment such as arthritis and osteoarthritis.

  14. Nicardipine-induced acute pulmonary edema: a rare but severe complication of tocolysis.

    PubMed

    Serena, Claire; Begot, Emmanuelle; Cros, Jérôme; Hodler, Charles; Fedou, Anne Laure; Nathan-Denizot, Nathalie; Clavel, Marc

    2014-01-01

    We report four cases of acute pulmonary edema that occurred during treatment by intravenous tocolysis using nicardipine in pregnancy patients with no previous heart problems. Clinical severity justified hospitalization in intensive care unit (ICU) each time. Acute dyspnea has begun at an average of 63 hours after initiation of treatment. For all patients, the first diagnosis suspected was pulmonary embolism. The patients' condition improved rapidly with appropriate diuretic treatment and by modifying the tocolysis. The use of intravenous nicardipine is widely used for tocolysis in France even if its prescription does not have a marketing authorization. The pathophysiological mechanisms of this complication remain unclear. The main reported risk factors are spontaneous preterm labor, multiple pregnancy, concomitant obstetrical disease, association with beta-agonists, and fetal lung maturation corticotherapy. A better knowledge of this rare but serious adverse event should improve the management of patients. Nifedipine or atosiban, the efficiency of which tocolysis was also studied, could be an alternative. PMID:25215245

  15. Snowfall induced severe pile-ups in southern Finland on 17 March 2005

    NASA Astrophysics Data System (ADS)

    Juga, I.; Hippi, M.

    2009-09-01

    Weather has a great impact on road traffic and several studies have shown that accident risk increases especially during wintry weather conditions. Heavy snowfall, rain or sleet on an icy road surface and formation of hoar frost can make the driving conditions hazardous. Poor visibility, caused by snowfall or dense fog can increase the accident risk significantly and severe pile-ups on highways are possible. The risk for accidents increases, when many drivers can't adjust their speed to the worsening driving conditions even though the hazard is visible. This study presents a severe pile-up case that occurred in southern Finland near Helsinki city on Thursday 17 March 2005. Before this occasion, cold and clear weather prevailed for many days and the driving conditions were mostly fair. On 17 March a low pressure was approaching southern Finland from west. Light snowfall reached the Helsinki metropolitan area early in the morning and it was followed by a band of dense snowfall. During the rush hours, just before 0800 h, pile-ups occurred on four separate highways near Helsinki city almost at the same time (within about ten minutes). In total, almost 300 cars were crashed, 3 persons died and more than 60 persons got injured. The occurrence of dense snowfall during the rush hours had a great impact on driving conditions. The drivers heading towards Helsinki from north or northeast drove at first in clear, dry conditions, with only local light snowfall. But the sudden worsening of weather (and visibility) was a surprise for many although warnings for poor driving conditions were issued the previous evening on radio and TV. In addition to this, automatic vehicle speed measurements showed that the mean speed that morning was only a few km/h lower than on a normal day. When studying the weather situation, it appeared that near the surface there was a thin layer of cold air (2 m temperature being -5…-8 degrees) and warmer air above it. In this kind of situation super

  16. Carbapenemase-producing Klebsiella pneumoniae

    PubMed Central

    Deresinski, Stan

    2014-01-01

    The continuing emergence of infections due to multidrug resistant bacteria is a serious public health problem. Klebsiella pneumoniae, which commonly acquires resistance encoded on mobile genetic elements, including ones that encode carbapenemases, is a prime example. K. pneumoniae carrying such genetic material, including both blaKPC and genes encoding metallo-β-lactamases, have spread globally. Many carbapenemase-producing K. pneumoniae are resistant to multiple antibiotic classes beyond β-lactams, including tetracyclines, aminoglycosides, and fluoroquinolones. The optimal treatment, if any, for infections due to these organisms is unclear but, paradoxically, appears to often require the inclusion of an optimally administered carbapenem. PMID:25343037

  17. The Regulation of Proresolving Lipid Mediator Profiles in Baboon Pneumonia by Inhaled Carbon Monoxide

    PubMed Central

    Dalli, Jesmond; Kraft, Bryan D.; Colas, Romain A.; Shinohara, Masakazu; Fredenburgh, Laura E.; Hess, Dean R.; Chiang, Nan; Welty-Wolf, Karen; Choi, Augustine M.; Piantadosi, Claude A.

    2015-01-01

    Strategies for the treatment of bacterial pneumonia beyond traditional antimicrobial therapy have been limited. The recently discovered novel genus of lipid mediators, coined “specialized proresolving mediators” (SPMs), which orchestrate clearance of recruited leukocytes and restore epithelial barrier integrity, have offered new insight into the resolution of inflammation. We performed lipid mediator (LM) metabololipidomic profiling and identification of LMs on peripheral blood leukocytes and plasma from a baboon model of Streptococcus pneumoniae pneumonia. Leukocytes and plasma were isolated from whole blood of S. pneumoniae–infected (n = 5–6 per time point) and control, uninfected baboons (n = 4 per time point) at 0, 24, 48, and 168 hours. In a subset of baboons with pneumonia (n = 3), we administered inhaled carbon monoxide (CO) at 48 hours (200–300 ppm for 60–90 min). Unstimulated leukocytes from control animals produced a proresolving LM signature with elevated resolvins and lipoxins. In contrast, serum-treated, zymosan-stimulated leukocytes and leukocytes from baboons with S. pneumoniae pneumonia produced a proinflammatory LM signature profile with elevated leukotriene B4 and prostaglandins. Plasma from baboons with S. pneumoniae pneumonia also displayed significantly reduced LM–SPM levels, including eicosapentaenoic acid–derived E-series resolvins (RvE) and lipoxins. CO inhalation increased levels of plasma RvE and lipoxins relative to preexposure levels. These results establish the leukocyte and plasma LM profiles biosynthesized during S. pneumoniae pneumonia in baboons and provide evidence for pneumonia-induced dysregulation of these proresolution programs. Moreover, these SPM profiles are partially restored with inhaled low-dose CO and SPM, which may shorten the time to pneumonia resolution. PMID:25568926

  18. Cryptococcus neoformans as a cause of bronchiolitis obliterans organizing pneumonia.

    PubMed

    Kessler, Alexander T; Al Kharrat, Tamim; Kourtis, Athena P

    2010-06-01

    The most frequent manifestations of Cryptococcus neoformans (CN) disease are systemic infections in immunocompromised patients and localized pulmonary disease in immunocompetent individuals. Such pulmonary cryptococcosis can range from asymptomatic infection to frank pneumonia that can be severe. Bronchiolitis obliterans organizing pneumonia (BOOP) is a rare severe form of pneumonitis caused by a variety of infectious and toxic agents or connective tissue diseases. BOOP due to Cryptococcus neoformans has very rarely been reported; there have been only five such case reports, mostly in immunocompromised patients. We report herein on a case of CN-associated BOOP in an immunocompetent individual and discuss the diagnosis and treatment of this entity. PMID:20169387

  19. Human Amnion-Derived Mesenchymal Stem Cell Transplantation Ameliorates Dextran Sulfate Sodium-Induced Severe Colitis in Rats.

    PubMed

    Onishi, Reizo; Ohnishi, Shunsuke; Higashi, Ryosuke; Watari, Michiko; Yamahara, Kenichi; Okubo, Naoto; Nakagawa, Koji; Katsurada, Takehiko; Suda, Goki; Natsuizaka, Mitsuteru; Takeda, Hiroshi; Sakamoto, Naoya

    2015-01-01

    Mesenchymal stem cells (MSCs) are a valuable cell source in regenerative medicine. Recently, several studies have shown that MSCs can be easily isolated from human amnion. In this study, we investigated the therapeutic effect of human amnion-derived MSCs (AMSCs) in rats with severe colitis. Colitis was induced by the administration of 8% dextran sulfate sodium (DSS) from day 0 to day 5, and AMSCs (1 × 10(6) cells) were transplanted intravenously on day 1. Rats were sacrificed on day 5, and the colon length and histological colitis score were evaluated. The extent of inflammation was evaluated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry. The effect of AMSCs on the inflammatory signals was investigated in vitro. AMSC transplantation significantly ameliorated the disease activity index score, weight loss, colon shortening, and the histological colitis score. mRNA expression levels of proinflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and migration inhibitory factor (MIF) were significantly decreased in the rectums of AMSC-treated rats. In addition, the infiltration of monocytes/macrophages was significantly decreased in AMSC-treated rats. In vitro experiments demonstrated that activation of proinflammatory signals induced by TNF-α or lipopolysaccharide (LPS) in immortalized murine macrophage cells (RAW264.7) was significantly attenuated by coculturing with AMSCs or by culturing with a conditioned medium obtained from AMSCs. Although the phosphorylation of IκB induced by TNF-α or LPS was not inhibited by the conditioned medium, nuclear translocation of NF-κB was significantly inhibited by the conditioned medium. Taken together, AMSC transplantation provided significant improvement in rats with severe colitis, possibly through the inhibition of monocyte/macrophage activity and through inhibition of NF-κB activation. AMSCs could be considered as a new cell source for the

  20. In vivo and in vitro studies on the roles of neutrophil extracellular traps during secondary pneumococcal pneumonia after primary pulmonary influenza infection

    PubMed Central

    Narayana Moorthy, Anandi; Narasaraju, T.; Rai, Prashant; Perumalsamy, R.; Tan, K. B.; Wang, Shi; Engelward, Bevin; Chow, Vincent T. K.

    2013-01-01

    Seasonal influenza virus infections may lead to debilitating disease, and account for significant fatalities annually worldwide. Most of these deaths are attributed to the complications of secondary bacterial pneumonia. Evidence is accumulating to support the notion that neutrophil extracellular traps (NETs) harbor several antibacterial proteins, and trap and kill bacteria. We have previously demonstrated the induction of NETs that contribute to lung tissue injury in severe influenza pneumonia. However, the role of these NETs in secondary bacterial pneumonia is unclear. In this study, we explored whether NETs induced during pulmonary influenza infection have functional significance against infections with Streptococcus pneumoniae and other bacterial and fungal species. Our findings revealed that NETs do not participate in killing of Streptococcus pneumoniae in vivo and in vitro. Dual viral and bacterial infection elevated the bacterial load compared to animals infected with bacteria alone. Concurrently, enhanced lung pathogenesis was observed in dual-infected mice compared to those challenged with influenza virus or bacteria alone. The intensified NETs in dual-infected mice often appeared as clusters that were frequently filled with partially degraded DNA, as evidenced by punctate histone protein staining. The severe pulmonary pathology and excessive NETs generation in dual infection correlated with exaggerated inflammation and damage to the alveolar-capillary barrier. NETs stimulation in vitro did not significantly alter the gene expression of several antimicrobial proteins, and these NETs did not exhibit any bactericidal activity. Fungicidal activity against Candida albicans was observed at similar levels both in presence or absence of NETs. These results substantiate that the NETs released by primary influenza infection do not protect against secondary bacterial infection, but may compromise lung function. PMID:23467809

  1. Fatal Pneumonitis Induced by Oxaliplatin: Description of Three Cases

    PubMed Central

    Pontes, L.B.; Armentano, D.P.D.; Soares, A.; Gansl, R.C.

    2012-01-01

    We describe 3 fatal cases of interstitial pneumonitis rapidly evolving to pulmonary fibrosis and death after the administration of oxaliplatin as part of the FOLFOX regimen. Due to the widespread use of oxaliplatin in oncology, clinicians should be aware of the risk and severity of oxalipatin-induced interstitial pneumonia. PMID:22539922

  2. Cardiac-specific overexpression of inducible nitric oxide synthase does not result in severe cardiac dysfunction.

    PubMed

    Heger, Jacqueline; Gödecke, Axel; Flögel, Ulrich; Merx, Marc W; Molojavyi, Andrei; Kühn-Velten, W Nikolaus; Schrader, Jürgen

    2002-01-11

    Nitric oxide (NO), a potent regulator of myocardial contractility, has been implicated in the development of heart failure; however, no study exists describing the relation between expression of inducible nitric oxide synthase (iNOS), formation of NO in vivo, and cardiac contractility. We have therefore generated transgenic (TG) mice overexpressing iNOS under the cardiospecific alpha-myosin heavy chain (alpha-MHC) promoter. In vitro, iNOS activity in hearts of two transgenic lines was 260- to 400-fold above controls (wild type [WT]), but TG mice were viable and appeared normal. Ventricular mass/body weight ratio did not differ; heart rate and cardiac output as well as mean arterial blood pressure were decreased by 10%. NO(x) levels of hearts and blood of TG mice were 2.5- and 2-fold above WT controls, respectively. In the isolated heart, release of the NO oxidation products nitrate and nitrite, an index of in vivo NOS activity, was 40-fold over WT. However, cardiac hemodynamics and levels of ATP and phosphocreatine were unaltered. The high iNOS activity was associated with reduced cardiac L-arginine in TG hearts to only 15% of the WT, indicating limited substrate availability, whereas L-citrulline was 20-fold elevated. Our findings demonstrate that the heart can tolerate high levels of iNOS activity without detrimental functional consequences. The concept that iNOS-derived NO is the triggering factor in the pathomechanism leading to heart failure therefore needs to be reevaluated. PMID:11786524

  3. Apoptosis induced in Jurkat cells by several agents is preceded by intracellular acidification.

    PubMed Central

    Gottlieb, R A; Nordberg, J; Skowronski, E; Babior, B M

    1996-01-01

    We have previously shown that in neutrophils deprived of granulocyte colony-stimulating factor, apoptosis is preceded by acidification and that the protection against apoptosis conferred on neutrophils by granulocyte colony-stimulating factor is dependent upon delay of this acidification. To test the hypothesis that acidification could be a general feature of apoptosis, we examined intracellular pH changes in another cell line. Jurkat cells, a T-lymphoblastoid line, were induced to undergo apoptosis with anti-Fas IgM, cycloheximide, or exposure to short-wavelength UV light. We found that acidification occurred in response to treatment with these agents and that acidification preceded DNA fragmentation. Jurkat cells were also found to possess an acid endonuclease that is active below pH 6.8, compatible with a possible role for this enzyme in chromatin digestion during apoptosis. Incubation of the cells with the bases imidazole or chloroquine during treatment with anti-Fas antibody or cycloheximide or after UV exposure decreased apoptosis as assessed by nuclear morphology and DNA content. The alkalinizing effect of imidazole and chloroquine was shown by the demonstration that the percentage of cells with an intracellular pH below 6.8 after treatment with anti-Fas antibody, cycloheximide, or UV was diminished in the presence of base as compared with similarly treated cells incubated in the absence of base. We conclude that acidification is an early event in programmed cell death and may be essential for genome destruction. Images Fig. 5 PMID:8570610

  4. Cathepsin B regulates the appearance and severity of mercury-induced inflammation and autoimmunity.

    PubMed

    Toomey, Christopher B; Cauvi, David M; Hamel, John C; Ramirez, Andrea E; Pollard, K Michael

    2014-12-01

    Susceptibility and resistance to systemic autoimmunity are genetically regulated. This is particularly true for murine mercury-induced autoimmunity (mHgIA) where DBA/2J mice are considered resistant to disease including polyclonal B cell activation, autoantibody responses, and immune complex deposits. To identify possible mechanisms for the resistance to mHgIA, we exposed mHgIA sensitive B10.S and resistant DBA/2J mice to HgCl2 and assessed inflammation and pro-inflammatory responses at the site of exposure and subsequent development of markers of systemic autoimmunity. DBA/2J mice showed little evidence of induration at the site of exposure, expression of proinflammatory cytokines, T cell activation, or autoantibody production, although they did exhibit increased levels of total serum IgG and IgG1. In contrast B10.S mice developed significant inflammation together with increased expression of inflammasome component NLRP3, proinflammatory cytokines IL-1β, TNF-α, and IFN-γ, hypergammaglobulinemia, splenomegaly, CD4(+) T-cell activation, and production of autoantibodies. Inflammation in B10.S mice was associated with a selective increase in activity of cysteine cathepsin B but not cathepsins L or S. Increased cathepsin B activity was not dependent on cytokines required for mHgIA but treatment with CA-074, a cathepsin B inhibitor, led to transient reduction of local induration, expression of inflammatory cytokines, and subsequent attenuation of the systemic adaptive immune response. These findings demonstrate that sensitivity to mHgIA is linked to an early cathepsin B regulated inflammatory response which can be pharmacologically exploited to abrogate the subsequent adaptive autoimmune response which leads to disease.

  5. Cardiac-specific overexpression of inducible nitric oxide synthase does not result in severe cardiac dysfunction.

    PubMed

    Heger, Jacqueline; Gödecke, Axel; Flögel, Ulrich; Merx, Marc W; Molojavyi, Andrei; Kühn-Velten, W Nikolaus; Schrader, Jürgen

    2002-01-11

    Nitric oxide (NO), a potent regulator of myocardial contractility, has been implicated in the development of heart failure; however, no study exists describing the relation between expression of inducible nitric oxide synthase (iNOS), formation of NO in vivo, and cardiac contractility. We have therefore generated transgenic (TG) mice overexpressing iNOS under the cardiospecific alpha-myosin heavy chain (alpha-MHC) promoter. In vitro, iNOS activity in hearts of two transgenic lines was 260- to 400-fold above controls (wild type [WT]), but TG mice were viable and appeared normal. Ventricular mass/body weight ratio did not differ; heart rate and cardiac output as well as mean arterial blood pressure were decreased by 10%. NO(x) levels of hearts and blood of TG mice were 2.5- and 2-fold above WT controls, respectively. In the isolated heart, release of the NO oxidation products nitrate and nitrite, an index of in vivo NOS activity, was 40-fold over WT. However, cardiac hemodynamics and levels of ATP and phosphocreatine were unaltered. The high iNOS activity was associated with reduced cardiac L-arginine in TG hearts to only 15% of the WT, indicating limited substrate availability, whereas L-citrulline was 20-fold elevated. Our findings demonstrate that the heart can tolerate high levels of iNOS activity without detrimental functional consequences. The concept that iNOS-derived NO is the triggering factor in the pathomechanism leading to heart failure therefore needs to be reevaluated.

  6. Severity of Hematuria Effects Resolution in Patients Treated with Hyperbaric Oxygen Therapy for Radiation-Induced Hematuria

    PubMed Central

    Liss, Michael A.; Osann, Kathryn; Cho, Jane; Chua, Walter C.; Dash, Atreya

    2014-01-01

    Introduction We investigated the differences between prostate cancer patients with radiation-induced hematuria treated with hyperbaric oxygen (HBO) therapy that did or did not have a resolution of hematuria. Materials and Methods We performed a retrospective review of prostate cancer patients with radiation-induced hematuria who underwent HBO from April 2000 to March 2010. We performed an analysis of demographic data and severity of hematuria in those who had resolution of or persistent hematuria. Additionally, prostate-specific antigen (PSA) data were also obtained during the study period. Results Overall, 11/22 men had resolution of hematuria after HBO therapy with a median follow-up of 2.2 (0.35–13.6) years. The Radiation Therapy Oncology Group (RTOG) grade of hematuria is predictive of final hematuria outcome (resolution vs. persistent) after HBO (p = 0.026). No significant PSA changes were noted before and after HBO therapy. Conclusions The RTOG hematuria grade is associated with the resolution of hematuria after HBO therapy for radiation-induced hematuria in men treated for prostate cancer. This information may be helpful during shared medical decision-making regarding utility of HBO therapy in the context of severity of hematuria. PMID:23919985

  7. Childhood pneumonia as a global health priority and the strategic interest of the Bill & Melinda Gates Foundation.

    PubMed

    Adegbola, Richard A

    2012-04-01

    Pneumonia kills more children than any other disease--more than HIV/AIDS, malaria, and measles combined. Introduction of vaccines against pneumococcus and Haemophilus influenzae type b (the most important causes of severe pneumonia in young children), increasing resistance to antibiotics, and changes in HIV prevalence will likely change patterns of pneumonia etiology in developing countries. Studies such as Pneumonia Etiology Research for Child Health (PERCH) that take advantage of new diagnostic technologies are needed to provide an updated and more precise description of the microbial causes of pneumonia and to inform decisions around treatment algorithms and vaccine development and introduction. In recognition of its importance for global health and especially its significance as an ongoing cause of gross inequity in risks, The Bill & Melinda Gates Foundation has made pneumonia an important part of its global health strategy and PERCH a centerpiece of its Pneumonia Program.

  8. Childhood pneumonia as a global health priority and the strategic interest of the Bill & Melinda Gates Foundation.

    PubMed

    Adegbola, Richard A

    2012-04-01

    Pneumonia kills more children than any other disease--more than HIV/AIDS, malaria, and measles combined. Introduction of vaccines against pneumococcus and Haemophilus influenzae type b (the most important causes of severe pneumonia in young children), increasing resistance to antibiotics, and changes in HIV prevalence will likely change patterns of pneumonia etiology in developing countries. Studies such as Pneumonia Etiology Research for Child Health (PERCH) that take advantage of new diagnostic technologies are needed to provide an updated and more precise description of the microbial causes of pneumonia and to inform decisions around treatment algorithms and vaccine development and introduction. In recognition of its importance for global health and especially its significance as an ongoing cause of gross inequity in risks, The Bill & Melinda Gates Foundation has made pneumonia an important part of its global health strategy and PERCH a centerpiece of its Pneumonia Program. PMID:22403237

  9. Retrospective investigation of the clinical effects of tazobactam/piperacillin and sulbactam/ampicillin on aspiration pneumonia caused by Klebsiella pneumoniae.

    PubMed

    Tsukada, Hiroki; Sakai, Kunihiko; Cho, Hiromi; Kimura, Yuka; Tetsuka, Takafumi; Nakajima, Haruhiko; Ito, Kazuhiko

    2012-10-01

    Klebsiella pneumoniae is an important causative bacterium of aspiration pneumonia in many elderly patients. We retrospectively investigated the clinical effects of the early treatment of aspiration pneumonia and background factors in 24 patients from whom Klebsiella pneumoniae was isolated. Sulbactam/ampicillin (SBT/ABPC) was selected for early treatment in 12 of the 24 patients diagnosed with aspiration pneumonia, and tazobactam/piperacillin (TAZ/PIPC) was selected for the other patients. The effective rates and success rates of early treatment were significantly higher in the TAZ/PIPC group than in the SBT/ABPC group (p = 0.003 and 0.027, respectively). Although no significant difference was noted because of the limited number of cases, the survival rates after 30 days were 91.7 and 58.3 % in the TAZ/PIPC and SBT/ABPC groups, respectively. Several bacteria isolated with Klebsiella pneumoniae were resistant bacteria, such as methicillin-resistant Staphylococcus aureus or Pseudomonas aeruginosa, and no anaerobe or extended-spectrum β-lactamase-producing Klebsiella pneumoniae was isolated. Thirteen and 11 of the 24 cases were classified as healthcare-associated pneumonia (HCAP) and hospital-acquired pneumonia (HAP), respectively, with no case classified as community-acquired pneumonia (CAP). As population aging progresses, the frequency of aspiration pneumonia classified as HCAP will increase. To cover anaerobes, it is necessary to select antibacterial drugs, such as TAZ/PIPC, for early treatment in consideration of resistant gram-negative bacteria to improve the outcome, and not drugs with weak activity against these bacteria.

  10. Berberine ameliorates severe acute pancreatitis‑induced intestinal barrier dysfunction via a myosin light chain phosphorylation‑dependent pathway.

    PubMed

    Liang, Hong-Yin; Chen, Tao; Yan, Hong-Tao; Huang, Zhu; Tang, Li-Jun

    2014-05-01

    Berberine is a traditional drug used to treat gastrointestinal disorders in China and has been demonstrated to attenuate intestinal barrier dysfunction in certain animal models. However, the effects of berberine on pancreatitis-induced intestinal barrier dysfunction are yet to be fully elucidated. This study aimed to investigate the effect of berberine pretreatment on the attenuation of intestinal barrier dysfunction induced by severe acute pancreatitis (SAP). A total of 36 rats were randomly divided into Sham, SAP and SAP plus berberine groups. Pancreatitis was induced using retrograde injection of 3% Na-taurocholate into the pancreatic duct. Histological examinations of the pancreas were performed and intestinal barrier dysfunction was characterized by histological measurements and the assessment of serum diamine oxidase activity and endotoxin levels. Zonula occludens-1 and occludin mRNA and protein expression, as well as myosin light chain (MLC) phosphorylation, were assessed. SAP rat models were successfully established. Berberine treatment was found to have no significant effect on the histological changes in the pancreas, but was observed to ameliorate the intestinal mucosal barrier damage and membrane permeability associated with SAP. Although berberine exerted minimal effects on tight junction proteins in the ilea of SAP rats, it was observed to significantly inhibit SAP-induced MLC phosphorylation. To the best of our knowledge, this is the first study to demonstrate that berberine attenuates SAP‑induced intestinal barrier dysfunction in vivo. In addition, this study shows that the effect of berberine on intestinal barrier function may be associated with the inhibition of SAP‑induced upregulation of MLC phosphorylation.

  11. Severe Hypotension, Hypoxia, and Subcutaneous Erythema Induced by Indigo Carmine Administration during Open Prostatectomy

    PubMed Central

    Voelzke, Bryan B.

    2016-01-01

    Indigo carmine (also known as 5,5′-indigodisulfonic acid sodium salt or indigotine) is a blue dye that is administered intravenously to examine the urinary tract and usually is biologically safe and inert. Indigo carmine rarely may cause adverse reactions. We treated a 66-year-old man who had general anesthesia and radical retropubic prostatectomy for prostate cancer. He had a previous history of allergy to bee sting with nausea, vomiting, and dizziness. Within 1 minute after injection of indigo carmine for evaluation of the ureters, the patient developed hypotension to 40 mmHg, severe hypoxia (the value of SpO2 (peripheral capillary oxygen saturation) was 75% on 40% inspired oxygen concentration), poor air movement and bilateral diffuse wheezing on auscultation, and marked subcutaneous erythema at the upper extremities. After treatment with 100% oxygen, epinephrine (total, 1.5 mg), hydrocortisone (100 mg), diphenhydramine (50 mg), albuterol nebulizer (0.083%), and continuous infusion of epinephrine (0.15 μg/kg/min), the vital signs became stable, and he recovered completely. In summary, indigo carmine rarely may cause life-threatening anaphylactic or anaphylactoid reaction that may necessitate rapid treatment to stabilize cardiovascular, hemodynamic, and pulmonary function.

  12. Severe Hypotension, Hypoxia, and Subcutaneous Erythema Induced by Indigo Carmine Administration during Open Prostatectomy

    PubMed Central

    Voelzke, Bryan B.

    2016-01-01

    Indigo carmine (also known as 5,5′-indigodisulfonic acid sodium salt or indigotine) is a blue dye that is administered intravenously to examine the urinary tract and usually is biologically safe and inert. Indigo carmine rarely may cause adverse reactions. We treated a 66-year-old man who had general anesthesia and radical retropubic prostatectomy for prostate cancer. He had a previous history of allergy to bee sting with nausea, vomiting, and dizziness. Within 1 minute after injection of indigo carmine for evaluation of the ureters, the patient developed hypotension to 40 mmHg, severe hypoxia (the value of SpO2 (peripheral capillary oxygen saturation) was 75% on 40% inspired oxygen concentration), poor air movement and bilateral diffuse wheezing on auscultation, and marked subcutaneous erythema at the upper extremities. After treatment with 100% oxygen, epinephrine (total, 1.5 mg), hydrocortisone (100 mg), diphenhydramine (50 mg), albuterol nebulizer (0.083%), and continuous infusion of epinephrine (0.15 μg/kg/min), the vital signs became stable, and he recovered completely. In summary, indigo carmine rarely may cause life-threatening anaphylactic or anaphylactoid reaction that may necessitate rapid treatment to stabilize cardiovascular, hemodynamic, and pulmonary function. PMID:27610263

  13. Recovery from and consequences of severe iatrogenic lymphopenia (induced to treat autoimmune diseases)

    PubMed Central

    Storek, Jan; Zhao, Zhao; Lin, Eugene; Berger, Thomas; McSweeney, Peter A.; Nash, Richard A.; Akatsuka, Yoshiki; Metcalf, Monja D.; Lu, Hailing; Kalina, Tomas; Reindl, Markus; Storb, Rainer; Hansen, John A.; Sullivan, Keith M.; Kraft, George H.; Furst, Daniel E.; Maloney, David G.

    2010-01-01

    To ascertain the consequences of severe leukopenia and the tempo of recovery, we studied the immunity of 56 adult patients treated for multiple sclerosis or systemic sclerosis with autologous CD34 cell transplantation using extremely lymphoablative conditioning. NK cell, monocyte, and neutrophil counts recovered to normal by 1 month; dendritic cell and B cell counts by 6 months; and T cell counts by 2 years posttransplant, although CD4 T cell counts remained borderline low. Initial peripheral expansion was robust for CD8 T cells but only moderate for CD4 T cells. Subsequent thymopoiesis was slow, especially in older patients. Importantly, levels of antibodies, including autoantibodies, did not drop substantially. Infections were frequent during the first 6 months, when all immune cells were deficient, and surprisingly rare (0.21 per patient year) at 7–24 months posttransplant, when only T cells (particularly CD4 T cells) were deficient. In conclusion, peripheral expansion of CD8 but not CD4 T cells is highly efficient. Prolonged CD4 lymphopenia is associated with relatively few infections, possibly due to antibodies produced by persisting pretransplant plasma cells. PMID:15507394

  14. Surgical revascularisation in patients with severe limb ischaemia induces a pro-thrombotic state.

    PubMed

    Collins, P; Ford, I; Greaves, M; Macaulay, E; Brittenden, J

    2006-08-01

    Platelet and coagulation activation are implicated in the increased incidence of ischaemic events seen in patients with peripheral arterial disease. This study aimed to assess the effect of surgical revascularisation on platelet aggregation and coagulation in patients with severe limb ischaemia (SLI). Twenty-two patients had blood samples taken: prior to surgery, on reperfusion, 2, 24 and 48 h post-surgery. Platelet aggregation through COX-mediated and thrombin receptor activator peptide (TRAP)-stimulated GPIIb/IIIa pathways was measured by the Ultegra point of care system. Thrombin-antithrombin III Complex (TAT) and D-dimer were measured by ELISA. COX-mediated aggregation increased significantly at reperfusion and remained elevated at 24 h [median increase from baseline of 9% (range -16 to 33%) P = 0.011]. TRAP-stimulated aggregation increased significantly at reperfusion and remained elevated at 2 h post-surgery [median increase 18% (range -71 to 45%); P = 0.007]. TAT levels were significantly elevated from reperfusion and remained so at 48 h (P < 0.003), whereas D-dimer only increased at 24 h (P = 0.014). For the first time, we have demonstrated that in patients with SLI, platelet aggregation is increased following surgery and there is a mismatch in the balance between the coagulation and fibrinolytic pathways despite the use of aspirin and heparin. Thus in the early post-operative these patients exhibit a pro-thrombotic state. PMID:16928603

  15. Severe Hypotension, Hypoxia, and Subcutaneous Erythema Induced by Indigo Carmine Administration during Open Prostatectomy.

    PubMed

    Nandate, Koichiro; Voelzke, Bryan B

    2016-01-01

    Indigo carmine (also known as 5,5'-indigodisulfonic acid sodium salt or indigotine) is a blue dye that is administered intravenously to examine the urinary tract and usually is biologically safe and inert. Indigo carmine rarely may cause adverse reactions. We treated a 66-year-old man who had general anesthesia and radical retropubic prostatectomy for prostate cancer. He had a previous history of allergy to bee sting with nausea, vomiting, and dizziness. Within 1 minute after injection of indigo carmine for evaluation of the ureters, the patient developed hypotension to 40 mmHg, severe hypoxia (the value of SpO2 (peripheral capillary oxygen saturation) was 75% on 40% inspired oxygen concentration), poor air movement and bilateral diffuse wheezing on auscultation, and marked subcutaneous erythema at the upper extremities. After treatment with 100% oxygen, epinephrine (total, 1.5 mg), hydrocortisone (100 mg), diphenhydramine (50 mg), albuterol nebulizer (0.083%), and continuous infusion of epinephrine (0.15 μg/kg/min), the vital signs became stable, and he recovered completely. In summary, indigo carmine rarely may cause life-threatening anaphylactic or anaphylactoid reaction that may necessitate rapid treatment to stabilize cardiovascular, hemodynamic, and pulmonary function. PMID:27610263

  16. Presepsin (Scd14) as a Marker of Serious Bacterial Infections in Chemotherapy Induced Severe Neutropenia

    PubMed Central

    Olad, Elham; Sedighi, Iraj; Mehrvar, Azim; Tashvighi, Maryam; Fallahazad, Vahid; Hedayatiasl, Amirabbas; Esfahani, Hossein

    2014-01-01

    Objective: Timely detection of serious bacterial infections or prediction of sepsis and death is of paramount importance in neutropenic patients especially in oncology settings. The aim of this study was to determine a rapid and secure predictor of sepsis in severe neutropenic cancer children. Methods: In addition to blood culture, we have evaluated serum soluble CD14 on this role and measured it in 39 neutropenic episodes in Mahak pediatric oncology center from September 2012 to January 2013. Fifteen episodes had positive bacterial cultures and 18 had fever. The mean sCD14 values were compared in the presence or absence of fever, positive blood culture and other clinical conditions. Also, mean levels compared in different white cell counts and different four combination settings of fever and blood culture. Findings: It was statistically higher in febrile episodes, in the presence of oral mucositis, indwelling catheter infection, otitis media, and post toxic epidermal necrolysis sepsis and in instances of death within 15 days. Leukocyte count did not affect sCD14 level and in combinations of fever and blood culture, mean sCD14 values were ranked as follow: febrile culture negatives, febrile culture positives, afebrile culture positives and afebrile culture negatives. Conclusion: Although sCD14 was not sensitive in detection of bacteremia, in the absence of clinically detectable source of infection, it was significantly higher in culture positives. PMID:26019777

  17. Intranuclear interactomic inhibition of NF-κB suppresses LPS-induced severe sepsis

    SciTech Connect

    Park, Sung-Dong; Cheon, So Yeong; Park, Tae-Yoon; Shin, Bo-Young; Oh, Hyunju; Ghosh, Sankar; Koo, Bon-Nyeo; Lee, Sang-Kyou

    2015-08-28

    Suppression of nuclear factor-κB (NF-κB) activation, which is best known as a major regulator of innate and adaptive immune responses, is a potent strategy for the treatment of endotoxic sepsis. To inhibit NF-κB functions, we designed the intra-nuclear transducible form of transcription modulation domain (TMD) of RelA (p65), called nt-p65-TMD, which can be delivered effectively into the nucleus without influencing the cell viability, and work as interactomic inhibitors via disruption of the endogenous p65-mediated transcription complex. nt-p65-TMD effectively inhibited the secretion of pro-inflammatory cytokines, including TNF-α, IL-1β, or IL-6 from BV2 microglia cells stimulated by lipopolysaccharide (LPS). nt-p65-TMD did not inhibit tyrosine phosphorylation of signaling mediators such as ZAP-70, p38, JNK, or ERK involved in T cell activation, but was capable of suppressing the transcriptional activity of NF-κB without the functional effect on that of NFAT upon T-cell receptor (TCR) stimulation. The transduced nt-p65-TMD in T cell did not affect the expression of CD69, however significantly inhibited the secretion of T cell-specific cytokines such as IL-2, IFN-γ, IL-4, IL-17A, or IL-10. Systemic administration of nt-p65-TMD showed a significant therapeutic effect on LPS-induced sepsis model by inhibiting pro-inflammatory cytokines secretion. Therefore, nt-p65-TMD can be a novel therapeutics for the treatment of various inflammatory diseases, including sepsis, where a transcription factor has a key role in pathogenesis, and further allows us to discover new functions of p65 under normal physiological condition without genetic alteration. - Highlights: • The nt-p65-TMD is intra-nuclear interactomic inhibitor of endogenous p65. • The nt-p65-TMD effectively inhibited the secretion of pro-inflammatory cytokines. • The excellent therapeutic potential of nt-p65-TMD was confirmed in sepsis model.

  18. Azathioprine-induced Acute Pancreatitis in Patients with Inflammatory Bowel Diseases—A Prospective Study on Incidence and Severity

    PubMed Central

    Mohl, Wolfgang; Bokemeyer, Bernd; Bündgens, Burkhard; Büning, Jürgen; Miehlke, Stephan; Hüppe, Dietrich; Maaser, Christian; Klugmann, Tobias; Kruis, Wolfgang; Siegmund, Britta; Helwig, Ulf; Weismüller, Joseph; Drabik, Attyla; Stallmach, Andreas

    2016-01-01

    Background and Aims: Azathioprine [AZA] is recommended for maintenance of steroid-free remission in inflammatory bowel disease IBD. The aim of this study has been to establish the incidence and severity of AZA-induced pancreatitis, an idiosyncratic and major side effect, and to identify specific risk factors. Methods: We studied 510 IBD patients [338 Crohn’s disease, 157 ulcerative colitis, 15 indeterminate colitis] with initiation of AZA treatment in a prospective multicentre registry study. Acute pancreatitis was diagnosed in accordance with international guidelines. Results: AZA was continued by 324 [63.5%] and stopped by 186 [36.5%] patients. The most common cause of discontinuation was nausea [12.2%]. AZA-induced pancreatitis occurred in 37 patients [7.3%]. Of these: 43% were hospitalised with a median inpatient time period of 5 days; 10% had peripancreatic fluid collections; 24% had vomiting; and 14% had fever. No patient had to undergo nonsurgical or surgical interventions. Smoking was the strongest risk factor for AZA-induced acute pancreatitis [p < 0.0002] in univariate and multivariate analyses. Conclusions: AZA-induced acute pancreatitis is a common adverse event in IBD patients, but in this study had a mild course in all patients. Smoking is the most important risk factor. PMID:26468141

  19. Piperine ameliorates the severity of cerulein-induced acute pancreatitis by inhibiting the activation of mitogen activated protein kinases.

    PubMed

    Bae, Gi-Sang; Kim, Min-Sun; Jeong, Jinsu; Lee, Hye-Youn; Park, Kyoung-Chel; Koo, Bon Soon; Kim, Byung-Jin; Kim, Tae-Hyeon; Lee, Seung Ho; Hwang, Sung-Yeon; Shin, Yong Kook; Song, Ho-Joon; Park, Sung-Joo

    2011-07-01

    Piperine is a phenolic component of black pepper (Piper nigrum) and long pepper (Piper longum), fruits used in traditional Asian medicine. Our previous study showed that piperine inhibits lipopolysaccharide-induced inflammatory responses. In this study, we investigated whether piperine reduces the severity of cerulein-induced acute pancreatitis (AP). Administration of piperine reduced histologic damage and myeloperoxidase (MPO) activity in the pancreas and ameliorated many of the examined laboratory parameters, including the pancreatic weight (PW) to body weight (BW) ratio, as well as serum levels of amylase and lipase and trypsin activity. Furthermore, piperine pretreatment reduced the production of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 during cerulein-induced AP. In accordance with in vivo results, piperine reduced cell death, amylase and lipase activity, and cytokine production in isolated cerulein-treated pancreatic acinar cells. In addition, piperine inhibited the activation of mitogen-activated protein kinases (MAPKs). These findings suggest that the anti-inflammatory effect of piperine in cerulein-induced AP is mediated by inhibiting the activation of MAPKs. Thus, piperine may have a protective effect against AP.

  20. Social stress-enhanced severity of Citrobacter rodentium induced colitis is CCL2-dependent and attenuated by probiotic Lactobacillus reuteri

    PubMed Central

    Mackos, Amy R.; Galley, Jeffrey D.; Eubank, Timothy D.; Easterling, Robert S.; Parry, Nicola M.; Fox, James G.; Lyte, Mark; Bailey, Michael T.

    2015-01-01

    Psychological stressors are known to affect colonic diseases but the mechanisms by which this occurs, and whether probiotics can prevent stressor effects, are not understood. Because inflammatory monocytes that traffic into the colon can exacerbate colitis, we tested whether CCL2, a chemokine involved in monocyte recruitment, was necessary for stressor-induced exacerbation of infectious colitis. Mice were exposed to a social disruption stressor that entails repeated social defeat. During stressor exposure, mice were orally challenged with Citrobacter rodentium to induce a colonic inflammatory response. Exposure to the stressor during challenge resulted in significantly higher colonic pathogen levels, translocation to the spleen, increases in colonic macrophages, and increases in inflammatory cytokines and chemokines. The stressor-enhanced severity of C. rodentium-induced colitis was not evident in CCL2−/− mice, indicating the effects of the stressor are CCL2-dependent. Additionally, we tested whether probiotic intervention could attenuate stressor-enhanced infectious colitis by reducing monocyte/macrophage accumulation. Treating mice with probiotic Lactobacillus reuteri reduced CCL2 mRNA levels in the colon, and attenuated stressor-enhanced infectious colitis. These data demonstrate that probiotic L. reuteri can prevent the exacerbating effects of stressor exposure on pathogen-induced colitis, and suggest that one mechanism by which this occurs is through a down-regulation of the chemokine CCL2. PMID:26422754

  1. Measles pneumonia in young adults. An analysis of 106 cases.

    PubMed

    Gremillion, D H; Crawford, G E

    1981-10-01

    Measles occurred in 3,220 Air Force recruits between January 1976 and July 1979 and was complicated by pneumonia in 106 cases (3.3 percent). Although no deaths occurred, the illness was characterized as clinically severe with high fever and prolonged hospitalization (mean, 14.5 days). Bacterial superinfection as documented by transtracheal aspiration occurred in 35 cases (30.3 percent) and was caused by Hemophilus influenzae (18), Hemophilus parainfluenzae (two), Neisseria meningitidis (nine), Streptococcus pneumoniae (three), Streptococcus pyogenes (two) and Moraxella kingae (one). Clinical evidence of bronchospasm was present in 18 patients (17 percent) and required bronchodilators in six. Other complications included liver function abnormalities (31 percent), otitis media (29 percent) and sinusitis (25 percent). Measles pneumonia in adolescents is clinically severe with a generally benign outcome.

  2. Incidence of childhood pneumonia: facility-based surveillance estimate compared to measured incidence in a South African birth cohort study

    PubMed Central

    le Roux, David M; Myer, Landon; Nicol, Mark P; Zar, Heather J

    2015-01-01

    Background Pneumonia is the leading cause of childhood mortality and a major contributor to childhood morbidity, but accurate measurement of pneumonia incidence is challenging. We compared pneumonia incidence using a facility-based surveillance system to estimates from a cohort study conducted contemporaneously in the same community in Cape Town, South Africa. Methods A surveillance system was developed in six public sector primary care clinics and in a regional referral hospital, to detect childhood pneumonia cases. Nurses recorded all children presenting to facilities who met WHO case definitions of pneumonia, and hospital records were reviewed. Estimates of pneumonia incidence and severity were compared with incidence rates based on active surveillance in the Drakenstein Child Health Study. Results From June 2012 until September 2013, the surveillance system detected 306 pneumonia episodes in children under 1 year of age, an incidence of 0.20 episodes/child-year (e/cy) (95% CI 0.17 to 0.22 e/cy). The incidence in the cohort study from the same period was 0.27 e/cy (95% CI 0.23 to 0.32 e/cy). Pneumonia incidence in the surveillance system was almost 30% lower than in the birth cohort; incidence rate ratio 0.72 (95% CI 0.58 to 0.89). In the surveillance system, 18% were severe pneumonia cases, compared to 23% in the birth cohort, rate ratio 0.81 (95% CI 0.55 to 1.18). Conclusions In this setting, facility-based pneumonia surveillance detected fewer cases of pneumonia, and fewer severe cases, compared to the corresponding cohort study. Facility pneumonia surveillance using data collected by local healthcare workers provides a useful estimate of the epidemiology of childhood pneumonia but may underestimate incidence and severity. PMID:26685027

  3. Mycoplasma pneumoniae: Current Knowledge on Nucleic Acid Amplification Techniques and Serological Diagnostics.

    PubMed

    Loens, Katherine; Ieven, Margareta

    2016-01-01

    Mycoplasma pneumoniae (M. pneumoniae) belongs to the class Mollicutes and has been recognized as a common cause of respiratory tract infections (RTIs), including community-acquired pneumonia (CAP), that occur worldwide and in all age groups. In addition, M. pneumoniae can simultaneously or sequentially lead to damage in the nervous system and has been associated with a wide variety of other acute and chronic diseases. During the past 10 years, the proportion of LRTI in children and adults, associated with M. pneumoniae infection has ranged from 0 to more than 50%. This variation is due to the age and the geographic location of the population examined but also due to the diagnostic methods used. The true role of M. pneumoniae in RTIs remains a challenge given the many limitations and lack of standardization of the applied diagnostic tool in most cases, with resultant wide variations in data from different studies. Correct and rapid diagnosis and/or management of M. pneumoniae infections is, however, critical to initiate appropriate antibiotic treatment and is nowadays usually done by PCR and/or serology. Several recent reviews, have summarized current methods for the detection and identification of M. pneumoniae. This review will therefore provide a look at the general principles, advantages, diagnostic value, and limitations of the most currently used detection techniques for the etiological diagnosis of a M. pneumoniae infection as they evolve from research to daily practice. PMID:27064893

  4. Comparison of beetroot extracts originating from several sites using time-resolved laser-induced fluorescence spectroscopy

    NASA Astrophysics Data System (ADS)

    Rabasović, M. S.; Šević, D.; Terzić, M.; Marinković, B. P.

    2012-05-01

    Beetroot (Beta vulgaris) juice contains a large number of fluorophores which can fluoresce. There is a growing interest in beetroot extracts analysis. In contrast, there is only limited information about beetroot obtained without sample preparation and/or extraction of components from the sample. In this work, we continue our previous study (Rabasović et al 2009 Acta Phys. Pol. A 116 570-2), analyzing and comparing beetroot extracts from several sites, using the time-resolved laser-induced fluorescence technique to measure the fluorescence of samples at different excitation wavelengths (340-470 nm) and for different sample dilutions.

  5. Organising pneumonia caused by transtuzumab (Herceptin) therapy for breast cancer.

    PubMed

    Radzikowska, E; Szczepulska, E; Chabowski, M; Bestry, I

    2003-03-01

    The case of a 49-yr-old female, who developed fever, effort dyspnoea and cough, with patchy migratory bilateral pulmonary infiltrates 6 weeks after starting transtuzumab therapy, following breast-conserving surgery with adjuvant chemoradiotherapy and hormone therapy for breast carcinoma, is reported here. Chest radiograph and thin section computed tomography demonstrated alveolar opacities with air bronchogram in both lungs. A lung biopsy was performed in a nonirradiated area of the contralateral lung and revealed a typical histological pattern of organising pneumonia (previously known as bronchiolitis obliterans organising pneumonia). Transtuzumab therapy was discontinued and subsequent gradual clinical and radiological improvement was observed. After 3 months, complete resolution of symptoms and radiographical abnormalities were noted. This is the first case report that suggests that transtuzumab therapy might induce the development of lung infiltrates with the histological appearance of organising pneumonia.

  6. Antigen exposure in the late light period induces severe symptoms of food allergy in an OVA-allergic mouse model.

    PubMed

    Tanabe, Kana; Kitagawa, Eri; Wada, Misaki; Haraguchi, Atsushi; Orihara, Kanami; Tahara, Yu; Nakao, Atsuhito; Shibata, Shigenobu

    2015-09-30

    The mammalian circadian clock controls many physiological processes that include immune responses and allergic reactions. Several studies have investigated the circadian regulation of intestinal permeability and tight junctions known to be affected by cytokines. However, the contribution of circadian clock to food allergy symptoms remains unclear. Therefore, we investigated the role of the circadian clock in determining the severity of food allergies. We prepared an ovalbumin food allergy mouse model, and orally administered ovalbumin either late in the light or late in the dark period under light-dark cycle. The light period group showed higher allergic diarrhea and weight loss than the dark period group. The production of type 2 cytokines, IL-13 and IL-5, from the mesenteric lymph nodes and ovalbumin absorption was higher in the light period group than in the dark period group. Compared to the dark period group, the mRNA expression levels of the tight junction proteins were lower in the light period group. We have demonstrated that increased production of type 2 cytokines and intestinal permeability in the light period induced severe food allergy symptoms. Our results suggest that the time of food antigen intake might affect the determination of the severity of food allergy symptoms.

  7. Pneumocystis jirovecii pneumonia in developing countries*

    PubMed Central

    De Armas Rodríguez, Y.; Wissmann, G.; Müller, A.L.; Pederiva, M.A.; Brum, M.C.; Brackmann, R.L.; Capó De Paz, V.; Calderón, E.J.

    2011-01-01

    Pneumocystis pneumonia (PcP) is a serious fungal infection among immunocompromised patients. In developed countries, the epidemiology and clinical spectrum of PcP have been clearly defined and well documented. However, in most developing countries, relatively little is known about the prevalence of pneumocystosis. Several articles covering African, Asian and American countries were reviewed in the present study. PcP was identified as a frequent opportunistic infection in AIDS patients from different geographic regions. A trend to an increasing rate of PcP was apparent in developing countries from 2002 to 2010. PMID:21894262

  8. [Management of pneumonia in the elderly].

    PubMed

    Piette, François; Bornand, Anne; Cotto, Elise

    2011-10-01

    Pneumonias in elderly are frequent and severe. They require an accurate assessment following clinical, biological and radiological steps. Each of them can contribute to give answers to the following questions: does this patient need emergency hospitalisation? Is the infection really bacterial and pulmonary? Should antibiotics be started? Which others treatments should be associated for the infection itself and for comorbid conditions? Concerning prevention, every effort must be done to decrease the incidence of these infections, especially vaccination. Pulmonary infections in nursing home need specific attention: cumulation of bad prognosis factors, risk of epidemic propagation, and vaccination of all people caring patients when required.

  9. Neutrophil apoptosis: a marker of disease severity in sepsis and sepsis-induced acute respiratory distress syndrome

    PubMed Central

    Fialkow, Léa; Fochesatto Filho, Luciano; Bozzetti, Mary C; Milani, Adriana R; Rodrigues Filho, Edison M; Ladniuk, Roberta M; Pierozan, Paula; de Moura, Rafaela M; Prolla, João C; Vachon, Eric; Downey, Gregory P

    2006-01-01

    Introduction Apoptosis of neutrophils (polymorphonuclear neutrophils [PMNs]) may limit inflammatory injury in sepsis and acute respiratory distress syndrome (ARDS), but the relationship between the severity of sepsis and extent of PMN apoptosis and the effect of superimposed ARDS is unknown. The objective of this study was to correlate neutrophil apoptosis with the severity of sepsis and sepsis-induced ARDS. Methods A prospective cohort study was conducted in intensive care units of three tertiary hospitals in Porto Alegre, southern Brazil. Fifty-seven patients with sepsis (uncomplicated sepsis, septic shock, and sepsis-induced ARDS) and 64 controls were enrolled. Venous peripheral blood was collected from patients with sepsis within 24 hours of diagnosis. All surgical groups, including controls, had their blood drawn 24 hours after surgery. Control patients on mechanical ventilation had blood collected within 24 hours of initiation of mechanical ventilation. Healthy controls were blood donors. Neutrophils were isolated, and incubated ex vivo, and apoptosis was determined by light microscopy on cytospun preparations. The differences among groups were assessed by analysis of variance with Tukeys. Results In medical patients, the mean percentage of neutrophil apoptosis (± standard error of the mean [SEM]) was lower in sepsis-induced ARDS (28% ± 3.3%; n = 9) when compared with uncomplicated sepsis (57% ± 3.2%; n = 8; p < 0.001), mechanical ventilation without infection, sepsis, or ARDS (53% ± 3.0%; n = 11; p < 0.001) and healthy controls (69% ± 1.1%; n = 33; p < 0.001) but did not differ from septic shock (38% ± 3.7%; n = 12; p = 0.13). In surgical patients with sepsis, the percentage of neutrophil apoptosis was lower for all groups when compared with surgical controls (52% ± 3.6%; n = 11; p < 0.001). Conclusion In medical patients with sepsis, neutrophil apoptosis is inversely proportional to the severity of sepsis and thus may be a marker of the severity of

  10. What Are the Signs and Symptoms of Pneumonia?

    MedlinePlus

    ... Twitter. What Are the Signs and Symptoms of Pneumonia? The signs and symptoms of pneumonia vary from ... have sudden changes in mental awareness. Complications of Pneumonia Often, people who have pneumonia can be successfully ...

  11. [Clinical effect of continuous infusion of meropenem on bacterial pneumonia in the elderly].

    PubMed

    Okimoto, Niro; Kibayashi, Takashi; Mimura, Kimihiro; Yamato, Kenji; Kurihara, Takeyuki; Honda, Yoshihiro; Osaki, Kohichi; Asaoka, Naoko; Ohba, Hideo

    2006-06-01

    We studied the clinical effect of continuous infusion over 24 hours of meropenem (MEPM) on bacterial pneumonia in the elderly (over 65). The subjects were 26 patients (community-acquired pneumonia: moderate, n = 9; severe, n= 4; hospital-acquired pneumonia: group III, n = 13) whose performance status was 3 or 4. MEPM 1.0g/day was infused continuously for 7-14 days, and its clinical efficacy, bacteriological efficacy, and side effects were examined prospectively. It was effective in 23 of the 26 patients (community-acquired pneumonia: moderate, 8/9; severe, 3/4; hospital-acquired pneumonia: group III, 12/13; efficacy rate: 88.5%). Bactericidal effects were obtained in 3 strains of Klebsiella pneumoniae, 2 strains of Streptococcus pneumoniae, 2 strains of methicillin-sensitive Staphlococcus aureus, 1 strain of Streptococcus agalactiae and 1 strain of Proteus mirabilis, but not in 2 strains of methicillin-resistant S. aureus, 1 strain of Pseudomonas aeruginosa and 1 strain of Serratia marcescens. Mild abnormal laboratory findings were observed in 2 patients: elevation of GPT, gamma-GTP, BUN and elevation of ALP. Based on the above, continuous infusion of MEPM on bacterial pneumonia in the elderly obtained excellent clinical effects. Further study is needed to compare the efficacy of continuous versus intermittent administration of MEPM.

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

    PubMed Central

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

    2016-01-01

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

  13. Matrix metalloproteinase 9-induced increase in intestinal epithelial tight junction permeability contributes to the severity of experimental DSS colitis.

    PubMed

    Nighot, Prashant; Al-Sadi, Rana; Rawat, Manmeet; Guo, Shuhong; Watterson, D Martin; Ma, Thomas

    2015-12-15

    Recent studies have implicated a pathogenic role for matrix metalloproteinases 9 (MMP-9) in inflammatory bowel disease. Although loss of epithelial barrier function has been shown to be a key pathogenic factor for the development of intestinal inflammation, the role of MMP-9 in intestinal barrier function remains unclear. The aim of this study was to investigate the role of MMP-9 in intestinal barrier function and intestinal inflammation. Wild-type (WT) and MMP-9(-/-) mice were subjected to experimental dextran sodium sulfate (DSS) colitis by administration of 3% DSS in drinking water for 7 days. The mouse colonic permeability was measured in vivo by recycling perfusion of the entire colon using fluorescently labeled dextran. The DSS-induced increase in the colonic permeability was accompanied by an increase in intestinal epithelial cell MMP-9 expression in WT mice. The DSS-induced increase in intestinal permeability and the severity of DSS colitis was found to be attenuated in MMP-9(-/-) mice. The colonic protein expression of myosin light chain kinase (MLCK) and phospho-MLC was found to be significantly increased after DSS administration in WT mice but not in MMP-9(-/-) mice. The DSS-induced increase in colonic permeability and colonic inflammation was attenuated in MLCK(-/-) mice and MLCK inhibitor ML-7-treated WT mice. The DSS-induced increase in colonic surface epithelial cell MLCK mRNA was abolished in MMP-9(-/-) mice. Lastly, increased MMP-9 protein expression was detected within the colonic surface epithelial cells in ulcerative colitis cases. These data suggest a role of MMP-9 in modulation of colonic epithelial permeability and inflammati