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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously demonstrated that pneumococcal extracts contain a highly specific inhibitor of human neutrophil elastase (HNE). We now show that the active inhibitor in these extracts is a high-molecular-weight, heat-stable substance that appears to be RNA, since inhibitory activity of pneumococcal extracts is decreased by incubation with ribonuclease but not by incubation with deoxyribonuclease or proteinase K. Moreover, metabolically labeled ([3H]uridine) pneumococcal RNA, isolated by phenol extraction followed by ethanol precipitation, strongly inhibits HNE. Pneumococcal capsular polysaccharide, although polyanionic, is only weakly inhibitory toward HNE and is not a major source of elastase-inhibitory activity in pneumococcal extracts. On the other hand, the capsule of Haemophilus influenzae type b contains polyribosylribitol phosphate. This highly charged polyanion possesses HNE-inhibitory activity, but only under special circumstances to be discussed below. Pneumococci (type I, type II smooth, type II rough) and H. influenzae (type b) all release HNE-inhibitory activity into their culture medium during growth. By contrast, Klebsiella pneumoniae and Staphylococcus aureus release little (if any) stable HNE-inhibitory activity during growth. We propose that some bacterial pneumonias may spare host tissue because polyanions released by the invading microorganisms (e.g. RNA from autolysing pneumococci) inhibit elastase released from inflammatory neutrophils and thereby modulate accompanying tissue proteolysis. Pneumonias caused by microorganisms that do not release stable polyanionic inhibitors of HNE (e.g., Staphylococcus and Klebsiella) may be correspondingly more injurious to the lung.
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PMID:Inhibition of human neutrophil elastase by bacterial polyanions. 244 47

A 56-year-old man was transferred to our department from the department of oral surgery, with a high fever and a cough. He had inhaled a fibrinolysin-deoxyribonuclease mixture (Elase) to treat inflammation in the oral cavity after resection of an oral tumor. A chest X-ray film showed diffuse patchy shadows in both lung fields. Bronchoalveolar lavage fluid had an abnormally high number of lymphocytes and transbronchial lung biopsy revealed interstitial infiltration by lymphocytes and histiocytes, with granulomatous lesions. The patient was treated with steroids, and his clinical condition improved markedly. He accidentally inhaled the drug again, and the coughing and fever began again. The drug lymphocyte stimulation test was positive only for the fibrinolysin-deoxyribonuclease mixture. Based on these findings, we diagnosed pneumonitis induced by this fibrinolysin-deoxyribonuclease mixture. To our knowledge, this is the first reported case of pneumonitis caused by this fibrinolysin-doxyribonuclease mixture.
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PMID:[Pneumonitis in a patient who inhaled a fibrinolysin-deoxyribonuclease mixture]. 858 26

Respiratory insufficiency due to respiratory syncytial virus (RSV) bronchiolitis is partly due to the abundance of thickened mucus and the inability to clear it from the airways. Mucus in RSV bronchiolitis contains necrotic inflammatory and epithelial cells. The viscoelastic properties of purulent airway secretions are largely due to the presence of highly polymerized deoxyribonucleic acid (DNA). Recombinant human deoxyribonuclease (rhDNase) is known to liquefy such mucus in patients with cystic fibrosis, whereas case reports described a beneficial effect in other respiratory disorders. The authors hypothesized that rhDNase would diminish atelectasis and mucus plugging in infants with severe RSV bronchiolitis. Two infants with RSV bronchiolitis with massive unilateral atelectasis in whom mechanical ventilation was imminent due to exhaustion, and three mechanically ventilated infants (two neonates, one with bronchopulmonary dysplasia) with RSV bronchiolitis with pneumonia received treatment with 2.5 mg nebulized rhDNase twice daily. Following administration of nebulized recombinant human deoxyribonuclease, clinical and radiological parameters improved quickly. Mechanical ventilation could be avoided in two infants while in three infants on artificial ventilation, clinical recovery started following the first dose of the drug. A therapeutic trial of recombinant human deoxyribonuclease may be an option in the treatment for atelectasis in severe or complicated respiratory syncytial virus bronchiolitis in infancy.
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PMID:DNase treatment for atelectasis in infants with severe respiratory syncytial virus bronchiolitis. 1171 80

Parapneumonic effusions are seen in up to 57% of patients with pneumonia. The majority of these effusions are noninfected and resolve with standard antibiotic treatment for the associated pneumonia. However, parapneumonic effusions in a minority of cases become infected and require prompt chest tube drainage and occasionally thoracic surgery. Patients may present in a variety of ways from florid sepsis to weight loss and anorexia; such diversity mandates a high index of suspicion among physicians. The role of the combination of intrapleural deoxyribonuclease (DNase) and tissue plasminogen activator (t-PA) to aid fluid drainage shows promise but needs further assessment in large trials with surgery and mortality as primary end points.
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PMID:The approach to the patient with a parapneumonic effusion. 2121 2

Empyema thoracis causes high mortality, and its incidence is increasing in both children and adults. Parapneumonic effusions (PPEs) develop in about one-half of patients hospitalized with pneumonia, and their presence increases mortality by about four-fold. PPEs can be divided into simple PPEs, complicated PPEs, and frank empyema. Two guideline statements on the management of PPEs in adults have been published by the British Thoracic Society (BTS) and the American College of Chest Physicians; a third guideline statement published by the BTS focused on management of PPEs in children. The two adult guideline statements recommend drainage of the pleural space in complicated PPEs and frank empyema. They also recommend the use of intrapleural fibrinolysis in those who do not show improvement. The pediatric guideline statement recommends adding intrapleural fibrinolysis to those treated by tube thoracostomy if they have loculated pleural space or thick pus. Published guideline statements on the management of complicated PPEs and empyema in adults and children recommend the use of intrapleural fibrinolysis in those who do not show improvement after pleural space drainage. However, published clinical trial reports on the use of intrapleural fibrinolysis for the treatment of pleural space sepsis suffer from major design and methodologic limitations. Nevertheless, published reports have shown that the use of intrapleural fibrinolysis does not reduce mortality in adults with parapneumonic effusions and empyema. However, intrapleural fibrinolysis enhances drainage of infected pleural fluid and may be used in patients with large collections of infected pleural fluid causing breathlessness or respiratory failure, but a proportion of these patients will ultimately need surgery for definite cure. Intrapleural streptokinase and urokinase seem to be equally efficacious in enhancing infected pleural fluid drainage in adults. In most of the published studies in adults, the use of intrapleural fibrinolysis was not associated with serious side effects. There is emerging evidence that the combination of intrapleural tissue plasminogen activator (tPA) and deoxyribonuclease (DNase) is significantly superior to tPA or DNase alone or placebo in improving pleural fluid drainage in patients with pleural space infection. In children, intrapleural fibrinolysis has not been shown to reduce mortality, but has been shown to enhance drainage of the pleural space and was safe. In addition, two prospective, randomized trials have shown that intrapleural fibrinolysis is as effective as video-assisted thoracoscopic surgery for the treatment of childhood empyema and is a more cost-effective treatment and therefore should be the primary treatment of choice.
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PMID:Intrapleural therapy in management of complicated parapneumonic effusions and empyema. 2229 7

A parapneumonic effusion is the collection of exudative fluid in the pleural space associated with a concurrent pulmonary infection. Parapneumonic effusions account for approximately one-third of all effusions, and about 40% of patients with pneumonia develop a concomitant effusion. Patients with pneumonia who develop an effusion have an increased risk of morbidity and mortality. Some of the excess mortality is due to mismanagement of the parapneumonic effusion. Bacterial and white cell metabolism can rapidly turn a simple exudative parapneumonic effusion into a multiloculated purulent empyema with low pH and high lactate dehydrogenase levels. The optimal approach to treating parapneumonic effusions and pleural empyemas remains controversial. Accepted management consists of systemic antibiotics and drainage of the pleural cavity, which is achieved by either medical chest tube drainage or surgery. Several investigators have studied the efficacy and safety of intrapleural fibrinolytics in the treatment of pleural effusion and empyema. Intrapleural instillation of fibrinolytic agents is undertaken to dissolve fibrinous clots and membranes, to prevent fluid sequestration, and hence to improve drainage. Recombinant deoxyribonuclease has been reported to improve drainage in a single patient who did not respond to fibrinolytic therapy.
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PMID:Update on the role of intrapleural fibrinolytic therapy in the management of complicated parapneumonic effusions and empyema. 2298 84

Pleural infection remains a common and serious respiratory condition with important implications for patients and health-care services. This review will cover the management of pleural infection including medical treatment, the role of intrapleural agents and surgical treatment. We discuss the directions that future research in this important area might take. Increasing incidence of pleural infection has been reported worldwide without a clear explanation. The pathogens responsible for pleural infection differ from those in pneumonia. Proper antibiotic selection and pleural fluid drainage remain the cornerstones of treatment. There is no evidence in adult pleural infection to support the routine use of intrapleural fibrinolytics to alter clinically meaningful outcomes; however, combined intrapleural tissue plasminogen activator (tPA) and deoxyribonuclease (DNase) therapy may have a future role. The role of medical thoracoscopy remains unproven. Surgical referral should be considered in patients who fail to respond to standard medical management after 5 to 7 days. Despite advances in microbiology, medical management, and surgery, the mortality of pleural infection at one year remains approximately 20% for the last two decades. Future studies are required to validate predictive scores for patients' stratification (RAPID score) and the role of fibrinolytics (combination of tPA plus DNase). Surgical drainage remains a vital treatment option, but ongoing research is required to define the group of patients who would benefit most and when, in the disease course, this treatment should be offered.
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PMID:Management of parapneumonic effusions and empyema. 2546 62

Pleural space infections are increasing in incidence and continue to have high associated morbidity, mortality, and need for invasive treatments such as thoracic surgery. The mechanisms of progression from a non-infected, pneumonia-related effusion to a confirmed pleural infection have been well described in the scientific literature, but the route by which pathogenic organisms access the pleural space is poorly understood. Data suggests that not all pleural infections can be related to lung parenchymal infection. Studies examining the microbiological profile of pleural infection inform antibiotic choice and can help to delineate the source and pathogenesis of infection. The development of radiological methods and use of clinical indices to predict which patients with pleural infection will have a poor outcome, as well as inform patient selection for more invasive treatments, is particularly important. Randomised clinical trial and case series data have shown that the combination of an intrapleural tissue plasminogen activator and deoxyribonuclease therapy can potentially improve outcomes, but the use of this treatment as compared with surgical options has not been precisely defined, particularly in terms of when and in which patients it should be used.
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PMID:Pleural infection: past, present, and future directions. 2617 76

Atelectases, over-inflation of ventilated regions of the lung, and consecutive pneumothoraces are life-threatening conditions in mechanically ventilated infants with acute respiratory distress syndrome-type respiratory syncytial virus-pneumonia. The accumulation of viscous secretions secondary to impaired mucociliary clearance in the more proximal parts of the bronchial tree is the prerequisite for atelectases and also prevents the delivery of inhaled medications to the more distal parts of the lung. Herein, we describe four moderately premature infants with respiratory failure on mechanical ventilation, displaying a total of 20 radiologically verified new atelectases that were treated by bronchoscopic interventions with consecutive suctioning of secretions, restoration of the surfactant film within the airways, and deposition of recombinant human deoxyribonuclease at the first segment level of the bronchial tree. On 13 occasions (65%), resolution of atelectases was proven by chest X-ray and resulted in improved lung function. We conclude that these bronchoscopic interventions may contribute to the restoration of the gas exchange area in moderately premature infants with acute respiratory distress syndrome-type respiratory syncytial virus-pneumonia.
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PMID:Bronchoscopic interventions with surfactant and recombinant human deoxyribonuclease for acute respiratory distress syndrome-type respiratory syncytial virus-pneumonia in moderately preterm infants: Case series. 2748 60

Elizabethkingia miricola is a Gram-negative non-fermenting rod emerging as a life-threatening human pathogen. The multidrug-resistant (MDR) carbapenemase-producing clinical isolate E. miricola EM_CHUV was recovered in the setting of severe nosocomial pneumonia. In this study, the genome of E. miricola EM_CHUV was sequenced and a functional analysis was performed, including a comparative genomic study with Elizabethkingia meningoseptica and Elizabethkingia anophelis. The resistome of EM_CHUV revealed the presence of a high number of resistance genes, including the presence of the blaGOB-13 and blaB-9 carbapenemase-encoding genes. Twelve mobility genes, with only two of them located in the proximity of resistance genes, and four potential genomic islands were identified in the genome of EM_CHUV, but no prophages or CRISPR sequences. Ten restriction-modification system (RMS) genes were also identified. In addition, we report the presence of a putative conjugative plasmid (pEM_CHUV) that does not encode any antibiotic resistance genes. Altogether, these findings point towards a limited number of DNA exchanges with other bacteria and suggest that multidrug resistance is an intrinsic trait of E. miricola owing to the presence of a high number of resistance genes within the bacterial core genome.
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PMID:Genome of the carbapenemase-producing clinical isolate Elizabethkingia miricola EM_CHUV and comparative genomics with Elizabethkingia meningoseptica and Elizabethkingia anophelis: evidence for intrinsic multidrug resistance trait of emerging pathogens. 2791 93


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