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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cystic fibrosis (CF) is the commonest, fatal, autosomal recessive disorder and is associated with lung sepsis, pancreatic failure and elevated sweat electrolytes. The CF gene on chromosome 7 encodes a protein identified as CF transmembrane conductance regulator (CFTR) which regulates chloride ion transport in epithelial cell membranes. Almost 100 mutations have been identified in this gene which cause defective chloride-channel control. Recently, this abnormality has been reversed in affected CF cells in vitro by retrovirus-mediated transfer of a normal gene. Fifty years ago, most cases died in childhood, but now up to 80% reach adulthood. Chronic lung sepsis is the principal cause of death, and intensive antibiotic therapy with chest physiotherapy is used to control this. Advanced lung disease can be successfully treated by heart-lung transplantation. Nebulised recombinant DNase and antineutrophil elastase agents such as alpha-1-antitrypsin and secretory leucoprotease inhibitor are potentially promising new therapies. Pancreatic insufficiency is managed by high-calorie diets and enteric coated enzyme supplements. Other prominent gastrointestinal complications include meconium ileus equivalent, biliary cirrhosis and cholelithiasis. Specially dedicated CF centres have led to improved survival rates and allow experienced staff to treat the many complications of CF while promoting research in this multisystem disorder.
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PMID:Cystic fibrosis in adolescents and adults. The coming of age of cystic fibrosis. 155 Dec 44

In the previous report, we showed that the reticuloendothelial system (RES), especially the liver, played an important role in the etiology of bacteremia or sepsis as the major protective system. In this study, to investigate the role of Kupffer cells in the etiology of bacteremia, we isolated and cultured murine Kupffer cells using a technique involving perfusion with collagenase and DNase. We compared the adherence and phagocytosis rate of two groups of isolated bacteria from bacteremic mice by these cells. One group was bacteria causing systemic bacteremia consisted of P. aeruginosa and M. morganii, and the other was bacteria causing portal bacteremia consisted of E. coli, E. cloacae, K. pneumoniae and Enterococci. As a consequence, the following facts were revealed. 1. The bacterial phagocytosis and adherence rate by Kupffer cells were significantly higher in bacteria causing portal bacteremia than in bacteria causing systemic bacteremia. These data were correlated to each blood clearance rate from mice. 2. Blood clearance rate reflected mainly adherence of Kupffer cells to bacteria, and it was suggested that these adherence were one of the most important factor to protect the hosts from the advance of bacteremia from the portal to the systemic. 3. In the case of using peritoneal macrophage, we couldn't find the same correlation, so the possibility was suggested that the above phenomenon was specific to Kupffer cells.
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PMID:[Investigation on the etiology of sepsis by using experimental mouse model with leukocytopenia. 3. The role of Kupffer cells in the etiology of bacteremia]. 214 72

The comparative study of the signs of pathogenicity in enterobacteria (119 strains) isolated from the blood of 145 patients with the clinical symptoms of sepsis and from the feces of healthy persons (560 strains from 220 persons) has demonstrated that the same species of opportunistic microorganisms may essentially differ in the formation of DNase, RNase, as well as in their capacity for the positive reaction with Congo red. The possibility of using the above-mentioned signs of pathogenicity for diagnostic purposes as additional signs for the differentiation of virulent cultures of opportunistic enterobacteria from avirulent ones is suggested.
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PMID:[Biological properties of opportunistic enterobacteria isolated from the blood of patients]. 409 Aug 14

Sepsis and septic shock, the systemic immunologic and pathophysiologic response to overwhelming infection, are associated with perturbation of a variety of metabolic cell pathways and with multiple organ failure (MOF) including cardiac depression. This depression has been attributed to the effect of several circulating and locally produced proinflammatory mediators. Recent data suggest that bacterial nucleic acids can produce profound systemic inflammatory responses characterized by circulatory shock in intact animals. In this study, bacterial DNA and RNA derived from pathogenic clinical S. aureus and E. coli isolates are shown to induce early concentration-dependent depression of maximum extent and peak velocity of contraction of electrically paced neonatal rat ventricular myocytes in culture. Significant but more modest depression was generated by a nonpathogenic E. coli isolate. Pretreatment with a DNase or RNase abrogated this effect. Further, synthetic, double-stranded RNA (dsRNA) also induced concentration-dependent depression of myocyte contraction, with the effect also being prevented by pretreatment with RNase. These data suggest that bacterial DNA and RNA may contribute to myocardial depression during bacterial sepsis and septic shock.
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PMID:Bacterial DNA and RNA induce rat cardiac myocyte contraction depression in vitro. 1517 38

Cystic fibrosis is characterised by chronic bronchopulmonary sepsis. Various therapeutic modalities attempt to enhance the clearance of airway secretions. Dornase alfa (recombinant human deoxyribonuclease) reduces the viscoelasticity of sputum from patients with cystic fibrosis by depolymerising extracellular DNA. The drug is administered as an aerosol using a jet nebuliser at a dosage of 2.5mg once daily. It improves pulmonary function and reduces the risk of respiratory exacerbations requiring parenteral antibacterials. Various clinical trials have demonstrated a heterogeneous response to dornase alfa and have been unable to predict which groups of patients benefit from treatment. Patient selection is further complicated because some individuals do not exhibit improvements in lung function, but benefit in terms of a decrease in infective exacerbations. All patients with cystic fibrosis who produce purulent sputum are potential candidates for dornase alfa therapy. We suggest that compliant patients be considered for treatment with dornase alfa, irrespective of disease severity, but should be closely monitored and be assessed at regular intervals to monitor treatment response.
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PMID:Dornase alfa. 1803 Nov 6

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

A variety of inflammatory stimuli induces NETs. These structures consist of a network of chromatin strands associated with predominately granule proteins, including MPO. NETs exhibit antimicrobial activity, which is proposed to augment the more-established mechanism of phagosomal killing. They may also be detrimental to the host in situations such as chronic inflammation or severe sepsis. The objective of this study was to establish whether MPO associated with NETs is active and able to kill bacteria. Neutrophils were stimulated with PMA to release NETs. Peroxidase activity measurements were performed and showed that enzymatically active MPO was released from the neutrophils, 2-4 h after stimulation, concomitant with NET formation. Approximately 30% of the total cellular MPO was released, with the majority bound to the NETs. The bound enzyme retained its activity. Staphylococcus aureus were not killed when added to preformed NETs under our assay conditions. However, addition of H(2)O(2) to the bacteria in the presence of NETs resulted in MPO-dependent killing, which was observed with NETs in situ and with NETs when they were removed from the neutrophils by limited DNase digestion. Our results show that the enzymatic activity of MPO on NETs could contribute to antimicrobial activity or tissue injury when NETs are released from neutrophils at sites of infection or inflammation.
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PMID:Myeloperoxidase associated with neutrophil extracellular traps is active and mediates bacterial killing in the presence of hydrogen peroxide. 2237 74

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

Increasing incidence of pleural infection has been reported worldwide in recent decades. The pathogens responsible for pleural infection are changing and differ from those in community acquired pneumonia. The main treatments for pleural infection are antibiotics and drainage of infected pleural fluid. The efficacy of intrapleural fibrinolytics remains unclear, although a recent randomized control study showed that the novel combination of tissue plasminogen activator and deoxyribonuclease had improved clinical outcomes. Surgical drainage is a critical treatment in patient with progression of sepsis and failure in tube drainage.
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PMID:Pleural infection and empyema. 2485 Nov 28

Sepsis is characterized by systemic activation of coagulation and inflammation in response to microbial infection. Although cell-free DNA (cfDNA) released from activated neutrophils has antimicrobial properties, it may also exert harmful effects by activating coagulation and inflammation. The authors aimed to determine whether deoxyribonuclease (DNase) administration reduces cfDNA levels, attenuates coagulation and inflammation, suppresses organ damage, and improves outcome in a cecal ligation and puncture (CLP) model of polymicrobial sepsis. Healthy C57Bl/6 mice were subjected to CLP, a surgical procedure involving two punctures of the ligated cecum, or sham surgery (no ligation/puncture). Mice were given DNase or saline by intraperitoneal injection 2, 4, or 6 h after surgery. Two hours after treatment, organs were harvested and plasma levels of cfDNA, interleukin-6 (IL-6), IL-10, thrombin-antithrombin complexes, lung myeloperoxidase, creatinine, alanine transaminase, and bacterial load were quantified. Survival studies were also performed. The CLP-operated mice had rapid time-dependent elevations in cfDNA that correlated with elevations in IL-6, IL-10, and thrombin-antithrombin complexes and had organ damage in the lungs and kidneys. Administration of DNase at 2 h after CLP resulted in increased IL-6 and IL-10 levels and organ damage in the lungs and kidneys. In contrast, DNase administration at 4 or 6 h after CLP resulted in reduced cfDNA and IL-6 levels, increased IL-10, and suppressed organ damage and bacterial dissemination. Deoxyribonuclease administration every 6 h after CLP also rescued mice from death. Our studies are the first to demonstrate that delayed but not early administration of DNase may be protective in experimental sepsis.
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PMID:Delayed but not Early Treatment with DNase Reduces Organ Damage and Improves Outcome in a Murine Model of Sepsis. 2600 20


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