Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although activation of Toll-like receptor 4 (TLR4)-positive cells is essential for eliminating Gram-negative bacteria, overactivation of these cells by the TLR4 ligand LPS initiates a systemic inflammatory reaction and shock. Here we demonstrate that SPRET/Ei mice, derived from Mus spretus, exhibit a dominant resistance against LPS-induced lethality. This resistance is mediated by bone marrow-derived cells. Macrophages from these mice exhibit normal signaling and gene expression responses that depend on the myeloid differentiation factor 88 adaptor protein, but they are impaired in IFN-beta production. The defect appears to be specific for IFN-beta, although the SPRET/Ei IFN-beta promoter is normal. In vivo IFN-beta induction by LPS or influenza virus is very low in SPRET/Ei mice, but IFN-beta-treatment restores the sensitivity to LPS, and IFN type 1 receptor-deficient mice are also resistant to LPS. Because of the defective induction of IFN-beta, these mice are completely resistant to Listeria monocytogenes and highly sensitive to Leishmania major infection. Stimulation of SPRET/Ei macrophages leads to rapid down-regulation of IFN type 1 receptor mRNA expression, which is reflected in poor induction of IFN-beta-dependent genes. This finding indicates that the resistance of SPRET/Ei mice to LPS is due to disruption of a positive-feedback loop that amplifies IFN-beta production. In contrast to TLR4-deficient mice, SPRET/Ei mice resist both LPS and sepsis induced with Klebsiella pneumoniae.
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PMID:The wild-derived inbred mouse strain SPRET/Ei is resistant to LPS and defective in IFN-beta production. 1645 98

Fever is a phylogenetically ancient host reaction to invading microorganisms and other noxious stimuli. Poikylothermic organisms can reach febrile temperatures by seeking a hot environment in response to a higher set point in their thermoregulatory center. Endothermic organisms produce febrile temperatures through endogenous heat production at the expenditure of a higher metabolic rate. Nevertheless, fever has been conserved during evolution through millennia, obviously because of its advantage for host defense. Despite of these arguments most doctors, nurses and patients treat fever with antipyretics. The role of fever for the recovery from low risk infections is marginal at best. A large study of ibuprofen in patients with severe sepsis could not establish a positive or negative role on the course or final outcome of the infection in an intensive care setting. These clinical observations seemingly contradict findings in severe experimental bacterial infections in rodents but it has to be taken into consideration that these animals, in contrast to patients, received no antibiotic treatment. In patients with influenza-like illnesses non-steroidal antirhumatics (NSAR) improve fever and wellbeing with little or no evidence for undesired side-effects. It therefore appears appropriate to treat patients with these and similar infections with NSAR. Antipyretic therapy in special patient groups such as brain injury victims, patients with cardiac or respiratory failure or dementia has not been established to be indicated to overcome a worsening of these organs to fail during infections. In children with a history of fever convulsions prevention or lowering of fever does not reduce recurrence. In patients with strokes it appears advisable however to use antipyretics in case of fever despite of a present lack of a proven beneficial effect. In conclusion symptomatic antipyretic therapy should be considered for low risk infections if patient suffering from fever. For more severe infections antipyretic therapy can be applied on an individual basis without too much hope to improve outcome or cause a severe worsening of prognosis.
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PMID:[Fever--useful or noxious symptom that should be treated?]. 1661 88

Infectious complications in individuals with chronic kidney disease (CKD) pose a significant source of morbidity and mortality. The overall scope of major infectious complications has, however, received little attention even though some of these events may be preventable. We reviewed infectious hospitalization rates in the CKD and end-stage renal disease (ESRD) populations, comparing them with the non-CKD and non-ESRD groups. We also reviewed preventive vaccination rates for influenza, pneumonia, and pneumococcal pneumonia to assess areas of potential improvement. We reviewed the medical literature and present findings based on hospitalization rates for pneumonia, sepsis/bacteremia, and urinary tract infections in the Medicare CKD, ESRD, and non-CKD populations. Vaccination rates were determined from submitted claims for services with specific codes for the vaccinations. Regardless of the primary cause for the development of CKD, primary kidney disease or secondary to hypertension, diabetes mellitus, or other chronic condition, patient outcomes after the development of infections were 3 to 4 times worse than in the non-CKD population. Influenza vaccination rates were 52%, far less than the target of 90%. Pneumococcal pneumonia vaccination rate was only 13.5%, far less than recommended. CKD is associated with significant major infectious complications, which occur at rates 3 to 4 times the general population. Providers can improve prevention by using fewer dialysis catheters and increasing vaccination rates for influenza and pneumococcal pneumonia.
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PMID:Infectious complications in chronic kidney disease. 1681 25

Overwhelming infection in asplenic patients is a well documented occurrence in the literature. The introduction of immunization with polyvalent pneumococcal, Hemophilus Influenza and meningococcal vaccines significantly cut down the incidence of post-splenectomy sepsis and mortality. However, the issue of prophylactic antibiotic therapy in these patients remains inconclusive. There are contradictory reports bouncing between life-long treatment to no treatment. There are also more flexible approaches emerging from patient difficulties complying with a prolonged therapy. This debate calls for developing a better predictive approach based on genetic profiling of patients with different susceptibility to infectious pathogens, host-pathogens interactions as well as to identify the impact of factors such as age, on immunological competence.
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PMID:Post-splenectomy antibiotic prophylaxis--unfinished story: to treat or not to treat? 1693 44

Infectious muscle diseases have very different aetiologies. The viral myositides are proved by clinical and laboratory evidences in various etiologic settings (Influenza A and B, Coxsackie and HIV). The bacterial myositis was considered in the near past a tropical disease, but in our days with migration of people from South to North and the endemia of AIDS it became a problem of the "civilized" world. On the other hand, tuberculous endemia in Central-Eastern Europe, including Romania, results in quite high incidence of osteoarticular tuberculosis. In this section the authors take into consideration some clinical entities, such as psoas abscess, postanginal sepsis, beta-haemolytic streptococcus infection and that caused by Koch bacillus. Other rare musculoskeletal infections such as gas gangrene and non-clostridial anaerobic myonecrosis are also reviewed. Immune depression caused by underlying diseases, therapies, alcoholism or old age is often encountered. The parasitic aetiologies include infestations with Trichinella spiralis, Cysticercus cellulosae, Toxoplasma and Amoeba. The contribution of imagistic methods to diagnosis is emphasised. Ultrasonography associated with CT imaging are usually used, while MRI should be reserved for cases in which axial skeleton is involved. The management is based on appropriate antibiotic therapy and surgery.
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PMID:Infectious muscle disease. 1723 94

Incidence of influenza, the most frequent infectious disease in Poland decreased 72% to 336,919 cases (882.4 per 100,000 population). Number of bacterial foodborne infections and intoxications remain high--19,870 cases (52.0 per 100,000). 79.6% of them were caused by Salmonella. In 17.0% of them etiologic factor was not found. Number of cases of diarrhea among children 0-2 (viral, bacterial and of unknown origin) was 16,361 (2,326 per 100,000). Among them 5,672 were viral. This number includes rotaviral infections as probably the dominant component. There was noted decrease of incidence of newly diagnosed cases of viral hepatitis B (4.1 per 100,000) which'dropped to the level below the incidence of viral hepatitis C (5,6). Hepatitis A remains at the low level (0.25 per 100,000). Level of newly diagnosed cases of AIDS (170 cases, 0.45 per 100,000) is 19% higher then in the previous year. The major problem with HIV reporting is low fraction of reported risk factors. Infectious diseases caused 0.68 % of deaths. Mortality from infectious diseases was 6.5 per 100,000 population and was significantly higher among men (8.6) then among women (4.5). In urban settings mortality from infectious diseases was higher (7.0 per 100,000) then in the country (5.8). In particular districts (voivodeships) mortality indices remained in the range of 4.6 (kujawsko-pomorskie) to 9.8 (lubuskie). The highest number of deaths was caused by tuberculosis and its late sequels (34.2%). Attention should be given to the increased number of deaths due to sepsis (34.0%, without neonatal sepsis).
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PMID:[Infectious diseases in Poland in 2004]. 1724 56

Previous studies have demonstrated that animals exposed to Streptococcus pneumoniae while recovering from influenza A virus infection exhibit exacerbated disease symptoms. However, many of the current animal models exploring dual viral and bacterial synergistic exacerbations of respiratory disease have utilized mouse-adapted influenza virus and strains of Streptococcus pneumoniae that in themselves are highly lethal to mice. Here we describe a mouse model of bacterial superinfection in which a mild, self-limiting influenza virus infection is followed by mild, self-limiting superinfection with S. pneumoniae serotype 3. S. pneumoniae superinfection results in rapid dissemination of the bacterium from the respiratory tract and systemic spread to all major organs of the mice, resulting in fatal septicemia. This phenomenon in mice was observed in superinfected animals undergoing an active viral infection as well as in mice that had completely cleared the virus 7 to 8 days prior to superinfection. Neutrophils were the predominant cellular inflammatory infiltrate in the lungs of superinfected mice compared to singly infected animals. Among other cytokines and chemokines, the neutrophil activator granulocyte colony-stimulating factor (G-CSF) was found to be significantly overexpressed in the spleens, lungs, and brains of superinfected animals. High G-CSF protein levels were observed in sera and lung lavage fluid from superinfected animals, suggesting that G-CSF is a major contributor to synergistic exacerbation of disease leading to fatal septicemia.
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PMID:Filamentous influenza A virus infection predisposes mice to fatal septicemia following superinfection with Streptococcus pneumoniae serotype 3. 1740 70

This review summarizes the origins of the insight that excess production of pro-inflammatory cytokines caused a constellation of changes that contribute to pathophysiology of disease. This connection was made following the original 1975 TNF (tumor necrosis factor) publication from New York describing how activated macrophages kill tumors. The study caught the eye of a group in London who were trying to understand how the same in vivo macrophage activation would protect mice against the erythrocytic protozoan parasites that cause malaria and babesiosis. Based on collaborative research between these two groups, it was argued in 1981 that TNF and related cytokines initiated events that caused pathology, as well as parasite death within red cells in these infectious diseases. This proved to be a key conceptual advance. It was also argued that the pathology of bacterial sepsis logically had TNF origins. Once TNF was cloned in 1985, allowing its specific analysis in serum and neutralization in vivo, the involvement of this cytokine in infectious disease pathology was pursued by a number of groups. Some researchers found that once "their" cytokine was cloned and sequenced, they had been unwittingly expanding knowledge on TNF for several years. By the late 1980s excess TNF production was proposed to be central to acute systemic viral diseases. This family of cytokines is now at the centre of investigations to understand the mechanisms of acute systemic viral diseases, including influenza and the hemorrhagic viral diseases. With its implication as the master regulator of other inflammatory cytokines in the synovial membrane, TNF has also become the major cytokine in the pathogenesis of chronic inflammatory disease. Its neutralization has proven to be a potent treatment for rheumatoid arthritis and Crohn's disease.
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PMID:How TNF was recognized as a key mechanism of disease. 1749 63

Acute hypercytokinaemia represents an imbalance of pro-inflammatory and anti-inflammatory cytokines, and is believed to be responsible for the development of acute respiratory distress syndrome and multiple organ failure in severe cases of avian (H5N1) influenza. Although neuraminidase inhibitors are effective in treating avian influenza, especially if given within 48 h of infection, it is harder to prevent the resultant hypercytokinaemia from developing if the patient does not seek timely medical assistance. Steroids have been used for many decades in a wide variety of inflammatory conditions in which hypercytokinaemia plays a role, such as sepsis and viral infections, including severe acquired respiratory syndromes and avian influenza. However, to date, the results have been mixed. Part of the reason for the discrepancies might be the lack of understanding that low doses are required to prevent mortality in cases of adrenal insufficiency. Adrenal insufficiency, as defined in the sepsis/shock literature, is a plasma cortisol rise of at least 9 microg dl(-1) following a 250 microg dose of adrenocorticotropin hormone (ACTH), or reaching a plasma cortisol concentration of >25 microg dl(-1) following a 1-2 microg dose of ACTH. In addition, in the case of hypercytokinaemia induced by potent viruses, such as H5N1, systemic inflammation-induced, acquired glucocorticoid resistance is likely to be present. Adrenal insufficiency can be overcome, however, with prolonged (7-10 or more days) supraphysiological steroid treatment at a sufficiently high dose to address the excess activation of NF-kappaB, but low enough to avoid immune suppression. This is a much lower dose than has been typically used to treat avian influenza patients. Although steroids cannot be used as a monotherapy in the treatment of avian influenza, there might be a potential role for their use as an adjunct treatment to antiviral therapy if appropriate dosages can be determined. In this paper, likely mechanisms of adrenal insufficiency are discussed, drawing from a broad background of literature sources.
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PMID:A rationale for using steroids in the treatment of severe cases of H5N1 avian influenza. 1757 50

Complete Center for Disease Control death certificate records and Centers for Medicare and Medicaid Services 100% Standard Analytic File for hospice claims for 2002 were used to describe the whole population of hospice users and nonusers in the United States. The overall hospice utilization rate for persons 65 years and older was 28.6%. Hospice utilization varied by cause of death, and was highest for individuals with malignancies (65%), kidney disease and nephritis (55%), and Alzheimer's disease (41%). Hospice utilization was lowest for conditions leading to rapid or unexpected death, such as accidents and suicide (0%), influenza and pneumonia (3%), and sepsis (6%). Considerable geographic differences in hospice utilization existed, with hospice use higher in the South and the Southwest and lower in the Midwest and the Northeast. State-specific usage rates ranged from 8% in Alaska to 49% in Arizona. Our findings highlight opportunities for the hospice industry to provide more care, opportunities defined by diagnostic and geographic axes.
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PMID:Geographic variation in hospice use in the United States in 2002. 1759 May 66


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