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)

NF-kappaB activation, and elevated concentrations of macrophage migration inhibitory factor (MIF), tumor necrosis factor-alpha (TNF-alpha), interleukin-1(IL-1), IL-6, free radicals, inducible nitric oxide (iNO), and stress hyperglycemia occurs in sepsis and this leads to systemic inflammatory response and myocardial depression seen in sepsis and septic shock. Conversely, insulin suppresses production of MIF, TNF-alpha, IL-1, IL-6, and free radicals, enhances endothelial NO generation, and enhances the production of anti-inflammatory cytokines IL-4, and IL-10, corrects stress hyperglycemia and improves myocardial function. This supports my earlier proposal that insulin (with or without glucose and potassium) therapy to maintain euglycemia suppresses the inflammatory response, improves myocardial function, and thus, is of benefit in acute myocardial infarction, sepsis andseptic shock.
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PMID:Insulin in sepsis and septic shock. 1462 Oct 41

Individuals vary considerably in their susceptibility to infection and in their ability to recover from apparently similar infectious processes. These differences can be partially explained by polymorphisms of the genes encoding proteins involved in mediating and controlling the innate immune response, the inflammatory cascade, coagulation, and fibrinolysis. It is evident from experimental studies that dysregulation of the coagulation system, which is characteristic of the pathophysiology of septic shock (a procoagulant and antifibrinolytic state), contributes to systemic inflammation and death in sepsis. Several genetic variations in proteins that increase coagulation or impair anticoagulation and fibrinolysis have been described. Thus, polymorphisms have been reported in prothrombin, fibrinogen, factor V, tissue factor, endothelial protein C receptor, and plasminogen activator inhibitor-1 genes. Some of them are associated with an increased risk of pulmonary emboli, acute myocardial infarction, stroke, and severe sepsis. Hence, the deletion polymorphism (4G) within the promoter region of the plasminogen activator inhibitor-1 gene leads to impaired fibrinolysis and influences the severity and outcome of meningococcal disease and the susceptibility to severe sepsis and multiple organ failure after trauma. The factor V Leiden mutation is associated with thrombotic events and has been reported to exacerbate purpura fulminans in meningococcal infection. Surprisingly, this genetic variant seems to provide a survival advantage in severe sepsis, underlying the extreme complexity of the interaction between inflammation and coagulation. The study of genetic polymorphisms might provide important insights into the pathogenesis of severe sepsis and could make it possible to identify individuals who are at risk of developing or dying of severe infections. As genetic associations are discovered, medical practice can become more preemptive, using the predictive ability of genetics to anticipate disease and recommend therapy.
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PMID:Importance of hemostatic gene polymorphisms for susceptibility to and outcome of severe sepsis. 1511 37

Adrenomedullin (AM) is a peptide that possesses potentially beneficial properties. Since the initial discovery of the peptide by Kitamura et al. in 1993, the literature has been awash with reports describing its novel mechanisms of action and huge potential as a therapeutic target. Strong evidence now exists that AM is able to act as an autocrine, paracrine, or endocrine mediator in a number of biologically significant functions, including the endothelial regulation of blood pressure, protection against organ damage in sepsis or hypoxia, and the control of blood volume through the regulation of thirst. Its early promise as a potential mediator/modulator of disease was not, however, entirely as a result of the discovery of physiological functions but due more to the observation of increasing levels measured in plasma in direct correlation with disease progression. In health, AM circulates at low picomolar concentrations in plasma in 2 forms, a mature 52-amino acid peptide and an immature 53-amino acid peptide. Plasma levels of AM have now been shown to be increased in a number of pathological states, including congestive heart failure, sepsis, essential hypertension, acute myocardial infarction, and renal impairment. These earliest associations have been further supplemented with evidence of a role for AM in other pathologies including, most intriguingly, cancer. In this review, we offer a timely review of our current knowledge on AM and give a detailed account of the putative role of AM in those clinical areas in which the best therapeutic opportunities might exist.
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PMID:The clinical relevance of adrenomedullin: a promising profile? 1546 89

Although frequently asymptomatic, homozygous C2 deficiency (C2D) is known to be associated with severe infections and rheumatic disease. We describe the clinical findings in 40 persons with C2D from 33 families identified in Sweden over 25 years. Medical records covering 96% of the accumulated person-years were reviewed, giving a mean observation time of 39 years (range, 1-77 yr). Severe infection was the predominant clinical manifestation in the cohort: 23 patients had a past history of invasive infections, mainly septicemia or meningitis caused by Streptococcus pneumoniae, and 12 patients had repeated infections of this kind. Nineteen patients had at least 1 episode of pneumonia, and recurrent pneumonia was documented in 10 patients. Repeated infections occurred mainly during infancy and childhood. Systemic lupus erythematosus was found in 10 patients. Another 7 patients had undifferentiated connective tissue disease (n = 4) or vasculitis (n = 3). We found no correlation between susceptibility to invasive infection and rheumatologic disease. Cardiovascular disease occurred at a high rate, with a total of 10 acute myocardial infarctions and 5 cerebrovascular episodes in 6 patients. Causes of death among the C2D patients were infection (n = 5), acute myocardial infarction (n = 3), and cancer (n = 1). We suggest that severe infection may be the principal clinical manifestation of C2D. We also provide novel evidence for a possible role of C2D in the development of atherosclerosis consistent with findings in mannan-binding deficiency and experimental C3 deficiency. In addition, we confirm the well-known association between C2D and systemic lupus erythematosus.
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PMID:Hereditary C2 deficiency in Sweden: frequent occurrence of invasive infection, atherosclerosis, and rheumatic disease. 1564 97

Inflammation is an important indicator of tissue injury. In the acute form, there is usually accumulation of fluids and plasma components in the affected tissues. Platelet activation and the appearance in blood of abnormally increased numbers of polymorphonucleocytes, lymphocytes, plasma cells and macrophages usually occur. Infectious disorders such as sepsis, meningitis, respiratory infection, urinary tract infection, viral infection, and bacterial infection usually induce an inflammatory response. Chronic inflammation is often associated with diabetes mellitus, acute myocardial infarction, coronary artery disease, kidney diseases, and certain auto-immune disorders, such as rheumatoid arthritis, organ failures and other disorders with an inflammatory component or etiology. The disorder may occur before inflammation is apparent. Markers of inflammation such as C-reactive protein (CRP) and urinary trypsin inhibitors have changed our appraisal of acute events such as myocardial infarction; the infarct may be a response to acute infection and (or) inflammation. We describe here the pathophysiology of an anti-inflammatory agent termed urinary trypsin inhibitor (uTi). It is an important anti-inflammatory substance that is present in urine, blood and all organs. We also describe the anti-inflammatory agent bikunin, a selective inhibitor of serine proteases. The latter are important in modulating inflammatory events and even shutting them down.
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PMID:Pathophysiology and diagnostic value of urinary trypsin inhibitors. 1565 36

Total 198 episodes of Duke "definite" infective endocarditis (IE) in 192 patients observed over last 10 years were studied [141 males and 51 females, mean age 27.6+/-12.7 years (range 4-68 years)]. Majorities of patients (76.5%) were below 40 years of age. Rheumatic heart disease (RHD) was the commonest underlying heart disease (present in 46.9% patients). Probable source of infection could be identified in only 16.6% episodes. None of our patient was intravenous drug abuser. Fever (90.0%), anemia (81.0%), clubbing (58.1%), splenomegaly (60.6%), changing/new murmur (22.7%) were the common clinical findings. Vegetations were present in 89.9% episodes. Blood cultures were positive in 134 (67.7%) episodes (streptococci in 23.2%, staphylococci in 19.7%, gram negative in 13.6%, enterococci in 8.1%, polymicrobial and fungal in 1.5% episodes each). Complications were cardiovascular [congestive heart failure (CHF) in 41.9%, atrioventricular block in 1.5%, cardiac temponade and acute myocardial infarction in 0.5% each), neurological in 16.6%, renal in 13.1% and embolisms in total 21.7% episodes. Total 182 (91.9%) episodes in 176 patients were managed completely [(medical in 140 (76.9%) and surgical in 42 (23.1%) episodes] while patients in remaining 16 (8.1%) episodes left against medical advises before completion of therapy. Total 21% patients (37 out of 176 completely treated patients) died during therapy (cause of deaths; CHF in 11, septicemia in 10, cerebral embolism in 7, post cardiac surgery in 5, ruptured cerebral mycotic aneurysm in 2, ventricular tachycardia in 2 patients). On stepwise logistic regression analysis; cardiac abscess and CHF were independent predictors of cardiac surgery. Similarly, CHF, renal failure and prosthetic valve dysfunction were independent predictors of mortality. To conclude, spectrum of IE in our country is different from the west, but quite similar as reported from developed countries about 40 years ago. IE in our country occurs in relatively younger population with RHD as the commonest underlying heart disease. Streptococci are still the commonest responsible microorganisms. Morbidity and mortality are still high. Early cardiac surgery, whenever indicated, helps in improving outcome of these patients.
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PMID:Characteristics of infective endocarditis in a developing country-clinical profile and outcome in 192 Indian patients, 1992-2001. 1568 75

The objective of the study was to assess the efficacy of antiviral therapy in patients with hepatitis C virus (HCV) recurrence after liver transplantation (OLT). We included 30 patients of mean age 56 years, who experienced HCV recurrence after OLT. Mean time from OLT to the beginning of therapy was 57 months (median: 43 months). All of them were on monotherapy: tacrolimus (n = 21), cyclosporine (n = 6), and mycophenolate mofetil (n = 3). Fourteen had previously been diagnosed with allograft HCV cirrhosis. Patients were treated with peginterferon alpha 2b (1.5 mug/kg/weekly SC) and ribavirin (10.6 mg/kg/d) for 48 (genotypes 1, 4) or 24 weeks (genotypes 2, 3). After a mean follow-up of 20 months, two patients had died due to biliary sepsis (while on therapy) and acute myocardial infarction (7 months after the end of therapy). End of treatment virological response was achieved in 19 patients (63.3%) and sustained virological response (SUR) in 14 (46.7%). Comparing cirrhotic and noncirrhotic patients, SVR was achieved in seven patients in both groups (50% vs 43.8%; P = .732). Every patient had some adverse event; in 11 patients (36.7%) it was withdrawn (seven cirrhotic and four noncirrhotic; P < .05), and in 12 the starting dose was decreased (40%). There were neither rejection episodes nor cirrhotic complications during therapy, but infections were more common in cirrhotic patients (57% vs 25%; P < .05). In HCV cirrhotic transplanted patients the sustained virological response to combined antiviral therapy was similar to that in noncirrhotic patients, but severe adverse events including infections were much more common.
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PMID:Peginterferon and ribavirin in patients with HCV cirrhosis after liver transplantation. 1596 80

In Germany, the mortality from sepsis remains high, and up to 60,000 patients die from it each year. Thus, sepsis is the third most common cause of death. More deaths occur only from coronary heart disease and acute myocardial infarction. In the last 3-4 years, substantial progress in sepsis therapy has been made. Based on these achievements, there is hope of reducing sepsis mortality by 25% in the next few years. Implementing new medical evidence in this context into daily clinical intensive care remains a major hurdle. The early diagnosis of sepsis prior to the onset of clinical deterioration is of particular interest, because this would increase the possibility of early and specified treatment, which is in turn the major determining factor of mortality in septic patients.
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PMID:[New approaches to intensive care for sepsis]. 1607 47

An ideal cardiac biochemical marker should have not only high sensitivity but also high specificity to myocardial infarction. The creatine kinase-MB, a relatively specific cardiac marker, could be elevated in situations other than acute myocardial infarction, such as renal failure, muscular injury, and myopathy. Although these are more specific than creatine kinase-MB, cardiac troponins have also been reported to be elevated in conditions other than acute myocardial infarction, such as chronic renal failure, acute myocarditis, cardiomyopathy, congestive heart failure, pulmonary embolism, rhabdomyolysis, sepsis, and left ventricular hypertrophy. With the ongoing research in this field, future holds hopes of finding an ideally specific marker of myocardial infarction, but until then biochemical markers should be used in conjunction with clinical assessment and electrocardiography in making the diagnosis of myocardial infarction, and the patients should not be treated merely on the basis of elevated serum levels of cardiac biochemical markers.
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PMID:Role of biochemical markers in diagnosis of myocardial infarction. 1616 23

The pathogenic, diagnostic and therapeutic landscape of sepsis is no longer confined to the intensive care unit: many patients from other portals of entry to care, both outside and within the hospital, progress to severe disease. Approaches that have led to improved outcomes with other diseases (e.g., acute myocardial infarction, stroke and trauma) can now be similarly applied to sepsis. Improved understanding of the pathogenesis of severe sepsis and septic shock has led to the development of new therapies that place importance on early identification and aggressive management. This review emphasizes approaches to the early recognition, diagnosis and therapeutic management of sepsis, giving the clinician the most contemporary and practical approaches with which to treat these patients.
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PMID:Early and innovative interventions for severe sepsis and septic shock: taking advantage of a window of opportunity. 1624 3


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