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)

There is currently a vast literature available on the changes in thyroid function tests that occur during non-thyroidal illness. The aetiology of these changes is, however, controversial, especially with respect to whether they play an adaptive role for the organism in order to cope with stress or whether they represent primary pathology of the pituitary-thyroid axis. This is particularly true for critically ill patients, in whom the most significant changes in thyroid function are observed. The changes include low levels of thyroxine and very low levels of tri-iodothyronine, which would, on the surface, appear to indicate hypothyroidism. Therapy with thyroid hormone, as either L-T4 or L-T3, has therefore been suggested because of these low values for thyroid hormones in the blood. It is, however, unclear whether treating these patients with thyroid hormone is beneficial or harmful. Multiple studies have addressed this issue with patients with cardiac disease, sepsis, pulmonary disease (e.g. acute respiratory distress syndrome) or severe infection, or with burn and trauma patients. In spite of a very large number of published studies, it is very difficult to form clear recommendations for treatment with thyroid hormone in the intensive care unit. Instead, we find the evidence far from compelling, and would advise withholding thyroid hormone therapy in the critical care setting in the absence of clear clinical or laboratory evidence for hypothyroidism.
Best Pract Res Clin Endocrinol Metab 2001 Dec
PMID:The controversy of the treatment of critically ill patients with thyroid hormone. 1180 May 18

Adequate adrenocortical function is essential to survive critical illness. Most critically ill patients display an elevated plasma cortisol level, reflecting activation of the pituitary-adrenal axis, which is considered to be a homeostatic adaptation. In the setting of critical illness, the failure of an appropriate neuroendocrine response can lead to the picture of vasopressor-dependent refractory hypotension. This state of relative or functional adrenal insufficiency is characterized by an inadequate production of cortisol in relation to an increased demand during periods of severe stress, particularly prolonged critical illness such as multi-organ failure. This clinical entity, however, lacks clear-cut diagnostic criteria. What are the appropriate cortisol concentrations in the critically ill? Should base-line and adrenocorticotropic hormone-stimulated cortisol concentrations be assessed? The classical adrenocorticotropic hormone stimulation test is often used, but there are problems with interpreting its results. Other diagnostic tools, such as the low-dose adrenocorticotropic hormone test and relative eosinophilia, are promising but also lack proper criteria. A prompt response to hydrocortisone treatment is a major clue to the diagnosis. Recent studies with stress doses of hydrocortisone in sepsis and septic shock have shown a marked haemodynamic improvement, but whether patients with relative adrenal dysfunction benefit most from this treatment and whether there is definitely an effect on outcome is still undecided.
Best Pract Res Clin Endocrinol Metab 2001 Dec
PMID:Relative adrenal failure in intensive care: an identifiable problem requiring treatment? 1180 May 21

Despite the considerable advances made in understanding the pathophysiology of systemic inflammation during critical illness, clinical progress has been elusive as it remains a very deadly condition. Cortisol and thyroid hormone levels can be as predictive of outcome as the commonly used severity parameters (i.e. APACHE). Indeed, levels of endocrine humoral substances such as arachidonic acids, nitric oxide, endothelin, calcitonin precursors, leptin and adenosine correlate with the severity and outcome of critical illness. Furthermore, calcitonin precursors represent a potentially new hormokine paradigm, being transcriptionally activated in all cells in response to infection. The cytokines are immune markers that often correlate with severity and outcome, but their release is transient. In contrast, the so-called acute phase proteins, such as C-reactive protein and serum amyloid A, are highly sensitive to inflammatory activity and can be important markers of severity and outcome. Leukocyte esterase, adhesion molecules, platelet activating factor and activated protein C are additional humoral immune markers; the replacement of the latter has been shown to be a promising therapeutic option. Natriuretic peptides are neurocrine humoral markers that have important cardiovascular implications. The level of macrophage migrating inhibitory factor, released by the pituitary, is elevated in sepsis and counteracts glucocorticoid action. Cellular markers to severe stress include the enhanced expression of protective substances in the form of heat shock proteins. High mobility group-1 is a DNA-binding protein and a late mediator of the inflammatory response. Apoptotic markers such as the soluble fas ligand are also elevated in inflammation. In summary, during critical illness, the endocrine, immune and nervous systems elaborate a multitude of humoral markers, the roles of which merit further scrutiny in order to improve therapeutic outcome.
Best Pract Res Clin Endocrinol Metab 2001 Dec
PMID:Humoral markers of severity and prognosis of critical illness. 1180 May 23

During infection microbes attack host tissues, causing damage to specific organs, sepsis or even death. For proliferation microbes desperately need iron for which they have to compete with the host. Micro-organisms have developed an abundant number of strategies to acquire iron from their specific environment and to transport the element to sites of incorporation into biologically important molecules. As part of the non-specific defence mechanisms against infection, the body modifies iron metabolism in order to make iron less available for micro-organisms. Such processes have a profound effect on the immune system and are also expressed in other forms of inflammation. Microbial iron transport systems are explored as targets for antibiotic treatment and vaccines. In particular, iron chelators, used for the treatment of iron overload may become important drugs for fighting bacterial and viral infections.
Best Pract Res Clin Haematol 2002 Jun
PMID:Iron and infection: competition between host and microbes for a precious element. 1240 15

Procalcitonin (PCT) is increasingly recognised as an important diagnostic parameter in clinical evaluation of the critically ill. This prospective study was designed to investigate PCT as a diagnostic marker of infection in critically ill patients with sepsis. Eighty-five adult ICU patients were studied. Four groups were defined on the basis of clinical, laboratory and bacteriologic findings as systemic inflammatory response syndrome (SIRS) (n = 10), sepsis (n = 16), severe sepsis (n = 18) and septic shock (n = 41). Data were collected including C-reactive protein (CRP), PCT levels and Sequential Organ Failure Assessment and Acute Physiology and Chronic Health Evaluation II scores on each ICU day. PCT levels were significantly higher in patients with severe sepsis and septic shock (19.25 +/- 43.08 and 37.15 +/- 61.39 ng/ml) than patients with SIRS (0.73 +/- 1.37 ng/ml) (P < 0.05 for each comparison). As compared with SIRS patients, plasma PCT levels were significantly higher in infected patients (21.9 +/- 47.8 ng/ml), regardless of the degree of sepsis (P < 0.001). PCT showed a higher sensitivity (73% versus 35%) and specificity (83% versus 42%) compared to CRP in identifying infection as a cause of the inflammatory response. Best cut-off levels were 1.31 ng/ml for PCT and 13.9 mg/dl for CRP. We suggest that PCT is a more reliable marker than CRP in defining infection as a cause of systemic inflammatory response.
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PMID:Reliability of procalcitonin as a severity marker in critically ill patients with inflammatory response. 1250 May 12

Cholestasis of sepsis is a form of hepatocellular cholestasis that occurs as a result of sepsis. Usually, prior to the development of cholestasis, the manifestations of sepsis dominate the clinical picture. The occurrence of cholestasis is without direct bacterial involvement of the biliary system and appears to be mediated systemically by pro-inflammatory cytokines. These cytokines are released in response to the vigorous inflammatory reaction mediated by endotoxinaemia and bacterial wall lipopolysaccharides. The principal cytokines involved are the pro-inflammatory tumour necrosis factor-alpha (TNF-alpha), interleukin (IL) 1-beta and IL-6. Interplay between these cytokines and a series of hepatocyte membrane transporters appears to result in the cholestasis. Management principles focus upon the control of sepsis.
Best Pract Res Clin Gastroenterol 2003 Jun
PMID:Gastrointestinal disorders of the critically ill. Cholestasis of sepsis. 1276 1

Shock liver describes a collecting pool of critically ill patients in whom the elevation of liver function tests or overt hepatic dysfunction is apparent. Different grades of shock liver affect about 50% of all intensive-care patients, varying from a mild elevation of serum aminotransferase and bilirubin levels in septic patients to an acute onset of high serum aminotransferases after haemodynamic shock. Abnormalities can subside within days or progressively deteriorate when persistent hepatic microcirculatory failure is present. Although hepatic injury in critically ill patients influences mortality rates it is underdiagnosed. The underlying pathophysiology involves changes in the portal and arterial blood supply as well as in microcirculation. Cross-talk between hepatocytes, Kupffer cells and endothelial cells, leading to an inflammatory response mediated primarily by tumour necrosis factor-alpha (TNF-alpha), is central to shock liver. The liver is a victim of shock inducers, and can also be the orchestrator of the inflammatory response syndrome (IRS). Hepatic injury by TNF-alpha is modulated by the prevalent pro-inflammatory or anti-inflammatory mediator profile elaborated by Kupffer cells. Kupffer cells additionally participate in the clearance of endotoxin, bacteria and inflammatory mediators and are thereby capable of preventing IRS. The hepatocyte undergoes dramatic alterations in synthetic activity, biliary transport, bile flow and glucose metabolism. Although standard determinations of aminotransferases, coagulation studies, glucose, lactate and bilirubin can detect hepatic injury they only partially reflect the cellular mechanisms driving shock liver. The management of shock liver is focused on the prevention of precipitating causes by controlling sepsis, circulation parameters and metabolism in addition to the cautious monitoring of therapeutic measures that can increase hepatic injury, which include intravenous nutrition, mechanical ventilation and catecholamine administration.
Best Pract Res Clin Gastroenterol 2003 Jun
PMID:Gastrointestinal disorders of the critically ill. Shock liver. 1276 2

Biliary sludge develops commonly in critically ill patients and may be associated with biliary colic, acute pancreatitis or acute cholecystitis. Sludge often resolves upon resolution of the underlying pathogenetic factor. It is generally diagnosed on sonography. Treatment of sludge itself is unnecessary unless further complications develop. Acute acalculous cholecystitis also develops frequently in critically ill patients. It may be difficult to diagnose in these patients, manifesting only as unexplained fever, leukocytosis or sepsis. Sonography and hepatobiliary scintigraphy are the most useful diagnostic tests. Management decisions should take into account the underlying co-morbid conditions. For many patients, percutaneous cholecystostomy may be the best management option. Cholecystostomy may also provide definitive drainage as patients recover and underlying critical illness resolves.
Best Pract Res Clin Gastroenterol 2003 Jun
PMID:Gastrointestinal disorders of the critically ill. Biliary sludge and cholecystitis. 1276 3

Non-occlusive mesenteric ischaemia is characterized by gastrointestinal ischaemia with normal vessels. In gastroenterology it is recognized as rare disease occasionally causing acute bowel infarction or ischaemic colitis. From intensive care literature this disorder is recognized as an early phenomenon during circulatory stress. This early mucosal ischaemia then leads to increased permeability, bacterial translocation, and further mucosal hypoperfusion. The damage is produced mainly during reperfusion following ischaemia with fresh inflow of oxygen and outflow of waste products into the systemic circulation. The mechanisms underlying non-occlusive mesenteric ischaemia include macrovascular vasoconstriction, hypoperfusion of the tips of the villi and shunting. It is very common in critically ill and perioperative patients, but also occurs in pancreatitis, renal failure and sepsis. Treatment options include aggressive fluid resuscitation and careful choice of vasoactive drugs. Control of reperfusion damage and new endothelin-antagonists are potentially useful new treatment options.
Best Pract Res Clin Gastroenterol 2003 Jun
PMID:Non-occlusive mesenteric ischaemia: a common disorder in gastroenterology and intensive care. 1276 7

Protein C is a vitamin-K-dependent zymogen, whose congenital deficiency state leads to increased risk for venous thrombosis. Activated Protein C (aPC) exerts its anticoagulant function by inhibiting the cofactors in the clotting cascade, Factors Va and VIIIa. In addition, aPC displays anti-inflammatory, anti-apoptotic and profibrinolytic activities. A recombinant form of human aPC (rhAPC) is the first drug reported to improve survival in patients with severe sepsis. The major toxicity associated with treatment is bleeding. Appropriate use of rhAPC depends on an understanding of its mechanisms of action and risk:benefit profile. The goals of this review are: to describe the Protein C pathway; to discuss the definitions, epidemiology and pathophysiology of severe sepsis; to provide a conceptual framework for understanding the role of rhAPC in this syndrome; and to address frequently asked questions about the day-to-day use of this agent.
Best Pract Res Clin Haematol 2004 Mar
PMID:Natural anticoagulant inhibitors: activated Protein C. 1517 65


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