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

Cytokines mediate and control immune and inflammatory responses. Complex interactions exist between cytokines, inflammation and the adaptive responses in maintaining homeostasis, health, and well-being. Like the stress response, the inflammatory reaction is crucial for survival and is meant to be tailored to the stimulus and time. A full-fledged systemic inflammatory reaction results in stimulation of four major programs: the acute-phase reaction, the sickness syndrome, the pain program, and the stress response, mediated by the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Common human diseases such as atopy/allergy, autoimmunity, chronic infections and sepsis are characterized by a dysregulation of the pro- versus anti-inflammatory and T helper (Th)1 versus Th2 cytokine balance. Recent evidence also indicates the involvement of pro-inflammatory cytokines in the pathogenesis of atherosclerosis and major depression, and conditions such as visceral-type obesity, metabolic syndrome and sleep disturbances. During inflammation, the activation of the stress system, through induction of a Th2 shift, protects the organism from systemic 'overshooting' with Th1/pro-inflammatory cytokines. Under certain conditions, however, stress hormones may actually facilitate inflammation through induction of interleukin (IL)-1, IL-6, IL-8, IL-18, tumor necrosis factor-alpha and C-reactive protein production and through activation of the corticotropin-releasing hormone/substance P-histamine axis. Thus, a dysfunctional neuroendocrine-immune interface associated with abnormalities of the 'systemic anti-inflammatory feedback' and/or 'hyperactivity' of the local pro-inflammatory factors may play a role in the pathogenesis of atopic/allergic and autoimmune diseases, obesity, depression, and atherosclerosis. These abnormalities and the failure of the adaptive systems to resolve inflammation affect the well-being of the individual, including behavioral parameters, quality of life and sleep, as well as indices of metabolic and cardiovascular health. These hypotheses require further investigation, but the answers should provide critical insights into mechanisms underlying a variety of common human immune-related diseases.
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PMID:Cytokine dysregulation, inflammation and well-being. 1616 5

Nutrition support in the critically ill patient is challenging but is even more difficult in a morbidly obese patient. This case report chronicles the care of a 6-foot-tall, 256-kg male (body mass index 76.5 kg/m(2)) who spent over a month in the intensive care unit for respiratory failure, sepsis, and acute renal failure. Parenteral nutrition was provided throughout his critical care course. One of the major difficulties encountered was determining his nutritional needs. A hypocaloric nutritional regimen was used, along with moderate protein provisions. Numerous electrolyte imbalances occurred, including hypercalcemia that did not resolve by eliminating calcium from the parenteral nutrition solution. Enteral nutrition was desired but was not used initially because of a need for vasopressors, a diagnosis of pancreatitis, difficulty in documenting feeding tube placement because of diagnostic limitations secondary to the patient's large size, and concern about managing stools. Eventually, oral intake and supplemental enteral feeding were initiated. Nutrition support team members worked closely with the interdisciplinary care team to develop strategies to manage the nutritional problems related to his obesity. A discussion of the various nutritional issues encountered in the care of this patient is provided. Reasonable nutritional status was achieved, but this case reflects some of the challenges encountered in caring for the nutritional needs of select patient populations in clinical practice and the need for increased research and guidelines in this area.
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PMID:Nutrition support in the morbidly obese, critically ill patient. 1621 17

The problem of obesity has reached epidemic proportions in the USA. More than 50% of adults are obese or overweight. The only therapeutic intervention that provides effective long-term weight loss for the severely obese is bariatric surgery. Roux-en-Y gastric bypass is the most commonly performed bariatric operation in the USA. Anastomotic leaks can cause life-threatening sepsis in the immediate postoperative period or delayed presentations with fistulas. Fibrin sealant and bovine pericardium have been used to reinforce the anastomosis in order to decrease the rate of this dreaded complication. This review will summarize current literature on the subject.
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PMID:Staple-line buttressing material in gastric-bypass surgery. 1629 71

Pyruvic acid, an intermediate metabolite of glucose, an effective scavenger of reactive oxygen species (ROS), inhibits tumor necrosis factor-alpha production and NF-kappaB signaling pathways, reduces circulating levels of HMGB1 (high mobility group B1), decreases COX-2 (cyclo-oxygenase-2), iNOS (inducible nitric oxide synthase), and IL-6 (interleukin-6) mRNA expression in liver, ileal mucosa, and colonic mucosa in animal models with endotoxemia. These studies suggest that pyruvate has potent anti-oxidant and anti-inflammatory actions. Insulin influences the production of pyruvate by its action on glucose metabolism and pyruvate is an insulin secretagogue. This suggests that in metabolic syndrome X, obesity, hypertension, diabetes mellitus, and cancer (where insulin resistance is common due to enhanced TNF-alpha production) pyruvate plays a role. This may have relevance to the use of glucose-insulin-potassium regimen in these clinical conditions, sepsis, and cancer.
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PMID:Pyruvate is an endogenous anti-inflammatory and anti-oxidant molecule. 1664 87

With nearly a third of American adults considered be obese, it is increasingly important that orthopaedic surgeons be familiar with management issues pertinent to these patients. Preoperative examination must assess cardiopulmonary status and other comorbid conditions, most notably diabetes. Intraoperative considerations include requirements for special equipment, patient positioning, intravenous line placement, central monitoring lines, and anesthesia specific to the physiologic changes in obese patients. Postoperatively, obese patients have higher rates of deep vein thrombosis and wound sepsis than do nonobese patients, and they may differ from other patients in supplemental oxygen requirements, medication dosing, and outcomes in intensive care units. Obese patients can successfully undergo virtually all orthopaedic procedures; however, the procedures are frequently more technically challenging, and obese patients appear to have higher rates of prosthetic failure, infection, hardware failure, and fracture malunion, although many of these complications can be minimized by appropriate countermeasures.
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PMID:Perioperative management of the obese orthopaedic patient. 1682 90

The blood-brain barrier (BBB) prevents the unrestricted movement of peptides and proteins between the brain and blood. However, some peptides and regulatory proteins can cross the BBB by saturable and non-saturable mechanisms. Leptin and insulin each cross the BBB by their own transporters. Impaired transport of leptin occurs in obesity and accounts for peripheral resistance; that is, the condition wherein an obese animal loses weight when given leptin directly into the brain but not when given leptin peripherally. Leptin transport is also inhibited in starvation and by hypertriglyceridemia. Since hypertriglyceridemia occurs in both starvation and obesity, we have postulated that the peripheral resistance induced by hypertriglyceridemia may have evolved as an adaptive mechanism in response to starvation. Insulin transport is also regulated. For example, treatment of mice with lipopolysaccharide (LPS) increases insulin transport across the BBB by about threefold. Since many of the actions of CNS insulin oppose those of peripheral insulin and since LPS releases proinflammatory cytokines, enhanced transport of insulin across the BBB could be a mechanism which promotes insulin resistance in sepsis. The brain endothelial cells which comprise the BBB secrete many substances including cytokines. Such secretion can be stimulated from one side of the BBB with release into the other side. For example, it appears that adiponectin can inhibit release of interleukin-6 from brain endothelial cells. Overall, the BBB represents an important interface in mediating gut-brain axes.
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PMID:The blood-brain barrier as a regulatory interface in the gut-brain axes. 1690 39

Obesity has reached epidemic proportions over the last few decades. Obesity is associated with increased morbidity and mortality in hypertension, cardiovascular diseases, stroke, and cancer and is feared to decrease overall life expectancy over the next few decades. There is a growing body of evidence suggesting that obesity is a chronic inflammatory disease. Obesity is becoming a cause of concern in critically ill patients as well. Sepsis is the number one cause of morbidity and mortality in noncoronary artery disease critical care units all over the world and is associated with a high cost of care. An increase in morbidity in obese septic patients compared with lean people is a cause of growing concern. Laboratory evidence suggests that there is exaggeration in the inflammatory and prothrombogenic phenotype assumed by obese compared with lean septic animals. The exact mechanisms underlying this phenomenon are unknown. This article reviews some of the pathophysiological processes responsible for the underlying inflammation in obesity and sepsis and reviews the literature for the association of the two.
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PMID:Obesity and sepsis. 1694 44

Hyperglycemia in critical illness is a common complication and a strong independent risk factor for morbidity and death. Intensive insulin therapy decreases this risk by up to 50%. It is unclear to what extent this benefit is due to reversal of glucotoxicity or to a direct effect of insulin, because antiinflammatory effects of insulin have already been described, but the underlying mechanisms are still poorly understood. The insulin receptor is expressed on resting neutrophils, monocytes, and B cells, but is not detectable on T cells. However, significant up-regulation of insulin receptor expression is observed on activated T cells, which suggests an important role during T cell activation. Exogenous insulin in vitro induced a shift in T cell differentiation toward a T helper type 2 (Th2)-type response, decreasing the T helper type 1 to Th2 ratio by 36%. This result correlated with a corresponding change in cytokine secretion, with the interferon-gamma to IL-4 ratio being decreased by 33%. These changes were associated with increased Th2-promoting ERK phosphorylation in the presence of insulin. Thus, we demonstrate for the first time that insulin treatment influences T cell differentiation promoting a shift toward a Th2-type response. This effect of insulin in changing T cell polarization may contribute to its antiinflammatory role not only in sepsis, but also in chronic inflammation associated with obesity and type 2 diabetes.
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PMID:Potential antiinflammatory role of insulin via the preferential polarization of effector T cells toward a T helper 2 phenotype. 1700 95

Anaesthesia to obese patients is a challenge due to specific changes in respiratory and circulatory functions. Obese patients have a higher risk of acquiring nosocomial infections, including wound sepsis. The place for minimal invasive surgery to limit complications in these patients is unresolved. There is need for prophylactic administration of antitrombotics and antibiotics administered on a weight-adjusted basis. The risk induced from anaesthesia and surgery correlates with comorbidity rather than BMI. Obese patients should not be discriminated against when considering a surgical option.
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PMID:[The obese patient]. 1716 58

The measurement of cardiac troponins (cTn) is of considerable usefulness in the diagnosis of acute coronary syndrome. Abnormal levels of serum cTn are occasionally found in patients who are not suffering a myocardial infarction. This may be observed in several well-known situations including pulmonary embolism, pericarditis, myocarditis, coronary vasospasm, sepsis, congestive heart failure, supraventricular tachycardia with hemodynamic compromise, re-nal insufficiency, and prolonged strenuous endurance exercise. Endogenous antibodies such as heterophile antibodies, rheumatoid factor, and other autoantibodies are known to interfere with the immunoassay measurements of many different analytes, including the widely used Abbot AxSYM cTnI analyzer. Other sources of circulating antibodies include immunotherapies, vaccinations, or blood transfusions that may interfere with these immunoassays as well. We examine the case of a 48-year-old man with a history of hypercholesterolemia and obesity who presented with chest pain and was found to have elevated Tn I levels on two separate occasions. Further work-up revealed that the Tn I levels were spuriously elevated because the patient's blood revealed a normal cTnI level when mixed with polyethylene glycol to inactivate any antibodies interfering with the cTnI assay.
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PMID:Falsely elevated cardiac troponin I levels. 1732 64


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