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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diagnostic medicine has seen significant changes during the past decade. The emergence of proteomics and genomics has significantly increased our understanding of disease. These fields have also revealed the vast array of proteins that are expressed in various disease processes, such as cancer. Measurement of these unique proteins expressed in certain diseases may offer diagnostic clues or allow patient prognosis to be assessed. Another approach is to measure the effects that these ligands have on the structure and function of albumin. Albumin is known to play an important role in modulating the serum concentrations of various proteins produced by tumor cells. In this review, we introduce the reader to the technique of spin labeling followed by electron paramagnetic resonance spectroscopy. This method is a powerful tool for evaluating the structural and functional changes that can occur to albumin following the binding of various ligands. We describe the utility of this technique for the diagnosis of cancer and sepsis, as well as some other novel potential applications.
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PMID:Application of spin label electron paramagnetic resonance in the diagnosis and prognosis of cancer and sepsis. 1878 41

Albumin has been used for volume resuscitation and supplementation in critically ill patients for over 50 years. While regarded as a "gold standard" colloid solution, albumin is associated with substantial cost, and questions have been raised about its safety and efficacy. A large-scale randomised controlled trial (the Saline vs. Albumin Fluid Evaluation [SAFE] study) demonstrated that albumin and saline were clinically equivalent treatments for intravascular volume resuscitation in a heterogenous population of critically ill patients. However, in patients with traumatic brain injury, albumin was associated with a significantly higher mortality and cannot be recommended for acute resuscitation of such patients. A potential beneficial role of albumin in patients with severe sepsis, particularly malaria, requires further study. Extrapolation of the results of the SAFE study to other, synthetic, colloid solutions requires caution, and a randomised controlled trial comparing albumin, starch and crystalloids in patients with severe sepsis is warranted. The safety of synthetic colloids in patients with traumatic brain injury should not be assumed. Although hypoalbuminaemia is associated with increased mortality, use of albumin for volume resuscitation of critically ill patients with a serum albumin concentration < or =25 g/L is not associated with reductions in mortality, duration of ICU stay or mechanical ventilation, or in use of renal replacement therapy. Similarly, there is no substantive evidence to justify the use of hyperoncotic albumin solutions for resuscitation or supplementation in critically ill patients. Albumin is a safe and effective resuscitation solution in critically ill patients without traumatic brain injury. However, the acquisition costs of albumin and synthetic colloids are more than those of crystalloids, and, as yet, colloids have not been proven to confer substantive benefits over crystalloids such as saline.
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PMID:Albumin is a blood product too - is it safe for all patients? 1928 47

A decade ago, albumin dialysis was introduced as a new extracorporeal detoxification method for patients with liver failure. Today, the molecular adsorbent recirculating system is the most frequently used type of albumin dialysis and most studied liver-support technique. Numerous preclinical and clinical studies demonstrated the importance of albumin as a scavenger for molecules with pathophysiological relevance in liver failure. Albumin dialysis enables the selective regeneration of albumin. The resulting increase of albumin binding capacity is paralleled by improvement of central and local hemodynamics and liver, brain, and kidney functions. The treatment can contribute to liver regeneration and prolongation of patient survival in the context of acute liver failure, decompensated chronic liver disease, and bridging of patients to liver transplantation. Proper patient selection is critical for clinical success. Aggressive treatment of infections and sepsis seems to be a decisive prerequisite for its safe and efficient use. Cautious anticoagulation with heparin is the common standard. Citrate use is recommended for patients prone to bleeding. Taken together, albumin dialysis represents a valuable therapeutic tool for the treatment of various types of liver failure. Ongoing and future studies will help define the optimal patient selection and technical process parameters such as session length and frequency of treatment.
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PMID:Albumin dialysis MARS: knowledge from 10 years of clinical investigation. 1973 6

Despite evidence from clinical studies and meta-analyses that resuscitation with colloids or crystalloids is equally effective in critically ill patients, and despite reports from high-quality clinical trials and meta-analyses regarding nephrotoxic effects, increased risk of bleeding, and a trend toward higher mortality in these patients after the use of hydroxyethyl starch (HES) solutions, colloids remain popular and the use of HES solutions is increasing worldwide. We investigated the major rationales for colloid use, namely that colloids are more effective plasma expanders than crystalloids, that synthetic colloids are as safe as albumin, that HES solutions have the best risk/benefit profile among the synthetic colloids, and that the third-generation HES 130/0.4 has fewer adverse effects than older starches. Evidence from clinical studies shows that comparable resuscitation is achieved with considerably less crystalloid volumes than frequently suggested, namely, <2-fold the volume of colloids. Albumin is safe in intensive care unit patients except in patients with closed head injury. All synthetic colloids, namely, dextran, gelatin, and HES have dose-related side effects, which are coagulopathy, renal failure, and tissue storage. In patients with severe sepsis, higher doses of HES may be associated with excess mortality. The assumption that third-generation HES 130/0.4 has fewer adverse effects is yet unproven. Clinical trials on HES 130/0.4 have notable shortcomings. Mostly, they were not performed in intensive care unit or emergency department patients, had short observation periods of 24 to 48 hours, used cumulative doses below 1 daily dose limit (50 mL/kg), and used unsuitable control fluids such as other HES solutions or gelatins. In conclusion, the preferred use of colloidal solutions for resuscitation of patients with acute hypovolemia is based on rationales that are not supported by clinical evidence. Synthetic colloids are not superior in critically ill adults and children but must be considered harmful depending on the cumulative dose administered. Safe threshold doses need to be determined in studies in high-risk patients and observation periods of 90 days. Such studies on HES 130/0.4 are still lacking despite its widespread and increasing use. Because there are safer and equally effective alternatives in the form of crystalloids, use of synthetic colloids should be avoided except in the context of clinical studies.
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PMID:The efficacy and safety of colloid resuscitation in the critically ill. 2178 29

Extracorporeal liver support has been a much studied topic throughout the last 50 years. Albumin dialysis as a therapeutic option for patients with acute liver failure or acute decompensation of chronic liver disease was introduced in the mid-nineties. The Molecular Adsorbent Recirculating System (MARS) is based on the concept of albumin dialysis and allows for the removal of protein-bound as well as water-soluble toxins. Besides its role as a sufficient volume expander human serum albumin is an important scavenger for molecules with pathophysiological relevance in liver failure. Albumin dialysis enables the selective regeneration of patient's albumin resulting in an increase of albumin binding capacity. Clinically, an improvement of central and local hemodynamics as well as liver-, brain-, and kidney-functions were observed. Thus, the treatment can contribute to liver regeneration and stabilization of vital organ functions and thus help to bridge patients to liver transplantation or to recovery of native liver function. Proper patient selection is critical for clinical success. Aggressive treatment of infections and sepsis seems to be a decisive pre-requisite for its safe and efficient use. Cautious anticoagulation with heparin is the common standard. Citrate use is recommended for patients prone to bleeding. Today, albumin dialysis MARS is among the best studied liver support methods. It appears as a valuable therapeutic tool for the treatment of various complications of of liver failure, especially hemodynamic instability and hepatic encephalopathy. Further studies will need to help defining the optimal patient selection and technical process parameters such as session length and frequency of treatment.
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PMID:Extracorporeal liver support-albumin dialysis with the Molecular Adsorbent Recirculating System (MARS). 2156 51

Albumin has been the focus of literally thousands of articles since its first use in the clinical setting during World War II. Despite being at the centre of several clinical controversies, many questions still remain regarding the use and abuse of albumin. The major physiologic functions include maintaining colloid osmotic pressure, binding and transport of metabolically active molecules, serving as an antioxidant, use as a surrogate marker of nutritional status and predictor of outcome in elective surgical populations, having an anti-thrombotic influence on platelets, aiding in acid-base balance and having a protective influence on capillary membrane integrity. Albumin will continue to be widely used in clinical medicine despite many of the drawbacks. It now appears the benefits in the use of albumin in most cases outweigh the risks. The clinical implications of hypoalbuminaemia as an indicator of surgical or intensive care unit (ICU) outcome or nutritional status is clearly disease- and organ specific. The use of albumin as a volume expander appears to have limited, if any, benefit over crystalloid. The "secondary" benefits of albumin in specific surgical and intensive-care conditions, such as sepsis and organ dysfunction, are numerous and are well supported in the current literature.
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PMID:Hypoalbuminaemia in the perioperative period: clinical significance and management options. 2192 4

Human serum albumin (HSA) is used as an important plasma volume expander in clinical practice. However, the infused HSA may extravasate into the interstitial space and induce peripheral edema in treating the critical illness related to marked increase in capillary permeability. Such poor intravascular retention also demands a frequent administration of HSA. We hypothesize that increasing the molecular weight of HSA by PEGylation may be a potential approach to decrease capillary permeability of HSA. In the present study, HSA was PEGylated in a site-specific manner and the PEGylated HSA carrying one chain of polyethylene glycol (PEG) (20 kDa) per HSA molecule was obtained. The purity, PEGylated site and secondary structure of the modified protein were characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), thiol group blockage method and circular dichroism (CD) measurement, respectively. In addition, the pharmacokinetics in normal mice was investigated, vascular permeability of the PEGylated HSA was evaluated in lipopolysaccharide (LPS)-induced lung injury mouse model and the pharmacodynamics was investigated in LPS-induced sepsis model with systemic capillary leakage. The results showed that the biological half-life of the modified HSA was approximately 2.3 times of that of the native HSA, PEG-HSA had a lower vascular permeability and better recovery in blood pressure and haemodilution was observed in rats treated with PEG-HSA. From the results it can be inferred that the chemically well-defined and molecularly homogeneous PEGylated HSA is superior to HSA in treating capillary permeability increase related illness because of its longer biological half-life and lower vascular permeability.
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PMID:Site-specific chemical modification of human serum albumin with polyethylene glycol prolongs half-life and improves intravascular retention in mice. 2238 12

Along with redistributive shock, myocardial dysfunction is now recognized as highly prevalent in early severe sepsis. Indeed, aside from their distinct loading potency, resuscitation fluids have been poorly investigated as to their specific molecular impact on myocardial dysfunction. The objective of this study was to evaluate the load-independent biological impact of different resuscitation fluids on endotoxin-induced myocardial dysfunction. Adult rats implanted with a central venous catheter were given an intraperitoneal injection of endotoxin (lipopolysaccharides [LPSs], Escherichia coli, 10 mg/kg) or normal saline (sham) and subsequently infused or not with similar "fluid potency" loading resuscitation fluid (normal saline, albumin [Alb], or hypertonic saline solution) for 6 to 24 h, followed by echocardiographic and hemodynamic monitoring together with biochemical and histopathologic evaluation. Intervention was to assess the selective influence of load-independent fluid infusion on the aforementioned parameters in groups of animals challenged or not with LPS. At comparative plasma volumes, Alb improved myocardial homeostasis after LPS challenge by (i) reducing left ventricular relative wall diastolic thickness, interstitial space enlargement, and endogenous Alb content; (ii) limiting cardiac apoptosis and sustaining extracellular signal-regulated mitogen-activated protein kinase activation; and (iii) enhancing the expression pattern of heme-oxygenase 1/inducible nitric oxide synthase. Hypertonic saline solution was also cardioprotective by early prevention of myocardial dysfunction and by reducing cardiac apoptosis. Fluid infusions have distinct load-independent structural/biological impacts on endotoxin-induced myocardial dysfunction. Albumin and hypertonic saline solution are the most pleiotropic fluids in protecting the heart after a "sepsis" hit.
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PMID:Resuscitation fluids and endotoxin-induced myocardial dysfunction: is selection a load-independent differential issue? 2277 10

Since the introduction of human serum albumin as a plasma expander in the 1940s, considerable research has allowed a better understanding of its biochemical properties and potential clinical benefits. Albumin has a complex structure, which is responsible for a variety of biological functions. In disease, the albumin molecule is susceptible to modifications that may alter its biological activity. During the last decades, different methods to measure albumin function have been developed. Recent studies have shown that not only albumin concentration but also albumin function is reduced in liver failure. This observation led to the concept of effective albumin concentration, which represents the fact that plasma albumin concentration does not reflect its function. Indeed, in liver disease albumin function is several times less than its concentration. In patients with cirrhosis, albumin infusion reduces mortality in patients with spontaneous bacterial peritonitis and improves outcome following large volume paracentesis. In combination with vasoconstrictors, albumin is useful in the management of patients with hepatorenal syndrome. Its role is being investigated in a large number of indications, which rely on its volume and nonvolume expansion functions such as stroke, severe sepsis, Alzheimer's disease, malaria, burns, and ovarian hyperstimulation syndrome. This review explores the above concepts, reviews the available evidence for the use of albumin in liver diseases, defines therapeutic limitations, and explores the challenges that should be addressed in future research.
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PMID:Albumin: pathophysiologic basis of its role in the treatment of cirrhosis and its complications. 2342 99

Colloids are frequently used for fluid expansion in the intensive care unit, although its use on several clinical scenarios remains unproven of any relevant clinical benefit. The purpose of this article was to carry out a narrative review regarding the safety and efficacy of colloids in patients with sepsis and septic shock, with emphasis on the most commonly used colloids, albumin and starches. Colloids are effective fluid expanders and are able to restore the hemodynamic profile with less total volume than crystalloids. These properties appear to be preserved even in patients with sepsis with increased capillary permeability. However, some colloids are associated with renal impairment and coagulation abnormalities. Starch use was associated with increased mortality in two large clinical trials. Also, starches probably have significant renal adverse effects and may be related to more need for renal replacement therapy in severe sepsis. Albumin is the only colloid that has been shown safe in patients with sepsis and that may be associated with improved outcomes on specific subpopulations. No trial so far found any robust clinical end point favoring colloid use in patients with sepsis. Because there is no proven benefit of the use of most colloids in patients with sepsis, its use should not be encouraged outside clinical trials. Albumin is the only colloid solution that has proven to be safe, and its use may be considered on hypoalbuminemic patients with sepsis. Nevertheless, there are no robust data to recommend routine albumin administration in sepsis. Starch use should be avoided in patients with sepsis because of the recent findings of a multicenter randomized study until further evidence is available.
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PMID:Colloids in sepsis: evenly distributed molecules surrounded by uneven questions. 2348 2


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