Current opinion in critical care
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Curr Opin Crit Care · Oct 2004
ReviewNonlinear dynamics, complex systems, and the pathobiology of critical illness.
The review considers problems in critical illness and critical care in the context of complex systems science. Normal physiology is characterized by nonlinear dynamics, and it appears that the pathophysiology of critical illness alters those dynamics. ⋯ Physiologic dynamics in health and in critical illness appear to reflect complex, interconnected systems biology. Alterations in illness and during recovery may provide important clues to the underlying structure of the system. With knowledge of the structure, therapy could be better focused toward supporting both function and dynamics, offering hope for improved outcomes.
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Despite substantial advances in our understanding of the biology of sepsis and inflammation, improvements in clinical outcomes have been more sporadic and, with few notable exceptions, are related to improvements in supportive care rather than to specific therapies. As a result, morbidity, mortality, and cost remain high. Investigation into the genetic determinants of this response span a broad spectrum and include those aimed at deciphering the mechanisms and involved pathways on a molecular level, to those aiming to identify how genetic variation may be clinically important. While it is clear that gene sequencing and manipulation of experimental models have provided insight into the biology of the inflammatory response to infection, these technologies and their application to the study of naturally occurring human genetic variation have yet to provide the same insight or clinical benefit. The purpose of this review is to summarize what is known about the genetic determinants of the inflammatory response. We make particular reference to this broad scope of investigation introduced above but with a focus on the present status of studies examining the role of human genetic variation in the risk for and outcome from severe bacterial infection, or sepsis. ⋯ Naturally occurring genetic variants in important inflammatory mediators such as TNF-alpha and TLR4 appear to alter inflammatory responses in numerous experimental and a few clinical models of inflammation. However, inconsistencies exist in the literature regarding the association between these genetic variants and disease (eg, sepsis) susceptibility and prognosis. The main limitations relate to the translation of experimental observations into reproducible genotype-phenotype associations. The reasons for these are multifactorial and include deficiencies in study design (insufficient sample size), and the complexities introduced by background genetic heterogeneity.
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This review discusses the physiology of natriuretic peptides as a group and brain natriuretic peptide (BNP) in more detail. It will also highlight implications for the use of the natriuretic peptides in the diagnosis and treatment of patients with cardiovascular disease. ⋯ Current data suggest that single and serial plasma measurement of BNP concentrations is a useful tool in the diagnosis and risk stratification of patients with heart disease. Nesiritide, the human recombinant form of BNP, is a new promising parenteral treatment in decompensated heart failure.
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Severe sepsis and septic shock are common and deadly conditions for which the epidemiology, pathogenesis, and management continue to evolve. Recent publications (2003 and early 2004) have been systematically reviewed for important new original research and scholarly reviews, with an emphasis on clinical advances in adults. ⋯ The works reviewed reflect the advances in the care of patients with sepsis.