User:Robert Badgett/ms4
Vic
Treatment
Human recombinant activated protein C can reduce 28-day mortality among patients with multiple-organ dysfunction syndrome according to a randomized controlled trial.[1] The relative risk reduction was 21.8%. For patients at similar risk to those in this study (33.9% had 28-day mortality), this leads to an absolute risk reduction of 7.4% and 13.5 patients must be treated for one to benefit (number needed to treat = 13.5). Click here to adjust these results for patients at higher or lower risk of 28-day mortality.
Etiology
Since Multiple Organ Dysfunction Syndrome is well-established as the final stage of a continuum (Systemic Inflammatory Response Syndromeà sepsisàsevere sepsisàmultiple organ dysfunction syndrome), current investigators are looking into genetic targets for possible gene therapy to prevent the sepsis cascade from occurring. Some authorshave conjectured that the inactivation of NF-KB and AP-1 would be appropriate targets in preventing sepsis and Systemic Inflammatory Response Syndrome. [2] These two genes are proinflammatory. However, the negative side of inactivation of these genes is that they are essential components of a normal healthy immune response.
Additionally, some authors have developed a mouse model sepsis via cecal ligation and puncture(CLP). [3] Male Balb/c mice subjected to CLP were given an Il-10-carrying vector]] or an empty control vector. Lung, Liver and kidney tissue destruction were measured by assessing myeloperoxidase and malonialdehyde activity. They assessed the level neutrophil infiltration in lung and liver tissue. IL-10 protein expression was measured using immunohistochemistry. Additionally the expression of Tumor necrosis factor Alpha mRNA was measured at 3,8, and 24 hours after CLP using [[reverse transcription polymerase chain reaction. Their results show significantly reduced organ damage by IL-10 gene transfer, as quantified by reduced myeloperoxidase activity in the lung, liver, and kidney. The malonialdehyde level was not affected by the transfer into the liver. Also the reduced portal tract neutrophilic infiltration and preserved ultrastructure of the hepatocytes also showed that tissue function was not impaired. The lung and kidney TNF-alpha mRNA expression was suppressed markedly in the IL-10 gene therapy group, but liver TNF-alpha mRNA expression varied over time. The investigators concluded that increased IL-10 expression significantly attenuated sepsis-induced Multiplicity of infection.