Disease relevance of Sepsis

• Aerosolized surfactant in adults with sepsis-induced acute respiratory distress syndrome. Exosurf Acute Respiratory Distress Syndrome Sepsis Study Group [1].
• Neutropenia, anemia, intravenous-catheter-related adverse events, and sepsis were more common in the group given intravenous ganciclovir [2].
• BACKGROUND: Vitamin A supplementation may reduce the risk of chronic lung disease and sepsis in extremely-low-birth-weight infants [3].
• CONCLUSIONS: Pretreatment with sheep anti-TNF-alpha Fab suppresses Jarisch-Herxheimer reactions that occur after penicillin treatment for louse-borne relapsing fever, reduces the associated increases in plasma concentrations of interleukin-6 and interleukin-8, and may be useful in other forms of sepsis [4].
• Yersinia sepsis in patients with iron overload treated with deferoxamine [5].

Psychiatry related information on Sepsis

• Cases were selected on the basis of (1) adequate clinical histories of nonsteroidal anti-inflammatory drug usage, (2) no neuropathological findings other than Alzheimer disease, and (3) no generalized sepsis at death [6].
• The most common signs of toxicosis after treatment with mitoxantrone were vomiting, anorexia, diarrhea, lethargy, sepsis secondary to myelosuppression, and seizures [7].
• We introduce the term "virulent" Crohn's disease to describe those patients with most or all of the following: young age at onset, multiple surgical procedures, short bowel/malabsorption, chronic steroid therapy, narcotic addiction, and sepsis [8].
• Clinical trial of interactive and videotaped educational interventions reduce infection, reactive depression, and rehospitalizations for sepsis in patients on home parenteral nutrition [9].
• We report on a 26-y-old male subject with a past medical history of epilepsy and intravenous drug abuse, who presented with imminent sepsis and respiratory failure [10].

High impact information on Sepsis

• Treatment of human diseases with recombinant human IL-1Ra showed an absence of benefit in sepsis syndrome [11].
• Dysfunction of endothelial protein C activation in severe meningococcal sepsis [12].
• Plasma thrombomodulin levels in the children with meningococcal sepsis (median, 6.4 ng per liter) were higher than those in the controls (median, 3.6 ng per liter; P=0.002) [12].
• Recombinant human activated protein C for severe sepsis [13].
• METHODS: We assessed the integrity of the endothelium and the expression of thrombomodulin and the endothelial protein C receptor in biopsy specimens of purpuric lesions from 21 children with meningococcal sepsis (median age, 41 months), as compared with control skin-biopsy specimens [12].

Chemical compound and disease context of Sepsis

• Two hundred fifty-eight patients with suspected sepsis were treated with tobramycin or gentamicin in a prospective, randomized, double-blind trial [14].
• Ibuprofen in patients with sepsis [15].
• BACKGROUND: In patients with sepsis the production of arachidonic acid metabolites by cyclooxygenase increases, but the pathophysiologic role of these prostaglandins is unclear [16].
• Medication errors with inhalant epinephrine mimicking an epidemic of neonatal sepsis [17].
• Our data suggest that in patients with established ARDS due to sepsis, aspiration, or a mixed cause, high-dose methylprednisolone does not affect outcome [18].
• The strong relationship of serum Ang-2 with serum tumor necrosis factor-alpha suggests that the latter may participate in the regulation of Ang-2 production in sepsis [19].

Biological context of Sepsis

• TREM-1: a new regulator of innate immunity in sepsis syndrome [20].
• CONCLUSIONS: In this murine model, inhibiting gut epithelial apoptosis by overexpression of Bcl-2 was associated with a survival advantage in P aeruginosa pneumonia-induced sepsis [21].
• Tumor necrosis factor-alpha blockade prevents neutrophil CD18 receptor upregulation and attenuates acute lung injury in porcine sepsis without inhibition of neutrophil oxygen radical generation [22].
• Since systemic and local vasodilatation are hallmarks of sepsis and infection, we studied the direct effect of IL-1 on vascular contractility [23].
• Conclusions: Renal failure is common in patients with cirrhosis and sepsis unrelated to spontaneous bacterial peritonitis and is associated with arterial underfilling and renal vasoconstriction [24].

Anatomical context of Sepsis

• These data indicate that sepsis causes an excessive production of C5a, which compromises the bactericidal function of neutrophils [25].
• Tumor necrosis factor (TNF) released by lipopolysaccharide (LPS)-stimulated mononuclear phagocytes is a critical mediator of sepsis [26].
• Nitric oxide (NO), a free radical that is negatively inotropic in the heart and skeletal muscle, is produced in large amounts during sepsis by an NO synthase inducible (iNOS) by LPS and/or cytokines [27].
• Granulocyte hyporesponsiveness towards TNF in sepsis (with elevated blood levels of endotoxin and TNF) might be a mechanism of self-protection or, to the contrary, might impair a possibly central mode of host defense [28].
• Tumor necrosis factor (TNF alpha), both by direct action and by trafficking cells of the immune system, is implicated in cardiopulmonary derangements and PMN-mediated microvascular injury associated with gram-negative sepsis [22].

Gene context of Sepsis

• Neutralization of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) or interleukin-1 (IL-1), decreases mortality in several animal models of sepsis [29].
• Mice lacking neutrophil elastase reveal impaired host defense against gram negative bacterial sepsis [30].
• Here we report a mutation in a gene coding for a putative transmembrane protein, PGRP-LC, which reduces survival to Gram-negative sepsis but has no effect on the response to Gram-positive bacteria or natural fungal infections [31].
• Destructive mutations of Tlr4 predispose to the development of Gram-negative sepsis, leaving most aspects of immune function intact [32].
• These data implicate IL-10 as a candidate for treatment of bacterial sepsis, and more generally as an effective antiinflammatory reagent [33].
• Treatment with transcutaneous vagus nerve stimulation inhibited HMGB1 levels and improved survival in mice with polymicrobial sepsis, even when administered 24 hrs after the onset of disease [34].
• Our data suggest that a tandem repeat polymorphism (AC)n at position -665 in the CXCL2 gene may be an independent predictor of mortality for severe sepsis [35].
• Orally administered probiotics prevented liver and intestinal damage in a mouse model of sepsis through a PPARgamma-dependent mechanism [36].

Analytical, diagnostic and therapeutic context of Sepsis

• In animal models, inhibition of cyclooxygenase by treatment with ibuprofen before the onset of sepsis reduces physiologic abnormalities and improves survival [16].
• Longitudinal studies of anti-P activity in two patients with psychosis revealed that anti-P levels increased before and during the active phases of psychosis but not during sepsis or other exacerbations of SLE, and that the elevations were selective for anti-P antibodies, as opposed to anti-DNA antibodies [37].
• Notably, blockade of TREM-1 protects mice against LPS-induced shock, as well as microbial sepsis caused by live Escherichia coli or caecal ligation and puncture [38].
• The preliminary results of clinical trials in humans indicate possible efficacy of IL-1ra in sepsis syndrome, rheumatoid arthritis, and GVHD [39].
• In an attempt to understand their biologic basis of action, we used a fluid-phase radioimmunoassay to measure binding between bacterial lipopolysaccharide (LPS) and two IgM mAbs directed to lipid A that are being evaluated for the treatment of gram-negative bacterial sepsis [40].

References