Definition of a new score for severity of generalizedNeisseria meningitidis infection

Abstract

Neisseria meningitidis infection may present as meningitis or as severe, fulminant sepsis. In order to classify individual patients early according to the expected course of the disease, we developed a score named Neisseria sepsis index [NESI]. The NESI was defined using the parameters heart rate, mean arterial blood pressure, base excess and presence of acute subcutaneous bleeding and/or skin necroses (minimal value [= no evidence for sepsis] NESI 0; maximum value [= most severe sepsis] NESI 8). Seventeen patients with documented, systemic N. meningitidis infection were prospectively assessed for the terminal complement complex (TCC), serum tumour necrosis factor alpha (TNF alpha) levels (as laboratory parameters for severity of sepsis) and NESI score. The evaluation was immediately performed when the patients were admitted to the hospital. The 17 patients showed the following distribution of data: NESI 0 (n = 4), NESI 1 (n = 6), NESI 2 (n = 0), NESI 3 (n = 1), NESI 4 (n = 2), NESI 5 (n = 2), NESI 6 (n = 0), NESI 7 (n = 1), NESI 8 (n = 1). Mortality was 4/17 patients, all had NESI > or = 5. TCC values ranged from 647-6461 ng/ml (normal range: 130-360 ng/ml); and was not correlated to NESI. TNF alpha values ranged from 10-910 pg/ml and were correlated to NESI (r2 = 0.71, n = 17, P < 0.001). In patients with fatal outcome, TNF alpha was 600 +/- 160 pg/ml (mean +/- SEM) and in surviving patients 130 +/- 50 pg/ml (mean +/- SEM). TNF alpha was increased in 15/17 patients when compared to normal controls (< 27 pg/ml). CONCLUSION. The NESI is based on few clinical, objective data, that are available in every hospital. NESI appears to offer an instrument: (1) for making decisions in regard to appropriate monitoring and treatment of vital organ function; and (2) for assessing the quality of care for this life-threatening infection.

Life-threatening heart failure in meningococcal septic shock in children: non-invasive measurement of cardiac parameters is of important prognostic value

“…In combination with a validated severity score [11,20,27,38,45,46] such as the GMSPS, the SF oers a simple and reliable method for a direct therapeutic approach in combination with standard hemodynamic monitoring. Due to the characteristic demonstration of petechiae, purpura and ecchymoses, MSS is the only form of sepsis that can be diagnosed at the bedside.…”

Functionality of intrinsic disorder in tumor necrosis factor‐α and its receptors

“…This TNFR1 domain was shown to possess a structure typical to the members of the death domain superfamily, consisting of six antiparallel ahelices (residues 328-336, 342-349, 353-361, 367-380, 389-398, and 403-412) [193]. 40 A for the backbone atoms, the Nand C-terminal tails of this domain (residues 344-354 and 442-454) were highly disordered, likely due to the high content of proline residues, and loops connecting a-helices were characterized by high structural flexibility [193]. 40 A for the backbone atoms, the Nand C-terminal tails of this domain (residues 344-354 and 442-454) were highly disordered, likely due to the high content of proline residues, and loops connecting a-helices were characterized by high structural flexibility [193].…”

“…Although the helical part of this domain was rather well-organized, with the RMSD for the 20 NMR structures about the mean coordinate positions for residues composing the helical elements being 0. 40 A for the backbone atoms, the Nand C-terminal tails of this domain (residues 344-354 and 442-454) were highly disordered, likely due to the high content of proline residues, and loops connecting a-helices were characterized by high structural flexibility [193]. Figure 7 represents the results of the functional disorder analysis in human TNF-a receptors by D 2 P 2 computational tool (http://d2p2.pro/) [167] and shows that both proteins are predicted to have significant levels of intrinsic disorder, especially in their cytoplasmic domains.…”

“…In healthy individuals, TNF is not generally detectable, whereas raised serum and tissue levels of this protein are detected during infectious and under inflammatory conditions [39,40], with the severity of infections being correlated with the TNF serum levels [36,41,42]. Although TNF-a is mainly produced by activated macrophages, it can be synthetized by a wide range of cells, including neutrophils, Kupffer cells, fibroblasts, smooth and cardiac muscle cells, astrocytes, mast cells, keratinocytes, natural killer (NK) cells, T and B lymphocytes, tumor cells, and endothelial cells [35,43,44].…”

Specific TNF-alpha Inhibition in Cerebral Aneurysm formation and Subarachnoid Hemorrhage

“…Similarly this enzyme is involved in the processing of TNF-alpha receptors which are released by its action to produce circulating forms that act to neutralize the actions of TNF-alpha [8]. TNF-alpha is undetectable in healthy individual and rises primarily in inflammatory or infectious conditions [9,10]. TNF-alpha is undetectable in healthy individual and rises primarily in inflammatory or infectious conditions [9,10].…”