Best zero level for external ICP transducer

Background: Continuous monitoring of intracranial pressure (ICP) was introduced in the 1950s. For correct ICP recordings, the zero-reference point for the external pressure gauge must be placed next to a head anatomical structure. We evaluated different anatomical points as zero reference for the ICP device at different head positions and their relation to brain centre (BC), foramen of Monro (Monro), and brain surface. Methods: Patients referred for neuroimaging due to e.g. headache all having normal 3D MRI scans were selected. Monro, BC, Orbit(O), external auditory meatus (EAM), and orbito-meatal (OM) line were identified and projected to mid-sagittal, or axial images. Each scan was evaluated like lying supine, 45° head elevations, upright, and 45° lateral position. Distances from skin to brain surface, BC, and Monro were measured. All values are presented as mean ± SD and/or range in millimetre. For conversion to mmHg, millimetre was multiplied by 0.074. Results: Twenty MRI scans were examined. A zero reference at EAM or glabella was ideal at BC when head was strict supine or in the lateral position. At 45° head elevation, an overestimation of the BC-ICP by 4.8 ± 0.8 and in upright 5.6 ± 0.5 mmHg was found, and 45° lateral underestimated ICP-BC by 6.3 ± 1.0 mmHg. Monro was situated 45 ± 5 mm rostral to the mid-OM line and 24 (18–31) mm inferior and 13 (8–17) mm in front of BC. A zero-reference point aligned with the highest point of the head underestimated BC-ICP and Monro-ICP. If the ICP reading was added 5.9 or 6.3 mmHg, respectively, a deviation from BC-ICP was ≤ 1.8 mmHg and Monro-ICP was ≤ 0.9 mmHg in all head positions. Conclusions: EAM and glabella are defined anatomical structures representing BC when strict supine or lateral but with 12 mmHg variation with different head positions used in clinical practice. The OM line follows Monro at head elevation, but not when the head is turned. When the highest external point on the head is used, ICP values at brain surface as well as Monro and BC are underestimated. This underestimation is fairly constant and, when corrected for, provides the most exact ICP reading

NEPHRITOGENIC ACTIVITY OF STREPTOCOCCUS PYOGENES emm1 AND emm12 GENOTYPES ISOLATED FROM PATIENTS AND ASYMPTOMATIC CARRIERS

In this paper the nephritogenic activity of Streptococcus pyogenes genotype emm1 and emm12 clinical isolates from scarlet fever patients and healthy children was considered. As earlier established, strains of these types differ in Fc-binding profile, interacting with native IgG and immune complexes (IC), respectively. As expected, all the type emm1 strains bound native IgG; besides, ICs interacted only with strains from patients but not with those from carriers. In contrast, all type emm12 strains appeared to be negative for native IgG, whereas ICs were bound by strains from patients exclusively. None of the tested strains bound IgG3. By immunization of rabbits, binding of native IgG as well as ICs was associated with increasing of anti-IgG antibodies titer, formation of ICs, «crescent» deposition of IgG and C3-complement, local production of the proinflammatory cytokine TNFα, аnd also with accumulation of lymphocytes in kidney tissue. These signs indicated immune inflammation, leading to experimental membrane-proliferative glomerulonephritis (PSGN). It is known that PSGN development depends on IC-binding by tissue FcγR, on complement activation as well as on tissue infiltration by macrophages/monocytes. According to the data of morphometric evaluation the nephritogenic activity of the type emm12 strains exceeded those of type emm1. On testing of three IC-binding emm12 strains in six rabbits, typical PSGN developed in 5 of them and an abortive process in 1 animal. In case of five IgG-binding type emm1 strains, out of ten rabbits full-blown PSGN was observed only in 3 of them, but abortive changes in 5 and negative result in 2 animals. No pathologic changes were elicited by the «carrier» strains of either genotype; the inability of these to bind ICs, according to literature data, could be explained by mutation in the Mga-regulator gene thereby impeding M-proteins synthesis. We conclude that isolation of type emm12 IC-binding strains at acute streptococcal infection should be considered a high risk-factor for postinfectious sequelae development. The rabbit model of PSGN used in this research thus allowed to reveal some main stages and features of its pathogenesis

CAPACITY OF GROUP A (TYPE M12) STREPTOCOCCI TO BIND IMMUNE COMPLEXES AND THEIR ROLE IN PATHOGENESIS OF POST-STREPTOCOCCAL GLOMERULONEPHRITIS

Abstract. In former studies, using an experimental rabbit model of acute post-streptococcal glomerulonephritis (GAS), we have proven a role of M-like Fc-binding streptococcal proteins (IgG FcBPs) for initiating destructive/degenerative lesions of renal glomeruli that are characteristic to membranous/proliferative and destructive glomerulonephritis. This activity was shown for the strains of types 1, 22 and 49. Their clinical isolates are able to bind Fc fragment of human and rabbit IgG, and are considered as an etiological agent of glomerulonephritis. It is well known that GAS strains of M12 serotype (commonly nephritogenic) are not able to interact with IgG monomers, and usually bind aggregated IgG, in spite of participation of IgG FcBPs in the both events.In present study, the GAS reference strain M12(1800) and twenty-one clinical strains of M12 type isolated from the patients with acute poststreptococcal glomerulonephritis (APSGN) were tested for binding with two artificial immune complexes (ICs): (i) peroxidase – antiperoxidase rabbit IgG (PAP) and (ii) tetanus toxoid – anti-tetanus human IgG (TAT). Streptococcal strain M12 (1800), as well as the majority of clinical isolates (19 strains) were strongly positive for the binding of both ICs tested. Using previously described model of experimental streptococcal glomerulonephritis rabbits were injected with heat-killed M12(1800) and each of two clinical isolates M12(257) and M12(305), positive and negative for the binding of ICs, respectively. Renal tissue material of rabbits injected with M12(1800) and M12(257), but not M12(305), showed strong inflammatory and degenerative changes compatible with pattern observed in APSGN. Streptococcal strains M12(1800) and M12(257), in contrast to strain M12(305), induced circulating anti-IgG, tissue deposition of IgG and C3 as well as secretion of IL-1β, Il-6 and TNF-α by the glomerular mesangial and endothelial cells. Our experimental data suggest that the IC-binding ability of type M12 streptococci should be of importance for the nephritogenic potential of these GAS serotype strains

PURIFIED IGG F C-BINDING PROTEINS FROM M22 GROUP A STREPTOCOCCUS ARE ABLE TO INDUCE EXPERIMENTAL GLOMERULONEPHRITIS

Abstract. Pathogenesis of acute post-streptococcal glomerulonephritis (APSGN), a major complication of group A streptococcal (GAS) throat or skin disease, remains unclear. Over years, various theories were based on distinct streptococcal extracellular factors, as well as immunological mimicry of streptococci for renal tissue antigens was considered. Previously we reported that a lot of clinical GAS isolates with proven nephritogenic ability show a non-immune binding of monomeric or aggregated IgG. Moreover, using a rabbit model of APSGN, we obtained evidence for important causative role of streptococcal IgG Fc-binding proteins (IgG FcBPs) belonging to the M family surface proteins. I.e., rabbits injected by whole IgG FcBP-positive streptococci showed induction of renal glomerular changes, with deposition of IgG and complement C3, resembling the picture recorded in human APSGN. These typical renal changes were always preceded by development of circulating anti-IgG antibodies. Present study was performed in the same rabbit model. Both purified IgG FcBPs isolated from type M22 GAS were found to elicit glomerular degenerative damage of renal glomeruli comparable to those caused by whole bacteria, as well as induce anti-IgG antibodies, deposition of IgG and C3 complement and production of proinflammatory cytokines (IL-1β, TNFα, IL-6) by glomerular mesangial and endothelial cells. By contrast, rabbits injected with proteins A or G, IgG FcBPs of S. aureus and group G streptococci, respectively, exhibited only low levels of circulating anti-IgG and reversible glomerular changes. In these settings, we have not observed any features of membranousproliferative glomerulonephritis (GN) resembling morphological traits of acute post-streptococcal GN in humans. These data correlated with results obtained after injection of intact Staphylococcus aureus (Cowan 1 strain) or group G streptococci (G148 strain). Both microbial types are known to harbor IgG Fc-binding proteins (А and G, respectively). These results support the idea that GAS IgG FcBPs are unique in their ability to initiate strong post-streptococcal glomerular changes and could be considered as important factors in pathogenesis of APSGN similar to acute post-streptococcal GN in humans