Air spaces of the temporal bone: a morphometric analysis with clinical implications.

BACKGROUND: The main objective of the present study was to analyse the morphological variations of the air spaces of the temporal bone, that is, the pneumatized and air-filled spaces of the temporal bone cavities. MATERIALS AND METHODS: A total of 99 sides were analysed. Temporal bone pneumatic spaces (TBPS) were defined as the free spaces inside the cavities of the temporal bone filled with air, excluding the volume of the structures present in the investigated region. Total volumes of TBPS were calculated as the sum of total volumes of mastoid air cells (MAC), tympanic cavity (TC), and external auditory canal (EAC). Analyses were performed considering the general population and the female and male subgroups. RESULTS: The overall results obtained on Polish population were set as follows: the median total volume of TBPS was demonstrated at 7882.58 mm3 (lower quartile [LQ]: 6200.56 mm3; higher quartile [HQ]: 10393.16 mm3). The median volume of MAC was set at 5813.05 mm3 (LQ: 4224.94 mm3; HQ: 8181.81 mm3). The median of the total volume of the EAC was demonstrated at 1294.36 mm3 (LQ: 1099.68 mm3; HQ: 1627.84 mm3). CONCLUSIONS: In the present study, the morphometric properties of the temporal bone cavities were analysed. The results showed that the total volume of the MAC was, on average, lower in women than in men. This should be taken into account when performing procedures on the mastoid, such as mastoidectomies. It is hoped that the results of this study can help reduce potential surgical complications associated with otological procedures.

The occipital-vertebral anastomosis revisited.

BACKGROUND: The goal of the study was to provide relevant data about the location and prevalence of the occipital artery-vertebral artery (OA-VA) anastomosis in patients without visible occlusive disease, as well as to thoroughly discuss the clinical significance of these anastomotic channels. Furthermore, the morphometric properties of the OA and its branches were also analysed. MATERIALS AND METHODS: A retrospective study was carried out to indicate anatomical variations, their prevalence, and morphometrical data on the OA and its branches. The study was performed on 55 randomly selected computed tomography angiographies (CTA) of the head and neck region. Each CTA result was analysed bilaterally. Thus, 110 results were originally assessed. RESULTS: The OA median maximal diameter was demonstrated at 4.85 mm (lower quartile [LQ]: 4.11; upper quartile [UQ]: 5.53) and the median maximal diameter of VA at 3.60 mm (LQ: 2.79; UQ: 4.38). The distances between OA and its branches were also measured giving a median result of 21.73, 30.29, 60.84, 34.88, 18.02, 55.16 mm for the lower and upper sternocleidomastoid branch, meningeal branch, mastoid branch, and descending branch, respectively. The median distance between OA and its first anastomosis was set to be 51.15 mm (LQ: 37.20; UQ: 60.10). Moreover, a set of additional measurements was carried out in order to create a three-dimensional anatomical heat-map of the occurrence of the OA-VA anastomosis. CONCLUSIONS: Knowledge about the anatomy of the OA-VA anastomosis might be of immense importance to avoid potentially fatal complications during embolisation of the OA and its branches.

Correlation of morphological and radiological characteristics of degenerative disc disease in lumbar spine: a cadaveric study.

BACKGROUND: Intervertebral disc (IVD) degeneration plays a crucial role in the pathophysiology of low back pain. Several grading systems have been developed for both morphological and radiological assessment. The aim of this study was to assess the morphological and radiological characteristics of IVD degeneration and validate popular radiological Pfirrmann scale against morphological Thompson grading system. MATERIALS AND METHODS: Full spinal columns (vertebrae L1-S1 and IVD between them) were harvested from cadavers through an anterior dissection. Magnetic resonance imaging scans of all samples were conducted. Then, all vertebral columns were cut in the midsagittal plane and assessed morphologically. RESULTS: A total of 100 lumbar spine columns (446 IVDs) were included in the analysis of the degeneration grade. Morphologic Thompson scale graded the majority of discs as grade 2 and 3 (44.2% and 32.1%, respectively), followed by grade 4 (16.8%), grade 1 (5.8%) and grade 5 (1.1%). The radiologic Pfirrmann grading system classified 44.2% of discs as grade 2, 32.1% as grade 3, 16.8% as grade 4, 5.8% as grade 1, and 1.1% as grade 5. The analysis on the effect of age on degeneration revealed significant, although moderate, positive correlation with both scales. Analysis of the agreement between scales showed weighted Cohen's kappa equal to 0.61 (p < 0.001). Most of the disagreement occurred due to a 1 grade difference (91.5%), whereas only 8.5% due to a 2 grade difference. CONCLUSIONS: With the increase of the prevalence of IVD disease in the population, reliable grading systems of IVD degeneration are crucial for spine surgeons in their clinical assessment. While overall there is agreement between both grading systems, clinicians should remain careful when using Pfirrmann scale as the grades tend to deviate from the morphological assessment.

Clearance of infection with Mycobacterium bovis BCG in mice is enhanced by treatment with S28463 (R-848), and its efficiency depends on expression of wild-type Nramp1 (resistance allele).

The mouse bcg host resistance gene is known to control the activation of host macrophages for killing of intracellular parasites like Leishmania donovani as well as intracellular bacteria, including Mycobacterium bovis BCG and Salmonella enterica serovar Typhimurium. The Nramp1 gene has been mapped to this locus and affects the efficiency of macrophage activation. It has been shown that imidazoquinoline compounds, including S28463, are able to improve the clearance of a number of intracellular pathogens such as herpes simplex virus 2, human papillomavirus, and Leishmania. The goal of this study was to determine whether S28463 is efficient against infection with another intracellular pathogen, M. bovis BCG, and to determine the molecular basis underlying this effect. To achieve this, B10A.Nramp1(r) and B10A.Nramp1(-/-) mice were infected with M. bovis BCG and treated with S28463. The bacterial content in the spleen from these mice was assayed by a colony-forming assay. In addition, in vitro experiments were performed using bone marrow-derived macrophage cell lines from these mice. These cells were treated with S28463 and/or gamma interferon (IFN-gamma), and nitric oxide (NO) production was measured. Our study was able to show that S28463 acts in synergy with IFN-gamma to increase the production of NO in vitro. We were also able to demonstrate that mice that carried the resistant allele of the Nramp1 gene and were infected with M. bovis BCG responded to treatment with S28463, resulting in a decreased bacterial load after 2 weeks of treatment. Mice that do not express the Nramp1 gene responded only to a very large dose of S28463, and the response was not as efficient as that observed in mice carrying a wild-type Nramp1 allele. Our data provide evidence for the potential of S28463 as an immunomodulator that may be helpful in designing efficient strategies to improve host defense against mycobacterial infection.

Glutarimide: a carrier transporting drug through cell membranes.

It is suggested that glutarimide moiety (2,6-piperidinedione) with the intact imide group (OC-NH-CO) and substituted at alpha or beta position in the ring, is acting as the carrier molecule (vector), which transports biologically active substituents (functional groups) through cell membranes. The results obtained from quantum chemical calculations and experimental studies indicate that structural features and physicochemical properties of glutarimide moiety are remarkably similar with those of uracil derivatives. Therefore, glutarimide drug may interact with specific receptors involved in transport of uracil and thymine nucleosides and it may easily cross biological membranes. (c) 2000 Harcourt Publishers Ltd.

Recurrent injury event-time analysis.

Public health decision making based on data sources that are characterized by a lack of independence and other complicating factors requires the development of innovative statistical techniques. Studies of injuries in occupational cohorts require methods to account for recurrent injuries to workers over time and the temporary removal of workers from the 'risk set' while recuperating. In this study, the times until injury events are modelled in an occupational cohort of employees in a large power utility company where employees are susceptible to recurrent events. The injury history over a ten-year period is used to compare the hazards of specific jobs, adjusted for age when first hired, and race/ethnicity differences. Subject-specific random effects and multiple event-times are accommodated through the application of frailty models which characterize the dependence of recurrent events over time. The counting process formulation of the proportional hazards regression model is used to estimate the effects of covariates for subjects with discontinuous intervals of risk. In this application, subjects are not at risk of injury during recovery periods or other illness, changes in jobs, or other reasons. Previous applications of proportional hazards regression in frailty models have not needed to account for the changing composition of the risk set which is required to adequately model occupational injury data. Published in 1999 by John Wiley & Sons, Ltd. This article is a US Government work and is in the public domain in the United States.

Attenuation of MHC class II expression in macrophages infected with Mycobacterium bovis bacillus Calmette-Guérin involves class II transactivator and depends on the Nramp1 gene.

The natural resistance associated macrophage protein 1 (Nramp1) gene determines the ability of murine macrophages to control infection with a group of intracellular pathogens, including Salmonella typhimurium, Leishmania donovani, and Mycobacterium bovis bacillus Calmette-Guérin (BCG). The expression of the resistant allele of the Nramp1 gene in murine macrophages is associated with a more efficient expression of several macrophage activation-associated genes, including class II MHC loci. In this study, we investigated the molecular mechanisms involved in IFN-gamma-induced MHC class II expression in three types of macrophages: those expressing a wild-type allele of the Nramp1 gene (B10R and 129/Mphi), those carrying a susceptible form of the Nramp1 gene (B10S), and those derived from 129-Nramp1-knockout mice (129/Nramp1-KO). Previously, we published results showing that Ia protein expression is significantly higher in the IFN-gamma-induced B10R macrophages, compared with its susceptible counterpart. In this paper, we also show that the higher expression of Ia protein in B10R cells is associated with higher I-Abeta mRNA expression, which correlates with a higher level of IFN-gamma-induced phosphorylation of the STAT1-alpha protein and subsequently with elevated expression of class II transactivator (CIITA) mRNA, compared with B10S. Furthermore, we demonstrate that the infection of macrophages with M. bovis BCG results in a down-regulation of CIITA mRNA expression and, consequently, in the inhibition of Ia induction. Therefore, our data explain, at least in part, the molecular mechanism involved in the inhibition of I-Abeta gene expression in M. bovis BCG-infected macrophages activated with IFN-gamma.

Phenotypic difference between Bcg(r) and Bcg(s) macrophages is related to differences in protein-kinase-C-dependent signalling.

Mice of diverse genetic backgrounds may be classified as being either resistant or susceptible to infection with Mycobacteria. These phenotypes appear to be determined by a single gene on chromosome 1, the Bcg gene, and are expressed at the level of the macrophage in vitro. When compared to macrophages from mice of the susceptible phenotype (Bcg[s]), macrophages from mice of the resistant phenotype (Bcg[r]) show enhanced functional properties including increased expression of MHC class II molecules, increased nitric oxide production, and greater capacity to inhibit the growth of several intracellular pathogens. The bacteriostatic activity of B10R and B10S macrophages correlated with the amount of nitric oxide produced by the macrophages. Since protein kinase C (PKC) has been shown to be involved in the induction of a range of macrophage functional activities, experiments were conducted to examine the possibility that phenotypic differences between Bcg(r) and Bcg(s) macrophages may be related to differences in PKC-dependent signalling. Macrophage cell lines were derived from mice congenic at the Bcg locus that are either resistant (B10R) or susceptible (B10S) to infection with Mycobacteria. In the basal state, PKC-specific activity was significantly increased in the cytosolic fractions of B10R cells when compared to B10S cells. Following phorbol myristate acetate (PMA) treatment and following the stimulation with Mycobacteria bovis BCG, PKC-specific activity increased significantly in membrane fractions of both B10R and B10S cells, but the absolute level was significantly greater in particulate fractions from B10R macrophages. Furthermore, B10R cells had a superior ability to phosphorylate endogenous substrates compared to B10S macrophages. Scatchard analysis of phorbol ester receptors revealed no differences between B10R and B10S cells. In contrast, the sensitivity of partially purified PKC from B10S cells to activation in vitro by diacylglycerol was decreased by approximately 50% when compared to enzyme from B10R cells. Western-blotting analysis using antibodies specific for PKC isoforms (alpha, beta, delta, epsilon, zeta and eta) showed similar levels of PKC isoforms present in B10R and B10S cells. To examine whether differences in PKC activity of B10R and B10S cells had functional consequences, the induction of c-fos gene expression was compared in the two cell lines. In response either to infection with M. bovis BCG or to stimulation with PMA, c-fos mRNA levels in B10R macrophages were increased 2-4-fold in comparison to B10S macrophages. Since we have previously found that the bacteriostatic activity of B10R and B10S macrophages correlated with the amount of nitric oxide produced by the macrophages, we have tested if the enhancement of PKC activity in these macrophages affects their ability to produce nitric oxide. We have found that interferon-gamma-(IFNgamma)-induced secretion of nitric oxide by B10R macrophages could be augmented a few fold by the activation of PKC whereas, in B10S macrophages stimulated with IFNgamma, nitric oxide release could be augmented by only about 10-20%. These results indicate that the differences in PKC activity between B10R and B10S macrophages may contribute to altered responsiveness to IFNgamma that results in different production of effector molecules crucial for bacteriostatic activity against M. bovis BCG.

Regional tracheal blood flow during conventional and high-frequency jet ventilation in suckling pigs.

OBJECTIVE: To determine whether intubation and ventilation with either conventional mechanical ventilation or high-frequency jet ventilation, using dry or humidified gas, could induce regional tracheal ischemia and serve as a basis for the tracheal necrosis observed clinically during ventilation. DESIGN: Prospective, multiple group, controlled experimental study. SETTING: Medical school research laboratory. SUBJECTS: Twenty, 3- to 5-wk-old suckling pigs. INTERVENTIONS: Anesthetized, closed-chest piglets were intubated and ventilated for 30 mins with conventional mechanical ventilation and then ventilated for 2 additional hrs with either conventional mechanical ventilation or high-frequency jet ventilation. Groups were also ventilated, using both modes of ventilation, with either 37 degrees C humidified gas or 25 degrees C dry gas. MEASUREMENTS AND MAIN RESULTS: Blood flow groups were compared during spontaneous breathing, conventional mechanical ventilation, high-frequency jet ventilation and both ventilation modes, using 37 degrees C humidified or 22 degrees C dry inspired gas. Groups were compared, using an analysis of variance with a Newman-Keul's post-test. Regional tracheal blood flow was measured, using radioactive microspheres. Cardiac output and organ blood flows were also monitored. Tracheal blood flow increased 10.3-fold within 30 mins after intubation, but there were no significant differences in regional or total tracheal blood flow between conventional mechanical ventilation and high-frequency jet ventilation, using 37 degrees C humidified gas. Tracheal blood flow was increased further using high-frequency jet ventilation and 25 degrees C dry gas but not conventional mechanical ventilation with dry gas. Although ventilation reduced cardiac output by approximately 30%, there were no significant differences in organ distribution between modes of ventilation. CONCLUSIONS: Acute tracheal hyperemia occurred with intubation and ventilation with both conventional mechanical ventilation and high-frequency jet ventilation but no differences were observed between ventilation modes. Hyperemia was further increased with cool, dry inspired gas, using high-frequency jet ventilation but not conventional mechanical ventilation. Although acute tracheal ischemia was not produced by high-frequency jet ventilation or conventional mechanical ventilation, factors which alter the balance between arterial supply and metabolic demand or induce inflammation may contribute to the tracheal necrosis reported during sustained ventilation.

[Integration of DNA oscillatory vector pSV neo to genome of NIH3T3: importance in investigations of transformation with c-Ha-ras oncogene]. / Integracja DNA wektora wahadlowego pSVneo do genomu komórek NIH3T3: znaczenie w badaniach transformacji onkogenem c-Ha-ras.

Main aim of this study was evaluation of application of stable clones of transforming cells, containing DNA of plasmid vector for the investigation of oncogenes. Plasmid vector was constructed basing on pSV2neo vector, containing activated oncogene c-Ha-ras-1, derived from pT 24-C3 which was followed by evaluation of phenotypic and genetic changes in standard line of NIH3T3 mouse fibroblast line after transfection with constructed plasmid. After two weeks of culture in selective conditions, transformants resistant to geneticin were obtained and analysis of clones was performed after transfection with constructed vector containing ras oncogene and after transfection pSV2neo. Analysis of efficiency of cloning and transformation basing on growth independent from placement and morphology and investigation of karyotypes demonstrated similar irregularities in both investigated groups and subchromosomal aberrations of NIH3T3 cells were even more frequent than in initial lines of NIH3T3 cells. Southern hybridization with pSV2neo-ras probe demonstrated that only restrictive DNA fragments, obtained by Pst1 enzyme contain copies of neo in cell genomes. Integration of gene cf geneticin-resistance increases thus normally unstable genetically NIH3T3 cells.