Publications

Schistosomiasis is one of the most common causes of pulmonary arterial hypertension worldwide, but the pathogenic mechanism by which the host inflammatory response contributes to vascular remodeling is unknown. We sought to identify signaling pathways that play protective or pathogenic roles in experimental Schistosoma-induced pulmonary vascular disease via whole-lung transcriptome analysis. Wild-type mice were experimentally exposed to Schistosoma mansoni ova by intraperitoneal sensitization followed by tail-vein augmentation, and the phenotype was assessed by right ventricular catheterization and tissue histology, as well as RNA and protein analysis. Whole-lung transcriptome analysis by microarray and RNA sequencing was performed, and RNA sequencing was analyzed according to two bioinformatics methods. Functional testing of the candidate IL-6 pathway was determined using IL-6 knockout mice and the signal transducers and activators of transcription protein-3 (STAT3) inhibitor S3I-201. Wild-type mice exposed to S. mansoni demonstrated increased right ventricular systolic pressure and thickness of the pulmonary vascular media. Whole-lung transcriptome analysis determined that the IL-6-STAT3-nuclear factor of activated T cells c2(NFATc2) pathway was up-regulated, as confirmed by PCR and the immunostaining of lung tissue from S. mansoni-exposed mice and patients who died of the disease. Mice lacking IL-6 or treated with S3I-201 developed pulmonary hypertension, associated with significant intima remodeling after exposure to S. mansoni. Whole-lung transcriptome analysis identified the up-regulation of the IL-6-STAT3-NFATc2 pathway, and IL-6 signaling was found to be protective against Schistosoma-induced intimal remodeling.

Presensitization with Mtb-derived trehalose 6,6'-dimycolate (TDM; cord factor) followed by challenge with the same glycolipid species resulted in elicitation of stronger inflammatory responses than when mice were similarly challenged with M. bovis-derived TDM. Mice presensitized to the homologous Mtb-derived TDM demonstrated cachexic over a 6 day period, whereas similarly presensitized mice challenged with the M. bovis-derived TDM, or with emulsion control, did not experience weight loss. Examination of inflammatory responses demonstrated increased lung histopathology in the Mtb-derived TDM challenged group, evidenced by severe tissue disruption, cellular influx, vascular occlusion and lymphocytic cuffing, and endothelial cell damage. Histological analysis demonstrated that lung pathology in the M. bovis challenged group was strikingly similar to that of the acute model challenge. Examination of proinflammatory mediators also showed findings consistent with histological manifestation, with significantly elevated TNF-α and IL-1β, as well as IFN-γ, in the homologous TDM challenged group relative to all other groups. Overall, these findings indicate a difference in hypersensitive immune responses to TDM derived from different mycobacterial strains. Development of specific adaptive immune responses to the Mtb-derived TDM were demonstrated that had limited cross-reactivity to that of M. bovis, thus strongly suggesting the presence of hypersensitive epitopes exclusive to Mtb TDM not present on M. bovis-derived TDM.

OBJECTIVE

The majority of orthopaedic surgeons rely on a lateral fluoroscopic image to assess reduction during patella fracture osteosynthesis. However, a comprehensive radiographic description of the lateral view of the patella has not been performed previously, and no accessory views to better visualize specific anatomic features have been developed. The purpose of this study was to provide a detailed anatomic description of all radiographic features of the true lateral of the patella, describe reproducible accessory views for assessing specific features of the patella, and demonstrate their utility in a fracture model.

METHODS

Twelve cadaver knee specimens free of patellofemoral pathology were used, and imaging was performed using standard C-arm fluoroscopy. For each specimen, a true lateral radiographic projection of the patella was obtained and distinct features were noted. Next, an arthrotomy was made and steel wire was contoured and fixed to various anatomic regions of the patella so as to obliterate the radiographic densities on the true lateral projection, thus confirming their anatomic correlation. Ideal views of the lateral and medial facets themselves were determined using radiographic markers and varying amounts of internal or external rotation of the specimen. Last, a transverse osteotomy was created in each patella and the ability of the true lateral and accessory views to detect malreduction was assessed.

RESULTS

The true lateral projection of the patella was obtained with the limb in neutral alignment. Constant radiographic features of the lateral view of the patella include the articular tangent, a secondary articular density of variable length, and a dorsal cortical density. The articular tangent was produced by the central ridge between the medial and lateral facets in all specimens. The secondary articular density was created by a confluence of the edge of the lateral and edge of the medial facets in 5 patellas, a confluence of the edge of the lateral facet and the intersection of the odd and medial facets in 6 patellas, and the edge of the lateral facet alone in 1 patella. The edge of the lateral facet gave a constant contribution to the appearance of the secondary articular density in all cases. A distinct accessory view of the tangent of the lateral facet could be seen with an average of 17 degrees of patella external rotation (range, 12-35 degrees), and the tangent of the medial facet with an average of 26.5 degrees of internal rotation (range, 15-45 degrees). These accessory views were better able to visualize malreduction than the single lateral projection in a fracture model in all specimens.

CONCLUSIONS

Described here is a comprehensive description of the true lateral radiographic view of the patella and accessory views. These views can be used in the evaluation of minimally displaced patella fractures if a computerized tomography is not desired to better assess the true amount of displacement and when assessing intraoperative reduction during patella fracture osteosynthesis.