Investigation of the effect of intrauterine inflammation and infection on fetal brain injury using human and animal models

In recent years, increased focus has been placed on the role of intrauterine infection and inflammation in the pathogenesis of fetal brain injury leading to neurodevelopmental disorders such as cerebral palsy. At present, the mechanisms by which inflammatory processes during pregnancy cause this effect on the fetus are poorly understood. Our previous work has indicated an association between experimentally-induced intrauterine infection, increased proinflammatory cytokines, and increased white matter injury in the guinea pig fetus. In order to further elucidate the pathways by which inflammation in the maternal system or the fetal membranes leads to fetal impairment, a number of studies investigating aspects of the disease process have been performed. These studies represent a body of work encompassing novel research and results in a number of human and animal studies. Using a guinea pig model of inflammation, increased amniotic fluid proinflammatory cytokines and fetal brain injury were found after a maternal inflammatory response was initiated using endotoxin. In order to more closely monitor the fetal response to chorioamnionitis, a model using the chronically catheterized fetal ovine was carried out. This study demonstrated the adverse effects on fetal white matter after intrauterine exposure to bacterial inoculation, though the physiological parameters of the fetus were relatively stable throughout the experimental protocol, even when challenged with intermittent hypoxic episodes. The placenta is an important mediator between mother and fetus during gestation, though its role in the inflammatory process is largely undefined. Studies on the placental role in the inflammatory process were undertaken, and the limited ability of proinflammatory cytokines and endotoxin to cross the placenta are detailed herein. Neurodevelopmental disorders can be monitored in animal models in order to determine effective disease models for characterization of injury and use in therapeutic strategies. Our characterizations of postnatal behaviour in the guinea pig model using motility monitoring and spatial memory testing have shown small but significant differences in pups exposed to inflammatory processes in utero. The data presented herein contributes a breadth of knowledge to the ongoing elucidation of the pathways by which fetal brain injury occurs. Determining the pathway of damage will lead to discovery of diagnostic criteria, while determining the vulnerabilities of the developing fetus is essential in formulating therapeutic options.

Functional and Physiological Determinants of Perceived Disability in Individuals Diagnosed with Osteoarthritis of the Hip

Objectives: The main objective of this pilot study was to investigate which standardized functional and physiological test best predicted perceived disability in a single group of 21 individuals diagnosed with osteoarthritis of the hip. Design: Men and women between 60 and 70 years old with osteoarthritis of the hip were selected. If participants passed study criteria, the Western Ontario McMaster University questionnaire (WOMAC), 6 Minute Walk Test (6MWT) and Timed up and Go (TUG), strength testing and aerobic testing were obtained in one single assessment. Results: Regression analysis revealed that wait time, hip abduction strength of the affected side, Aerobic Capacity (VO2 Peak), hip Extension Peak Torque, hip Flexion Peak Torque, TUG and 6MWT were significantly correlated with the WOMAC. Yet, the 6MWT had the highest significant correlation (r = -0.86, p ≤ 0.0001); R2 = 0.75 or 75% with the WOMAC total scores, (r = -0.82, p ≤ 0.0001); R2 = 0.67 or 67% with the WOMAC function and (r = -0.60, p = .002); R2 = 0.36 or 36% with the WOMAC stiffness. While the VO2 Peak revealed the highest significant correlation (r = 0.76, p ≤ .0001); R2 = 0.57 or 57% with the WOMAC pain. Conclusions: The 6MWT and the VO2 Peak seem to be essential functional and physiological assessment tools to determine perceived disability in individuals with hip OA. The perceived disability may provide new or comprehensive knowledge of the disability problems experienced by individuals with osteoarthritis of the hip, and the association of patient perception with objective measures of functional and physiological capacity might strengthen the clinical value of this knowledge.