Micro-CT evaluation of bone defects: Applications to osteolytic bone metastases,bone cysts,and fracture

Bone defects can occur in various forms and present challenges to performing a standard micro-CT evaluation of bone quality because most measures are suited to homogeneous structures rather than ones with spatially focal abnormalities. Such defects are commonly associated with pain and fragility. Research involving bone defects requires quantitative approaches to be developed if micro-CT is to be employed. In this study, we demonstrate that measures of inter-microarchitectural bone spacing are sensitive to the presence of focal defects in the proximal tibia of two distinctly different mouse models: a burr-hole model for fracture healing research, and a model of osteolytic bone metastases. In these models, the cortical and trabecular bone compartments were both affected by the defect and were, therefore, evaluated as a single unit to avoid splitting the defects into multiple analysis regions. The burr-hole defect increased mean spacing (Sp) by 27.6%, spacing standard deviation (SpSD) by 113%, and maximum spacing (Sp_max) by 72.8%. Regression modeling revealed SpSD (β = 0.974, p < 0.0001) to be a significant predictor of the defect volume (R² = 0.949) and Sp_max (β = 0.712, p < 0.0001) and SpSD (β = 0.271, p = 0.022) to be significant predictors of the defect diameter (R² = 0.954). In the mice with osteolytic bone metastases, spacing parameters followed similar patterns of change as reflected by other imaging technologies, specifically bioluminescence data which is indicative of tumor burden. These data highlight the sensitivity of spacing measurements to bone architectural abnormalities from 3D micro-CT data and provide a tool for quantitative evaluation of defects within a bone.     

A regulated RNA binding protein also possesses aconitase activity.

A clone for the iron-responsive element (IRE)-binding protein (IRE-BP) has been transfected and expressed in mouse fibroblasts. The IRE-BP gene product binds IREs with high affinity and specificity. Amino acid alignments reveal that the IRE-BP is 30% identical to mitochondrial aconitase. The 18 active site residues of mitochondrial aconitase are identical to those in the IRE-BP, suggesting that the IRE-BP may possess aconitase activity. After purification of native IRE-BP and immunoaffinity purification of transfected and expressed IRE-BP, we demonstrate that the purified IRE-BP has aconitase activity.     

Risk factors for aortic valve dysfunction in children with discrete subvalvar aortic stenosis

Aortic regurgitation (AR) is a known complication of discrete subvalvar aortic stenosis (DSS), and its detection often triggers referral for surgery. However, risk factors for aortic valve dysfunction in children with DSS remain incompletely defined. The primary goal of this study was to determine independent risk factors for moderate or severe AR at mid-term follow-up in patients with DSS. Clinical records and echocardiograms of 220 patients with DSS (109 patients had DSS resection and 111 had no surgery) were analyzed. The primary outcome variable was AR grade (based on the width of the vena contracta) at latest follow-up. Age at diagnosis, gender, and duration of follow-up (median 7.2 years, range 1 to 20.4) did not differ significantly between medical and surgical patients. By multivariate analysis, independent risk factors for moderate to severe AR (n = 30) were older age at diagnosis of DSS (odds ratio [OR] for age > or =17 years 5.13, p = 0.024), previous balloon or surgical aortic valvuloplasty (OR 19.6, p <0.001), and a longer follow-up period (OR for 1-year increase 1.15, p = 0.032). Excluding patients with previous surgical or balloon aortic valvuloplasty, a higher maximal Doppler gradient was an independent risk factor for moderate to severe AR (OR for peak gradient > or =50 mm Hg 10.8, p = 0.001). Independent predictors of low-risk patients (none or trivial AR and peak gradient < or =30 mm Hg) included thin and mobile aortic valve leaflets (OR 7.86, p = 0.006) and an associated ventricular septal defect (OR 2.18, p = 0.019). These clinical and echocardiographic variables can be used to stratify risk of aortic valve dysfunction in patients with DSS and aid in timing of surgical resection.     

Myocardial protection with mild hypothermia

Mild hypothermia, 32-35° C, is very potent at reducing myocardial infarct size in rabbits, dogs, sheep, pigs, and rats. The benefit is directly related to reduction in normothermic ischaemic time, supporting the relevance of early and rapid cooling. The cardioprotective effect of mild hypothermia is not limited to its recognized reduction of infarct size, but also results in conservation of post-ischaemic contractile function, prevention of no-reflow or microvascular obstruction, and ultimately attenuation of left ventricular remodelling. The mechanism of the anti-infarct effect does not appear to be related to diminished energy utilization and metabolic preservation, but rather to survival signalling that involves either the extracellular signal-regulated kinases and/or the Akt/phosphoinositide 3-kinase/mammalian target of rapamycin pathways. Initial clinical trials of hypothermia in patients with ST-segment elevation myocardial infarction were disappointing, probably because cooling was too slow to shorten normothermic ischaemic time appreciably. New approaches to more rapid cooling have recently been described and may soon be available for clinical use. Alternatively, it may be possible to pharmacologically mimic the protection provided by cooling soon after the onset of ischaemia with an activator of mild hypothermia signalling, e.g. extracellular signal-regulated kinase activator, that could be given by emergency medical personnel. Finally, the protection afforded by cooling can be added to that of pre- and post-conditioning because their mechanisms differ. Thus, myocardial salvage might be greatly increased by rapidly cooling patients as soon as possible and then giving a pharmacological post-conditioning agent immediately prior to reperfusion.