Predicting Hip Fracture Type With Cortical Bone Mapping (CBM) in the Osteoporotic Fractures in Men (MrOS) Study

Hip fracture risk is known to be related to material properties of the proximal femur, but fracture prediction studies adding richer quantitative computed tomography (QCT) measures to dual‐energy X‐ray (DXA)‐based methods have shown limited improvement. Fracture types have distinct relationships to predictors, but few studies have subdivided fracture into types, because this necessitates regional measurements and more fracture cases. This work makes use of cortical bone mapping (CBM) to accurately assess, with no prior anatomical presumptions, the distribution of properties related to fracture type. CBM uses QCT data to measure the cortical and trabecular properties, accurate even for thin cortices below the imaging resolution. The Osteoporotic Fractures in Men (MrOS) study is a predictive case‐cohort study of men over 65 years old: we analyze 99 fracture cases (44 trochanteric and 55 femoral neck) compared to a cohort of 308, randomly selected from 5994. To our knowledge, this is the largest QCT‐based predictive hip fracture study to date, and the first to incorporate CBM analysis into fracture prediction. We show that both cortical mass surface density and endocortical trabecular BMD are significantly different in fracture cases versus cohort, in regions appropriate to fracture type. We incorporate these regions into predictive models using Cox proportional hazards regression to estimate hazard ratios, and logistic regression to estimate area under the receiver operating characteristic curve (AUC). Adding CBM to DXA‐based BMD leads to a small but significant (p < 0.005) improvement in model prediction for any fracture, with AUC increasing from 0.78 to 0.79, assessed using leave‐one‐out cross‐validation. For specific fracture types, the improvement is more significant (p < 0.0001), with AUC increasing from 0.71 to 0.77 for trochanteric fractures and 0.76 to 0.82 for femoral neck fractures. In contrast, adding DXA‐based BMD to a CBM‐based predictive model does not result in any significant improvement. © 2015 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.     

B-cell lymphoma after angioimmunoblastic lymphadenopathy: a case with oligoclonal gene rearrangements associated with Epstein-Barr virus

We describe a patient with angioimmunoblastic lymphadenopathy with dysproteinemia (AILD), who subsequently developed large-cell immunoblastic lymphoma of B-cell immunophenotype. At the time of the initial diagnosis, histologic examination of an inguinal lymph node showed typical features of AILD, and there was no evidence of a monoclonal B-cell population by immunohistochemical analysis. In situ hybridization and Southern blot analysis for Epstein-Barr virus (EBV) were negative. At autopsy 2 years later, the patient had widespread lymph node and organ involvement by large-cell immunoblastic lymphoma of B-cell immunophenotype. Southern blot analysis performed on DNA extracted from lymph nodes, liver, and spleen showed two patterns of Ig heavy chain and kappa light chain gene rearrangements. The T-cell receptor beta chain gene was in the germline configuration. Analysis with an EBV terminal repeat region probe showed two clonal populations that paralleled the Ig gene rearrangement studies. Double-labeling immunohistochemistry and in situ hybridization confirmed the presence of EBV within the neoplastic B cells. The data support the hypothesis that EBV was not etiologically related to AILD in this case, and that EBV proliferation may occur after the onset of the disease. Further, the data suggest that some B-cell lymphomas that arise in the setting of AILD resemble EBV-associated B-cell lymphomas that arise in other immunodeficiency states.     

Calculation of aortic regurgitation orifice area by Doppler echocardiography: an application of the continuity equation.

The evaluation of aortic regurgitation by current echocardiographic techniques has been qualitative and load-dependent. The area of the regurgitant orifice, which is theoretically independent of haemodynamic conditions, has not been determined non-invasively. In 20 patients with various degrees of aortic regurgitation, this area was determined by use of the continuity equation applied during diastole. The velocity-time integrals were determined at the supravalvar (VTIs) and regurgitant orifice (VTIj) levels by pulsed and continuous wave Doppler respectively. The cross sectional area at the supravalvar level (As) was also measured by cross sectional echocardiography. The regurgitant orifice is given by: (As x VTIs)/VTIj. Other non-invasive measurements of the aortic regurgitation severity were also recorded: (a) an overall echo score (1-5+) given blindly by two echocardiographers, (b) the maximal proximal jet width by colour Doppler, (c) left ventricular end systolic and end diastolic volumes and left ventricular mass. The regurgitant area ranged from 0.25 to 1.7 cm2 and this area accorded with the overall echo score and the maximal proximal jet width measured by colour Doppler. The aortic regurgitation orifice area can be calculated non-invasively and it may be a quantitative measure of the severity of aortic regurgitation.     

Suppression of DNA synthesis in hepatoma cells exposed to glucocorticoid hormone in vitro

Glucocorticoid hormone is shown to markedly suppress DNA synthesis in a line of rat hepatoma cells in vitro. In the presence of 300 nM hydrocortisone or 30 nM dexamethasone the incorporation of radioactive thymidine falls to 50% of control levels by 36 hr, and at higher concentrations of hormone inhibition can be noted as early as 12 hr and is nearly complete by 24 hr. This inhibition of radioactive thymidine incorporation reflects a true suppression of DNA synthesis, is accompanied by a corresponding inhibition of cell proliferation, and is readily reversible upon subsequent removal of hormone. In contrast to previously described effects of the glucocorticoid hormones on various cells of lymphoid origin, the inhibition of DNA synthesis in these hepatoma cells is not accompanied by appreciable cell lysis or by degradation of preformed DNA, and even when [(3)H]thymidine incorporation into DNA is inhibited by 90% or more, incorporation of [(14)C]uridine into RNA proceeds with little change. These findings all parallel previous observations on the effects of glucocorticoid hormone on the livers of intact animals and suggest that studies on the mechanism of the inhibition of DNA synthesis in the present more isolated system may lead to a better understanding of the means by which these compounds inhibit liver growth in vivo.Despite the ready suppressibility of DNA synthesis in these hepatoma cells and in two other cell lines of liver origin, none of these cell lines was found to be inducible for tyrosine aminotransferase. The apparent dissociation between two "steroid-sensitive" phenomena is of interest and warrants further investigation.     

The effect of light-emitting diode and laser on mandibular growth in rats

Objective:To evaluate the effect of a light-emitting diode (LED) and/or low-level laser (LLL) with or without the use of anterior bite jumping appliances (also known as functional appliances [FAs]) on mandibular growth in rats.Materials and Methods:Thirty-six 8-week-old male Sprague-Dawley rats weighing 200 g were obtained from Charles River Canada (St. Constant, QC, Canada) and were divided into six groups of six animals each. Groups were as follows: group 1: LLL; group 2: LLL + FA; group 3: LED; group 4: LED + FA; group 5: FA; and group 6: control (no treatment). Mandibular growth was evaluated by histomorphometric and micro computed tomographic (microCT) analyses.Results:The LED and LED + FA groups showed an increase in all condylar tissue parameters compared with other groups.Conclusion:The LED-treated groups showed more mandibular growth stimulation compared with the laser groups.     

Spatial orientation of atherosclerotic plaque in non-branching coronary artery segments

It has been postulated that atherosclerotic plaque deposition is spatially related to regions of low shear in non-branching vessel segments. Intravascular ultrasound (IVUS) allows precise spatial orientation of coronary artery plaque formation in humans. The objective of this study was to test the hypothesis that coronary plaques have a higher prevalence on the myocardial side in regions that encounter low surface shear stress. IVUS allows the determination of the inner versus the outer curve of the vessel based on vascular and perivascular landmarks. We studied 30 consecutive patients pre-intervention using IVUS and measured vessel area, lumen area and plaque area (vessel-lumen area) during a motorized pullback at 1 mm intervals. Vessel segments near a side branch (within two times the diameter of the vessel) were excluded from analysis because of flow disturbances. All plaques were classified as concentric or eccentric and all eccentric plaques were further divided with respect to their spatial orientation in the vessel into quadrants: myocardial (inner curve, lower shear stress), epicardial (outer curve, higher shear stress) and lateral (two quadrants intermediate). A total of 613 cross-sections were analyzed in 14 left anterior descending, six left circumflex, and ten right coronary arteries. Plaque distribution was found to be concentric in 321 (52.4%) and eccentric in 292 (47.6%) cross sections. Of all eccentric plaques, 184 cross sections were oriented toward the myocardial side (62.6%) compared to only 54 toward the epicardial side (17.3%) and 54 in the 2 lateral quadrants (19.5%, P<0.001). No difference in plaque area (6.75+/-2.70 vs. 6.76+/-2.60 mm(2)), vessel area (15.28+/-4.73 vs. 15.35+/-4.40 mm(2)), or plaque thickness (1.26+/-0.37 vs. 1.25+/-0.43 mm) was noted between myocardial or epicardial plaques. These results suggest that atherosclerotic plaques develop more frequently on the myocardial side of the vessel wall, which may relate to lower shear stress. However, plaque size is similar on the epicardial and myocardial side.