Radiotherapy of unusual benign disease

Four different case reports are presented with a review of the literature in which radiation therapy was used for the treatment of four rare benign diseases: pyogenic granuloma of the middle ear, juvenile xanthogranuloma of the iris, a fourth ventricle choroid plexus papilloma, and an ovarian lymphangioma associated with peritoneal lymphangiomatosis. A trial of radiation therapy was given in each case, because of extenuating circumstances. We hope that the information presented here will contribute to current guidelines used in weighting patient benefits versus potential risks of therapy when ionizing radiation is considered as a mode of therapy for benign disorders.     

On Lamb and Rayleigh wave convergence in viscoelastic tissues

Characterization of the viscoelastic material properties of soft tissue has become an important area of research over the last two decades. Our group has been investigating the feasibility of using a shear wave dispersion ultrasound vibrometry (SDUV) method to excite Lamb waves in organs with plate-like geometry to estimate the viscoelasticity of the medium of interest. The use of Lamb wave dispersion ultrasound vibrometry to quantify the mechanical properties of viscoelastic solids has previously been reported. Two organs, the heart wall and the spleen, can be readily modeled using plate-like geometries. The elasticity of these two organs is important because they change in pathological conditions. Diastolic dysfunction is the inability of the left ventricle (LV) of the heart to supply sufficient stroke volumes into the systemic circulation and is accompanied by the loss of compliance and stiffening of the LV myocardium. It has been shown that there is a correlation between high splenic stiffness in patients with chronic liver disease and strong correlation between spleen and liver stiffness. Here, we investigate the use of the SDUV method to quantify the viscoelasticity of the LV free-wall myocardium and spleen by exciting Rayleigh waves on the organ's surface and measuring the wave dispersion (change of wave velocity as a function of frequency) in the frequency range 40–500 Hz. An equation for Rayleigh wave dispersion due to cylindrical excitation was derived by modeling the excised myocardium and spleen with a homogenous Voigt material plate immersed in a nonviscous fluid. Boundary conditions and wave potential functions were solved for the surface wave velocity. Analytical and experimental convergence between the Lamb and Rayleigh waves is reported in a finite element model of a plate in a fluid of similar density, gelatin plate and excised porcine spleen and left-ventricular free-wall myocardium.     

Large-scale reorganization of the tonotopic map in mouse auditory midbrain revealed by MRI

The cortex is thought to be the primary site of sensory plasticity, particularly during development. Here, we report that large-scale reorganization of the mouse auditory midbrain tonotopic map is induced by a specific sound-rearing environment consisting of paired low- (16 kHz) and high-frequency (40 kHz) tones. To determine the potential for plasticity in the mouse auditory midbrain, we used manganese-enhanced MRI to analyze the midbrain tonotopic maps of control mice during normal development and mice reared in the two-tone (16 + 40 kHz) environment. We found that the tonotopic map emerged during the third postnatal week in normal mice. Before 3 weeks, a larger percentage of auditory midbrain responded to each of the suprathreshold test frequencies, despite the fact that the primary afferent projections are in place even before hearing onset. By 3 weeks, the midbrain tonotopic map of control mice was established, and manganese-enhanced MRI showed a clear separation between the 16- and 40-kHz responses. Two-tone rearing dramatically altered the appearance of these discrete frequency-specific responses. A significant volume of the auditory midbrain became responsive to both rearing frequencies, resulting in a large-scale reorganization of the tonotopic map. These results indicate that developmental plasticity occurs on a much greater scale than previously appreciated in the mammalian auditory midbrain.     

40 MHz Doppler characterization of umbilical and dorsal aortic blood flow in the early mouse embryo

Physiological study of the developing mouse circulation has lagged behind advances in molecular cardiology. Using an innovative high-frequency Doppler system, we noninvasively characterized circulatory hemodynamics in early mouse embryos. We used image-guided 43 MHz pulsed-wave (PW) Doppler ultrasound to study the umbilical artery and vein, or dorsal aorta in 109 embryos. Studies were conducted on embryonic days (E) 9.5-14.5. Heart rate, peak blood flow velocities, and velocity time integrals in all vessels increased from E9.5-14.5, indicating increasing stroke volume and cardiac output. Heart rate, ranging from 192 bpm (E9.5) to 261 bpm (E14.5), was higher than previously reported. Placental impedance, assessed by the time delay between the peaks of the umbilical arterial and venous waveforms and by venous pulsatility, decreased with gestation. Acceleration time, a load-independent Doppler index of cardiac contractility, remained constant but seemed sensitive to heart rate. High-frequency PW Doppler is a powerful tool for the quantitative, noninvasive investigation of early mouse circulatory development.     

Triglyceride Recrystallized Phytosterols in Fat-Free Milk Improve Lipoprotein Profiles More Than Unmodified Free Phytosterols in Hypercholesterolemic Men and Women

Objective: Foods incorporating plant sterols (PS) consistently decrease serum low-density lipoprotein cholesterol (LDL-C), although results vary depending on the PS form and food matrix. The objective was to study the effect of a novel triglyceride-recrystallized phystosterol (TRP) incorporated into fat-free milk on markers of cardiovascular risk compared to unmodified free sterols alone in the same fat-free milk.

Methods: Hypercholesterolemic men and women (n = 13 males/7 females; 56 ±10 years; body mass index 27.3 ±5.9 kg/m²) participated in 3 sequential 4-week phases of 480 mL milk consumption. During phase 1 (control) all subjects consumed 2% milk containing no PS, followed by phase 2 with fat-free milk containing free PS (2 g/d fPS) and phase 3 with fat-free milk with TRP (2 g/d). After each phase, determinations of lipoprotein cholesterol distribution, particle concentration via nuclear magnetic resonance (NMR), apolipoproteins, inflammatory markers, and fat-soluble dietary antioxidants were made.

Results: Body mass, body composition, dietary energy and macronutrients, and physical activity were unaffected throughout the study. Compared to the control 2% milk, LDL-C was significantly (p < 0.05) decreased by fPS (?9.1%) and was further decreased by TRP (?15.4%); reductions with TRP were significantly greater. Total LDL particle concentration was decreased to a greater extent after TRP (?8.8%) than fPS (?4.8%; p < 0.05). Only TRP significantly decreased serum levels of apolipoprotein B (apoB; ?6%), interleukin-8 (IL-8; ?11%) and monocyte chemotactic protein-1 (MCP-1; ?19%). Plasma α- and γ-tocopherols and carotenoids, normalized to cholesterol, remained unchanged throughout the study with the exception that β-carotene was lowered by 18%.

Conclusion: In summary, TRP in fat-free milk may provide cardiovascular benefits beyond that of fPS by inducing more substantial decreases in LDL cholesterol and particle concentration, associated with declines in markers of vascular inflammation.     

Grape polyphenols reduce blood pressure and increase flow-mediated vasodilation in men with metabolic syndrome

We evaluated the effects of grape polyphenols in individuals classified with metabolic syndrome (MetS). Men (n = 24) aged 30-70 y were randomly assigned to consume either a freeze-dried grape polyphenol powder (GRAPE) or a placebo for 30 d in a double-blind, crossover design, separated by a 3-wk washout period. Participants were asked to maintain their usual diet and physical activity during the study and abstain from consuming polyphenol-rich foods. MetS criteria including blood pressure (BP) and markers of vascular endothelial function including brachial artery flow-mediated vasodilation (FMD), plasma total nitrite + nitrate (NOx) to estimate NO production, plasma soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured at the end of each dietary period. Systolic BP (P < 0.0025) and plasma sICAM-1 concentrations (P < 0.025) were lower, whereas the FMD response was higher (P < 0.0001), during the GRAPE compared with the placebo period. In addition, changes in sVCAM-1 concentrations between periods were positively correlated with changes in systolic BP (r = 0.45; P < 0.05). Although NOx concentrations did not differ between periods, changes in systolic BP were negatively correlated with changes in NOx concentrations (r = -0.44; P < 0.05), indicating the vasodilating properties of NO. Other MetS variables did not differ between the GRAPE and placebo periods. These results suggest that GRAPE polyphenols may potentiate vasorelaxation and reduce BP and circulating cell adhesion molecules, resulting in improvements in vascular function.     

Morphological Transition of Paracoccidioides brasiliensis Conidia to Yeast Cells: In Vivo Inhibition in Females

Clinical paracoccidioidomycosis is 13 times more common in men than in women. Estrogen inhibits the transition of mycelia or conidia (the saprophytic form of Paracoccidoides brasiliensis) to yeasts (the parasitic form) in vitro. Here, we show that, in male mice that were infected intranasally (mimicking natural infection) the transition of conidia in bronchoalveolar lavage fluids to intermediate forms and yeasts occurred over 24 to 96 h; CFU and yeasts (shown by histopathology) increased subsequently. In females, transition did not occur and infection cleared. These events in vivo are consistent with epidemiological and in vitro observations, suggesting that female hormones block transition and are responsible for resistance.