Noninvasive finding of local repolarization changes in the heart using dipole models and simplified torso geometry

Two inverse methods using dipole models for noninvasive assessment of local repolarization changes were investigated and compared in the simulation study. Lesions with changed repolarization were modeled by shortening of the action potential durations in ventricular regions typically influenced by occlusion of coronary arteries. Corresponding body surface potentials were computed using a multiple dipole model of the cardiac generator and an inhomogeneous torso model. Position of each lesion was then estimated by an inverse solution to a single dipole and to a group of five neighbouring dipoles. For both methods the lesion localization error was evaluated and its dependence on the lesion size and the noise in input data was studied. When no noise was present in the input data, the use of the inverse method to a group of dipoles instead of a single dipole resulted in an unsubstantial reduction of the mean localization error of small lesions from 0.6 to 0.5 cm. For medium and especially for large lesions the mean localization errors decreased significantly from 1.1 to 0.6 cm and from 2.3 to 1.0 cm, respectively. The inverse solution to a group of five dipoles was more sensitive to noise. However, for large lesions it still gave better results than the solution to a single dipole if the signal to noise ratio was higher than 30 dB.     

Tumor growth inhibition through targeting liposomally bound curcumin to tumor vasculature

Increasing number of Phase I/II clinical studies have demonstrated clinical potential of curcumin for treatment of various types of human cancers. Despite significant anti-tumor efficacies and bio-safety profiles of curcumin, poor systemic bioavailability is retarding its clinical success. Efforts are now being directed toward developing stable formulations of curcumin using various drug delivery systems. To this end, herein we report on the development of a new tumor vasculature targeting liposomal formulation of curcumin containing a lipopeptide with RGDK-head group and two stearyl tails, di-oleyolphosphatidylcholine (DOPC) and cholesterol. We show that essentially water insoluble curcumin can be solubilized in fairly high concentrations (~ 500 μg/mL) in such formulation. Findings in the Annexin V/Propidium iodide (PI) binding based flow cytometric assays showed significant apoptosis inducing properties of the present curcumin formulation in both endothelial (HUVEC) and tumor (B16F10) cells. Using syngeneic mouse tumor model, we show that growth of solid melanoma tumor can be inhibited by targeting such liposomal formulation of curcumin to tumor vasculature. Results in immunohistochemical staining of the tumor cryosections are consistent with tumor growth inhibition being mediated by apoptosis of tumor endothelial cells. Findings in both in vitro and in vivo mechanistic studies are consistent with the supposition that the presently described liposomal formulation of curcumin inhibits tumor growth by blocking VEGF-induced STAT3 phosphorylation in tumor endothelium. To the best of our knowledge, this is the first report on inhibiting tumor growth through targeting liposomal formulation of curcumin to tumor vasculatures.     

Quantification of left ventricular internal flow from cardiac magnetic resonance images in patients with dyssynchronous heart failure

PURPOSE: To develop a method for quantifying left ventricular (LV) internal flow as a measure of dyssynchrony using standard cine cardiac magnetic resonance (CMR) images. MATERIALS AND METHODS: CMR images were obtained from 10 healthy controls and 10 patients with dyssynchronous heart failure (class III/IV, LV ejection fraction <35%, pattern seen in an electrocardiogram QRS duration > 150 msec). The LV volume was reconstructed and divided into 16 regions. Internal flow was defined as the sum of the regional volume changes minus the global volume change during each time step in the cardiac cycle. Internal flow fraction (IFF) was defined as the total internal flow as a percentage of stroke volume during systole (IFF(systole)), diastole (IFF(diastole)), or the whole cycle (IFF(whole)). RESULTS: IFF(whole) was significantly increased in the patients (9.9 +/- 5.0% vs. 1.5 +/- 0.5% in the controls, P < 0.001). An IFF(whole) threshold of 4% discriminated between patients and controls with 90% sensitivity and 100% specificity. IFF(diastole) (2.3 +/- 0.8%) was greater than IFF(systole) (0.8 +/- 0.5%) in the normal controls (P < 0.001) while the patients had similar IFF(diastole) (7.8 +/- 4.2%) and IFF(systole) (12.0 +/- 7.8%). CONCLUSION: Left ventricular internal flow fraction can be quantified from standard CMR images. In this preliminary study, Left ventricular internal flow fraction discriminated patients with dyssynchronous heart failure from normal controls with 95% accuracy.     

Effect of acute versus chronic theophylline administration on acute restraint stress-induced increase of pentylenetetrazol seizure threshold in mice

Various stressful paradigms were found to induce anticonvulsant effects in different seizure models. Methylxanthines, such as theophylline might contribute to the reduction of restraint-induced stress. Therefore, in this study the influence of acute restraint stress on pentylenetetrazol (PTZ) seizure thresholds as well as the effect of acute and chronic theophylline pretreatment on stress-induced modulation of the seizure threshold were assessed in mice. The onset of the three consecutive seizure phases: myoclonic twitch (MTW), generalized clonus (GNCL) and tonic hind limb extension (THE) was delayed after exposure to a 2 h restraint stress by 34%, 23% and 24%, respectively. In nonstressed mice, acute theophylline injection (100 mg/kg, i.p.) decreased the threshold only for THE. However, in stressed animals, the pretreatment with the methylxanthine significantly enhanced the dose of the convulsant producing the same seizure phase. In nonstressed mice, long-term theophylline treatment (50 mg/kg, twice daily for 14 days) increased PTZ threshold for all three seizure phases. In contrast, in chronically treated with theophylline mice exposed to restraint stress, significant decrease in the PTZ threshold for all seizure phases compared to control stressed animals have been observed. These results suggest that, depending on the treatment regimen (acute versus chronic), theophylline specifically and differentially modulates the anticonvulsant effect of restraint stress in mice.     

Adherence to continuous positive airway pressure treatment in patients with Alzheimer's disease and obstructive sleep apnea.

OBJECTIVE: This analysis examined whether patients with Alzheimer disease (AD) tolerate continuous positive airway pressure (CPAP). METHOD: Thirty patients with AD were randomized to CPAP or sham CPAP and completed sleep, depression, and quality-of-life questionnaires. Participants could choose to continue treatment after the trial. RESULTS: Patients wore CPAP for 4.8 hours per night. More depressive symptoms were associated with worse adherence (rS=-0.37; N=30, p<0.04). Patients who continued using CPAP had fewer depressive symptoms (t [19]=2.45, p=0.02) and better adherence (t [19]=2.32, p=0.03) during the trial. CONCLUSION: Patients with AD with obstructive sleep apnea can tolerate CPAP. Adherence and long-term use may be more difficult among those patients with more depressive symptoms.     

TVT-S in the U position��anatomical study

Introduction and hypothesis  

The objective is to describe the anatomical position of tension-free vaginal tape Secur (TVT-S) in the U position regarding possible injury and fixation site.