Citations

Background— The congenital long-QT syndrome (LQTS) is an important cause of sudden cardiac death in children without structural heart disease. However, specific risk factors for life-threatening cardiac events in children with this genetic disorder have not been identified. Methods and Results— Cox proportional-hazards regression modeling was used to identify risk factors for aborted cardiac arrest or sudden cardiac death in 3015 LQTS children from the International LQTS Registry who were followed up from 1 through 12 years of age. The cumulative probability of the combined end point was significantly higher in boys (5%) than in girls (1%; P <0.001). Risk factors for cardiac arrest or sudden cardiac death during childhood included corrected QT interval [QTc] duration >500 ms (hazard ratio [HR]; 2.72; 95% confidence interval [CI], 1.50 to 4.92; P =0.001) and prior syncope (recent syncope [<2 years]: HR, 6.16; 95% CI 3.41 to 11.15; P <0.001; remote syncope [≥2 years]: HR, 2.67; 95% CI, 1.22 to 5.85; P =0.01) in boys, whereas prior syncope was the only significant risk factor among girls (recent syncope: HR, 27.82; 95% CI, 9.72 to 79.60; P <0.001; remote syncope: HR, 12.04; 95% CI, 3.79 to 38.26; P <0.001). β-Blocker therapy was associated with a significant 53% reduction in the risk of cardiac arrest or sudden cardiac death ( P =0.01). Conclusions— LQTS boys experience a significantly higher rate of fatal or near-fatal cardiac events than girls during childhood. A QTc duration >500 ms and a history of prior syncope identify risk in boys, whereas prior syncope is the only significant risk factor among girls. β-Blocker therapy is associated with a significant reduction in the risk of life-threatening cardiac events during childhood.

Arterial wall stiffness can be associated with various diseases. The stiffness of an artery can be assessed by measurement of the pulse wave velocity (PWV). Usually, PWV is estimated using the foot-to-foot method. However, the foot of the pressure wave is not very clear due to reflected waves. Also, the blood pressure wave generated by the heart is normally a low frequency wave, hence the time resolution is low. PWV is an average indicator of artery stiffness between two measuring locations, therefore, it is not easy to identify local stiffness. In this paper a short external pulse is generated in an artery by the radiation force of ultrasound. The propagation velocity of the pulse wave is measured along the artery. The temporal resolution of this method, which is in the range of microseconds, is much higher than the conventional pressure PWV method, and therefore allows the wave velocity to be measured accurately over a few millimeters.

In paper, we report our recent results of using the air force ultrasound transducer to study the resonance of rubber tubes. Experiments were carried out on a rubber latex tube. Seven resonant frequencies were measured between 50 Hz and 200 Hz. Theoretical calculation of the resonant frequency on the tube was done with the wave propagation approach. The relative differences of the seven resonant frequencies between the experiment and the theory are less than 6 %. This research shows that the air force ultrasound transducer can be used for tube resonance measurement.

AbstractThe immunoglobulin free light chain (FLC) assay is an invaluable tool for following patients with oligosecretory plasma cell dyscrasia. Baseline values have also been shown to be prognostic in all plasma cell disorders tested. A looming question, however, is the role it should play in following myeloma patients with disease that is measurable using serum and urine electrophoresis. We used the data and stored samples from a mature Eastern Cooperative Oncology Group clinical trial (E9486) to assess serum levels of FLC at baseline and after 2 months of alkylator-based therapy. For serial determinations, the absolute level of involved serum FLC or the difference of the involved and uninvolved FLC is preferred over the ratio of involved to uninvolved FLC. FLC response after 2 months of therapy was superior to early M-protein measurement to predict overall response. The ideal cut-point for FLC change appears to be between 40% and 50% reduction. The correlation between serial measurements of serum FLC and urine M-protein is inadequate to abolish the serial 24-hour urine protein. Although baseline values of FLC are prognostic in newly diagnosed myeloma patients, serial measurements do not appear to have added value in patients who have M-proteins measurable by electrophoresis.

The cardiac neural crest is a subpopulation of neural crest cells (NCCs) that originates from the dorsal neural tube and later migrates to the heart and pharyngeal arch (PA), where they contribute to distinct aspects of cardiogenesis and PA patterning. Wnt family members have been implicated in general neural crest induction; however, the molecular mechanisms underlying the specification of distinct cell types such as cardiac NCCs remain unclear. Here, we have identified cysteine-rich intestinal protein 2 ( crip2 ), a gene encoding for a LIM domain–containing protein, as a novel marker for cardiac NCCs in zebrafish. We observed a dynamic expression pattern for crip2 , with expression being detected in the premigratory NCCs in rhombomere 6 (r6), migrating NCCs, ventricular cardiomyocytes, and aortic vessels in PAs 3 to 6. Interestingly, expression of wnt3a was detected in regions of the dorsal neural tube encompassing r6, and reduction of wnt3a led to disrupted expression of crip2 in r6, abnormal migration of NCCs, and defective cardiac function, as well as PA development. Furthermore, these phenotypes could be recapitulated by reduction of crip2 and rescued by overexpression of crip2 . In summary, our data suggest a specific role for Wnt3a in the development of cardiac NCCs. We propose that this function of wnt3a in r6 is partially mediated by crip2 expression in the premigratory cardiac NCCs, which subsequently affects cardiac function and PA patterning.

A hallmark of the pathology of Alzheimer's disease is the accumulation of the microtubule-associated protein tau into fibrillar aggregates. Recent studies suggest that they accumulate because cytosolic chaperones fail to clear abnormally phosphorylated tau, preserving a pool of toxic tau intermediates within the neuron. We describe a mechanism for tau clearance involving a major cellular kinase, Akt. During stress, Akt is ubiquitinated and degraded by the tau ubiquitin ligase CHIP, and this largely depends on the Hsp90 complex. Akt also prevents CHIP-induced tau ubiquitination and its subsequent degradation, either by regulating the Hsp90/CHIP complex directly or by competing as a client protein with tau for binding. Akt levels tightly regulate the expression of CHIP, such that, as Akt levels are suppressed, CHIP levels also decrease, suggesting a potential stress response feedback mechanism between ligase and kinase activity. We also show that Akt and the microtubule affinity-regulating kinase 2 (PAR1/MARK2), a known tau kinase, interact directly. Akt enhances the activity of PAR1 to promote tau hyperphosphorylation at S262/S356, a tau species that is not recognized by the CHIP/Hsp90 complex. Moreover, Akt1 knockout mice have reduced levels of tau phosphorylated at PAR1/MARK2 consensus sites. Hence, Akt serves as a major regulator of tau biology by manipulating both tau kinases and protein quality control, providing a link to several common pathways that have demonstrated dysfunction in Alzheimer's disease.

The mechanical response of tissues to external forces has gained considerable interest in medical diagnosis. One approach to imaging tissue elastic properties is to apply an external force on the surface of the body. Another approach is to generate a localized force inside the tissue with the radiation force of ultrasound. In this paper, a new method is developed to estimate tissue’s elasticity based on surface wave speed measurement. The theory of surface wave speed is developed for estimating tissue’s elasticity. Experiments are carried out on a tissue-mimicking ultrasound phantom. An amplitude modulated ultrasound signal of a few hundred hertz is used to generate a localized force in the phantom. The surface wave fields are measured with a laser vibrometer. It shows that the surface wave speed can be used for inversely estimating tissue’s elastic properties based on tissue’s surface measurement.

We report three cases of solitary fibrous tumor (SFT) arising in the orbit. All patients presented with nontender swelling of the affected eye, and one patient presented with nasolacrimal duct obstruction. All three patients had well-circumscribed tumors that had histologic features identical to those of SFT of the pleura (fibrous mesothelioma). The neoplastic cells were purely fibrogenic. They were reactive with antivimentin and CD-34 and demonstrated no smooth muscle or neural differentiation (nonreactive with antibodies to actin, desmin, and S 100 protein). KP-1 (CD-68) immunoreactivity was present focally within the neoplastic cells in all three tumors; however, it was strongly positive within tumor infiltrating macrophages. Electron microscopy per formed on one tumor showed fine fibroblastic differentiation with phagocytic activity confined to infiltrating macrophages. SFT of the orbit is a distinct pathologic entity that merits distinction within the broad group of orbital fibrous tumors. Int J Surg Pathol 2(3):193-198, 1995