Cavitation mediated rat lung bioeffects from diagnostic ultrasound

Several animal models have exhibited petechial hemorrhage in the lung within the current FDA output limit of diagnostic ultrasound systems. To elucidate the mechanism of damage, seven rat lungs were simultaneously exposed or sham exposed in vivo to 6‐MHz pulsed Doppler ultrasound and interrogated with a confocally aligned 30‐MHz active cavitation detector (ACD) [R. A. Roy, S. Madanshetty, and R. E. Apfel, J. Acoust. Soc. Am. 20, 2451–2455 (1990)]. The right lung lobes of four 200 g rats were insonified with an ATL HDI 3000 6.0‐MHz Doppler pulse for 1.5 min and three rats were sham exposed. At the termination of ultrasound or sham exposure, each animal was immediately euthanized with sodium pentobarbital (200 mg/kg IP) and lung tissues were removed intact, inflated with buffered formalin, and examined by a pathologist who was blind to the exposure conditions. Histologically, damage was observed in the lungs exposed to ultrasound as extravasation of erythrocytes into the alveolar spaces. The ACD signal received was analyzed for the presence of increased scattering and radiated noise from inertial cavitation. The variance of the sequentially obtained ACD received pulses correlated with the damage in the exposed lungs. We conclude that inertial cavitation mediated the damage from diagnostic ultrasound

BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas

Activating point mutations of the BRAF gene have been recently reported in papillary thyroid carcinomas. In this study, we analyzed 320 thyroid tumors and six anaplastic carcinoma cell lines and detected BRAF mutations in 45 (38%) papillary carcinomas, two (13%) poorly-differentiated carcinomas, three (10%) anaplastic carcinomas, and five (83%) thyroid anaplastic carcinoma cell lines but not in follicular, Hurthle cell, and medullary carcinomas, follicular and Hurthle cell adenomas, or benign hyperplastic nodules. All mutations involved a T-->A transversion at nucleotide 1796. In papillary carcinomas, BRAF mutations were associated with older age, classic papillary carcinoma or tall cell variant histology, extrathyroidal extension, and more frequent presentation at stages III and IV. All BRAF-positive poorly differentiated and anaplastic carcinomas contained areas of preexisting papillary carcinoma, and mutation was present in both the well-differentiated and dedifferentiated components. These data indicate that BRAF mutations are restricted to papillary carcinomas and poorly differentiated and anaplastic carcinomas arising from papillary carcinomas. They are associated with distinct phenotypical and biological properties of papillary carcinomas and may participate in progression to poorly differentiated and anaplastic carcinomas