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This paper provides information on the safety of ultrasonic diagnostic procedures as currently used in veterinary practice. The known mechanisms of action are described and selected literature on biological effects of ultrasound is reviewed. Current international consensus is presented on the safety of medical ultrasound with respect to thermal effects. To date, there is no independently verified clinical evidence that the level of exposure delivered to the tissues during scanned grey-scale ('B-mode') imaging has any adverse effects. Lung haemorrhage has been observed in animal experiments using diagnostic exposures, but the effects have not been reported in the foetus. Equipment that uses pulsed Doppler transmits higher acoustic outputs in a stationary beam, and can produce temperature increases that may have significant biological consequences. When considering sonographic and pulsed Doppler examinations of the prenatal animal, the safety margins are small and the operator should be aware of the acoustic output of the equipment, the exposure time, and the sensitivity of target tissues.

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Introduction: While estrogen receptor (ER) status has been used as the primary factor influencing the use of selective estrogen receptor modulators (SERMs), a number of ER-positive patients will relapse on this therapy. It has been postulated that SERM-resistance may be modulated by aberrant growth factor signaling, for which progesterone receptor (PR) status may be a surrogate. PR status, however, is frequently not considered as a strong prognostic or predictive marker in ER-positive patients. We sought to define the effect of PR-status on outcomes in such patients treated with SERMs. Methods: The North American Fareston versus Tamoxifen Adjuvant (NAFTA) Trial is an investigator-initiated, multicenter, prospective trial that randomized patients with resected hormone-receptor positive breast cancers to receive either adjuvant tamoxifen (20 mg po daily) or toremifene (60 mg po daily) for five years. Between July 1998 and December 2002, 1692 ER-positive positive patients were randomized. PR was missing for 15 patients. The remaining 1677 (1424 PR-positive and 253 PR-negative) patients formed the cohort of interest for this analysis. The impact of PR status on overall (OS) and disease-free survival (DFS) was assessed using Kaplan Meier and Cox Proportional Hazards modeling. Results: The median patient age was 67 (range; 41-100) with a median tumor size of 1.2 cm (range; 0.01-14.00 cm). PR-positive status was correlated with node-negative disease (91.3% vs. 87.0%, p=0.035) and low grade tumors (34.9% vs. 27.7%, p=0.009), but was not associated with tumor size (p=0.533) or patient age (p=0.067). With a median follow-up of 59 months, the 5-year actuarial OS and DFS of PR-negative patients was significantly worse than that of PR-positive patients (88.5% vs. 94.3%, p=0.009 and 86.1% vs. 92.5%, p=0.003, respectively). Controlling for tumor size, grade and lymph node status, PR-negative status continued to predict worse DFS (OR=1.561; 95% CI: 1.013-2.406, p=0.043), although it lost significance in terms of OS (OR=1.619; 95% CI: 0.980-2.674, p=0.060). Conclusion: PR-negative status is an independent predictor of worse DFS in ER-positive patients treated with SERMs. These data support the hypothesis that PR-negative status may signal a higher rate of SERM-resistance, and should be considered in adjuvant therapy decisionmaking. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-10.