Standardized pretreatment breast MRI--accuracy and influence on mastectomy decisions.

BACKGROUND AND OBJECTIVES: Routine pretreatment breast magnetic resonance imaging in newly diagnosed cancer patients remains controversial. We assess MRI accuracy and influence on mastectomy decisions after institution of standardized pretreatment MRI. METHODS: A prospectively collected database of 74 consecutive new invasive breast cancer patients with pretreatment breast MRI was reviewed for treatment choice, radiologic, and pathologic results. Thirty-eight of 72 patients with available surgical records underwent mastectomy. Mastectomy preoperative and operative electronic records were reviewed for treatment decision analysis. RESULTS: Seventeen of 72 (23.6%) invasive breast cancer patients were likely influenced to undergo mastectomy by new information from MRI. MRI reported that the multifocal/multicentric (MF/MC) rate was 20 of 72 (27.8%) versus 19 of 72 (26.4%) by surgical pathology. MRI sensitivity for MF/MC disease was 89.5% versus 11.8% for mammography. MRI specificity was 84.2%. All three false positives declined recommended preoperative biopsies. MRI MF/MC diagnosis highly correlated with pathology results, P < 0.001. CONCLUSIONS: Increased mastectomy rate from 29 to 52.8% after standardization of pre-treatment breast MRI for invasive cancer is largely due to MRI findings of increased extent of disease. These MRI findings correlate well with pathologic findings and appear to justify the performance of mastectomies in these patients.

Comparison of the discriminative stimulus effects of salvinorin A and its derivatives to U69,593 and U50,488 in rats.

BACKGROUND AND RATIONALE: Research interests regarding the psychopharmacology of salvinorin A have been motivated by the recreational use and widespread media focus on the hallucinogenic plant, Salvia divinorum. Additionally, kappa opioid (KOP) receptor ligands may have therapeutic potential in the treatment of some neuropsychiatric conditions, including drug dependence and mood disorders. Salvinorin A is a selective KOP agonist, but only a few studies have explored the discriminative stimulus effects of this compound. OBJECTIVE: This study compared the discriminative stimulus effects of salvinorin A and two synthetic derivatives of salvinorin B to the KOP agonists, U69,593 and U50,488. MATERIALS AND METHODS: Sixteen male Sprague-Dawley rats trained to discriminate U69,593 (0.13 mg/kg, s.c., N = 8) or U50,488 (3.0 mg/kg, i.p., N = 8) under a fixed-ratio 20 schedule of food reinforcement were administered substitution tests with salvinorin A (0.125-3.0 mg/kg, i.p.). The animals trained to discriminate U69,593 were also administered substitution tests with salvinorin B ethoxymethyl ether (0.005-0.10 mg/kg, i.p.) and salvinorin B methoxymethyl ether (0.03-0.10 mg/kg, i.p.). Another eight rats were trained to discriminate 2.0 mg/kg salvinorin A and tested with U69,593 (0.04-0.32 mg/kg) and U50,488 (0.4-3.2 mg/kg). RESULTS: Salvinorin A and both synthetic derivatives of salvinorin B substituted completely for U69,593. Additionally, cross-generalization was observed between salvinorin A and both KOP agonists. CONCLUSION: These findings support previous reports indicating that the discriminative stimulus effects of salvinorin A are mediated by kappa receptors. Future studies may assist in the development and screening of salvinorin A analogs for potential pharmacotherapy.