MR findings of hepatic cavernous hemangioma after intraarterial infusion of iodized oil

Magnetic resonance (MR) imaging was performed on five tumors of three patients who had hepatic hemangiomas. Four tumors were given an intraarterial infusion of 3–8 ml of iodized oil, while one tumor was not. MR images were obtained at 2.0 or 0.5 T. A single spin echo sequence with TE of 30 ms and TR of 500 ms and a double echo sequence with TEs of 60 and 150 ms and TR of 2000 ms, were used to produce relatively T1-, T2-weighted, and heavily T2-weighted images, respectively. Follow-up MR imaging was done 1–5 months after infusion of iodized oil. On relatively T1 weighted images, hemangiomas showed iso or hypointensity. On T2-weighted images, all tumors showed hyperintensity. However, on heavily T2-weighted images, tumors with iodized oil showed heterogeneous, slight hyperintensity, while tumors without iodized oil showed characteristic appearance of marked hyperintensity in hemangiomas. In hepatic cavernous hemangiomas with intraarterial infusion of iodized oil, familiarity with this unusual MR intensity of tumors on heavily T2-weighted images is useful to avoid the incorrect diagnosis and to reduce the frequency of inappropriate hepatic resection.     

Effectiveness of raloxifene on bone mineral density and serum lipid levels in post-menopausal women with low BMD after discontinuation of hormone replacement therapy

OBJECTIVE: To evaluate the effect of raloxifene on bone mineral density (BMD) and serum lipid levels in post-menopausal women who had discontinued hormone replacement therapy (HRT). METHODS: Thirty-four post-menopausal women with low BMD who had taken 60 mg of raloxifene daily for 12 months after discontinuing HRT were evaluated retrospectively. Information about their demographics, fracture history, BMD, lipid profiles and adverse events were collected from medical records and intranet database. The outcome measures were changes in the spine (L2-L4) and femur BMD, serum lipid concentrations, fracture rate and tolerability. RESULTS: The post-menopausal women had a significant increase in their spine (L2-L4) and femur BMD from their baseline BMD [spine, 2.9 +/- 4.6% (P < 0.001); femur, 3.0 +/- 6.6% (P = 0.01)]. Serum low-density lipoprotein (LDL) cholesterol was significantly reduced by 22.6% below baseline after 12 months (P = 0.007). No fractures were observed during therapy. Raloxifene was well tolerated. The most common adverse event was hot flash, which was generally mild. CONCLUSIONS: Raloxifene increases BMD at important skeletal sites, and lowers LDL cholesterol with tolerable adverse events.     

Systemic and specific delivery of small interfering RNAs to the liver mediated by apolipoprotein A-I.

Tissue-targeted delivery of small interfering RNA (siRNA) must be achieved before RNA interference (RNAi) technology can be used in practical therapeutic approaches. In this study, the potential of apolipoprotein A-I (apo A-I) for the systemic delivery of nucleic acids to the liver is demonstrated using real-time in vivo imaging. As a proof of concept, synthetic siRNAs against hepatitis B virus (HBV) were formulated into complexes of apo A-I and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)/cholesterol (DTC-Apo) and injected intravenously (i.v.) into a mouse model carrying replicating HBV. We show that administration of these nanoparticles can significantly reduce viral protein expression by receptor-mediated endocytosis. The advantages of the apo A-I-mediated siRNA delivery method are its liver specificity, its effectiveness at low doses (< or = 2 mg/kg) in only a single treatment, and its persistent antiviral effect up to 8 days. The liver-targeted gene silencing was also shown by in vivo images, in which bioluminescent signals emitted from the liver were efficiently reduced after i.v. administration of luciferase-specific siRNA and DTC-Apo lipoplex. Thus, our unique approach to siRNA delivery creates a foundation for the development of a new class of promising therapeutics against hepatitis viruses or hepatocyte genes related to tumor growth.     

Predictive value of pretreatment metabolic activity measured by fluorodeoxyglucose positron emission tomography in patients with metastatic advanced gastric cancer: the maximal SUV of the stomach is a prognostic factor

Purpose

Few studies have evaluated metabolic activity by ¹⁸F-FDG PET as a prognostic factor in advanced gastric cancer (AGC). We investigated its prognostic role in metastatic AGC.

Methods

We enrolled 82 patients with metastatic AGC, who were treatment-naive and underwent pretreatment ¹⁸F-FDG PET/CT scanning. In each patient, the maximal standardized uptake value (SUVmax) was measured in each target lesion. Stomach_SUVmax was defined as SUVmax in the stomach, while Total_SUVmax was defined as the highest SUVmax among all the target lesions.

Results

The stomach was the organ most frequently displaying the highest SUVmax among all the target lesions (in 67.1?% of patients). A Total_SUVmax value of 11.5 was the value with the maximum sum of sensitivity and specificity from receiver-operating characteristic curves for progression-free survival (PFS). PFS was significantly longer in patients with a Total_SUVmax value <11.5 than in those with a Total_SUVmax value ≥11.5 (P?=?0.023); however, overall survival (OS) was not (P?=?0.055). A Stomach_SUVmax value of 6.0 was derived by similar methods. PFS and OS were significantly longer in those with a Stomach_SUVmax value <6.0 than in those with a Stomach_SUVmax value ≥6.0 (P?=?0.001 and P?=?0.006, respectively). Furthermore, those with a low Total_SUVmax and those with a low Stomach_SUVmax showed better chemotherapeutic responses (P?=?0.016 and P?=?0.034, respectively). Among patients with histologically undifferentiated carcinomas, those with lower Total_SUVmax and those with lower Stomach_SUVmax showed longer median PFS (P?=?0.027 and P?=?0.005, respectively) and OS (P?=?0.009 and P <0.001, respectively). Multivariate analysis demonstrated Stomach_SUVmax as an independent predictor of PFS (P?=?0.002) and OS (P?=?0.038).

Conclusion

Pretreatment metabolic activity may be a useful prognostic marker in patients with metastatic AGC undergoing palliative chemotherapy. Notably, Stomach_SUVmax was the single, most robust factor predicting prognosis.     

Cardiovascular Safety Pharmacology of Sibutramine

Sibutramine is an anorectic that has been banned since 2010 due to cardiovascular safety issues. However, counterfeit drugs or slimming products that include sibutramine are still available in the market. It has been reported that illegal sibutramine-contained pharmaceutical products induce cardiovascular crisis. However, the mechanism underlying sibutramine-induced cardiovascular adverse effect has not been fully evaluated yet. In this study, we performed cardiovascular safety pharmacology studies of sibutramine systemically using by hERG channel inhibition, action potential duration, and telemetry assays. Sibutramine inhibited hERG channel current of HEK293 cells with an IC₅₀ of 3.92 μM in patch clamp assay and increased the heart rate and blood pressure (76 Δbpm in heart rate and 51 ΔmmHg in blood pressure) in beagle dogs at a dose of 30 mg/kg (per oral), while it shortened action potential duration (at 10 μM and 30 μM, resulted in 15% and 29% decreases in APD₅₀, and 9% and 17% decreases in APD₉₀, respectively) in the Purkinje fibers of rabbits and had no effects on the QTc interval in beagle dogs. These results suggest that sibutramine has a considerable adverse effect on the cardiovascular system and may contribute to accurate drug safety regulation.