PSC-833 reverses multidrug resistance by P-glycoprotein at concentrations ≤ ≤ ≤ ≤1000 ng/ml. A phase I study of PSC-833 and doxorubicin was conducted to determine the maximum tolerated dose and to investigate pharmacokinetics. PSC-833 was intravenously infused as a 2-h loading dose (LD) and a subsequent 24-h continuous dose (CD). Doxorubicin was infused over 5 min, 1 h after the LD. The starting dose was 1 mg/kg for both LD and CD with 30 mg/m 2 doxorubicin; these dosages were increased to 2 and 10 mg/kg and 50 mg/m 2 , respectively. Thirty-one patients were treated. Nausea/ vomiting was controllable with granisetron and dexamethasone. Neutropenia and ataxia were dose limiting. Steady-state concentrations of PSC-833 > > > >1000 ng/ml were achieved at a 2 mg/kg LD and a 10 mg/kg CD. Ex-vivo bioassay revealed that activity in serum for reversing multidrug resistance was achieved in all patients; IC 50 of P-glycoprotein expressing 8226/Dox 6 in patients' serum was decreased from 5.9 to 1.3 µ µ µ µg/ml (P < < < <0.0001) by PSC-833 administration. Doxorubicin clearance was 24.3 ± ± ± ±13.7 (mean ± ± ± ±SD) liter/h/m 2 , which was lower than the 49.0 ± ± ± ±16.9 liter/h/m 2 without PSC-833 (P < < < <0.0001). The relationship between doxorubicin exposure and neutropenia did not differ between patients treated and not treated with PSC-833. The recommended phase II dose of PSC-833 was 2 and 10 mg/kg for LD and CD, respectively, which achieved a sufficient concentration in serum to reverse drug resistance, as confirmed by bioassay. The dose of doxorubicin should be reduced to 40 mg/m 2 , not because of the pharmacodynamic interaction between PSC-833 and doxorubicin affecting hematopoiesis, but because of pharmacokinetic interaction.

Summary:Parosteal lipoma is a rare tumor, accounting for approximately 0.3% of all lipomas. Bony lesions are often found in patients with this tumor (59.2%), making the differential diagnosis of malignant tumors important. Our case was a 64-year-old male patient who complained of a 25 × 15-cm mass on his right thigh that had grown rapidly over a 2-month period. On magnetic resonance imaging, a high-intensity lesion was observed on the surface of the femur beneath the vastus medialis muscle on T1 and T2 images, with low intensity on a T1 fat suppression image. No significant bony changes were detected. During total tumor resection, the tumor was found on the femur with tight continuity, with tiny areas of spiculation palpable on the bone surface. The exact tumor size was 18 × 13 × 6 cm. The pathological diagnosis was lipoma, the same result as in the former open biopsy. This case was the largest parosteal lipoma of the femur reported without periosteal changes. In cases of deep parosteal lipomas, the detection of rapidly progressive and growing pseudotumors with ossification or chondromatous changes implies malignancy. A preoperative biopsy is mandatory and must be followed by careful planning and preparation for handling in malignant cases. Plastic surgeons should therefore keep the diagnosis of parosteal lipoma in mind to provide appropriate (not too much or too little) surgical treatment.

Background: When frostbite thaws, reperfusion injury has a crucial impact on tissue injury, and production of free radicals induces further tissue damage. This study examined whether extract of Ginkgo biloba 761 could ameliorate frostbite injury as a free radical scavenger. Methods: Seventy-five Fisher 344 rats were divided into five groups of 15, and frostbite injury was created in each animal by sandwiching the left hind foot between a frozen magnet (−78.5°C) and a room-temperature magnet. Group I received saline; groups II, III, and IV received extract of Ginkgo biloba 761 (200, 100, and 50 mg/kg, respectively); and group V received superoxide dismutase (12 mg/kg). All drugs were injected intraperitoneally three times at 24-hour intervals. The wound surface area was measured throughout the wound healing period. Wounds were also harvested at various times to count cells stained by monoclonal antibodies for 4-hydroxy-2-nonenal and 8-hydroxy-2′-deoxyguanosine. Results: Compared to group I, the wound surface area was significantly smaller in groups II and III on days 1 and 3 after wound creation. Histologic examination revealed significantly more 4-hydroxy-2-nonenal–stained cells and 8-hydroxy-2′-deoxyguanosine–stained cells in group I compared to other groups on day 1. However, there was no difference in the total healing period among the groups. A higher dose test of extract of Ginkgo biloba 761 (300 mg/kg daily) induced animal death, probably because of toxicity. Conclusion: Extract of Ginkgo biloba 761 demonstrated a protective effect against frostbite in the present model and probably alleviated reperfusion injury by reducing tissue peroxidation.