Neoadjuvant chemotherapy combined with regional hyperthermia (RHT) for locally advanced primary or recurrent high-risk adult soft-tissue sarcomas (STS) of adults: long-term results of a phase II study.

In this phase II study, activity and safety of neoadjuvant regional hyperthermia (RHT) combined with chemotherapy was investigated in 59 patients with primary advanced or recurrent high-risk soft-tissue sarcoma (STS). Patients received four EIA cycles consisting of etoposide, ifosfamide and doxorubicin combined with RHT followed by surgical resection and adjuvant treatment. The overall objective response (OR) rate was 17%, with one complete (2%) and eight partial (15%) responses. In addition, 13 minor responses (25%) were seen. At time of surgery, complete necrosis (pCR) occurred in 6 patients and >75% necrosis (favourable histological response (FHR)) in 12 patients. At the completion of protocol treatment, 36 patients were rendered disease-free which was significantly associated with the initial radiographic and/or pathological tumour response (P=0.004). Treatment-related toxicity was acceptable overall. At a medium follow-up of 82 months, local treatment failure occurred in 33 patients, median overall survival (OS) was 52 months, and the 5-year survival rate was 49% (95% confidence interval (CI): 36-61%). OS which did not differ for extremity versus non-extremity STS (P=0.21) was better for patients responding to EIA combined with RHT (P<0.01).

A (2)H NMR study of macroscopically aligned bilayer membranes containing interfacial hydroxyl residues.

The polar interface of membranes containing phosphatidylglycerol or cholesterol was studied by (2)H nuclear magnetic resonance (NMR) as a function of membrane hydration. The membranes were macroscopically aligned and hydrated with deuterium oxide. Water uptake and membrane annealing was achieved under NMR control, using a novel hydration technique. Well-resolved (2)H quadrupolar doublets were obtained from individual hydroxyl residues and from the interlamellar water. The response of the phosphatidylglycerol headgroup and of the cholesterol molecule to the spontaneous evaporation of interlamellar water could be thus monitored continuously. It is shown that the phosphatidylglycerol headgroup undergoes changes of conformation and average orientation with respect to the membrane surface and that the off-axis motion of the cholesterol molecule decreases. The deuteron exchange between hydroxyl residues and surface-associated D(2)O was determined by an inversion transfer technique. The exchange rates of the hydroxyl residues in the phosphatidylglycerol headgroup were different and depended strongly on the total hydration of the membrane. Significantly lower and almost hydration-independent rates were obtained for cholesterol. These results will be discussed with reference to earlier reports on the headgroup dynamics of phosphatidylglycerol and on the interaction of cholesterol with the membrane-water interface.

Contribution of copper binding to the inhibition of lipid oxidation by plasmalogen phospholipids.

The role of plasmalogen phospholipids for copper-induced lipid oxidation was evaluated. Using 1H-NMR we observed that the copper (CuSO4)-promoted oxidative degradation of polyunsaturated fatty acids in micellar solution was dose-dependently attenuated by the plasmalogen lysoplasmenylethanolamine from bovine brain (lysoBP-PtdEtn). This was due to a direct interaction of copper ions with the plasmalogen-specific enol ether double bond. The enol ether methine 1H signal decreased on the addition of copper, saturation being reached at a molar ratio of lysoBP-PtdEtn to copper of 1:1. The original 1H signal was recovered almost completely after the addition of EDTA. Enrichment of micelles and low-density lipoproteins (LDLs) with plasmalogen phospholipids led to a decrease in the Cu(II) concentration in the aqueous media. After loading of LDLs in vitro with BP-PtdEtn, the LDL-dependent formation of Cu(I) was decreased, in particular in particles experimentally supplemented with alpha-tocopherol. The suppression of copper-promoted lipid oxidation that was observed in the presence of plasmalogen phospholipids plus alpha-tocopherol was greater than the sum of the protective effects elicited by the two substances alone. In conclusion, the formation of a complex between copper ions and the plasmalogens accounts partly for their inhibition of copper-induced lipid oxidation.

Arthroscopic arthropathy: iatrogenic arthroscopic joint lesions in animals.

Damage to the articular cartilage does occur, on occasion, during the course of diagnostic arthroscopy and arthroscopic surgery. Because of this, we decided to do an arthroscopic gross and histologic study of the alterations in the articular cartilage and the underlying bone that we produced in the joints of dogs. Depending upon the instruments used and the depth of the lesion created, various types of lesions were produced in the cartilage, including track-like fissures, patch-like defects, and even superficial damage to the subchondral bone. Superficial lesions reaching only to the transitional zone were repaired by a smoothing of the edges of the defects. In the deeper lesions, repair consisted of a flat fibrous covering with sclerosis of the subchondral bone. These defects were followed for a period of 6 months, and in no case did a complete filling in occur. We realize that this animal experimental study is not a model for human osteoarthritis, but it casts some light on the importance of iatrogenic lesions of the joint. This study was carried out for the purpose of drawing attention to damage of the articular cartilage that can occur during arthroscopic surgery, especially in narrow joint spaces. These findings underline the need for responsible and effective education in the field of diagnostic and therapeutic arthroscopy.