[Sir Harold D. Gillies, pioneer of plastic surgery]. / Sir Harold Gillies, pionier van plastische chirurgie.

In the First World War, large numbers of soldiers perished because machine guns and artillery bombardments had rendered the old techniques of combat and weapons hopelessly outdated. In addition to the many deaths, many soldiers were also seriously injured. At the outbreak of the First World War, ENT surgeon Harold D. Gillies signed up with the Royal Army Medical Corps. He used his knowledge of reconstructive surgery in a creative and innovative manner to treat the severely mutilating facial injuries. He thus improved the established techniques of nose reconstruction, skin grafts and facial reconstruction. At the end of the First World War, he had operated on about 11,000 casualties. Surgeons from every part of the world adopted his new principles and Gillies thus created the specialism of plastic and reconstructive surgery. Some of the techniques developed by Gillies are even still in use today.

Minocycline inhibits apoptotic cell death in a murine model of partial flap loss.

For breast reconstruction, the deep inferior epigastric perforator (DIEP) flap has become standard therapy. A feared complication is partial or even total flap loss. In a novel murine model of partial DIEP flap loss, the contribution of apoptotis to flap loss was investigated. The clinically available apoptosis-inhibiting compound minocycline was tested for its ability to reduce cell death. The effect of minocycline on cell proliferation was studied in cell cultures of breast carcinoma. In 12 mice, pedicled DIEP flaps were raised, which were subjected to 15 minutes of ischemia and 4 days of reperfusion. Six mice were treated with minocycline 2 hours before surgery and every 24 hours for 4 days. Apoptosis was revealed by injecting annexin A5 30 minutes before sacrifice. Annexin A5 binds to phosphatidylserines, which are expressed on the cell membrane during apoptotis. Prior to sacrifice, necrosis was measured using planimetry. Minocycline reduced cell death after 4 days from 35.9% (standard deviation = 10.6) to 13.9% (standard deviation = 8.0; P < 0.05). Apoptosis, as shown by annexin A5 binding in nontreated animals, was abundant. Minocycline did not influence tumor growth in cell cultures of human breast cancer. Minocycline treatment leads to increased DIEP flap viability in mice. This study widens the perspective in the improvement of free flap survival in patients.

Bringing cell death alive.

The role of apoptosis in ischemia and reperfusion of the heart has been widely debated. This controversy has been continued because of the lack of an apoptosis detection method that allowed obtaining detailed kinetic and quantitative information on apoptosis. Here we focus on recent findings that look into the detection of apoptosis following ischemia and reperfusion in the heart in animal models and in patients using Annexin-A5 based image technology. Following cardiac cell damage, one major characteristic finding is that apoptotic cells express phosphatidylserines (PS) on the outer leaflet of their cell membrane, serving as a "remove me" signal for the immune system. Annexin-A5, a native plasma protein with a high affinity for PS, can be used to measure this mode of cell death. Several Annexin-A5 based imaging systems have been developed to measure apoptosis from cell culture up to patients. In this review, implications, limitations, and clinical relevance of cell death imaging will be discussed.