The fillet foot for endweight-bearing cover of below knee amputations

Four patients with five severely traumatized lower legs but preserved feet were treated with fillet flaps from the foot to cover an elective, below knee amputation stump. The posterior tibial neurovascular bundle nourished and innervated this flap. While the posterior tibial artery and vein may be cut and re-anastomosed to prevent kinking and occlusion, the posterior tibial nerve should always be kept in continuity to maintain the quality of sensation to this flap. Four flaps survived and one necrosed secondary to venous insufficiency. Due to its innervation and the unique qualities of heel skin, the flap is very durable and has endweight-bearing capabilities. This has permitted the fitting of an endweight-bearing, total contact, fully extended, below knee prosthesis that appears to offer significant improvement in ease of use and normality of gait pattern over standard patellar tendon-bearing prostheses.     

Long microvenous allografts in rabbit femoral arteries and veins

In this study the patency of long microvenous allografts in rabbits with and without immunosuppressive drug therapy was investigated. Eighty-two microvenous autografts (controls) and allografts were transplanted into rabbit femoral vessels. Veno-venous autograft controls were 100% patent at 3 weeks. Rejection of non-immunosuppressed veno-venous allografts consistently produced occlusion between 15-20 days. Thrombus filled the lumen, and a leucocyte invasion destroyed the graft wall. In contrast vein allografts into arteries were 100% patent at 3 weeks; this was reduced to 50% at 4 weeks. Low (5 mg/kg/day) and high (20 mg/kg/day) doses of hydrocortisone over 21 days improved the 3 week patency in veno-venous allografts to 28.5% and 57.0% respectively. Cyclosporin A (15 mg/kg/day) over 8 or 22 days significantly increased the patency rate of veno-venous allografts to 100%. Only cyclosporin A treated rabbits maintained allografts of normal vein morphology to 3 weeks.     

Production and characterization of genetically engineered antibody molecules

Expression of antibody heavy- and light-chain genes by transfection permits the production of monoclonal antibodies with improved biological and antigen-binding properties. The immunoglobulin genes are placed in vectors containing a gene for encoding a protein that provides a biochemically selectable function in eukaryotic cells; these vectors are transfected into myeloma and hybridoma cells. Selection of drug-resistant cells permits the efficient isolation of the rare cells that express the transfected DNA. By placing heavy and light chains on plasmids with different selectable markers, one can deliver heavy- and light-chain genes simultaneously to the same cell. The transfected immunoglobulin genes are efficiently expressed and the proteins produced are a faithful mirror of the genes that were introduced. Using the standard techniques of genetic engineering and gene transfection, we can now produce antibodies of widely varying structures, including chimeric antibodies with segments derived from different species. These antibodies provide useful reagents to study structure-function relationships within the antibody molecule. Ultimately it will be possible to produce a new generation of antibody molecules with improved antigen-binding properties and effector functions.     

The significance of resection length on the patency rate, and the histopathology, of experimentally avulsed and microsurgically repaired blood vessels

The significance of resection length on patency rate, and the histopathology, of microsurgically repaired avulsed blood vessels was examined at 3 weeks in two groups of experimentally avulsed rabbit femoral arteries repaired by different surgeons and in a single series of avulsed and repaired veins. All veins were patent 3 weeks after avulsion and microsurgical repair. Histopathology indicated that the vast majority of lesions in veins were removed at resection. Surgeon A achieved 75% patent arteries and Surgeon B achieved 100% arterial patency (resecting 3.7 mm more on average than Surgeon A). Histopathology revealed numerous luminal circumferential lesions remained in the avulsed artery wall following resection. These lesions were sites of smooth muscle cell proliferation and neointima formation. Although similar arterial damage occurs in human avulsion, considerably lower patency rates are achieved for human arterial avulsion repair than were reported in this experimental study. Factors in addition to vessel wall damage must therefore be involved in thrombosis and occlusion of repaired avulsed arteries. Such factors might be lengthy ischaemia time and severe spasm.     

Convection-enhanced delivery of macromolecules in the brain.

For many compounds (neurotrophic factors, antibodies, growth factors, genetic vectors, enzymes) slow diffusion in the brain severely limits drug distribution and effect after direct drug administration into brain parenchyma. We investigated convection as a means to enhance the distribution of the large and small molecules 111In-labeled transferrin (111In-Tf; M(r), 80,000) and [14C]sucrose (M(r), 359) over centimeter distances by maintaining a pressure gradient during interstitial infusion into white matter to generate bulk flow through the brain interstitium. The volume of distribution (Vd) containing > or = 1% concentration of infusion solution increased linearly with the infusion volume (Vi) for 111In-Tf(Vd/Vi, 6:1) and [14C]sucrose (Vd/Vi, 13:1). Twenty-four hours after infusion, the distribution of 111In-Tf was increased and more homogeneous, and penetration into gray matter had occurred. By using convection to supplement simple diffusion, enhanced distribution of large and small molecules can be obtained in the brain while achieving drug concentrations orders of magnitude greater than systemic levels.