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N M Edwards

Publications and source records attributed to N M Edwards.

41 records · Page 3Linked to original sources
PubMed1991

Binding of preformed xenoantibodies to porcine bioprosthetic valves.

We have investigated whether preformed antibodies against xenoantigens bind to cellular elements remaining on porcine bioprosthetic valves after various methods of preservation. Fresh porcine valves treated with either acetone, 4% formaldehyde, or 0.625% glutaraldehyde, as well as an unfixed valve, were incubated with antiserum against porcine xenoantigens. This serum was prepared using the affinity purification method with porcine lymphocytes as the target. The valves were stained with secondary fluorescein-conjugated antibody against immunoglobulin M or immunoglobulin G and examined under fluorescent microscopy. Intense binding of immunoglobulin M to the endocardium was observed in the unfixed valve as well as in valves fixed in acetone and formaldehyde. Glutaraldehyde fixation eliminated binding of antibody. Binding was not noted within the connective tissue. No binding of antiimmunoglobulin G was noted on the endocardium of any of the sections. Examination of three glutaraldehyde-treated porcine valves explanted from the aortic position after 10 years in situ showed no immunoglobulin deposition. These results demonstrate the elimination of antigenicity to preformed antibodies in the endocardium and connective tissue of glutaraldehyde-preserved porcine valves. The findings may, in part, explain the poor performance of formaldehyde-preserved bioprosthetic xenograft valves in the past and support the use of glutaraldehyde as a preferred agent for preservation of bioprosthetic endovascular materials.

Animals↗
PubMedDate not supplied

Natural antipig xenoantibody is absent in neonatal human serum.

BACKGROUND: Discordant xenotransplantation represents an attractive alternative to allotransplantation in light of the current shortage of donor organs suitable for heart allotransplantation. Unfortunately, discordant xenotransplantation is still limited by hyperacute rejection, a process thought to be mediated by natural antixenodonor antibodies. On the basis of our previous findings that cytotoxic natural xenoantibodies are immunoglobulin M in nature and that natural immunoglobulin M xenoantibodies are barely detectable in neonatal baboon serum, we postulated that immunoglobulin M xenoantibodies may be absent from newborn human serum. METHODS: Neonatal human sera were obtained from the cord blood of normal term infants and pooled. Pooled adult human sera were used as a control. A whole cell enzyme-linked immunosorbent assay and a complement-mediated cytotoxicity assay were performed to determine the binding and cytotoxicity of these xenoantibodies to pig aortic endothelial cells and pig lymphocytes. RESULTS: Neonatal human sera did not show binding of immunoglobulin M xenoantibodies to pig aortic endothelial cells or lymphocytes. However, low level binding of immunoglobulin G xenoantibodies was detected to pig endothelial cells and lymphocytes. In contrast, adult human sera showed significant binding of both natural immunoglobulin M and G xenoantibodies to pig aortic endothelial cells and lymphocytes. In addition, adult human immunoglobulin M xenoantibodies bound with similar avidity to both cultured adult and neonatal pig aortic endothelial cells. Although neonatal human sera were not cytotoxic to target cells, adult sera were cytotoxic to both pig aortic endothelial cells and pig lymphocytes. Our findings indicate that neonatal human sera lack natural antipig immunoglobulin M xenoantibodies, and therefore, neonatal human serum is not cytotoxic to pig endothelial cells or lymphocytes. Like adult pig endothelial cells, neonatal pig endothelial cells may also express similar membrane xenoantigens recognized by natural immunoglobulin M xenoantibodies. CONCLUSIONS: The absence of cytotoxic natural immunoglobulin M xenoantibodies in the neonate suggests that discordant xenotransplantation may be feasible in the neonate.

Adult↗
PubMedDate not supplied

Pediatric retransplantation.

Previous studies have attempted to outline the efficacy of heart retransplantation in adults. A limited number of these retransplantation procedures have been performed in children; however, no study to date has evaluated the risk of heart retransplantation in this specific patient population. We conducted a retrospective review of 17 pediatric (non-neonatal) heart transplant recipients who subsequently underwent heart retransplantation. Thirteen male and four female patients underwent retransplantation at four different institutions between 1974 and 1992. Patient age at the time of primary transplantation ranged from 2 to 19 years (mean, 12.5 years) and from 3 to 30 years (mean, 16 years) at retransplantation. The time interval between transplantation procedures ranged from 2 days to 15.6 years and was not predictive of patient outcome. Follow-up after retransplantation ranged from 1 day to 11 years (mean, 2.8 years). All patients were New York Heart Association class 3 or class 4 at the time of retransplantation. After retransplantation all survivors were New York Heart Association class 1. No patient had mechanical device implantation or extracorporeal membrane oxygenation bridge-to-transplantation at primary transplantation or retransplantation. The indication for retransplantation was transplant coronary artery disease (TxCAD) in seven patients (41.2%), acute rejection in four (23.5%), chronic rejection in one (5.8%), chronic rejection associated with TxCAD in four (23.5%), and intraoperative donor organ failure in one (5.8%). No significant difference occurred in linearized rates of rejection or infection or in actuarial freedom from rejection or infection when secondary grafts were compared with primary grafts in patients undergoing retransplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗