Familial amyloid polyneuropathy (FAP) is a fatal autosomal dominant disorder. Progressive peripheral and autonomic neuropathy are associated with neural and visceral deposition of amyloid, derived most commonly from the Met-30 variant of the plasma protein transthyretin. We have reported previously that orthotopic liver transplantation causes prompt replacement of variant transthyretin by the donor wild-type in the plasma. We now report clinical outcome 1-2 years after transplantation. Three of the first four patients have improved general wellbeing, walking ability, and bowel function, and one of them has regained normal bladder and bowel function. There has been little objective improvement in peripheral neuropathy. The fourth patient, who had the most severe neurological deficits and a complicated postoperative course, has not improved but there has been no further deterioration in contrast to the inexorable progression before transplantation. Quantitative scintigraphy with radiolabelled serum amyloid P component showed visceral amyloid deposits in all three patients studied; in two who were followed serially the deposits regressed after transplantation in association with the clinical improvement. Another FAP patient who was also monitored prospectively for 2 years but who did not undergo transplantation, showed, as expected, progression of neuropathy and increased visceral amyloid deposition. Liver transplantation does therefore have important benefits in FAP during the first 2 years after surgery. Neurological decline is halted and amyloid deposits can be mobilised. The best timing and long-term results of the procedure must now be established.

Adult↗

PubMed1993

15-Deoxyspergualin prolongs pancreatic islet allo- and xenograft survival in mice.

The new immunosuppressant 15-deoxyspergualin was evaluated in allogeneic and xenogeneic pancreatic islet transplantation. In the allograft study 500 collagenase-isolated C57BL/6 mouse islets were transplanted under the renal capsule of alloxan-diabetic C57BL/Ks mice that were either 15-deoxyspergualin-treated (n = 15) or given saline only (n = 8). When 15-deoxyspergualin was given (5 mg/kg b.wt. intraperitoneally) until day 28 after transplantation in a special dosage schedule, 10 out of 15 animals were normoglycaemic one week after transplantation and 6 were still normoglycaemic after ten weeks. All 8 control animals were hyperglycaemic after 18 days. Light microscopy showed graft rejection in hyperglycaemic mice, but only mild infiltration of lymphocytes in the grafts of normoglycaemic animals. In the xenograft study C57BL/Ks mice were transplanted under the renal capsule with 500-750 foetal porcine islet-like cell clusters. The grafts were examined for evidence of rejection with light microscopy at different time points after implantation. In the control animals given saline only (n = 37) there was progressive evidence of rejection starting on day seven. In 15-deoxyspergualin treated animals (2.5 mg/kg intraperitoneally; n = 27) there was significantly less infiltration at days 7, 14 and 21. After 32 days there was, however, no difference between controls and 15-deoxyspergualin treated mice. A doubling of the 15-deoxyspergualin dose (5.0 mg/kg intraperitoneally; n = 5) did not further improve the survival of the xenografted islet-like cell clusters. There was no synergistic effect when cyclosporine A (12.5 mg/kg intraperitoneally) was added to the 15-deoxyspergualin therapy (n = 34).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993