Managing the risks of facial transplantation.
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Biomedical subjects
Publications and source records attributed to Shehan Hettiaratchy.
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The hair-tourniquet syndrome involves circumferential strangulation of an appendage by a human hair or fibre and usually affects infants under the age of 2. It is an emergency condition that induces progressive oedema, ischaemia and tissue necrosis and can lead to the autoamputation of digits or other strangulated structures. Though the majority of cases are accidental, a proportion may be due to nonaccidental injury. The prompt diagnosis and treatment of the condition is vital to attain a good outcome and prevent further harm to the child. We report a case of hair-tourniquet syndrome affecting multiple toes of an infant, and suggest that awareness of the condition should be increased to help prevent its potential complications.
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BACKGROUND: Tolerance to composite tissue allografts might allow the widespread clinical use of reconstructive allotransplantation if protocols to achieve this could be rendered sufficiently nontoxic. The authors investigated whether tolerance could be generated in miniature swine to composite tissue allografts across a major histocompatibility (MHC) barrier. A clinically relevant tolerance protocol involving hematopoietic cell transplantation without the need for irradiation or myelosuppressive drugs was tested. METHODS: Seven recipient animals were transiently T-cell depleted and a short course of cyclosporine was initiated. Twenty-four hours later, a donor hematopoietic cell transplant consisting of cytokine-mobilized peripheral blood mononuclear cells or bone marrow cells and a heterotopic limb transplant were performed. In vitro anti-donor responsiveness was assessed by mixed-lymphocyte reaction and cell-mediated lympholysis assays. Acceptance of the limb allografts was determined by gross and histologic appearance. Chimerism in the peripheral blood and lymphohematopoietic organs was assessed by flow cytometry. RESULTS: All seven experimental animals accepted the musculoskeletal elements but rejected the skin of the allografts. All but one of the animals displayed donor-specific unresponsiveness in vitro. The animals that received cytokine mobilized-peripheral blood mononuclear cells showed chimerism but had clinical evidence of graft-versus-host disease (GVHD). None of the animals that received bone marrow cells showed stable chimerism and none developed GVHD. CONCLUSIONS: This protocol can achieve tolerance to the musculoskeletal elements of composite tissue allografts across an MHC barrier in miniature swine. Stable chimerism does not appear to be necessary for tolerance and may not be desirable because of the risk of GVHD.
Composite tissue allotransplantation (CTA) holds great potential for reconstructive surgery. The recent hand transplants have made this a clinical reality. However, concerns about CTA have divided the medical community. The current transplants require life-long immunosuppression, which could place the recipients at risk of serious complications. In addition despite potent immunosuppression, chronic rejection may still negate any early favourable results. This article will outline the clinical experience of CTA, the major problems of the technique and the potential solutions to these problems.
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A high incidence of a post-transplant lymphoproliferative disorder (PTLD) is observed in miniature swine conditioned for allogeneic hematopoietic cell transplantation using a protocol involving T-cell depletion and cyclosporine therapy. This study was designed to assess contributing factors to disease development. Forty-six animals were studied including 12 (26%) that developed PTLD. A number of risk factors for PTLD were examined, including degree of immunosuppression, degree of MHC mismatch and infection by a porcine lymphotrophic herpesvirus (PLHV-1). Flow cytometry was used to measure host and donor T- and B-cell levels in the peripheral blood. Porcine lymphotrophic herpesvirus viral load was determined by quantitative PCR. Animals developing PTLD had significantly lower levels of T cells on the day of transplant. Cyclosporine levels did not differ significantly between animals with and without PTLD. Animals receiving transplants across a two-haplotype mismatch barrier showed an increased incidence of PTLD. All animals with PTLD had significant increases in PLHV-1 viral loads. Porcine lymphotrophic herpesvirus viral copy numbers remained at low levels in the absence of disease. The availability of a preclinical large-animal model with similarities to PTLD of humans may allow studies of the pathogenesis and treatment of that disorder.
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OBJECTIVE: To review the first clinical cases of composite tissue allotransplantation (CTA) for reconstructive surgery and to discuss the outcome of and indications for these procedures in the context of chronic immunosuppression. SUMMARY BACKGROUND DATA: The first human hand transplant was performed in 1998. This procedure, as well as other composite tissue transplants, offers the potential for correcting untreatable large tissue defects. However, concerns remain regarding obligatory chronic immunosuppression and long-term functional results. METHODS: All the CTAs performed in humans that have been published or documented were reviewed. The preexisting clinical conditions and surgical procedures and the immunosuppressive therapy are described. The functional results and the complications or side effects of the treatment are detailed. RESULTS: Vascularized tendons (two cases), vascularized femoral diaphyses (three cases), knees (five cases), hands (four bilateral and seven unilateral cases), larynx (one case), and nonvascularized peripheral nerves (seven cases) have been transplanted in humans in the past decade. Rejection was prevented in most cases without difficulty. Early results are encouraging, particularly for hand and larynx transplants, but will need to be evaluated in the long term and in a larger number of patients. CONCLUSIONS: CTA holds great potential for reconstructive surgery but is at present restricted by the risks of chronic immunosuppression and uncertain long-term results.
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