1,721,005 research outputs found

    The International Registry on Hand and Composite Tissue allotransplantation

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    The International Registry on Hand and Composite Tissue Transplantation includes hand and face allotransplantations: 39 patients who received 57 upper extremity transplantations (18 bilateral and 21 single transplantations--17 right and 4 left allografted hands); and 15 cases of partial or total face allotransplantation. The recipients of upper extremity allotransplantations are: 32 males and 7 females, median age 32 years. In 57.9% of cases, the level of amputation was at the wrist. The followup periods range from 6 months to 13 years. The recipients of face allotransplantations are: 12 males and 3 females, median age 34 years. In the majority of cases, the deficit included cheek, nose, chin, lips, and perioral area. The patients presented impairment of swallowing, eating, and speaking. The follow-up periods range from 8 months to 6 years. In hand and face transplantation, the imunosuppressive therapy included: tacrolimus, mycophenolate mofetil, and steroids. Polyclonal or monoclonal antibodies were used for induction. Within the first post-transplant year, eighty-five percent of hand and face recipients experienced at least one episode of acute rejection, which was reversible when promptly treated. Side-effects included: opportunistic infections, metabolic complications, and malignancies. Hand-grafted patients developed protective sensibility: 90% of them tactile sensibility and 82.3% also a discriminative sensibility. Motor recovery enabled patients to perform most daily activities. Face-grafted patients improved their aesthetic aspects and enhanced some activities such as eating, drinking, and speaking, living a normal social life. Five upper allotransplantation losses occurred. One of these patients who underwent simultaneous face and bilateral hand transplantation died on day 65. Hand and face transplantations are successful procedures, however, careful evaluation of patients before and after transplantation, and their compliance are indispensable

    World experience after more than a decade of clinical hand transplantation: Update on the French program

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    The first hand transplantation was realized in Lyon and the results achieved in this case showed the feasibility of the surgical technique, the efficacy of the immunosuppressive protocol, the limited adverse effects and the importance of a patient's compliance and rehabilitation to ensure graft viability and functional recovery. Based on these findings and the positive results achieved in other single hand transplants realized around the world the authors performed also the first double hand transplantation, then followed by other four cases. The recipients received the same immunosuppressive treatment including tacrolimus, prednisone, mycophenolate mofetil and antithymocyte globulins for induction, nevertheless they showed some episodes of acute rejection episodes which reversed after a prompt treatment. All the bilateral hand grafted patients showed a relevant sensorimotor recovery particularly of sensibility and activity of intrinsic muscles. They were able to perform the majority of daily activities and to lead a normal social life. On the basis of the authors' experience the results achieved in hand allotransplantation are very encouraging as major adverse effects due to surgery and immunosuppressive regimen did not occur and patients' quality of life improved considerably

    Concerns on clinical application of composite tissue allotransplantation

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    Composite tissue allograft has become a clinical reality: hands, vascularized femoral diaphyses, abdominal walls, a larynx have all been transplanted throughout the world. Conventional immunosuppressive protocol has shown to be sufficient and effective. Rejection has been prevented in most cases and when it did occur it was successfully reversed. Skin has been confirmed as the principal target of acute and chronic rejection. There has been no mortality or early graft losses and, particularly in hand transplantation, the survival graft rate is 91% with a follow-up period ranging from 6 months to 61 months. The side effects of immunosuppression are limited and include primarily transient hyperglycemia, an increase in creatinine values and some opportunistic infections (i.e. cytomegalovirus infection). Nerve regeneration and cortical reorganization have been demonstrated in hand transplantation. Functional results have been encouraging particularly for hand and larynx transplantation. Appropriate indications and patient selection, based particularly on patient motivation and compliance, are essential requirements for composite tissue allograft success

    Self-renewal capacity of human epidermal Langerhans cells: observations made on a composite tissue allograft

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    Epidermal Langerhans cells (LC) are dendritic, antigen-presenting cells residing within mammalian epidermis and mucosal epithelia. When massively depleted, they are replaced by cells of bone-marrow origin. However, their renewal within normal skin under steady-state conditions is not precisely known. We observed that epidermal LC within a human hand allograft remain stable in the long term (10 years) and are not replaced by cells of recipient's origin; furthermore, we observed a Langerhans cell in mitosis within the epidermis 8 years postgraft. These results show that under almost physiological conditions, human LC renew in the epidermis by local mitoses of preexisting cells

    Fifteen years later: main lessons from composite tissue allografts.

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    Composite tissue allografts (CTA) are also called "reconstructive transplantation" as they are a valid alternative approach to repairing complex tissue defects. These procedures are still considered "experimental" and their therapeutic value remains to be validated. An immunosuppressive treatment similar to that used in solid organ transplantation allows CTA survival and function despite a high rate of acute rejection (AR) episodes. Clinical experience seems to confirm that skin is the most antigenic tissue and the first target of AR episodes, which are easy to reverse and do not seem to adversely influence graft survival and function when promptly treated. Chronic rejection can also occur in CTA, although its features are still unclear. Upper-extremity or face-transplanted patients show a relevant sensorimotor recovery. Patients are able to perform the majority of daily activities and to lead normal social lives. Global cortical remodeling occurs in the months following transplantation, reversing the functional reorganization induced by the amputation. Appropriation of the graft occurs in parallel with functional recovery. The patients' compliance is essential for the success of CTAs as well as careful recipient selection and patient follow-up to prevent complications of long-term immunosuppression

    Re-emergence of hand-muscle representations in human motor cortex after hand allograft

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    The human primary motor cortex (M1) undergoes considerable reorganization in response to traumatic upper limb amputation. The representations of the preserved arm muscles expand, invading portions of M1 previously dedicated to the hand, suggesting that former hand neurons are reassigned to the control of remaining proximal upper limb muscles. Hand allograft offers a unique opportunity to study the reversibility of such long-term cortical changes. We used transcranial magnetic stimulation in patient LB, who underwent bilateral hand transplantation 3 years after a traumatic amputation, to longitudinally track both the emergence of intrinsic (from the donor) hand muscles in M1 as well as changes in the representation of stump (upper arm and forearm) muscles. The same muscles were also mapped in patient CD, the first bilateral hand allograft recipient. Newly transplanted intrinsic muscles acquired a cortical representation in LB's M1 at 10 months postgraft for the left hand and at 26 months for the right hand. The appearance of a cortical representation of transplanted hand muscles in M1 coincided with the shrinkage of stump muscle representations for the left but not for the right side. In patient CD, transcranial magnetic stimulation performed at 51 months postgraft revealed a complete set of intrinsic hand-muscle representations for the left but not the right hand. Our findings show that newly transplanted muscles can be recognized and integrated into the patient's motor cortex

    Human hand transplantation: what have we learned?

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    Hand transplantation may become an important procedure for upper limb functional restoration. To date, 18 patients have been undergone 24 hand operations in the world. Initial results are extremely promising; the functional results are apparently superior to those obtained with prostheses. We report on the combined French and Italian experience of six patients (eight hands), which is based on a jointly devised protocol and represents the largest available clinical series. Six male patients aged 43, 33, 35, 32, 33, and 22 years received either a single right hand-dominant transplantation (four cases) or a simultaneous double hand transplantation (two cases). The time since the amputation ranged from 3 to 22 years. The level of transplantation was at the wrist in five cases (six hands) and at the distal forearm in two cases (two hands). Cold ischemia averaged 11.5 hours. Three patients simultaneously received additional full-thickness skin taken from the donor and transplanted onto their left hip area. This skin served as a source for biopsies and as an additional area to monitor rejection (distant sentinel skin graft). The immunosuppressive protocol included polyclonal antibodies (three patients) or monoclonal anti-CD 25 antibody (three patients), tacrolimus, mycophenolate mofetil, and prednisolone. No surgical complications occurred. Skin rejection occurred at least once in all patients at a mean of 40 days postoperatively. Three patients recovered protective and some discriminative sensation in their palm and fingers. Two patients are recovering sensation, but are still in the early phases of the regenerative process, due to the short time since the transplantation. One patient was not compliant with the immunosuppressive therapy, and underwent uncontrolled rejection and reamputation

    Absence of c4d deposition in human composite tissue (hands and face) allograft biopsies: an immunoperoxidase study

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    Deposition of the C4d complement degradation product has been shown to be a marker of antibody-mediated rejection of solid organ allografts, including kidney, heart, liver, and lung. We investigated whether C4d deposition also would be useful in monitoring rejection in human composite tissue allografts. A total of 60 mucocutaneous formalin-fixed, paraffin-embedded and four frozen biopsy specimens from four patients with composite tissue allografts (three hands, one face) taken during a period of 7 days to 7 years after graft were immunostained for C4d by an immunoperoxidase and an immunofluorescence technique, respectively. C4d deposition was not found in any of the specimens studied, even though several of them showed pathological signs of rejection. No human leukocyte antigen alloantibodies were detected in any of the patients during the study period. These results suggest that humoral rejection occurs rarely, if at all, in the setting of human composite tissue allografts
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