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M Lanzetta

Publications and source records attributed to M Lanzetta.

At least 19 recordsLinked to original sources
PubMed2006

Bilateral hand transplantation: six years after the first case.

In this study we present our experience concerning bilateral hand transplantation. Two cases were performed: the first in January 2000 and the second in April 2003. Both recipients received the same immunosuppressive treatment, which was similar to those used in solid organ transplantation, including tacrolimus, prednisone and mycophenolate mofetil while antithymocyte globulins were added for induction. Both recipients presented two episodes of acute rejection (maculopapular lesions) in the first 3 months after transplantation; however, these were easily reversed after a few days increasing oral steroid doses and using topical immunosuppressants. The first recipient presented hyperglycemia and serum sickness while the second recipient suffered a thrombosis of the right ulnar artery and an osteomyelitis of left ulna. All the complications were successfully treated. Functional Magnetic Resonance Imaging (fMRI) showed that cortical hand representation progressively shifted from the lateral to the medial region in the motor cortex. After 6 and 2 years respectively, they 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. The first recipient has been working since 2003. They are both satisfied with their grafted hands.

Adolescent↗
PubMed2005

Donor leukocytes combine with immunosuppressive drug therapy to prolong limb allograft survival.

Donor leukocytes administered at the time of transplantation may prolong organ allograft survival. This study examined the effectiveness of donor leukocyte injection combined with immunosuppression for limb transplantation across the strong histocompatibility barrier of a Brown Norway donor to a Lewis recipient. Eight animals received 6 x 10(7) donor leukocytes injected on the day of transplantation. From day 1, FK506 (2 mg/kg/d), mycophenolate mofetil (MMF) (15 mg/kg/d), and prednisone (0.5 mg/kg/d) were administered for 2 weeks. After week 2, prednisone and MMF were both tapered by 20% of the initial dosage per week. After week 7, the animals received only FK506 (2 mg/kg/d). From week 8, FK506 was tapered to the maintenance dose of 0.8 mg/kg/d at week 10 and was stopped on week 24. A control group of 8 animals underwent identical treatment except that the leukocyte injection was omitted. Rejection was observed in both groups during FK506 monotherapy; however, the onset of early rejection episodes was significantly later, the period for reversal of the first rejection was significantly shorter, and the dosage of FK506 at the time of rejection was significantly lower among leukocyte-treated recipients. After completion of immunosuppression, survival was modestly prolonged in the leukocyte-treated group. One animal is surviving without immunosuppression on day 234. This trial of donor leukocyte injection combined with immunosuppression in limb transplantation showed a modest, but significant, improvement in outcome.

Animals↗
PubMed2005

Donor leukocytes combined with delayed immunosupressive drug therapy prolong limb allograft survival.

Donor leukocytes administered at the time of transplantation may prolong organ allograft survival. Delayed administration of calcineurin inhibitors, such as FK506 or cyclosporine, may enhance their efficacy. Herein the effectiveness of this strategy to promote limb transplant survival was investigated in the strong histocompatibility barrier of Brown-Norway donor to Lewis recipients. Donor leukocytes (6 x 10(7) intravenously) were injected on the day of transplantation followed on day 1 to 14 with mycophenolate mofetil (MMF; 15 mg/kg/d) and prednisone, (0.5 mg/kg/d) which were then tapered by 20% each week and stopped at week 7. Administration of of FK506 (2 mg/kg/d) was started on day 4 and continued for 8 weeks, then tapered for 4 weeks to a maintenance dose of 0.8 mg/kg/d, which was continued for 12 weeks (group A; n = 8). A control group (n = 8) underwent identical treatment save for donor leukocyte injection but rather commencement of FK506 on day 1. Rejection was common during FK506 tapering in both groups. However group A showed a significantly later onset, a shorter period for reversal of the first rejection, and a significantly lower dosage of FK506 at the time of rejection. After the completion of immunosuppression, rejection occurred significantly later in group A than the control group with one animal surviving without immunosuppression on day 344. This is the first trial of a donor leukocyte injection combined with delayed FK506 administration in limb transplantation, which suggested that it could produce a modest but significant improvement in outcome.

Animals↗
PubMed2004

Human hand transplantation: what have we learned?

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.

Adolescent↗
PubMed2004

Experimental limb transplantation, part I: identification of an effective tapered triple combination immunosuppressive regime.

Limb transplantation was performed across the Brown Norway to Fischer 344 histocompatibility barrier in rats to evaluate the effects of triple combination immunosuppressive therapeutic regimens. Sixty rats were divided into five groups: group I (F344 to F344) isograft controls group II (BN to F344) allograft controls received no immunosuppressive treatment. Groups III and V (BN to F344) received various exposures to tacrolimus (TRL), mycophenolate mofetil (MMF) and prednisolone (Pred) for two weeks: namely, group III: TRL 0.5 mg/kg/d; MMF 10 mg/kg/d; Pred 0.5 mg/kg/d; group IV: TRL 2 mg/kg/d, MMF 15 mg/kg/d, Pred 0.5 mg/kg/d; and group V: TRL 3 mg/kg/d; MMF 20 mg/kg/d; Pred 0.5 mg/kg/d. After 2 weeks, group III and V animals underwent a simultaneous 20% taper of Pred and MMF each further week such that by week 7 the animals were only on TRL. At this time TRL was tapered at the same rate (20% every week) to a maintenance dose of 0.6 mg/kg/d. Evidence of rejection was sought by daily visual observation for swelling, redness, erythema, edema, or skin necrosis. Salvage treatment was used only if rejection occurred after the first 7 weeks, namely, reversing to 100% of the initial TRL dose in that group for 2 weeks with a subsequent taper. Skin and muscle biopsies were obtained from grafted limbs on day 3, 13, 24, 35, and at the endpoint (9 months or uncontrollable rejection). There was no rejection in group I, while all animals showed acute rejection as expected in group II. All group III rats displayed a similar though delayed acute rejection, showing that the regimen was not therapeutic. Rats in group IV displayed the best results, namely, 10 of 12 (83%) with no rejection or side effects at 9 months. Rats in group V displayed numerous, unacceptable side effects due to overtreatment with a 1-month mortality rate of 50%. This study shows that low-dose TRL in combination with MMF and Pred may achieve excellent long-term results of composite tissue transplants. TRL can be used alone as maintenance therapy following an initial loading dose and a tapering period. Rejection is easily reversed by only temporarily increasing the TRL dose.

Animals↗
PubMed2004

Experimental limb transplantation, part II: excellent return of function and indefinite survival after withdrawal of immunosuppression.

In this study the three components of an immunosuppressive combination therapy were gradually withdrawn in a rat limb transplantation model to evaluate the effects on long-term survival of the grafted limbs, rejection rate, and functional recovery. The procedure was performed in 16 rats across a strong Brown Norway to Fischer 344 histocompatibility barrier. Eight animals served as a control group that was not given any antirejection therapy and rejected their limb within a few days. The remaining eight animals were administered a 2-week course of immunosuppressive therapy including tacrolimus (TRL; 2 mg/kg/d), mycophenolate mofetil (MMF; 15 mg/kg/d), and prednisolone (Pred; 0.5 mg/kg/d). At 2 weeks, Pred and MMF were simultaneously tapered by 20% of the dosage every week; by week 7 the animals were on TRL only. TRL was then tapered at the same rate (20% every week) to a maintenance dose of 0.6 mg/kg/d at week 12. After 6 months the immunosuppression was stopped. Four of 8 animals did not reject throughout the study up, to the 1-year endpoint. At this stage they show excellent functional outcomes, evaluated by clinical tests and walking tract analysis. The remaining four rats developed a rejection at an average of 267 days postoperatively (range 224 to 302 days), corresponding to an average of 87 days (range 44 to 122 days) without any immunosuppression. They were sacrificed as soon as rejection was confirmed for histological examination of the various tissues. This study showed that a triple combination therapy provides excellent long-term functional outcomes of the transplanted limbs, with no rejection episodes, no side effects, or complications, even 6 months after withdrawal of all immunosuppressive components, suggesting the possible emergence of tolerance.

Animals↗
PubMed2004

Experimental limb transplantation, part III: induction of tolerance in the rigorous strain combination of Brown Norway donor to Lewis recipient.

The complete withdrawal of immunosuppressive therapy after hind-limb transplantation across a strong histocompatibility barrier (Brown-Norway to Lewis) included a low-dose combination of FK506, mycophenolate mofetil (MMF), and prednisone. MMF and prednisone were tapered and withdrawn between weeks 2 and 7. From weeks 8 to 24, Group 1 animals (n=23) had FK506 tapered; for those in Group 2 (n=11) the dose of FK506 was not changed. At week 24, FK506 was stopped. The six limb grafts in Group 1 (26%) that achieved the 1-year end-point uneventfully showed chimerism by bone marrow and skin grafting supporting the presence of donor-specific tolerance. Rejection, which was common during tapering of FK506, was reversed by salvage therapy. All limbs were rejected postwithdrawal in Group 2. This study showed that tapering of FK506 combined with salvage therapy may allow long-term survival of some transplanted limbs after complete withdrawal of immunosuppressive therapy despite a complete MHC barrier.

Animals↗
PubMed2004

Concerns on clinical application of composite tissue allotransplantation.

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.

Hand Transplantation↗
PubMed2002

[First transplantation of two hands: results after 18 months].

AIM OF THE STUDY: The previous results achieved in single hand transplantations confirmed the feasibility of this procedure and encouraged us to perform the first human double hand transplantation, which was performed in January 2000. In the present study we reported the results obtained eighteen months after transplantation. PATIENT AND METHODS: The recipient was a 33-year old man suffering from a traumatic amputation of both hands in 1996. Surgery included procurement of the upper extremities from a 18-year old multiorgan cadaveric donor, preparation of the graft and recipient's stumps, transplantation of the hands, which included bone fixation, arterial and venous anastomoses, nerve suture, joining of tendons and muscles, and skin closure. Immunosuppressive protocol included tacrolimus, prednisone and mycophenolate mofetil. An intensive rehabilitation program was performed. Follow-up included immunological tests, skin biopsies, arteriography, bone scintigraphy, electromyography and brain functional magnetic resonance imaging. RESULTS: No surgical complications, infectious complications and graft-versus-host-disease occurred. Two episodes of acute skin rejection were demonstrated and they were completely reversed increasing steroid dose. Nerve regeneration and cortical reorganization were shown. Sensorimotor recovery was encouraging and life quality improved. CONCLUSION: This double hand transplantation showed that conventional immunosuppressive protocol is effective and safe as well as that functional results are at least as good as those achieved in replanted upper extremities.

Adult↗
PubMed2000

Tissue specificity in rat peripheral nerve regeneration through combined skeletal muscle and vein conduit grafts.

Diffusible factors from the distal stumps of transected peripheral nerves exert a neurotropic effect on regenerating nerves in vivo (specificity). This morphological study was designed to investigate the existence of tissue specificity in peripheral nerve fiber regeneration through a graft of vein filled with fresh skeletal muscle. This tubulization technique demonstrated experimental and clinical results similar to those obtained with traditional autologous nerve grafts. Specifically, we used Y-shaped grafts to assess the orientation pattern of regenerating axons in the distal stump tissue. Animal models were divided into four experimental groups. The proximal part of the Y-shaped conduit was sutured to a severed tibial nerve in all experiments. The two distal stumps were sutured to different targets: group A to two intact nerves (tibial and peroneal), group B to an intact nerve and an unvascularized tendon, group C to an intact nerve and a vascularized tendon, and group D to a nerve graft and an unvascularized tendon. Morphological evaluation by light and electron microscopy was conducted in the distal forks of the Y-shaped tube. Data showed that almost all regenerating nerve fibers spontaneously oriented towards the nerve tissue (attached or not to the peripheral innervation field), showing a good morphological pattern of regeneration in both the early and late phases of regeneration. When the distal choice was represented by a tendon (vascularized or not), very few nerve fibers were detected in the corresponding distal fork of the Y-shaped graft. These results show that, using the muscle-vein-combined grafting technique, regenerating axons are able to correctly grow and orientate within the basement membranes of the graft guided by the neurotropic lure of the distal nerve stump.

Animals↗
PubMed2000

Nerve stripping: new treatment for neuromas of the palmar cutaneous branch of the median nerve.

We present a new method for the treatment of painful neuromas of the palmar cutaneous branch of the median nerve. A preliminary cadaver study was done to investigate the extraneural and intraneural course of the palmar cutaneous branch of the median nerve with respect to the main trunk of the median nerve. Seven patients presented with a painful neuroma following previous surgery on the palmar aspect of the wrist. The neuroma was dissected and excised by stripping the whole of the palmar cutaneous branch from the main trunk of the median nerve. In all cases complete relief from pain and discomfort was achieved. The resulting area of numbness in the palm did not represent a significant problem.

Adult↗
PubMed1999

Human hand allograft: report on first 6 months.

BACKGROUND: Long-term survival of animal limb allografts with new immunosuppressant combinations and encouraging results of autologous limb replantations led us to believe that clinical application of hand transplantation in human beings was viable. METHODS: On Sept 23, 1998, we transplanted the right distal forearm and hand of a brain-dead man aged 41 years on to a man aged 48 years who had had traumatic amputation of the distal third of his right forearm. The donor's arm was irrigated with UW organ preservation solution at 4 degrees C, amputated 5 cm above the elbow, and transported in a cool container. We dissected the donor limb and the recipient's arm simultaneously to identify anatomical structures. Appropriate lengths of viable structures were matched. Transplantation involved bone fixation, arterial and venous anastomoses (ischaemic time 12.5 h), nerve sutures, joining of muscles and tendons, and skin closure. Immunosuppression included antithymocyte globulins, tacrolimus, mycophenolic acid, and prednisone. Maintenance therapy included tacrolimus, mycophenolic acid, and prednisone. Follow-up included routine post-transplant laboratory tests, skin biopsies, intensive physiotherapy, and psychological support. FINDINGS: The initial postoperative course was uneventful. No surgical complications were seen. Immunosuppression was well tolerated. Mild clinical and histological signs of cutaneous rejection were seen at weeks 8-9 after surgery. These signs disappeared after prednisone dose was increased (from 20 mg/day to 40 mg/day) and topical application of immunosuppressive creams (tacrolimus, clobetasol). Intensive physiotherapy led to satisfactory progress of motor function. Sensory progress (Tinel's sign) was excellent and reached the wrist crease (20 cm) on day 100 for the median and ulnar nerves, and at least 24 cm to the palm by 6 months when deep pressure, but not light touch sensation, could be felt at the mid palm. INTERPRETATION: Hand allotransplantation is technically feasible. Currently available immunosuppression seems to prevent acute rejection. If no further episode of rejection occurs, the functional prognosis of this graft should be similar to if not better than that reported in large series of autoreconstruction.

Adenosine↗
PubMed1999

Assessment of tissue blood flow following small artery welding with an intraluminal dissolvable stent.

Using the technique of radioactive 51Cr-labeled biological microspheres, this study evaluated arterial blood flow following small vessel anastomosis by CO2 laser welding and a dissolvable stent in the lumen. A total of 30 Sprague-Dawley rats were divided into two groups. Group A: 11 rats had their femoral arteries ligated on one side. The contralateral side served as a control, with the artery transected and repaired using conventional microsuturing. Group B: 19 rats had their femoral arteries transected and repaired using CO2 laser welding and an intraluminal dissolvable stent technique. The contralateral side was again used as a control using conventional microsuturing. At 1 hr postoperatively, 51Cr-labeled biological microspheres were injected centripetally into the left common carotid artery and the legs and thighs immediately harvested for measurement of radioactivity. All repaired arteries were patent (30/30 in the microsuturing group and 19/19 in the stented welding group), with no detectable stenosis or dilation at the repaired site. Statistical analysis showed that tissue radioactivity (cpm/g) in the ligated group (3,972 +/- 384 in thighs and 3,142 +/- 742 in legs) was significantly lower than in the microsuturing group (7,132 +/- 1,723 in thighs and 6,557 +/- 1,469 in legs) (P < 0.01). In the ligated group, a significant reduction of blood flow was seen in the legs when compared with the thighs (P < 0.05). There was no significant difference in radioactivity when comparing the microsuturing control with the stented welding group, in both thighs (7,064 +/- 2,599 and 7,006 +/- 2,406, respectively; P > 0.05) and legs (6,386 +/- 1,703 and 6,288 +/- 1,757, respectively; P > 0.05). This study provided evidence that the dissolvable stent placed intraluminally does not impair blood circulation and that when coupled with CO2 laser welding offers a high-quality alternative to conventional small vessel anastomosis.

Absorbable Implants↗
PubMed1999

[The first transplantation of a hand in humans. Early results].

The first hand allograft was performed on September 23, 1998. The right distal forearm and hand of a brain dead donor was transplanted to a 48 year old recipient who had undergone a traumatic amputation of the distal third of his right forearm. The donor's arm was irrigated with organ preservation solution (UW) and transported to Lyon in a cool container. Two teams simultaneously dissected the donor's limb and the recipient's stump to identify anatomical structures. Transplantation involved bone fixation, arterial and venous anastomoses, nerve sutures, joining of the muscles and tendons, and skin closure. Immunosuppression consisted of anti-lymphocyte, polyclonal and monoclonal antibodies, tacrolimus, mycophenolic acid, and prednisone. Mild clinical and histological signs of rejection occurred at week 9 after surgery. They disappeared with adjustments of the immunosuppressant doses. Seven months after surgery the patient was in good general condition. Intensive physiotherapy led to satisfactory progress of motor function. Sensory progress is excellent, reaching the fingertips. A longer follow-up is necessary to appreciate the final result. In the absence of further rejection, the functional prognosis of the graft should be similar to that reported after successful autoreconstruction.

Adenosine↗
PubMed1999

Reconstruction of high ulnar nerve lesions by distal double median to ulnar nerve transfer.

Ulnar nerve lesions around the elbow often carry an unfavorable prognosis due to insufficient sensory and intrinsic muscle recovery. We present a series of 7 cases in which restoration of ulnar innervated intrinsic muscles of the hand and of skin sensibility was achieved. This was accomplished by a distal connection of the anterior interosseous nerve and the superficial sensory palmar branch of the median nerve to the motor and sensory components of the ulnar nerve at Guyon's canal. The length of the follow-up period ranged from 1 to 3.5 years. Results were graded by the Highet-Zachary scale. Good motor and sensory recovery was obtained in 6 cases; only return of protective sensation occurred in the remaining case.

Adult↗
PubMed1999

Emergency reconstruction of a collateral ligament of a metacarpophalangeal joint using Dacron material.

We present a case in which an open wound involving the ulnar collateral ligament of the metacarpophalangeal joint of the little finger was treated by ligament reconstruction using a strip of Dacron material, nerve grafting and coverage by a posterior interosseous artery pedicled flap. At a long term follow-up of 4 years, the joint was stable and had a full range of movement.

Bone Screws↗