Pinpointing the moment of allograft rejection.
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Animals↗
Biomedical subjects
M J Fealy
Publications and source records attributed to M J Fealy.
Femur lengthening with a vascularized tibia bone flap.
A vascularized tibial bone flap based on a single nutrient vessel has been previously proposed for use in long-bone reconstruction. While the routine use of the tibia for donor bone tissue is precluded by its essential weight-bearing function, in select cases it provides a useful alternative to standard donor bone sources. Cadaver dissection was performed to confirm the endosteal and periosteal vascular anatomy of the tibia. The presence of a consistent nutrient vessel was confirmed. Selective dye injection demonstrated a dual cortical blood supply based on both the endosteal nutrient vessel and multiple periosteal perforator vessels. Inclusion of both vascular supplies maximizes perfusion of bone and periosteum, thus potentially optimizing bone healing and osseous union. Based on these findings, the vascularized tibial bone flap was applied to a clinical case. A 45-year-old male veteran sustained a right proximal femur fracture in a motor vehicle accident. Multiple attempts at fusion with open reduction, internal fixation, grafting, and nonvascularized fibular onlay strut with cerclage wires were all unsuccessful. The patient presented with a chronic right femur nonunion with painful pseudoarthrosis; frozen knee joint; and an internally rotated, 20.3-cm shortened, nonfunctional lower limb. Femur length proximal to the nonunion was less than 15 cm. A maximum amputation stump length is recommended for optimal prosthetic function. A 15-cm pedicled tibial bone flap based on the posterior tibial endosteal and periosteal vascular supply was reversed and plated to the proximal femur to provide a stump of adequate length to optimize prosthetic fitting and function. The tibia is essential for normal weight-bearing, but in select cases may be sacrificed for use in long-bone reconstruction. Expanded use of tibial vascularized allografts in long-bone reconstruction may be made possible following future development of effective and safe immunosuppressive therapy. Transfer based on the posterior tibial pedicle, which includes the endosteal nutrient vessel as well as the periosteal supply via the tibialis posterior muscle, maximizes bone perfusion. The pedicle is of sufficient length to be used for positioning the tibia in the thigh or for free transfer to distant sites.
Amputation Stumps↗
Association of down-regulation of cytokine activity with rat hind limb allograft survival.
Cytokines are short-acting protein modulators of many physiologic processes including graft rejection. An understanding of the production, action, and interaction of cytokines may lead to better appreciation of the complex mechanism of graft rejection. The potential would then exist for more selective and less-toxic means of modulating the immune response. A rat hind limb allograft model with major immunohistoincompatibility was used to study the local mRNA expression of IL-1 alpha, IL-2, IL-6, gamma interferon (gamma INF), platelet-derived growth factor-alpha (PDGF-alpha), basic fibroblast growth factor (FGF), and transforming growth factor-beta (TGF-beta) during acute allograft rejection. A 14-day postoperative course of immunosuppressive therapy with FK506 or rapamycin was administered. In situ hybridization was performed on serial full-thickness skin punch biopsies of the untreated rejecting limb allograft and compared with tissue from treated allografts, isografts, and to normal limb tissue. A sequential pattern of cytokine mRNA expression was demonstrated which progressed in a time-dependent manner and paralleled observed clinical rejection. Maximal cytokine mRNA expression correlated with peak graft rejection. Cellular expression of IL-1 alpha, IL-2, IL-6, gamma-INF, FGF, and TGF-beta mRNA was suppressed with FK506 to below isograft levels, and clinical rejection was not observed with the doses, routes, and schedules used. Rapamycin was ineffective in suppressing cytokine expression, and allograft rejection was not prevented. Isografts demonstrated no evidence of rejection. The in situ hybridization technique demonstrates a time-dependent, selective expression of cytokines within rejecting allograft tissue, and the modification of this response with immunosuppressive therapy. Down-regulation of cytokine expression is associated with clinical allograft survival.
Animals↗
Intraosseous ganglion cyst of the scaphoid.
Intraosseous ganglion cysts are rare causes of hand and wrist pain. Differential diagnosis of painful cystic radiolucent carpal lesions includes osteoid osteoma and osteoblastoma. Isolated cases of ganglion cysts occurring in the lunate, scaphoid, pisiform, hamate, triquetrum, capitate, metacarpal, and phalanx have been reported. A case of intra-articular intraosseous ganglion cyst of the scaphoid is presented. A 49-year-old right-handed woman presented with a 3- to 4-month history of progressive left-wrist pain. No history of trauma was reported. Conservative treatment with anti-inflammatory medications before referral was unsuccessful. Examination revealed marked tenderness in the region of the volar scaphoid proximal pole as well as tenderness overlying the dorsal radial styloid. No palpable masses were present. Wrist motion was not limited. Grip strength was symmetric. Radiographic studies revealed a cystic lesion eroding the radial-volar surface of the scaphoid waist. Magnetic resonance imaging studies demonstrated the cystic lesion to be of the penetrating type, originating from the radiocarpal joint and eroding into the scaphoid. The patient underwent radial styloidectomy, excision of the ganglion cyst, curettage of the scaphoid lesion, and bone grafting with radial styloid bone. Intraosseous carpal ganglion cysts, although rare, present with chronic wrist pain and should be included in the differential diagnosis.
Bone Cysts↗
Efficacy of rapamycin and FK 506 in prolonging rat hind limb allograft survival.
OBJECTIVE: Graft rejection and the toxicity of current immunosuppressive regimens preclude the application of microsurgical advances to transplantation of limbs or other nonessential parts. If limb transplantation is to become a clinical reality, newer, safer, more effective immunosuppressive agents are needed. SUMMARY BACKGROUND DATA: Rapamycin (RPM) and FK 506 are fungal macrolide antibiotics with effective immunosuppressive properties demonstrated in several animal models. RPM is more potent and effective than is FK 506 in rat cardiac allografts and has demonstrated synergy with cyclosporine (CsA) in limb allograft models. METHODS: An orthotopic rat hind limb allograft model (Brown-Norway [RT-1n] to Lewis [RT-1(1)] rats was used. RPM (doses, 3.0, 4.5, and 6.0 mg/kg/day) was administered intraperitoneally on postoperative days 1 to 14. FK 506 (6 mg/kg/day) was administered orally on postoperative 1 to 14 and 1 to 90 and at rejection onset (10 mg/kg/day for salvage). CsA with RPM (postoperative days 1 to 14) was used to assess synergy, with CsA alone serving as the control. Other controls included untreated and placebo-treated allografted animals. The permutation test and Mann-Whitney test were applied to the data. RESULTS: The mean survival times were assessed as follows: (1) control (placebo, untreated), 5 days; (2) RPM groups, 9.5, 10.6, and 8.7 days; (3) 14-day FK 506, 28 days; (4) 90-day FK 506, > 90 days; (5) CsA, 17.3 days; and (6) CsA with RPM, 19.3 days. FK 506 significantly prolonged graft survival compared with RPM (Permutation Test, p < 0.001 and Mann-Whitney Test, p < 0.05). FK 506 salvage reversed early rejection. High-dose RPM produced significant toxicity. Synergy between CsA and RPM was not demonstrated. CONCLUSIONS: FK 506 prolongs allograft survival, reverses early rejection, and prevents rejection without clinical toxicity when given continually. RPM does not prevent rejection in this model and produces significant toxicity at high doses. FK 506 may be a first step in making limb transplantation a clinical reality in reconstructive surgery.
Animals↗