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PubMed1981

[The allogeneic liver transplantation. I. Morphological and functional patterns in pig liver allografts (author's transl)].

Pigs usually reject MHC incompatible liver allografts less aggressively than skin or kidney allografts. Orthotopic liver allografts can survive undefinitely without any immunosuppression. The liver is considered to be an immunologically privileged organ. Despite this phenomenon, morphological changes and deranged liver function due to rejection reaction are regularly seen; their intensity depends on the histocompatibility antigen disparity between donor and recipient. In long-term survivors the continuous exposure of the recipient's immune system to the liver allograft results in an increasing fibrosis which can turn into liver cirrhosis being considered as the result of chronic rejection. The cholestasis represents a remarkable feature, which is mainly due to perfusion, infection and immunological reaction.

Animals↗

PubMed1975

Surface properties and functional characteristics of infiltrating cells harvested from acutely rejecting cardiac allografts in inbred rats.

Viable, functioning effector cells exerting donor specific cytotoxic properties have been removed, with their surface properties intact, from acutely rejecting cardiac allografts in rats to define immunological events occurring within the grafts themselves. Macrophages comprised 15 to 25% of the cells harvested; lymphocytes comprised about 75%. A few polymorphonuclear leukocytes (approximately 5%) were present consistently. Lymphocytes bearing surface Ig, B cells, made up 35 to 47% of the mononuclear cells collected. The remaining lymphocytes were presumptive T cells. The surfact attributes of the infiltrating cells were compared to those of cells from recipient peripheral blood, spleen and lymph nodes, and to those from isografted controls. Many of the B lymphocytes possessed Fc receptors but were virtually unable to form erythrocyteantibody complement (EAC) rosettes, in contrast to splenocytes which formed approximately 30% EAC rosettes. Specific cytotoxicity against donor alloantigen-bearing cells, as tested in a 51Cr release assay, was shown to be a T cell function by serial fractionation experiments. Peak cytotoxicity of infiltrating T cells occurred early during the rejection process, while that of cells from recipient blood and lymphoid tissues occurred only following complete graft destruction. Antibody-dependent lymphocyte-mediated cytotoxicity (Ab-LMC) was demonstrated following gentle trypsinization or overnight incubation of the cells. Differing effector cell populations could be distinguished by treatment of anti-Ig and complement; direct donor-specific lymphocyte-mediated cytotoxicity was not disrupted by this treatment, while Ab-LMC was abolished.

Animals↗

PubMed1995

Experimental tracheal revascularization and transplantation.

Vascularized tracheal allografts would expand the domain of tracheal reconstructive surgery. The functional capability of vascularized tracheal allografts is closely correlated with immunologic parameters contributing to graft survival, about which little information is currently available. An orthotopic transplant model was developed that allows assessment of allograft function by examining healing at the graft-host junction and graft integrity during normal respiration.

Animals↗

PubMed1999

Role of inducible nitric oxide synthase in transplant arteriosclerosis.

1. Transplant arteriosclerosis is a major obstacle to long-term allograft survival. Nitric oxide (NO) has been implicated as a mediator in the development of this disease. 2. We and others have shown that inducible nitric oxide synthase (iNOS) is up-regulated in allografts with transplant arteriosclerosis. Despite the acute cytotoxic effects produced by high levels of NO, a chronic increase in NO availability is protective against neointimal hyperplasia, mainly by suppressing the inflammatory cell recruitment and neointimal smooth muscle cell accumulation. 3. Currently, we have the technology to directly transfer the iNOS gene to allografts. We have demonstrated that this exciting strategy is feasible and therapeutic and may improve the long-term survival and function of allografts. Future challenges include optimizing the methods and the vectors of gene delivery.

Animals↗

PubMed2006

Short-term anti-CD40 ligand costimulatory blockade induces tolerance to peripheral nerve allografts, resulting in improved skeletal muscle function.

BACKGROUND: Reconstruction of long or multiple peripheral nerve defects with peripheral nerve autografts may not be possible due to insufficient quantities of donor nerve. There are promising preliminary data that nerve allografting has the potential to improve functional outcome and quality of life after devastating nerve injuries or large tumor resections. The authors previously demonstrated that blockade of the CD40/CD40 ligand costimulatory pathway, via anti-CD40 ligand monoclonal antibody (MR1) therapy, induces tolerance to peripheral nerve allografts in mice. In this study, the authors sought to correlate the immunomodulatory effects of MR1 treatment with functional muscle recovery after peripheral nerve allografting in the murine model. METHODS: In the mouse hindlimb model, peroneal nerve isografts (C57BL/6 into C57BL/6) and allografts (BALB/c into C57BL/6) were utilized to reconstruct 0.8-cm peroneal nerve gaps. MR1 versus vehicle was administered on days 0, 1, and 2. At 60 days after transplantation, splenocyte production of interferon-gamma and interleukins 2, 4, and 5 were quantified using ELISPOT analysis, and in vitro maximum tetanic isometric force of the extensor digitorum longus muscle was measured. RESULTS: At 60 days after transplantation, immunomodulation persisted in MR1-treated, allografted animals, as evidenced by significantly muted interferon-gamma, interleukin 4, and interleukin 2 splenocyte production. Functional extensor digitorum longus muscle recovery after nerve allografting and MR1 administration was improved due to the tolerance induced by MR1 compared with untreated allograft recipients. CONCLUSIONS: Three-day inductive therapy with MR1 produces 60-day immunologic tolerance to peripheral nerve allografts, as evidenced by dramatic decreases in interferon-gamma, interleukin 4, and interleukin 2 production, and results in increased muscle force recovery. This work emphasizes the potential promise of CD40-CD40 ligand costimulatory blockade in reducing or eliminating peripheral nerve allograft rejection.

Animals↗

PubMed1983

Limiting dilution analysis of canine alloantigen-reactive T lymphocytes.

A sensitive limiting dilution assay for the determination of canine cytotoxic T lymphocyte precursors (CTL-P) has been developed. Murine second MLC supernatant as a source of Interleukin 2 (IL 2) was used to expand stimulated CTL-P to numbers that were easily detectable with the classic 51Cr lysis assay. The frequencies of CTL-P that reacted to allogeneic stimulator cells in canine peripheral blood ranged from 1:1000 to 1:2000 lymphocytes. During in vitro stimulation in a mixed leukocyte culture a rapid increase in frequency was noted, and at day 7 a frequency as high as 1:5.4 was found. The presence of irradiated stimulator cells during limiting dilution culture restricted proliferation of the CTL-P; only those which recognized the stimulator cells proliferated. The determination of cytotoxicity in large numbers of individual microcultures with CTL-P seeded at clonal conditions toward 2 allogeneic target cells permitted quantitation of the frequency of CTL-P with specificity for different alloantigens. These techniques greatly facilitate monitoring of cellular immune reactions after renal allografting because both determination of the influence of cytostatic drug treatment on CTL-P frequency, and analysis of the specificity and function of allograft infiltrating cells are now possible.

Animals↗

PubMedDate not supplied

Functional and histopathologic studies of primate pulmonary allografts preserved for 24 hours with a form of modified extracellular solution.

BACKGROUND: The purpose of this investigation was to evaluate the efficacy of a solution (Ep4) for long-term hypothermic pulmonary allograft preservation in a primate model using both functional and histopathologic criteria. METHODS: Twenty-seven Japanese monkeys were divided into donor group and three study groups. The animals in group I underwent acute left lung transplantation (n = 5). Group II consisted of animals which received left pulmonary allografts preserved for 24 hours by simple hypothermic immersion in Ep4 solution (n = 6). The temporary contralateral (right) pulmonary artery occlusion test was performed immediately after transplantation and on postoperative day 7 to assess lung function in the allografts. This test was also performed in the control group (group III, n = 5). The recipient animals in groups I and II were also subjected to serial open lung biopsies and bronchoscopic assessments after transplantation. RESULTS: Temporary right pulmonary artery occlusion did not show any significant differences in gas exchange capacity and pulmonary hemodynamics between groups I and II. Histopathologic examination did not show significant differences in the pulmonary allografts between groups I and II for a period of 4 weeks after transplantation. Serial bronchoscopic and histologic examinations also showed no significant differences in bronchial healing between these two groups. CONCLUSIONS: Long-term hypothermic pulmonary allograft preservation with Ep4 solution does not impair pulmonary function immediately after transplantation. The results of this study indicate that extracellular electrolyte composition solutions such as Ep4 should be subjected to clinical trials.

Animals↗

PubMed2000

Acellular bladder matrix allografts in the regeneration of functional bladders: evaluation of large-segment (> 24 cm) substitution in a porcine model.

OBJECTIVES: To evaluate the use of a large-segment (> 24 cm2) bladder substitution with porcine bladder acellular matrix allograft (BAMA) in a large animal model. Materials and methods Bladders were harvested from pigs at the time of necropsy and subjected to detergent and enzymatic extractions to render them acellular. The BAMA produced had the surgical handling and suture-retaining properties of normal bladder tissue. Six pigs had BAMA segments implanted under general anaesthesia, through a low midline abdominal incision and after partial cystectomy. The defect was repaired with a BAMA patch (mean size 43.88 cm2, range 12-72), with no urinary diversion. Two animals each were then killed at 9, 16 and 30 days and the bladders explanted. The native bladder and BAMA patch were analysed morphometrically to evaluate cellular re-population and matrix re-organization. RESULTS: All animals survived surgery; there were no urinary leaks and no stones detected in any of the bladders. At 9 days there was a diffuse infiltration with acute inflammatory cells, but no areas of necrosis. There were isolated areas of smooth muscle cell (SMC) infiltration of the BAMA. At 16 days the luminal surface was lined with a single layer of urothelium, there was stromal infiltration with disorganized SMC and angiogenesis, with mature vessels in the BAMA patch. At 30 days the urothelium was multilayered with organizing groups of SMCs and angiogenesis. The highest cell density was at the periphery of the repopulated BAMA patch, decreasing towards the centre. CONCLUSIONS: The implantation of large patches of BAMA is technically feasible and may prove to be a viable surgical alternative to bladder augmentation with intestinal segments. The advantages of BAMA include the potential for complete and functional regeneration of a bladder substitute. This model provides a tool with which to obtain a better understanding of the cellular and molecular aspects of matrix re-population.

Animals↗

PubMed1998

Induction of donor-specific tolerance to rat nerve allografts with portal venous donor alloantigen and anti-ICAM-1/LFA-1 monoclonal antibodies.

BACKGROUND: Expendable autologous nerve available for repair of nerve injuries is limited. Cadaveric allografts could provide adequate nerve for grafting but are susceptible to rejection and currently require chronic systemic immunosuppression. METHODS: Age-matched Buffalo (RT1B) rats randomly assigned to 7 experimental groups received either a Lewis (RT1L) rat posterior tibial-sciatic nerve allograft or a Buffalo (RT1B) syngeneic isograft. Recipients were treated with anti-intercellular adhesion molecule-1 (anti-ICAM-1) and anti-leukocyte function-associated antigen-1 (anti-LFA-1) monoclonal antibodies (mAbs), intraportally administered ultraviolet B (UVB)-irradiated donor splenocytes, a combination of mAbs and UVB-irradiated donor splenocytes, or no immunosuppression. RESULTS: Histologic, electrophysiologic, and functional evaluation of nerve allografts 8 weeks after transplantation revealed a synergistic improvement in nerve allograft regeneration when monoclonal antibodies were combined with UVB-irradiated donor splenocytes. In vitro immunologic assessment correlated with the in vivo allograft function by demonstrating a donor-specific suppression of the recipient's response in mixed lymphocyte culture (MLC), cytotoxic T lymphocyte assay (CTL), and reduced T cell interleukin-2 production in both the group receiving UVB-irradiated alloantigen alone and the group receiving a combination of UVB antigen and mAbs. CONCLUSIONS: The combined use of mAbs directed against ICAM-1 and LFA-1 adhesion molecules with intraportally administered UVB modified donor antigen prevents nerve allograft rejection and synergistically improves nerve regeneration.

Animals↗

PubMed1996

The role of immunosuppression in the long-term survival of tracheal allografts.

OBJECTIVES: To assess the functional aspects of vascularized tracheal allograft transplant models and the long-term fate of these allografts. To examine the effects of cyclosporin A (CsA), 10 mg/kg per day, on the long-term survival of vascularized tracheal allografts and the presence and significance of host immune tolerance after cessation of immunosuppression. DESIGN: In a rabbit model, tracheal allografts were orthotopically transplanted after an initial period of heterotopic fascia revascularization. A full-thickness skin allograft from the same donor was used as an external monitor of the rejection process. Treatment with CsA was discontinued (group 2) or given intermittently (group 3) after an initial course of continuous CsA administration varying from 2 to 10 weeks. The first group received a continuous regimen of CsA for 10 weeks. MAIN OUTCOME MEASURES: Tracheal and skin allograft deterioration, microcirculation of tracheal transplant, mucociliary clearance, and histopathologic examination. RESULTS: Tracheal allografts under continuous immunosuppression with CsA, 10 mg/kg per day, showed no rejection and remained functional with preservation of mucociliary activity. After an initial course of CsA to achieve solid tracheal union, subsequent cessation and intermittent pulsing of the immunosuppressant were insufficient in maintaining indefinite graft survival. Chronic allograft rejection with simultaneous endothelial graft repopulation could be induced by intermittent pulsing of CsA, which led to prolonged allograft survival in some group 3 animals. CONCLUSION: Continuous immunosuppression is necessary to preserve an optimal morphological and functional condition of tracheal allografts.

Animals↗

PubMed1990

Outcome of renal transplantation in patients with a functioning graft for 20 years or more.

In the present study long-term morbidity, quality of life and over-all rehabilitation were assessed in 14 patients with a functioning renal allograft for 20 years or longer. Followup ranged from 20 to 27 years (mean 22.5 years). All patients enjoyed excellent and stable renal function, and the mean serum creatinine level at 20 years was 1.3 mg. per dl. Complications related to long-term immunosuppressive therapy comprised infection in 8 patients (57%), malignancy in 7 (50%), cardiovascular disease in 6 (43%), cataracts in 3 (21%) and avascular necrosis of the hip in 2 (14%). Over-all quality of life was excellent in 13 patients who were able to return to work, participate in pre-illness levels of activity and enjoy sexual activity. While successful renal transplantation allows patients with end stage renal failure to resume relatively normal lives, these patients remain prone to complications resulting from long-term immunosuppressive therapy.

Aged↗

PubMed1992

Histopathological findings in well-functioning, long-term renal allografts.

One hundred and twenty-eight patients with a first cadaveric kidney allograft participated in a prospective, randomized, clinical trial comparing triple treatment, consisting of initial low-dose cyclosporine (CsA), azathioprine (Aza) and methylprednisolone (MP), with all possible combinations of two immunosuppressive drugs. A protocol core biopsy was performed on all patients with a functioning graft two years after transplantation. The histological findings were evaluated blindly and correlated to possible risk factors for renal allograft damage. The most common histological features were diffuse fibrosis in 62% of biopsies, tubular atrophy in 64% and diffuse inflammation in 30%. Two other important findings were glomerulosclerosis (43%) and vascular intimal proliferation (36%). The histological findings were scored mostly mild. A total of 77% (69 of 89) of patients had normal or only slightly increased serum creatinine. Decreased graft function was related to increased interstitial fibrosis, inflammation, glomerulosclerosis, mesangial matrix increase of glomeruli, intimal proliferation of vessels and tubular atrophy. These findings are characteristic, but not pathognomonic, of chronic renal allograft rejection both in experimental models and in humans. Possible risk factors were correlated to graft histology. Donor age correlated strongly with mesangial matrix increase, intimal proliferation, and tubular atrophy; there was no correlation with interstitial changes. The number of acute rejections and cold ischaemia time did not correlate with any one of the histological findings at two years following transplantation. Cyclosporine dose and concentration had a negative correlation to interstitial inflammation. A "chronic allograft damage index" was eventually created for the comparison of the four different treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Alloantigen-dependent endothelial phenotype and lymphokine mRNA expression in rejecting murine cardiac allografts.

Recent studies suggest that graft microvascular endothelia may play an important role in the regulation of rejection. Alloantigen-dependent changes in microvascular endothelial phenotype may be associated with differences in infiltrate function in allografts vs. isografts, as reflected in alloantigen-specific CTL accumulation and cytokine production. To correlate cytokine production with differences in microvascular endothelial phenotype during allograft inflammation, we used PCR to identify cytokine mRNAs isolated from pooled cardiac isografts and allografts on days 1, 3, and 5 after transplantation. Graft microvascular endothelia express an inflamed phenotype associated with wound healing and the repair of tissue damage due to mechanical trauma, ischemia, and/or reperfusion injury--i.e., high levels of ICAM-1 expression and MECA-32 mAb reactivity. By day 1 in both isografts and allografts, mRNAs for the cytokines IL1 alpha, IL6, TNF, LT, and TGF beta are upregulated or induced. By the third day in cardiac allografts, an antigen-dependent endothelial phenotype is expressed, characterized by the presence of cell surface VCAM-1. Concomitantly, mRNAs for the lymphokines IL2 and IFN gamma are detected, followed by IL4 mRNA by day 5. The expression of VCAM-1 by allograft endothelia may influence the inflammatory process, by physically recruiting specific T cell subpopulations into the response and/or by delivering additional signals to the infiltrating cells. Eventually, these and other regulatory events occurring at these early times initiate a process that later results in alloreactive tissue destruction.

Animals↗

PubMed1991

Cystic transformation in native kidneys in renal allograft recipients with long-standing good function.

Acquired renal cystic disease develops in the native kidneys of patients with renal allografts with long-standing poor function. However, there has been no long-term prospective study of the regression or development of cysts in native kidneys of renal allograft recipients with good long-term function (serum creatinine: 114 +/- 24 mumol/l). We followed 61 renal allograft recipients for 63.5 +/- 29.0 months (mean +/- SD) using computed tomography (CT scan) every 1 or 2 years after transplantation. The cyst grade at pretransplantation was significantly reduced at the first study after transplantation (0.98 +/- 1.39 vs. 0.57 +/- 0.96; p less than 0.01). Baseline study after transplantation revealed that the incidence of cysts in native kidneys was 22/61 (36.1%) and 26/61 (42.6%) in the follow-up study. In 32 patients (52.5%), there were no visible cysts in the native kidneys. In 9 patients (14.8%), there was no change in the number of cysts during follow-up, while in another 9 patients the number of cysts decreased. On the other hand, the number of cysts increased in 11 patients (18.0%) during follow-up. The mean follow-up duration was longer in the group with an increased number of cysts than in the groups with no visible cysts or a decrease in number. Biochemical analysis of cyst fluid from newly developed cysts in 2 patients showed differences from the pattern in acquired renal cystic disease of hemodialysis patients. These results indicate that after regression of acquired cysts in most allograft recipients, no or only a few cysts persist in patients with good graft function. The remaining cysts continue to regress further in some patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2000

Serological markers of recurrent beta cell destruction in diabetic patients undergoing pancreatic transplantation.

BACKGROUND: Besides alloimmunity to transplanted pancreatic tissue, recurrent autoimmune beta cell destruction is an additional limitation to successful clinical pancreatic allografts in type 1 diabetic patients. METHODS: We studied the prevalence of autoantibodies to glutamate decarboxylase (GAD) 65 and tyrosine phosphatase (IA-2) in 68 C-peptide-negative diabetic patients receiving pancreatic allografts. Sera from patients were obtained immediately before grafting. A second blood sample was analyzed at the time of graft failure in patients who returned to hyperglycemia and during the same follow-up period in those who experienced a functional pancreatic allograft. Patients were classified according to clinical outcome into chronic graft failure (group A, n=20), acute graft failure and/or arterial thrombosis (n=7), or functional pancreatic graft (group C, n=41). Sera from patients were screened for the presence of specific autoantibodies using an islet cell autoantibody assay, a combi-GAD and IA-2 test, and individual GAD and IA-2 assays. RESULTS: Patients from group A had significantly higher combi-test values than patients from group C (13+/-16 vs. 4.5+/-12 units, P<0.02) and higher anti-GAD65 antibody (Ab) levels (0.19+/-0.3 vs. 0.04+/-0.13 units, P<0.01) immediately before grafting. After graft failure in group A, both anti-GAD65 and anti-IA-2 Ab levels increased from baseline, but only the increase in anti-IA-2 Ab levels reached statistical significance (0.28+/-0.12 vs. 15+/-34, P=0.03). When compared with group C, patients from group A had higher anti-GAD65 Abs (0.29+/-0.35 vs. 0.05+/-0.16, P<0.001) after graft failure. Interestingly, the number of double-Ab-positive patients rose from 5% to 35% in group A, whereas it remained at 5% in group C. In pancreatic transplants with bladder drainage, the presence of anti-GAD65 and/or anti-IA2 Abs was not associated with a reduction in urinary amylase levels. This suggests that a loss of endocrine function was not associated with exocrine failure in patients from group A. CONCLUSIONS: We can conclude from the present study that peripheral autoimmune markers are useful in diabetic patients receiving pancreatic allografts.

Adult↗

PubMed2004

Renal transplant survival from older donors: a single center experience.

HYPOTHESIS: Despite the observation that kidney transplantations from older donors have an increased risk of failure, the percentage of kidney donors 55 years and older has increased. We explored the risk of allograft failure in a single transplantation center with older (55-79 years) vs younger (18-54 years) donors. DESIGN: Retrospective cohort review with a mean follow-up of 32 months. SETTING: Academic transplant center. PATIENTS: Consecutive recipients (n = 324) of renal transplants from adult donors. INTERVENTIONS: Patients were divided into 4 groups based on donor status (living or deceased) and donor age (< or =54 or > or =55 years). MAIN OUTCOME MEASURES: Allograft survival and function, incidence of acute rejection. RESULTS: Recipients of older donor kidneys were significantly older (53.6 vs 43.6 years, P<.001). Seven allografts (12.7%) failed from 55 transplants from donors 55 years and older, compared with 41 allografts (15.2%) from 269 younger donors (P =.63). Renal function was superior following renal transplantation using younger donors (P =.004). However, renal function was acceptable in all groups, with a mean +/- SD serum creatinine level of 1.7 +/- 0.4 mg/dL (150 +/- 35 micro mol/L) among recipients of older donor kidneys. Allograft survival at 1, 2, and 3 years, censored for death with allograft function, did not differ when comparing older vs younger donors. CONCLUSIONS: Most patients receiving allografts from older donors do well. Older donor kidneys provide suitable renal function for many patients on dialysis awaiting transplantation.

Adolescent↗

PubMed1995

Effects of liver transplantation on bile formation and biliary lipid secretion in the Sprague-Dawley rat.

Altered hepatic secretory function after orthotopic liver transplantation constitutes a major perioperative clinical problem. Cholestasis and cholesterol gallstone formation are among the most frequent complications reported. Such changes in the allograft secretory function can be secondary to many factors like graft injury due to preservation and marked rejection, surgical complications, immunosuppressive therapy, and sepsis. The effects of liver transplantation per se on bile formation and biliary lipid secretion are unknown. The rat model of orthotopic liver transplantation was used to characterize better the true effect of transplantation without the influence of these confounding variables. Twenty-four-hour bile collections were performed on nine transplanted versus nine liver-denervated (sham) rats 4 weeks after surgery, and nine normal Sprague-Dawley rats. The liver allografts showed mild lymphocytic infiltration in portal tracts and the serum alanine transaminase levels were not significantly elevated. Bile flow and the secretion of bile salts and bilirubin under basal conditions were unchanged. Bile salt pool size, synthesis rate, and bile acid composition did not differ among the three groups. However, cholesterol secretion was dramatically reduced (50%) in the transplanted rats and decreased 31% in the liver-denervated rats (P < .001 and .01, respectively), resulting in a more favorable cholesterol saturation index (CSI = 0.29 for transplanted and 0.32 for sham versus 0.45 for normal controls; P < .01). Thus, liver transplantation with its attendant denervation did not impair hepatic secretory function, but rather improved biliary lipid composition despite mild rejection.

Alanine Transaminase↗

PubMed2000

Fractures in large-segment allografts.

Segment skeletal defects that result from resection of a malignant bone neoplasm commonly are reconstructed with large segment allografts. Excellent functional results after these reconstructions and significant complications have been reported. Although it is known that a common complication seen with the use of allografts is allograft fracture, the factors associated with allograft fracture are not entirely clear. In this study, the hypothesis was examined that allograft reconstructions, which use internal fixation devices that penetrate the cortex of the allograft, are associated with an increased risk of fracture. Findings from large segment allograft reconstructions in 74 patients with a minimum followup of 36 months were studied. These 74 patients include 35 patients whose outcomes were reported previously and now have additional followup and 39 patients whose outcomes are being reported for the first time. Thirty-one of the 74 (42%) allografts fractured, and the mean time to fracture was 26 months. When the fixation techniques resulted in cortical penetration of the allograft, fractures occurred in 27 of the 43 (63%) allografts, and when fixation of the graft to the host bone required no cortical penetration, only four of the 31 (13%) allografts fractured. Fractures occurred in 12 of 15 (80%) tibial allografts and in only two of 17 (12%) proximal femoral allografts; however, the anatomic site was not statistically independent of method of fixation because 14 of the 15 tibial grafts had cortical penetration and 15 of the 17 proximal femoral grafts had no cortical penetration. The authors' analysis indicates that internal fixation devices that require cortical penetration are associated with an increased risk of allograft fracture.

Adolescent↗