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Sample records for allogeneic bone graft

  1. Optimal graft source for allogeneic hematopoietic stem cell transplant: bone marrow or peripheral blood?

    PubMed

    Adhikari, Janak; Sharma, Priyadarshani; Bhatt, Vijaya Raj

    2016-08-01

    Peripheral blood (PB), compared with bone marrow graft, has higher stem cell content, leads to faster engraftment and is more convenient for collection. Consequently, the use of PB graft has significantly increased in recent years. Although the use of PB graft is acceptable or even preferred to bone marrow graft in matched related donor allogeneic transplant due to a possibility of improved survival, PB graft increases the risk of chronic graft-versus-host disease and associated long-term toxicities in the setting of matched unrelated donor allogeneic transplant. In haploidentical transplant, mitigation of graft-versus-host disease with the use of post-transplant cyclophosphamide is a hypothesis-generating possibility; however, available studies have significant limitations to draw any definite conclusion. PMID:27168462

  2. Apoptosis of ileal crypt epithelia after allogeneic bone marrow transplantation without graft-versus-host disease

    PubMed Central

    Kreft, Andreas; Russo, Alexandra; Lux, Steffi; Waiz, Lioudmila; Seidmann, Larissa; Faber, Jörg; Kirkpatrick, Charles J

    2015-01-01

    Key Clinical Message Intestinal crypt cell apoptosis may occur after allogeneic bone marrow transplantation without clinically overt graft-versus-host disease. We describe this phenomenon in a case of a 12-year-old girl who had segments of the ileum resected because of a relapse of acute lymphoblastic leukemia. The diagnostic difficulties are discussed. PMID:25984309

  3. BET bromodomain inhibition suppresses graft-versus-host disease after allogeneic bone marrow transplantation in mice

    PubMed Central

    Sun, Yaping; Wang, Ying; Toubai, Tomomi; Oravecz-Wilson, Katherine; Liu, Chen; Mathewson, Nathan; Wu, Julia; Rossi, Corinne; Cummings, Emily; Wu, Depei; Wang, Shaomeng

    2015-01-01

    Acute graft-versus-host disease (GVHD) is the major obstacle of allogeneic bone marrow transplantation (BMT). Bromodomain and extra-terminal (BET) protein inhibitors selectively block acetyl-binding pockets of the bromodomains and modulate histone acetylation. Here, we report that inhibition of BET bromodomain (BRD) proteins with I-BET151 alters cytokine expression in dendritic cells (DCs) and T cells, including surface costimulatory molecules, in vitro and in vivo cytokine secretion, and expansion. Mechanistic studies with I-BET151 and JQ1, another inhibitor, demonstrate that these effects could be from disruption of association between BRD4 and acetyl-310 RelA of nuclear factor kappa B. Short-term administration early during BMT reduced GVHD severity and improved mortality in two different allogeneic BMT models but retained sufficient graft-versus-tumor effect. Thus inhibiting BRD proteins may serve as a novel approach for preventing GVHD. PMID:25778533

  4. Bone marrow ablation followed by allogeneic marrow grafting during first complete remission of acute nonlymphocytic leukemia

    SciTech Connect

    Forman, S.J.; Spruce, W.E.; Farbstein, M.J.

    1983-03-01

    Of 33 patients who had undergone allogeneic bone marrow transplantation during first complete remission of acute nonlymphocytic leukemia, 21 patients have now been followed in continued complete remission for 6-64 mo (median greater than 18 mo) without maintenance chemotherapy. The median age of the surviving patients is 27 yr. Transplant-related complications occurring throughout the first year after marrow grafting were fatal in 7 patients, and leukemic recurrence led to the death of 5 patients. The actuarial long-term disease-free survival is 60% and the actuarial remission rate is 79%.

  5. Bone Grafts

    MedlinePlus

    A bone graft transplants bone tissue. Surgeons use bone grafts to repair and rebuild diseased bones in your hips, knees, spine, and sometimes other bones and joints. Grafts can also repair bone loss caused by some ...

  6. Allogeneic Versus Autologous Derived Cell Sources for Use in Engineered Bone-Ligament-Bone Grafts in Sheep Anterior Cruciate Ligament Repair

    PubMed Central

    Mahalingam, Vasudevan D.; Behbahani-Nejad, Nilofar; Horine, Storm V.; Olsen, Tyler J.; Smietana, Michael J.; Wojtys, Edward M.; Wellik, Deneen M.; Arruda, Ellen M.

    2015-01-01

    The use of autografts versus allografts for anterior cruciate ligament (ACL) reconstruction is controversial. The current popular options for ACL reconstruction are patellar tendon or hamstring autografts, yet advances in allograft technologies have made allogeneic grafts a favorable option for repair tissue. Despite this, the mismatched biomechanical properties and risk of osteoarthritis resulting from the current graft technologies have prompted the investigation of new tissue sources for ACL reconstruction. Previous work by our lab has demonstrated that tissue-engineered bone-ligament-bone (BLB) constructs generated from an allogeneic cell source develop structural and functional properties similar to those of native ACL and vascular and neural structures that exceed those of autologous patellar tendon grafts. In this study, we investigated the effectiveness of our tissue-engineered ligament constructs fabricated from autologous versus allogeneic cell sources. Our preliminary results demonstrate that 6 months postimplantation, our tissue-engineered auto- and allogeneic BLB grafts show similar histological and mechanical outcomes indicating that the autologous grafts are a viable option for ACL reconstruction. These data indicate that our tissue-engineered autologous ligament graft could be used in clinical situations where immune rejection and disease transmission may preclude allograft use. PMID:25397361

  7. Allogeneic versus autologous derived cell sources for use in engineered bone-ligament-bone grafts in sheep anterior cruciate ligament repair.

    PubMed

    Mahalingam, Vasudevan D; Behbahani-Nejad, Nilofar; Horine, Storm V; Olsen, Tyler J; Smietana, Michael J; Wojtys, Edward M; Wellik, Deneen M; Arruda, Ellen M; Larkin, Lisa M

    2015-03-01

    The use of autografts versus allografts for anterior cruciate ligament (ACL) reconstruction is controversial. The current popular options for ACL reconstruction are patellar tendon or hamstring autografts, yet advances in allograft technologies have made allogeneic grafts a favorable option for repair tissue. Despite this, the mismatched biomechanical properties and risk of osteoarthritis resulting from the current graft technologies have prompted the investigation of new tissue sources for ACL reconstruction. Previous work by our lab has demonstrated that tissue-engineered bone-ligament-bone (BLB) constructs generated from an allogeneic cell source develop structural and functional properties similar to those of native ACL and vascular and neural structures that exceed those of autologous patellar tendon grafts. In this study, we investigated the effectiveness of our tissue-engineered ligament constructs fabricated from autologous versus allogeneic cell sources. Our preliminary results demonstrate that 6 months postimplantation, our tissue-engineered auto- and allogeneic BLB grafts show similar histological and mechanical outcomes indicating that the autologous grafts are a viable option for ACL reconstruction. These data indicate that our tissue-engineered autologous ligament graft could be used in clinical situations where immune rejection and disease transmission may preclude allograft use. PMID:25397361

  8. Allogeneic bone marrow transplantation in models of experimental autoimmune encephalomyelitis: evidence for a graft-versus-autoimmunity effect.

    PubMed

    Van Wijmeersch, Bart; Sprangers, Ben; Rutgeerts, Omer; Lenaerts, Caroline; Landuyt, Willy; Waer, Mark; Billiau, An D; Dubois, Bénédicte

    2007-06-01

    Autologous hematopoietic stem cell transplantation (HSCT) is being explored in the treatment of severe multiple sclerosis (MS), and is based on the concept of "resetting" the immune system. The use of allogeneic HSCT may offer additional advantages, such as the replacement of the autoreactive immune compartment by healthy allogeneic cells and development of a graft-versus-autoimmunity (GVA) effect. However, in clinical practice, the genetic susceptibility to MS of allogeneic stem cell donors is generally unknown, and GVA may therefore be an important mechanism of action. Experimental autoimmune encephalomyelitis (EAE)-susceptible and -resistant mouse strains were used to determine the roles of genetic susceptibility, level of donor-chimerism, and alloreactivity in the therapeutic potential of syngeneic versus allogeneic bone marrow transplant (BMT) for EAE. After transplantation and EAE induction, animals were evaluated for clinical EAE and ex vivo myelin oligodendrocyte glycoprotein-specific proliferation. Early after BMT, both syngeneic and allogeneic chimeras were protected from EAE development. On the longer term, allogeneic but not syngeneic BMT conferred protection, but this required high-level donor-chimerism from EAE-resistant donors. Importantly, when EAE-susceptible donors were used, robust protection from EAE was obtained when active alloreactivity, induced by donor lymphocyte infusions, was provided. Our findings indicate the requirement of a sufficient level of donor-chimerism from a nonsusceptible donor in the therapeutic effect of allogeneic BMT. Importantly, the data indicate that, independently of genetic susceptibility, active alloreactivity is associated with a GVA effect, thereby providing new evidence to support the potential role of allogeneic BMT in the treatment of MS. PMID:17531772

  9. Three-Dimensional Bone Regeneration of Alveolar Ridge Defects Using Corticocancellous Allogeneic Block Grafts: Histologic and Immunohistochemical Analysis.

    PubMed

    Jun, Choong-Man; Yun, Jeong-Ho

    2016-01-01

    In this study, the effectiveness of a corticocancellous block allograft for restoring alveolar ridge defects in preparation for the placement of dental implants was assessed. Significant ridge defects in four partially edentulous patients were reconstructed using an irradiated corticocancellous allogeneic block soaked in platelet-rich plasma, which was also covered with a resorbable collagen membrane. After 5 or 6 months, the sites were reentered and a trephine bone core specimen was obtained from each augmented site for histologic, histomorphometric, and immunohistochemical assessment. In all four cases, histologic evaluation of the augmented site showed areas of new vital bone formation around the graft material (mean newly formed bone fraction, 23.7%; mean total mineralized tissue fraction, 40.1%), in which osteocytes were frequently observed within the lacunae. Immunohistochemical analysis showed the presence of biomarkers commonly related to active bone formation (alkaline phosphatase, osteocalcin, and bone morphogenetic protein-2), confirming that the biochemical environment was conducive to new bone formation. The findings of this study demonstrate that the use of allogeneic block grafts for restoring alveolar ridge defects prior to the placement of dental implants may be an effective and advantageous alternative to autograft procedures. PMID:26697555

  10. Increased incidence of murine graft-versus-host disease after allogeneic bone marrow transplantation by previous infusion of syngeneic bone marrow cells

    SciTech Connect

    Waer, M.; Ang, K.K.; van der Schueren, E.; Vandeputte, M.

    1984-10-01

    Different groups of BALB/c mice received supralethal total-body irradiation (TBI; 8.5 Gy, day 0). When 30 x 10(6) allogeneic (C57B1) bone marrow (BM) cells were infused with or without 10 x 10(6) syngeneic (BALB/c) bM cells on day 1, many animals (60%) died from graft-versus-host disease (GVHD). Typing of peripheral blood leukocytes for donor antigens showed that, respectively, 22/22 and 17/21 of the mice in both groups became chimeric. When syngeneic bone marrow was given on day 1 and allogeneic bone marrow on day 2 after TBI, a similar number of animals (21/23) became chimeric, but GVHD occurred more frequently in this group (25/26 mice, P less than 0.01). When the syngeneic bone marrow cells were replaced by spleen cells, or when the transplantation of allogeneic bone marrow was delayed till days 3 or 6 after TBI, almost all mice rejected the allogeneic BM graft and became long-term survivors. BALB/c mice receiving 30 x 10(6) C57B1 BM cells after 17 daily fractions of 0.2 Gy of total lymphoid irradiation (TLI), showed a high incidence of chimerism (15/17) and in none of the latter animals was GVHD observed. Despite the high incidence of GVHD in the mice receiving allogeneic BM after TBI and syngeneic BM transplantation, as compared with mice prepared with TLI which do not develop GVHD, suppressor cells were as easily induced after TBI and syngeneic BM transplantation as after TLI.

  11. Effect of peripheral lymphoid cells on the incidence of lethal graft versus host disease following allogeneic mouse bone marrow transplantation

    SciTech Connect

    Almaraz, R.; Ballinger, W.; Sachs, D.H.; Rosenberg, S.A.

    1983-02-01

    Experiments were performed to study the role of circulating lymphoid cells in the incidence of lethal graft versus host disease (GVHD) in radiation-induced fully allogeneic mouse chimeras. The incidence of GVHD was reduced significantly in BALB/c leads to C57BL/6 radiation chimeras if bone marrow donors were exsanguinated immediately prior to marrow harvest. Chimeras resulting from the injection of bone marrow from bled donors exhibited only donor cells in spleen, bone marrow and peripheral blood and normal levels of Thy 1+ and Ia+ cells were found in each of these lymphoid compartments. The addition of as few as 3 X 10(4) peripheral mononuclear cells to the marrow from exsanguinated donors uniformly led to lethal GVHD. /sup 51/Cr-labeled cell traffic studies revealed that prior exsanguination of marrow donors led to about a 70% reduction in the number of circulating mononuclear cells contaminating the bone marrow at the time of marrow harvest. This decrease in contaminating peripheral cells was calculated to be in the appropriate range to account for the decreased GVHD seen when marrow from exsanguinated donors was used. It thus appears that peripheral cells contaminating marrow can be an important factor in causing lethal GVHD in allogeneic radiation chimeras.

  12. Effects of T cell depletion in radiation bone marrow chimeras. III. Characterization of allogeneic bone marrow cell populations that increase allogeneic chimerism independently of graft-vs-host disease in mixed marrow recipients

    SciTech Connect

    Sykes, M.; Chester, C.H.; Sundt, T.M.; Romick, M.L.; Hoyles, K.A.; Sachs, D.H. )

    1989-12-01

    The opposing problems of graft-vs-host disease vs failure of alloengraftment severely limit the success of allogeneic bone marrow transplantation as a therapeutic modality. We have recently used a murine bone marrow transplantation model involving reconstitution of lethally irradiated mice with mixtures of allogeneic and syngeneic marrow to demonstrate that an allogeneic bone marrow subpopulation, removed by T cell depletion with rabbit anti-mouse brain serum and complement (RAMB/C), is capable of increasing levels of allogeneic chimerism. This effect was observed in an F1 into parent genetic combination lacking the potential for graft-vs-host disease, and radiation protection studies suggested that it was not due to depletion of stem cells by RAMB/C. We have now attempted to characterize the cell population responsible for increasing allogeneic chimerism in this model. The results indicate that neither mature T cells nor NK cells are responsible for this activity. However, an assay involving mixed marrow reconstitution in an Ly-5 congenic strain combination was found to be more sensitive to small degrees of stem cell depletion than radiation protection assays using three-fold titrations of bone marrow cells. Using this assay, we were able to detect some degree of stem cell depletion by treatment with RAMB/C, but not with anti-T cell mAb. Nevertheless, if the effects of alloresistance observed in this model are considered, the degree of stem cell depletion detected by such mixing studies in insufficient to account for the effects of RAMB/C depletion on levels of allogeneic chimerism, suggesting that another cell population with this property remains to be identified.

  13. The triterpenoid CDDO-Me delays murine acute graft-versus-host disease with the preservation of graft-versus-tumor effects after allogeneic bone marrow transplantation

    PubMed Central

    Li, Minghui; Sun, Kai; Redelman, Doug; Welniak, Lisbeth A.; Murphy, William J.

    2010-01-01

    The occurrence of acute graft-versus-host disease (GVHD) and tumor relapse represent the two major obstacles impeding the efficacy of allogeneic bone marrow transplantation (BMT) in cancer. We have previously shown that the synthetic triterpenoid CDDO can inhibit murine early acute GVHD but anti-tumor effects were not assessed. In the current study, we found that a new derivative of CDDO, CDDO-Me, had an increased ability to inhibit allogeneic T cell responses and induce cell death of alloreactive T cells in vitro. Administration of CDDO-Me to mice following allogeneic BMT resulted in significant and increased protection from acute lethal GVHD compared to CDDO. This correlated with reduced TNF-α production, reduced donor T cell proliferation and decreased adhesion molecule (α4β7 integrin) expression on the donor T cells. CDDO-Me was also superior to CDDO in inhibiting leukemia growth in vitro. When CDDO-Me was administered following an allogeneic BMT to leukemia-bearing mice, significant increases in survival were observed. These findings suggest that CDDO-Me is superior to CDDO in delaying acute GVHD while preserving or possibly even augmenting GVT effects. PMID:20338256

  14. Bone Grafts

    MedlinePlus

    ... repair and rebuild diseased bones in your hips, knees, spine, and sometimes other bones and joints. Grafts can also repair bone loss caused by some types of fractures or cancers. Once your body accepts the bone ...

  15. Esthetic outcome of implant-based reconstructions in augmented bone: comparison of autologous and allogeneic bone block grafting with the pink esthetic score (PES)

    PubMed Central

    2014-01-01

    Introduction To determine the esthetic outcome of implant-based reconstructions after autologous and allogeneic bone grafting. Methods From 2003 to 2009, 67 patients underwent alveolar ridge augmentation and were enrolled in the study, 41 meet the inclusion criteria and 31 agreed to take part in the study. Patients were 18-69 years old (mean: 49.3 ± 13.8 years), and predominantly female. Patients received bone block grafts either autologous (n = 48) (AUBB) or allografts (ABB) (n = 19). Implants were inserted 4-7 months (autografts) or 5-6 months (allografts) after bone grafting. The Pink Esthetic Score (PES) as well as radiographic and subjective assessments were employed for the outcome analysis. The PES was assessed twice within one month based on digital photographic images that were randomly rearranged between evaluations by three independent, experienced investigators. Results Across all observations and investigators, the average PES was 7.5 ± 2.6 without differences between implants inserted in auto- and allografted bone, respectively. Patients assessed the allograft procedures as less painful and would have repeated it more often. The intra-rater reliability was excellent (correlation coefficients 0.7-0.9). The inter-observer agreement was lower (correlation coefficients 0.6-0.8). Conclusions Bone grafting with ABB allografts yields equivalent results to autologous grafting, and patients appreciate the omission of bone harvesting. The PES is a reliable method but should be performed by the same individual. PMID:24885136

  16. Absence of P-selectin in Recipients of Allogeneic Bone Marrow Transplantation Ameliorates Experimental Graft-versus-Host-Disease

    PubMed Central

    Lu, Sydney X.; Holland, Amanda M.; Na, Il-Kang; Terwey, Theis H.; Alpdogan, Onder; Bautista, Jhoanne L.; Smith, Odette M.; Suh, David; King, Christopher; Kochman, Adam; Hubbard, Vanessa M.; Rao, Uttam K.; Yim, Nury; Liu, Chen; Laga, Alvaro C.; Murphy, George; Jenq, Robert; Zakrzewski, Johannes L.; Penack, Olaf; Dykstra, Lindsay; Bampoe, Kevin; Perez, Lia; Furie, Bruce; Furie, Barbara; van den Brink, Marcel R.M.

    2013-01-01

    Alloreactive T cells are crucial for graft-versus-host-disease (GVHD) pathophysiology, and modulating their trafficking patterns has been efficacious in ameliorating experimental disease. We report here that P-selectin, a glycoprotein found on resting and inflamed endothelium, is important for donor alloreactive T cells trafficking into GVHD target organs such as the intestines and skin. Compared with wildtype recipients of allogeneic bone marrow transplantation (allo-BMT), P-selectin−/− recipients exhibit decreased GVHD mortality and decreased GVHD of the skin, liver and small bowels. This was associated with diminished infiltration of alloactivated T cells into the Peyer's Patches and small bowels, coupled with increased numbers of donor T cells in the spleen and secondary lymphoid organs (SLO). Surprisingly however, donor T cells deficient for PSGL1, the most well-described P-selectin ligand, mediated similar GVHD as WT T cells, and accumulated in SLO and target organs in similar numbers as WT T cells. This suggests that P-selectin may be required for trafficking into inflamed tissues but not SLO, and that donor T cells may utilize multiple P-selectin ligands apart from PSGL1 to interact with P-selectin and traffic into inflamed tissues during GVHD. We conclude that targeting P-selectin may be a viable target for GVHD prophylaxis or treatment. PMID:20622117

  17. Prevention of graft rejection in allogeneic bone marrow transplantation. II. Preclinical studies with three radiation protocols

    SciTech Connect

    Malilay, G.P.; Sevenich, E.A.; Filipovich, A.H. )

    1990-09-01

    Three radiotherapeutic regimens were compared in vitro to determine their immunosuppressive potential against non-MHC-restricted cytotoxic cells. Assays of natural killer and lymphokine-activated killer function, and cytotoxicity against allogeneic cells were used to quantitate the cytotoxic potential of peripheral blood mononuclear cells from healthy individuals following irradiation with a single dose of 1000 cGy on day 0, 1320 cGy of fractionated radiation (165 cGy b.i.d. x 4 days), or split-dose irradiation consisting of 1000 cGy on day 0 followed 5 or 7 days later by 500 cGy. Both irradiated and nonirradiated (control) PBMC cultures were maintained in culture with medium containing interleukin-2, immunophenotyped, and assayed for cytotoxicity from 1 to 8 days after irradiation. Single dose and fractionated-dose irradiation resulted in a progressive decline in cytotoxic capacity, with an 80% inhibition of both NK and LAK cell activity 8 days after onset of irradiation. The split dose of 500 cGy administered 7 days after a dose of 1000 cGy was found to be the most effective in eliminating NK (93% inhibition) and LAK (100% inhibition) cytotoxicity. These data indicate that split-dose irradiation may result in greater immunosuppression than single-dose or fractionated irradiation.

  18. The effect of peripheral lymphoid cells on the incidence of lethal graft versus host disease following allogeneic mouse bone marrow transplantation

    SciTech Connect

    Almaraz, R.; Ballinger, W.; Sachs, D.H.; Rosenberg, S.A.

    1983-02-01

    Experiments were performed to study the role of circulating lymphoid cells in the incidence of lethal graft versus host disease (GVHD) in radiation-induced fully allogeneic mouse chimeras. The incidence of GVHD was reduced significantly in BALB/c leads to C57BL/6 radiation chimeras if bone marrow donors were exsanguinated immediately prior to marrow harvest. Chimeras resulting from the injection of bone marrow from bled donors exhibited only donor cells in spleen, bone marrow and peripheral blood and normal levels of Thy 1+ and Ia+ cells were found in each of these lymphoid compartments. The addition of as few as 3 X 10(4) peripheral mononuclear cells to the marrow from exsanguinated donors uniformly led to lethal GVHD. /sup 51/Cr-labeled cell traffic studies revealed that prior exsanguination of marrow donors led to about a 70% reduction in the number of circulating mononuclear cells contaminating the bone marrow at the time of marrow harvest. This decrease in contaminating peripheral cells was calculated to be in the appropriate range to account for the decreased GVHD seen when marrow from exsanguinated donors was used. It thus appears that peripheral cells contaminating marrow can be an important factor in causing lethal GVHD in allogeneic radiation chimeras. These results raise the possibility that the fulminant GVHD seen in human marrow transplantation is in part due to the major contamination of bone marrow with peripheral blood that results from the techniques currently used for human bone marrow harvest.

  19. Effect of selective T cell depletion of host and/or donor bone marrow on lymphopoietic repopulation, tolerance, and graft-vs-host disease in mixed allogeneic chimeras (B10 + B10. D2----B10)

    SciTech Connect

    Ildstad, S.T.; Wren, S.M.; Bluestone, J.A.; Barbieri, S.A.; Stephany, D.; Sachs, D.H.

    1986-01-01

    Reconstitution of lethally irradiated mice with a mixture of T cell-depleted syngeneic plus T cell-depleted allogeneic bone marrow (B10 + B10.D2----B10) leads to the induction of mixed lymphopoietic chimerism, excellent survivals, specific in vivo transplantation tolerance to subsequent donor strain skin grafts, and specific in vitro unresponsiveness to allogeneic donor lymphoid elements as assessed by mixed lymphocyte reaction (MLR) proliferative and cell-mediated lympholysis (CML) cytotoxicity assays. When B10 recipient mice received mixed marrow inocula in which the syngeneic component had not been T cell depleted, whether or not the allogeneic donor marrow was treated, they repopulated exclusively with host-type cells, promptly rejected donor-type skin allografts, and were reactive in vitro to the allogeneic donor by CML and MLR assays. In contrast, T cell depletion of the syngeneic component of the mixed marrow inocula resulted in specific acceptance of allogeneic donor strain skin grafts. Such animals were specifically unreactive to allogeneic donor lymphoid elements in vitro by CML and MLR, but were reactive to third party. When both the syngeneic and allogeneic marrow were T cell depleted, variable percentages of host- and donor-type lymphoid elements were detected in the mixed reconstituted host. When only the syngeneic bone marrow was T cell depleted, animals repopulated exclusively with donor-type cells. Although these animals had detectable in vitro anti-host (B10) reactivity by CML and MLR and reconstituted as fully allogeneic chimeras, they exhibited excellent survival and had no in vivo evidence for graft-vs-host disease. Experiments in which untreated donor spleen cells were added to the inocula in this last group suggest that the presence of T cell-depleted syngeneic bone marrow cells diminishes graft-vs-host disease and the mortality from it.

  20. [Allogenic hematopoietic stem cell transplantation in acquired aplastic anemia: first experience of the National Center for Bone Marrow Grafting].

    PubMed

    Abdelkefi, A; Ladeb, S; Ben Othman, T; Torjman, L; Jeddi, R; Ben Abdeladhim, A

    2001-10-01

    Bone marrow transplantation from HLA-identical sibling offers cure and leads to restoration of normal hematopoiesis and long-term survival in 60-80% of recipients. From february 1998 to october 1999, seven patients with aplastic anemia (2 very severe aplastic anemia and 5 severe aplastic anemia), with a median age of 22 years (14-39), received a transplant from an HLA-identical sibling donor. All patients had sustained engraftment. Only one patient developed grade IV acute graft-versus-host disease. One patient died in the 22th day of systemic mycobacterial infection and one in the 79th day of acute graft-versus-host disease. The remaining 5 patients are alive and have a complete hematological recovery, with a median follow-up of 6 months (1,5-12). There are at least two reasons for the improved survival of patients with aplastic anemia who where treated by HLA-indentical bone marrow transplantation. One is the decreased incidence of graft rejection that has resulted from the more judicious use of transfusions before bone marrow transplantation, and improvements in the immunosuppressive qualities of the conditioning programs. Another reason for improved survival is the decrease in the incidence and severity of acute graft-versus-host disease. PMID:11910688

  1. Increased Type 1 Immune Response in the Bone Marrow Immune Microenvironment of Patients with Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation.

    PubMed

    Wang, Yu-Tong; Kong, Yuan; Song, Yang; Han, Wei; Zhang, Yuan-Yuan; Zhang, Xiao-Hui; Chang, Ying-Jun; Jiang, Zheng-Fan; Huang, Xiao-Jun

    2016-08-01

    Poor graft function (PGF) is a severe complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The question of whether the bone marrow (BM) immune microenvironment is involved in the pathogenesis of PGF remains unresolved. In total, 10 patients with PGF, 30 matched patients with good graft function after allo-HSCT, and 15 healthy donors were enrolled in this nested case-control study. The Th1, Th2, Tc1, Tc2, and active phenotypes were analyzed by flow cytometry. IFN-γ and IL-4 levels in BM plasma were evaluated using cytometric beads assay. Relative to other subjects, patients with PGF had significantly higher proportions of stimulated CD4(+) and CD8(+) T cells that produced IFN-γ (Th1 and Tc1 cells) but notably decreased proportions of IL-4-producing T cells (Th2 and Tc2 cells), resulting in a shift of the IFN-γ/IL-4 ratio towards a type 1 response and an elevated percentage of activated CD8(+) T cells. Changes in IFN-γ and IL-4 levels in BM plasma were consistent with the cellular results. Our results suggest that dysregulated T cell responses may contribute to the occurrence of PGF after HSCT. PMID:27131864

  2. Bone grafts in dentistry

    PubMed Central

    Kumar, Prasanna; Vinitha, Belliappa; Fathima, Ghousia

    2013-01-01

    Bone grafts are used as a filler and scaffold to facilitate bone formation and promote wound healing. These grafts are bioresorbable and have no antigen-antibody reaction. These bone grafts act as a mineral reservoir which induces new bone formation. PMID:23946565

  3. Human mesenchymal stromal cells attenuate graft-versus-host disease and maintain graft-versus-leukemia activity following experimental allogeneic bone marrow transplantation.

    PubMed

    Auletta, Jeffery J; Eid, Saada K; Wuttisarnwattana, Patiwet; Silva, Ines; Metheny, Leland; Keller, Matthew D; Guardia-Wolff, Rocio; Liu, Chen; Wang, Fangjing; Bowen, Theodore; Lee, Zhenghong; Solchaga, Luis A; Ganguly, Sudipto; Tyler, Megan; Wilson, David L; Cooke, Kenneth R

    2015-02-01

    We sought to define the effects and underlying mechanisms of human, marrow-derived mesenchymal stromal cells (hMSCs) on graft-versus-host disease (GvHD) and graft-versus-leukemia (GvL) activity. Irradiated B6D2F1 mice given C57BL/6 BM and splenic T cells and treated with hMSCs had reduced systemic GvHD, donor T-cell expansion, and serum TNFα and IFNγ levels. Bioluminescence imaging demonstrated that hMSCs redistributed from lungs to abdominal organs within 72 hours, and target tissues harvested from hMSC-treated allogeneic BMT (alloBMT) mice had less GvHD than untreated controls. Cryoimaging more precisely revealed that hMSCs preferentially distributed to splenic marginal zones and regulated T-cell expansion in the white pulp. Importantly, hMSCs had no effect on in vitro cytotoxic T-cell activity and preserved potent GvL effects in vivo. Mixed leukocyte cultures containing hMSCs exhibited decreased T-cell proliferation, reduced TNFα, IFNγ, and IL-10 but increased PGE2 levels. Indomethacin and E-prostanoid 2 (EP2) receptor antagonisms both reversed while EP2 agonism restored hMSC-mediated in vitro T-cell suppression, confirming the role for PGE2 . Furthermore, cyclo-oxygenase inhibition following alloBMT abrogated the protective effects of hMSCs. Together, our data show that hMSCs preserve GvL activity and attenuate GvHD and reveal that hMSC biodistribute to secondary lymphoid organs wherein they attenuate alloreactive T-cell proliferation likely through PGE2 induction. PMID:25336340

  4. Subclinical pulmonary function defects following autologous and allogeneic bone marrow transplantation: relationship to total body irradiation and graft-versus-host disease

    SciTech Connect

    Tait, R.C.; Burnett, A.K.; Robertson, A.G.; McNee, S.; Riyami, B.M.; Carter, R.; Stevenson, R.D. )

    1991-06-01

    Pulmonary function results pre- and post-transplant, to a maximum of 4 years, were analyzed in 98 patients with haematological disorders undergoing allogeneic (N = 53) or autologous bone marrow transplantation (N = 45) between 1982 and 1988. All received similar total body irradiation based regimens ranging from 9.5 Gy as a single fraction to 14.4 Gy fractionated. FEV1/FVC as a measure of airway obstruction showed little deterioration except in patients experiencing graft-versus-host disease in whom statistically significant obstructive ventilatory defects were evident by 6 months post-transplant (p less than 0.01). These defects appeared to be permanent. Restrictive ventilatory defects, as measured by reduction in TLC, and defects in diffusing capacity (DLCO and KCO) were also maximal at 6 months post-transplant (p less than 0.01). Both were related, at least in part, to the presence of GVHD (p less than 0.01) or use of single fraction TBI with absorbed lung dose of 8.0 Gy (p less than 0.05). Fractionated TBI resulted in less marked restricted ventilation and impaired gas exchange, which reverted to normal by 2 years, even when the lung dose was increased from 11.0 Gy to between 12.0 and 13.5 Gy. After exclusion of patients with GVHD (30% allografts) there was no significant difference in pulmonary function abnormalities between autograft and allograft recipients.

  5. Mechanism of protection from graft-vs-host disease in murine mixed allogeneic chimeras. I. Development of a null cell population suppressive of cell-mediated lympholysis responses and derived from the syngeneic bone marrow component

    SciTech Connect

    Sykes, M.; Eisenthal, A.; Sachs, D.H.

    1988-05-01

    Splenocyte populations from whole body-irradiated recipients of mixed T cell-depleted (TCD) syngeneic and allogeneic (complete H-2 disparity) bone marrow, or of TCD syngeneic marrow alone, contain cells with the ability to suppress the generation of cell-mediated lympholysis responses in vitro. This activity, which is present by 8 days after bone marrow transplantation and persists for several weeks, has been analyzed for possible veto-like or other specificity. Although reproducible patterns of suppression were observed, depending both on host strain and on the genetic combination of the response examined, the overall suppression in vitro most closely resembles that which has been ascribed to natural suppressor cells in other systems. The suppression appears to be mediated by a non-T cell, non-B cell, nonadherent, asialo GM1-negative population. Cold target inhibition and CTL activity of chimeric cells have been ruled out as factors contributing to the observed suppression. Significantly, in mixed chimeras, suppression was found to be mediated exclusively by cells which were syngeneic to the recipient in both recipient strains tested. The rapid development of this suppressive activity may explain the resistance to graft-vs-host disease conferred on whole body-irradiated mice by the addition of TCD syngeneic marrow to an allogeneic graft-vs-host disease-producing inoculum.

  6. Effects of bone marrow mesenchymal stem cells on hematopoietic recovery and acute graft-versus-host disease in murine allogeneic umbilical cord blood transplantation model.

    PubMed

    Li, Zhen Yu; Wang, Chun Qing; Lu, Guang; Pan, Xiu Ying; Xu, Kai Lin

    2014-09-01

    To investigate the effect of bone marrow mesenchymal stem cells (MSC) on hematopoietic recovery and acute graft-versus-host disease (GVHD) in a murine allogeneic umbilical cord blood transplantation (allo-UCBT) model. MSCs were obtained from C57/BL mouse bone marrow. The MSC phenotypes were identified by flow cytometry (FCM), and their ability to differentiate into osteoblasts and adipocytes was tested. Once murine allo-UCBT and aGVHD models were established, mice were divided into five groups: (1) total body irradiation (TBI) group, each mouse receiving 0.3 ml sterile saline infusion after TBI and used as control; (2) UCB group, receiving 2 × 10(6) umbilical cord blood mononuclear cells (UCB-MNC) after TBI; (3) UCB+MSC group, receiving 2 × 10(6) UCB-MNC and 2 × 10(7) MSC after TBI; (4) UCB+SC group, receiving 2 × 10(6) UCB-MNC and 2 × 10(6) spleen cells after TBI; and (5) UCB+SC+MSC group, receiving 2 × 10(6) UCB-MNC, 2 × 10(7) MSC and 2 × 10(6) spleen cells after TBI. To evaluate the engraftment of HSC, the white blood cells, red blood cells, and platelets counts were tested at different time points after transplantation, and the ratio of chimerism was identified by FCM. The acute GVHD clinical scores, recipient mice survival, and the histopathological analyses were used to evaluate the effect of MSC on acute GVHD. MSCs were successfully obtained in vitro and FCM analysis showed that these cells are highly positive for CD90.2, CD44, and negative for CD34, CD45, and they are capable to differentiate into osteoblasts and adipocytes after being induced. Compared to UCB group, the UCB+MSC mice had shorter duration of myelosuppression and higher percentage of donor-derived cells which was up to 22.87 ± 4.3 % and the white blood cell (WBC), red blood cell (RBC), and platelet counts started to increase by day 6 after transplantation. Moreover, the average survival time for UCB+MSC mice was 25.0 ± 10.55 days, while for the UCB group it was 15.5 ± 12.50 days

  7. Arthroscopic Treatment of Subchondral Bony Cyst in Early Osteoarthritis of the Hip Joint Using Allogeneic Bone Graft: A Report of Two Cases

    PubMed Central

    Lee, Gi-Soo; Kang, Chan; Lee, Jung-Bum; Noh, Chang-Kyun

    2015-01-01

    Subchondral bony cyst, large solitary or multiple cysts in acetabular dome usually exacerbate progression to degenerative osteoarthritis in the hip joint. But it can be treated through arthroscopic intervention. We report two cases that treated by arthroscopic curettage and bone graft for subchondral bony cysts in early osteoarthritis of the hip joint, and it may delay progression to moderate osteoarthritis.

  8. Proximal Tibial Bone Graft

    MedlinePlus

    ... Complications Potential problems after a PTBG include infection, fracture of the proximal tibia and pain related to the procedure. Frequently Asked Questions If proximal tibial bone graft is taken from my knee, will this prevent me from being able to ...

  9. Biology of cancellous bone grafts.

    PubMed

    Heiple, K G; Goldberg, V M; Powell, A E; Bos, G D; Zika, J M

    1987-04-01

    Despite 30 years of experimental bone grafting research, the fresh cancellous bone graft remains the most osteogenic and reliable bone grafting material. Recent experimental data suggest that modification of the graft-host interaction by antigen matching or immune manipulation may allow increasingly successful use of allografts. PMID:3550570

  10. Bone Grafts in Craniofacial Surgery

    PubMed Central

    Elsalanty, Mohammed E.; Genecov, David G.

    2009-01-01

    Reconstruction of cranial and maxillofacial defects is a challenging task. The standard reconstruction method has been bone grafting. In this review, we shall describe the biological principles of bone graft healing, as pertinent to craniofacial reconstruction. Different types and sources of bone grafts will be discussed, as well as new methods of bone defect reconstruction. PMID:22110806

  11. Bone grafts and their substitutes.

    PubMed

    Fillingham, Y; Jacobs, J

    2016-01-01

    The continual cycle of bone formation and resorption is carried out by osteoblasts, osteocytes, and osteoclasts under the direction of the bone-signaling pathway. In certain situations the host cycle of bone repair is insufficient and requires the assistance of bone grafts and their substitutes. The fundamental properties of a bone graft are osteoconduction, osteoinduction, osteogenesis, and structural support. Options for bone grafting include autogenous and allograft bone and the various isolated or combined substitutes of calcium sulphate, calcium phosphate, tricalcium phosphate, and coralline hydroxyapatite. Not all bone grafts will have the same properties. As a result, understanding the requirements of the clinical situation and specific properties of the various types of bone grafts is necessary to identify the ideal graft. We present a review of the bone repair process and properties of bone grafts and their substitutes to help guide the clinician in the decision making process. PMID:26733632

  12. Avascular necrosis of bone after allogeneic bone marrow transplantation: clinical findings, incidence and risk factors.

    PubMed

    Socié, G; Sélimi, F; Sedel, L; Frija, J; Devergie, A; Esperou Bourdeau, H; Ribaud, P; Gluckman, E

    1994-03-01

    In the present study we describe the incidence, clinical course, and management of avascular necrosis of bone following allogeneic bone marrow transplantation, and identify risk factors related to its development. All patients developing avascular necrosis of bone after allogeneic bone marrow transplantation between January 1974 and September 1992 were included in the analysis and were studied using the Hôpital Saint Louis Bone Marrow Transplant Database and hospital records. 27/727 allogeneic transplant recipients developed avascular necrosis leading to an 8.1% incidence at 5 years, by product limit estimate, ranging from 5% to 11.2%. Symptoms developed 119-1747 d (median 398 d) after transplantation. In these 27 patients a total of 52 joints were affected (mean 1.92 per patient, range 1-7). The hip joint was most often affected (69% of patients). All patients had joint pain that led to diagnosis by means of standard radiographs with or without the help of technetium-99 scans and/or magnetic resonance imaging. All but three patients received steroid therapy for acute graft-versus-host disease. Among 10 factors tested, three were shown to be significantly linked to an increased risk for developing avascular necrosis by multivariate analysis: male gender (relative risk (RR) 4.72, P = 0.002), age older than 16 (RR = 3.87, P = 0.004), and acute graft-versus-host disease requiring steroid therapy (RR = 6.30, P = 0.0002). 10 patients (37%) required joint replacement within 19 months (range 2-42) following diagnosis of avascular necrosis. In conclusion, avascular necrosis of bone is a frequent late complication of allogeneic bone marrow transplantation causing significant morbidity and requiring replacement surgery in one-third of affected patients. In this 18-year single-centre survey, older age, male gender and steroid therapy given for acute graft-versus-host disease were shown to independently increase the risk of avascular necrosis of bone. PMID:8043445

  13. Alveolar bone grafting

    PubMed Central

    Lilja, Jan

    2009-01-01

    In patients with cleft lip and palate, bone grafting in the mixed dentition in the residual alveolar cleft has become a well-established procedure. The main advantages can be summarised as follows: stabilisation of the maxillary arch; facilitation of eruption of the canine and sometimes facilitation of the lateral incisor eruption; providing bony support to the teeth adjacent to the cleft; raising the alar base of the nose; facilitation of closure of an oro-nasal fistula; making it possible to insert a titanium fixture in the grafted site and to obtain favourable periodontal conditions of the teeth within and adjacent to the cleft. The timing of the ABG surgery take into consideration not only eruption of the canine but also that of the lateral incisor, if present. The best time for bone grafting surgery is when a thin shell of bone still covers the soon erupting lateral incisor or canine tooth close to the cleft. PMID:19884665

  14. Bone Grafting the Cleft Maxilla

    MedlinePlus

    ... amount of bone from one place (usually the hip, head, ribs, or leg) and placing it in ... adjacent teeth into the bone graft; 2) prosthetic replacement (dental bridge); or 3) dental metallic bone implants. ...

  15. Amalgamation of allogenic bone graft, platelet-rich fibrin gel, and PRF membrane in auto-transplantation of an impacted central incisor

    PubMed Central

    Chaudhary, Zainab; Kumar, Yuvika Raj; Mohanty, Sujata; Khetrapal, Ambica

    2015-01-01

    “Social six” teeth refers to the maxillary incisors and canines that play a vital role in the appearance of an individual and absence of any one of them has a significant psycho-social impact. Hence, early treatment and rehabilitation of the same are extremely important. A multitude of treatment options ranging from orthodontic extrusion, extraction followed by implant placement, fixed partial denture, and auto-transplantation have been advocated. This case report discusses the unique amalgamation of platelet-rich fibrin (PRF), demineralized freeze-dried bone graft with use of PRF membrane during auto-transplantation of an impacted central incisor. The authors have focused on maximum usage of autogenous materials in the most economic and least invasive manner. Furthermore, this amalgamation has been used to provide rehabilitation in the least span of time. PMID:26097366

  16. [Bone grafts in orthopedic surgery].

    PubMed

    Zárate-Kalfópulos, Barón; Reyes-Sánchez, Alejandro

    2006-01-01

    In orthopedic surgery the demand for the use of bone grafts increases daily because of the increasing quantity and complexity of surgical procedures. At present, the gold standard is the autologous bone graft but the failure rate, morbidity of the donor site and limited availability have stimulated a proliferation for finding materials that work as bone graft substitutes. In order to have good success, we must know the different properties of these choices and the environment where the graft is going to be used. As bone graft substitutes and growth factors become clinical realities, a new gold standard will be defined. Tissue engineering and gene therapy techniques have the objective to create an optimum bone graft substitute with a combination of substances with properties of osteconduction, osteogenesis and osteoinduction. PMID:16875525

  17. Secondary alveolar bone grafting: our experience with olecranon bone graft.

    PubMed

    Nadal, Emmanuela; Sabás, Mariana; Dogliotti, Pedro; Espósito, Raquel

    2010-03-01

    Management of alveolar cleft has dramatically changed during the last century: secondary alveolar bone grafting is now an integral part of cleft palate and craniofacial center's protocols. The objectives of alveolar repair and bone grafting are as follows: providing a continuous and stable maxillary dental arch, closure of oronasal fistulae, adequate bone for tooth eruption or orthodontic movement, and nasal base support, improving facial aesthetic. Although cancellous iliac bone is the donor site selected more frequently, bone grafts harvested from different sites have been advocated to decrease donor site morbidity.The aim of this study was to propose and evaluate the use of olecranon as a donor site in 24 patients with secondary alveolar cleft. The graft is taken as a single piece to fit the alveolar cleft defect, and it includes periosteum and corticocancellous bone to improve early vascularization and greater volume maintenance. PMID:20186086

  18. [Allogenic bone marrow transplantation complications. Part II].

    PubMed

    Saloua, L; Tarek, B O; Abderrahman, A; Abdeladhim, B A

    2000-03-01

    Bone marrow transplantation increase the chances of cure of many hematology and also neoplasms cancers. The procedure is however a cause of expected mortality and morbidity. The complications are represented by mucocutaneous, toxicity graft versus host disease, veno-occlusive disease and most importantly injections consequences all this complications needs to be prevented and treated considering the risk associated to the moderling immunosuppression. PMID:11026816

  19. Correction of enzyme deficiency in mice by allogeneic bone marrow transplantation with total lymphoid irradiation

    SciTech Connect

    Slavin, S.; Yatziv, S.

    1980-12-05

    Enzyme deficiency was corrected in mice after allogeneic bone marrow transplantation with occurrence of graft versus host disease. Beta-Glucuronidase-deficient C3H/HeJ mice were treated with total lymphoid irradiation. Normal bone marrow cells (30 x 10(6)) from BALB/o to C3H/HeJ chimeras (> 90 percent circulating donor-type cells) without graft versus host disease. Beta-Glucuronidase activity increases to normal levels in all chimeras as measured in the liver and in the plasma. Activity was maintained throughout an observation period of 7 months.

  20. 5-Azacytidine as Salvage Treatment in Relapsed Myeloid Tumors after Allogeneic Bone Marrow Transplantation

    PubMed Central

    Bolaños-Meade, Javier; Smith, B. Douglas; Gore, Steven D.; McDevitt, Michael A.; Luznik, Leo; Fuchs, Ephraim J.; Jones, Richard J.

    2011-01-01

    Relapse after allogeneic blood or marrow transplantation carries a very poor prognosis. Current strategies for management that include donor lymphocyte infusions (DLIs) and salvage chemotherapies are usually toxic and ineffective. Here we report the outcome of 10 patients with myeloid malignancies that received 5-azacytidine after a failed allogeneic bone marrow transplant. Of the 10 patients, 6 achieved a complete remission, 1 had stable disease, and 3 progressed after a median of 6 cycles administered. Only 1 patient has died (of disease progression), and no flares of graft-versus-host disease (GVHD) were observed with 5-azacytidine. As of latest follow-up, the median overall survival (OS) for the group was 422.5 days (127–1411). These results further suggest that 5-azacytidine is an active agent after failing an allogeneic bone marrow transplant, and prospective studies are warranted. PMID:20951817

  1. Use of lymphokine-activated killer cells to prevent bone marrow graft rejection and lethal graft-vs-host disease

    SciTech Connect

    Azuma, E.; Yamamoto, H.; Kaplan, J. )

    1989-09-01

    Prompted by our recent finding that lymphokine-activated killer (LAK) cells mediate both veto and natural suppression, we tested the ability of adoptively transferred LAK cells to block two in vivo alloreactions which complicate bone marrow transplantation: resistance to transplanted allogeneic bone marrow cells, and lethal graft-vs-host disease. Adoptive transfer of either donor type B6D2 or recipient-type B6 lymphokine-activated bone marrow cells, cells found to have strong LAK activity, abrogated or inhibited the resistance of irradiated B6 mice to both B6D2 marrow and third party-unrelated C3H marrow as measured by CFU in spleen on day 7. The ability of lymphokine-activated bone marrow cells to abrogate allogeneic resistance was eliminated by C lysis depletion of cells expressing asialo-GM1, NK1.1, and, to a variable degree, Thy-1, but not by depletion of cells expressing Lyt-2, indicating that the responsible cells had a LAK cell phenotype. Similar findings were obtained by using splenic LAK cells generated by 3 to 7 days of culture with rIL-2. Demonstration that allogeneic resistance could be blocked by a cloned LAK cell line provided direct evidence that LAK cells inhibit allogeneic resistance. In addition to inhibiting allogeneic resistance, adoptively transferred recipient-type LAK cells prevented lethal graft-vs-host disease, and permitted long term engraftment of allogeneic marrow. Irradiation prevented LAK cell inhibition of both allogeneic resistance and lethal graft-vs-host disease. These findings suggest that adoptive immunotherapy with LAK cells may prove useful in preventing graft rejection and graft-versus-host disease in human bone marrow transplant recipients.

  2. Immune transfer studies in canine allogeneic marrow graft donor-recipient pairs

    SciTech Connect

    Grosse-Wilde, H.; Krumbacher, K.; Schuening, F.D.; Doxiadis, I.; Mahmoud, H.K.; Emde, C.; Schmidt-Weinmar, A.; Schaefer, U.W.

    1986-07-01

    Transfer of immunity occurring with bone marrow grafting was studied using the dog as a preclinical model. Allogeneic bone marrow transplantation (BMT) was performed between DLA-identical beagle litter-mates. The donors were immunized with tetanus toxoid (TT) or sheep red blood cells (SRBC), and their humoral response was monitored by hemagglutination. The recipients of bone marrow from TT-immunized donors showed a marked increase of antibody titer one week posttransplantation, while in the recipients of marrow from SRBC immunized donors the antibody titers were considerably lower. Within the following 60 days the antibody titers in both groups diminished gradually to pregrafting levels. Control experiments in which cell-free plasma from donors immunized with TT and SRBC respectively was transfused indicated that the initial rise of specific antibody titers after marrow grafting is likely to be due to a passive transfer of humoral immunity. A single challenge of these marrow graft recipients with the respective antigen 15-18 weeks posttransplantation led to a secondary type of humoral immune response. It could be demonstrated that transfer of memory against TT or SRBC was independent from the actual antibody titer and the time of vaccination of the donor. One dog was immunized with TT after serving as marrow donor. When the donor had shown an antibody response, a peripheral blood leukocytes (PBL) transfusion was given to his chimera. Subsequent challenge of the latter resulted in a secondary type of specific antibody response. This indicates that specific cellular-bound immunological memory can be transferred after BMT from the donor to his allogeneic bone marrow chimera by transfusion of peripheral blood leukocytes. The data may be of importance in clinical BMT to protect patients during the phase of reduced immune reactivity by transfer of memory cells.

  3. Allogeneic versus xenogeneic immune reaction to bioengineered skin grafts.

    PubMed

    Erdag, Gulsun; Morgan, Jeffrey R

    2004-01-01

    There are conflicting reports on the survival and immune reaction to allografts and xenografts of cultured skin substitutes (CSS). In this study, we investigated the allogeneic and xenogeneic responses to CSS of human keratinocytes and genetically engineered CSS expressing keratinocyte growth factor (KGF) that forms a hyperproliferative epidermis. CSS (control and KGF modified) and neonatal human foreskins were evaluated by immunohistochemistry for the expression of MHC class I and II. To study allograft rejection, grafts were transplanted to human peripheral blood mononuclear cell (huPBMC)-reconstituted SCID mice. To study xenograft rejection, grafts were transplanted to immunocompetent mice. Graft survival and immune reaction were assessed visually and microscopically. After transplantation, control CSS formed a normal differentiated epidermis, whereas KGF CSS formed a hyperproliferative epidermis. Control and KGF CSS expressed class I similar to neonatal foreskin, but did not express class II. In the allograft model, rejection of neonatal foreskins was between 5 and 9 days. In contrast, neither control nor KGF CSS was rejected by huPBMC-SCID mice. Histology showed dense mononuclear cell infiltration in human foreskins, with few, if any, mononuclear cells in control or KGF CSS. In contrast to the allogeneic reaction, CSS (control and KGF) were rejected in the xenograft model, but rejection was delayed (9-21 days) compared with neonatal skin (5-8 days). Humanized SCID mice rejected allografts of human neonatal foreskins, but did not reject control CSS or KGF CSS, even though the KGF CSS formed a hyperproliferative epidermis. Rejection of control and KGF CSS by immunocompetent mice in a xenograft model was comparable and their survival was significantly prolonged compared with neonatal skin. These results demonstrate that control CSS and hyperproliferative KGF CSS are less immunogenic than normal human skin and that sustained hyperproliferation of the epidermis

  4. Primary Graft Failure after Myeloablative Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies

    PubMed Central

    Olsson, Richard F.; Logan, Brent R.; Chaudhury, Sonali; Zhu, Xiaochun; Akpek, Görgün; Bolwell, Brian J.; Bredeson, Christopher N.; Dvorak, Christopher C.; Gupta, Vikas; Ho, Vincent T.; Lazarus, Hillard M.; Marks, David I.; Ringdén, Olle T.H.; Pasquini, Marcelo C.; Schriber, Jeffrey R.; Cooke, Kenneth R.

    2015-01-01

    Clinical outcomes after primary graft failure (PGF) remain poor. Here we present a large retrospective analysis (n=23,272) which investigates means to prevent PGF and early detection of patients at high risk. In patients with hematologic malignancies, who underwent their first myeloablative allogeneic hematopoietic cell transplantation, PGF was reported in 1,278 (5.5%), and there was a marked difference in PGFs using peripheral blood stem cell compared to bone marrow grafts (2.5 vs. 7.3%; P<0.001). A 4-fold increase of PGF was observed in myeloproliferative disorders compared to acute leukemia (P<0.001). Other risk factors for PGF included recipient age below 30, HLA-mismatch, male recipients of female donor grafts, ABO-incompatibility, busulfan/cyclophosphamide conditioning, and cryopreservation. In bone marrow transplants, total nucleated cell doses ≤2.4 × 108/kg were associated with PGF (OR 1.39; P<0.001). The use of tacrolimus-based immunosuppression and granulocyte colony-stimulating factor were associated with decreased PGF risk. These data, allow clinicians to do more informed choices with respect to graft source, donor selection, conditioning and immunosuppressive regimens to reduce the risk of PGF. Moreover, a novel risk score determined on day 21 post-transplant may provide the rationale for an early request for additional hematopoietic stem cells. PMID:25772027

  5. The Use of Cultured Allogenic Keratinocyte Grafting in a Patient with Epidermolysis Bullosa Simplex

    PubMed Central

    Shin, Kee Cheol; Park, Bo Young; Kim, Woo Seob; Bae, Tae Hui

    2011-01-01

    Epidermolysis bullosa (EB) is a rare genetic disease that is known for continuous skin blistering caused by minor trauma. The skin blisters and bullae that develop often cause skin defects. There is no definitive treatment for EB, only symptomatic relief. We report our experience with cultured allogenic keratinocyte grafting in a newborn patient with EB simplex who had unhealed raw surfaces and was not a skin grafting candidate. The skin lesions of the patient were covered with cultured allogenic keratinocyte grafts and re-epithelialized quickly with no scarring. Allogenic keratinocyte grafting reduced pain and produced noticeable improvements in the unhealed wounds. We think that allogenic keratinocyte grafting can play an important role in the management of patients with EB simplex. PMID:22346287

  6. Reduced incidence of acute graft versus host disease (GVHD) of the gut in Chinese carriers of Helicobacter pylori during allogeneic bone marrow transplantation.

    PubMed

    Au, W Y; Wong, R W M; Wong, B C Y; Lie, A K W; Liang, R; Leung, A Y H; Kwong, Y-L

    2004-01-01

    Helicobacter pylori ( H. Pylori) infection is associated with gastritis and peptic ulcer, but its relationship with gut graft versus host disease (GVHD) is unknown. We investigated the association between H. Pylori carriage and incidence and severity of mucosal toxicity and GVHD in 128 consecutive matched sibling stem cell transplantation (SCT) recipients. Using a verified enzyme linked immunosorbant assay (ELISA), 43.5% of patients had H. Pylori exposure before SCT. There was absolute concordance between serological and breath test data in 40 prospective cases. There was no increased risk in WHO grade 3 or 4 mucositis in H. Pylori carriers. Significant (grade II or above) overall GVHD was only predicted by preceding mucositis (p<0.001), while gut GVHD was associated with increased age (p=0.001) and mucositis (p=0.022). Despite increased incidence with age, H. Pylori carriage was associated with significantly reduced risk of gut GVHD (p=0.04) but not overall GVHD. The reduced risk of immune-mediated gut inflammation in H. Pylori carriers after SCT may be related to the known reduced incidence of inflammatory bowel disease in chronic H. Pylori carriers. PMID:14551739

  7. Bone grafts, bone substitutes and orthobiologics

    PubMed Central

    Roberts, Timothy T.; Rosenbaum, Andrew J.

    2012-01-01

    The biology of fracture healing is better understood than ever before, with advancements such as the locking screw leading to more predictable and less eventful osseous healing. However, at times one’s intrinsic biological response, and even concurrent surgical stabilization, is inadequate. In hopes of facilitating osseous union, bone grafts, bone substitutes and orthobiologics are being relied on more than ever before. The osteoinductive, osteoconductive and osteogenic properties of these substrates have been elucidated in the basic science literature and validated in clinical orthopaedic practice. Furthermore, an industry built around these items is more successful and in demand than ever before. This review provides a comprehensive overview of the basic science, clinical utility and economics of bone grafts, bone substitutes and orthobiologics. PMID:23247591

  8. Allogenic versus autologous cancellous bone in lumbar segmental spondylodesis: a randomized prospective study

    PubMed Central

    Strube, Patrick; Funk, Julia F.; Gross, Christian; Mönig, Hans-Joachim; Perka, Carsten; Pruss, Axel

    2009-01-01

    The current gold standard in lumbar fusion consists of transpedicular fixation in combination with an interbody interponate of autologous bone from iliac crest. Because of the limited availability of autologous bone as well as the still relevant donor site morbidity after iliac crest grafting the need exists for alternative grafts with a comparable outcome. Forty patients with degenerative spinal disease were treated with a monosegmental spondylodesis (ventrally, 1 PEEK-cage; dorsally, a screw and rod system), and randomly placed in two groups. In group 1, autogenous iliac crest cancellous bone was used as a cage filling. In group 2 the cages were filled with an allogenic cancellous bone graft. Following 3, 6, 9 and 12 months, the clinical outcome was determined on the basis of: the Oswestry Low Back Pain Disability Questionnaire; patient satisfaction; patient willingness to undergo the operation again; and a visual analog scale for pain. The radiological outcome was based on both fusion rate (radiographs, computed tomography), and on the bone mineral density of the grafts. After 6 months, the X-rays of the patients in group 2 had a significantly lower rate of fusion. Aside from this, there were no further significant differences. After 12 months, radiological results showed a similar fusion rate in both groups. Donor site complications consisted of five patients with hematoma, and three patients with persistent pain in group 1. No implant complications were observed. If a bone bank is available for support and accepting the low risk of possible transmission of infectious diseases, freeze–dried allogenic cancellous bone can be used for monosegmental spondylodeses. The results demonstrated an equivalent clinical outcome, as well as similar fusion rates following a 12-month period. This is in despite of a delayed consolidation process. PMID:19148687

  9. Effect of Vacuum-Assisted Closure Combined with Open Bone Grafting to Promote Rabbit Bone Graft Vascularization

    PubMed Central

    Hu, Chao; Zhang, Taogen; Ren, Bin; Deng, Zhouming; Cai, Lin; Lei, Jun; Ping, Ansong

    2015-01-01

    Background Patients with composite bone non-union and soft tissue defects are difficult to treat. Vacuum-assisted closure (VAC) combined with open bone grafting is one of the most effective treatments at present. The aim of the present study was to preliminarily investigate the effect and mechanism of VAC combined with open bone grafting to promote rabbit bone graft vascularization, and to propose a theoretical basis for clinical work. Material/Methods Twenty-four New Zealand white rabbits were randomly divided into an experimental and a control group. Allogeneic bones were grafted and banded with the proximal femur with a suture. The experimental group had VAC whereas the control group had normal wound closure. The bone vascularization rate was compared based on X-ray imaging, fluorescent bone labeling (labeled tetracycline hydrochloride and calcein), calcium content in the callus, and expression of fibroblast growth factor-2 (FGF-2) in bone allografts by Western blot analysis at the 4th, 8th, and 12th week after surgery. Results At the 4th, 8th, and 12th week after surgery, the results of the tests demonstrated that the callus was larger, contained more calcium (p<0.05), and expressed FGF-2 at higher levels (p<0.05) in the experimental group than in the control group. Fluorescent bone labeling showed the distance between the two fluorescent ribbons was significantly shorter in the control group than in the experimental group at the 8th and 12th week after surgery. Conclusions VAC combined with open bone grafting promoted rabbit bone graft vascularization. PMID:25913359

  10. Allogeneic and autologous bone marrow transplantation for acute nonlymphocytic leukemia.

    PubMed

    Hurd, D D

    1987-12-01

    Current results show that 50% of young patients with ANLL who undergo allogeneic BMT experience prolonged DFS and may be cured. Encouraging results with high-dose chemo/radiotherapy and autologous BMT are likewise being reported. In addition, some studies using intensive postremission treatment without BMT have shown results comparable to many transplant series. As better ways of preventing GVHD are found, the morbidity and mortality of allogeneic BMT should be reduced and the benefits of transplantation for curing patients with ANLL should be increased. However, the applicability of allogeneic BMT will remain limited due to the availability of compatible donors whether related or unrelated. Further studies are needed in the use of postremission intensive therapy with and without autologous bone marrow support. However, results to date should engender the same degree of enthusiastic optimism that followed the early reports of improved outcome with allogeneic BMT when applied to first remission patients. PMID:3321445

  11. Chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor promotes sciatic nerve repair

    PubMed Central

    Zhang, Yanru; Zhang, Hui; Katiella, Kaka; Huang, Wenhua

    2014-01-01

    A chemically extracted acellular allogeneic nerve graft can reduce postoperative immune rejection, similar to an autologous nerve graft, and can guide neural regeneration. However, it remains poorly understood whether a chemically extracted acellular allogeneic nerve graft combined with neurotrophic factors provides a good local environment for neural regeneration. This study investigated the repair of injured rat sciatic nerve using a chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor. An autologous nerve anastomosis group and a chemical acellular allogeneic nerve bridging group were prepared as controls. At 8 weeks after repair, sciatic functional index, evoked potential amplitude of the soleus muscle, triceps wet weight recovery rate, total number of myelinated nerve fibers and myelin sheath thickness were measured. For these indices, values in the three groups showed the autologous nerve anastomosis group > chemically extracted acellular nerve graft + ciliary neurotrophic factor group > chemical acellular allogeneic nerve bridging group. These results suggest that chemically extracted acellular nerve grafts combined with ciliary neurotrophic factor can repair sciatic nerve defects, and that this repair is inferior to autologous nerve anastomosis, but superior to chemically extracted acellular allogeneic nerve bridging alone. PMID:25221592

  12. Chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor promotes sciatic nerve repair.

    PubMed

    Zhang, Yanru; Zhang, Hui; Katiella, Kaka; Huang, Wenhua

    2014-07-15

    A chemically extracted acellular allogeneic nerve graft can reduce postoperative immune rejection, similar to an autologous nerve graft, and can guide neural regeneration. However, it remains poorly understood whether a chemically extracted acellular allogeneic nerve graft combined with neurotrophic factors provides a good local environment for neural regeneration. This study investigated the repair of injured rat sciatic nerve using a chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor. An autologous nerve anastomosis group and a chemical acellular allogeneic nerve bridging group were prepared as controls. At 8 weeks after repair, sciatic functional index, evoked potential amplitude of the soleus muscle, triceps wet weight recovery rate, total number of myelinated nerve fibers and myelin sheath thickness were measured. For these indices, values in the three groups showed the autologous nerve anastomosis group > chemically extracted acellular nerve graft + ciliary neurotrophic factor group > chemical acellular allogeneic nerve bridging group. These results suggest that chemically extracted acellular nerve grafts combined with ciliary neurotrophic factor can repair sciatic nerve defects, and that this repair is inferior to autologous nerve anastomosis, but superior to chemically extracted acellular allogeneic nerve bridging alone. PMID:25221592

  13. Is Bone Grafting Necessary in Opening Wedge High Tibial Osteotomy? A Meta-Analysis of Radiological Outcomes

    PubMed Central

    Han, Jae Hwi; Kim, Hyun Jung; Song, Jae Gwang; Yang, Jae Hyuk; Bhandare, Nikhl N; Fernandez, Aldrich Raymund; Park, Hyung Jun

    2015-01-01

    Purpose Bone grafting in opening wedge high tibial osteotomy (OWHTO) is still controversial. The purpose of this study is to compare the radiological outcomes of OWHTO with bone graft (autogenous, allogenous, and synthetic bone graft) and those without bone graft. Materials and Methods PubMed, MEDLINE, EMBASE and Cochrane Register of Studies databases were searched using specific inclusion and exclusion criteria for radiological studies involving OWHTO with bone graft and without bone graft groups. All reported delayed union, nonunion and correction loss were analyzed. Data were searched from the time period of January 2000 through July 2014. In addition, a modified Coleman methodology score (CMS) system was used to assess the methodological quality of the included studies. Results Twenty-five studies with a mean CMS value of 77 (range, 61 to 85 score) were included. In total, 1,841 patients underwent OWHTO using 4 different procedures for bone graft: autobone graft (n=352), allobone graft (n=547), synthetic bone graft (n=541) and no bone graft (n=401). There was a similar tendency for delayed union, nonunion and correction loss rate among the osteotomy space filling methods. Conclusions The meta-analysis showed there was a similar tendency for radiological union and correction maintenance among patients undergoing OWHTO regardless of the type of bone in all of the studies. However, the currently available evidence is not sufficient to strongly support the superiority of OWHTO with bone graft to OWHTO without bone graft. PMID:26675553

  14. Bone Marrow GvHD after Allogeneic Hematopoietic Stem Cell Transplantation

    PubMed Central

    Szyska, Martin; Na, Il-Kang

    2016-01-01

    The bone marrow is the origin of all hematopoietic lineages and an important homing site for memory cells of the adaptive immune system. It has recently emerged as a graft-versus-host disease (GvHD) target organ after allogeneic stem cell transplantation (alloHSCT), marked by depletion of both hematopoietic progenitors and niche-forming cells. Serious effects on the restoration of hematopoietic function and immunological memory are common, especially in patients after myeloablative conditioning therapy. Cytopenia and durable immunodeficiency caused by the depletion of hematopoietic progenitors and destruction of bone marrow niches negatively influence the outcome of alloHSCT. The complex balance between immunosuppressive and cell-depleting treatments, GvHD and immune reconstitution, as well as the desirable graft-versus-tumor (GvT) effect remains a great challenge for clinicians. PMID:27066008

  15. Bone Marrow GvHD after Allogeneic Hematopoietic Stem Cell Transplantation.

    PubMed

    Szyska, Martin; Na, Il-Kang

    2016-01-01

    The bone marrow is the origin of all hematopoietic lineages and an important homing site for memory cells of the adaptive immune system. It has recently emerged as a graft-versus-host disease (GvHD) target organ after allogeneic stem cell transplantation (alloHSCT), marked by depletion of both hematopoietic progenitors and niche-forming cells. Serious effects on the restoration of hematopoietic function and immunological memory are common, especially in patients after myeloablative conditioning therapy. Cytopenia and durable immunodeficiency caused by the depletion of hematopoietic progenitors and destruction of bone marrow niches negatively influence the outcome of alloHSCT. The complex balance between immunosuppressive and cell-depleting treatments, GvHD and immune reconstitution, as well as the desirable graft-versus-tumor (GvT) effect remains a great challenge for clinicians. PMID:27066008

  16. Allogeneic adipose-derived stem cells promote survival of fat grafts in immunocompetent diabetic rats.

    PubMed

    Zhang, Jun; Bai, Xiaozhi; Zhao, Bin; Wang, Yunchuan; Su, Linlin; Chang, Peng; Wang, Xujie; Han, Shichao; Gao, Jianxin; Hu, Xiaolong; Hu, Dahai; Liu, Xiaoyan

    2016-05-01

    Autologous adipose-derived stem cells (ADSCs) can protect fat grafts in cell-assisted lipotransfer (CAL). However, diabetes alters the intrinsic properties of ADSCs and impairs their function so that they lack these protective effects. We investigate whether allogeneic ADSCs from healthy donors could protect fat grafts in immunocompetent diabetic rats. Syngeniec adipose tissues and ADSCs were derived from diabetic Lewis (LEW) rats, whereas allogeneic ADSCs were from healthy brown-Norway rats. A grafted mixture containing 0.7 ml granule fat and 0.3 ml 6 × 10(6) allogeneic/syngeneic ADSCs was injected subcutaneously on the skulls of diabetic LEW rats. Fat samples were harvested to evaluate the levels of injury and vascularization as shown by perilipin A, CD34 and VEGF at 14 days. The immune response was evaluated with a lymphocytotoxicity test and the CD4/CD8 ratio in peripheral blood at 14 days. The volume retention of fat grafts was measured at 3 months. Healthy allogeneic ADSCs increased the expression levels of perilipin A, CD34 and VEGF at 14 days. The volume retention of fat grafts was improved by allogeneic ADSCs at 3 months. ADSCs were demonstrated to have low immunogenicity by the lymphocyte proliferation test and immunophenotype including MHC and co-stimulatory markers. The lymphocytotoxicity test and CD4/CD8 ratio indicated no obvious immune response elicited by allogeneic ADSCs. Thus, healthy allogeneic ADSCs can promote the survival of fat grafts in this immunocompetent diabetic rat model, with little or no obvious immune rejection. PMID:26662284

  17. Facilitation of allogeneic bone marrow transplantation by a T cell-specific immunotoxin containing daunomycin

    SciTech Connect

    Xie, S.S.; Inazawa, M.; Sinha, N.; Sawada, S.; Vergidis, R.; Diener, E.

    1987-12-01

    Daunomycin coupled via an acid-sensitive spacer to monoclonal Thy-1.2-specific antibody was used to purge T lymphocytes from a 1:1 mixture of murine C57BL/6J bone marrow and spleen cells prior to engraftment in fully allogeneic, irradiated BALB/c recipients. Treatment of bone marrow with the immunotoxin at a concentration used for purging had no effect on the viability of committed hematopoietic progenitor or multipotent stem cells. All of the recipients of purged bone marrow were at least 80% chimeric for donor peripheral blood cells and none developed graft-versus-host disease. Out of 50 chimeras, 49 were still alive more than 200 days posttransplantation. The chimeras were shown to be tolerant to donor tissue as tested by mixed lymphocyte reactivity, cell-mediated cytotoxicity, and skin grafting. The same tests revealed full immunocompetence of chimeras to third-party alloantigens. In vivo IgM and IgG antibody responses to sheep red blood cells were similar in magnitude in allogeneically and syngeneically reconstituted mice.

  18. Strontium doping of bone graft extender

    PubMed Central

    2011-01-01

    Background and purpose Allografts are often used during revision hip replacement surgery for stabilization of the implant. Resorption of the allograft may exceed new bone formation, and instability of the prosthesis can develop. We investigated whether strontium could regulate the imbalance of fast resorption of allograft and slower formation of new bone, because it is both an anabolic and an anticatabolic agent. Method Strontium was added to the implant interface environment by doping a hydroxyapatite bone graft extender. 10 dogs each received 2 experimental titanium implants. The implants were inserted within a 2.7-mm concentric gap in cancellous bone. The gap was filled with 50% (v/v) allograft mixed with 50% bone graft extender. The extender either had 5% strontium doping (SrHA) or was undoped (HA). After 4 weeks, osseointegration and mechanical fixation were evaluated by histomorphometry and by push-out test. Results SrHA bone graft extender induced a 1.2-fold increase in volume of new bone, a 1.2-fold increase in allograft remaining in the gap, and a 1.4-fold increase in surface area of the bone graft extender material in contact with new bone compared to HA bone graft extender. All these increases were statistically significant. SrHA bone graft extender did not significantly improve ongrowth of bone onto the implants or improve any of the mechanical push-out parameters compared to HA bone graft extender. Interpretation Doping of the HA bone graft extender with 5% strontium increased gap healing, preserved more of the allograft in the gap, and increased the ongrowth of bone onto the bone graft extender material, but did not improve mechanical fixation. PMID:21895497

  19. Vascularized bone graft for scaphoid nonunions.

    PubMed

    Mih, Alexander D

    2004-09-01

    Scaphoid fracture nonunion remains a challenging problem that may persist despite traditional methods of bone grafting and internal fixation. The alteration of wrist mechanics created by nonunion as well as the development of avascular necrosis leads to degenerative change of the radiocarpal joint accompanied by loss of motion and pain. The use of a vascularized bone graft has the theoretical benefit of increased blood flow that exceeds that of nonvascularized grafts. Numerous sources of vascularized bone graft have been described, including those from remote sites as well as from the carpus and distal radius. Knowledge of the blood supply to the distal radius has allowed for development of several vascularized bone graft harvest sites. The results of vascularized bone grafting from the distal radius have been encouraging, with numerous authors reporting the successful treatment of scaphoid nonunions. PMID:16518108

  20. Pancytopenia after allogeneic bone marrow transplant due to copper deficiency.

    PubMed

    Hudspeth, Michelle; Turner, Amy; Miller, Nicole; Lazarchick, John

    2014-05-01

    Pancytopenia occurring 1 year or later after allogeneic bone marrow transplantation typically prompts a primary consideration for relapse. We present the case of a 15-year old-girl who underwent transplantation for therapy-related myelodysplasia secondary to Ewing sarcoma treatment who developed pancytopenia with myelodysplasia 1 year after transplant due to copper deficiency. Copper deficiency is an important consideration in the evaluation of pancytopenia and myelodysplasia in pediatric patients. PMID:23652881

  1. Long-term survival of murine allogeneic bone marrow chimeras: effect of anti-lymphocyte serum and bone marrow dose

    SciTech Connect

    Norin, A.J.; Emeson, E.E.; Veith, F.J.

    1981-02-01

    Graft-vs-host disease (GVHD) and failure of donor stem cells to engraft permanently are two major obstacles to successful bone marrow transplantation. The effect of a single large dose of anti-lymphocyte serum (ALS) on mice receiving various numbers of H-2 incompatible bone marrow cells was evaluated. Most animals receiving lethal total body irradiation (TBI) and allogeneic marrow died within 45 days due to GVHD. Mice that were given ALS 6 to 24 h before TBI and bone marrow 24 h after irradiation survived in good health for more than 200 days. These cell preparations caused lethal GVHD in third party mice indicating that the lack of alloreactivity was specific to the strain in which the unresponsiveness was originally induced.

  2. Secondary neuroendocrine tumor after allogeneic bone marrow transplantation.

    PubMed

    Tamura, Shinichi; Ishida, Hiroyuki; Naito, Takeshi; Kondo, Osamu; Inoue, Masami; Kawa, Keisei; Kawabata, Kenji; Hojo, Hiroshi; Ouchi, Kazutaka; Imamura, Toshihiko

    2015-12-01

    Here we report a case of aggressive neuroendocrine tumor (NET), which is an extremely rare secondary solid tumor that occurs after allogeneic hematopoietic cell transplantation (allo-HSCT). A patient with chronic active Epstein-Barr virus infection received allo-HSCT from an HLA-DR two allele-mismatched unrelated donor. Four years later, he developed NET with multiple metastases. He received thoraco-abdominal irradiation as a conditioning regimen, and developed repeated episodes of intestinal graft-versus-host disease, for which he received long-term immunosuppressive therapy. Although these factors may be potential contributing factors to the development of secondary NET, the exact pathogenesis remains unclear. PMID:26711919

  3. Storage of Allogeneic Vascular Grafts: Experience From a High-Volume Liver Transplant Institute

    PubMed Central

    Aydin, Cemalettin; Ince, Volkan; Otan, Emrah; Akbulut, Sami; Koc, Cemalettin; Kayaalp, Cuneyt; Yilmaz, Sezai

    2013-01-01

    Allogeneic vascular grafts are often required for vascular reconstruction during living donor liver transplantation. Such grafts are obtained prior to use, making storage conditions a critical issue for maintaining the integrity of the tissue to ensure a successful transplantation. This study describes an optimized storage protocol currently in use at a high-volume liver transplant center. Twenty-nine allogeneic vascular graft tissues obtained during cardiovascular surgery or from cadaveric donors were stored respectively in sterile 50 mL of Ringer lactate solution, without any preservation solutions or antimicrobials, at −22°C for a maximum of 3 months. Prior to use in vascular reconstruction, grafts were thawed in 0.9% NaCl solution at 37°C, and 1 × 0.5-cm2 tissue samples were collected for microbial culturing and viral serology. ABO compatibility was not performed for any patients receiving vascular grafts. During this prospective study, all 29 allogeneic vascular grafts were used for back-table vascular reconstruction in living donor liver transplantation procedures. A total of 16 grafts were from the saphenous vein, 10 were from the iliac vein, and 3 were from the iliac artery. Bacterial growth was not detected in any tissue samples taken from the stored grafts. No vascular graft-related complications occurred during the 5 months of follow-up. The successful vascular reconstructions achieved with all 29 study grafts demonstrate that the simple, inexpensive storage method described herein is feasible and safe. Randomized, controlled studies should be carried out to further optimize and standardize the technique. PMID:23701155

  4. Storage of allogeneic vascular grafts: experience from a high-volume liver transplant institute.

    PubMed

    Aydin, Cemalettin; Ince, Volkan; Otan, Emrah; Akbulut, Sami; Koc, Cemalettin; Kayaalp, Cuneyt; Yilmaz, Sezai

    2013-01-01

    Allogeneic vascular grafts are often required for vascular reconstruction during living donor liver transplantation. Such grafts are obtained prior to use, making storage conditions a critical issue for maintaining the integrity of the tissue to ensure a successful transplantation. This study describes an optimized storage protocol currently in use at a high-volume liver transplant center. Twenty-nine allogeneic vascular graft tissues obtained during cardiovascular surgery or from cadaveric donors were stored respectively in sterile 50 mL of Ringer lactate solution, without any preservation solutions or antimicrobials, at -22°C for a maximum of 3 months. Prior to use in vascular reconstruction, grafts were thawed in 0.9% NaCl solution at 37°C, and 1 × 0.5-cm(2) tissue samples were collected for microbial culturing and viral serology. ABO compatibility was not performed for any patients receiving vascular grafts. During this prospective study, all 29 allogeneic vascular grafts were used for back-table vascular reconstruction in living donor liver transplantation procedures. A total of 16 grafts were from the saphenous vein, 10 were from the iliac vein, and 3 were from the iliac artery. Bacterial growth was not detected in any tissue samples taken from the stored grafts. No vascular graft-related complications occurred during the 5 months of follow-up. The successful vascular reconstructions achieved with all 29 study grafts demonstrate that the simple, inexpensive storage method described herein is feasible and safe. Randomized, controlled studies should be carried out to further optimize and standardize the technique. PMID:23701155

  5. Response of canine bone to a synthetic bone graft material.

    PubMed

    St John, K R; Zardiackas, L D; Black, R J; Armstrong, R

    1993-01-01

    A model simulating a spiral diaphyseal fracture with butterfly fragments and bone loss was utilized to evaluate an hydroxyapatite/tricalcium phosphate, and collagen composite bone graft substitute in twelve dogs. The resultant grafted and contralateral control femora were tested in torsion at one year. This study examines the histological response to the graft material as well as crack propagation and fracture surface morphology using light microscopy and SEM. SEM and gross evaluation of the grafted bones revealed that 8/12 had fractured through bone outside the osteotomy site and all fractures included bone outside the graft site. No graft material was demonstrated at the points of initiation or termination of fracture for any of the bones. It was apparent that recorticalization had begun to occur at the graft site but the canal had not yet fully formed. The HA/TCP was seen to be tightly bound in tissue which had the appearance of new bone. Bone was found to be in direct apposition to the surface of the ceramic and within pores with no intervening soft tissue. Much of the new bone had remodeled into well organized Haversian systems with some patchy areas of woven bone and osteoid seen with polarized light illumination. PMID:10148784

  6. Bone Marrow Graft in Man after Conditioning by Antilymphocytic Serum*

    PubMed Central

    Mathé, G.; Amiel, J. L.; Schwarzenberg, L.; Choay, J.; Trolard, P.; Schneider, M.; Hayat, M.; Schlumberger, J. R.; Jasmin, Cl.

    1970-01-01

    Allogeneic bone marrow grafts carried out after previous administration of antilymphocytic serum alone were attempted in 16 patients. Of these, six had acute myeloblastic leukaemia, four acute lymphoblastic leukaemia, and one a blast cell crisis in polycythaemia vera. Ten of these patients were in an overt phase of the disease and resistant to chemotherapy, while nine had complete agranulocytosis. In five of these patients erythrocyte and leucocyte antigenic markers demonstrated the establishment of the graft. One patient had thalassaemia major, and four others had aplasia of the bone marrow, in one case due to chloramphenicol poisoning and in another to virus hepatitis. The grafts were successful in the last two patients and transformed their clinical condition. No signs of early acute secondary disease were noted in any of the patients, either when the donor had been given antilymphocytic serum or when he was untreated. The grafts had no adoptive immunotherapeutic effect on the acute leukaemia. These observations have clearly shown that antilymphocytic serum has an immunosuppressive effect in man when it is used alone. PMID:4909449

  7. Engineering anatomically shaped human bone grafts

    PubMed Central

    Grayson, Warren L.; Fröhlich, Mirjam; Yeager, Keith; Bhumiratana, Sarindr; Chan, M. Ete; Cannizzaro, Christopher; Wan, Leo Q.; Liu, X. Sherry; Guo, X. Edward; Vunjak-Novakovic, Gordana

    2009-01-01

    The ability to engineer anatomically correct pieces of viable and functional human bone would have tremendous potential for bone reconstructions after congenital defects, cancer resections, and trauma. We report that clinically sized, anatomically shaped, viable human bone grafts can be engineered by using human mesenchymal stem cells (hMSCs) and a “biomimetic” scaffold-bioreactor system. We selected the temporomandibular joint (TMJ) condylar bone as our tissue model, because of its clinical importance and the challenges associated with its complex shape. Anatomically shaped scaffolds were generated from fully decellularized trabecular bone by using digitized clinical images, seeded with hMSCs, and cultured with interstitial flow of culture medium. A bioreactor with a chamber in the exact shape of a human TMJ was designed for controllable perfusion throughout the engineered construct. By 5 weeks of cultivation, tissue growth was evidenced by the formation of confluent layers of lamellar bone (by scanning electron microscopy), markedly increased volume of mineralized matrix (by quantitative microcomputer tomography), and the formation of osteoids (histologically). Within bone grafts of this size and complexity cells were fully viable at a physiologic density, likely an important factor of graft function. Moreover, the density and architecture of bone matrix correlated with the intensity and pattern of the interstitial flow, as determined in experimental and modeling studies. This approach has potential to overcome a critical hurdle—in vitro cultivation of viable bone grafts of complex geometries—to provide patient-specific bone grafts for craniofacial and orthopedic reconstructions. PMID:19820164

  8. Onlay Bone Grafts in Head and Neck Reconstruction

    PubMed Central

    Yazar, Sukru

    2010-01-01

    Bone grafts are used in a variety of clinical situations and can be divided into two categories: treatment of bone gaps (inlay bone grafting) and bone projection (onlay bone grafting). Cortical grafts are useful in situations requiring immediate mechanical strength. These grafts can survive with or without complete revascularization or resorption and are primarily used by plastic surgeons in the treatment of bone volume deficiency. Cancellous grafts, in contrast, have no mechanical strength and therefore require additional support to bridge bone defects. Thus, they are used primarily for the treatment of bone gaps and in general revascularize quickly, resorb completely, and stimulate significant new bone formation. PMID:22550447

  9. Isolation, cultivation and characterisation of pigeon osteoblasts seeded on xenogeneic demineralised cancellous bone scaffold for bone grafting.

    PubMed

    Harvanová, Denisa; Hornák, Slavomír; Amrichová, Judita; Spaková, Tímea; Mikes, Jaromír; Plsíková, Jana; Ledecký, Valent; Rosocha, Ján

    2014-09-01

    Avian osteoblasts have been isolated particularly from chicken embryo, but data about other functional tissue sources of adult avian osteoblast precursors are missing. The method of preparation of pigeon osteoblasts is described in this study. We demonstrate that pigeon cancellous bone derived osteoblasts have particular proliferative capacity in vitro in comparison to mammalian species and developed endogenous ALP. Calcium deposits formation in vitro was confirmed by alizarin red staining. Only a few studies have attempted to investigate bone grafting and treatment of bone loss in birds. Lack of autologous bone grafts in birds has prompted investigation into the use of avian xenografts for bone augmentation. Here we present a method of xenografting of ostrich demineralised cancellous bone scaffold seeded with allogeneic adult pigeon osteoblasts. Ostrich demineralised cancellous bone scaffold supported proliferation of pigeon osteoblasts during two weeks of co - cultivation in vitro. Scanning electron microscopy demonstrated homogeneous adult pigeon osteoblasts attachment and distribution on the surface of xenogeneic ostrich demineralised cancellous bone. Our preliminary in vitro results indicate that demineralised cancellous bone from ostrich tibia could provide an effective biological support for growth and proliferation of allogeneic osteoblasts derived from cancellous bone of pigeons. PMID:24915787

  10. Avascular necrosis of bone after allogeneic hematopoietic cell transplantation in children and adolescents.

    PubMed

    Li, Xiaxin; Brazauskas, Ruta; Wang, Zhiwei; Al-Seraihy, Amal; Baker, K Scott; Cahn, Jean-Yves; Frangoul, Haydar A; Gajewski, James L; Hale, Gregory A; Hsu, Jack W; Kamble, Rammurti T; Lazarus, Hillard M; Marks, David I; Maziarz, Richard T; Savani, Bipin N; Shah, Ami J; Shah, Nirali; Sorror, Mohamed L; Wood, William A; Majhail, Navneet S

    2014-04-01

    We conducted a nested case-control study within a cohort of 6244 patients to assess risk factors for avascular necrosis (AVN) of bone in children and adolescents after allogeneic transplantation. Eligible patients were ≤21 years of age, received their first allogeneic transplant between 1990 and 2008 in the United States, and had survived ≥ 6 months from transplantation. Overall, 160 patients with AVN and 478 control subjects matched by year of transplant, length of follow-up and transplant center were identified. Patients and control subjects were confirmed via central review of radiology, pathology, and/or surgical procedure reports. Median time from transplant to diagnosis of AVN was 14 months. On conditional logistic regression, increasing age at transplant (≥5 years), female gender, and chronic graft-versus-host disease (GVHD) were significantly associated with increased risks of AVN. Compared with patients receiving myeloablative regimens for malignant diseases, lower risks of AVN were seen in patients with nonmalignant diseases and those who had received reduced-intensity conditioning regimens for malignant diseases. Children at high risk for AVN include those within the age group where rapid bone growth occurs as well as those who experience exposure to myeloablative conditioning regimens and immunosuppression after hematopoietic cell transplantation for the treatment of GVHD. More research is needed to determine whether screening strategies specifically for patients at high risk for developing AVN with early interventions may mitigate the morbidity associated with this complication. PMID:24388803

  11. Controlling Bone Graft Substitute Microstructure to Improve Bone Augmentation.

    PubMed

    Sheikh, Zeeshan; Drager, Justin; Zhang, Yu Ling; Abdallah, Mohamed-Nur; Tamimi, Faleh; Barralet, Jake

    2016-07-01

    Vertical bone augmentation procedures are frequently carried out to allow successful placement of dental implants in otherwise atrophic ridges and represent one of the most common bone grafting procedures currently performed. Onlay autografting is one of the most prevalent and predictable techniques to achieve this; however, there are several well documented complications and drawbacks associated with it and synthetic alternatives are being sought. Monetite is a bioresorbable dicalcium phosphate with osteoconductive and osteoinductive potential that has been previously investigated for onlay bone grafting and it is routinely made by autoclaving brushite to simultaneously sterilize and phase convert. In this study, monetite disc-shaped grafts are produced by both wet and dry heating methods which alter their physical properties such as porosity, surface area, and mechanical strength. Histological observations after 12 weeks of onlay grafting on rabbit calvaria reveal higher bone volume (38%) in autoclaved monetite grafts in comparison with the dry heated monetite grafts (26%). The vertical bone height gained is similar for both the types of monetite grafts (up to 3.2 mm). However, it is observed that the augmented bone height is greater in the lateral than the medial areas of both types of monetite grafts. It is also noted that the higher porosity of autoclaved monetite grafts increases the bioresorbability, whereas the dry heated monetite grafts having lower porosity but higher surface area resorb to a significantly lesser extent. This study provides information regarding two types of monetite onlay grafts prepared with different physical properties that can be further investigated for clinical vertical bone augmentation applications. PMID:27214877

  12. High proportions of regulatory T cells in PBSC grafts predict improved survival after allogeneic haematopoietic SCT

    PubMed Central

    Danby, R D; Zhang, W; Medd, P; Littlewood, T J; Peniket, A; Rocha, V; Roberts, D J

    2016-01-01

    Regulatory T cells (Tregs) modulate immune responses and improve survival in murine transplant models. However, whether the Treg content of allogeneic cell grafts influences the outcome in human haematopoietic stem cell (HSC) transplantation is not well established. In a prospective study of 94 adult allogeneic PBSC transplants (60% unrelated; 85% reduced intensity conditioning), the median Treg (CD3+CD4+CD25+FOXP3+CD127dim/−) dose transplanted was 4.7 × 106/kg, with Tregs accounting for a median of 2.96% of CD4+ T cells. Patients transplanted with grafts containing a Treg/CD4+ T-cell ratio above the median had a 3-year overall survival of 75%, compared with 49% in those receiving grafts with a Treg/CD4+ T-cell ratio below the median (P=0.02), with a 3-year non-relapse mortality of 13% and 35%, respectively (P=0.02). In multivariate analysis, a high graft Treg/CD4+ T-cell ratio was an independent predictor of lower non-relapse mortality (hazard ratio (HR), 0.30; P=0.02), improved overall survival (HR, 0.45; P=0.03) and improved sustained neutrophil (HR, 0.52; P=0.002), platelet (HR, 0.51; P<0.001) and lymphocyte (HR, 0.54; P=0.009) recovery. These data support the hypothesis that the proportion of Tregs in allogeneic HSC grafts influences clinical outcome and suggest that Treg therapies could improve allogeneic HSC transplantation. PMID:26389831

  13. Delayed Minimally Invasive Injection of Allogenic Bone Marrow Stromal Cell Sheets Regenerates Large Bone Defects in an Ovine Preclinical Animal Model

    PubMed Central

    Berner, Arne; Henkel, Jan; Woodruff, Maria A.; Steck, Roland; Nerlich, Michael; Schuetz, Michael A.

    2015-01-01

    Cell-based tissue engineering approaches are promising strategies in the field of regenerative medicine. However, the mode of cell delivery is still a concern and needs to be significantly improved. Scaffolds and/or matrices loaded with cells are often transplanted into a bone defect immediately after the defect has been created. At this point, the nutrient and oxygen supply is low and the inflammatory cascade is incited, thus creating a highly unfavorable microenvironment for transplanted cells to survive and participate in the regeneration process. We therefore developed a unique treatment concept using the delayed injection of allogenic bone marrow stromal cell (BMSC) sheets to regenerate a critical-sized tibial defect in sheep to study the effect of the cells’ regeneration potential when introduced at a postinflammatory stage. Minimally invasive percutaneous injection of allogenic BMSCs into biodegradable composite scaffolds 4 weeks after the defect surgery led to significantly improved bone regeneration compared with preseeded scaffold/cell constructs and scaffold-only groups. Biomechanical testing and microcomputed tomography showed comparable results to the clinical reference standard (i.e., an autologous bone graft). To our knowledge, we are the first to show in a validated preclinical large animal model that delayed allogenic cell transplantation can provide applicable clinical treatment alternatives for challenging bone defects in the future. PMID:25834121

  14. A composite graft material containing bone particles and collagen in osteoinduction in mouse.

    PubMed

    Tsai, Chung-Hung; Chou, Ming-Yung; Jonas, Mecrehild; Tien, Yung-Tico; Chi, Emily Y

    2002-01-01

    Demineralized allogenic bone matrices (DABM) and demineralized freeze-dried bone allograft (DFDBA) have been successfully used as bone-graft materials in the treatment of acquired and congenital cranio-maxillofacial defects and in some orthopedic surgery. However, these bone-graft "powders" have many shortcomings. For example, placement of particulate graft material in a hemorrhaging site can result in inadequacies or inaccurate attachment as well as loss of the graft materials. To minimize the inadequacies of powderlike graft materials, xenogenic collagen isolated from human tendon, skin, or bone was added to the bone-graft particles to form a composite spongelike implant. This material is commercially available and consists of 60% collagen and 40% DFDBA (DynaGraft, GenSci Co., Irvine, CA). The goal of this study was to evaluate the characteristics of composite graft implants in the mineralization process in an animal model in comparison with DFDBA powder and pure collagen. Seventy-two Swiss Webster mice were divided into three groups: an experimental group implanted with DynaGraft, two comparison groups implanted with either DFDBA or collagen only. All the graft materials were surgically implanted and inserted into the left thigh muscle. Mice were humanely killed at 1, 2, 3, 4, 6, 8, and 12 weeks. Then the muscle tissues in the vicinity of the implants were excised and processed for histology. Paraffin sections were stained with hematoxylin and eosin (H&E), the Von Kossa method, and Masson's trichrome. Some selected specimens were processed for transmission electron microscopic observation. After 1 week of implantation, the DynaGraft group showed calcium deposition on the collagen material and on the periphery of the DFDBA particles. Increased calcification and bone-forming cells were observed at 4-6 weeks. After 8 weeks, the implant formed a calcified nodule and only heavily mineralized connective tissue was observed at the implanted site. The group implanted

  15. Voriconazole-Induced Periostitis Mimicking Chronic Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation

    PubMed Central

    Oh, Annie; Rondelli, Damiano; Patel, Pritesh

    2016-01-01

    Voriconazole is an established first-line agent for treatment of invasive fungal infections in patients undergoing allogeneic stem cell transplantation (ASCT). It is associated with the uncommon complication of periostitis. We report this complication in a 58-year-old female undergoing HSCT. She was treated with corticosteroids with minimal improvement. The symptoms related to periostitis can mimic chronic graft-versus-host disease in patients undergoing HSCT and clinicians should differentiate this from other diagnoses and promptly discontinue therapy. PMID:27403356

  16. Antitumor immunomodulatory activity of allogenic bone marrow cells on TiNi scaffold

    NASA Astrophysics Data System (ADS)

    Kokorev, O. V.; Hodorenko, V. N.; Cherdyntseva, N. V.; Gunther, V. E.

    2016-08-01

    The present study was undertaken to evaluate the feasibility of modulation of anti-tumor response by allogenic bone marrow cell transplantation into porous TiNi-based scaffold. Transplantation of bone marrow cells into porous TiNi-based scaffold leads to antitumor (35%) and antimetastatic (55%) effects. The lifetime of tumor-bearing animals and implanted allogenic bone marrow cells in incubator of TiNi increases up to 60%. The possible mechanisms of the effect of allogenic cells on tumor process are the stimulation of endogenous effectors of antitumor immunity.

  17. Strength comparison of allogenic bone screws, bioabsorbable screws, and stainless steel screw fixation.

    PubMed

    Rano, James A; Savoy-Moore, Ruth T; Fallat, Lawrence M

    2002-01-01

    Allogenic bone screws are new to the fixation market and have yet to be tested against current fixation materials. An in vitro comparison of the same sizes of stainless steel, bioabsorbable, and allogenic bone screws was undertaken to assess screw resistance to the forces of bending, pullout, and shear. Using aluminum plates to support the screws, forces up to 1000 Newtons were applied to six to eight samples of each type of screw. During each test, stainless steel screws withstood the maximum force that could be exerted by the testing apparatus without failing (bending, 113.9 +/- 11.8 N mean +/- SE; pullout 999.1 +/- 33.7 N; and shear, 997.5 +/- 108.8 N). In each test, compared to bioabsorbable screws, allogenic bone screws failed faster (pullout, allogenic: 12.4 +/- 1.1 seconds vs. bioabsorbable, 120.6 +/- 13.8 seconds; p = .001; bending, allogenic: 53.4 +/- 4.8 seconds vs. bioabsorbable, 201.9 +/- 11.1 seconds; p = .001; shear, allogenic 13.5 +/- 1.4 seconds vs. bioabsorbable, 43.8 +/- 0.9 seconds; p = .001) under equivalent (pullout: bioabsorbable, 385.0 +/- 18.4 N vs. allogenic, 401.0 +/- 35.9 N; p = .001) or lower (bending, allogenic: 4.7 +/- 0.2 N vs. bioabsorbable, 11.0 +/- 0.9 N; p = .675; shear, allogenic: 312.1 +/- 15.5 N vs. bioabsorbable 680.9 +/- 8.5 N; p = .001) loads, and in a highly variable fashion. Overall, the bioabsorbable screws withstood the forces of bending, pullout, and shear better than the allogenic screws, and stainless steel screws outperformed both bioabsorbable and allogenic screws. Despite these results, allogenic screws could still be useful in compliant patients who would benefit from their osteoconductive properties. PMID:11858609

  18. Allogeneic clonal mesenchymal stem cell therapy for refractory graft-versus-host disease to standard treatment: a phase I study.

    PubMed

    Yi, Hyeon Gyu; Yahng, Seung-Ah; Kim, Inho; Lee, Je-Hwan; Min, Chang-Ki; Kim, Jun Hyung; Kim, Chul Soo; Song, Sun U

    2016-01-01

    Severe graft-versus-host disease (GVHD) is an often lethal complication of allogeneic hematopoietic stem cell transplantation (HSCT). The safety of clinical-grade mesenchymal stem cells (MSCs) has been validated, but mixed results have been obtained due to heterogeneity of the MSCs. In this phase I study, the safety of bone marrow-derived homogeneous clonal MSCs (cMSCs) isolated by a new subfractionation culturing method was evaluated. cMSCs were produced in a GMP facility and intravenously administered to patients who had refractory GVHD to standard treatment resulting after allogeneic HSCT for hematologic malignancies. After administration of a single dose (1×10(6) cells/kg), 11 patients were evaluated for cMSC treatment safety and efficacy. During the trial, nine patients had 85 total adverse events and the rate of serious adverse events was 27.3% (3/11 patients). The only one adverse drug reaction related to cMSC administration was grade 2 myalgia in one patient. Treatment response was observed in four patients: one with acute GVHD (partial response) and three with chronic GVHD. The other chronic patients maintained stable disease during the observation period. This study demonstrates single cMSC infusion to have an acceptable safety profile and promising efficacy, suggesting that we can proceed with the next stage of the clinical trial. PMID:26807024

  19. Transplantation tolerance in primates following total lymphoid irradiation and allogeneic bone marrow injection. I. Orthoptic liver allographs

    SciTech Connect

    Myburgh, J.A.; Smit, J.A.; Browde, S.; Hill, R.R.H.

    1980-05-01

    Fractionated total lymphoid irradiation (TLI) and allogeneic bone marrow (BM) injection have been reported to produce stable chimerism without graft-versus-host disease (GVHD) in inbred mice and rats and mongrel dogs, and transplantation tolerance for skin and heart grafts in rodents. This concept has been studied in outbred chacma baboons receiving orthotopic liver allografts with the use of five different irradiation protocols. Eight fractions of 200 rad to the whole torso, followed immediately by allogeneic BM injections, and liver grafts from the BM donors 3 to 4 weeks later resulted in markedly prolonged survivals of 63 to 106 days in four baboons (median survival of untreated controls 19 days). Only one of the four animals died directly from the effects of rejection. BM chimerism was demonstrated in two baboons. There were no clinical or histological signs of GVHD in any of the animals. Two fractions of TLI, totaling 800 rad, 23 hr apart and followed immediately by BM injection and liver grafting resulted in profound thrombocytopenia and death form intraperitoneal hemorrhage in four of five baboons. In one animal BM injection and liver transplantation were delayed for 75 days. The baboon is still alive more than 6 months later. Three groups received single doses of 300, 400, and 500 rad to the whole torso, followed by allogeneic BM injections 1 and 2 weeks later, and liver transplants from their BM donors after an additional 3 to 4 weeks. The four baboons receiving 300 rad survived for 42, 86, 123, and >180 days. Two of the four baboons receiving 400 rad died of septic intraabdominal complications with minimal or no evidence of rejection. Fourh of the five baboons receiving 500 rad died from rejection.

  20. Extramedullary relapse after allogeneic bone marrow transplantation plus buffy-coat in two high risk patients.

    PubMed

    Salutari, P; Sica, S; Micciulli, G; Rutella, S; Di Mario, A; Leone, G

    1996-01-01

    In order to obtain an additional graft versus leukemia effect (GVL) and rapid engraftment, donor leukocyte infusion (DLI) was added to unseparated, sex-mismatched allogeneic bone marrow transplantation in two male patients (age 21, 26) affected by high risk hematological malignancies (refractory T-ALL, refractory B-LBL in leukemic phase). Graft versus host disease (GVHD) prophylaxis consisted of methotrexate (MTX) alone. DLI were obtained after G-CSF 16 ug/kg/day sc. A total of 2.36 and 5.8 x 10(6)/kg MNC, 5.4 and 11 x 10(6)/kg CD34+ cells, 1.3 and 1.3 x 10(6)/kg CD3+ lymphocytes, respectively, were infused. Hemopoietic recovery occurred promptly. Complete chimerism was detected by cytogenetic examination. One patient developed an extramedullary relapse that first involved the cranial nerves, and then the testes, soft tissue and skin; the other patient developed central nervous system disease and then bilateral paravertebral masses with progressive paraplegia. Despite complete medullary remission with normal female karyotype, both patients died from extramedullary progression of their disease. Our observation shows that, at least in high risk patients, no additional GVHD or GVL effect was evident after donor leukocyte infusion. Extramedullary relapse was not prevented despite good control of medullary disease. PMID:8641654

  1. Morphological and immunohistological changes in the skin in allogeneic bone marrow recipients.

    PubMed Central

    Sloane, J P; Thomas, J A; Imrie, S F; Easton, D F; Powles, R L

    1984-01-01

    Skin biopsies from leukaemic patients undergoing allogeneic bone marrow transplantations and treated prophylactically with cyclosporin A were analysed using histological, morphometric, and immunohistological techniques. Samples from donors were used to establish normal values. Biopsies taken from recipients two days before grafting were all histologically normal, but on immunohistological staining half of them showed a reduction in the number of epidermal Langerhans' cells and 29% a reduction in T inducer lymphocytes. Thirty two biopsies were taken from patients with rashes at various times after transplantation: 14 showed lichenoid changes consistent with graft versus host disease, three eczematous tissue reactions, two vesicular lesions, and 12 no histological abnormality. One sample showed changes intermediate between the lichenoid and eczematous forms. The numbers of epidermal Langerhans' cells were low during the first few weeks after transplantation and were normal or raised later regardless of histological appearances. Unlike epidermal Langerhans' cells, significant reductions in the numbers of lymphocytes were not seen. Lesions of all histological types contained mixtures of T inducer and T suppressor/cytotoxic cells, although the eczematous and vesicular lesions contained higher proportions of T inducer cells. Epidermal infiltrates invariably contained T suppressor/cytotoxic cells but infiltration of epidermis by T inducer cells occurred only in the presence of normal numbers of epidermal Langerhans' cells. Natural killer cells were not identified. The immunological appearances of the various histological subgroups thus change with time after transplantation. Images PMID:6381547

  2. Cellular bone matrices: viable stem cell-containing bone graft substitutes

    PubMed Central

    Skovrlj, Branko; Guzman, Javier Z.; Al Maaieh, Motasem; Cho, Samuel K.; Iatridis, James C.; Qureshi, Sheeraz A.

    2015-01-01

    BACKGROUND CONTEXT Advances in the field of stem cell technology have stimulated the development and increased use of allogenic bone grafts containing live mesenchymal stem cells (MSCs), also known as cellular bone matrices (CBMs). It is estimated that CBMs comprise greater than 17% of all bone grafts and bone graft substitutes used. PURPOSE To critically evaluate CBMs, specifically their technical specifications, existing published data supporting their use, US Food and Drug Administration (FDA) regulation, cost, potential pitfalls, and other aspects pertaining to their use. STUDY DESIGN Areview of literature. METHODS A series of Ovid, Medline, and Pubmed-National Library of Medicine/National Institutes of Health (www.ncbi.nlm.nih.gov) searches were performed. Only articles in English journals or published with English language translations were included. Level of evidence of the selected articles was assessed. Specific technical information on each CBM was obtained by direct communication from the companies marketing the individual products. RESULTS Five different CBMs are currently available for use in spinal fusion surgery. There is a wide variation between the products with regard to the average donor age at harvest, total cellular concentration, percentage of MSCs, shelf life, and cell viability after defrosting. Three retrospective studies evaluating CBMs and fusion have shown fusion rates ranging from 90.2% to 92.3%, and multiple industry-sponsored trials are underway. No independent studies evaluating spinal fusion rates with the use of CBMs exist. All the commercially available CBMs claim to meet the FDA criteria under Section 361, 21 CFR Part 1271, and are not undergoing FDA premarket review. The CBMs claim to provide viable MSCs and are offered at a premium cost. Numerous challenges exist in regard to MSCs’ survival, function, osteoblastic potential, and cytokine production once implanted into the intended host. CONCLUSIONS Cellular bone matrices may

  3. Bone-grafting materials in implant dentistry.

    PubMed

    Misch, C E; Dietsh, F

    1993-01-01

    There are three classes of bone-grafting materials based upon the mode of action. Autogenous bone is an organic material and forms bone by osteogenesis, osteoinduction, and osteoconduction. Allografts such as demineralized freeze-dried bone are osteoinductive and osteoconductive and may be cortical and/or trabecular in nature. Alloplasts such as hydroxyapatite and tricalcium phosphate may be synthetic or natural, vary in size, and are only osteoconductive. They can be divided into three types based upon the porosity of the product and include dense, macroporous, and microporous materials. In addition, alloplastic materials may be crystalline or amorphous. These materials have different properties and therefore indications. The use of the three classes of materials in diverse combinations depends upon the size and topography of the bony defect. Small defects or defects with four walls of host bone can be repaired with alloplasts alone or allografts in combination with alloplasts. The loss of three or more bony walls mandates the addition of autogenous bone to the graft or the use of a small pore membrane. The larger the defect, the more autogenous bone is required. The different indications of bone substitutes are discussed as to their specific applications in implant dentistry. PMID:8142935

  4. Repair of tegmen defect using cranial particulate bone graft.

    PubMed

    Greene, Arin K; Poe, Dennis S

    2015-01-01

    Bone paté is used to repair cranial bone defects. This material contains bone-dust collected during the high-speed burring of the cranium. Clinical and experimental studies of bone dust, however, have shown that it does not have biological activity and is resorbed. We describe the use of bone paté using particulate bone graft. Particulate graft is harvested with a hand-driven brace and 16mm bit; it is not subjected to thermal injury and its large size resists resorption. Bone paté containing particulate graft is much more likely than bone dust to contain viable osteoblasts capable of producing new bone. PMID:25465655

  5. Rejection of the second allogeneic graft in a child with Fanconi anemia reversed by antilymphocyte globulin and donor lymphocyte infusion.

    PubMed

    Abdelkefi, Abderrahman; Ben Othman, T; Ladeb, S; Torjman, L; Ben Abdeladhim, A

    2003-01-01

    Rejection after allogeneic bone marrow transplantation for Fanconi anemia (FA) is a complication with a high risk of mortality. We describe a patient who, following a second episode of rejection after a second allogeneic stem cell transplantation, was successfully treated with antilymphocyte globulin, followed by donor lymphocyte infusion. At three and a half years after donor lymphocyte infusion, she is alive with a Karnofsky score of 90%. Her molecular chimerism is of donor origin. Thus, donor lymphocyte infusion can be considered as a therapy option for rejection after allogeneic bone marrow transplantation for FA. PMID:14671621

  6. Percutaneous Vertebroplasty Using Fresh Frozen Allogeneic Bone Chips as Filler

    PubMed Central

    Lee, Song; Kim, Dae Geun; Shin, Won Sik

    2014-01-01

    Background Vertebroplasty is not free from cement related complications. If an allograft is used as a filler, most of them can be averted. Methods Forty consecutive cases of osteoporotic vertebral fracture were divided into two groups by self-selection. The study and the control groups underwent vertebroplasty with fresh frozen allogeneic bone chips and bone cement, respectively. Clinical results were assessed at preoperation, postoperative day 1 and months 3, 6, and 12 by 10-grade visual analog scale (VAS), and radiological results were assessed at the same time by vertebral kyphotic angle (VKA) and local kyphotic angle (LKA). The results were compared within and between the groups. Survival function was analyzed. The criteria of an event were clinical or radiological deterioration versus pre-index surgery state. Results VAS was improved in the study group from 8.4 ± 0.8 to 5.2 ± 1.4, 6.4 ± 1.2, 5.5 ± 2.7, and 3.7 ± 1.4 at postoperative day 1 and months 3, 6, and 12, respectively, and in the control group from 8.4 ± 1.2 to 3.2 ± 1.1, 3.2 ± 1.7, 3.2 ± 2.7, and 2.5 ± 1.7, respectively (within group, p < 0.001; between groups, p < 0.001). VKA was improved in the study group from 18.9° ± 8.0° to 15.2° ± 6.1° (p = 0.046) and in the control group from 14.7° ± 5.2° to 10.3° ± 4.7° (p < 0.001) at postoperative day 1. LKA was not improved in the study group but was improved in the control group from 16.8° ± 11.7° to 14.3° ± 9.6° (p = 0.015). Correction angle was 2.7° ± 4.6°, -7.9° ± 5.3°, -7.2° ± 5.2°, and -7.4° ± 6.3° at postoperative day 1 and months 3, 6, and 12, respectively, in the study group and 4.3° ± 3.7°, 0.7° ± 3.6°, 0.7° ± 4.2°, and 0.1° ± 4.4°, respectively, in the control group. Correction loss was significant in both groups (p < 0.001) and more serious in the study group (p < 0.001). The 6-month survival rate was 16.7% in the study group and 64.3% in the control group (p = 0.003; odds ratio, 5

  7. Long-term outcomes of the use of allogeneic, radiation-sterilised bone blocks in reconstruction of the atrophied alveolar ridge in the maxilla and mandible.

    PubMed

    Krasny, Marta; Krasny, Kornel; Fiedor, Piotr; Zadurska, Małgorzata; Kamiński, Artur

    2015-12-01

    Increasingly dental surgeons face the challenge of reconstruction of the height and/or thickness of the alveolar ridge as more and more patients wish to have permanent restoration of their dental defects based on intraosseous implants. Evaluation of human allogeneic bone tissue grafts in reconstruction of atrophied alveolar ridge as a pre-implantation procedure. The material comprised 21 patients aged 19-63, treated between 2009 and 2012 by the same surgeon. Restoration of bone tissue defects was performed with allogeneic, frozen, radiation-sterilised, corticocancellous blocks. The study included 26 grafting procedures with 7 procedures consisting in reconstruction of the alveolar ridge in the mandible and 19 in the maxilla. In all the cases the atrophied alveolar ridge was successfully reconstructed, which allowed placement of intraosseous implants in compliance with the initial treatment plan. After the treatment was completed the patients reported for follow-up annually. The average time of follow-up amounted to 39 months (28-50 months). None of the implants was lost during the follow-up period. There was one case of gingival recession causing aesthetics deterioration of the prosthetic restoration. In three cases the connector became unscrewed partially, which was corrected at the same visit. Frozen, radiation-sterilised, allogeneic bone blocks constitute good and durable bone-replacement material allowing effective and long-lasting reconstruction of the atrophied alveolar ridge to support durable, implant-based, prosthetic restoration. PMID:26162810

  8. Transient increase of serum IgD levels after allogeneic bone-marrow transplantation.

    PubMed Central

    Korver, K; Radl, J; Schellekens, P T; Vossen, J M

    1988-01-01

    Serum IgD levels were followed longitudinally twice a week for up to 100 days in 60 children undergoing allogeneic bone-marrow transplantation (n = 52) or immunosuppression (n = 8) for the treatment of leukaemia, severe aplastic anaemia or severe combined immunodeficiency. In 40 out of the 49 post-transplantation periods analysed (82%), a transient sharp increase of serum IgD was detected, irrespective of initial disease. A similar peak was found in one out of five children after immunosuppressive treatment. A second IgD peak was only recorded in grafted patients (14/49 post-transfusion periods). Peak levels of IgD ranged from 1.3 to 185.7 IU/ml (median 12.2 IU/ml), which represents a 2.6 to 22.4-fold increase over 'baseline' levels. In the transplanted leukaemia and aplastic anaemia patients, the rise of serum IgD occurred at the same time (geometric mean 16 days after transplantation) and was shown to represent heterogeneous polyclonal IgD in six of them. The onset of the serum IgD peak was significantly delayed in children suffering from severe combined immunodeficiency (P less than 0.05) and was demonstrated in one patient to consist of homogeneous IgD. No relation was found between either the occurrence of clinical acute graft-versus-host disease or infections after treatment, and the time of onset of IgD elevations. To detect transient serum IgD peaks as described here, frequent sampling of sera is necessary. The origin of the early IgD peaks seems to reside within the recipient's cells by an unknown mechanism. The late IgD peaks are most probably an expression of gradual reconstitution of the immune system following bone-marrow transplantation. PMID:3044651

  9. Improved graft-versus-host disease-free, relapse-free survival associated with bone marrow as the stem cell source in adults

    PubMed Central

    Mehta, Rohtesh S.; de Latour, Regis Peffault; DeFor, Todd E; Robin, Marie; Lazaryan, Aleksandr; Xhaard, Aliénor; Bejanyan, Nelli; de Fontbrune, Flore Sicre; Arora, Mukta; Brunstein, Claudio G.; Blazar, Bruce R.; Weisdorf, Daniel J.; MacMillan, Margaret L.; Socie, Gerard; Holtan, Shernan G.

    2016-01-01

    We previously reported that bone marrow grafts from matched sibling donors resulted in best graft-versus-host disease-free, relapse-free survival at 1-year post allogeneic hematopoietic cell transplantation. However, pediatric patients comprised the majority of bone marrow graft recipients in that study. To better define this outcome in adults and pediatric patients at 1- and 2-years post- allogeneic hematopoietic cell transplantation, we pooled data from the University of Minnesota and the Hôpital Saint-Louis in Paris, France (n=1901). Graft-versus-host disease-free, relapse-free survival was defined as the absence of grade III–IV acute graft-versus-host disease, chronic graft-versus-host disease (requiring systemic therapy or extensive stage), relapse and death. In adults, bone marrow from matched sibling donors (n=123) had best graft-versus-host disease-free, relapse-free survival at 1- and 2-years, compared with peripheral blood stem cell from matched sibling donors (n=540) or other graft/donor types. In multivariate analysis, peripheral blood stem cells from matched sibling donors resulted in a 50% increased risk of events contributing to graft-versus-host disease-free, relapse-free survival at 1- and 2-years than bone marrow from matched sibling donors. With limited numbers of peripheral blood stem cell grafts in pediatric patients (n=12), graft-versus-host disease-free, relapse-free survival did not differ between bone marrow and peripheral blood stem cell graft from any donor. While not all patients have a matched sibling donor, graft-versus-host disease-free, relapse-free survival may be improved by the preferential use of bone marrow for adults with malignant diseases. Alternatively, novel graft-versus-host disease prophylaxis regimens are needed to substantially impact graft-versus-host disease-free, relapse-free survival with the use of peripheral blood stem cell. PMID:27036159

  10. Lung function after bone marrow grafting

    SciTech Connect

    Depledge, M.H.; Barrett, A.; Powles, R.L.

    1983-02-01

    Results of a prospective lung function study are presented for 48 patients with acute myeloid leukemia (AML) treated with total body irradiation (TBI) and bone marrow transplantation (BMT) at the Royal Marsden Hospital between 1978 and 1980. Patients with active disease or who were in remission following cytoreductive chemotherapy had mildly impaired gas exchange prior to grafting. After TBI and BMT all patients studied developed progressive deterioration of lung function during the first 100 days, although these changes were subclinical. Infection and graft-versus-host disease (GvHD) were associated with further worsening of restrictive ventilatory defects and diffusing capacity (D/sub L/CO). Beyond 100 days, ventilatory ability returned to normal and gas transfer improved, although it failed to reach pre-transplant levels. There was no evidence of progressive pulmonary fibrosis during the first year after grafting.

  11. Early vancomycin-resistant enterococcus (VRE) bacteremia after allogeneic bone marrow transplantation is associated with a rapidly deteriorating clinical course.

    PubMed

    Avery, R; Kalaycio, M; Pohlman, B; Sobecks, R; Kuczkowski, E; Andresen, S; Mossad, S; Shamp, J; Curtis, J; Kosar, J; Sands, K; Serafin, M; Bolwell, B

    2005-03-01

    Vancomycin-resistant enterococcal (VRE) infection is a growing threat. We studied the incidence, risk factors, and clinical course of early-onset VRE bacteremia in allogeneic hematopoietic stem cell transplant recipients. We carried out a chart review of 281 allogeneic hematopoietic stem cell transplant recipients from 1997-2003, including preparative regimen, diagnosis, status of disease, graft-versus-host disease prophylaxis, antimicrobial therapy, and survival. VRE bacteremia developed in 12/281 (4.3%) recipients; 10 (3.6%) were within 21 days of transplant. Diagnoses were acute leukemia (7), NHL (2), and MDS (1). In all, 70% had refractory/relapsed disease; 30% were in remission. In total, 50% had circulating blasts. Nine of 10 had matched unrelated donors (7/9 with CD8+ T-cell depletion). The average time to positive VRE cultures was 15 days; average WBC was 0.05, and 80% had concomitant infections. Despite treatment, all patients died within 73 days of VRE bacteremia. Intra-abdominal complications were common. Causes of death included bacterial or fungal infection, multiorgan failure, VOD, ARDS, and relapse. A total of 60% of patients engrafted neutrophils, but none engrafted platelets. Early VRE bacteremia after allogeneic bone marrow transplant is associated with a rapidly deteriorating clinical course, although not always directly due to VRE. Early VRE may be a marker for the critical condition of these high-risk patients at the time of transplant. PMID:15640812

  12. PHYSICOCHEMICAL CHARACTERIZATION OF LYOPHILIZED BOVINE BONE GRAFTS

    PubMed Central

    Galia, Carlos Roberto; Lourenço, André Luis; Rosito, Ricardo; Souza Macedo, Carlos Alberto; Camargo, Lourdes Maria Araujo Quaresma

    2015-01-01

    To evaluate the physicochemical characteristics of lyophilized bovine grafts manufactured on a semi-industrial scale (Orthogen; Baumer S/A*) in accordance with a protocol previously developed by the authors. Methods: The lyophilized bovine bone grafts were characterized by means of scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), X-ray diffractometry (XRD), thermogravimetric (TG) analysis, differential exploratory scanning calorimetry (DSC) and Fourier-transform infrared (FT-IR) spectroscopy. Results: Ca was the main component (60%) found in the samples, followed by P (28%) and O (5%). The mean (sd) pore size was 316 μm (146.7), ranging from 91.2 to 497.8 μm, and 333.5 μm (304.8), ranging from 87.2 to 963.9 μm, at 50x and 150x magnification, respectively. The hydroxyapatite peaks were at 26°C and 32°C, and mass losses were observed between 250°C and 640°C, corresponding to organic material and water. Two temperature transitions (45.67°C and 91.89°C) showed denaturation of type 1 collagen and dehydration of hydroxyapatite. Conclusion: The physicochemical assessment of lyophilized bovine bone grafts in accordance with the protocol developed at semi-industrial scale confirmed that this product presents excellent biocompatibility, with characteristics similar to natural bone. PMID:27027036

  13. Immune Reconstitution and Graft-Versus-Host Reactions in Rat Models of Allogeneic Hematopoietic Cell Transplantation

    PubMed Central

    Zinöcker, Severin; Dressel, Ralf; Wang, Xiao-Nong; Dickinson, Anne M.; Rolstad, Bent

    2012-01-01

    Allogeneic hematopoietic cell transplantation (alloHCT) extends the lives of thousands of patients who would otherwise succumb to hematopoietic malignancies such as leukemias and lymphomas, aplastic anemia, and disorders of the immune system. In alloHCT, different immune cell types mediate beneficial graft-versus-tumor (GvT) effects, regulate detrimental graft-versus-host disease (GvHD), and are required for protection against infections. Today, the “good” (GvT effector cells and memory cells conferring protection) cannot be easily separated from the “bad” (GvHD-causing cells), and alloHCT remains a hazardous medical modality. The transplantation of hematopoietic stem cells into an immunosuppressed patient creates a delicate environment for the reconstitution of donor blood and immune cells in co-existence with host cells. Immunological reconstitution determines to a large extent the immune status of the allo-transplanted host against infections and the recurrence of cancer, and is critical for long-term protection and survival after clinical alloHCT. Animal models continue to be extremely valuable experimental tools that widen our understanding of, for example, the dynamics of post-transplant hematopoiesis and the complexity of immune reconstitution with multiple ways of interaction between host and donor cells. In this review, we discuss the rat as an experimental model of HCT between allogeneic individuals. We summarize our findings on lymphocyte reconstitution in transplanted rats and illustrate the disease pathology of this particular model. We also introduce the rat skin explant assay, a feasible alternative to in vivo transplantation studies. The skin explant assay can be used to elucidate the biology of graft-versus-host reactions, which are known to have a major impact on immune reconstitution, and to perform genome-wide gene expression studies using controlled combinations of minor and major histocompatibility between the donor and the recipient

  14. A prospective study on the effectiveness of newly developed autogenous tooth bone graft material for sinus bone graft procedure

    PubMed Central

    Jun, Sang-Ho; Ahn, Jin-Soo; Lee, Jae-Il; Ahn, Kyo-Jin; Yun, Pil-Young

    2014-01-01

    PURPOSE The purpose of this prospective study was to evaluate the effectiveness of newly developed autogenous tooth bone graft material (AutoBT)application for sinus bone graft procedure. MATERIALS AND METHODS The patients with less than 5.0 mm of residual bone height in maxillary posterior area were enrolled. For the sinus bone graft procedure, Bio-Oss was grafted in control group and AutoBT powder was grafted in experimental group. Clinical and radiographic examination were done for the comparison of grafted materials in sinus cavity between groups. At 4 months after sinus bone graft procedure, biopsy specimens were analyzed by microcomputed tomography and histomorphometric examination for the evaluation of healing state of bone graft site. RESULTS In CT evaluation, there was no difference in bone density, bone height and sinus membrane thickness between groups. In microCT analysis, there was no difference in total bone volume, new bone volume, bone mineral density of new bone between groups. There was significant difference trabecular thickness (0.07 µm in Bio-Oss group Vs. 0.08 µm in AutoBT group) (P=.006). In histomorphometric analysis, there was no difference in new bone formation, residual graft material, bone marrow space between groups. There was significant difference osteoid thickness (8.35 µm in Bio-Oss group Vs. 13.12 µm in AutoBT group) (P=.025). CONCLUSION AutoBT could be considered a viable alternative to the autogenous bone or other bone graft materials in sinus bone graft procedure. PMID:25551014

  15. Bone scintigraphy in evaluating the viability of composite bone grafts revascularized by microvascular anastomoses, conventional autogenous bone grafts, and free non-revascularized periosteal grafts

    SciTech Connect

    Berggren, A.; Weiland, A.J.; Ostrup, L.T.

    1982-07-01

    Researchers studied the value of bone scintigraphy in the assessment of anastomotic patency and bone-cell viability in free bone grafts revascularized by microvascular anastomoses in twenty-seven dogs. The dogs were divided into three different groups, and scintigraphy was carried out using technetium-labeled methylene diphosphonate in composite bone grafts revascularized by microvascular anastomoses, conventional autogenous bone grafts, and periosteal grafts placed in different recipient beds. The viability of the grafts were evaluated by histological examination and fluorescence microscopy after triple labeling with oxytetracycline on the first postoperative day, alizarin complexone on the fourth postoperative day, and DCAF on the eleventh postoperative day. A positive scintiscan within the first week following surgery indicated patent microvascular anastomoses, and histological study and fluorescence microscopy confirmed that bone throughout the graft was viable. A positive scintiscan one week after surgery or later does not necessarily indicate microvascular patency or bone-cell survival, because new bone formed by creeping substitution on the surface of a dead bone graft can result in this finding.

  16. Use of leflunomide in an allogeneic bone marrow transplant recipient with refractory cytomegalovirus infection.

    PubMed

    Avery, R K; Bolwell, B J; Yen-Lieberman, B; Lurain, N; Waldman, W J; Longworth, D L; Taege, A J; Mossad, S B; Kohn, D; Long, J R; Curtis, J; Kalaycio, M; Pohlman, B; Williams, J W

    2004-12-01

    Ganciclovir-resistant cytomegalovirus (CMV) infection is an emerging problem in transplant recipients. Foscarnet resistance and cidofovir resistance have also been described, but no previous reports have suggested treatment regimens for patients with CMV refractory to all three of these drugs. Leflunomide, an immunosuppressive drug used in rheumatoid arthritis and in rejection in solid-organ transplantation, has been reported to have novel anti-CMV activity. However, its clinical utility in CMV treatment has not been described previously. We report an allogeneic bone marrow transplant recipient who developed CMV infection refractory to sequential therapy with ganciclovir, foscarnet, and cidofovir. The patient was ultimately treated with a combination of leflunomide and foscarnet. Both phenotypic and genotypic virologic analysis was performed on sequential CMV isolates. The patient's high CMV-DNA viral load became undetectable on leflunomide and foscarnet, but the patient, who had severe graft-versus-host disease (GVHD) of the liver, expired with progressive liver failure and other complications. We concluded that leflunomide is a new immunosuppressive agent with anti-CMV activity, which may be useful in the treatment of multiresistant CMV. However, the toxicity profile of leflunomide in patients with underlying GVHD remains to be defined. PMID:15489872

  17. Second Allogeneic Hematopoietic Cell Transplantation for Patients with Fanconi Anemia and Bone Marrow Failure.

    PubMed

    Ayas, Mouhab; Eapen, Mary; Le-Rademacher, Jennifer; Carreras, Jeanette; Abdel-Azim, Hisham; Alter, Blanche P; Anderlini, Paolo; Battiwalla, Minoo; Bierings, Marc; Buchbinder, David K; Bonfim, Carmem; Camitta, Bruce M; Fasth, Anders L; Gale, Robert Peter; Lee, Michelle A; Lund, Troy C; Myers, Kasiani C; Olsson, Richard F; Page, Kristin M; Prestidge, Tim D; Radhi, Mohamed; Shah, Ami J; Schultz, Kirk R; Wirk, Baldeep; Wagner, John E; Deeg, H Joachim

    2015-10-01

    A second allogeneic hematopoietic cell transplantation (HCT) is the sole salvage option for individuals who develop graft failure after their first HCT. Data on outcomes after second HCT in patients with Fanconi anemia (FA) are scarce. Here we report outcomes after second allogeneic HCT for FA (n = 81). The indication for second HCT was graft failure after the first HCT. Transplantations were performed between 1990 and 2012. The timing of the second HCT predicted subsequent graft failure and survival. Graft failure was high when the second HCT was performed less than 3 months from the first. The 3-month probability of graft failure was 69% when the interval between the first HCT and second HCT was less than 3 months, compared with 23% when the interval was longer (P < .001). Consequently, the 1-year survival rate was substantially lower when the interval between the first and second HCTs was less than 3 months compared with longer (23% vs 58%; P = .001). The corresponding 5-year probability of survival was 16% and 45%, respectively (P = .006). Taken together, these data suggest that fewer than one-half of patients with FA undergoing a second HCT for graft failure are long-term survivors. There is an urgent need to develop strategies to reduce the rate of graft failure after first HCT. PMID:26116087

  18. Vertical Guided Bone Regeneration using Titanium-reinforced d-PTFE Membrane and Prehydrated Corticocancellous Bone Graft

    PubMed Central

    Cucchi, Alessandro; Ghensi, Paolo

    2014-01-01

    Guided bone regeneration (GBR) standard protocols call for filling the space underneath the membrane with autogenous bone or a mixture composed of autogenous bone particles and allogeneic bone tissue or heterologous biomaterials. This work describes the case of a GBR performed to restore a vertical bone defect with simultaneous placement of a dental implant in the posterior mandible that was carried out using a high density d-PTFE membrane and corticocancellous porcine-derived bone without the addition of any autogenous bone. Bone regeneration was assessed by histological analysis of a biopsy sample collected from the grafted site nine months after the surgery. Intraoral radiographs taken at follow-up visits showed complete maintenance of the peri-implant bone levels for up to two years after prosthesis delivery. The regenerated site successfully supported functional loading of the implant. The present case report suggests that the use of a heterologous bone substitute alone to restore a vertical defect in a GBR procedure can be as effective as the standard protocol, while avoiding the drawbacks associated with a second surgical site opening. PMID:25419250

  19. Mandibular Tori: A source of autogenous bone graft

    PubMed Central

    Santhanakrishnan, Muthukumar; Rangarao, Suresh

    2014-01-01

    Restoration of lost alveolar bone support remains as one of the main objectives of periodontal surgery. Amongst the various types of bone grafts available for grafting procedures, autogenous bone grafts are considered to be the gold standard in alveolar defect reconstruction. Although there are various sources for autogenous grafts including the mandibular symphysis and ramus, they are almost invariably not contiguous with the area to be augmented. An alternative mandibular donor site that is continuous with the recipient area and would eliminate the need for an extra surgical site is the tori/exostoses. Bone grafting was planned for this patient as there were angular bone loss present between 35-36 and 36-37. As the volume of bone required was less and bilateral tori were present on the lingual side above the mylohyoid line, the tori was removed and used as a source of autogenous bone graft, which were unnecessary bony extensions present on the mandible and continuous with the recipient area. Post-operative radiographs taken at 6 and 12 month intervals showed good bone fill and also areas of previous pockets, which did not probe after treatment indicates the success of the treatment. The use of mandibular tori as a source of autogenous bone graft should be considered whenever a patient requires bone grafting procedure to be done and presents with a tori. PMID:25624635

  20. Genetic tracing of arterial graft flow surface endothelialization in allogeneic marrow transplanted dogs.

    PubMed

    Shi, Q; Wu, M H; Fujita, Y; Ishida, A; Wijelath, E S; Hammond, W P; Wechezak, A R; Yu, C; Storb, R F; Sauvage, L R

    1999-01-01

    In order to trace genetically the source of fallout endothelialization on arterial grafts, six beagle dogs with successful autologous bone marrow transplantation received composite tandem aortic grafts with an isolated, totally impervious Dacron graft and a porous Dacron graft for 12 weeks. For impervious segments, five of 12 fresh tissue samples were Factor VIII/von Willebrand factor + (FVIII/vWF) and seven had faint or negative signals; three of the FVIII/vWF + samples had alpha-actin + smooth muscle cells. Polymerase chain reaction (PCR) study showed eight had a pure donor DNA genotype and four had donor/host mixed, with the donor predominant. Of 12 AgNO3-stained samples, 11 showed pure donor type and one had donor/host mixed, with the donor predominant. For porous segments, all 12 fresh samples had positive flow surface FVIII/vWF and alpha-actin cells. PCR showed all these samples and all 12 AgNO3-stained samples had donor/host mixed type, but the host pattern was predominant. Porous graft healing appears to involve both cellular fallout and tissue ingrowth, and bone-marrow-derived cells may be a source for fallout. PMID:10073768

  1. The effects of early postoperative radiation on vascularized bone grafts

    SciTech Connect

    Evans, H.B.; Brown, S.; Hurst, L.N. )

    1991-06-01

    The effects of early postoperative radiation were assessed in free nonvascularized and free vascularized rib grafts in the canine model. The mandibles of one-half of the dogs were exposed to a cobalt 60 radiation dose of 4080 cGy over a 4-week period, starting 2 weeks postoperatively. The patency of vascularized grafts was confirmed with bone scintigraphy. Histological studies, including ultraviolet microscopy with trifluorochrome labeling, and histomorphometric analyses were performed. Osteocytes persist within the cortex of the vascularized nonradiated grafts to a much greater extent than in nonvascularized, nonradiated grafts. Cortical osteocytes do not persist in either vascularized or nonvascularized grafts subjected to radiation. New bone formation is significantly retarded in radiated grafts compared with nonradiated grafts. Periosteum and endosteum remained viable in the radiated vascularized grafts, producing both bone union and increased bone turnover, neither of which were evident to any significant extent in nonvascularized grafts. Bone union was achieved in vascularized and non-vascularized nonradiated bone. In the radiated group of dogs, union was only seen in the vascularized bone grafts.

  2. Allogeneic adipose-derived stem cells regenerate bone in a critical-sized ulna segmental defect.

    PubMed

    Wen, Congji; Yan, Hai; Fu, Shibo; Qian, Yunliang; Wang, Danru; Wang, Chen

    2016-07-01

    Adipose-derived stem cells (ASCs) with multilineage potential can be induced into osteoblasts, adipocytes and chondrocytes. ASCs as seed cell are widely used in the field of tissue engineering, but most studies either use autologous cells as the source or an immunodeficient animal as the host. In our present study, we explored the feasibility of applying allogeneic ASCs and demineralized bone matrix (DBM) scaffolds for repairing tubular bone defects without using immunosuppressive therapy. Allogeneic ASCs were expanded and seeded on DBM scaffolds and induced to differentiate along the osteogenic lineage. Eight Sprague-Dawley (SD) rats were used in this study and bilateral critical-sized defects (8 mm) of the ulna were created and divided into two groups: with ASC-DBM constructs or DBM alone. The systemic immune response and the extent of bone healing were evaluated post-operatively. Twenty-four weeks after implantation, digital radiography (DR) testing showed that new bones had formed in the experimental group. By contrast, no bone tissue formation was observed in the control group. This study demonstrated that allogeneic ASCs could promote bone regeneration and repair tubular bone defects combined with DBM by histologically typical bone without systemic immune response. PMID:25819682

  3. Fatal B-cell lymphoproliferative syndrome in allogeneic marrow graft recipients. A clinical, immunobiological and pathological study.

    PubMed

    Simon, M; Bartram, C R; Friedrich, W; Arnold, R; Schmeiser, T; Hampl, W; Müller-Hermelink, H K; Heymer, B

    1991-01-01

    We have studied four cases of fatal B-cell lymphoproliferative syndrome (LPS) developing among 333 patients (incidence 1.2%) treated with allogeneic bone marrow transplantation (BMT). All four patients had received a T-cell depleted graft. Onset of the first clinical symptoms (palpable lymph node enlargement in three and IgA-lambda paraproteinemia in two patients) occurred between 41 and 188 days post-BMT (median 76 days). The course of the LPS was rapidly progressive in all cases, leading to death in 2-5 weeks. The peripheral blood showed progressive pancytopenia with disproportionally high numbers of activated NK cells, apparently compensating for the T-cell deficiency. Post-mortem histological studies disclosed polymorphic B-cell proliferations, most pronounced in the lymph nodes, spleen, liver, lungs and kidneys. Lymphohemopoietic cells were of donor origin in three patients. In the fourth patient, graft failure suggested a host origin for the proliferating cells. Immunophenotyping and gene rearrangement analysis revealed polyclonal proliferation in one patient, monoclonal proliferation in another patient, and an oligoclonal pattern in the other two patients. The clinical behavior of the LPS was independent of clonality. Immunohistologically, the proliferating cells showed characteristics of relatively mature B-cells in three cases, and pre-B-cell features in one case. Epstein Barr virus (EBV) serology indicated seroconversion (primary infection) in one child, and chronic active EBV infection in both adults. EBV DNA as well as EBV nuclear antigen (EBNA) were detected in infiltrated tissues of all four patients. The labeling pattern on in situ hybridization suggested a replicative EBV infection comparable to that in lymphoblastoid cell lines. We conclude that EBV-associated LPS developing as a result of post-transplant immunodeficiency is a distinct clinicopathologic entity, differing from non-Hodgkin's lymphoma (including Burkitt's lymphoma) and infectious

  4. Comparative Biomechanical and Microstructural Analysis of Native versus Peracetic Acid-Ethanol Treated Cancellous Bone Graft

    PubMed Central

    Rauh, Juliane; Despang, Florian; Baas, Jorgen; Liebers, Cornelia; Pruss, Axel; Günther, Klaus-Peter; Stiehler, Maik

    2014-01-01

    Bone transplantation is frequently used for the treatment of large osseous defects. The availability of autologous bone grafts as the current biological gold standard is limited and there is a risk of donor site morbidity. Allogenic bone grafts are an appealing alternative, but disinfection should be considered to reduce transmission of infection disorders. Peracetic acid-ethanol (PE) treatment has been proven reliable and effective for disinfection of human bone allografts. The purpose of this study was to evaluate the effects of PE treatment on the biomechanical properties and microstructure of cancellous bone grafts (CBG). Forty-eight human CBG cylinders were either treated by PE or frozen at −20°C and subjected to compression testing and histological and scanning electron microscopy (SEM) analysis. The levels of compressive strength, stiffness (Young's modulus), and fracture energy were significantly decreased upon PE treatment by 54%, 59%, and 36%, respectively. Furthermore, PE-treated CBG demonstrated a 42% increase in ultimate strain. SEM revealed a modified microstructure of CBG with an exposed collagen fiber network after PE treatment. We conclude that the observed reduced compressive strength and reduced stiffness may be beneficial during tissue remodeling thereby explaining the excellent clinical performance of PE-treated CBG. PMID:24678514

  5. Allogeneic unrelated bone marrow transplantation from older donors results in worse prognosis in recipients with aplastic anemia.

    PubMed

    Arai, Yasuyuki; Kondo, Tadakazu; Yamazaki, Hirohito; Takenaka, Katsuto; Sugita, Junichi; Kobayashi, Takeshi; Ozawa, Yukiyasu; Uchida, Naoyuki; Iwato, Koji; Kobayashi, Naoki; Takahashi, Yoshiyuki; Ishiyama, Ken; Fukuda, Takahiro; Ichinohe, Tatsuo; Atsuta, Yoshiko; Mori, Takehiko; Teshima, Takanori

    2016-05-01

    Allogeneic bone marrow transplantation is an essential therapy for acquired aplastic anemia and prognosis has recently improved. However, engraftment failure and graft-versus-host disease are potential fatal complications. Various risk factors for poor prognosis have been identified, such as patient age and human-leukocyte antigen disparity, but the relationship between donor age and prognosis is still unknown. Therefore, we performed a cohort study to compare the prognosis of unrelated bone marrow transplantation from younger and older donors using the registry database in Japan. We evaluated 427 patients (age 16-72 years) with aplastic anemia who underwent bone marrow transplantation from younger (≤39 years, n=281) or older (≥40 years, n=146) unrelated donors. Overall survival of the older donor group was significantly inferior to that of the younger donor group (adjusted hazard ratio 1.64; 95% confidence interval 1.15-2.35; P<0.01). The incidence of fatal infection was significantly higher in the older donor group (13.7% vs. 7.5%; P=0.03). Primary engraftment failure and acute graft-versus-host disease were significantly more frequent in the older donor group (9.7% vs. 5.0%; adjusted hazard ratio 1.30; P=0.01, and 27.1% vs. 19.7%; adjusted hazard ratio 1.56; P=0.03, respectively). Acute graft-versus-host disease was related to a worse prognosis in the whole cohort. This study showed the inferiority of older donors in aplastic anemia; thus, donor age should be considered when multiple donors are available. A large-scale prospective study is warranted to establish a better donor selection algorithm for bone marrow transplantation in aplastic anemia. PMID:26858357

  6. Allogeneic unrelated bone marrow transplantation from older donors results in worse prognosis in recipients with aplastic anemia

    PubMed Central

    Arai, Yasuyuki; Kondo, Tadakazu; Yamazaki, Hirohito; Takenaka, Katsuto; Sugita, Junichi; Kobayashi, Takeshi; Ozawa, Yukiyasu; Uchida, Naoyuki; Iwato, Koji; Kobayashi, Naoki; Takahashi, Yoshiyuki; Ishiyama, Ken; Fukuda, Takahiro; Ichinohe, Tatsuo; Atsuta, Yoshiko; Mori, Takehiko; Teshima, Takanori

    2016-01-01

    Allogeneic bone marrow transplantation is an essential therapy for acquired aplastic anemia and prognosis has recently improved. However, engraftment failure and graft-versus-host disease are potential fatal complications. Various risk factors for poor prognosis have been identified, such as patient age and human-leukocyte antigen disparity, but the relationship between donor age and prognosis is still unknown. Therefore, we performed a cohort study to compare the prognosis of unrelated bone marrow transplantation from younger and older donors using the registry database in Japan. We evaluated 427 patients (age 16–72 years) with aplastic anemia who underwent bone marrow transplantation from younger (≤39 years, n=281) or older (≥40 years, n=146) unrelated donors. Overall survival of the older donor group was significantly inferior to that of the younger donor group (adjusted hazard ratio 1.64; 95% confidence interval 1.15–2.35; P<0.01). The incidence of fatal infection was significantly higher in the older donor group (13.7% vs. 7.5%; P=0.03). Primary engraftment failure and acute graft-versus-host disease were significantly more frequent in the older donor group (9.7% vs. 5.0%; adjusted hazard ratio 1.30; P=0.01, and 27.1% vs. 19.7%; adjusted hazard ratio 1.56; P=0.03, respectively). Acute graft-versus-host disease was related to a worse prognosis in the whole cohort. This study showed the inferiority of older donors in aplastic anemia; thus, donor age should be considered when multiple donors are available. A large-scale prospective study is warranted to establish a better donor selection algorithm for bone marrow transplantation in aplastic anemia. PMID:26858357

  7. Assessment of the autogenous bone graft for sinus elevation

    PubMed Central

    Peng, Wang; Cho, Hyun-Young; Pae, Sang-Pill; Jung, Bum-Sang; Cho, Hyun-Woo; Seo, Ji-Hoon

    2013-01-01

    Objectives The posterior maxillary region often provides a limited bone volume for dental implants. Maxillary sinus elevation via inserting a bone graft through a window opened in the lateral sinus wall has become the most common surgical procedure for increasing the alveolar bone height in place of dental implants in the posterior maxillary region. The purpose of this article is to assess the change of bone volume and the clinical effects of dental implant placement in sites with maxillary sinus floor elevation and autogenous bone graft through the lateral window approach. Materials and Methods In this article, the analysis data were collected from 64 dental implants that were placed in 24 patients with 29 lacks of the bone volume posterior maxillary region from June 2004 to April 2011, at the Department of Oral and Maxillofacial Surgery, Inha University Hospital. Panoramic views were taken before the surgery, after the surgery, 6 months after the surgery, and at the time of the final follow-up. The influence of the factors on the grafted bone material resorption rate was evaluated according to the patient characteristics (age and gender), graft material, implant installation stage, implant size, implant placement region, local infection, surgical complication, and residual alveolar bone height. Results The bone graft resorption rate of male patients at the final follow-up was significantly higher than the rate of female patients. The single autogenous bone-grafted site was significantly more resorbed than the autogenous bone combined with the Bio-Oss grafted site. The implant installation stage and residual alveolar height showed a significant correlation with the resorption rate of maxillary sinus bone graft material. The success rate and survival rate of the implant were 92.2% and 100%, respectively. Conclusion Maxillary sinus elevation procedure with autogenous bone graft or autogenous bone in combination with Bio-Oss is a predictable treatment method for

  8. Supercritical carbon dioxide-processed resorbable polymer nanocomposites for bone graft substitute applications

    NASA Astrophysics Data System (ADS)

    Baker, Kevin C.

    Numerous clinical situations necessitate the use of bone graft materials to enhance bone formation. While autologous and allogenic materials are considered the gold standards in the setting of fracture healing and spine fusion, their disadvantages, which include donor site morbidity and finite supply have stimulated research and development of novel bone graft substitute materials. Among the most promising candidate materials are resorbable polymers, composed of lactic and/or glycolic acid. While the characteristics of these materials, such as predictable degradation kinetics and biocompatibility, make them an excellent choice for bone graft substitute applications, they lack mechanical strength when synthesized with the requisite porous morphology. As such, porous resorbable polymers are often reinforced with filler materials. In the presented work, we describe the use of supercritical carbon dioxide (scCO2) processing to create porous resorbable polymeric constructs reinforced by nanostructured, organically modified Montmorillonite clay (nanoclay). scCO2 processing simultaneously disperses the nanoclay throughout the polymeric matrix, while imparting a porous morphology to the construct conducive to facilitating cellular infiltration and neoangiogenesis, which are necessary components of bone growth. With the addition of as little as 2.5wt% of nanoclay, the compressive strength of the constructs nearly doubles putting them on par with human cortico-cancellous bone. Rheological measurements indicate that the dominant mode of reinforcement of the nanocomposite constructs is the restriction of polymer chain mobility. This restriction is a function of the positive interaction between polymer chains and the nanoclay. In vivo inflammation studies indicate biocompatibility of the constructs. Ectopic osteogenesis assays have determined that the scCO2-processed nanocomposites are capable of supporting growth-factor induced bone formation. scCO 2-processed resorbable

  9. The origin of IgG production and homogeneous IgG components after allogeneic bone marrow transplantation.

    PubMed

    van Tol, M J; Gerritsen, E J; de Lange, G G; van Leeuwen, A M; Jol-van der Zijde, C M; Oudeman-Gruber, N J; de Vries, E; Radl, J; Vossen, J M

    1996-01-15

    Pediatric recipients (n = 25) of an allogeneic bone marrow (BM) graft were selected on the basis of informative IgG allotype (Gm) differences between the BM donor and the recipient. To investigate the kinetics of the appearance of IgG of donor origin and the disappearance of IgG of recipient origin, G1m and G2m allotype levels were quantified in sera obtained at regular intervals between 3 months and 5 years after BM transplantation (BMT). For this quantification, a dot immunobinding assay (DIBA) has been developed. In 19 of 22 informative recipients, the Gm allotype distribution had reached the range of values expected on the basis of the Gm phenotype of the donor within 6 months after BMT. Remarkably, IgG of recipient origin persisted in 15 of 18 informative recipients until last follow up, ie, for several years after BMT. In addition to the origin of total IgG production, the origin of homogeneous IgG components (H-IgG) appearing after BMT was investigated. H-IgG of donor origin could be detected as early as 3 weeks after BMT, but also H-IgG of recipient origin were present in 8 of 13 informative recipients for a period of up to 1 year after BMT. We conclude that host-type IgG-producing cells were not eradicated by the (myeloablative) conditioning regimen and persisted in a high number of graft recipients. It is our hypothesis that lack of graft-versus-host disease (GVHD) in the majority of these recipients results in the persistence of IgG-producing cells of host origin. These observations may be relevant for the evaluation of patients who received allogeneic BMT for the treatment of multiple myeloma. PMID:8555508

  10. Graft rejection by cytolytic T cells. Specificity of the effector mechanism in the rejection of allogeneic marrow

    SciTech Connect

    Nakamura, H.; Gress, R.E. )

    1990-02-01

    Cellular effector mechanisms of allograft rejection remain incompletely described. Characterizing the rejection of foreign-marrow allografts rather than solid-organ grafts has the advantage that the cellular composition of the marrow graft, as a single cell suspension, can be altered to include cellular components with differing antigen expression. Rejection of marrow grafts is sensitive to lethal doses of radiation in the mouse but resistant to sublethal levels of radiation. In an effort to identify cells mediating host resistance, lymphocytes were isolated and cloned from spleens of mice 7 days after sublethal TBI (650 cGy) and inoculation with allogeneic marrow. All clones isolated were cytolytic with specificity for MHC encoded gene products of the allogeneic marrow donor. When cloned cells were transferred in vivo into lethally irradiated (1025 cGy) recipients unable to reject allogeneic marrow, results utilizing splenic 125IUdR uptake indicated that these MHC-specific cytotoxic clones could suppress marrow proliferation. In order to characterize the effector mechanism and the ability of the clones to affect final engraftment, double donor chimeras were constructed so that 2 target cell populations differing at the MHC from each other and from the host were present in the same marrow allograft. Results directly demonstrated an ability of CTL of host MHC type to mediate graft rejection and characterized the effector mechanism as one with specificity for MHC gene products.

  11. [Detection of mixed lymphoid chimerism after allogeneic bone marrow transplantation: demonstration by interphase cytogenetics in paraffin-embedded tissue].

    PubMed

    Friedrich, T; Ott, G; Kalla, J; Helbig, W; Schwenke, H; Kubel, M; Pönisch, W; Feyer, P; Friedrich, A

    1994-01-01

    In bone marrow transplantation (BMT) the detection of residual host lymphoid or haematopoietic cells surviving conditioning therapy is because of its association to graft-versus-host disease, graft-versus-leukemia reaction, and relapse of leukemia a matter of great interest. We studied the occurrence of this mixed lymphoid chimerism (MC) in the formol-fixed lymphatic tissue of lymph nodes and spleen from 21 autopsies after allogeneic sex-mismatched BMT (5 females, 16 males, survival 5 to 1140 days after BMT). In situ hybridisation with biotinylated centromer-specific anti-X- and anti-Y-chromosome probes was performed on pepsin-digested paraffin sections. The number of double X-, single X-, and Y-chromosome bearing cells was analysed microscopically. Because of artefacts only 14 cases remained for valid investigation. MC was detected in 6 cases (5 out of 11 males 5 days to 840 days and 1 out of 3 females 76 days after BMT). MC occurred after whole body irradiation with 10 Gy (n = 5) and 7 Gy (n = 1). In 1 autopsy relapse of leukemia caused host cell infiltration. Cases with MC did not express histological signs of acute or chronic graft-versus-host disease, but 5 out of 8 with complete lymphoid chimerism did. The sensitivity of interphase cytogenetics on paraffin embedded tissue is low. PMID:7534002

  12. Transplantation tolerance in primates after total lymphoid irradiation and allogeneic bone marrow injection

    SciTech Connect

    Smit, J.A.; Hill, R.R.H.; Myburgh, J.A.; Browde, S.

    1980-08-01

    After total lymphoid irradiation (TLI), allogeneic bone marrow (BM) injection, and organ transplantation in baboons, there is a prolonged period of reduced lymphocyte proliferative responsiveness to polyclonal mitogens and allogeneic lymphocytes. The effect observed is greater with the use of fractionated TLI than after single doses of irradiation. Suppressor cell activity can be demonstrated in vitro in most animals by inhibition of mixed lymphocyte reactivity (MLR) by mitomycin-treated recipient lymphocytes harvested after TLI, with or without allogeneic BM injection, and organ transplantation. Preliminary data suggest the presence of both donor-specific and nondonor-specific suppression, although other interpretations are possible, and suppressor phenomena may not be responsible for the transplantation tolerance observed.

  13. Dynamic of bone marrow fibrosis regression predicts survival after allogeneic stem cell transplantation for myelofibrosis.

    PubMed

    Kröger, Nicolaus; Zabelina, Tatjana; Alchalby, Haefaa; Stübig, Thomas; Wolschke, Christine; Ayuk, Francis; von Hünerbein, Natascha; Kvasnicka, Hans-Michael; Thiele, Jürgen; Kreipe, Hans-Heinrich; Büsche, Guntram

    2014-06-01

    We correlate regression of bone marrow fibrosis (BMF) on day 30 and 100 after dose- reduced allogeneic stem cell transplantation (allo-SCT) in 57 patients with primary or post-essential thrombocythemia/polycythemia vera myelofibrosis with graft function and survival. The distribution of International Prognostic Scoring System (IPSS) risk score categories was 1 patient with low risk, 5 patients with intermediate-1 risk, 18 patients with intermediate-2 risk, and 33 patients with high risk. Before allo-SCT, 41 patients (72%) were classified as XXX [myclofibrosis (MF)]-3 and 16 (28%) were classified as MF-2 according to the World Health Organization criteria. At postengraftment day +30 (±10 days), 21% of the patients had near-complete or complete regression of BMF (MF-0/-1), and on day +100 (±20 days), 54% were MF-0/-1. The 5-year overall survival rate at day +100 was 96% in patients with MF-0/-1 and 57% for those with MF-2/-3 (P = .04). There was no difference in BMF regression at day +100 between IPSS high-risk and low/intermediate-risk patients. Complete donor cell chimerism at day +100 was seen in 81% of patients with MF-0/-1 and in 31% of those with MF-2/-3. Patients with MF-2/-3 at day +100 were more likely to be transfusion-dependent for either RBCs (P = .014) or platelets (P = .018). Rapid BMF regression after reduced-intensity conditioning allo-SCT resulted in a favorable survival independent of IPSS risk score at transplantation. PMID:24589549

  14. Activity of host-derived T cells which differentiate in nude mice grafted with co-isogenic or allogeneic thymuses.

    PubMed

    Kindred, B; Loor, F

    1974-05-01

    If nude mice are grafted with a neonatal thymus, host type precursor cells develop within the graft thymus and after about 6 wk the T-cell population of the thymus, spleen, and lymph nodes is of host type. However, immunological responsiveness produced in nude mice in this manner is incomplete: (a) the ability to react to T-cell mitogens in vitro is greater than in untreated nudes but lower than in normal mice; (b) the response to T-cell dependent antigens is less than normal; and (c) the rejection of skin grafts is slower than in normal animals. Whether host precursor cells which differentiate in an allogeneic thymus are able to reject skin grafts from thymus donor strain appears to depend on the strain combination used. PMID:4596513

  15. [Busulfan and cycosporin in bone graft children].

    PubMed

    Bertolle, V; Martin, P; Bleyzac, N; Aulagner, G

    2004-05-01

    Most drugs exhibit both inter- and intra-individual pharmacokinetic and pharmacodynamic variability. This variability explains the different responses observed in patients exposed to standard doses and must be taken into consideration when the therapeutic window is narrow. Population pharmacokinetics provides mean (or median) values of pharmacokinetic parameters as well as the distribution pattern and the statistical relationship with covariables in a group of individuals presenting common characteristics. Among the different methods developed for population pharmacokinetics, the data pool method, as well as the two-step and one-step methods (NONMEM and NPEM) are attractive. Population models can then be developed using bayesian logistics to obtain an estimation of the pharmacokinetic parameters of a given patient and predict the most adapted dose in light of the therapeutic target (residual serum concentration, mean concentration.). Busulfan is an alkylizing agent used instead of radiotherapy for pre-graft preparation before bone marrow grafts in children. This compound requires dose monitoring because of its narrow therapeutic window: under-dosing raises the risk of graft rejection; inversely over-dosing can cause potentially fatal complications such as occlusive venous disease. Interindividual variability is characteristic of busulfan kinetics. Several factors can explain part of this variability: age, underlying disease, changes in liver function, drug bioavailability, chronobiology. The short treatments used (most protocols have 16 doses given in four days) require rapid monitoring to propose effective adjustments. In this context, use of bayesian logistics to estimate the patient's pharmokinetic parameters is very useful for correct dosing. This type of monitoring could also be used for other compounds such as cyclosporine, with a narrow therapeutic window. PMID:15243350

  16. Reconstitution of the CD45RO(+) and CD20(+) lymphoid marrow population following allogeneic bone marrow transplantation for Ph(+) CML.

    PubMed

    Thiele, J; Kvasnicka, H M; Beelen, D W; Welter, A; Schneider, S; Leder, L D; Schaefer, U W

    2001-02-01

    Following bone marrow transplantation (BMT) investigations on the recovery of the B and T lymphocyte populations have focused on the peripheral blood and only marginally regard the bone marrow. An immunohistochemical and morphometric study was performed on 352 trephine biopsies derived from 123 patients with chronic myelogenous leukemia (CML) at standardized endpoints before and after allogeneic BMT and compared to a control group. The purpose of this investigation was to quantify the B-CD20(+) and T-CD45RO(+) lymphocyte subsets and to determine possible relationships with the occurrence of acute and chronic GVHD. Moreover, we studied the dynamics of lymphocyte repopulation in the post-transplant period, correlations with the total peripheral lymphocyte count and differences associated with sibling vs alternate HLA-compatible (unmanipulated) marrow grafts. Morphometric analysis revealed a very fast regeneration of CD45RO(+) and CD20(+) marrow lymphocytes in the first 2 weeks following BMT. In less than 2 months, in most patients, the post-transplant quantity of lymphocytes was comparable to that of the normal bone marrow. This finding was opposed to the profound depression of the absolute lymphocyte count in the peripheral blood. No relevant relationships could be calculated between engraftment status and the lymphocyte repopulation in the bone marrow. On the other hand, significant correlations were calculable between the development of (chronic and acute) GVHD including severity with the number of CD45RO(+) lymphocytes. In non-related graft constellations a more frequent evolution of acute grade III + IV GVHD was detectable. This complication was accompanied by an increased quantity of CD45RO(+) lymphocytes in the marrow. PMID:11313672

  17. Booster irradiation to the spleen following total body irradiation. A new immunosuppressive approach for allogeneic bone marrow transplantation

    SciTech Connect

    Lapidot, T.; Singer, T.S.; Salomon, O.; Terenzi, A.; Schwartz, E.; Reisner, Y.

    1988-10-15

    Graft rejection presents a major obstacle for transplantation of T cell-depleted bone marrow in HLA-mismatched patients. In a primate model, after conditioning exactly as for leukemia patients, it was shown that over 99% of the residual host clonable T cells are concentrated in the spleen on day 5 after completion of cytoreduction. We have now corroborated these findings in a mouse model. After 9-Gy total body irradiation (TBI), the total number of Thy-1.2+ cells in the spleen reaches a peak between days 3 and 4 after TBI. The T cell population is composed of both L3T4 (helper) and Lyt-2 (suppressor) T cells, the former being the major subpopulation. Specific booster irradiation to the spleen (5 Gy twice) on days 2 and 4 after TBI greatly enhances production of donor-type chimera after transplantation of T cell-depleted allogeneic bone marrow. Similar enhancement can be achieved by splenectomy on day 3 or 4 after TBI but not if splenectomy is performed 1 day before TBI or 1 day after TBI, strengthening the hypothesis that, after lethal TBI in mice, the remaining host T cells migrate from the periphery to the spleen. These results suggest that a delayed booster irradiation to the spleen may be beneficial as an additional immunosuppressive agent in the conditioning of leukemia patients, in order to reduce the incidence of bone marrow allograft rejection.

  18. Interleukin-22 in Graft-Versus-Host Disease after Allogeneic Stem Cell Transplantation

    PubMed Central

    Lamarthée, Baptiste; Malard, Florent; Saas, Philippe; Mohty, Mohamad; Gaugler, Béatrice

    2016-01-01

    Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potential curative treatment for hematologic malignancies and non-malignant diseases. Because of the lower toxicity of reduced intensity conditioning, the number of transplants is in constant increase. However, allo-HSCT is still limited by complications, such as graft-versus-host disease (GVHD), which is associated with important morbidity and mortality. Acute GVHD is an exacerbated inflammatory response that leads to the destruction of healthy host tissues by donor immune cells. Recently, the contribution of innate immunity in GVHD triggering has been investigated by several groups and resulted in the identification of new cellular and molecular effectors involved in GVHD pathogenesis. Interleukin-22 (IL-22) is produced by both immune and adaptive cells and has both protective and inflammatory properties. Its role in GVHD processes has been investigated, and the data suggest that its effect depends on the timing, the target tissue, and the origin of the producing cells (donor/host). In this review, we discuss the role of IL-22 in allo-HSCT and GVHD. PMID:27148267

  19. Extracoporeal photopheresis treatment of acute graft-versus-host disease following allogeneic haematopoietic stem cell transplantation

    PubMed Central

    Flinn, Aisling M.; Gennery, Andrew R.

    2016-01-01

    Acute graft-versus-host disease (aGvHD) continues to be a major obstacle to allogeneic haematopoietic stem cell transplantation. Thymic damage secondary to aGvHD along with corticosteroids and other non-selective T lymphocyte-suppressive agents used in the treatment of aGvHD concurrently impair thymopoiesis and negatively impact on immunoreconstitution of the adaptive immune compartment and ultimately adversely affect clinical outcome. Extracorporeal photopheresis (ECP) is an alternative therapeutic strategy that appears to act in an immunomodulatory fashion, potentially involving regulatory T lymphocytes and dendritic cells. By promoting immune tolerance and simultaneously avoiding systemic immunosuppression, ECP could reduce aGvHD and enable a reduction in other immunosuppression, allowing thymic recovery, restoration of normal T lymphopoiesis, and complete immunoreconstitution with improved clinical outcome. Although the safety and efficacy of ECP has been demonstrated, further randomised controlled studies are needed as well as elucidation of the underlying mechanisms responsible and the effect of ECP on thymic recovery. PMID:27408705

  20. MicroRNAs as biomarkers for graft-versus-host disease following allogeneic stem cell transplantation.

    PubMed

    Tomuleasa, Ciprian; Fuji, Shigeo; Cucuianu, Andrei; Kapp, Markus; Pileczki, Valentina; Petrushev, Bobe; Selicean, Sonia; Tanase, Alina; Dima, Delia; Berindan-Neagoe, Ioana; Irimie, Alexandru; Einsele, Hermann

    2015-07-01

    Allogeneic hematopoietic stem cell transplantation (HCT) is a well-established treatment for many malignant and non-malignant hematological disorders. As frequent complication in up to 50 % of all patients, graft-versus-host disease (GVHD) is still the main cause for morbidity and non-relapse mortality. Diagnosis of GVHD is usually done clinically, even though confirmation by pathology is often used to support the clinical findings. Effective treatment requires intensified immunosuppression as early as possible. Although several promising biomarkers have been proposed for an early diagnosis, no internationally recognized consensus has yet been established. Here, microRNAs (miRs) represent an interesting tool since miRs have been recently reported to be an important regulator of various cells, including immune cells such as T cells. Therefore, we could assume that miRs play a key role in the pathogenesis of acute GVHD, and their detection might be an interesting possibility in the early diagnosis and monitoring of acute GVHD. Recent studies additionally demonstrated the implication of miRs in the pathogenesis of acute GVHD. In this review, we aim to summarize the previous reports of miRs, focusing on the pathogenesis of acute GVHD and possible implications in diagnostic approaches. PMID:25900787

  1. Allogeneic Bone Marrow Transplantation in Patients With Primary Immunodeficiencies

    ClinicalTrials.gov

    2009-10-14

    Immunologic Deficiency Syndromes; Chediak-Higashi Syndrome; Common Variable Immunodeficiency; Graft Versus Host Disease; X-Linked Lymphoproliferative Syndrome; Familial Erythrophagocytic Lymphohistiocytosis; Hemophagocytic Lymphohistiocytosis; X-linked Agammaglobulinemia; Wiskott-Aldrich Syndrome; Chronic Granulomatous Disease; X-linked Hyper IgM Syndrome; Severe Combined Immunodeficiency; Leukocyte Adhesion Deficiency Syndrome; Virus-Associated Hemophagocytic Syndrome

  2. Bone graft substitutes for spine fusion: A brief review

    PubMed Central

    Gupta, Ashim; Kukkar, Nitin; Sharif, Kevin; Main, Benjamin J; Albers, Christine E; El-Amin III, Saadiq F

    2015-01-01

    Bone graft substitutes are widely used in the field of orthopedics and are extensively used to promote vertebral fusion. Fusion is the most common technique in spine surgery and is used to treat morbidities and relieve discomfort. Allograft and autograft bone substitutes are currently the most commonly used bone grafts to promote fusion. These approaches pose limitations and present complications to the patient. Numerous alternative bone graft substitutes are on the market or have been developed and proposed for application. These options have attempted to promote spine fusion by enhancing osteogenic properties. In this review, we reviewed biology of spine fusion and the current advances in biomedical materials and biological strategies for application in surgical spine fusion. Our findings illustrate that, while many bone graft substitutes perform well as bone graft extenders, only osteoinductive proteins (recombinant bone morphogenetic proteins-2 and osteogenic protein-1) provide evidence for use as both bone enhancers and bone substitutes for specific types of spinal fusion. Tissue engineered hydrogels, synthetic polymer composites and viral based gene therapy also holds the potential to be used for spine fusion in future, though warrants further investigation to be used in clinical practice. PMID:26191491

  3. Bone graft substitutes for spine fusion: A brief review.

    PubMed

    Gupta, Ashim; Kukkar, Nitin; Sharif, Kevin; Main, Benjamin J; Albers, Christine E; El-Amin Iii, Saadiq F

    2015-07-18

    Bone graft substitutes are widely used in the field of orthopedics and are extensively used to promote vertebral fusion. Fusion is the most common technique in spine surgery and is used to treat morbidities and relieve discomfort. Allograft and autograft bone substitutes are currently the most commonly used bone grafts to promote fusion. These approaches pose limitations and present complications to the patient. Numerous alternative bone graft substitutes are on the market or have been developed and proposed for application. These options have attempted to promote spine fusion by enhancing osteogenic properties. In this review, we reviewed biology of spine fusion and the current advances in biomedical materials and biological strategies for application in surgical spine fusion. Our findings illustrate that, while many bone graft substitutes perform well as bone graft extenders, only osteoinductive proteins (recombinant bone morphogenetic proteins-2 and osteogenic protein-1) provide evidence for use as both bone enhancers and bone substitutes for specific types of spinal fusion. Tissue engineered hydrogels, synthetic polymer composites and viral based gene therapy also holds the potential to be used for spine fusion in future, though warrants further investigation to be used in clinical practice. PMID:26191491

  4. A comparison between regimens containing chemotherapy alone (busulfan and cyclophosphamide) and chemotherapy (V. RAPID) plus total body irradiation on marrow engraftment following allogeneic bone marrow transplantation.

    PubMed

    Reynolds, M; McCann, S R

    1989-10-01

    The effect of two conditioning regimens given prior to allogeneic bone marrow transplantation (BMT) on the kinetics of engraftment were compared. 5 patients received busulfan and cyclophosphamide: 7 patients received daunorubicin, vincristine, cytosine arabinoside, methylprednisone and VM-26 plus total body irradiation (TBI). Bone marrow progenitors (BFU-E, CFU-E, CFU-GM, CFU-F) were assayed up to 3 months post-BMT. All progenitors were severely depressed in spite of peripheral blood recovery. There was no stromal recovery in any adult patient post-BMT. There was no significant difference in time to engraftment, or colony forming units, or between patients conditioned with chemotherapy alone or chemotherapy plus TBI. We were unable to detect effects of graft-versus-host disease or cytomegalic viral infection on bone marrow progenitors or peripheral blood recovery in this study. PMID:2684682

  5. Bioreactor Cultivation of Anatomically Shaped Human Bone Grafts

    PubMed Central

    Temple, Joshua P.; Yeager, Keith; Bhumiratana, Sarindr; Vunjak-Novakovic, Gordana; Grayson, Warren L.

    2015-01-01

    In this chapter, we describe a method for engineering bone grafts in vitro with the specific geometry of the temporomandibular joint (TMJ) condyle. The anatomical geometry of the bone grafts was segmented from computed tomography (CT) scans, converted to G-code, and used to machine decellularized trabecular bone scaffolds into the identical shape of the condyle. These scaffolds were seeded with human bone marrow-derived mesenchymal stem cells (MSCs) using spinner flasks and cultivated for up to 5 weeks in vitro using a custom-designed perfusion bioreactor system. The flow patterns through the complex geometry were modeled using the FloWorks module of SolidWorks to optimize bioreactor design. The perfused scaffolds exhibited significantly higher cellular content, better matrix production, and increased bone mineral deposition relative to non-perfused (static) controls after 5 weeks of in vitro cultivation. This technology is broadly applicable for creating patient-specific bone grafts of varying shapes and sizes. PMID:24014312

  6. Eradication of Epstein-Barr virus by allogeneic bone marrow transplantation: implications for sites of viral latency.

    PubMed Central

    Gratama, J W; Oosterveer, M A; Zwaan, F E; Lepoutre, J; Klein, G; Ernberg, I

    1988-01-01

    Wild-type strains of Epstein-Barr virus (EBV) can be distinguished on the basis of variations in the molecular weight of virus-encoded, growth transformation-associated proteins. This approach was used to study the persistence of EBV in two seropositive recipients of allogeneic bone marrow transplants. The first patient received marrow from her EBV-seronegative brother, became EBV seronegative after grafting, and remained so for greater than 1200 days. Subsequently, she became infected with a new EBV strain that differed from her pretransplant strain but was indistinguishable from the virus isolated from her husband. The second patient received marrow from his EBV-seropositive brother. This patient showed only a transient decrease in IgG antibodies to EBV capsid antigen. His pretransplant strain differed from the virus of his donor. On days 252 and 915 after transplantation, lymphoblastoid cell lines were grown from the peripheral blood of the patient and were found to carry exclusively the virus of the donor. These results suggest that the latently EBV-infected host cells reside in a cellular compartment that can be destroyed by graft-versus-host reactivity, irradiation, or cytotoxic drugs. Hemopoietic tissue is the most likely candidate. Images PMID:2847171

  7. Calcium carbonate powder containing gentamicin for mixing with bone grafts.

    PubMed

    Coraça-Huber, Débora; Hausdorfer, Johann; Fille, Manfred; Nogler, Michael; Kühn, Klaus-Dieter

    2014-08-01

    Bone grafts are used for reconstructing bone defects caused by implant-associated complications, trauma, and tumors. Surgery with bone allografts is complex and time consuming; therefore, it is prone to a higher infection rate (2.0%-2.5%). In the case of site infection, systemically administered antibiotics cannot reach the infected bone graft. This study evaluated the use of resorbable bone graft substitute powder (HERAFILL; Heraeus Medical GmbH, Wehrheim, Germany) as a bone void-filling material as well as an antibiotic carrier for mixing with bone grafts. The antibiotic activity of the bone chips mixed with HERAFILL powder was measured by drug release tests and bacterial susceptibility with Bacillus subtilis, Staphylococcus epidermidis, and Staphylococcus aureus. HERAFILL powder was added to the bone chips (bone chips/HERAFILL; w/w = 1:1), mixed with a spatula, and vortexed for 1 minute. Gentamicin base release was evaluated in phosphate-buffered saline for up to 7 days using B subtilis bioassay. Antimicrobial efficacy was tested with S aureus and S epidermidis. The average amount of gentamicin base released from bone chips mixed with HERAFILL at 0 to 12 hours was 99.66 mg/mL. On day 7, the gentamicin base released 0.42 mg/mL. The elution released from bone chips mixed with HERAFILL promoted the formation of a zone of inhibition on S epidermidis and S aureus plates. This study confirmed the capacity of bone grafts to act as antibiotic carriers once mixed with HERAFILL powder. Bone chips mixed with HERAFILL showed efficacy against S aureus and S epidermidis. PMID:25102500

  8. Cytogenetic conversion following allogeneic bone marrow transplantation for advanced chronic myelogenous leukemia

    SciTech Connect

    McGlave, P.B.; Miller, W.J.; Hurd, D.D.; Arthur, D.C.; Kim, T.

    1981-11-01

    We performed a pilot study to test the effectiveness of allogeneic bone marrow transplantation in the treatment of chronic myelogenous leukemia. Five patients in the advanced stages of chronic myelogenous leukemia (four in blast crisis, one in accelerated phase) with abnormal chromosomes underwent matched-sibling allogeneic bone marrow transplantation after preparation with busulfan, vincristine, cyclophosphamide, and fractionated total body irradiation. Engraftment and conversion to normal chromosome patterns after transplantation occurred in all five patients. None of the patients reverted to an abnormal chromosome pattern or demonstrated clinical or hematologic evidence of recurrent disease during the course of this study; however, longest survival from transplant was 248 days. Allogeneic bone marrow transplantation can eradicate the abnormal clone even in far advanced chronic myelogenous leukemia and can provide normal hematopoiesis. We suggest that clinical complications of chemotherapeutic toxicity and infection were responsible for the short survival in this group of patients, and that these complications could be decreased by performing transplantation in the chronic phase or early accelerated phase of the disease.

  9. Peripheral blood stem cell graft compared to bone marrow after reduced intensity conditioning regimens for acute leukemia: a report from the ALWP of the EBMT.

    PubMed

    Savani, Bipin N; Labopin, Myriam; Blaise, Didier; Niederwieser, Dietger; Ciceri, Fabio; Ganser, Arnold; Arnold, Renate; Afanasyev, Boris; Vigouroux, Stephane; Milpied, Noel; Hallek, Michael; Cornelissen, Jan J; Schwerdtfeger, Rainer; Polge, Emmanuelle; Baron, Frédéric; Esteve, Jordi; Gorin, Norbert C; Schmid, Christoph; Giebel, Sebastian; Mohty, Mohamad; Nagler, Arnon

    2016-02-01

    Increasing numbers of patients are receiving reduced intensity conditioning regimen allogeneic hematopoietic stem cell transplantation. We hypothesized that the use of bone marrow graft might decrease the risk of graft-versus-host disease compared to peripheral blood after reduced intensity conditioning regimens without compromising graft-versus-leukemia effects. Patients who underwent reduced intensity conditioning regimen allogeneic hematopoietic stem cell transplantation from 2000 to 2012 for acute leukemia, and who were reported to the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation were included in the study. Eight hundred and thirty-seven patients receiving bone marrow grafts were compared with 9011 peripheral blood transplant recipients after reduced intensity conditioning regimen. Median follow up of surviving patients was 27 months. Cumulative incidence of engraftment (neutrophil ≥0.5×10(9)/L at day 60) was lower in bone marrow recipients: 88% versus 95% (P<0.0001). Grade II to IV acute graft-versus-host disease was lower in bone marrow recipients: 19% versus 24% for peripheral blood (P=0.005). In multivariate analysis, after adjusting for differences between both groups, overall survival [Hazard Ratio (HR) 0.90; P=0.05] and leukemia-free survival (HR 0.88; P=0.01) were higher in patients transplanted with peripheral blood compared to bone marrow grafts. Furthermore, peripheral blood graft was also associated with decreased risk of relapse (HR 0.78; P=0.0001). There was no significant difference in non-relapse mortality between recipients of bone marrow and peripheral blood grafts, and chronic graft-versus-host disease was significantly higher after peripheral blood grafts (HR 1.38; P<0.0001). Despite the limitation of a retrospective registry-based study, we found that peripheral blood grafts after reduced intensity conditioning regimens had better overall and leukemia-free survival than bone marrow grafts

  10. Peripheral blood stem cell graft compared to bone marrow after reduced intensity conditioning regimens for acute leukemia: a report from the ALWP of the EBMT

    PubMed Central

    Savani, Bipin N.; Labopin, Myriam; Blaise, Didier; Niederwieser, Dietger; Ciceri, Fabio; Ganser, Arnold; Arnold, Renate; Afanasyev, Boris; Vigouroux, Stephane; Milpied, Noel; Hallek, Michael; Cornelissen, Jan J.; Schwerdtfeger, Rainer; Polge, Emmanuelle; Baron, Frédéric; Esteve, Jordi; Gorin, Norbert C.; Schmid, Christoph; Giebel, Sebastian; Mohty, Mohamad; Nagler, Arnon

    2016-01-01

    Increasing numbers of patients are receiving reduced intensity conditioning regimen allogeneic hematopoietic stem cell transplantation. We hypothesized that the use of bone marrow graft might decrease the risk of graft-versus-host disease compared to peripheral blood after reduced intensity conditioning regimens without compromising graft-versus-leukemia effects. Patients who underwent reduced intensity conditioning regimen allogeneic hematopoietic stem cell transplantation from 2000 to 2012 for acute leukemia, and who were reported to the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation were included in the study. Eight hundred and thirty-seven patients receiving bone marrow grafts were compared with 9011 peripheral blood transplant recipients after reduced intensity conditioning regimen. Median follow up of surviving patients was 27 months. Cumulative incidence of engraftment (neutrophil ≥0.5×109/L at day 60) was lower in bone marrow recipients: 88% versus 95% (P<0.0001). Grade II to IV acute graft-versus-host disease was lower in bone marrow recipients: 19% versus 24% for peripheral blood (P=0.005). In multivariate analysis, after adjusting for differences between both groups, overall survival [Hazard Ratio (HR) 0.90; P=0.05] and leukemia-free survival (HR 0.88; P=0.01) were higher in patients transplanted with peripheral blood compared to bone marrow grafts. Furthermore, peripheral blood graft was also associated with decreased risk of relapse (HR 0.78; P=0.0001). There was no significant difference in non-relapse mortality between recipients of bone marrow and peripheral blood grafts, and chronic graft-versus-host disease was significantly higher after peripheral blood grafts (HR 1.38; P<0.0001). Despite the limitation of a retrospective registry-based study, we found that peripheral blood grafts after reduced intensity conditioning regimens had better overall and leukemia-free survival than bone marrow grafts. However

  11. Secondary Alveolar Bone Grafting (CLEFTSiS) 2007-2010.

    PubMed

    Paterson, Michael; Rae, Jennifer; Paterson, Paul; Gilgrass, Toby; Devlin, Mark; McIntyre, Grant

    2016-03-01

    Objective To determine whether alveolar bone graft outcomes for unilateral and bilateral cleft lip and palate patients have continued to improve since the reorganization of cleft services in Scotland in 2000. Design Retrospective analysis of postoperative anterior occlusal radiographs. Patients and Participants Eighty-one of 106 patients who were eligible for alveolar bone grafting between 2007 and 2010 had suitable postoperative radiographs available. Interventions Twenty-seven percent of the patients (n = 22) had presurgical orthodontic intervention. All patients underwent alveolar bone grafting with bone harvested from the iliac crest. Main Outcome Measures The Kindelan bone-fill index was used to evaluate success. Weighted kappa statistics were used to assess intra- and interobserver reproducibility. A comparison was made with results from 2000 to 2004 to assess any improvement. Chi-square tests (or Fisher exact test) were used to determine whether outcomes differed depending on the laterality of the cleft, use of presurgical expansion, or age at bone grafting. Results Interobserver scoring agreement was good (weighted kappa = .383). Intraobserver reproducibility was greater (weighted kappas of .835 and .620). Success was achieved in 99% of bone grafts, compared with 76% in the period from 2000 to 2004 (P < .001). There was no statistically significant relationship between the laterality of the cleft (P = 1.000), use of presurgical expansion (P = 1.000), or age at time of bone grafting and outcome (P = .259). Conclusion Scottish secondary alveolar bone graft outcomes improved during 2007 to 2010 in comparison to the 2000 to 2004 results. PMID:26914161

  12. Induction of allogeneic unresponsiveness by supralethal irradiation and bone marrow reconstitution. [Dogs

    SciTech Connect

    Rapaport, F.T.; Bachvaroff, R.J.; Akiyama, N.; Sato, T.

    1980-09-01

    Supralethally irradiated dogs were reconstituted wth their own stored bone marrow and were challenged at various time intervals with a kidney allograft. The data suggest that transplanted bone marrow cells may participate directly in the events leading to allogenic unresponsiveness. The time interval between marrow cell replacement and kidney allotransplantation required for optimal results suggest that at least one cycle of cell turnover by the replaced stem cells is needed in order to produce unresponsiveness. Host irradiation and reconstitution with stored autologous marrow may be useful in the treatment of certain forms of cancer.

  13. Hydroxyapatite crystals as a bone graft substitute in benign lytic lesions of bone

    PubMed Central

    Gupta, Anil Kumar; Kumar, Praganesh; Keshav, Kumar; Singh, Anant

    2015-01-01

    Background: Bone grafts are required to fill a cavity created after curettage of benign lytic lesions of the bone. To avoid the problems associated at donor site with autologous bone graft, we require allograft or bone graft substitutes. We evaluated the healing of lytic lesions after hydroxyapatite (HA) grafting by serial radiographs. Materials and Methods: Forty cases of benign lytic lesions of bone were managed by simple curettage and grafting using HA blocks. Commercially available HA of bovine origin (Surgiwear Ltd., Shahjahanpur, India) was used for this purpose. Mean duration of followup was 34.8 months (range 12–84 months). Mean patient age was 19.05 years (range 3–55 years). Radiological staging of graft incorporation was done as per criteria of Irwin et al. 2001. Results: In our series, two cases were in stage I. A total of 11 cases were in stage II and 27 were in stage III. Graft incorporation was radiologically complete by 15 months. Clinical recovery was observed before radiological healing. The average time taken to return to preoperative function was 3 months. Recurrence was observed in giant cell tumor (n = 3) and chondromyxoid fibroma (n = 1). There was no incidence of graft rejection, collapse, growth plate disturbances or antigenic response. Conclusions: We conclude that calcium HA is biologically acceptable bone graft substitute in the management of benign lytic lesions of bone. PMID:26806973

  14. The Use of Bone Graft Substitute in Hand Surgery

    PubMed Central

    Liodaki, Eirini; Kraemer, Robert; Mailaender, Peter; Stang, Felix

    2016-01-01

    Abstract Bone defects are a very common problem in hand surgery, occurring in bone tumor surgery, in complicated fractures, and in wrist surgery. Bone substitutes may be used instead of autologous bone graft to avoid donor site morbidity. In this article, we will review our experience with the use of Cerament bone void filler (Bonesupport, Lund, Sweden) in elective and trauma hand surgery. A prospective clinical study was conducted with 16 patients treated with this bone graft substitute in our department over a period of 3.5 years. Twelve patients (2 female, 10 male; with an average age of 42.42 years) with monostoic enchondroma of the phalanges were treated and 4 patients (1 female, 3 male; with an average age of 55.25 years) with complicated metacarpal fractures with bone defect. Data such as postoperative course with rating of pain, postoperative complications, functional outcome assessment at 1, 2, 3, 6 months, time to complete remodeling were registered. Postoperative redness and swelling after bone graft substitute use was noticed in 7 patients with enchondroma surgery due to the thin soft-tissue envelope of the fingers. Excellent total active motion of the involved digit was noticed in 10 of 12 enchondroma patients and in all 4 fracture patients at 2-month follow-up. In summary, satisfying results are described, making the use of injectable bone graft substitute in the surgical treatment of enchondromas, as well as in trauma hand surgery a good choice. PMID:27310946

  15. The Palatal Bone Block Graft for Onlay Grafting Combined with Maxillary Implant Placement: A Case Series.

    PubMed

    Gluckman, Howard; Du Toit, Jonathan; Salama, Maurice

    2016-01-01

    The aim of this study was to introduce an intraoral bone block harvesting technique--the palatal bone block graft (PBBG)--as an alternative harvest site for autogenous bone blocks. The PBBG technique was used to onlay graft esthetic zone defects simultaneous to implant placement in five patients. Measurable objectives were used to evaluate outcomes, and treatment was reassessed at up to 6 years. Defects of the maxilla were successfully grafted with PBBG in all five cases, and tissues remained stable at 1- and 6-year follow-ups. Harvesting an autogenous bone block from the palate is an advantageous, predictable, and reproducible method for augmenting buccofacial defects at implant placement, and may be considered as an alternative to conventional intraoral bone block donor sites when treating the maxilla. PMID:27333009

  16. Bone Density and Structure in Long-Term Survivors of Pediatric Allogeneic Hematopoietic Stem Cell Transplantation

    PubMed Central

    Mostoufi-Moab, Sogol; Ginsberg, Jill P.; Bunin, Nancy; Zemel, Babette; Shults, Justine; Leonard, Mary B.

    2015-01-01

    Children requiring allogeneic hematopoietic stem cell transplantation (alloHSCT) have multiple risk factors for impaired bone accrual. The impact of alloHSCT on volumetric bone mineral density (vBMD) and cortical structure has not been addressed. Tibia peripheral quantitative computed tomography (pQCT) scans were obtained in 55 alloHSCT recipients, ages 5–26 years, a median of 7 (range 3–16) years after alloHSCT. pQCT outcomes were converted to sex- and race- specific Z-scores relative to age based on reference data in >700 concurrent healthy participants. Cortical section modulus (Zp; a summary measure of cortical bone structure and strength), muscle and fat area Z-scores were further adjusted for tibia length for age Z-scores. AlloHSCT survivors had lower height Z-scores (−1.21 ± 1.25 vs. 0.23 ± 0.92; p<0.001), vs. reference participants; BMI Z-scores did not differ. AlloHSCT survivors had lower trabecular vBMD [−1.05 (95% CI −1.33, −0.78), p<0.001], cortical Zp [−0.63 (−0.91, −0.35), p<0.001], and muscle [−1.01 (−1.30, −0.72), p<0.001] Z-scores and greater fat [0.82 (0.54,1.11), p<0.001] Z-scores, vs. reference participants. Adjustment for muscle deficits eliminated Zp deficits in alloHSCT. Total body irradiation (TBI) was associated with lower trabecular vBMD (−1.30 ± 1.40 vs. −0.49 ± 0.88; p=0.01) and muscle (−1.34 ± 1.42 vs. −0.34 ± 0.87; p<0.01) Z-scores. Growth hormone deficiency (GHD) was associated with lower Zp Z-scores (−1.64 ± 2.47 vs. −0.28 ± 1.24; p=0.05); however, muscle differences were not significant (−1.69 ± 1.84 vs. −0.78 ± 1.01; p=0.09). History of graft vs. host disease was not associated with pQCT outcomes. In summary, alloHSCT was associated with significant deficits in trabecular vBMD, cortical geometry, and muscle area years after transplantation. TBI and GHD were significant risk factors for musculoskeletal deficits. Future studies are needed to determine the metabolic and fracture

  17. Effects of T cell depletion in radiation bone marrow chimeras. I. Evidence for a donor cell population which increases allogeneic chimerism but which lacks the potential to produce GVHD

    SciTech Connect

    Sykes, M.; Sheard, M.; Sachs, D.H.

    1988-10-01

    The opposing problems of graft-vs-host disease (GVHD) and failure of alloengraftment present major obstacles to the application of bone marrow transplantation (BMT) across complete MHC barriers. The addition of syngeneic T-cell-depleted (TCD) bone marrow (BM) to untreated fully allogeneic marrow inocula in lethally irradiated mice has been previously shown to provide protection from GVHD. We have used this model to study the effects of allogeneic T cells on levels of chimerism in recipients of mixed marrow inocula. The results indicate that T cells in allogeneic BM inocula eliminate both coadministered recipient-strain and radioresistant host hematopoietic elements to produce complete allogeneic chimerism without clinical GVHD. To determine the role of GVH reactivity in this phenomenon, we performed similar studies in an F1 into parent combination, in which the genetic potential for GVHD is lacking. The presence of T cells in F1 marrow inocula led to predominant repopulation with F1 lymphocytes in such chimeras, even when coadministered with TCD-recipient-strain BM. These results imply that the ability of allogeneic BM cells removed by T cell depletion to increase levels of allochimerism may be mediated by a population which is distinct from that which produces GVHD. These results may have implications for clinical BM transplantation.

  18. Ocular Graft Versus Host Disease Following Allogeneic Stem Cell Transplantation: A Review of Current Knowledge and Recommendations

    PubMed Central

    Nassiri, Nariman; Eslani, Medi; Panahi, Nekoo; Mehravaran, Shiva; Ziaei, Alireza; Djalilian, Ali R.

    2013-01-01

    Graft versus host disease (GVHD) is a common complication of allogeneic stem cell transplantation (allo-SCT). Ocular GVHD develops in approximately 40-60% of patients following allo-SCT and its most common clinical manifestations include keratoconjunctivitis sicca and cicatricial conjunctivitis. Ocular GVHD may lead to severe ocular surface disease, which can significantly diminish quality of life and restrict daily activities. It is thus important to monitor the condition closely since with timely diagnosis, irreversible damage can be avoided. The current review will focus on updated information regarding ocular GVHD. PMID:24653823

  19. Tissue-Engineered Autologous Grafts for Facial Bone Reconstruction

    PubMed Central

    Bhumiratana, Sarindr; Bernhard, Jonathan C.; Alfi, David M.; Yeager, Keith; Eton, Ryan E.; Bova, Jonathan; Shah, Forum; Gimble, Jeffrey M.; Lopez, Mandi J.; Eisig, Sidney B.; Vunjak-Novakovic, Gordana

    2016-01-01

    Facial deformities require precise reconstruction of the appearance and function of the original tissue. The current standard of care—the use of bone harvested from another region in the body—has major limitations, including pain and comorbidities associated with surgery. We have engineered one of the most geometrically complex facial bones by using autologous stromal/stem cells, without bone morphogenic proteins, using native bovine bone matrix and a perfusion bioreactor for the growth and transport of living grafts. The ramus-condyle unit (RCU), the most eminent load-bearing bone in the skull, was reconstructed using an image-guided personalized approach in skeletally mature Yucatan minipigs (human-scale preclinical model). We used clinically approved decellularized bovine trabecular bone as a scaffolding material, and crafted it into an anatomically correct shape using image-guided micromilling, to fit the defect. Autologous adipose-derived stromal/stem cells were seeded into the scaffold and cultured in perfusion for 3 weeks in a specialized bioreactor to form immature bone tissue. Six months after implantation, the engineered grafts maintained their anatomical structure, integrated with native tissues, and generated greater volume of new bone and greater vascular infiltration than either non-seeded anatomical scaffolds or untreated defects. This translational study demonstrates feasibility of facial bone reconstruction using autologous, anatomically shaped, living grafts formed in vitro, and presents a platform for personalized bone tissue engineering. PMID:27306665

  20. Tissue-engineered autologous grafts for facial bone reconstruction.

    PubMed

    Bhumiratana, Sarindr; Bernhard, Jonathan C; Alfi, David M; Yeager, Keith; Eton, Ryan E; Bova, Jonathan; Shah, Forum; Gimble, Jeffrey M; Lopez, Mandi J; Eisig, Sidney B; Vunjak-Novakovic, Gordana

    2016-06-15

    Facial deformities require precise reconstruction of the appearance and function of the original tissue. The current standard of care-the use of bone harvested from another region in the body-has major limitations, including pain and comorbidities associated with surgery. We have engineered one of the most geometrically complex facial bones by using autologous stromal/stem cells, native bovine bone matrix, and a perfusion bioreactor for the growth and transport of living grafts, without bone morphogenetic proteins. The ramus-condyle unit, the most eminent load-bearing bone in the skull, was reconstructed using an image-guided personalized approach in skeletally mature Yucatán minipigs (human-scale preclinical model). We used clinically approved decellularized bovine trabecular bone as a scaffolding material and crafted it into an anatomically correct shape using image-guided micromilling to fit the defect. Autologous adipose-derived stromal/stem cells were seeded into the scaffold and cultured in perfusion for 3 weeks in a specialized bioreactor to form immature bone tissue. Six months after implantation, the engineered grafts maintained their anatomical structure, integrated with native tissues, and generated greater volume of new bone and greater vascular infiltration than either nonseeded anatomical scaffolds or untreated defects. This translational study demonstrates feasibility of facial bone reconstruction using autologous, anatomically shaped, living grafts formed in vitro, and presents a platform for personalized bone tissue engineering. PMID:27306665

  1. Microvascular anastomoses for bone grafts in the treatment of massive defects in bone.

    PubMed

    Weiland, A J; Daniel, R K

    1979-01-01

    Six patients with large defects in bone are described in whom we performed microvascular anastomoses of grafted fibular vessels (arteries and veins) to vessels in the recipient site. Two other patients, with massive loss of bone and skin, were treated by grafting of osteocutaneous composites also using microvascular anastomoses. All but one defect healed successfully. There is a wide potential for applications of these two techniques in the treatment of large segmental bone defects secondary to trauma or following tumor resection. PMID:365868

  2. High-dose, post-transplantation cyclophosphamide to promote graft-host tolerance after allogeneic hematopoietic stem cell transplantation

    PubMed Central

    Luznik, Leo

    2010-01-01

    Graft-versus-host disease, or GVHD, is a major complication of allogeneic hematopoietic stem cell transplantation (alloHSCT) for the treatment of hematologic malignancies. Here, we describe a novel method for preventing GVHD after alloHSCT using high-dose, post-transplantation cyclophosphamide (Cy). Post-transplantation Cy promotes tolerance in alloreactive host and donor T cells, leading to suppression of both graft rejection and GVHD after alloHSCT. High-dose, post-transplantation Cy facilitates partially HLA-mismatched HSCT without severe GVHD and is effective as sole prophylaxis of GVHD after HLA-matched alloHSCT. By reducing the morbidity and mortality of alloHSCT, post-transplantation Cy may expand the applications of this therapy to the treatment of autoimmune diseases and non-malignant hematologic disorders such as sickle cell disease. PMID:20066512

  3. The current status of free vascularized bone grafts.

    PubMed

    Taylor, G I

    1983-01-01

    In the last decade, free vascularized bone transfer has become an established technique, with success rates above 90 per cent reported in most series. These operations have special application for those situations in which the bone defect is large, the recipient bed is poorly vascularized, and there is an associated soft tissue deficiency. The donor sites now include the fibula, iliac crest, rib, metatarsal, radius, and scapula. Because this is a rapidly expanding field of surgical endeavor, much of the work is unpublished and information in some instances has been obtained necessarily from recent clinical meetings and by personal communication with surgeons. Our experience of 41 bone transfers, using the fibula and the iliac crest as the donor grafts, over a 9-year period has been presented. In general, the fibula is recommended for the reconstruction of a long bone. In the lower extremity it should be placed within the medullary cavity of the recipient bone ends so as to be sited in the line of the weight-bearing stress. The iliac osteocutaneous graft is ideal for reconstructing the mandible and other curved bones but can be used also for shorter defects of the tibia. With appropriate osteotomies the curvature of this bone can be increased or straightened to satisfy the requirements of the recipient site. Stress fracture of a long graft is not uncommon in the lower extremity, especially in adults. Nevertheless, this is followed usually by rapid formation of callus at the fracture site and hypertrophy of the bone. The use of angiography, replica bone models, and trial operations on cadavers is recommended in planning. Operative refinements include a simpler dissection of the fibula with a thinner sleeve of muscle; shaping the iliac bone graft while it is still attached at the donor site; and the suture of vein grafts to the bone graft on a side table when the pedicle is too short. Finally, it must be remembered that these are still relatively sophisticated

  4. Bone graft complications: what can we do to prevent them?

    NASA Astrophysics Data System (ADS)

    Tandon, Rahul; Herford, Alan S.

    2014-03-01

    Introduction: Bone grafts are commonly used in oral and maxillofacial surgery, helping to restore missing bone structure and provide osseous support. In spite of their reported success, complications can and do arise. Examples include loosening and resorption of the graft, infection, and complete loss of the graft. These complications can potentially lead to larger defects, necessitating additional procedures to correct the problem. This not only causes great discomfort to the patient, but also drains considerable time and resources away from the clinician. Thus, improvements on identifying ways to identify and prevent these complications are constantly being sought. We have performed a literature review and identified several areas in the field of optics that could potentially help solve our problem. Optical Techniques: Raman spectroscopy has been shown to provide a transcutaneous measurement of bone mineral and matrix Raman bands. This could potentially provide surgeons with the ability to more accurately assess bone graft osseointegration. In-vivo near-infrared optical imaging could potentially provide accurate diagnosis of pathologic lesions such as osteosarcoma. Contrast-enhanced ultrasound could be used to detect vascular disturbances and other information related to the transplantation of osseous components. Conclusion: Bone graft complications can be one of the most devastating consequences of osseous surgery. As surgeons, we are constantly searching for ways to identify them earlier and prevent them. We hope that by presenting areas that could be used, we can gain a better insight to ways in which both fields can benefit.

  5. Ferritin as an early marker of graft rejection after allogeneic hematopoietic stem cell transplantation in pediatric patients.

    PubMed

    Döring, Michaela; Cabanillas Stanchi, Karin Melanie; Feucht, Judith; Queudeville, Manon; Teltschik, Heiko-Manuel; Lang, Peter; Feuchtinger, Tobias; Handgretinger, Rupert; Müller, Ingo

    2016-01-01

    Diagnosis of adverse events following hematopoietic stem cell transplantation (HSCT) is mainly assigned to clinical symptoms or biopsies and thus rather unspecific and/or invasive. Studies indicate a distinct role of serum ferritin in HSCT and its correlation with adverse events such as graft-versus-host disease (GvHD), veno-occlusive disease (VOD), or infections. However, published data on the relevance of ferritin as a prognostic marker for post-transplant adverse events is rare, especially in pediatric patients. The present study analyzes ferritin plasma concentrations of 138 pediatric patients after HSCT between 2007 and 2010 including the control group (n = 21). Given the initial results regarding ferritin as a significant predictor for acute graft rejection after allogeneic HSCT in 9 of the 138 pediatric patients, serum ferritin of all pediatric patients (n = 27) who experienced graft rejection between 2007 and 2014 was analyzed. In addition, laboratory parameters including C-reactive protein (CRP), lactate dehydrogenase (LDH), fibrinogen, and D-dimer as possible differentiation markers for graft rejection were determined. In 24 (88.9 %) of the 27 pediatric patients with graft rejection, a significant increase of ferritin levels was observed 1 to 7 days prior to (P < 0.0001) and at the time of graft rejection (P < 0.0001). Moreover, there was an increase of D-dimer, CRP, LDH, and fibrinogen 1-7 days before graft rejection. Ferritin increased significantly at time of VOD (P = 0.0067), at time of intestinal (P < 0.0001) and skin GvHD (P < 0.0001), and at time of sepsis (P = 0.0005) and bacteremia (P = 0.0029). Ferritin might serve as a readily available identification marker for differentiation and identification of adverse events after HSCT in combination with other laboratory markers. PMID:26611853

  6. New bone formation by allogeneic mesenchymal stem cell transplantation in a patient with perinatal hypophosphatasia.

    PubMed

    Tadokoro, Mika; Kanai, Rie; Taketani, Takeshi; Uchio, Yuji; Yamaguchi, Seiji; Ohgushi, Hajime

    2009-06-01

    Mesenchymal stem cells (MSCs) can show osteogenic differentiation capability when implanted in vivo, as well as cultured in vitro; therefore we attempted to use allogeneic MSCs for an 8-month-old patient with hypophosphatasia. MSCs were obtained by culture expansion of fresh marrow from the patient's father. Some of the MSCs were further cultured under osteogenic conditions on a culture dish or porous hydroxyapatite ceramics, resulting in cultured osteoblasts and osteogenic constructs, respectively. The MSCs and osteoblasts were injected into the patient, and the constructs were implanted locally. After traditional bone marrow transplantation, the MSCs, osteoblasts, and osteogenic constructs were used for treatment and to improve the patient's respiratory condition and skeletal abnormality. The condition worsened again, and an MSC booster shot was administered. At the same time, the construct was retrieved. The respiratory condition improved, and the retrieved construct showed de novo bone derived from both donor and patient cells. We demonstrated the importance of allogeneic MSC transplantation for hypophosphatasia and the constructs as an alternative to bone fragments that provided further osteogenic capability in the patient. PMID:19446101

  7. Four successful pregnancies in a patient with mucopolysaccharidosis type I treated by allogeneic bone marrow transplantation.

    PubMed

    Remérand, G; Merlin, E; Froissart, R; Brugnon, F; Kanold, J; Janny, L; Deméocq, F

    2009-12-01

    To date, little is known about the fertility of women suffering from mucopolysaccharidosis type I (MPS I). We report on a female patient with MPS I treated by allogeneic bone marrow transplantation (BMT) at the age of 4 years (after a conditioning regimen containing busulfan 16 mg/kg and cyclophosphamide 100 mg/kg) who had four successful pregnancies without any reproductive assistance. Clinical and biological examinations of the children were normal. On the basis of this case, we discuss the fertility counselling of female MPS I patients at the time of BMT. PMID:19280364

  8. Effects of xenogeneic, allogeneic and isogeneic thymus grafts on lymphocyte populations in peripheral lymphoid organs of the nude rat.

    PubMed

    Hougen, H P; Klausen, B; Stenvang, J P; Kraemmer, J; Rygaard, J

    1987-04-01

    In order to gain information about the effect of xenografted, allografted and isografted thymic tissue on peripheral lymphoid organs of immune-deficient rats, athymic nude LEW rats of ninth backcross-intercross were grafted with fetal calf and neonatal BDIX and LEW thymus. Adrenalectomy was also performed in some animals in order to obtain a possible enhancement of the immunological reconstitution. Both groups of isogeneic-thymus-grafted animals had more T helper cells than the nude controls. Furthermore, they had more densely populated paracortical areas in the inguinal lymph nodes and higher lymphocyte counts in the thoracic duct lymph. Finally, the inguinal lymph nodes contained germinal centres. Xenogeneic and allogeneic thymus transplants did not induce constant changes in the parameters observed compared with the untreated nudes. No clear difference was observed between the adrenalectomized and non-adrenalectomized thymic-isografted animals. We therefore conclude that of all the experimental animals examined the isografted nude rats show by far the best response and that adrenalectomy seems unnecessary for the success of neonatal isogeneic thymus grafts. We also conclude that the isogeneic-thymus-grafted nude rat is a suitable tool for immunological reconstitution studies. PMID:3496487

  9. Scalded Skin of Rat Treated by Using Fibrin Glue Combined with Allogeneic Bone Marrow Mesenchymal Stem Cells

    PubMed Central

    Yang, Yadong; Li, Ying; Fang, Guojian; Zhang, Keji

    2014-01-01

    Background It is difficult to achieve satisfactory results with the traditional treatment of large-area skin defects and deep burns. Objective To test the treatment effect of an active dressing film made of a mixture of fibrin glue and bone marrow mesenchymal stem cells (BMSCs) for repairing burn wounds on the skin of rats. Methods Two scald wounds were made on the back of each rat. A total of 30 scald wounds were randomly divided into 3 groups, with 10 wounds in each group. In the experimental treatment group, the scald wounds were covered with the fibrin glue and BMSC mixture. The wounds of the experimental control group were covered with fibrin glue only. No intervention was administered to the blank control group. Thirty days after treatment, pathological sections were cut from the scalded local tissues of all rats from the 3 groups and observed with a microscope. Results The speed of scald wound healing in the experimental treatment group was faster than the other 2 groups. In the experimental treatment group, histopathological analysis revealed that the sebaceous glands showed obviously proliferous at the edge of the new tissue and gradually extended to the deep dermal layer of the new tissue. Conclusion BMSCs may have an active role in promoting skin tissue repair and generating skin appendages. Allogeneic BMSCs mixed with fibrin glue can contribute to the quick formation of a film-like gel over the scald wounds, which might be of significance for emergency treatment and skin-grafting operations. PMID:24966626

  10. Osteostimulatory effect of bone grafts on fibroblast cultures

    PubMed Central

    Fathima, Hameed; Harish

    2015-01-01

    Objective: We analyzed the morphological changes and alkaline phosphatase (ALP) level in fibroblast, which is indicative of their functional ability when cultured in three different commercially available graft materials with osseoconductive property. Materials and Methods: Fibroblasts obtained from fifth passage were seeded within three different bone substitutes (bovine hydroxyapatite [HA] [Osseo-graft®], β-tricalciumphosphate [RTR®], bovine HA [Bio-oss®]) and incubated under standard cell culture conditions. 10 samples in each group were evaluated for cell morphology and alkaline phosphates activity using scanning electron microscopy and spectrophotometric analysis on the 7th day of culture. Results: Fibroblast cultured with RTR® showed changes in morphology and increase in ALP activity when compared to fibroblast cultured with Osseo-graft® and Bio-oss®. Conclusion: Alkaline phosphatase activity was observed in fibroblasts when cultured with three types of commercially available bone grafts. ALP activity was highest when cultured with β-tricalcium phosphate graft material indicating its better bone regenerating capacity of this graft material. PMID:26283815

  11. Osteofibrous Dysplasia managed with Extraperiosteal excision, Autologous free fibular graft and bone graft substitute

    PubMed Central

    Abraham, Vineet T; Marimuthu, Chandrasekaran; Subbaraj, Ravichandran; Rengarajan, Nandakumar

    2015-01-01

    Introduction: Osteofibrous Dysplasia is a rare benign self-limiting fibro-osseous lesion most commonly seen in the diaphysis of the tibia. Its incidence is reported to be 0.2% of all primary bone tumors. It occurs in the first two decades of life with a slight male preponderance. Surgical options include extra periosteal resection, autologous graft, limb lengthening procedures etc. There are no case reports mentioning the use of synthetic bone graft to fill the defect following extraperiosteal excision. Case Report: A 13 year old girl presented with pain and swelling of the (R) leg since 2 months following a trivial injury at school. Examination revealed a 5×3cm tender swelling on the anteromedial aspect of the middle third tibia. Radiographs and MRI, revealed an eccentric expansile lytic lesion, which was multilocular and was present at the junction of the metaphysis and diaphysis on the antero -medial aspect of tibia. The cortex had ballooned out and there was a possibility of an impending fracture. Biopsy was done which revealed osteofibrous dysplasia. We did an extraperiosteal excision of the lesion. To fill the cavity we harvested 10 cm of the contralateral fibula and since there was still space in the cavity, we packed bone graft substitute (hydroxyapatite crystals) into the defect. The surgical management of osteofibrous dysplasia is controversial. Various methods of treatment of such cases have been described in literature. The use of synthetic graft is an option in these patients as it reduces morbidity; and in our case we had good graft incorporation with this method. Conclusion: Extraperiosteal Excision of Osteofibrous dysplasia combined with autologous free fibular graft and bone graft substitute is a good surgical option to prevent recurrence and mange bone defects in this rare lesion. PMID:27299018

  12. Donor origin of circulating endothelial progenitors after allogeneic bone marrow transplantation.

    PubMed

    Ikpeazu, C; Davidson, M K; Halteman, D; Browning, P J; Brandt, S J

    2000-01-01

    Endothelial cell precursors circulate in blood and express antigens found on hematopoietic stem cells, suggesting that such precursors might be subject to transplantation. To investigate, we obtained adherence-depleted peripheral blood mononuclear cells from 3 individuals who had received a sex-mismatched allogeneic bone marrow transplant (BMT) and cultured the cells on fibronectin-coated plates with endothelial growth factors. The phenotype of the spindle-shaped cells that emerged in culture was characterized by immunofluorescent staining, and the origin of the cells was determined using a polymerase chain reaction (PCR)-based assay for polymorphic short tandem repeats (STRs). The cells manifested a number of endothelial characteristics-such as von Wlllebrand factor, CD31, and Flk-1/KDR expression; Bandeiraea simplicifolia lectin 1 binding; and acetylated low-density lipoprotein uptake-but lacked expression of certain markers of activation or differentiation, including intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and the epitope for the anti-endothelial cell antibody P1H12. For each patient and at all time points studied (ranging from 5 to 52 months after transplantation), STR-PCR analysis showed that cultured cells and nucleated blood cells came exclusively from the bone marrow donor. These results demonstrate that circulating endothelial progenitors are both transplantable and capable of long-term repopulation of human allogeneic BMT recipients. PMID:10905767

  13. [Bone gammagraphy for evaluating free vascularized bone grafts in mandibular reconstruction].

    PubMed

    Serra, J M; Paloma, V; Mesa, F; Ballesteros, A; Richter, J A

    1989-01-01

    In oncology jaw reconstruction, the probability of infection, sequestration and failure in scarring is high. For this reason, we use a vascularized free bone graft, whose direct blood flow makes it much more resistant to support the attendant properly. The use of bone scintigraphy by means of three phases acquisition technique is very effective to evaluate the viability of these vascularized grafts during the first days after surgery, in order to adjust the attendant treatments and to prevent the possible complications. PMID:2641826

  14. Morsellized bone grafting compensates for femoral bone loss in revision total knee arthroplasty. An experimental study.

    PubMed

    van Loon, C J; de Waal Malefijt, M C; Verdonschot, N; Buma, P; van der Aa, A J; Huiskes, R

    1999-01-01

    This study was undertaken to examine the contribution of uncontained morsellized bone graft to the structural properties of a femoral reconstruction in total knee arthroplasty and to serve as a basis for an in vivo animal study. Ten human distal femora with a standard unicondylar uncontained medial bone defect were prepared to fit a femoral component of a cruciate sacrificing TKA. A cyclic axial load of 750 N was applied to the medial part of the femoral component in the presence of impacted morsellized bone graft. After removal of the bone graft, the cyclic loading was repeated for the unsupported situation. None of the grafts collapsed and all cement mantles stayed intact during the experiments. Elastic deformation during cyclic loading was significantly less when graft was added while time-dependent deformation was not affected. We conclude that impacted morsellized bone graft, used for reconstruction of uncontained femoral bone loss in revision knee arthroplasty, may improve the structural resistance against loading. Further animal experimentation for in vivo application is warranted. PMID:9916775

  15. Prevention of Allogeneic Cardiac Graft Rejection by Transfer of Ex Vivo Expanded Antigen-Specific Regulatory T-Cells

    PubMed Central

    Takasato, Fumika; Morita, Rimpei; Schichita, Takashi; Sekiya, Takashi; Morikawa, Yasuhide; Kuroda, Tatsuo; Niimi, Masanori; Yoshimura, Akihiko

    2014-01-01

    The rate of graft survival has dramatically increased using calcineurin inhibitors, however chronic graft rejection and risk of infection are difficult to manage. Induction of allograft-specific regulatory T-cells (Tregs) is considered an ideal way to achieve long-term tolerance for allografts. However, efficient in vitro methods for developing allograft-specific Tregs which is applicable to MHC full-mismatched cardiac transplant models have not been established. We compared antigen-nonspecific polyclonal-induced Tregs (iTregs) as well as antigen-specific iTregs and thymus-derived Tregs (nTregs) that were expanded via direct and indirect pathways. We found that iTregs induced via the indirect pathway had the greatest ability to prolong graft survival and suppress angiitis. Antigen-specific iTregs generated ex vivo via both direct and indirect pathways using dendritic cells from F1 mice also induced long-term engraftment without using MHC peptides. In antigen-specific Treg transferred models, activation of dendritic cells and allograft-specific CTL generation were suppressed. The present study demonstrated the potential of ex vivo antigen-specific Treg expansion for clinical cell-based therapeutic approaches to induce lifelong immunological tolerance for allogeneic cardiac transplants. PMID:24498362

  16. Reconstruction of the mandible by bone graft and metal prosthesis.

    PubMed

    Kummoona, Raja

    2009-07-01

    This clinical research was carried out in the Maxillofacial Unit, Surgical Specialties Hospital, Medical City, Baghdad, and included 188 patients with mandibular defects. The patients' ages ranged from 4 to 70 years (mean, 37 years); 60 of them were female, and 128 were male. One hundred twenty-six patients represent 67.03% of total cases with benign and locally aggressive tumors and malignant tumors of the mandible and oral cavity. Eighty-four cases (44.68%) of these were benign, 42 cases (22.34%) were malignant tumors, and 62 patients constitute about 32.98% with mandibular defect of posttraumatic missile injuries. Reconstruction of the mandible were done by a variety of techniques ranging from immediate reconstruction of the mandible by chrome-cobalt prosthesis, Kirschner wire, rib graft and bone graft from the iliac crest, and other additional technique of reimplanted condyle, secured with bone graft, and Dacron osteomesh tray carrying cancellous bone harvested from iliac crest. Long-term follow-up ranged between 5 and 10 years.The aim of these study was to share experience and to present an interesting pathology and methods of reconstruction of the mandible by metal prosthesis and bone graft; the management of these cases was a difficult task to be approached in some cases and was a surgical challenge to us. PMID:19521256

  17. Chemotherapy and recombinant human granulocyte colony-stimulating factor primed donor leukocyte infusion for treatment of relapse after allogeneic bone marrow transplantation.

    PubMed

    Sica, S; Di Mario, A; Salutari, P; Rutella, S; Chiusolo, P; Rumi, C; Menichella, G; D'Onofrio, G; Leone, G

    1995-09-01

    Two patients affected by acute leukemia relapsed 10 and 12 months respectively after allogeneic bone marrow transplantation. They were treated with aggressive chemotherapy and then infused with HLA-identical donor leukocytes (DLI) collected after recombinant human granulocyte colony-stimulating factor (rhG-CSF) administration. A total of 5.6 and 6.3 x 10(6)/kg CD34+ cells, 2.7 and 3.0 x 10(4)/kg CFU-GM, 4.7 and 4.4 x 10(8)/kg MNC, 4.6 and 3.9 x 10(9)/kg PMN respectively were infused. Both patients achieved complete remission (CR) and complete chimerism was re-established. One patient developed grade IV acute graft-versus-host disease of the liver requiring immunosuppression and he died in CR from disseminated aspergillosis, 7 months after chemotherapy; one patient is alive in relapse 12 months after treatment. PMID:8535325

  18. Fecal calprotectin as a biomarker of intestinal graft versus host disease after allogeneic hematopoietic stem cell transplantation.

    PubMed

    Lorenz, Fryderyk; Marklund, Stefan; Werner, Mårten; Palmqvist, Richard; Wahlin, Björn Engelbrekt; Wahlin, Anders

    2015-01-01

    The diagnosis of gastrointestinal graft versus host disease (GI-GVHD) is based on clinical symptoms and histological findings. In clinical practice, it is often difficult to decide whether abdominal symptoms in an allogeneic transplant recipient are caused by GVHD or other disorders. Endoscopic biopsies are helpful in establishing the diagnosis, but endoscopy is not always possible to perform due to poor general condition of the patients. No biomarkers are routinely used to predict GVHD. The aim of fecal calprotectin and alpha-1 antitrypsin testing in our study was to find out whether determination of the concentrations of these proteins may be used as a screening method for enteric GVHD. We studied prospectively 51 patients, 8 of whom developed GI-GVHD. Our data demonstrate that elevated fecal calprotectin levels were significantly associated with presence of GI-GVHD. We found a positive association between high F-calprotectin and severe gastrointestinal GVHD. In bivariate analysis, only calprotectin but not alpha-1 antitrypsin was independently associated with GI-GVHD. Testing for fecal calprotectin after allogeneic stem cell transplantation may be a useful screening tool. PMID:25605402

  19. Fecal calprotectin as a biomarker of intestinal graft versus host disease after allogeneic hematopoietic stem cell transplantation

    PubMed Central

    Lorenz, Fryderyk; Marklund, Stefan; Werner, Mårten; Palmqvist, Richard; Wahlin, Björn Engelbrekt; Wahlin, Anders

    2015-01-01

    The diagnosis of gastrointestinal graft versus host disease (GI-GVHD) is based on clinical symptoms and histological findings. In clinical practice, it is often difficult to decide whether abdominal symptoms in an allogeneic transplant recipient are caused by GVHD or other disorders. Endoscopic biopsies are helpful in establishing the diagnosis, but endoscopy is not always possible to perform due to poor general condition of the patients. No biomarkers are routinely used to predict GVHD. The aim of fecal calprotectin and alpha-1 antitrypsin testing in our study was to find out whether determination of the concentrations of these proteins may be used as a screening method for enteric GVHD. We studied prospectively 51 patients, 8 of whom developed GI-GVHD. Our data demonstrate that elevated fecal calprotectin levels were significantly associated with presence of GI-GVHD. We found a positive association between high F-calprotectin and severe gastrointestinal GVHD. In bivariate analysis, only calprotectin but not alpha-1 antitrypsin was independently associated with GI-GVHD. Testing for fecal calprotectin after allogeneic stem cell transplantation may be a useful screening tool. PMID:25605402

  20. Reconstruction of the mandible by prefabricated autogenous bone grafts. An experimental study in minipigs.

    PubMed

    Schliephake, H; Langner, M

    1997-08-01

    The aim of the present experimental study was to evaluate the use of prefabricated bone grafts for reconstruction of the mandible. In 20 adult Göttingen minipigs, prefabricated bone grafts 10 x 12 x 40 mm in size were cultivated in scaffolds of pyrolized bovine bone under a polylactic membrane on the outside of the mandible during a period of five months. The grafts were harvested and transferred to bridge 2- and 4-cm lower mandibular border defects and discontinuity defects. Five animals served as ungrafted controls and evaluation of the grafts was performed three and five months after grafting. At both intervals and in both graft-length groups, the grafted bone volume was almost completely preserved inside the scaffolds and exhibited a slight (3 months) to marked (5 months) increase in bone density by appositional bone growth. The inserted screws were histologically integrated into the transplanted bone and the grafts were linked to the adjacent mandibular bone without intervening soft tissue. The grafts, which were transferred to bridge discontinuity defects, were likewise well preserved with direct fusion between the grafted bone and local bone. It was concluded that bone grafts can be prefabricated from underlying mandibular bone and used for the repair of mandibular defects of various length and shape. PMID:9258711

  1. Bortezomib for the prevention and treatment of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

    PubMed

    Al-Homsi, Ahmad Samer; Feng, Yuxin; Duffner, Ulrich; Al Malki, Monzr M; Goodyke, Austin; Cole, Kelli; Muilenburg, Marlee; Abdel-Mageed, Aly

    2016-09-01

    Allogeneic hematopoietic stem cell transplantation is the standard treatment for a variety of benign and malignant conditions. However, graft-versus-host disease (GvHD) continues to present a major barrier to the success and wide applicability of this procedure. Although current GvHD prevention and treatment regimens exclusively target T cells, bortezomib, a reversible proteasome inhibitor, possesses unique immune regulatory activities that span a wide variety of cellular processes of T and dendritic cells essential for the development of GvHD. Herein, we review the current understanding of the effects of bortezomib in vitro and in animal models and summarize the clinical data relevant to its use in the prevention and treatment of GvHD. We conclude with an outline of the remaining challenges and opportunities to optimize bortezomib's potential role in this setting. PMID:27224851

  2. The 'euthyroid sick syndrome': incidence, risk factors and prognostic value soon after allogeneic bone marrow transplantation.

    PubMed

    Vexiau, P; Perez-Castiglioni, P; Socié, G; Devergie, A; Toubert, M E; Aractingi, S; Gluckman, E

    1993-12-01

    We studied the incidence of thyroid function abnormalities observed soon after allogeneic bone marrow transplantations (BMT) and their predictive value on the overall prognosis. Free serum thyroxine, free serum triiodothyronine, total serum reverse triiodothyronine and serum thyrotropin levels were systematically measured in 78 patients before and 3 months after BMT. 41 (52%) had normal hormone levels and 37 (48%) had abnormal ones, among whom four (5%) had peripheral compensated hypothyroidism and 33 (43%) were described as having 'euthyroid sick syndrome' (low thyroxine state, or low T3 syndrome). Two factors strongly influenced the appearance of thyroid abnormalities: steroid dose at the time of thyroid function testing, and age (< or = 16 years/ > 16 years). Among the younger patients, 21 had no thyroid abnormalities, while five did. Among the older patients, 20 had no thyroid abnormalities, while 32 did (P < 0.001). The occurrence of thyroid abnormalities seemed to influence survival strongly, since the 30-month projected survival time was 83% for patients without abnormalities whereas it was 49% for patients with an abnormal profile (P < 0.001). In conclusion, evidence obtained among our population reveals that euthyroid sick syndrome indicates a poor prognosis and that it is very important to monitor thyroid hormone levels (particularly free hormones) soon after allogeneic BMT and regularly thereafter. PMID:7918043

  3. Bone Marrow Harvesting of Allogeneic Donors in an Outpatient Setting: A Single-Center Experience.

    PubMed

    Lisenko, Katharina; Stadtherr, Peter; Bruckner, Thomas; Pavel, Petra; Heilig, Christoph E; Schmitt, Anita; Puthenparambil, Joe; Brandt, Juliane; Ho, Anthony D; Dreger, Peter; Witzens-Harig, Mathias; Wuchter, Patrick

    2016-03-01

    The aim of this retrospective study was to assess the safety and efficacy of bone marrow (BM) harvesting of allogeneic donors in an outpatient setting. Data of 226 related and unrelated donors who underwent BM harvest under general anesthesia at our institution from 2002 to 2014 were analyzed. Sixteen patients were a priori planned for admission for social reasons and 210 patients underwent BM harvesting with the intention to perform this procedure on an outpatient basis. To identify factors that predispose for hospital admission, we retrospectively analyzed donor characteristics and collection parameters. Outpatient treatment was performed in 178 of 210 donors (85%), whereas 32 donors (15%) required admission for clinical reasons (mainly clinically relevant anemia and circulatory problems). These individuals were not significantly different in sex distribution, age, donor's body weight, and the proportion of related donors from those who were not admitted. However, we found a significantly higher collection volume per kilogram donor's body weight in inpatients compared with volume for outpatients (16 versus 13 mL/kg body weight, P < .001). Severe adverse events or deaths occurred neither in the inpatient nor in the outpatient setting. Our study demonstrated that BM harvest in an outpatient setting is safe and feasible for the majority of allogeneic donors. A high volume of BM represented a major risk factor for inpatient admission. PMID:26551634

  4. Second hematopoietic stem cell transplantation for the treatment of graft failure, graft rejection or relapse after allogeneic transplantation.

    PubMed

    Wolff, S N

    2002-04-01

    Failure to engraft after hematopoietic stem cell transplantation (graft dysfunction) or to sustain engraftment (graft rejection) is a formidable complication due to many possible factors. These include inadequate stem cell numbers, infections, graft-versus-host disease and immunological mediated processes. Fortunately, this complication is uncommon and can be overcome by additional hematopoietic stem cell infusions. Multiple treatment alternatives have been explored including hematopoietic growth factors, additional infusions of stem cells alone, with augmented immunosuppression or with additional cytotoxic therapy. Various sources of the additional stem cells are feasible including the original donor, using another donor, using stem cells collected from the marrow or after cytokine mobilization from the peripheral blood. This report will overview this complication and review the various studies that have attempted to define both cause and therapy. However, a lack of well-designed prospective studies has made definitive recommendations difficult although basic principles have been established. PMID:11979301

  5. The role of pattern-recognition receptors in graft-versus-host disease and graft-versus-leukemia after allogeneic stem cell transplantation.

    PubMed

    Heidegger, Simon; van den Brink, Marcel R M; Haas, Tobias; Poeck, Hendrik

    2014-01-01

    Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only treatment with curative potential for certain aggressive hematopoietic malignancies. Its success is limited by acute graft-versus-host disease (GVHD), a life-threatening complication that occurs when allo-reactive donor T cells attack recipient organs. There is growing evidence that microbes and innate pattern-recognition receptors (PRRs) such as toll-like receptors (TLR) and nod-like receptors (NLR) are critically involved in the pathogenesis of acute GVHD. Currently, a widely accepted model postulates that intensive chemotherapy and/or total-body irradiation during pre-transplant conditioning results in tissue damage and a loss of epithelial barrier function. Subsequent translocation of bacterial components as well as release of endogenous danger molecules stimulate PRRs of host antigen-presenting cells to trigger the production of pro-inflammatory cytokines (cytokine storm) that modulate T cell allo-reactivity against host tissues, but eventually also the beneficial graft-versus-leukemia (GVL) effect. Given the limitations of existing immunosuppressive therapies, a better understanding of the molecular mechanisms that govern GVHD versus GVL is urgently needed. This may ultimately allow to design modulators, which protect from GvHD but preserve donor T-cell attack on hematologic malignancies. Here, we will briefly summarize current knowledge about the role of innate immunity in the pathogenesis of GVHD and GVL following allo-HSCT. PMID:25101080

  6. G-CSF and Exenatide Might Be Associated with Increased Long-Term Survival of Allogeneic Pancreatic Islet Grafts

    PubMed Central

    Peixoto, Eduardo; Messinger, Shari; Mantero, Alejandro; Padilla-Téllez, Nathalia D.; Baidal, David A.; Alejandro, Rodolfo; Ricordi, Camillo; Inverardi, Luca

    2016-01-01

    Background Allogeneic human islet transplantation is an effective therapy for the treatment of patients with Type 1 Diabetes (T1D). The low number of islet transplants performed worldwide and the different transplantation protocols used limit the identification of the most effective therapeutic options to improve the efficacy of this approach. Methods We present a retrospective analysis on the data collected from 44 patients with T1D who underwent islet transplantation at our institute between 2000 and 2007. Several variables were included: recipient demographics and immunological characteristics, donor and transplant characteristics, induction protocols, and additional medical treatment received. Immunosuppression was induced with anti-CD25 (Daclizumab), alone or in association with anti-tumor necrosis factor alpha (TNF-α) treatments (Etanercept or Infliximab), or with anti-CD52 (Alemtuzumab) in association with anti-TNF-α treatments (Etanercept or Infliximab). Subsets of patients were treated with Filgrastim for moderate/severe neutropenia and/or Exenatide for post prandial hyperglycemia. Results The analysis performed indicates a negative association between graft survival (c-peptide level ≥ 0.3 ng/ml) and islet infusion volume, with the caveat that, the progressive reduction of infusion volumes over the years has been paralleled by improved immunosuppressive protocols. A positive association is instead suggested between graft survival and administration of Exenatide and Filgrastim, alone or in combination. Conclusion This retrospective analysis may be of assistance to further improve long-term outcomes of protocols for transplant of islets and other organs. PMID:27285580

  7. A preclinical study of stem subsidence and graft incorporation after femoral impaction grafting using porous hydroxyapatite as a bone graft extender.

    PubMed

    Howie, Donald W; McGee, Margaret A; Callary, Stuart A; Carbone, Angelo; Stamenkov, Roumen B; Bruce, Warrick J; Findlay, David M

    2011-10-01

    This preclinical in vivo screening study compared bone graft incorporation and stem subsidence in cemented hemiarthroplasty after femoral impaction bone grafting with either morselized allograft bone (n = 5, control group) or a 1:1 mix of allograft and porous hydroxyapatite ceramics (HA) granules (n = 5, HA group). At 14 weeks, there was excellent bone graft incorporation by bone, and the stems were well fixed in both groups. The median subsidence at the cement-bone interface, measured using radiostereometric analysis, was 0.14 and 0.93 mm in the control and HA groups, respectively. The comparable histologic results between groups and good stem fixation in this study support the conduct of a larger scale investigation of the use of porous HA in femoral impaction bone grafting at revision hip arthroplasty. PMID:21802252

  8. High Graft CD8 Cell Dose Predicts Improved Survival and Enables Better Donor Selection in Allogeneic Stem-Cell Transplantation With Reduced-Intensity Conditioning

    PubMed Central

    Reshef, Ran; Huffman, Austin P.; Gao, Amy; Luskin, Marlise R.; Frey, Noelle V.; Gill, Saar I.; Hexner, Elizabeth O.; Kambayashi, Taku; Loren, Alison W.; Luger, Selina M.; Mangan, James K.; Nasta, Sunita D.; Richman, Lee P.; Sell, Mary; Stadtmauer, Edward A.; Vonderheide, Robert H.; Mick, Rosemarie; Porter, David L.

    2015-01-01

    Purpose To characterize the impact of graft T-cell composition on outcomes of reduced-intensity conditioned (RIC) allogeneic hematopoietic stem-cell transplantation (alloHSCT) in adults with hematologic malignancies. Patients and Methods We evaluated associations between graft T-cell doses and outcomes in 200 patients who underwent RIC alloHSCT with a peripheral blood stem-cell graft. We then studied 21 alloHSCT donors to identify predictors of optimal graft T-cell content. Results Higher CD8 cell doses were associated with a lower risk for relapse (adjusted hazard ratio [aHR], 0.43; P = .009) and improved relapse-free survival (aHR, 0.50; P = .006) and overall survival (aHR, 0.57; P = .04) without a significant increase in graft-versus-host disease or nonrelapse mortality. A cutoff level of 0.72 × 108 CD8 cells per kilogram optimally segregated patients receiving CD8hi and CD8lo grafts with differing overall survival (P = .007). Donor age inversely correlated with graft CD8 dose. Consequently, older donors were unlikely to provide a CD8hi graft, whereas approximately half of younger donors provided CD8hi grafts. Compared with recipients of older sibling donor grafts (consistently containing CD8lo doses), survival was significantly better for recipients of younger unrelated donor grafts with CD8hi doses (P = .03), but not for recipients of younger unrelated donor CD8lo grafts (P = .28). In addition, graft CD8 content could be predicted by measuring the proportion of CD8 cells in a screening blood sample from stem-cell donors. Conclusion Higher graft CD8 dose, which was restricted to young donors, predicted better survival in patients undergoing RIC alloHSCT. PMID:26056179

  9. Quantitative Comparison of Volume Maintenance between Inlay and Onlay Bone Grafts in the Craniofacial Skeleton

    PubMed Central

    Sugg, Kristoffer B.; Rosenthal, Andrew H.; Ozaki, Wayne; Buchman, Steven R.

    2015-01-01

    Background Nonvascularized autologous bone grafts are the criterion standard in craniofacial reconstruction for bony defects involving the craniofacial skeleton. The authors have previously demonstrated that graft microarchitecture is the major determinant of volume maintenance for both inlay and onlay bone grafts following transplantation. This study performs a head-to-head quantitative analysis of volume maintenance between inlay and onlay bone grafts in the craniofacial skeleton using a rabbit model to comparatively determine their resorptive kinetics over time. Methods Fifty rabbits were divided randomly into six experimental groups: 3-week inlay, 3-week onlay, 8-week inlay, 8-week onlay, 16-week inlay, and 16-week onlay. Cortical bone from the lateral mandible and both cortical and cancellous bone from the ilium were harvested from each animal and placed either in or on the cranium. All bone grafts underwent micro–computed tomographic analysis at 3, 8, and 16 weeks. Results All bone graft types in the inlay position increased their volume over time, with the greatest increase in endochondral cancellous bone. All bone graft types in the onlay position decreased their volume over time, with the greatest decrease in endochondral cancellous bone. Inlay bone grafts demonstrated increased volume compared with onlay bone grafts of identical embryologic origin and microarchitecture at all time points (p < 0.05). Conclusions Inlay bone grafts, irrespective of their embryologic origin, consistently display less resorption over time compared with onlay bone grafts in the craniofacial skeleton. Both inlay and onlay bone grafts are driven by the local mechanical environment to recapitulate the recipient bed. PMID:23629083

  10. Differential Effect of MyD88 Signal in Donor T Cells on Graft-versus-Leukemia Effect and Graft-versus-Host Disease after Experimental Allogeneic Stem Cell Transplantation

    PubMed Central

    Lim, Ji-Young; Ryu, Da-Bin; Lee, Sung-Eun; Park, Gyeongsin; Choi, Eun Young; Min, Chang-Ki

    2015-01-01

    Despite the presence of toll like receptor (TLR) expression in conventional TCRαβ T cells, the direct role of TLR signaling via myeloid differentiation factor 88 (MyD88) within T lymphocytes on graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect after allogeneic stem cell transplantation (allo-SCT) remains unknown. In the allo-SCT model of C57BL/6 (H-2b) → B6D2F1 (H-2b/d), recipients received transplants of wild type (WT) T-cell-depleted (TCD) bone marrow (BM) and splenic T cells from either WT or MyD88 deficient (MyD88KO) donors. Host-type (H-2d) P815 mastocytoma or L1210 leukemia cells were injected either subcutaneously or intravenously to generate a GVHD/GVL model. Allogeneic recipients of MyD88KO T cells demonstrated a greater tumor growth without attenuation of GVHD severity. Moreover, GVHD-induced GVL effect, caused by increasing the conditioning intensity was also not observed in the recipients of MyD88KO T cells. In vitro, the absence of MyD88 in T cells resulted in defective cytolytic activity to tumor targets with reduced ability to produce IFN-γ or granzyme B, which are known to critical for the GVL effect. However, donor T cell expansion with effector and memory T-cell differentiation were more enhanced in GVHD hosts of MyD88KO T cells. Recipients of MyD88KO T cells experienced greater expansion of Foxp3- and IL4-expressing T cells with reduced INF-γ producing T cells in the spleen and tumor-draining lymph nodes early after transplantation. Taken together, these results highlight a differential role for MyD88 deficiency on donor T-cells, with decreased GVL effect without attenuation of the GVHD severity after experimental allo-SCT. PMID:26552489

  11. Differential Effect of MyD88 Signal in Donor T Cells on Graft-versus-Leukemia Effect and Graft-versus-Host Disease after Experimental Allogeneic Stem Cell Transplantation.

    PubMed

    Lim, Ji-Young; Ryu, Da-Bin; Lee, Sung-Eun; Park, Gyeongsin; Choi, Eun Young; Min, Chang-Ki

    2015-11-01

    Despite the presence of toll like receptor (TLR) expression in conventional TCRαβ T cells, the direct role of TLR signaling via myeloid differentiation factor 88 (MyD88) within T lymphocytes on graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect after allogeneic stem cell transplantation (allo-SCT) remains unknown. In the allo-SCT model of C57BL/6 (H-2(b)) → B6D2F1 (H-2(b/d)), recipients received transplants of wild type (WT) T-cell-depleted (TCD) bone marrow (BM) and splenic T cells from either WT or MyD88 deficient (MyD88KO) donors. Host-type (H-2(d)) P815 mastocytoma or L1210 leukemia cells were injected either subcutaneously or intravenously to generate a GVHD/GVL model. Allogeneic recipients of MyD88KO T cells demonstrated a greater tumor growth without attenuation of GVHD severity. Moreover, GVHD-induced GVL effect, caused by increasing the conditioning intensity was also not observed in the recipients of MyD88KO T cells. In vitro, the absence of MyD88 in T cells resulted in defective cytolytic activity to tumor targets with reduced ability to produce IFN-γ or granzyme B, which are known to critical for the GVL effect. However, donor T cell expansion with effector and memory T-cell differentiation were more enhanced in GVHD hosts of MyD88KO T cells. Recipients of MyD88KO T cells experienced greater expansion of Foxp3- and IL4-expressing T cells with reduced INF-γ producing T cells in the spleen and tumor-draining lymph nodes early after transplantation. Taken together, these results highlight a differential role for MyD88 deficiency on donor T-cells, with decreased GVL effect without attenuation of the GVHD severity after experimental allo-SCT. PMID:26552489

  12. Graft-versus-host disease and sialodacryoadenitis viral infection in bone marrow transplanted rats

    SciTech Connect

    Rossie, K.M.; Sheridan, J.F.; Barthold, S.W.; Tutschka, P.J.

    1988-06-01

    The effect of a localized viral infection on the occurrence of graft-vs.-host disease (GVHD) was examined in allogeneic rat bone marrow chimeras (ACI/LEW). Animals without clinical evidence of GVHD, 62 days after bone marrow transplant, were infected in salivary and lacrimal glands with sialodacryoadenitis virus (SDAV), and sacrificed 8-25 days postinfection. Using established histologic criteria, GVHD was found more frequently in salivary and lacrimal glands of SDAV-infected chimeras than uninfected chimeras. Skin and oral mucosa, tissues not infected by the virus, showed no differences in occurrence of GVHD, suggesting that the viral infection induced only local and not systemic GVHD. GVHD and SDAV infection, which are histologically similar, were differentiated by examining tissues for SDAV antigen using immunoperoxidase technique. Histologic changes were present for at least 1 week longer than viral antigen, suggesting they represented GVHD rather than viral infection. GVHD and SDAV infection were also differentiated by looking for a histologic feature characteristic of GVHD and not found in SDAV infection (periductal lymphocytic infiltrate). This was found in SDAV-infected chimeras more frequently than uninfected chimeras, suggesting that the viral infection somehow induced GVHD. Results showed a localized increase in the occurrence of GVHD subsequent to localized viral infection.

  13. Non-invasive imaging of allogeneic transplanted skin graft by 131I-anti-TLR5 mAb.

    PubMed

    Sun, Hukui; Yang, Guangjie; Liang, Ting; Zhang, Chao; Song, Jing; Han, Jiankui; Hou, Guihua

    2014-12-01

    Although (18)F-fluorodeoxyglucose ((18)F-FDG) uptake can be used for the non-invasive detection and monitoring of allograft rejection by activated leucocytes, this non-specific accumulation is easily impaired by immunosuppressants. Our aim was to evaluate a (131)I-radiolabelled anti-Toll-like receptor 5 (TLR5) mAb for non-invasive in vivo graft visualization and quantification in allogeneic transplantation mice model, compared with the non-specific radiotracer (18)F-FDG under using of immunosuppressant. Labelling, binding, and stability studies were performed. BALB/c mice transplanted with C57BL/6 skin grafts, with or without rapamycin treatment (named as allo-treated group or allo-rejection group), were injected with (131)I-anti-TLR5 mAb, (18)F-FDG, or mouse isotype (131)I-IgG, respectively. Whole-body phosphor-autoradiography and ex vivo biodistribution studies were obtained. Whole-body phosphor-autoradiography showed (131)I-anti-TLR5 mAb uptake into organs that were well perfused with blood at 1 hr and showed clear graft images from 12 hrs onwards. The (131)I-anti-TLR5 mAb had significantly higher graft uptake and target-to-non-target ratio in the allo-treated group, as determined by semi-quantification of phosphor-autoradiography images; these results were consistent with ex vivo biodistribution studies. However, high (18)F-FDG uptake was not observed in the allo-treated group. The highest allograft-skin-to-native-skin ratio (A:N) of (131)I-anti-TLR5 mAb uptake was significantly higher than the ratio for (18)F-FDG (7.68 versus 1.16, respectively). (131)I-anti-TLR5 mAb uptake in the grafts significantly correlated with TLR5 expression in the allograft area. The accumulation of (131)I-IgG was comparable in both groups. We conclude that radiolabelled anti-TLR5 mAb is capable of detecting allograft with high target specificity after treatment with the immunosuppressive drug rapamycin. PMID:25283154

  14. Injectable polyHIPEs as high-porosity bone grafts.

    PubMed

    Moglia, Robert S; Holm, Jennifer L; Sears, Nicholas A; Wilson, Caitlin J; Harrison, Dawn M; Cosgriff-Hernandez, Elizabeth

    2011-10-10

    Polymerization of high internal phase emulsions (polyHIPEs) is a relatively new method for the production of high-porosity scaffolds. The tunable architecture of these polyHIPE foams makes them attractive candidates for tissue engineered bone grafts. Previously studied polyHIPE systems require either toxic diluents or high cure temperatures which prohibit their use as an injectable bone graft. In contrast, we have developed an injectable polyHIPE that cures at physiological temperatures to a rigid, high-porosity foam. First, a biodegradable macromer, propylene fumarate dimethacrylate (PFDMA), was synthesized that has appropriate viscosity and hydrophobicity for emulsification. The process of surfactant selection is detailed with particular focus on the key structural features of both polymer (logP values, hydrogen bond acceptor sites) and surfactant (HLB values, hydrogen bond donor sites) that enable stable HIPE formation. Incubation of HIPEs at 37 °C was used to initiate radical cross-linking of the unsaturated double bond of the methacrylate groups to polymerize the continuous phase and lock in the emulsion geometry. The resulting polyHIPEs exhibited ~75% porosity, pore sizes ranging from 4 to 29 μm, and an average compressive modulus and strength of 33 and 5 MPa, respectively. These findings highlight the great potential of these scaffolds as injectable, tissue engineered bone grafts. PMID:21861465

  15. Injectable PolyHIPEs as High Porosity Bone Grafts

    PubMed Central

    Moglia, Robert S.; Holm, Jennifer L.; Sears, Nicholas A.; Wilson, Caitlin J.; Harrison, Dawn M.; Cosgriff-Hernandez, Elizabeth

    2011-01-01

    Polymerization of high internal phase emulsions (polyHIPEs) is a relatively new method for the production of high porosity scaffolds. The tunable architecture of these polyHIPE foams make them attractive candidates for tissue engineered bone grafts. Previously studied polyHIPE systems require either toxic diluents or high cure temperatures which prohibit their use as an injectable bone graft. In contrast, we have developed an injectable polyHIPE that cures at physiological temperatures to a rigid, high-porosity foam. First, a biodegradable macromer, propylene fumarate dimethacrylate (PFDMA), was synthesized that has appropriate viscosity and hydrophobicity for emulsification. The process of surfactant selection is detailed with particular focus on the key structural features of both polymer (log P values, hydrogen bond acceptor sites) and surfactant (HLB values, hydrogen bond donor sites) that enable stable HIPE formation. Incubation of HIPEs at 37°C was used to initiate radical crosslinking of the unsaturated double bond of the methacrylate groups to polymerize the continuous phase and lock in the emulsion geometry. The resulting polyHIPEs exhibited ~75% porosity, pore sizes ranging from 4 to 29 μm, and an average compressive modulus and strength of 33 and 5 MPa, respectively. These findings highlight the great potential of these scaffolds as injectable, tissue engineered bone grafts. PMID:21861465

  16. Tricortical Bone Grafts for Treatment of Malaligned Tibias and Fibulas

    PubMed Central

    Leduc, Stéphane; Gregush, Ronald; Ricci, William M.

    2009-01-01

    Malunions and malaligned nonunions of the tibia and fibula after fracture alter limb function and can be corrected only with surgical intervention. We sought to determine whether using tricortical portions of the iliac crest in conjunction with osteotomy and internal fixation could successfully treat malunions and malaligned nonunions of the tibia and fibula. Seventeen patients with either a malunion or a malaligned nonunion of the tibia or fibula were treated with an osteotomy, deformity correction, and placement of an autogenous iliac crest tricortical bone graft with open reduction and internal fixation (ORIF). The minimum followup was 3 months (average, 32 months; range, 3–118 months). Sixteen patients (94%) had clinical and radiographic evidence of healing at an average of 99 days (range, 43–229 days). Major complications occurred in four patients; one had a persistent nonunion, two had wound infections, and one underwent resection of the distal fibula for subsequent development of fibulotalar arthrosis after ankle arthrodesis. Minor complications occurred in two patients, one tendinitis and one persistent malunion. There were no complications at the iliac crest bone graft site. Autogenous iliac crest tricortical bone grafts, when used in conjunction with correction of alignment and stable internal fixation, are a reasonable option for treatment of nonunions and malaligned nonunions of the tibia and fibula. Level of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID:19145464

  17. Adiponectin and resistin in acute and chronic graft-vs-host disease patients undergoing allogeneic hematopoietic stem cell transplantation

    PubMed Central

    Robak, Oliver; Kuzmina, Zoya; Winkler, Andreas; Kalhs, Peter; Rabitsch, Werner; Greinix, Hildegard

    2016-01-01

    Aim To investigate the association of adiponectin and resistin levels in patients undergoing hematopoietic stem cell transplantation (HSCT) with the clinical outcome, including the occurrence of acute and chronic graft-vs-host disease (GVHD), non-relapse mortality, and overall survival. Methods We prospectively collected serum samples from 40 patients undergoing either autologous (n = 12; 10 male) or allogeneic (n = 28; 11 male) HSCT for up to 12 months post HSCT and determined adiponectin and resistin serum concentrations using enzyme-linked immunosorbent assay. Results There were no significant differences in adiponectin levels (18.5 vs 9.3 µg/mL, P = 0.071) and adiponectin/BMI ratio (0.82 vs 0.39, P = 0.068) between patients with acute GVHD grades 2-4 and autologous controls. However, resistin values were significantly lower in patients with acute GVHD grades 2-4 than in autologous controls (4.6 vs 7.3 ng/mL, P = 0.030). Adiponectin levels were higher in patients with chronic GVHD (n = 17) than in autologous controls (13.5 vs 7.6 µg/mL, P = 0.051), but the difference was not significant. Adiponectin/BMI ratio was significantly higher in patients with chronic GVHD than in autologous controls (0.59 vs 0.25, P = 0.006). Patients dying from relapse also had significantly lower adiponectin levels (8.2 µg/mL) and adiponectin/BMI ratio (0.3) on admission than surviving allogeneic (15.8 µg/mL, P = 0.030 and 0.7, P = 0.004) and surviving autologous patients (19.2 µg/mL, P = 0.031 and 0.7, P = 0.021). Conclusion Adiponectin and resistin levels were altered in patients with acute and chronic GVHD compared to autologous controls and were associated with overall survival and relapse mortality in patients undergoing allogeneic HSCT. PMID:27374827

  18. Early postoperative bone scintigraphy in the evaluation of microvascular bone grafts in head and neck reconstruction

    PubMed Central

    Schuepbach, Jonas; Dassonville, Olivier; Poissonnet, Gilles; Demard, Francois

    2007-01-01

    Background Bone scintigraphy was performed to monitor anastomotic patency and bone viability. Methods In this retrospective study, bone scans were carried out during the first three postoperative days in a series of 60 patients who underwent microvascular bone grafting for reconstruction of the mandible or maxilla. Results In our series, early bone scans detected a compromised vascular supply to the bone with high accuracy (p < 10-6) and a sensitivity that was superior to the sensitivity of clinical monitoring (92% and 75% respectively). Conclusion When performing bone scintigraphy during the first three postoperative days, it not only helps to detect complications with high accuracy, as described in earlier studies, but it is also an additional reliable monitoring tool to decide whether or not microvascular revision surgery should be performed. Bone scans were especially useful in buried free flaps where early postoperative monitoring depended exclusively on scans. According to our experience, we recommend bone scans as soon as possible after surgery and immediately in cases suspicious of vascularized bone graft failure. PMID:17448223

  19. Correlation between Density and Resorption of Fresh-Frozen and Autogenous Bone Grafts

    PubMed Central

    Manfredi, Edoardo; Consolo, Ugo; Marchetti, Claudio; Bonanini, Mauro; Salgarelli, Attilio; Macaluso, Guido M.

    2014-01-01

    Trial Design. This analysis compared the outcome of fresh-frozen versus autologous bone block grafts for horizontal ridge augmentation in patients with Cawood and Howell class IV atrophies. Methods. Seventeen patients received autologous grafts and 21 patients received fresh-frozen bone grafts. Patients underwent CT scans 1 week and 6 months after surgery for graft volume and density analysis. Results. Two autologous and 3 fresh-frozen grafts failed. Autologous and fresh-frozen grafts lost, respectively, 28% and 46% of their initial volume (P = 0.028). It is noteworthy that less dense fresh-frozen blocks lost more volume than denser grafts (61% versus 16%). Conclusions. According to these 6-month results, only denser fresh-frozen bone graft may be an acceptable alternative to autologous bone for horizontal ridge augmentation. Further studies are needed to investigate its behaviour at longer time points. PMID:25050354

  20. Allogeneic bone marrow transplantation for chronic myeloid leukemia using HLA identical sibling donors primed with G-CSF.

    PubMed

    Chen, Hui-Ren; Ji, Shu-Quan; Wang, Hang-Xiang; Yan, Hong-Ming

    2002-08-01

    Many studies have shown that G-CSF mobilized peripheral blood progenitor cell transplants (PBPCT) manifests faster recovery kinetics than conventional bone marrow transplants. This potential advantage of PBPCT still needs to be balanced against the risk of acute and chronic GVHD associating with the infusion of 10 - 15 fold higher donor lymphocyte number in unmanipulated allogeneic PBPCT than the marrow graft. To evaluate the effect of G-CSF primed bone marrow as a source of stem cells in the HLA-matched sibling transplantation, G-CSF primed with non-primed donor marrow in engraftment and incidence of GVHD for a homogenous group of patients with chronic myeloid leukemia (CML) were compared. Fifty patients with CML underwent bone marrow transplant, thirty-two donors (study group) were given G-CSF 3 - 4 micro g/kg per day for seven days prior to marrow harvest and eighteen donors (control group) had marrow harvest without G-CSF stimulation. Conditioning regimen consisted of total body irradiation and cyclophosphamide (CY), busulfan and CY, or busulfan, total body irradiation and CY. Both groups received same post-grafting GVHD prophylaxis and postgrafting G-CSF treatment. It was found that G-CSF primed donor marrow yielded with significantly higher number of total nucleated cells as well as CD34(+) cells and CFU-GM compared to non-G-CSF primed marrow (P = 0.001). The median engraftment time for absolute neutrophil (ANC > 0.5 x 10(9)/L) was day 15 (range 10 - 22) in the group of G-CSF primed vs day 21 in the non-primed donor group (P = 0.001). The median time for platelets (> 20 x 10(9)/L) was day 17.5 (range 13 - 28) in the group of G-CSF primed vs day 24 in non-primed group (P = 0.001). The incidence of acute GVHD grade II - IV in G-CSF primed donor group was surprisingly as low,as only two cases of thirty-two transplants (6.3%) with acute GVHD grade II limited to the skin. Whereas, five of eighteen patients (27.8%) in the control group developed acute GVHD grade II

  1. Enhancement of bone marrow allografts from nude mice into mismatched recipients by T cells void of graft-versus-host activity

    SciTech Connect

    Lapidot, T.; Lubin, I.; Terenzi, A.; Faktorowich, Y.; Erlich, P.; Reisner, Y. )

    1990-06-01

    Transplantation of 8 x 10(6) C57BL/6-Nu+/Nu+ (nude) bone marrow cells into C3H/HeJ recipients after conditioning with 8 Gy of total body irradiation has resulted in a markedly higher rate of graft rejection or graft failure compared to that found in recipients of normal C57BL/6 or C57BL/6-Bg+/Bg+ (beige) T-cell-depleted bone marrow. Mixing experiments using different numbers of nude bone marrow cells with or without mature thymocytes (unagglutinated by peanut agglutinin) revealed that engraftment of allogeneic T-cell-depleted bone marrow is T-cell dependent. To ensure engraftment, a large inoculum of nude bone marrow must be supplemented with a trace number of donor T cells, whereas a small bone marrow dose from nude donors requires a much larger number of T cells for engraftment. Marked enhancement of donor type chimerism was also found when F1 thymocytes were added to nude bone marrow cells, indicating that the enhancement of bone marrow engraftment by T cells is not only mediated by alloreactivity against residual host cells but may rather be generated by growth factors, the release of which may require specific interactions between T cells and stem cells or between T cells and bone marrow stroma cells.

  2. Success rate of implants placed in autogenous bone blocks versus allogenic bone blocks: A systematic literature review

    PubMed Central

    Motamedian, Saeed Reza; Khojaste, Moein; Khojasteh, Arash

    2016-01-01

    The aim of this study is to review and compare survival/success rate of dental implants inserted in autogenous and allogenic bone blocks (ALBs). A PubMed search was performed from January 1990 to June 2014 limited to English language and human studies. Studies that reported treatment outcome of implants inserted in augmented alveolar ridges with autogenous or ALBs were included. Primary search identified 470 studies. For autogenous bone block (ABB) 36 articles and for ALB 23 articles met the inclusion criteria. Evidence on implant survival/success rate of both techniques was limited to observational studies with relatively small sample sizes. Study design, treatment methods, follow-ups, defect location, and morphology varied among studies. The range of implant survival and success rates in ABB was from 73.8% to 100% and 72.8% to 100%, respectively. The corresponding numbers for ALB were 95.3–100% and 93.7–100%, respectively. A definite conclusion could not be reached. Future studies with long-term follow-ups are required to further elucidate this issue. PMID:27563613

  3. Success rate of implants placed in autogenous bone blocks versus allogenic bone blocks: A systematic literature review.

    PubMed

    Motamedian, Saeed Reza; Khojaste, Moein; Khojasteh, Arash

    2016-01-01

    The aim of this study is to review and compare survival/success rate of dental implants inserted in autogenous and allogenic bone blocks (ALBs). A PubMed search was performed from January 1990 to June 2014 limited to English language and human studies. Studies that reported treatment outcome of implants inserted in augmented alveolar ridges with autogenous or ALBs were included. Primary search identified 470 studies. For autogenous bone block (ABB) 36 articles and for ALB 23 articles met the inclusion criteria. Evidence on implant survival/success rate of both techniques was limited to observational studies with relatively small sample sizes. Study design, treatment methods, follow-ups, defect location, and morphology varied among studies. The range of implant survival and success rates in ABB was from 73.8% to 100% and 72.8% to 100%, respectively. The corresponding numbers for ALB were 95.3-100% and 93.7-100%, respectively. A definite conclusion could not be reached. Future studies with long-term follow-ups are required to further elucidate this issue. PMID:27563613

  4. Experimental and clinical analysis of a posterolateral lumbar appendicular bone graft fusion

    PubMed Central

    Wang, Jian-Wen; Xiao, Dong-Min; Wu, Hong; Ye, Ming; Li, Xiong

    2015-01-01

    Objective: This study aimed to investigate the animal experimental and clinical results of the bone graft fusion of a posterolateral lumbar appendicular bone. Methods: 1. Sixty rabbits were randomly divided into experimental and control groups. Posterolateral lumbar bone graft with the appendicular bone and iliac bones, respectively, was then performed on these two groups. A lumbar spine X-ray was performed on the postoperative 4th, 8th and 16th weeks, and the gray value changes of the bone graft fusion area were measured to calculate fusion rates. Histology analysis was also performed to observe and count osteoblasts. 2. The appendicular bones of 106 patients who suffered from lumbar disorders were cut during lumbar surgery, and a posterolateral lumbar bone graft was performed. The postoperative follow-up used the Steffee criteria to evaluate clinical efficacy and the White criteria to evaluate fusion conditions. Results: No significant difference was observed in the relative gray values of X-ray bone density, bone graft fusion rates, and osteoblast counts in the bone graft regions between the two groups (P > 0.05). The follow-up duration of the 106 patients were 4-8 years (6.12 years), the clinical efficacy rate was 85.85%, and the fusion rate was 83.02%. Conclusions: The animal experimental and clinical results of posterolateral lumbar bone graft fusion with autologous iliac and appendicular bones were similar. PMID:26885221

  5. Specific Biomimetic Hydroxyapatite Nanotopographies Enhance Osteoblastic Differentiation and Bone Graft Osteointegration

    PubMed Central

    Loiselle, Alayna E.; Wei, Lai; Faryad, Muhammad; Paul, Emmanuel M.; Lewis, Gregory S.; Gao, Jun; Lakhtakia, Akhlesh

    2013-01-01

    Impaired healing of cortical bone grafts represents a significant clinical problem. Cadaveric bone grafts undergo extensive chemical processing to decrease the risk of disease transmission; however, these processing techniques alter the bone surface and decrease the osteogenic potential of cells at the healing site. Extensive work has been done to optimize the surface of bone grafts, and hydroxyapatite (HAP) and nanotopography both increase osteoblastic differentiation. HAP is the main mineral component of bone and can enhance osteoblastic differentiation and bone implant healing in vivo, while nanotopography can enhance osteoblastic differentiation, adhesion, and proliferation. This is the first study to test the combined effects of HAP and nanotopographies on bone graft healing. With the goal of identifying the optimized surface features to improve bone graft healing, we tested the hypothesis that HAP-based nanotopographic resurfacing of bone grafts improves integration of cortical bone grafts by enhancing osteoblastic differentiation. Here we show that osteoblastic cells cultured on processed bones coated with specific-scale (50–60 nm) HAP nanotopographies display increased osteoblastic differentiation compared to cells on uncoated bone, bones coated with poly-l-lactic acid nanotopographies, or other HAP nanotopographies. Further, bone grafts coated with 50–60-nm HAP exhibited increased formation of new bone and improved healing, with mechanical properties equivalent to live autografts. These data indicate the potential for specific HAP nanotopographies to not only increase osteoblastic differentiation but also improve bone graft incorporation, which could significantly increase patient quality of life after traumatic bone injuries or resection of an osteosarcoma. PMID:23510012

  6. Long-term therapeutic efficacy of allogenic bone marrow transplantation in a patient with mucopolysaccharidosis IVA

    PubMed Central

    Chinen, Yasutsugu; Higa, Takeshi; Tomatsu, Shunji; Suzuki, Yasuyuki; Orii, Tadao; Hyakuna, Nobuyuki

    2014-01-01

    Mucopolysaccharidosis IVA (MPS IVA) is one of the lysosomal storage diseases. It is caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase. Deficiency of this enzyme leads to accumulation of the specific glycosaminoglycans keratan sulfate and chondroitin-6-sulfate. This accumulation has a direct impact on cartilage and bone development, resulting in systemic skeletal dysplasia. There is no curative therapy for this skeletal dysplasia. This report describes long-term therapeutic efficacy in a 15-year-old boy with a severe form of MPS IVA who received successful allogeneic bone marrow transplantation (BMT) from his HLA-identical carrier sister. The level of the GALNS enzyme in the recipient’s lymphocytes reached almost half of normal level within two years after BMT. For the successive 9+ years post-BMT, GALNS activity in his lymphocytes maintained the same level as the donor’s, and the level of urinary uronic acid was reduced. Lumbar bone mineral density increased around 50% one year later post-BMT and was kept consistent. Radiographs showed that the figures of trochanter major and minor appeared, while the epiphyseal dysplasia in the femoral cap was almost unchanged. Loud snoring and apnea disappeared. Vital capacity increased to around 20% for the first two years and was maintained. Activity of daily life (ADL) was improved in work/study efficacy, respiratory status, sleep, joint pain, and frequency of infection. In conclusion, the long-term study of hematopoetic stem cell transplantation has shown clinical improvements in respiratory function, radiograph findings, ADL, and biochemical findings, suggesting that it is a potential therapeutic option for patients with MPS IVA. PMID:25593792

  7. A Retrospective Analysis of the Retreatment of Failed Sinus Bone Grafts.

    PubMed

    Kim, Young-Kyun; Kim, Su-Gwan

    2016-06-01

    This analysis examined the types of retreatment in failed sinus bone grafts due to the development of maxillary sinusitis. Reoperation was performed in 7 patients. The types of reoperation included infection management, reconstruction of the sinus roof using a pedicled buccal fat pad and collagen membrane, oroantral fistula closure, sinus bone graft using an autogenous bone graft, and implant placement. In one case, sinusitis developed 14 months after the reoperation, but it was managed by incision, drainage, and administration of antibiotics. All sinus bone grafts that were performed during the retreatments were successful. PMID:27058356

  8. Nephrotic syndrome as a complication of chronic graft-versus-host disease after allogeneic haemopoietic stem cell transplantation.

    PubMed

    Wong, E; Lasica, M; He, S Z; Bajel, A; Roberts, A W; Mason, K D; Ritchie, D S; Szer, J

    2016-06-01

    Nephrotic syndrome (NS) is a rare complication following allogeneic haemopoietic stem cell transplantation (allo-HSCT), with limited current understanding of its pathogenesis. Here, we describe four cases of NS following allo-HSCT diagnosed at our institutions to identify key clinical and pathological features. In addition, a PubMed search was performed to identify existing reports that were pooled together with our cases for analysis. NS occurred as a late complication following allo-HSCT, with median onset 19.5 months after transplant (range: 3.9-84 months). The most common histopathology observed was membranous nephropathy; however, cases of minimal change disease have also been reported. There is a high incidence of prior extra-renal graft-versus-host disease (GvHD), with all four of our cases and 82% of published cases having prior GvHD. Glucocorticosteroids are the most common treatment, with variable degrees of response. Responses to immunosuppression with calcineurin inhibitors and rituximab have been described in steroid-refractory cases. PMID:27257151

  9. Does defibrotide prophylaxis decrease the risk of acute graft versus host disease following allogeneic hematopoietic cell transplantation?

    PubMed

    Tekgündüz, Emre; Kaya, Ali Hakan; Bozdağ, Sinem Civriz; Koçubaba, Şerife; Kayıkçı, Ömür; Namdaroğlu, Sinem; Uğur, Bilge; Akpınar, Seval; Batgi, Hikmetullah; Bekdemir, Filiz; Altuntaş, Fevzi

    2016-02-01

    There is some preliminary evidence, that veno-occlusive disease prophylaxis with defibrotide (DF) may also have a role in decreasing risk of acute graft-versus-host disease (aGvHD) by preventing tissue damage. In this study, we aimed to investigate the role of DF prophylaxis on the development of aGvHD at D + 180. One hundred ninety-five consecutive adult patients receiving allogeneic HCT were retrospectively evaluated in 3 groups: no DF, DF/post-HCT (DF D + 1 to D + 14) and DF/pre-HCT (DF for 14 days concurrently with conditioning). The total (p: 0.057) and grades III/IV (p: 0.051) aGvHD rates at D + 180 were 46.5%, 40%, 25.5% and 15.5%, 11.2%, 0% in patients on no DF, DF/post-HCT and DF/pre-HCT. DF may have a role in decreasing incidence and severity of aGvHD, especially if used concurrently with conditioning regimen. PMID:26922995

  10. COMPARATIVE STUDY OF BONE NEOFORMATION USING AUTOLOGOUS GRAFTING AND THREE REPLACEMENTS: BONE DEFECTS IN RATS

    PubMed Central

    Stein, Rodrigo Steffen; Silva, Jefferson Braga; Silva, Vinicius Duval da

    2015-01-01

    Objective: Compare the percentage of bone neoformation promoted by autologous bone grafting and three kinds of replacement materials with different characteristics in rats' femoral holes. Methods: Two holes measuring 5.4×2.7mm, were produced on each femur (right and left) of 14 isogenic Wistar rats. Each of the four defects produced was filled by autologous bone or by one of three tested materials-hydroxyapatite (HA), Genphos® (HA+ β-TCP) and GenMix® (a combined bovine bone graft). In the end of the 6-week (n = 6) and 12-week (n = 8) periods, the animals were sacrificed. The sections (stained with Picro-Sirius) were assessed by optical microscopy and specific software. Results: The groups with autologous bone were shown to be significantly superior to the others at both assessed times, showing a mean bone formation rate ± SD of 90.6 ± 10.8% in six weeks, and 98 ± 9.2% in 12 weeks (p > 0.0001 for both assessed times). In six weeks, the results for the other groups were the following: Genphos®, 46 ± 7.1%; HA, 43.1 ± 8.4%; and GenMix®, 57.3 ± 4.5%. In 12 weeks: Genphos®, 47.8 ± 11.1%; HA, 39.9 ± 5.4%; GenMix®, 59.7 ± 4.8%, significant (p = 0.007). Conclusions: In both assessed times, the three bone replacement materials tested in the study showed to be inferior to autologous bone graft for bone neoformation percentage. PMID:27022515

  11. Allogeneic Transplantation for Chronic Lymphocytic Leukemia

    PubMed Central

    Laurenti, Luca; Tarnani, Michela; Chiusolo, Patrizia; Sorà, Federica; Sica, Simona

    2010-01-01

    Even if Chronic lymphocytic leukemia (CLL) often has an indolent behavior with good responsiveness to cytoreductive treatment, about 20% of the patients, so called “poor-risk” patients, show an aggressive course and die within a few years despite early intensive therapies. Criteria for poor-risk disease according to the European Bone Marrow Transplantation (EBMT) CLL Transplant Consensus are: purine analogue refractoriness, early relapse after purine analogue combination therapy, CLL with p53 lesion requiring treatment. Allogeneic transplant has potential curative role in CLL, however burden with very high transplant related mortality (TRM) rates of 38–50%. A major advance in reducing the short-term morbidity and mortality of allogeneic stem cell transplantation (SCT) has been the introduction of non-myeloablative or reduced intensity conditioning (RIC) regimens to allow engraftment of allogeneic stem cells. There is no doubt that the crucial therapeutic principle of allo-SCT in CLL is graft versus leukemia (GVL) activity. The major complications of allogeneic SCT in CLL are: chronic graft-versus-host-disease (GVHD) affecting quality of life, high graft rejection and infection rates correlated with preexisting immunosuppression. Disease relapse remains the major cause of failure after RIC allo-HCT in CLL patients. Sensitive minimal residual disease (MRD) quantification has strong prognostic impact after transplant. PMID:21415973

  12. Guillain-Barré syndrome: report of two rare clinical cases occurring after allergenic bone grafting in oral maxillofacial surgery.

    PubMed

    Cicciù, Marco; Herford, Alan Scott; Bramanti, Ennio; Maiorana, Carlo

    2015-01-01

    Guillaine-Barré Syndrome (GBS), also known as post-infectious polyneuropathy or acute idiopathic polyneuritis, is an infrequent disorder of the peripheral nervous system. The cause of GBS is unknown. It has been associated in the past with microbial infections, vaccinations, surgical procedures and debilitation of the patient. The classic signs of GBS occurring in the two patients being reported here are muscle weakness, motor and sensory impairment and ascending paralysis with respiratory involvement. The documented cases involved GBS syndrome following oral and maxillofacial surgery in which allogeneic-banked freeze-dried bone have been utilized along with autogenous grafting. There were no incidents of viral infection, vaccination or the other prodromal incidents involved in these cases. It is believed that the description of these two cases would be of interest in that it may stimulate the reporting of similar anecdotal occurrences by other surgeons. Both patients fully recovered from the GBS and are presently alive and well. PMID:26261679

  13. Chronic myeloid leukemia relapsing ten years after allogenic bone marrow transplantation.

    PubMed

    Hino, Yutaro; Doki, Noriko; Yamamoto, Keita; Senoo, Yasushi; Sasajima, Satoshi; Sakaguchi, Masahiro; Hattori, Keiichiro; Kaito, Satoshi; Kurosawa, Shuhei; Harada, Kaito; Ikegawa, Shuntaro; Watanabe, Daisuke; Hagino, Takeshi; Yoshioka, Kosuke; Watakabe, Kyoko; Igarashi, Aiko; Najima, Yuho; Kobayashi, Takeshi; Kakihana, Kazuhiko; Sakamaki, Hisashi; Ohashi, Kazuteru

    2016-05-01

    A 58-year-old female was diagnosed with Philadelphia chromosome positive chronic myeloid leukemia (CML) in blast crisis (BC) in 2004. The patient received imatinib, which quickly induced molecular remission, and subsequently underwent bone marrow transplantation (BMT) from an unrelated human leukocyte antigen (HLA)-identical donor. The post-transplant clinical course was essentially uneventful. In 2014, ten years after the BMT, the patient was admitted to our hospital complaining of lymphadenopathy, and blasts were observed in peripheral blood. The patient was diagnosed as having a CML relapse in myeloid BC, with leukemic infiltration in lymph nodes, and was treated with dasatinib. Subsequently, pleural effusion developed and nilotinib was administered, which induced normal blood counts without blasts and partial cytogenetic remission, one month after administration. Six months after the relapse, this patient underwent a second BMT from an HLA-matched unrelated donor. Recent studies have demonstrated the cumulative incidence of CML relapse more than five years after allogeneic hematopoietic stem cell transplantation (allo-HSCT) to be higher than in acute myeloid leukemia. Although rare, the possibility of late relapse should be considered in patients diagnosed with CML after allo-HSCT. PMID:27263786

  14. Macrophage function in murine allogeneic bone marrow radiation chimeras in the early phase after transplantation

    SciTech Connect

    Roesler, J.; Baccarini, M.; Vogt, B.; Lohmann-Matthes, M.L. )

    1989-08-01

    We tested several of the functions of macrophages (M phi) in the early phase after allogeneic bone marrow transfer to get information about this important aspect of the nonspecific immune system in the T-cell-deficient recipient. On days 3-5 after transfer, the number of M phi was reduced in the spleen, liver, lungs, and peritoneal cavity (Pe). The phagocytosis of sheep red blood cells (SRBC) by these M phi was normal or even enhanced, as in the case of Pe-M phi. Already on days 8-12 after transfer, the number of M phi in spleen and liver exceeded that of controls, whereas the number was still reduced in lungs and Pe. We examined their ability to kill P815 tumor cells, to produce tumor necrosis factor-alpha (TNF alpha), to phagocytose SRBC, to produce reactive oxygen intermediates (ROI) in vitro and to kill Listeria monocytogenes in vivo. Most functions were normal and often even enhanced, depending on the organ origin, but the ability of Pe-M phi to produce ROI was reduced. Proliferative response to macrophage colony-stimulating factor (M-CSF) and killing of YAC-1 tumor cells revealed a high frequency of macrophage precursor cells in the spleen and liver and a high natural killer (NK) activity in the liver. Altogether, enhanced nonspecific immune function, especially preactivated M phi, may enable chimeras to survive attacks by opportunistic pathogens.

  15. Keratinocyte growth factor enhances DNA plasmid tumor vaccine responses after murine allogeneic bone marrow transplantation

    PubMed Central

    Jenq, Robert R.; King, Christopher G.; Volk, Christine; Suh, David; Smith, Odette M.; Rao, Uttam K.; Yim, Nury L.; Holland, Amanda M.; Lu, Sydney X.; Zakrzewski, Johannes L.; Goldberg, Gabrielle L.; Diab, Adi; Alpdogan, Onder; Penack, Olaf; Na, Il-Kang; Kappel, Lucy W.; Wolchok, Jedd D.; Houghton, Alan N.; Perales, Miguel-Angel

    2009-01-01

    Keratinocyte growth factor (KGF), which is given exogenously to allogeneic bone marrow transplantation (allo-BMT) recipients, supports thymic epithelial cells and increases thymic output of naive T cells. Here, we demonstrate that this improved T-cell reconstitution leads to enhanced responses to DNA plasmid tumor vaccination. Tumor-bearing mice treated with KGF and DNA vaccination have improved long-term survival and decreased tumor burden after allo-BMT. When assayed before vaccination, KGF-treated allo-BMT recipients have increased numbers of peripheral T cells, including CD8+ T cells with vaccine-recognition potential. In response to vaccination, KGF-treated allo-BMT recipients, compared with control subjects, generate increased numbers of tumor-specific CD8+ cells, as well as increased numbers of CD8+ cells producing interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). We also found unanticipated benefits to antitumor immunity with the administration of KGF. KGF-treated allo-BMT recipients have an improved ratio of T effector cells to regulatory T cells, a larger fraction of effector cells that display a central memory phenotype, and effector cells that are derived from a broader T-cell–receptor repertoire. In conclusion, our data suggest that KGF can function as a potent vaccine adjuvant after allo-BMT through its effects on posttransplantation T-cell reconstitution. PMID:19011222

  16. Catheter-related candidemia caused by Candida lipolytica in a patient receiving allogeneic bone marrow transplantation.

    PubMed

    D'Antonio, Domenico; Romano, Ferdinando; Pontieri, Eugenio; Fioritoni, Giuseppe; Caracciolo, Claudia; Bianchini, Stefano; Olioso, Paola; Staniscia, Tommaso; Sferra, Roberta; Boccia, Stefania; Vetuschi, Antonella; Federico, Giovanni; Gaudio, Eugenio; Carruba, Giuseppe

    2002-04-01

    Candida lipolytica was recovered from the blood and the central venous catheter in a patient receiving allogeneic bone marrow transplantation. Two C. lipolytica strains from different geographical areas and the ATCC 9773 strain of C. lipolytica were used as controls. C. lipolytica was identified by standard methods. MICs indicated antifungal susceptibilities to amphotericin B, fluconazole, and itraconazole for all strains. In vitro testing and scanning electron microscopy showed that C. lipolytica was capable of producing large amounts of viscid slime material in glucose-containing solution, likely responsible for the ability of the yeast to adhere to catheter surfaces. Restriction fragment length polymorphisms revealed an identical profile for all clinical isolates, unrelated to those observed for the control strains. This finding suggested the absence of microevolutionary changes in the population of the infecting strain, despite the length of the sepsis and the potential selective pressure of amphotericin B, which had been administered to the patient for about 20 days. The genomic differences that emerged between the isolates and the control strains were indicative of a certain degree of genetic diversity between C. lipolytica isolates from different geographical areas. PMID:11923360

  17. Effect of acute and chronic graft-versus-host disease on relapse and survival after reduced-intensity conditioning allogeneic transplantation for myeloma

    PubMed Central

    Ringdén, Olle; Shrestha, Smriti; da Silva, Gisela Tunes; Zhang, Mei-Jie; Dispenzieri, Angela; Remberger, Mats; Kamble, Rammurti; Freytes, Cesar O.; Gale, Robert Peter; Gibson, John; Gupta, Vikas; Holmberg, Leona; Lazarus, Hillard; McCarthy, Philip; Meehan, Kenneth; Schouten, Harry; Milone, Gustavo A.; Lonial, Sagar; Hari, Parameswaran N

    2011-01-01

    We evaluated the effect of acute and chronic graft-versus-host disease (GVHD) on relapse and survival after allogeneic haematopoietic stem cell transplantation (HSCT) for multiple myeloma (MM) using non-myeloablative conditioning (NMA) and reduced-intensity conditioning (RIC). The outcomes of 177 HLA-identical sibling HSCT recipients between 1997 and 2005 following NMA (n=98) or RIC (n=79) were analyzed. In 105 patients, autografting was followed by planned NMA/RIC allogeneic transplantation. The impact of GVHD was assessed as a time-dependent covariate using Cox models. The incidence of acute GVHD (grades I–IV) was 42% (95% confidence interval (CI) 35 – 49%) and of chronic GVHD at five years was 59% (95% CI 49 – 69%), with 70% developing extensive chronic GVHD. In multivariate analysis, acute GVHD (≥ grade I) was associated with an increased risk of TRM (relative risk (RR)=2.42; p=0.016), whereas limited chronic GVHD significantly decreased the risk of myeloma relapse (RR=0.35, p=0.035) and was associated with superior event-free survival (RR=0.40, p=0.027). Acute GVHD had a detrimental effect on survival, especially in those receiving autologous followed by allogeneic HSCT (RR=3.52; p=0.001). The reduction in relapse risk associated with chronic GVHD is consistent with a beneficial graft-versus-myeloma effect, but this did not translate into a survival advantage. PMID:21946381

  18. Anti-bacterial immunity to Listeria monocytogenes in allogeneic bone marrow chimera in mice

    SciTech Connect

    Onoe, K.; Good, R.A.; Yamamoto, K.

    1986-06-01

    Protection and delayed-type hypersensitivity (DTH) to the facultative intracellular bacterium Listeria monocytogenes (L.m.) were studied in allogeneic and syngeneic bone marrow chimeras. Lethally irradiated AKR (H-2k) mice were successfully reconstituted with marrow cells from C57BL/10 (B10) (H-2b), B10 H-2-recombinant strains or syngeneic mice. Irradiated AKR mice reconstituted with marrow cells from H-2-compatible B10.BR mice, (BR----AKR), as well as syngeneic marrow cells, (AKR----AKR), showed a normal level of responsiveness to the challenge stimulation with the listeria antigens when DTH was evaluated by footpad reactions. These mice also showed vigorous activities in acquired resistance to the L.m. By contrast, chimeric mice that had total or partial histoincompatibility at the H-2 determinants between donor and recipient, (B10----AKR), (B10.AQR----AKR), (B10.A(4R)----AKR), or (B10.A(5R)----AKR), were almost completely unresponsive in DTH and antibacterial immunity. However, when (B10----AKR) H-2-incompatible chimeras had been immunized with killed L.m. before challenge with live L.m., these mice manifested considerable DTH and resistance to L.m. These observations suggest that compatibility at the entire MHC between donor and recipient is required for bone marrow chimeras to be able to manifest DTH and protection against L.m. after a short-term immunization schedule. However, this requirement is overcome by a preceding or more prolonged period of immunization with L.m. antigens. These antigens, together with marrow-derived antigen-presenting cells, can then stimulate and expand cell populations that are restricted to the MHC (H-2) products of the donor type.

  19. A new harvest site for bone graft in anterior cruciate ligament revision surgery.

    PubMed

    Franceschi, Francesco; Papalia, Rocco; Di Martino, Alberto; Rizzello, Giacomo; Allaire, Robert; Denaro, Vincenzo

    2007-05-01

    During revision anterior cruciate ligament (ACL) surgery, femoral interference screws frequently require removal. This may lead to significant tunnel widening and possible graft fixation failure as a result. Solutions include drilling the revision tunnel in a different location, using stacked interference screws, or using bone graft to fill the defect. Autogenous iliac crest graft and allograft are both used, but there are significant comorbidities associated with each. We developed a new technique for harvesting autogenous bone graft that avoids many of the complications associated with other graft sources. By use of the existing surgical incision from the initial harvest of the bone-patellar tendon-bone autograft, bone from the medial tibial metaphyseal safe zone is harvested via an OATS tube harvester (Arthrex, Naples, FL). A bone plug 1 mm larger in size than the femoral defect is harvested and arthroscopically inserted via a press-fit technique. At 3 months after bone grafting, patients undergo revision ACL reconstruction. The proximal tibial metaphysis is a safe bone graft harvest site in revision ACL surgery and offers an effective method for filling large bony defects, allowing anatomic reconstruction of the ACL after bone healing has occurred. Furthermore, it eliminates the problems associated with allograft or use of a remote graft donor site. PMID:17478290

  20. Prevention of lethal graft vs Host disease following bone marrow transplantation (pretreatment of the inoculum with purine metabolic enzyme inhibitors)

    SciTech Connect

    Kennedy, D.W.

    1983-01-01

    A correlation between lymphocyte function and enzymes of the purine metabolic pathway has been shown. Abnormal levels of three of these enzymes - adenosine deaminase (ADA), 5'-nucleotidase (5'-NT), and purine nucleoside phosphorylase (PNP) - have been associated with defective lymphoid functions. Selective inhibition of one or more of these enzymes may result in elimination of specific lymphocyte populations from a bone marrow (BM) graft and thus prevent graft-vs-host disease (GVHD). To test this hypothesis, BM and spleen cells were pretreated with inhibitors of ADA or PNP before transplant to histoincompatible recipients. Germfree (GF) mice approximately 11 weeks of age were lethally X-irradiated with 1000 Rads. At 24 hours post irradiation the mice received 5 x 10/sup 6/ BM cells and 5 x 10/sup 6/ BM cells and 5 x 10/sup 6/ spleen cells i.v. from syngeneic donors or allogeneic donors. Prior to injection the mice were divided into 5 groups: (1) the inoculum was treated with a final concentration of 10 ..mu..M deoxycoformycin (dCF), and ADA inhibitor, and 100 ..mu..M deoxyadenosine (dAdo); (2) the inoculum was treated with a final concentration of 100 ..mu..M 8-aminoguanosine (8AGuo), an inhibitor of PNP, and 100 ..mu..M 2'-deoxyguanosine (2'dGuo); (3) allogenic controls; (4) syngeneic controls; and (5) radiation controls. In vitro experiments utilizing human peripheral blood and bone marrow demonstrated a severe immunosuppressive effect by the combination of 2'dCF and dAdo which was quick acting and not easily washed away. Treatment with 8A Guo + 2'dGuo also was immunosuppressive, but not as effective as the dCF and dAdo treatment. Both groups of drugs deserve further investigation for possible clinical application to BM transplantation.

  1. Radially and axially graded multizonal bone graft substitutes targeting critical-sized bone defects from polycaprolactone/hydroxyapatite/tricalcium phosphate.

    PubMed

    Ergun, Asli; Yu, Xiaojun; Valdevit, Antonio; Ritter, Arthur; Kalyon, Dilhan M

    2012-12-01

    Repair and regeneration of critical sized defects via the utilization of polymeric bone graft substitutes are challenges. Here, we introduce radially and axially graded multizonal bone graft substitutes fabricated from polycaprolactone (PCL), and PCL biocomposites with osteoconductive particles, that is, hydroxyapatite (HA), and β-tricalcium phosphate (TCP). The novel bone graft substitutes should provide a greater degree of freedom to the orthopedic surgeon especially for repair of critically sized bone defects. The modulus of the graft substitute could be tailored in the axial direction upon the systematic variation of the HA/TCP concentration, while in the radial direction the bone graft substitute consisted of an outer layer with high stiffness, encapsulating a softer core with greater porosity. The biocompatibility of the bone graft substitutes was investigated using in vitro culturing of human bone marrow-derived stromal cells followed by the analysis of cell proliferation and differentiation rates. The characterization of the tissue constructs included the enzymatic alkaline phosphates (ALP) activity, microcomputed tomography imaging, and polymerase chain reaction analysis involving the expressions of bone markers, that is, Runx2, ALP, collagen type I, osteopontin, and osteocalcin, overall demonstrating the differentiation of bone marrow derived stem cells (BMSCs) via osteogenic lineage and formation of mineralized bone tissue. PMID:22764839

  2. Radially and Axially Graded Multizonal Bone Graft Substitutes Targeting Critical-Sized Bone Defects from Polycaprolactone/Hydroxyapatite/Tricalcium Phosphate

    PubMed Central

    Ergun, Asli; Yu, Xiaojun; Valdevit, Antonio; Ritter, Arthur

    2012-01-01

    Repair and regeneration of critical sized defects via the utilization of polymeric bone graft substitutes are challenges. Here, we introduce radially and axially graded multizonal bone graft substitutes fabricated from polycaprolactone (PCL), and PCL biocomposites with osteoconductive particles, that is, hydroxyapatite (HA), and β-tricalcium phosphate (TCP). The novel bone graft substitutes should provide a greater degree of freedom to the orthopedic surgeon especially for repair of critically sized bone defects. The modulus of the graft substitute could be tailored in the axial direction upon the systematic variation of the HA/TCP concentration, while in the radial direction the bone graft substitute consisted of an outer layer with high stiffness, encapsulating a softer core with greater porosity. The biocompatibility of the bone graft substitutes was investigated using in vitro culturing of human bone marrow-derived stromal cells followed by the analysis of cell proliferation and differentiation rates. The characterization of the tissue constructs included the enzymatic alkaline phosphates (ALP) activity, microcomputed tomography imaging, and polymerase chain reaction analysis involving the expressions of bone markers, that is, Runx2, ALP, collagen type I, osteopontin, and osteocalcin, overall demonstrating the differentiation of bone marrow derived stem cells (BMSCs) via osteogenic lineage and formation of mineralized bone tissue. PMID:22764839

  3. Morbidity of harvesting of retromolar bone grafts: a prospective study.

    PubMed

    Nkenke, Emeka; Radespiel-Tröger, Martin; Wiltfang, Jörg; Schultze-Mosgau, Stefan; Winkler, Gerhard; Neukam, Friedrich Wilhelm

    2002-10-01

    20 retromolar bone grafts were harvested in outpatients for augmentation of the implant site from January to June 2000 (10 female, 10 male, 40.9 +/- 12.8 years, minimum 17 years, maximum 66 years). The aim of the study was to assess typical complications of this procedure in a prospective manner. For the determination of the superficial sensory function of the inferior alveolar and the lingual nerve, an objective method was used. The bone grafts were harvested for single tooth reconstruction. In 14 cases a ridge augmentation and in 6 cases an endoscopically controlled crestal sinus floor elevation was performed. Preoperatively, the height of bone above the cranial aspect of the inferior alveolar nerve in the retromolar region was assessed radiologically with known markers. The maximum mouth opening was determined. The superficial sensory function of the inferior alveolar and the lingual nerve was assessed with the Pointed-Blunt Test, the Two-Point-Discrimination Test and the objective method of the 'Pain and Thermal Sensitivity' Test (PATH Test). Moreover, the pulp sensitivity of the teeth of the donor site was determined by cold vitality testing. All tests were repeated 1 week postoperatively. Intraoperatively, the width of the retromolar region was measured with a caliper. The patients rated the operative strain on a visual analogue scale. The height of bone above the inferior alveolar nerve in the retromolar region was 11.0 +/- 2.2 mm. The width of the retromolar area was 14.2 +/- 1.9 mm. Postoperatively, the maximal mouth opening changed significantly (40.8 +/- 3.5 mm preoperatively, 38.9 +/- 3.7 mm postoperatively, P = 0.006). However, the reduction was not relevant clinically. A direct injury of the inferior alveolar or lingual nerve did not occur. A sensitivity impairment could not be detected for either of the nerves by the different test methods 1 week postoperatively. The operative strain related to the donor site was significantly less than the strain

  4. The improved biological response of shark tooth bioapatites in a comparative in vitro study with synthetic and bovine bone grafts.

    PubMed

    López-Álvarez, M; Pérez-Davila, S; Rodríguez-Valencia, C; González, P; Serra, J

    2016-01-01

    Autologous bone is considered to be the gold standard for bone tissue regeneration, providing more highly efficient functional responses compared to synthetic materials, and avoiding the rejection risks of allogenic grafts. However, it presents limitations for certain types of surgery due to its high resorption levels and donor site morbidity. Different biphasic synthetic composites, based onnon-apatitic calcium phosphates enriched with apatitic phases-such as hydroxyapatite, and bioderived bone grafts of bovine and porcine origin-are proposed as lower resorption materials due to their higher crystalline structure. The present work proposes two new sources of bioapatites for bone filler applications obtained from the dentine and enameloid of shark teeth, respectively. These bioapatites each present a characteristic apatite-based composition and additional enrichments of specific trace elements, such as magnesium and fluorine, with proven roles in bone metabolism. Their processing and physicochemical characterization (SEM, FT-Raman and XRD) is presented, together with an in vitro evaluation of osteogenic activity compared to a commercial bovine mineralized matrix and synthetic HA/β TCP grafts. The results proved the globular morphology (0.5-1.5 μm) and porosity (~50 μm and ~0.5-1 μm) of shark dentine bioapatites with biphasic composition: apatitic (hydroxyapatite and apatite-(CaF)), non-apatitic (whitlockite), and an apatitic phase (fluorapatite), organized in oriented crystals in enameloid bioapatites. An evaluation of the pre-osteoblast MC3T3-E1 morphology revealed the colonization of pores in dentine bioapatites and an aligned cell growth in the oriented enameloid crystals. A higher proliferation (p  <  0.01) was detected at up to 21 d in both the shark bioapatites and synthetic biphasic graft with respect to the bovine mineralized matrix. Finally, the great potential of porous biphasic dentine bioapatites enriched with Mg and the aligned

  5. Early predictors of transplant-related mortality (TRM) after allogeneic bone marrow transplants (BMT): blood urea nitrogen (BUN) and bilirubin.

    PubMed

    Bacigalupo, A; Oneto, R; Bruno, B; Soracco, M; Lamparelli, T; Gualandi, F; Occhini, D; Raiola, A; Mordini, N; Berisso, G; Bregante, S; Dini, G; Lombardi, A; Lint, M V; Brand, R

    1999-09-01

    Transplant-related mortality (TRM) following allo- geneic bone marrow transplantation (BMT) remains a major concern and early identification of patients at risk may be clinically relevant. In this study we describe a predictive score based on bilirubin and blood urea nitrogen (BUN) levels on day +7 after BMT. The patient population consisted of 309 consecutive patients who underwent BMT from sibling (n = 263) or unrelated donors (n = 46) for hematologic disorders between December 1990 and December 1996. Of 27 laboratory tests taken on day +7 after BMT, serum bilirubin (P = 0.02) and BUN (P = 0.007) were found to be independent predictors of TRM in multivariate analysis. The median levels of bilirubin (0.9 mg/dl) and of BUN (21 mg/dl) were then used as a cut-off and a score of 1 was given for values equal/greater than the median. There were 216 patients with scores 0-1 (low risk) on day +7 (bilirubin <0.9 and/or BUN <21) and 93 patients with score 2 (high risk) (bilirubin >/=0.9 and BUN >/=21): the latter had more grade III-IV acute graft-versus-host disease (P = 0.03), slower neutrophil (P = 0.02) and slower platelet engraftment (P = 0.002). The actuarial 5 year TRM is 22% for low risk vs44% for high risk patients (P = 0.0003). For HLA-identical siblings TRM is 20% vs35% (P = 0.01), for unrelated donors it is 20% vs 65% (P = 0.01). Day +7 score was highly predictive of TRM on multivariate analysis (hazard ratio 1.9, P < 0.01), after adjustment for year of transplant (P < 0.00001), unrelated vs sibling donors (P = 0.001), patient age (P = 0.01) and diagnosis (P = 0.01). These results were validated on an independent group of 82 allogeneic BMT recipients in a pediatric Unit who showed an actuarial TRM of 16% for low risk vs 46% for high risk patients (P = 0.002). This study suggests that it may be possible to identify patients with different risks of TRM on day +7 after BMT: high risk patients could be eligible for programs designed to intensify prophylaxis of post

  6. Specially modified stromal and immune microenvironment in injected bone marrow following intrabone transplantation facilitates allogeneic hematopoietic stem cell engraftment.

    PubMed

    Chen, Chen; Su, Yingjun; Chen, Jianwu; Song, Yajuan; Zhuang, Ran; Xiao, Bo; Guo, Shuzhong

    2016-07-01

    For allogeneic hematopoietic stem cell transplantation (HSCT), the first key step is the engraftment of hematopoietic stem cells (HSCs) across the major histocompatibility complex (MHC) barrier. Intrabone bone marrow transplantation (IBBMT) could replace more recipient stromal cells with donor cells and facilitate allogeneic organ transplantation compared with the conventional intravenous approach. However, it remains unknown whether and how IBBMT reconstructs the immune microenvironment for allogeneic HSCs. We explored where the BM microenvironment changes by determining BM stromal cell chimerism and measuring the change in CXCL-12 expression and regulatory T cells in recipient BM. We found that most stromal cells were replaced by allogeneic cells in the injected BM, with higher expression of immune regulatory cytokines (interleukin-10) compared with the contralateral BM and the intravenous group BM. This difference was independent of injury caused by intrabone injection. Consistent with the microenvironment modification, the allogeneic the engraftment rate and reconstitution capacity of HSCs were enhanced in the injected BM compared with the contralateral BM and intravenous group BM. Surgical removal of the injected bone at 7 days rather than 21 days reduced the levels of allogeneic granulocytes and HSCs in the peripheral blood. In conclusion, IBBMT specially modifies stromal cells in the injected BM which provide immune protective cues that improve the engraftment of allogeneic HSCs in an early period. PMID:27090963

  7. Osteoinductive PolyHIPE Foams as Injectable Bone Grafts.

    PubMed

    Robinson, Jennifer L; McEnery, Madison A P; Pearce, Hannah; Whitely, Michael E; Munoz-Pinto, Dany J; Hahn, Mariah S; Li, Huinan; Sears, Nicholas A; Cosgriff-Hernandez, Elizabeth

    2016-03-01

    We have recently fabricated biodegradable polyHIPEs as injectable bone grafts and characterized the mechanical properties, pore architecture, and cure rates. In this study, calcium phosphate nanoparticles and demineralized bone matrix (DBM) particles were incorporated into injectable polyHIPE foams to promote osteoblastic differentiation of mesenchymal stem cells (MSCs). Upon incorporation of each type of particle, stable monoliths were formed with compressive properties comparable to control polyHIPEs. Pore size quantification indicated a negligible effect of all particles on emulsion stability and resulting pore architecture. Alizarin red calcium staining illustrated the incorporation of calcium phosphate particles at the pore surface, while picrosirius red collagen staining illustrated collagen-rich DBM particles within the monoliths. Osteoinductive particles had a negligible effect on the compressive modulus (∼30 MPa), which remained comparable to human cancellous bone values. All polyHIPE compositions promoted human MSC viability (∼90%) through 2 weeks. Furthermore, gene expression analysis indicated the ability of all polyHIPE compositions to promote osteogenic differentiation through the upregulation of bone-specific markers compared to a time zero control. These findings illustrate the potential for these osteoinductive polyHIPEs to promote osteogenesis and validate future in vivo evaluation. Overall, this work demonstrates the ability to incorporate a range of bioactive components into propylene fumarate dimethacrylate-based injectable polyHIPEs to increase cellular interactions and direct specific behavior without compromising scaffold architecture and resulting properties for various tissue engineering applications. PMID:26739120

  8. Eggshell Derived Hydroxyapatite as Bone Graft Substitute in the Healing of Maxillary Cystic Bone Defects: A Preliminary Report

    PubMed Central

    Kattimani, Vivekanand S; Chakravarthi, P Srinivas; Kanumuru, Narasimha Reddy; Subbarao, Vummidisetti V; Sidharthan, A; Kumar, T S Sampath; Prasad, L Krishna

    2014-01-01

    Background: Since ancient times, use of graft materials to promote healing of defects of bone is wellknown. Traditionally, missing bone is replaced with material from either patient or donor. Multiple sources of bone grafts have been used to graft bone defects to stimulate bone healing. Hydroxyapatite is naturally occurring mineral component of bone, which is osteoconductive. This versatile biomaterial is derived from many sources. The aim of this study is to evaluate the efficacy of eggshell derived hydroxyapatite (EHA) in the bone regeneration of human maxillary cystic bone defects secondary to cystic removal/apicoectomy and compare the material properties of EHA in vitro. Materials and Methods: A total of eight maxillary bone defects were grafted after cystic enucleation and/or apicoectomy in the year 2008 and completed the study at 1 year. The patients were followed-up 2 weeks after surgery for signs and symptoms of infection or any other complications that may have been related to surgical procedure. Follow-up radiographs were obtained immediately after surgery followed by 1, 2, and 3 months to assess the efficacy of EHA in bone healing. Physicochemical characterization of the EHA was carried out in comparison with synthetic hydroxyapatite (SHA), also compared the biocompatibility of EHA using in vitro cytotoxicity test. Results: By the end of the 8th week, the defects grafted with EHA showed complete bone formation. However, bone formation in non-grafted sites was insignificant. The values of density measurements were equal or more than that of surrounding normal bone. These results indicate that the osseous regeneration of the bone defect filled with EHA is significant. EHA showed the superior material properties in comparison with SHA. Conclusion: EHA is a versatile novel bone graft substitute that yielded promising results. Because of its biocompatibility, lack of disease transfer risks, ease of use and unlimited availability, EHA remains a viable choice

  9. The outcome of intraoral onlay block bone grafts on alveolar ridge augmentations: A systematic review

    PubMed Central

    Aloy-Prósper, Amparo; Peñarrocha-Oltra, David; Peñarrocha-Diago, Maria A.

    2015-01-01

    Aim: The purpose of this study was to systematically review clinical studies examining the survival and success rates of implants placed with intraoral onlay autogenous bone grafts to answer the following question: do ridge augmentations procedures with intraoral onlay block bone grafts in conjunction with or prior to implant placement influence implant outcome when compared with a control group (guided bone regeneration, alveolar distraction, native bone or short dental implants.)? Material and Method: An electronic data banks and hand searching were used to find relevant articles on vertical and lateral augmentation procedures performed with intraoral onlay block bone grafts for dental implant therapy published up to October 2013. Publications in English, on human subjects, with a controlled study design –involving at least one group with defects treated with intraoral onlay block bone grafts, more than five patients and a minimum follow-up of 12 months after prosthetic loading were included. Two reviewers extracted the data. Results: A total of 6 studies met the inclusion criteria: 4 studies on horizontal augmentation and 2 studies on vertical augmentation. Intraoperative complications were not reported. Most common postsurgical complications included mainly mucosal dehiscences (4 studies), bone graft or membrane exposures (3 studies), complete failures of block grafts (2 studies) and neurosensory alterations (4 studies). For lateral augmentation procedures, implant survival rates ranged from 96.9% to 100%, while for vertical augmentation they ranged from 89.5% to 100%. None article studied the soft tissues healing. Conclusions: Survival and success rates of implants placed in horizontally and vertically resorbed edentulous ridges reconstructed with block bone grafts are similar to those of implants placed in native bone, in distracted sites or with guided bone regeneration. More surgical challenges and morbidity arise from vertical augmentations, thus short

  10. CD4+CD25+ regulatory T cell depletion improves the graft-versus-tumor effect of donor lymphocytes after allogeneic hematopoietic stem cell transplantation.

    PubMed

    Maury, Sébastien; Lemoine, François M; Hicheri, Yosr; Rosenzwajg, Michelle; Badoual, Cécile; Cheraï, Mustapha; Beaumont, Jean-Louis; Azar, Nabih; Dhedin, Nathalie; Sirvent, Anne; Buzyn, Agnès; Rubio, Marie-Thérèse; Vigouroux, Stéphane; Montagne, Olivier; Bories, Dominique; Roudot-Thoraval, Françoise; Vernant, Jean-Paul; Cordonnier, Catherine; Klatzmann, David; Cohen, José L

    2010-07-21

    Donor T cells play a pivotal role in the graft-versus-tumor effect after allogeneic hematopoietic stem cell transplantation. Regulatory T cells (T(reg)s) may reduce alloreactivity, the major component of the graft-versus-tumor effect. In the setting of donor lymphocyte infusion after hematopoietic stem cell transplantation, we postulated that T(reg) depletion could improve alloreactivity and likewise the graft-versus-tumor effect of donor T cells. The safety and efficacy of T(reg)-depleted donor lymphocyte infusion was studied in 17 adult patients with malignancy relapse after hematopoietic stem cell transplantation. All but one had previously failed to respond to at least one standard donor lymphocyte infusion, and none had experienced graft-versus-host disease. Two of the 17 patients developed graft-versus-host disease after their first T(reg)-depleted donor lymphocyte infusion and experienced a long-term remission of their malignancy. Four of the 15 patients who did not respond after a first T(reg)-depleted donor lymphocyte infusion received a second T(reg)-depleted donor lymphocyte infusion combined with lymphodepleting chemotherapy aimed to also eliminate recipient T(reg)s. All four developed acute-like graft-versus-host disease that was associated with a partial or complete and durable remission. In the whole cohort, graft-versus-host disease induction through T(reg) depletion was associated with improved survival. These results suggest that T(reg)-depleted donor lymphocyte infusion is a safe, feasible approach that induces graft-versus-host or graft-versus-tumor effects in alloreactivity-resistant patients. In patients not responding to this approach, the combination of chemotherapy-induced lymphodepletion of the recipient synergizes with the effect of T(reg)-depleted donor lymphocyte infusion. These findings offer a rational therapeutic approach for cancer cellular immunotherapy. PMID:20650872

  11. Allogeneic Blood Product Usage in Coronary Artery Bypass Grafting (CABG) with minimalized Extracorporeal Circulation System (MECC) Versus Standard On-Pump Coronary Artery Bypass Grafting

    PubMed Central

    Lisy, M.; Schmid, E.; Kozok, J.; Rosenberger, P.; Stock, U.A.; Kalender, G.

    2016-01-01

    Aim: Intraoperative allogeneic blood product transfusion (ABPT) in cardiac surgery is associated with worse overall outcome, including mortality. The objective of this study was to evaluate the ABPTs in minimalized extracorporeal cardiopulmonary (MECCTM) compared with standard open system on-pump coronary revascularization. Methods: Data of 156 patients undergoing myocardial revascularization between September 2008 and September 2010 were reviewed. 83 patients were operated by the MECC technique and 73 were treated by standard extracorporeal circulation (sECC). ABPT and overall early postoperative complications were analyzed. Results: Operative mortality and morbidity were similar in both groups. ABPT in the MECC group was significantly lower than in the sECC group both intraoperatively (7.2 vs. 60.3% of patients p<0.001) and during the first five postoperative days (19.3 vs. 57.5%; p<0.001). “Skin to skin”- (214 ± 45 vs. 232 ± 45 min; p=0.012), cardiopulmonary bypass (CPB) - (82 ± 25 vs. 95 ± 26 min; p=0.014), and X-clamp- times (50 ± 16 vs. 56 ± 17 min; p=0.024) were significantly lower in the MECC group than in the sECC group. Length of ICU (intensive care unit) - and hospital stay were also significantly lower in the MECC group vs. the sECC group (26.7 ± 20.2 vs. 54.5 ± 68.9 h; p<0.001, and 12.0 ± 4.1 vs. 14.5 ± 4.6 days; p<0.001). Conclusion: Application of MECC as on-pump coronary artery bypass graft (CABG) results in significantly lower ABPT as well as shorter ICU and in-hospital stay. In order to achieve these benefits of MECC autologous retrograde priming, Bispectral index (BIS) monitoring, intraoperative cell salvage, meticulous hemostasis and strict peri- and postoperative volume management are crucial. PMID:27499818

  12. Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey.

    PubMed

    Zeiser, R; Burchert, A; Lengerke, C; Verbeek, M; Maas-Bauer, K; Metzelder, S K; Spoerl, S; Ditschkowski, M; Ecsedi, M; Sockel, K; Ayuk, F; Ajib, S; de Fontbrune, F S; Na, I-K; Penter, L; Holtick, U; Wolf, D; Schuler, E; Meyer, E; Apostolova, P; Bertz, H; Marks, R; Lübbert, M; Wäsch, R; Scheid, C; Stölzel, F; Ordemann, R; Bug, G; Kobbe, G; Negrin, R; Brune, M; Spyridonidis, A; Schmitt-Gräff, A; van der Velden, W; Huls, G; Mielke, S; Grigoleit, G U; Kuball, J; Flynn, R; Ihorst, G; Du, J; Blazar, B R; Arnold, R; Kröger, N; Passweg, J; Halter, J; Socié, G; Beelen, D; Peschel, C; Neubauer, A; Finke, J; Duyster, J; von Bubnoff, N

    2015-10-01

    Despite major improvements in allogeneic hematopoietic cell transplantation over the past decades, corticosteroid-refractory (SR) acute (a) and chronic (c) graft-versus-host disease (GVHD) cause high mortality. Preclinical evidence indicates the potent anti-inflammatory properties of the JAK1/2 inhibitor ruxolitinib. In this retrospective survey, 19 stem cell transplant centers in Europe and the United States reported outcome data from 95 patients who had received ruxolitinib as salvage therapy for SR-GVHD. Patients were classified as having SR-aGVHD (n=54, all grades III or IV) or SR-cGVHD (n=41, all moderate or severe). The median number of previous GVHD-therapies was 3 for both SR-aGVHD (1-7) and SR-cGVHD (1-10). The overall response rate was 81.5% (44/54) in SR-aGVHD including 25 complete responses (46.3%), while for SR-cGVHD the ORR was 85.4% (35/41). Of those patients responding to ruxolitinib, the rate of GVHD-relapse was 6.8% (3/44) and 5.7% (2/35) for SR-aGVHD and SR-cGVHD, respectively. The 6-month-survival was 79% (67.3-90.7%, 95% confidence interval (CI)) and 97.4% (92.3-100%, 95% CI) for SR-aGVHD and SR-cGVHD, respectively. Cytopenia and cytomegalovirus-reactivation were observed during ruxolitinib treatment in both SR-aGVHD (30/54, 55.6% and 18/54, 33.3%) and SR-cGVHD (7/41, 17.1% and 6/41, 14.6%) patients. Ruxolitinib may constitute a promising new treatment option for SR-aGVHD and SR-cGVHD that should be validated in a prospective trial. PMID:26228813

  13. Fludarabine phosphate and melphalan: a reduced intensity conditioning regimen suitable for allogeneic transplantation that maintains the graft versus malignancy effect.

    PubMed

    Dasgupta, R K; Rule, S; Johnson, P; Davies, J; Burnett, A; Poynton, C; Wilson, K; Smith, G M; Jackson, G; Richardson, C; Wareham, E; Stars, A C; Tollerfield, S M; Morgan, G J

    2006-03-01

    Reduced intensity conditioning (RIC) for allogeneic stem cell transplantation allows stable donor cell engraftment with the maintenance of a graft versus malignancy effect. Many different regimens exist employing various combinations of chemotherapy, radiotherapy and T-cell depletion. We examined the role of non-T-cell depleted RIC regimens in 56 patients with haematological malignancies. Patients received fludarabine phosphate for 5 days (30 mg/m2 in 35 patients, 25 mg/m2 in 21 patients) and melphalan for 1 day (140 mg/m2 in 36 patients, 100 mg/m2 in 20 patients). Immunosuppression was with CyA alone in 33 patients and CyA/MTX in 23 patients. Twenty-four of the 26 patients with chimerism data showed >95% donor chimerism at 3 months post transplant. aGVHD occurred in 18% of patients receiving CyA/MTX compared to 53% of patients receiving CyA. The 100-day mortality rate was 0.16 (95%CI 0.08-0.28) and 1-year nonrelapse mortality was 0.24 (95%CI 0.13-0.38). Thirty-three patients remained alive and in CR at a median of 19 months post transplant (range 3-38 months). We have shown that patients transplanted with fludarabine phosphate, melphalan 100 mg/m2 and with CyA/MTX as post transplant immunosuppression can achieve good disease control with an acceptable level of toxicity. Further studies are required to confirm these findings. PMID:16435017

  14. Mogamulizumab Treatment Prior to Allogeneic Hematopoietic Stem Cell Transplantation Induces Severe Acute Graft-versus-Host Disease.

    PubMed

    Sugio, Takeshi; Kato, Koji; Aoki, Takatoshi; Ohta, Takanori; Saito, Noriyuki; Yoshida, Shuro; Kawano, Ichiro; Henzan, Hideho; Kadowaki, Masanori; Takase, Ken; Muta, Tsuyoshi; Miyawaki, Kohta; Yamauchi, Takuji; Shima, Takahiro; Takashima, Shuichiro; Mori, Yasuo; Yoshimoto, Goichi; Kamezaki, Kenjiro; Takenaka, Katsuto; Iwasaki, Hiromi; Ogawa, Ryosuke; Ohno, Yuju; Eto, Tetsuya; Kamimura, Tomohiko; Miyamoto, Toshihiro; Akashi, Koichi

    2016-09-01

    Mogamulizumab (MOG), a humanized anti-CC chemokine receptor 4 (CCR4) monoclonal antibody, has recently played an important role in the treatment of adult T cell leukemia/lymphoma (ATLL). Because CCR4 is expressed on normal regulatory T cells as well as on ATLL cells, MOG may accelerate graft-versus-host disease (GVHD) by eradicating regulatory T cells in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, there is limited information about its safety and efficacy in patients treated with MOG before allo-HSCT. In the present study, 25 patients with ATLL were treated with MOG before allo-HSCT, after which 18 patients (72%) achieved remission. The overall survival and progression-free survival at 1 year post-transplantation were 20.2% (95% CI, 6.0% to 40.3%) and 15.0% (95% CI, 4.3% to 32.0%), respectively. The cumulative incidence of acute GVHD was 64.0% (95% CI, 40.7% to 80.1%) for grade II-IV and 34.7% (95% CI, 15.8% to 54.4%) for grade III-IV. The cumulative incidence of transplantation-related mortality (TRM) was 49.0% (95% CI, 27.0% to 67.8%). Six of 7 patients with acute GVHD grade III-IV died from GVHD, which was the leading cause of death. In particular, a shorter interval from the last administration of MOG to allo-HSCT was associated with more severe GVHD. MOG use before allo-HSCT may decrease the ATLL burden; however, it is associated with an increase in TRM due to severe GVHD. Because MOG is a potent anti-ATLL agent, new treatment protocols should be developed to integrate MOG at suitable doses and timing of administration to minimize unwanted GVHD development. PMID:27220263

  15. Comparative study between cortical bone graft versus bone dust for reconstruction of cranial burr holes

    PubMed Central

    Worm, Paulo V.; Ferreira, Nelson P.; Faria, Mario B.; Ferreira, Marcelo P.; Kraemer, Jorge L.; Collares, Marcus V. M.

    2010-01-01

    Background: As a consequence of the progressive evolution of neurosurgical techniques, there has been increasing concern with the esthetic aspects of burr holes. Therefore, the objective of this study was to compare the use of cortical bone graft and bone dust for correcting cranial deformities caused by neurosurgical trephines. Methods: Twenty-three patients were enrolled for cranial burr hole reconstruction with a 1-year follow-up. A total of 108 burr holes were treated; 36 burr holes were reconstructed with autogenous cortical bone discs (33.3%), and the remaining 72 with autogenous wet bone powder (66.6%). A trephine was specifically designed to produce this coin-shaped bone plug of 14 mm in diameter, which fit perfectly over the burr holes. The reconstructions were studied 12 months after the surgical procedure, using three-dimensional quantitative computed tomography. Additionally, general and plastic surgeons blinded for the study evaluated the cosmetic results of those areas, attributing scores from 0 to 10. Results: The mean bone densities were 987.95 ± 186.83 Hounsfield units (HU) for bone fragment and 473.55 ± 220.34 HU for bone dust (P < 0.001); the mean cosmetic scores were 9.5 for bone fragment and 5.7 for bone dust (P < 0.001). Conclusions: The use of autologous bone discs showed better results than bone dust for the reconstruction of cranial burr holes because of their lower degree of bone resorption and, consequently, better cosmetic results. The lack of donor site morbidity associated with procedural low cost qualifies the cortical autograft as the first choice for correcting cranial defects created by neurosurgical trephines. PMID:21206899

  16. Bismuth 213-labeled anti-CD45 radioimmunoconjugate to condition dogs for nonmyeloablative allogeneic marrow grafts

    SciTech Connect

    Sandmaier, B M.; Bethge, W A.; Wilbur, D. Scott; Hamlin, Donald K.; Santos, E B.; Brechbiel, M W.; Fisher, Darrell R. ); Storb, R.

    2002-01-01

    To lower treatment-related mortality and toxicity of conventional marrow transplantation, a nonmyeloablative regimen using 200 cGy total-body irradiation (TBI) and mycophenolate mofetil (MMF) combined with cyclosporine (CSP) for postgrafting immunosuppression was developed. To circumvent possible toxic effects of external- beam gamma irradiation, strategies for targeted radiation therapy were investigated. We tested whether the short-lived (46 minutes) alpha-emitter Bi-213 conjugated to an anti-CD45 monoclonal antibody (mAb) could replace 200 cGy TBI and selectively target hematopoietic tissues in a canine model of nonmyeloablative DLA-identical marrow transplantation. Biodistribution studies using iodine 123-labeled anti-CD45 mAb showed uptake in blood, marrow, lymph nodes, spleen, and liver. In a dose-escalation study, 7 dogs treated with the Bi-213-anti-CD45 conjugate (Bi-213 dose, 0.1-5.9 mCi/kg[3.7-218 MBq/kg]) without marrow grafts had no toxic effects other than a mild, reversible suppression of blood counts. On the basis of these studies, 3 dogs were treated with 0.5 mg/kg Bi-213-labeled anti-CD45 mAb (Bi-213 doses, 3.6, 4.6, and 8.8 mCi/kg[133, 170, and 326 MBq/kg]) given in 6 injections 3 and 2 days before grafting of marrow from DLA-identical littermates. The dogs also received MMF (10 mg/kg subcutaneously twice daily the day of transplantation until day 27 afterward) and CSP (15 mg/kg orally twice daily the day before transplantation until 35 days afterward). Therapy was well tolerated except for transient elevations in levels of transaminases in 3 dogs, followed by, in one dog, ascites. All dogs achieved prompt engraftment and stable mixed hematopoietic chimerism, with donor contributions ranging from 30% to 70% after more than 27 weeks of follow-up. These results form the basis for additional studies in animals and the design of clinical trials using Bi-213 as a nonmyeloablative conditioning regimen with minimal toxicity.

  17. Effects of liquid nitrogen cryotherapy and bone grafting on artificial bone defects in minipigs: a preliminary study.

    PubMed

    Pogrel, M A; Regezi, J A; Fong, B; Hakim-Faal, Z; Rohrer, M; Tran, C; Schiff, T

    2002-06-01

    Liquid nitrogen cryotherapy has been advocated as an adjunct in the enucleation and curettage of locally aggressive lesions of the jaws. Simultaneous autogenous bone grafting has also been advocated to accelerate bone formation and reduce morbidity. There is, however, relatively little scientific basis for either of these hypotheses. In this study, nine Yucatan minipigs had artificial defects created in the mandible, which were treated with liquid nitrogen spray. Half of the defects were grafted with autogenous bone from the chin and half were closed primarily. Two animals were sacrificed 3 days postoperatively to measure the width of necrosis and the rest were sacrificed at 3 months to assess healing and new bone formation. It was found that drilling the artificial defects alone caused bone necrosis for a mean depth of 0.09 mm. Liquid nitrogen cryospray caused a mean depth of bone necrosis of 0.82 mm (range 0.51-1.52 mm). The defects that were bone grafted healed well clinically. Defects not bone grafted showed a 50% rate of wound breakdown and sequestrum formation with delayed healing. Vital staining showed a non-significantly greater rate of bone formation in the grafted defects. Digitally superimposed radiography showed a non-significantly greater bone density in the non-grafted defects at 3 months postoperatively. It appears that liquid nitrogen cryospray does devitalize an area of bone around defects in the mandible. The width of necrosis is usually less than 1 mm and subsequent healing is enhanced by autogenous bone grafting. This has clinical implications. PMID:12190137

  18. Unilateral Pedicle Screw Fixation with Bone Graft vs. Bilateral Pedicle Screw Fixation with Bone Graft or Cage: A Comparative Study

    PubMed Central

    Yang, Si-Dong; Chen, Qian; Ding, Wen-Yuan; Zhao, Jian-Qiang; Zhang, Ying-Ze; Shen, Yong; Yang, Da-Long

    2016-01-01

    Background The aim of this study was to explore the clinical efficacy of unilateral pedicle screw fixation with bone graft (UPSFB) in treating single-segment lumbar degenerative diseases (LDD), as compared to bilateral pedicle screw fixation with bone graft (BPSFB) or with cage (BPSFC). Material/Methods Medical records were retrospectively collected between 01/2010 and 02/2015 in Longyao County Hospital. According to surgical methods used, all patients were divided into 3 groups: UPSFB group, BPSFB group, and BPSFC group. Clinical outcomes were evaluated by blood loss, blood transfusion, duration of operation, hospital stay, postoperative complications, interbody fusion rate, reoperation rate, medical expenses, patient satisfaction survey, and JOA score. Results Ninety-five patients were included and underwent 2.5-year follow-up, with 7 patients lost to regular follow-up. As compared to the BPSFB group and BPSFC group, the UPSFB group had less blood loss and less blood transfusion, as well as shorter hospital stay (p<0.05). Medical expenses were far lower in the UPSFB group (p<0.001). There were no significant differences among the 3 groups in postoperative complications, interbody fusion rate, reoperation rate, JOA score, and patient satisfaction (all p>0.05). Conclusions As compared to BPSFB and BPSFC, UPSFB has the same reliability and effectiveness in treating single-segment LDD with unilateral radicular symptoms in a single lower extremity, with the additional advantage being less expensive. PMID:26988532

  19. Unilateral Pedicle Screw Fixation with Bone Graft vs. Bilateral Pedicle Screw Fixation with Bone Graft or Cage: A Comparative Study.

    PubMed

    Yang, Si-Dong; Chen, Qian; Ding, Wen-Yuan; Zhao, Jian-Qiang; Zhang, Ying-Ze; Shen, Yong; Yang, Da-Long

    2016-01-01

    BACKGROUND The aim of this study was to explore the clinical efficacy of unilateral pedicle screw fixation with bone graft (UPSFB) in treating single-segment lumbar degenerative diseases (LDD), as compared to bilateral pedicle screw fixation with bone graft (BPSFB) or with cage (BPSFC). MATERIAL AND METHODS Medical records were retrospectively collected between 01/2010 and 02/2015 in Longyao County Hospital. According to surgical methods used, all patients were divided into 3 groups: UPSFB group, BPSFB group, and BPSFC group. Clinical outcomes were evaluated by blood loss, blood transfusion, duration of operation, hospital stay, postoperative complications, interbody fusion rate, reoperation rate, medical expenses, patient satisfaction survey, and JOA score. RESULTS Ninety-five patients were included and underwent 2.5-year follow-up, with 7 patients lost to regular follow-up. As compared to the BPSFB group and BPSFC group, the UPSFB group had less blood loss and less blood transfusion, as well as shorter hospital stay (p<0.05). Medical expenses were far lower in the UPSFB group (p<0.001). There were no significant differences among the 3 groups in postoperative complications, interbody fusion rate, reoperation rate, JOA score, and patient satisfaction (all p>0.05). CONCLUSIONS As compared to BPSFB and BPSFC, UPSFB has the same reliability and effectiveness in treating single-segment LDD with unilateral radicular symptoms in a single lower extremity, with the additional advantage being less expensive. PMID:26988532

  20. Can we achieve bone healing using the diamond concept without bone grafting for recalcitrant tibial nonunions?

    PubMed

    Ollivier, M; Gay, A M; Cerlier, A; Lunebourg, A; Argenson, J N; Parratte, S

    2015-07-01

    The purpose of this study was to evaluate the efficacy and safety of a combination of recombinant human bone morphogenetic protein 7 (rhBMP-7) and resorbable calcium phosphate bone substitute (rCPBS) as a salvage solution for recalcitrant tibial fracture nonunions. Twenty consecutive patients, 16 male and four female, with a mean age of 46.8±15.7 years (21-78) and a mean body mass index (BMI) of 24.2±5.3kgm(-2) (21.5-28.5), suffering from 20 recalcitrant tibial fracture nonunions were included. The mean number of operations performed prior to the procedure was 3.3, with homolateral iliac crest bone grafts being used for all of the patients. All patients were treated with a procedure including debridement and decortications of the bone ends, nonunion fixation with a locking plate, and filling of the bony defect with a combined graft of rhBMP-7 (as osteoinductor) with an rCPBS (as scaffold). The mean follow-up was 14±2.7 months. Both clinical and radiological union occurred in 18 cases, within a mean time of 4.7±3.2 months. A recurrence of deep infection was diagnosed for one of the non-consolidated patients. No specific complication of rCPBS or rhBMP-7 was encountered. This study supports the view that the application of rCPBS combined with rhBMP-7, without any bone grafting, is safe and efficient in the treatment of recalcitrant bone union. PMID:25933808

  1. Transcutaneous Raman spectroscopy for assessing progress of bone-graft incorporation in bone reconstruction and repair

    NASA Astrophysics Data System (ADS)

    Okagbare, Paul I.; Esmonde-White, Francis W. L.; Goldstein, Steven A.; Morris, Michael D.

    2011-03-01

    Allografts and other bone-grafts are frequently used for a variety of reconstructive approaches in orthopaedic surgery. However, successful allograft incorporation remains uncertain. Consequently, there is significant need for methods to monitor the fate of these constructs. Only few noninvasive methods can fully assess the progress of graft incorporation and to provide information on the metabolic status of the graft, such as the mineral and matrix composition of the regenerated-tissue that may provide early indications of graft success or failure. For example, Computed-tomography and MRI provide information on the morphology of the graft/host interface. Limited information is also available from DXA. To address this challenge, we present here the implementation of a noninvasive Raman spectroscopy technique for in-vivo assessment of allograft incorporation in animal-model. In an animal use committee approved osseointegration experiment, a 3mm defect is created in rat's tibia. The defect is reconstructed using auto or allograft and Raman spectra are collected at several time-points during healing using an array of optical-fibers in contact with the skin of the rat over the tibia while the rat is anaesthetized. The array allows excitation and collection of Raman spectra through the skin at various positions around the tibia. Raman parameters such as mineral/matrix, carbonate/phosphate and cross-linking are recovered and monitored. The system is calibrated against locally-constructed phantoms that mimic the morphology, optics and spectroscopy of the rat. This new technology provides a non-invasive method for in-vivo assessment of bone-graft incorporation in animal-models and can be adapted for similar study in human subjects.

  2. A simplified arthroscopic bone graft transfer technique in chronic glenoid bone deficiency.

    PubMed

    Nebelung, Wolfgang; Reichwein, Frank; Nebelung, Sven

    2016-06-01

    In severe shoulder instability, chronic glenoid bone deficiency is a challenge for arthroscopic shoulder surgeons. This paper presents a new all-arthroscopic technique of iliac crest bone graft transfer for those patients. Transportation through the rotator interval and repositioning into the glenoid defect is achieved by use of a tracking suture, while fixation of the graft is performed by biodegradable or titanium double-helix screws. Overall, the feasibility and reproducibility of this new reconstruction technique in recreating the bony and soft tissue anatomy of the antero-inferior glenoid could be demonstrated. So far, preliminary outcomes of 24 patients operated on using this technique are promising. Level of evidence Case series with no comparison group, Level IV. PMID:24803016

  3. Tumour Transfer to Bone Graft Donor Site: A Case Report and Review of the Literature of the Mechanism of Seeding

    PubMed Central

    Dias, Richard G.; Carter, Simon R.; Grimer, Robert J.; Tillman, Roger M.

    2000-01-01

    Purpose. Transmission of malignant tumour cells to a bone graft donor site is a rare complication of bone grafting.We report a case of seeding of malignant fibrous histiocytoma from the femur to a pelvic bone graft donor site. Discussion. We review the literature, discuss the possible mechanism of tumour transfer and offer advice aimed at avoiding this complication. PMID:18521435

  4. Histological evaluation of the influence of magnetic field application in autogenous bone grafts in rats

    PubMed Central

    Puricelli, Edela; Dutra, Nardier B; Ponzoni, Deise

    2009-01-01

    Background Bone grafts are widely used in oral and maxillofacial reconstruction. The influence of electromagnetic fields and magnets on the endogenous stimulation of target tissues has been investigated. This work aimed to assess the quality of bone healing in surgical cavities filled with autogenous bone grafts, under the influence of a permanent magnetic field produced by in vivo buried devices. Methods Metal devices consisting of commercially pure martensitic stainless steel washers and titanium screws were employed. Thirty male Wistar rats were divided into 3 experimental and 3 control groups. A surgical bone cavity was produced on the right femur, and a bone graft was collected and placed in each hole. Two metallic washers, magnetized in the experimental group but not in the control group, were attached on the borders of the cavity. Results The animals were sacrificed on postoperative days 15, 45 and 60. The histological analysis of control and experimental samples showed adequate integration of the bone grafts, with intense bone neoformation. On days 45 and 60, a continued influence of the magnetic field on the surgical cavity and on the bone graft was observed in samples from the experimental group. Conclusion The results showed intense bone neoformation in the experimental group as compared to control animals. The intense extra-cortical bone neoformation observed suggests that the osteoconductor condition of the graft may be more susceptible to stimulation, when submitted to a magnetic field. PMID:19134221

  5. Survival and prognostic factors of invasive aspergillosis after allogeneic bone marrow transplantation.

    PubMed

    Ribaud, P; Chastang, C; Latgé, J P; Baffroy-Lafitte, L; Parquet, N; Devergie, A; Espérou, H; Sélimi, F; Rocha, V; Espérou, H; Sélimi, F; Rocha, V; Derouin, F; Socié, G; Gluckman, E

    1999-02-01

    To determine prognostic factors for survival in bone marrow transplant recipients with invasive aspergillosis (IA), we retrospectively reviewed 27 IA cases observed in our bone marrow transplantation unit between January 1994 and October 1994. On 30 September 1997, six patients were alive and disease-free. The median survival after IA diagnosis was 36 days. Of eight variables found to be related to survival according to the univariate analysis, graft-versus-host disease (GVHD) status at IA diagnosis (P = .0008) and the cumulative prednisolone dose taken during the week preceding IA diagnosis (CPDlw) (P < .0001) were selected by a backward stepwise Cox regression model. A three-stage classification was established: CPD1w of < or =7 mg/kg (3 of 8 patients died; 60-day survival rate, 88%), CPD1w of >7 mg/kg and no GVHD (9 of 10 patients died; 60-day survival rate, 20%), and CPD1w of >7 mg/kg and active acute grade 2 or more or extensive chronic GVHD (9 of 9 patients died; 30-day survival rate, 0) (P < .0001). PMID:10064251

  6. FDG PET/CT in Acute Tumefactive Multiple Sclerosis Occurring in a Case of Chronic Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation.

    PubMed

    Dong, Aisheng; Gao, Mingjun; Wang, Yang; Gao, Lei; Zuo, Changjing

    2016-09-01

    Tumefactive multiple sclerosis refers to the presentation of large demyelinating lesions (≥2 cm in diameter) mimicking brain tumors clinically and radiologically. We present the MRI and FDG PET/CT findings in a case with tumefactive multiple sclerosis, who had chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Head MRI showed 7 cerebral lesions with incomplete ring enhancement. All but one lesion had size more than 2 cm. All these demyelinating lesions showed increased uptake at the rims of the lesions with central hypometabolism. Stereotactic brain biopsy of the right frontal lesion revealed extensive macrophage and lymphocyte infiltration. PMID:26909714

  7. Decellularization and Delipidation Protocols of Bovine Bone and Pericardium for Bone Grafting and Guided Bone Regeneration Procedures

    PubMed Central

    Ferroni, Letizia; Guazzo, Riccardo; Sbricoli, Luca; De Benedictis, Giulia; Finotti, Luca; Isola, Maurizio; Bressan, Eriberto; Zavan, Barbara

    2015-01-01

    The combination of bone grafting materials with guided bone regeneration (GBR) membranes seems to provide promising results to restore bone defects in dental clinical practice. In the first part of this work, a novel protocol for decellularization and delipidation of bovine bone, based on multiple steps of thermal shock, washes with detergent and dehydration with alcohol, is described. This protocol is more effective in removal of cellular materials, and shows superior biocompatibility compared to other three methods tested in this study. Furthermore, histological and morphological analyses confirm the maintenance of an intact bone extracellular matrix (ECM). In vitro and in vivo experiments evidence osteoinductive and osteoconductive properties of the produced scaffold, respectively. In the second part of this study, two methods of bovine pericardium decellularization are compared. The osmotic shock-based protocol gives better results in terms of removal of cell components, biocompatibility, maintenance of native ECM structure, and host tissue reaction, in respect to the freeze/thaw method. Overall, the results of this study demonstrate the characterization of a novel protocol for the decellularization of bovine bone to be used as bone graft, and the acquisition of a method to produce a pericardium membrane suitable for GBR applications. PMID:26191793

  8. Histomorphometric Evaluation of Anorganic Bovine Bone Coverage to Reduce Autogenous Grafts Resorption: Preliminary Results

    PubMed Central

    Maiorana, Carlo; Beretta, Mario; Battista Grossi, Giovanni; Santoro, Franco; Scott Herford, Alan; Nagursky, Heiner; Cicciù, Marco

    2011-01-01

    Physiologic resorption due to remodeling processes affects autogenous corticocancellous grafts in the treatment of atrophic jawbone alveolar ridges. Such a situation in the past made overgrafting of the recipient site mandatory to get enough bone support to dental implants in order to perform a prosthetic rehabilitation. Anorganic bovine bone, conventionally used to treat alveolar bone deficiencies in implant surgery, showed a high osteoconductive property thanks to its micro and macrostructure very similar to that of human hydroxyapatite. An original technique provides for the application of a thin layer of anorganic bovine bone granules and a collagen membrane on the top of the corticocancellous onlay bone grafts to reduce in a remarkable way the graft resorption due to remodeling. The results of a clinical prospective study and a histomorphometric analysis done on autogenous grafts harvested from the iliac crest showed that the proposed technique is able to maintain the original bone volume of the corticocancellous blocks. PMID:21566694

  9. Multiple extramedullary relapses without bone marrow involvement after second allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia.

    PubMed

    Yoo, Sang Woo; Chung, Eun Jin; Kim, Sun Young; Ko, Jeong Hee; Baek, Hey Sung; Lee, Hyun Ju; Oh, Sung Hee; Jeon, Seok Cheol; Lee, Woong Soo; Park, Chan Kum; Lee, Chul Hoon

    2012-06-01

    EMR without BM involvement after allogeneic HSCT is extremely rare, especially in children; only a few cases have been reported. A two-yr-old boy was diagnosed with AML (M4) and underwent allogeneic HSCT in first complete remission with BM from HLA-matched unrelated donor without GVHD. Four yr later, he had a BM relapse and after induction and consolidation chemotherapy, he received a second HSCT from an unrelated donor using peripheral blood stem cells. His second post-transplant course was complicated by extensive chronic GVHD involving the skin, oral cavity, and lungs, which was treated with tacrolimus and corticosteroid. Two yr later, he noticed a mild swelling in the right cheek area. The BM showed a complete remission marrow and a soft tissue biopsy was compatible with granulocytic sarcoma. PET-CT showed multifocal bone involvements. He received chemotherapy, and the chloromas decreased in size. We report a case of diffuse EMR of AML without BM involvement after a second allogeneic HSCT. PMID:21923886

  10. Current status of bone graft options for anterior interbody fusion of the cervical and lumbar spine.

    PubMed

    Chau, Anthony Minh Tien; Xu, Lileane Liang; Wong, Johnny Ho-Yin; Mobbs, Ralph Jasper

    2014-01-01

    Anterior cervical discectomy and fusion (ACDF) and anterior lumbar interbody fusion (ALIF) are common surgical procedures for degenerative disc disease of the cervical and lumbar spine. Over the years, many bone graft options have been developed and investigated aimed at complimenting or substituting autograft bone, the traditional fusion substrate. Here, we summarise the historical context, biological basis and current best evidence for these bone graft options in ACDF and ALIF. PMID:23743981

  11. Experimental posterolateral spinal fusion with beta tricalcium phosphate ceramic and bone marrow aspirate composite graft

    PubMed Central

    Gupta, Ankit; Chauhan, Vijendra; Chauhan, Neena; Sharma, Sansar; Maheshwari, Rajesh; Agarwal, Atul

    2010-01-01

    Background: Beta tricalcium phosphate is commonly used in metaphyseal defects but its use in posterolateral spinal fusion remains controversial. There are very few published animal studies in which use of beta tricalcium phosphate has been evaluated in the posterolateral lumbar arthrodesis model. Hence we conducted a study to evaluate the potential of composite graft of beta tricalcium phosphate and bone marrow aspirate in comparison to autologous bone graft, when used for posterolateral spinal fusion. Materials and Methods: Single level posterolateral lumbar fusion was performed in 40 adult male Indian rabbits, which were assigned randomly into one of the four groups based on graft materials implanted; a) 3 gm beta tricalcium phosphate plus 3 ml bone marrow aspirate (Group I); b) 3 ml bone marrow aspirate alone (Group II); c) 3 gm beta tricalcium phosphate (Group III) and d) 3 gm autologous bone graft (Group IV). Each group had 10 rabbits. Half of the rabbits were sacrificed by injecting Phenobarbitone intraperitoneally after eight weeks and the remaining after 24 weeks, and were evaluated for fusion by X-rays, computed tomography (CT) scans, manual palpation test and histology. Results: Beta tricalcium phosphate used with bone marrow aspirate produced best results when compared to other groups (P =.0001). When beta tricalcium phosphate was used alone, fusion rates were better as compared to fusion achieved with autologous iliac crest bone graft though statistically not significant (P =0.07). Autologous bone graft showed signs of new bone formation. However, the rate of new bone formation was comparatively slow. Conclusion: Composite graft of beta tricalcium phosphate and bone marrow aspirate can be used as an alternative to autologous iliac crest bone graft. PMID:20924481

  12. Prolonged sirolimus administration after allogeneic hematopoietic cell transplantation is associated with decreased risk for moderate-severe chronic graft-versus-host disease.

    PubMed

    Pidala, Joseph; Kim, Jongphil; Alsina, Melissa; Ayala, Ernesto; Betts, Brian C; Fernandez, Hugo F; Field, Teresa; Jim, Heather; Kharfan-Dabaja, Mohamed A; Locke, Frederick L; Mishra, Asmita; Nishihori, Taiga; Ochoa-Bayona, Leonel; Perez, Lia; Riches, Marcie; Anasetti, Claudio

    2015-07-01

    Effective pharmacological strategies employed in allogeneic hematopoietic cell transplantation should prevent serious chronic graft-versus-host disease and facilitate donor-recipient immune tolerance. Based on demonstrated pro-tolerogenic activity, sirolimus (rapamycin) is an agent with promise to achieve these goals. In a long-term follow-up analysis of a randomized phase II trial comparing sirolimus/tacrolimus versus methotrexate/tacrolimus for graft-versus-host disease prevention in matched sibling or unrelated donor transplant, we examined the impact of prolonged sirolimus administration (≥ 1 year post-transplant). Median follow-up time for surviving patients at time of this analysis was 41 months (range 27-60) for sirolimus/tacrolimus and 49 months (range 29-63) for methotrexate/tacrolimus. Sirolimus/tacrolimus patients had significantly lower National Institutes of Health Consensus moderate-severe chronic graft-versus-host disease (34% vs. 65%; P=0.004) and late acute graft-versus-host disease (20% vs. 43%; P=0.04). While sirolimus/tacrolimus patients had lower prednisone exposure and earlier discontinuation of tacrolimus (median time to tacrolimus discontinuation 368 days vs. 821 days; P=0.002), there was no significant difference in complete immune suppression discontinuation (60-month estimate: 43% vs. 31%; P=0.78). Prolonged sirolimus administration represents a viable approach to mitigate risk for moderate-severe chronic and late acute graft-versus-host disease. Further study of determinants of successful immune suppression discontinuation is needed. PMID:25840599

  13. Prolonged sirolimus administration after allogeneic hematopoietic cell transplantation is associated with decreased risk for moderate-severe chronic graft-versus-host disease

    PubMed Central

    Pidala, Joseph; Kim, Jongphil; Alsina, Melissa; Ayala, Ernesto; Betts, Brian C.; Fernandez, Hugo F.; Field, Teresa; Jim, Heather; Kharfan-Dabaja, Mohamed A.; Locke, Frederick L.; Mishra, Asmita; Nishihori, Taiga; Ochoa-Bayona, Leonel; Perez, Lia; Riches, Marcie; Anasetti, Claudio

    2015-01-01

    Effective pharmacological strategies employed in allogeneic hematopoietic cell transplantation should prevent serious chronic graft-versus-host disease and facilitate donor-recipient immune tolerance. Based on demonstrated pro-tolerogenic activity, sirolimus (rapamycin) is an agent with promise to achieve these goals. In a long-term follow-up analysis of a randomized phase II trial comparing sirolimus/tacrolimus versus methotrexate/tacrolimus for graft-versus-host disease prevention in matched sibling or unrelated donor transplant, we examined the impact of prolonged sirolimus administration (≥ 1 year post-transplant). Median follow-up time for surviving patients at time of this analysis was 41 months (range 27–60) for sirolimus/tacrolimus and 49 months (range 29–63) for methotrexate/tacrolimus. Sirolimus/tacrolimus patients had significantly lower National Institutes of Health Consensus moderate-severe chronic graft-versus-host disease (34% vs. 65%; P=0.004) and late acute graft-versus-host disease (20% vs. 43%; P=0.04). While sirolimus/tacrolimus patients had lower prednisone exposure and earlier discontinuation of tacrolimus (median time to tacrolimus discontinuation 368 days vs. 821 days; P=0.002), there was no significant difference in complete immune suppression discontinuation (60-month estimate: 43% vs. 31%; P=0.78). Prolonged sirolimus administration represents a viable approach to mitigate risk for moderate-severe chronic and late acute graft-versus-host disease. Further study of determinants of successful immune suppression discontinuation is needed. PMID:25840599

  14. Should dermal scald burns in children be covered with autologous skin grafts or with allogeneic cultivated keratinocytes?--"The Viennese concept".

    PubMed

    Rab, Matthias; Koller, Rupert; Ruzicka, Margot; Burda, Gudrun; Kamolz, Lars Peter; Bierochs, Bettina; Meissl, Guenther; Frey, Manfred

    2005-08-01

    The treatment of scald burns in children is still under discussion. The aim of the present study was to evaluate an optimised treatment regime for scald burns in children. Between 1997 and 2002, 124 children underwent surgical intervention due to burn injuries. Thirty-six out of these 124 children were enrolled into the evaluation of our recent treatment protocol. Twenty-two children with scald burns covering an average body surface area (TBSA) of 18.5% were treated by early excision and coverage with allogeneic keratinocytes in case of partial thickness lesions (keratinocyte group). Fourteen children with a TBSA of 17.2% were treated with autologous skin grafts alone (skin graft group). Both groups were comparable according to age, burn depth and affected TBSA. The complete clinical follow-up examination of at least 17 months was performed in 12 out of 22 children of the keratinocyte group and in 9 out of 14 patients of the comparative group. Visible scar formations were classified according to the Vancouver Scar Scale (VSS) in each patient. The use of allogeneic keratinocytes led to complete epithelialisation within 12 days in 20 of the 22 cases. No secondary skin grafting procedures had to be done. Skin take rate at the sixth postoperative day was 100% in the skin graft group. Blood transfusions were administered intraoperatively according to the clinical need of the patients by the responsible anaesthesiologist. The mean volume of blood, which had to be transfused was 63.9 ml in the keratinocyte group and significantly lower than the volume of 151.4 ml, which was administered in the skin graft group (p=0.04). At follow up the VSS observed in areas covered by keratinocytes was 2.33 on the average and therefore, significantly lower than the VSS of 5.22 in skin grafted areas of the comparative group (p=0.04). In children the use of cultivated keratinocytes in partial thickness scald burns is a procedure, which renders constantly reliable results. It minimizes the

  15. Development of hydroxyapatite scaffolds for artificial bone grafts

    NASA Astrophysics Data System (ADS)

    Ajaal, Tawfik Taher

    The Taguchi method of experimental design is very well suited to improving the production process of the synthetic bone grafts for several reasons. First, it is very efficient and easy to apply, so that it does not require large amounts of time or resources to conduct a given set of experiments. This makes it possible to conduct a series of experiments that result in continuous process improvement. Second, the effect of many different process variables can be examined simultaneously, which ensures that beneficial factor combinations are not overlooked. Finally, using a Taguchi signal-to-noise ratio leads to concurrent optimization of the process and reduction of process variability. The application of Taguchi method was successful in optimizing the production process of the synthetic bone grafts. The compressive strength was doubled while maintaining the appropriate porosity level and microstructure for the bioactivity process. The mean value of the compression strength obtained was 5.8 MPa with density of 0.515 gm/cm3 for samples prepared from 45 pores per inch (PPI) foam reticulate, and 3.2 MPa with 0.422 gm/cm 3 for samples prepared from 30 PPI foam reticulate. Three levels of porosity were identified namely, macro, meso, and micro-porosity. The pore sizes were (350--400) mum, (100--120) mum and (2--6) mum respectively based on the used substrate. Using the Taguchi method in conjunction with a statistical experimental design, the various steps of the scaffold production process such as slurry preparation, coating process, drying, calcining and sintering processes were optimized. The final optimized process gave highly reproducible results.

  16. Effect of different storage media on the regenerative potential of autogenous bone grafts: a histomorphometrical analysis in rabbits.

    PubMed

    Rocha, Flaviana Soares; Batista, Jonas Dantas; Zanetta-Barbosa, Darceny; Dechichi, Paula

    2013-12-01

    The success of autogenous bone graft is related to the graft cell viability. In bone-grafting procedures, harvested grafts are often maintained in extraoral media while the recipient site is prepared. The aim of this study was to evaluate in vivo the effect of storage media over autogenous bone grafts during the transsurgical time. Two grafts were removed bilaterally from the calvaria of 18 rabbits. One graft was immediately fixed in the mandibular angle (control group), and the other was maintained in air exposure (dry group), 0.9% NaCl solution (saline group), or platelet-poor plasma (PPP group) during 30 minutes and stabilized in the symmetrical location of control grafts. After 28 days, the animals were euthanized and the bone fragments were removed, demineralized, and embedded in paraffin. Histological evaluation was performed under light microscope. Empty lacunae and bone graft area quantification were carried out for the sections. The histomorphometrical analysis revealed reduction of the graft area and increase of empty lacunae in the dry group when compared with control. No significant differences were found in the number of empty lacunae or bone graft area between the saline group and its control and also between the PPP group and its control. The dry group showed more empty lacunae and less graft area than the saline and PPP groups. In accordance with the results, PPP and physiologic solution demonstrated osteocyte preservation and bone graft area maintenance, being satisfactory storage media for autogenous bone grafts during the transsurgical period. PMID:21905882

  17. Reconstruction using 'triangular approximation' of bone grafts for orbital blowout fractures.

    PubMed

    Saiga, Atsuomi; Mitsukawa, Nobuyuki; Yamaji, Yoshihisa

    2015-10-01

    There are many orbital wall reconstruction materials that can be used in surgery for orbital blowout fractures. We consider autogenous bone grafts to have the best overall characteristics among these materials and use thinned, inner cortical tables of the ilium. A bone bender is normally used to shape the inner iliac table to match the orbital shape. Since orbital walls curve three-dimensionally, processing of bone grafts is not easy and often requires much time and effort. We applied a triangular approximation method to the processing of bone grafts. Triangular approximation is a concept used in computer graphics for polygon processing. In this method, the shape of an object is represented as combinations of polygons, mainly triangles. In this study, the inner iliac table was used as a bone graft, and cuts or scores were made to create triangular sections. These triangular sections were designed three-dimensionally so that the shape of the resulting graft approximated to the three-dimensional orbital shape. This method was used in 12 patients with orbital blowout fractures, which included orbital floor fractures, medial wall fractures, and combined inferior and medial wall fractures. In all patients, bone grafts conformed to the orbital shape and good results were obtained. This simple method uses a reasonable and easy-to-understand approach and is useful in the treatment of bone defects in orbital blowout fractures when using a hard graft material. PMID:26297418

  18. Histological assessment in grafts of highly purified beta-tricalcium phosphate (OSferion) in human bones.

    PubMed

    Ogose, Akira; Kondo, Naoki; Umezu, Hajime; Hotta, Tetsuo; Kawashima, Hiroyuki; Tokunaga, Kunihiko; Ito, Tomoyuki; Kudo, Naoko; Hoshino, Makiko; Gu, Wenguang; Endo, Naoto

    2006-03-01

    Prominent osteoconductive activity and the biodegradable nature of commercially available beta-tricalcium phosphate (beta-TCP, OSferion) have been documented in animal experiments. We analyzed four cases of involving grafted OSferion in human bone with respect to histological features by routine hematoxylin and eosin staining, silver impregnation, immunohistochemistry and in situ hybridization. OSferion affords early bioresorption by osteoclasts, vascular invasion of macropores and osteoblastic cell attachment on the surface on the ceramic surface 14 days after grafting. Prominent bone formation and direct bone connection between preexisting bone and OSferion were evident 28 days after grafting. Nearly the entire TCP surface was covered by lamellar bone; additionally, active osteoblastic lining and attachment of the osteoclast-like giant cells were not observed 72 weeks after grafting. Silver impregnation revealed the presence of collagen fibrils within probable micropores of OSferion. PMID:16165205

  19. Results of autogenous trephine biopsy needle bone grafting in fractures of radius and ulna.

    PubMed

    Lakhey, S; Shrestha, B P; Pradhan, R L; Pandey, B; Rijal, K P

    2005-01-01

    Cortico-Cancellous bone graft harvested from the anterior iliac crest by the conventional open method is associated with more morbidity and is more time consuming as compared to the percutaneous method using trephine biopsy needle. The aim of the study was to determine whether cancellous bone graft harvested from anterior iliac crest using trephine biopsy needle consistently achieved bone union in comminuted fractures and fractures of more than 3 weeks duration of radius and ulna and also to determine the morbidity at the donor site. Autogenous cancellous bone graft was harvested percutaneously from 28 iliac crests in 16 patients and applied at fracture sites of 30 forearm bones using a 4mm trephine biopsy needle after the fractures had been fixed with plate and screws. The patients were followed up regularly upto 6 to 9 months post - operatively in the OPD to determine the union status of the fractured bones and the morbidity at the donor site. 29 of the 30 fractures of the forearm bones united without any problems. The shaft of a trephine got bent during the harvesting procedure at the beginning of the study due to improper technique. Cancellous bone graft harvested from the anterior iliac crest results in predictable good union results in comminuted fractures of forearm bones and also fractures presenting after 3 weeks of injury. It is also an easier and quicker way of harvesting bone graft and is associated with lesser morbidity and earlier recovery as compared to conventional open method. PMID:16554860

  20. Ocular graft versus host disease in allogenic haematopoetic stem cell transplantation in a tertiary care centre in India

    PubMed Central

    Khan, Rehan; Nair, Sridevi; Seth, Tullika; Mishra, Pravas; Mahapatra, Manoranjan; Agarwal, Tushar; Tandon, Radhika; Vanathi, Murugesan

    2015-01-01

    Background & objectives: This study was aimed to report the occurrence of ocular graft versus host disease (oGVHD) in allogeneic haematopoietic stem cell transplantation (allo-HSCT) patients in a tertiary care hospital setting. Methods: A cross-sectional study of ocular surface of allo-HSCT patients was done. Slit lamp biomicroscopy, symptom score, tear meniscus height, fluorescein tear break-up time, Schirmer's test I, ocular surface staining, dry eye severity, ocular surface disease index score were done. Indications for allo-HSCT, human leukocyte antigen (HLA) matching, GVHD risk factor, systemic manifestation and treatment were also noted. Results: GVHD occurred in 44.4 per cent of 54 allo-HSCT patients (mean age 26.7 ± 12 yr) included in the study. GVHD risk factors identified included female gender, relapse, older age of donor, cytomagelo virus (CMV) reactivation, and multiparous female donors. oGVHD was noted in 31.5 per cent with mean time to occurrence being 17.8 ± 21.9 months after the allo-HSCT and was observed in 89.5 per cent of chronic GVHD cases. Acute GVHD (oral and dermatological) involvement showed a significant association with GVHD in our patients (P< 0.001, 0R 23.0, CI 6.4-82.1). Chronic GVHD was observed to be associated with the occurrence of oGVHD (dry eye) (P<0.001, OR = 24.0, CI 0.02 - 0.29). Of the 34 eyes with oGHVD, dry eye of level 3 severity was seen in 16, level 2 in six, level 1 in 12 eyes. Interpretation & conclusions: GVHD occurred in 44.4 per cent of the patients studied in the present study. Acute and chronic GVHD showed a strong association with oGVHD. Dry eye disease due to chronic oGVHD was observed in 17 (31.5%) of 54 allo-HSCT patient with chronic oGVHD occurring in 17 (89.4%) of chronic GVHD cases in allo-HSCT patients. Our study on oGVHD in post allo-HSCT patients in tertiary care centre points towards the fact that ocular morbidity due to dry eye disease as a result of oGVHD is a cause for concern in these patients

  1. Prospective Analysis of Secondary Alveolar Bone Grafting in Cleft Lip and Palate Patients

    PubMed Central

    Reddy, M Gokul Chandra; Babu, V Ramesh; Rao, V Eswar; Chaitanya, J Jaya; Allareddy, S; Reddy, C Charan Kumar

    2015-01-01

    Background: To assess the success of the uptake of bone graft in cleft alveolus of the cleft lip and palate patients, quantitatively through computed tomography (CT) scan 6 months postoperative. To assess the successful eruption of permanent lateral incisor or canine in the bone grafted area. Materials and Methods: The children age group of 9-21 years with unilateral cleft lip and palate came to the hospital, needing secondary alveolar bone grafting. A detailed history and clinical examination of the patient was taken. A 3D CT scan was taken and the volume of the cleft was measured pre-operatively. After ambulatory period, 3D CT scan of the alveolar cleft region was taken and volume of the bone grafted was measured and patient was discharged from the hospital. After 6 months, patient was recalled and again 3D CT scan was taken and the volume of remaining bone was measured. Results: The mean volume of the defect pre-operatively is 0.80 cm3 with a standard deviation of 0.36 cm3 with minimum volume of the defect 0.44 cm3 and maximum volume of the defect 1.60 cm3. The mean volume of the bone post-operative immediately after grafting is 1.01 cm3 with a standard deviation of 0.52 cm3 with minimum of bone volume is 0.48 cm3 and maximum of 2.06 cm3. The mean volume of the bone after 6 months after bone grafting is 0.54 cm3 with a standard deviation of 0.33 cm3, minimum bone volume of 0.22 cm3 and maximum bone volume of 1.42 cm3. Conclusion: The CT scan is a valuable radiographic imaging modality to assess and follow the clinical outcome of secondary alveolar bone grafting. PMID:25954076

  2. Graft-versus-lymphoma effect in refractory cutaneous T-cell lymphoma after reduced-intensity HLA-matched sibling allogeneic stem cell transplantation.

    PubMed

    Herbert, K E; Spencer, A; Grigg, A; Ryan, G; McCormack, C; Prince, H M

    2004-09-01

    Cutaneous T-cell lymphomas (CTCL) are rare diseases that, in their advanced stages or in transformation, have a poor prognosis. Autologous stem cell transplantation (Au-SCT) after high-dose therapy has yielded disappointing results. Allogeneic transplantation (allo-SCT) provides the potential advantage of an immune-mediated graft-versus-lymphoma (GVL) effect. Reduced-intensity allo-SCT potentially offers a GVL effect, but with diminished toxicity related to the induction regimen; however, published experience with this approach in CTCL is limited. We report a series of three patients (age 35-49) with advanced, refractory (n=2) or transformed (n=1) CTCL who underwent reduced-intensity allo-SCT in the context of active disease. All three survived the peri-transplant period and, despite later having disease relapse, all exhibited evidence of a GVL effect. Relapses of the disease were in the context of immune suppression for graft-versus-host disease (GVHD), and when immune suppression was reduced, responses were regained. A comparison is made of these results to those in a review of the published literature to date. We conclude that while a GVL can be achieved for CTCL with reduced-intensity allogeneic transplantation, the clinical benefits are short lived and novel approaches are required to obtain sustained remissions. PMID:15286686

  3. Impact of graft-versus-host disease on outcomes after allogeneic hematopoietic cell transplantation for adult T-cell leukemia: a retrospective cohort study.

    PubMed

    Kanda, Junya; Hishizawa, Masakatsu; Utsunomiya, Atae; Taniguchi, Shuichi; Eto, Tetsuya; Moriuchi, Yukiyoshi; Tanosaki, Ryuji; Kawano, Fumio; Miyazaki, Yasushi; Masuda, Masato; Nagafuji, Koji; Hara, Masamichi; Takanashi, Minoko; Kai, Shunro; Atsuta, Yoshiko; Suzuki, Ritsuro; Kawase, Takakazu; Matsuo, Keitaro; Nagamura-Inoue, Tokiko; Kato, Shunichi; Sakamaki, Hisashi; Morishima, Yasuo; Okamura, Jun; Ichinohe, Tatsuo; Uchiyama, Takashi

    2012-03-01

    Allogeneic hematopoietic cell transplantation (HCT) is an effective treatment for adult T-cell leukemia (ATL), raising the question about the role of graft-versus-leukemia effect against ATL. In this study, we retrospectively analyzed the effects of acute and chronic graft-versus-host disease (GVHD) on overall survival, disease-associated mortality, and treatment-related mortality among 294 ATL patients who received allogeneic HCT and survived at least 30 days posttransplant with sustained engraftment. Multivariate analyses treating the occurrence of GVHD as a time-varying covariate demonstrated that the development of grade 1-2 acute GVHD was significantly associated with higher overall survival (hazard ratio [HR] for death, 0.65; P = .018) compared with the absence of acute GVHD. Occurrence of either grade 1-2 or grade 3-4 acute GVHD was associated with lower disease-associated mortality compared with the absence of acute GVHD, whereas grade 3-4 acute GVHD was associated with a higher risk for treatment-related mortality (HR, 3.50; P < .001). The development of extensive chronic GVHD was associated with higher treatment-related mortality (HR, 2.75; P = .006) compared with the absence of chronic GVHD. Collectively, these results indicate that the development of mild-to-moderate acute GVHD confers a lower risk of disease progression and a beneficial influence on survival of allografted patients with ATL. PMID:22234682

  4. Effect of calvarial burring on resorption of onlay cranial bone graft.

    PubMed

    Hassanein, Aladdin H; Clune, James E; Mulliken, John B; Arany, Praveen R; Rogers, Gary F; Kulungowski, Ann M; Greene, Arin K

    2012-09-01

    Variable resorption occurs whenever calvarial bone graft is used for onlay cranioplasty. The recipient ectocortex may be burred to expose vessels and osteocytes to maximize healing. The purpose of this study was to determine whether abrading the recipient site improves the volume of onlay graft. The parietal bones of 17 rabbits were sectioned into split-thickness and full-thickness grafts. The right frontal cortex was abraded with a bur to punctate bleeding. Pairs of split-thickness (n = 48) or full-thickness (n = 20) grafts were onlayed to the burred right frontal bone and to the nonburred left frontal bone. Micro-computed tomography was used to determine graft volume immediately postoperatively and 16 weeks later. Histology, including tartrate-resistant acid phosphatase staining, was performed to quantify vascular channels and osteoclasts per high-power field 10 days postoperatively. Split-thickness graft volume decreased 58.0% when placed on the burred calvarial site, compared with grafts on the nonburred cortex (28.4%) (P = 0.01). Full-thickness grafts showed a similar trend: greater resorption (39.1%) when onlayed onto abraded calvaria compared with nonburred ectocortex (26.0%) (P = 0.11). Split-thickness graft orientation (cortical vs cancellous side in contact with the recipient site) did not affect resorption (P = 0.67). Onlay grafts placed on the burred recipient site had more vascular channels (11.8) and osteoclasts (5.7), compared with grafts over nonabraded cortex (3.4 and 4.2, respectively) (P < 0.05). Burring the recipient site cortex before onlay cranial bone grafting promotes resorption, possibly by increasing vascularization and osteoclastic activity. This technique cannot be recommended. PMID:22976644

  5. Graft-versus-Host Disease after HLA-Matched Sibling Bone Marrow or Peripheral Blood Stem Cell Transplantation: Comparison of North American Caucasian and Japanese Populations.

    PubMed

    Kanda, Junya; Brazauskas, Ruta; Hu, Zhen-Huan; Kuwatsuka, Yachiyo; Nagafuji, Koji; Kanamori, Heiwa; Kanda, Yoshinobu; Miyamura, Koichi; Murata, Makoto; Fukuda, Takahiro; Sakamaki, Hisashi; Kimura, Fumihiko; Seo, Sachiko; Aljurf, Mahmoud; Yoshimi, Ayami; Milone, Giuseppe; Wood, William A; Ustun, Celalettin; Hashimi, Shahrukh; Pasquini, Marcelo; Bonfim, Carmem; Dalal, Jignesh; Hahn, Theresa; Atsuta, Yoshiko; Saber, Wael

    2016-04-01

    The risk of acute graft-versus-host disease (GVHD) after HLA-matched sibling bone marrow transplantation (BMT) is lower in Japanese than in Caucasian patients. However, race may have differential effect on GVHD dependent on the graft source. North American Caucasian and Japanese patients receiving their first allogeneic BMT or peripheral blood stem cell transplantation from an HLA-matched sibling for leukemia were eligible. BMT was performed in 13% of the Caucasian patients and in 53% of the Japanese patients. On multivariate analysis, the interaction term between race and graft source was not significant in any of the models, indicating that graft source does not affect the impact of race on outcomes. The risk of grade III or IV acute GVHD was significantly lower in the Japanese patients compared with the Caucasian patients (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.57 to 0.96), which resulted in lower risk of nonrelapse mortality in the Japanese patients (HR, 0.69; 95% CI, 0.54 to 0.89). The risk of relapse was also lower in this group. The lower risks of nonrelapse mortality and relapse resulted in lower overall mortality rates among the Japanese patients. In conclusion, our data indicate that irrespective of graft source, the risk of severe acute GVHD is lower in Japanese patients, resulting in a lower risk of nonrelapse mortality. PMID:26762681

  6. Specificity of T cells invading the skin during acute graft-vs.-host disease after semiallogeneic bone marrow transplantation.

    PubMed Central

    Gaschet, J; Mahé, B; Milpied, N; Devilder, M C; Dréno, B; Bignon, J D; Davodeau, F; Hallet, M M; Bonneville, M; Vié, H

    1993-01-01

    The mechanisms responsible for skin lesions during acute graft-vs.-host disease (aGVHD) after allogeneic bone marrow transplantation (BMT) are poorly understood. The exact role of various effector cell populations and "major" (particularly HLA-DP) or "minor" antigens as target molecules is not known. To investigate the nature of cells responsible for tissue injury, we cultured T cells from skin biopsy first with interleukin 2 (IL-2) alone and then in polyclonal activation conditions to avoid in vitro antigenic sensitization before specificity testing. We applied this method to two biopsies performed during aGVHD after semiallogeneic BMT and obtained cytotoxic T cells against four graft mismatches: CD8+ T cells against HLA-A2.2 and HLA-B27 and CD4+ T cells against HLA-DP101 and HLA-DP401. This demonstrates that T cells with documented specificity can be obtained from an aGVHD lesion without antigenic selection. Moreover, these data directly implicate DP as a potential target antigen for aGVHD. Images PMID:8423212

  7. Recovery from CMV esophagitis after allogeneic bone marrow transplantation using non-myeloablative conditioning: the role of immunosuppression.

    PubMed

    Fiegl, Michael; Gerbitz, Armin; Gaeta, Antonia; Campe, Hartmut; Jaeger, Gundula; Kolb, Hans-Jochem

    2005-11-01

    Cytomegalovirus (CMV) positive recipients of CMV negative bone marrow bear a significantly higher risk of developing CMV disease compared to all other constellations. Here, we report a case of severe CMV induced esophagitis after allogeneic bone marrow transplantation for paroxysmal nocturnal hemoglobinuria. The patient developed the first symptoms between day 10 and 20 after dose reduced conditioning and HLA-matched unrelated stem cell transplantation. Esophageal tissue biopsies as well as peripheral blood proved positive for CMV DNA by PCR. Treatment with acyclovir, ganciclovir, foscarnet, cidofovir, and immunoglobulines resulted in elimination of CMV in peripheral blood but not in clinical improvement. Only tapering of cyclosporine at day +120 eventually led to the development of CMV-specific T-cells and resolution of esophagitis. PMID:16129661

  8. Donor Site Evaluation: Anterior Iliac Crest Following Secondary Alveolar Bone Grafting

    PubMed Central

    Vura, Nandagopal; Reddy K., Rajiv; R., Sudhir; G., Rajasekhar; Kaluvala, Varun Raja

    2013-01-01

    Introduction: The use of autogenous bone graft for Secondary alveolar bone grafting is well established in the treatment of cleft lip and palate patients. Aims and Objectives: To evaluate post-operative morbidity of anterior iliac crest graft after secondary alveolar bone grafting in cleft patients. Material and Methods: Forty patients during the period from July 2008 to March 2013, who underwent secondary alveolar bone grafting by harvesting graft from anterior iliac crest in Mamata Dental Hospital, Khammam, Andhra Pradesh, India are included in the present study. Unilateral and bilateral cleft patients who had undergone secondary alveolar bone grafting (SABG) with anterior iliac crest as their donor site have been selected and post- operative complications from the surgery were evaluated with the help of a questionnaire which included pain, gait disturbances, numbness and scar problems (infection, irritation). Results: Patients who were operated gave maximum score for pain as 8 on visual analogue scale. No pain was observed in any of the cases after 8 days, gait disturbances were seen in all patients (limping) for 2-6 days, there was no post-operative numbness with all the patients returning to their routine in 6- 15 days and 90% of the patients gave a satisfied response towards scar. Conclusion: From the results in our study the morbidity after harvesting bone from iliac crest was found to be moderate to low, which had minimal complications and were well tolerated and greater acceptance from the patient. PMID:24392424

  9. Impaction grafted bone chip size effect on initial stability in an acetabular model: Mechanical evaluation

    PubMed Central

    Holton, Colin; Bobak, Peter; Wilcox, Ruth; Jin, Zhongmin

    2013-01-01

    Introduction Acetabular bone defect reconstruction is an increasing problem for surgeons with patients undergoing complex primary or revision total hip replacement surgery. Impaction bone grafting is one technique that has favourable long-term clinical outcome results for patients who undergo this reconstruction method for acetabular bone defects. Creating initial mechanical stability of the impaction bone graft in this technique is known to be the key factor in achieving a favourable implant survival rate. Different sizes of bone chips were used in this technique to investigate if the size of bone chips used affected initial mechanical stability of a reconstructed acetabulum. Methodology Twenty acetabular models were created in total. Five control models were created with a cemented cup in a normal acetabulum. Then five models in three different groups of bone chip size were constructed. The three groups had an acetabular protrusion defect reconstructed using either; 2–4 mm3, 10 mm3 or 20 mm3 bone chip size for impaction grafting reconstruction. The models underwent compression loading up to 9500 N and displacement within the acetabular model was measured indicating the initial mechanical stability. Results This study reveals that, although not statistically significant, the largest (20 mm3) bone chip size grafted models have an inferior maximum stiffness compared to the medium (10 mm3) bone chip size. Interpretations Our study suggests that 10 mm3 size of bone chips provide better initial mechanical stability compared to smaller or larger bone chips. We dismissed the previously held opinion that the biggest practically possible graft is best for acetabular bone graft impaction. PMID:24396238

  10. Reconstruction of Beagle Hemi-Mandibular Defects with Allogenic Mandibular Scaffolds and Autologous Mesenchymal Stem Cells

    PubMed Central

    Luo, JinChao; Liu, HuaWei; Hu, Min; Yue, Wen

    2014-01-01

    Objective Massive bone allografts are frequently used in orthopedic reconstructive surgery, but carry a high failure rate of approximately 25%. We tested whether treatment of graft with mesenchymal stem cells (MSCs) can increase the integration of massive allografts (hemi-mandible) in a large animal model. Methods Thirty beagle dogs received surgical left-sided hemi-mandibular defects, and then divided into two equal groups. Bony defects of the control group were reconstructed using allografts only. Those of the experimental group were reconstructed using allogenic mandibular scaffold-loaded autologous MSCs. Beagles from each group were killed at4 (n = 4), 12 (n = 4), 24 (n = 4) or 48 weeks (n = 3) postoperatively. CT and micro-CT scans, histological analyses and the bone mineral density (BMD) of transplants were used to evaluate defect reconstruction outcomes. Results Gross and CT examinations showed that the autologous bone grafts had healed in both groups. At 48 weeks, the allogenic mandibular scaffolds of the experimental group had been completely replaced by new bone, which has a smaller surface area to that of the original allogenic scaffold, whereas the scaffold in control dogs remained the same size as the original allogenic scaffold throughout. At 12 weeks, the BMD of the experimental group was significantly higher than the control group (p<0.05), and all micro-architectural parameters were significantly different between groups (p<0.05). Histological analyses showed almost all transplanted allogeneic bone was replaced by new bone, principally fibrous ossification, in the experimental group, which differed from the control group where little new bone formed. Conclusions Our study demonstrated the feasibility of MSC-loaded allogenic mandibular scaffolds for the reconstruction of hemi-mandibular defects. Further studies are needed to test whether these results can be surpassed by the use of allogenic mandibular scaffolds loaded with a

  11. Histologic Evaluation of Critical Size Defect Healing With Natural and Synthetic Bone Grafts in the Pigeon ( Columba livia ) Ulna.

    PubMed

    Tunio, Ahmed; Jalila, Abu; Goh, Yong Meng; Shameha-Intan; Shanthi, Ganabadi

    2015-06-01

    Fracture and bone segment loss are major clinical problems in birds. Achieving bone formation and clinical union in a fracture case is important for the survival of the bird. To evaluate the efficacy of bone grafts for defect healing in birds, 2 different bone grafts were investigated in the healing of a bone defect in 24 healthy pigeons ( Columba livia ). In each bird, a 1-cm critical size defect (CSD) was created in the left ulna, and the fracture was stabilized with external skeletal fixation (ESF). A graft of hydroxyapatite (HA) alone (n = 12 birds) or demineralized bone matrix (DBM) combined with HA (n = 12 birds) was implanted in the CSD. The CSD healing was evaluated at 3 endpoints: 3, 6, and 12 weeks after surgery. Four birds were euthanatized at each endpoint from each treatment group, and bone graft healing in the ulna CSD was evaluated by histologic examination. The CSD and graft implants were evaluated for quality of union, cortex development, and bone graft incorporation. Results showed no graft rejection in any bird, and all birds had connective tissue formation in the defect because of the bone graft application. These results suggest that bone defect healing can be achieved by a combination of osteoinductive and osteoconductive bone graft materials for clinical union and new bone regeneration in birds. The combination of DBM and HA resulted in a better quality bone graft (P < .05) than did HA alone, but there was no significant differences in cortex development or bone graft incorporation at 3, 6, or 12 weeks. From the results of this study, we conclude that HA bone grafts, alone or in combination with DBM, with external skeletal fixation is suitable and safe for bone defect and fracture treatment in pigeons. PMID:26115209

  12. Progress in the prevention of cytomegalovirus infection after allogeneic bone marrow transplantation.

    PubMed

    Devergie, A; Traineau, R; Esperou-Bourdeau, H; Ribaud, P; Socié, G; Richard, P; Selimi, F; Hirsch, I; Gluckman, E

    1994-01-01

    There has been substantial progress in preventing and treating CMV infection. Prophylaxis with CMV screened blood products, IVIG and antiviral drugs (high dose acyclovir and/or Ganciclovir) considerably reduce the incidence of CMV disease and nearly eliminate CMV pneumonia after allogeneic BMT. PMID:8177726

  13. Piezo harvesting of bone grafts from the anterior iliac crest: A technical note

    PubMed Central

    Ylikontiola, Leena P.; Lehtonen, Ville; Sándor, George K.

    2016-01-01

    Background: Autogenous bone graft harvesting from the iliac crest is associated with donor site morbidity. The aim of this report is to describe the use of piezosurgery as an attempt at morbidity reduction. Materials and Methods: A piezosurgical handpiece and its selection of tips can easily be accommodated in an iliac crest wound to osteotomize and allow the harvest and delivery of autogenous bone grafts. Results: Corticocancellous blocks or cancellous strips of autogenous bone can be readily harvested using a piezosurgical technique at the anterior iliac crest. Conclusion: Piezosurgery avoids some of the traumatic aspects of harvesting bone associated with the use of conventional rotary instruments or saws.

  14. Kuhlmann vascularized bone grafting for treatment of Kienböck's disease: a case report

    PubMed Central

    Sbai, Mohamed Ali; Msek, Hichem; Benzarti, Sofien; Boussen, Monia; Maalla, Riadh

    2016-01-01

    Treatment of Kienböck's disease has historically been determined by staging, ulnar variance, and presence or absence of arthritic changes. With the advent of newer techniques of vascularized bone grafting, the status of the cartilage shell of the lunate has become another factor that can influence the procedure performed. The purpose of this article is to describe the technique of Kuhlmann vascularized bone graft for Kienböck's disease. In addition, the indications, contraindications, and outcomes are described.

  15. Kuhlmann vascularized bone grafting for treatment of Kienböck's disease: a case report.

    PubMed

    Sbai, Mohamed Ali; Msek, Hichem; Benzarti, Sofien; Boussen, Monia; Maalla, Riadh

    2016-01-01

    Treatment of Kienböck's disease has historically been determined by staging, ulnar variance, and presence or absence of arthritic changes. With the advent of newer techniques of vascularized bone grafting, the status of the cartilage shell of the lunate has become another factor that can influence the procedure performed. The purpose of this article is to describe the technique of Kuhlmann vascularized bone graft for Kienböck's disease. In addition, the indications, contraindications, and outcomes are described. PMID:27583101

  16. Bone graft and mesenchimal stem cells: clinical observations and histological analysis

    PubMed Central

    Bertolai, Roberto; Catelani, Carlo; Aversa, Alessandro; Rossi, Alessandro; Giannini, Domenico; Bani, Daniele

    2015-01-01

    Summary Autologous bone, for its osteoconductive, osteoinductive and osteogenetic properties, has been considered to be the gold standard for maxillary sinus augmentation procedures. Autograft procedures bring also some disadvantages: sometimes the limited amount of available intraoral bone makes necessary to obtain bone from an extraoral site, and this carries an associated morbidity. To overcome this problem we started using homologous freeze-dried bone in maxillary sinus augmentation procedures. This bone is industrially processed with γ-irradiation to eliminate its disease transmission potential and it’s considered safe, but this treatment also eliminates the osteoinductive and osteogenetic properties, making it just an inert scaffold for regeneration. Mesenchymal stem cells are successfully used in and orthopedic surgery for their amplification potential of healing mechanisms. We assumed that mesenchymal stem cells can restore the osteogenetic and osteoinductive properties in homologous bone grafts. The aim of this study was an histological evaluation of bone regeneration in maxillary sinus elevation using: 1) mesenchymal stem cells engineered freeze-dried bone allografts; 2) freeze-dried bone allografts. Twenty patients (10M, 10F) with a mean age of 55.2 years affected by severe maxillary atrophy were treated with bilateral maxillary sinus floor elevation. For each patient were randomly assigned a “test” side and a “control” side, different from each other exclusively in the composition of the graft material. The “control” sides were composed by corticocancellous freeze-dried bone chips and the “test” sides were composed by corticocancellous freeze-dried bone chips engineered in a bone marrow mesenchymal stem cells concentrate. After three months bone biopsies were performed on the grafts and histological specimens were made in order to evaluate the healed bone from an histological point of view. Histologically all the specimens showed

  17. Autogenous calvarium bone grafting as a treatment for severe bone resorption in the upper maxilla: a case report.

    PubMed

    Díaz-Romeral-Bautista, Migugel; Manchón-Miralles, Angel; Asenjo-Cabezón, Jorge; Cebrián-Carretero, José-Luis; Torres-García-Denche, Jesús; Linares-García-Valdecasas, Rafael

    2010-03-01

    Atrophic maxilla rehabilitation has been the subject of several studies for decades; despite this, there are still many different therapeutic choices for the best way to treat maxillary resorption in order to enable implant placement and integration. These possibilities include the optimal use of remaining bone structures, such as the pterygoid processes or zygomatic arch, which involves using zygomaticus and pterygoid implants in combination with standard implants placed in the residual bone; alternatively, regenerative techniques, alveolar bone expansion/distraction or bone grafting techniques may be used. Severe maxillary atrophy has a multifactorial aetiology; the most important factors being long evolution edentulism, hyperpneumatization of the maxillary sinus, post-traumatic deficit, bone loss after surgery (tumours, cysts) and periodontal problems or infection. In this report, we present a clinical case of onlay block reconstruction in an atrophic maxilla with harvested cranial calvarium bone grafts for successful future implant-supported oral rehabilitation. PMID:19767715

  18. Bone grafting, corticotomy, and orthodontics: treatment of cleft alveolus in a chinese cohort.

    PubMed

    Mao, Li-Xia; Shen, Guo-Fang; Fang, Bing; Xia, Yun-Hui; Ma, Xu-Hui; Wang, Bo

    2013-11-01

    Objective : A multimodal therapy was applied to solve a set of related problems including collapse of the posterior segment, high level gingival margin of canine, and resorption of grafted bone in a cohort of Chinese youngsters with cleft lip and palate. This study aimed to evaluate the benefits of this treatment procedure. Methods : Thirty patients with unilateral cleft lip and palate were included in this prospective study. All patients had previously undergone only cleft lip and palate repair and presented with alveolar cleft and an obvious step in the gingival margin between the canine tooth and the teeth beside it. A multimodal therapy that included bone grafting, corticotomy, and orthodontics was applied to solve these problems. Grafted bone volume, parallelism of the roots, root resorption, gingival margin, and mobility of the canine on the cleft side were established before surgery, 1 week after surgery, and after straightening of the canine. Results : Less than 25% of the grafted bone was reabsorbed in 25 of the 30 patients, while less than 50% was resorbed in the remaining five. The roots of the canines on the cleft side were mostly parallel to the adjacent teeth. Root resorption and mobility of the canines were slight. The difference in the gingival margin between the canines on the cleft side and the other side was small. Conclusions : Canines moved into the grafted bone safely and effectively, thus achieving a normal gingival margin and retaining grafted bone volume in one operation. PMID:22849663

  19. Osseous and dental outcomes of primary gingivoperiosteoplasty with iliac bone graft: A radiological evaluation.

    PubMed

    Touzet-Roumazeille, Sandrine; Vi-Fane, Brigitte; Kadlub, Natacha; Genin, Michaël; Dissaux, Caroline; Raoul, Gwenaël; Ferri, Joël; Vazquez, Marie-Paule; Picard, Arnaud

    2015-07-01

    Primary alveolar cleft repair has two main purposes: to restore normal morphology and normal function. Gingivoperiosteoplasty with bone grafting in mixed dentition has been a well-established procedure. We hypothesized that 1) performance of this surgery in deciduous dentition would provide favorable bone graft osseointegration, and 2) would improve the support of incisor teeth eruption, thereby avoiding maxillary growth disturbances. We conducted a retrospective study of clinical and tridimensional radiological data for 73 patients with alveolar clefts (with or without lip and palate clefts) who underwent gingivoperiosteoplasty with iliac bone graft in deciduous dentition. Pre- and post-operative Cone Beam Computed Tomography (CBCT) comparison allowed evaluation of the ratio between bone graft volume and initial cleft volume (BGV/ICV ratio), and measurement of central incisor teeth movements. This series of 73 patients included 44 males and 29 females, with a mean age of 5.5 years. Few complications were observed. Post-operative CBCT was performed at 7.4 months. The mean BGV/ICV ratio was 0.62. Axial rotation was significantly improved post-operatively (p = 0.004). Gingivoperiosteoplasty with iliac bone graft is safe when performed in deciduous dentition and results in a sufficient bone graft volume to support lateral incisor eruption and upper central incisor tooth position improvement. PMID:26004807

  20. Bone graft substitutes and bone morphogenetic proteins for osteoporotic fractures: what is the evidence?

    PubMed

    Van Lieshout, Esther M M; Alt, Volker

    2016-01-01

    Despite improvements in implants and surgical techniques, osteoporotic fractures remain challenging to treat. Among other major risk factors, decreased expression of morphogenetic proteins has been identified for impaired fracture healing in osteoporosis. Bone grafts or bone graft substitutes are often used for stabilizing the implant and for providing a scaffold for ingrowth of new bone. Both synthetic and naturally occurring biomaterials are available. Products generally contain hydroxyapatite, tricalcium phosphate, dicalcium phosphate, calcium phosphate cement, calcium sulfate (plaster of Paris), or combinations of the above. Products have been used for the treatment of osteoporotic fractures of the proximal humerus, distal radius, vertebra, hip, and tibia plateau. Although there is generally consensus that screw augmentation increased the biomechanical properties and implant stability, the results of using these products for void filling are not unequivocal. In osteoporotic patients, Bone Morphogenetic Proteins (BMPs) have the potential impact to improve fracture healing by augmenting the impaired molecular and cellular mechanisms. However, the clinical evidence on the use of BMPs in patients with osteoporotic fractures is poor as there are no published clinical trials, case series or case studies. Even pre-clinical literature on in vitro and in vivo data is weak as most articles focus on the beneficial role for BMPs for restoration of the underlying pathophysiological factors of osteoporosis but do not look at the specific effects on osteoporotic fracture healing. Limited data on animal experiments suggest stimulation of fracture healing in ovariectomized rats by the use of BMPs. In conclusion, there is only limited data on the clinical relevance and optimal indications for the use of bone graft substitute materials and BMPs on the treatment of osteoporotic fractures despite the clinical benefits of these materials in other clinical indications. Given the

  1. Long-term enzyme replacement therapy in beta-glucuronidase--deficient mice by allogeneic bone marrow transplantation

    SciTech Connect

    Yatziv, S.; Weiss, L.; Morecki, S.; Fuks, Z.; Slavin, S.

    1982-06-01

    Enzyme replacement therapy was successfully accomplished in beta-Glu-deficient C3H/HeJ mice after transplantation of BM cells obtained from normal BALB/c donors. Marrow recipients were prepared for transplantation by fractionated TLI. Enzyme activity increased from 20.5 +/- 7.0 nmol/mg of protein per hour to 180 +/- 30.2 in the liver (p less than 0.001) and from 8.2 +/- 2.0 to 17.5 +/- 5.0 nmol/ml/hr in the plasma (p less than 0.05) at 50 days after marrow infusion. Normal enzyme activity was maintained in treated mice for at least 100 days after marrow transplantation, as documented by repeated liver biopsies and examination of plasma samples. The marrow donors and the recipients were fully histoincompatible. Both immunologic rejection of the marrow allograft and GVHD were prevented by the prior conditioning of the recipients with TLI, resulting in bilateral transplantation tolerance of host vs. graft and graft vs. host. The data suggest that allogeneic BM transplantation may provide a possible therapeutic approach for certain enzyme deficiency syndromes.

  2. Allogeneic cell transplant expands bone marrow distribution by colonizing previously abandoned areas: an FDG PET/CT analysis.

    PubMed

    Fiz, Francesco; Marini, Cecilia; Campi, Cristina; Massone, Anna Maria; Podestà, Marina; Bottoni, Gianluca; Piva, Roberta; Bongioanni, Francesca; Bacigalupo, Andrea; Piana, Michele; Sambuceti, Gianmario; Frassoni, Francesco

    2015-06-25

    Mechanisms of hematopoietic reconstitution after bone marrow (BM) transplantation remain largely unknown. We applied a computational quantification software application to hybrid 18F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) images to assess activity and distribution of the hematopoietic system throughout the whole skeleton of recently transplanted patients. Thirty-four patients underwent PET/CT 30 days after either adult stem cell transplantation (allogeneic cell transplantation [ACT]; n = 18) or cord blood transplantation (CBT; n = 16). Our software automatically recognized compact bone volume and trabecular bone volume (IBV) in CT slices. Within IBV, coregistered PET data were extracted to identify the active BM (ABM) from the inactive tissue. Patients were compared with 34 matched controls chosen among a published normalcy database. Whole body ABM increased in ACT and CBT when compared with controls (12.4 ± 3 and 12.8 ± 6.8 vs 8.1 ± 2.6 mL/kg of ideal body weight [IBW], P < .001). In long bones, ABM increased three- and sixfold in CBT and ACT, respectively, compared with controls (0.9 ± 0.9 and 1.7 ± 2.5 vs 0.3 ± 0.3 mL/kg IBW, P < .01). These data document an unexpected distribution of transplanted BM into previously abandoned BM sites. PMID:25957389

  3. Applications of coronoid process as a bone graft in maxillofacial surgery.

    PubMed

    Sabhlok, Samrat; Waknis, Pushkar P; Gadre, Kiran S

    2014-03-01

    The coronoid process can be easily harvested as a donor bone by an intraoral approach during many maxillofacial surgery procedures. The purpose of this study was to evaluate the utility of autogenous coronoid process bone grafts for maxillofacial reconstructive surgery. Twelve patients, who underwent coronoid process grafts for reconstruction of maxillofacial deformities due to trauma, alveolar atrophy, or temporomandibular joint ankylosis, were included in the study. There were 3 orbital defects after extended maxillectomy, 1 blowout fracture of the orbit, 2 cases of reconstruction after temporomandibular joint ankylosis surgery, 1 case of additional chin augmentation following horizontal flip genioplasty, 1 defect of anterior wall of maxilla due to trauma, 2 mandibular defects, and 2 cases of bone augmentation for implants.We recommend the use of coronoid process of the mandible as a source for autogenous bone graft as it can provide sufficient bone in quantity and quality for selected maxillofacial reconstructions. PMID:24621702

  4. In Vivo Tracking of Systemically Administered Allogeneic Bone Marrow Mesenchymal Stem Cells in Normal Rats through Bioluminescence Imaging

    PubMed Central

    Cao, Juan; Hou, Shike; Ding, Hui; Liu, Ziquan; Song, Meijuan; Qin, Xiaojing; Wang, Xue; Yu, Mengyang; Sun, Zhiguang; Liu, Jinyang; Sun, Shuli; Xiao, Peixin

    2016-01-01

    Recently, mesenchymal stem cells (MSCs) are increasingly used as a panacea for multiple types of disease short of effective treatment. Dozens of clinical trials published demonstrated strikingly positive therapeutic effects of MSCs. However, as a specific agent, little research has focused on the dynamic distribution of MSCs after in vivo administration. In this study, we track systemically transplanted allogeneic bone marrow mesenchymal stem cells (BMSCs) in normal rats through bioluminescence imaging (BLI) in real time. Ex vivo organ imaging, immunohistochemistry (IHC), and RT-PCR were conducted to verify the histological distribution of BMSCs. Our results showed that BMSCs home to the dorsal skin apart from the lungs and kidneys after tail vein injection and could not be detected 14 days later. Allogeneic BMSCs mainly appeared not at the parenchymatous organs but at the subepidermal connective tissue and adipose tissue in healthy rats. There were no significant MSCs-related adverse effects except for transient decrease in neutrophils. These findings will provide experimental evidences for a better understanding of the biocharacteristics of BMSCs. PMID:27610137

  5. In Vivo Tracking of Systemically Administered Allogeneic Bone Marrow Mesenchymal Stem Cells in Normal Rats through Bioluminescence Imaging.

    PubMed

    Cao, Juan; Hou, Shike; Ding, Hui; Liu, Ziquan; Song, Meijuan; Qin, Xiaojing; Wang, Xue; Yu, Mengyang; Sun, Zhiguang; Liu, Jinyang; Sun, Shuli; Xiao, Peixin; Lv, Qi; Fan, Haojun

    2016-01-01

    Recently, mesenchymal stem cells (MSCs) are increasingly used as a panacea for multiple types of disease short of effective treatment. Dozens of clinical trials published demonstrated strikingly positive therapeutic effects of MSCs. However, as a specific agent, little research has focused on the dynamic distribution of MSCs after in vivo administration. In this study, we track systemically transplanted allogeneic bone marrow mesenchymal stem cells (BMSCs) in normal rats through bioluminescence imaging (BLI) in real time. Ex vivo organ imaging, immunohistochemistry (IHC), and RT-PCR were conducted to verify the histological distribution of BMSCs. Our results showed that BMSCs home to the dorsal skin apart from the lungs and kidneys after tail vein injection and could not be detected 14 days later. Allogeneic BMSCs mainly appeared not at the parenchymatous organs but at the subepidermal connective tissue and adipose tissue in healthy rats. There were no significant MSCs-related adverse effects except for transient decrease in neutrophils. These findings will provide experimental evidences for a better understanding of the biocharacteristics of BMSCs. PMID:27610137

  6. Comparison of the Application of Allogeneic Fibroblast and Autologous Mesh Grafting With the Conventional Method in the Treatment of Third-Degree Burns.

    PubMed

    Moravvej, Hamideh; Hormozi, Abdoljalil Kalantar; Hosseini, Seyed Nejat; Sorouri, Rahim; Mozafari, Naser; Ghazisaidi, Mohammad Reza; Rad, Mahnaz Mahmoudi; Moghimi, Mohammad Hossein; Sadeghi, Shahin Mohammad; Mirzadeh, Hamid

    2016-01-01

    Wound healing is a multipart process involving different cell types and growth factors. Third-degree burns are usually treated by early excision and skin grafting. Tissue engineering has been developed in this field in response to limitations associated with autografts. Allogeneic fibroblasts on meshed split thickness skin grafts (STSGs) are known to have useful properties in wound healing and can be used to construct a new model of living skin substitute. Fourteen patients were chosen from June 2009 until December 2010 as the sample for this study. After debridement and wound excision, meshed STSG was used to cover the entire wound. Alloskin (allofibroblasts cultured on a combination of silicone and glycosaminoglycan) was applied on one side and petroleum jelly-impregnated gauze (Iran Polymer and Petrochemical Institute) was applied on the other. The healing time, scar formation, and pigmentation score were assessed for the patients. All analyses were undertaken with SPSS 17 software. Alloskin demonstrated good properties compared to petroleum jelly-impregnated gauze. The average healing time and hypertrophic scar formation were significantly different between the two groups. In addition, the skin pigmentation score in the alloskin group was closer to normal. Alloskin grafting, including fibroblasts on meshed STSG, may be a useful method to reduce healing time and scar size and may require less autologous STSG in extensive burns where a high percentage of skin is burned and there is a lack of available donor sites. PMID:22683986

  7. Long-term outcome of dental implants after maxillary augmentation with and without bone grafting

    PubMed Central

    Machuca-Ariza, Jesús; Ruiz-Martos, Alberto; Ramos-Robles, Mª-Carmen; Martínez-Lara, Ildefonso

    2016-01-01

    Background This study aims to evaluate the technique of sinus bone reformation, which consists of elevating the sinus membrane and placement the implant without bone graft, compared with the widely-used technique involving raising the maxillary sinus and grafting, using animal hydroxyapatite as the filler, while simultaneously fixing the implants. Material and Methods This is a retrospective study on two groups of patients who underwent elevation of the sinus membrane and simultaneous placement of the implant. The grafting technique was applied to one group, while the other had no graft. An alveolar ridge height of 4 to 7 mm was necessary. Radiological control was undertaken at 6 months and one year post-prosthetic loading. In each group 38 implants were placed. Results No significant behavioural differences were observed in the implants according to the Albrektsson success criteria. Implant failure was observed in 2 implants from the bone grafting group (success rate 93%) and in 1 implant from the reformation group (success rate 97%). In this group, bone formation was observed on both sides of each implant, the bone gain was measured using image management software (2.7±0.9mm mesial and 2.6±0.9mm distal). There was no correlation between mesial and distal bone gain and implant´s length. Conclusions The results indicate that bone reformation is a valid technique in cases involving atrophy of the posterior maxilla. Primary stability, maintenance of space by the implant, and the formation of a blood clot are crucial in this technique in order to achieve bone formation around the implant. It is an alternative to the conventional technique of sinus lift with filling material, and has several advantages over this procedure, including a lower infection risk, as it does not involve a biomaterial, reduced cost, a simpler technique, and better acceptance by the patient. Key words:Bone formation, sinus membrane elevation, maxillary sinus, bone grafting. PMID:26827071

  8. Expression of SOCS1 and SOCS3 genes in human graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

    PubMed Central

    Lee, Tae Hyang; Lee, Ji Yoon; Park, Sohye; Shin, Seung Hwan; Yahng, Seung-Ah; Yoon, Jae-Ho; Lee, Sung-Eun; Cho, Byung-Sik; Kim, Yoo-Jin; Lee, Seok; Min, Chang-Ki; Kim, Dong-Wook; Lee, Jong-Wook; Min, Woo-Sung; Park, Chong-Won

    2013-01-01

    Background Suppressor of cytokine signaling genes (SOCS) are regarded as pivotal negative feedback regulators of cytokine signals, including the interferon-gamma (IFN-γ), granulocyte-colony stimulating factor, and interleukin families, released by T cells. A detailed understanding of the involvement of SOCS genes in graft-versus-host disease (GVHD) is critical to effectively manage GVHD, yet their expression patterns among recipients remain largely unexplored. Methods Expression levels of SOCS1 and SOCS3 were determined by real-time quantitative reverse transcription PCR (qRT-PCR) in patients with acute GVHD (aGVHD) and chronic GVHD (cGVHD), in a severity-dependent manner, after allogeneic hematopoietic stem cell transplantation (HSCT). A total of 71 recipients with AML (N=40), ALL (N=12), myelodysplastic syndromes (MDS; N=10), chronic myelogenous leukemia (CML; N=2), severe aplastic anemia (SAA; N=5), or others (N=2), who received allogeneic HSCT from human leukocyte antigen-identical siblings or unrelated donors between 2009 and 2011, were included in the present study. Results Overall, the expression levels of SOCS1 decreased in recipients with grade II to IV aGVHD and cGVHD when compared to normal donors and non-GVHD recipients. Interestingly, the expressions of SOCS1 decreased significantly more in cGVHD than in aGVHD recipients (P=0.0091). In contrast, SOCS3 expressions were similarly reduced in all the recipients. Conclusion This is the first study to show that SOCS1 and SOCS3 are differentially expressed in recipients following allogeneic HSCT, suggesting a prognostic correlation between SOCS genes and the development of GVHD. This result provides a new platform to study GVHD immunobiology and potential diagnostic and therapeutic targets for GVHD. PMID:23589790

  9. Experience of using vascularized bone grafts in reconstructive surgery of the upper limbs

    NASA Astrophysics Data System (ADS)

    Atamanov, E. A.; Keosyan, V. T.; Bryukhanov, A. V.; Tsaregorodtseva, E. M.; Danilov, A. V.

    2015-11-01

    The article describes the results of treatment patients with defects and diseases of bone tissue using bone grafting with vascularized bone grafts from different areas of the body. The results of treatment of 27 patients with bone tissue defects of the upper extremities are demonstrated. 16 of patients had scaphoid nonunion. 2 cases of nonunion were reported: one scaphoid nonunion due to unstable osteosynthesis and one lunate fragmentation nonunion in patient with late stage Kienbock`s disease. Vascularized bone graft from distal radius was used in both cases. We had two cases of delayed union at 18 months in surgical treatment of scaphoid. 2 patients had metacarpal bone defect, 1 patient with radius bone defect, 2 patients with SLAC (scapholunate advanced collapse), 2 patients with bone defect of the humerus, 1 patient with bone defect of the ulna. In all cases we used vascularized bone crafts from various anatomical areas. We achieved union in all other cases. The study shows high efficiency of upper extremity bone defect replacement methods.

  10. Prognostic Factors on the Graft-versus-Host Disease-Free and Relapse-Free Survival after Adult Allogeneic Hematopoietic Stem Cell Transplantation

    PubMed Central

    Liu, Yao-Chung; Chien, Sheng-Hsuan; Fan, Nai-Wen; Hu, Ming-Hung; Gau, Jyh-Pyng; Liu, Chia-Jen; Yu, Yuan-Bin; Hsiao, Liang-Tsai; Chiou, Tzeon-Jye; Tzeng, Cheng-Hwai; Chen, Po-Min; Liu, Jin-Hwang

    2016-01-01

    The cure of hematologic disorders by allogeneic hematopoietic stem cell transplantation (HSCT) is often associated with major complications resulting in poor outcome, including graft-versus-host disease (GVHD), relapse, and death. A novel composite endpoint of GVHD-free/relapse-free survival (GRFS) in which events include grades 3-4 acute GVHD, chronic GVHD requiring systemic therapy, relapse, or death is censored to completely characterize the survival without mortality or ongoing morbidity. In this regard, studies attempting to identify the prognostic factors of GRFS are quite scarce. Thus, we reviewed 377 adult patients undergoing allogeneic HSCT between 2003 and 2013. The 1- and 2-year GRFS were 40.8% and 36.5%, respectively, significantly worse than overall survival and disease-free survival (log-rank p < 0.001). European Group for Blood and Marrow Transplantation (EBMT) risk score > 2 (p < 0.001) and hematologic malignancy (p = 0.033) were poor prognostic factors for 1-year GRFS. For 2-year GRFS, EBMT risk score > 2 (p < 0.001), being male (p = 0.028), and hematologic malignancy (p = 0.010) were significant for poor outcome. The events between 1-year GRFS and 2-year GRFS predominantly increased in relapsed patients. With prognostic factors of GRFS, we could evaluate the probability of real recovery following HSCT without ongoing morbidity. PMID:27123006

  11. Effect of MMA-g-UHMWPE grafted fiber on mechanical properties of acrylic bone cement.

    PubMed

    Yang, J M; Huang, P Y; Yang, M C; Lo, S K

    1997-01-01

    Ultrahigh molecular weight polyethylene (UHMWPE) fibers were treated with argon plasma for 5 min, followed by uv irradiation in methyl methacrylate (MMA)-chloroform solution for 5 h to obtain MMA-g-UHMWPE grafted fiber. The grafting content was estimated by the titration of esterification method. The grafting amount of 5280 nmol/g was the largest for the MMA concentration at 18.75 vol%. To improve the mechanical properties of acrylic bone cement, pure UHMWPE fiber and MMA-g-UHMWPE fiber were added to the surgical Simplex. P radiopaque bone cement. The mechanical properties including tensile strength, tensile modulus, compressive strength, bending strength, and bending stiffness were measured. Dynamic mechanical analysis was also performed. By comparing the effect of the pure UHMWPE fiber and MMA-g-UHMWPE grafted fiber on the mechanical properties of acrylic bone cement, it was found that the acrylic bone cement with MMA-g-UHMWPE grafted fiber had a more significant reinforcing effect than that with untreated UHMWPE fiber. This might be due to the improvement of the interfacial bonding between the grafted fibers and the acrylic bone cement matrix. PMID:9421758

  12. Alternative method to treat oroantral communication and fistula with autogenous bone graft and platelet rich firbin

    PubMed Central

    Niedzielska, Iwona; Borgiel-Marek, Halina; Różanowski, Bartosz

    2016-01-01

    Background Removing a tooth from the jaw results in the occurrence of oroantral communication in beneficial anatomic conditions or in the case of a iatrogenic effect. Popularized treatments of the oroantral communication have numerous faults. Large bone defect eliminates the chance to introduce an implant. Purpose of this work was assessment of the usefulness of autogenous bone graft and PRF in normal bone regeneration in the site of oroantral communication. Material and Methods Bone regeneration in the site of oroantral communication was assessed in 20 patients. Bone defects were supplemented autogenous bone graft from mental protuberance in 14 cases and from oblique line in 6 cases. The graft was covered with a PRF membrane. Results In the study group in all cases closure of the oroantral communication was observed. The average width of the alveolar was 13 mm and the average height was 12.5 mm. In 3 patients an average increase of alveolar height of 1.5 mm was observed. Conclusions This method may be the best option to prepare alveolar for new implant and prosthetic solutions. Key words:Oroantral communication, oroantral fistula, autogenous bone graft, bone regeneration, platelet rich fibrin. PMID:27475687

  13. Minimally Invasive Harvest of a Quadriceps Tendon Graft With or Without a Bone Block

    PubMed Central

    Fink, Christian; Herbort, Mirco; Abermann, Elisabeth; Hoser, Christian

    2014-01-01

    The quadriceps tendon (QT) as a graft source for anterior cruciate ligament (ACL) and posterior cruciate ligament reconstruction has recently achieved increased attention. Although many knee surgeons have been using the QT as a graft for ACL revision surgery, it has never gained universal acceptance for primary ACL reconstruction. The QT is a very versatile graft that can be harvested in different widths, thicknesses, and lengths. Conventionally, the QT graft is harvested by an open technique, requiring a 6 to 8 cm longitudinal incision, which often leads to unpleasant scars. We describe a new, minimally invasive, standardized approach in which the QT graft can be harvested through a 2- to 3-cm skin incision and a new option of using the graft without a bone block. PMID:25264512

  14. Minimally invasive harvest of a quadriceps tendon graft with or without a bone block.

    PubMed

    Fink, Christian; Herbort, Mirco; Abermann, Elisabeth; Hoser, Christian

    2014-08-01

    The quadriceps tendon (QT) as a graft source for anterior cruciate ligament (ACL) and posterior cruciate ligament reconstruction has recently achieved increased attention. Although many knee surgeons have been using the QT as a graft for ACL revision surgery, it has never gained universal acceptance for primary ACL reconstruction. The QT is a very versatile graft that can be harvested in different widths, thicknesses, and lengths. Conventionally, the QT graft is harvested by an open technique, requiring a 6 to 8 cm longitudinal incision, which often leads to unpleasant scars. We describe a new, minimally invasive, standardized approach in which the QT graft can be harvested through a 2- to 3-cm skin incision and a new option of using the graft without a bone block. PMID:25264512

  15. Autologous cranial particulate bone graft: an experimental study of onlay cranioplasty.

    PubMed

    Clune, James E; Mulliken, John B; Glowacki, Julie; Arany, Praveen R; Kulungowski, Ann M; Rogers, Gary F; Greene, Arin K

    2011-01-01

    The purpose of this study was to determine whether particulate bone graft maintains its volume when used for onlay cranioplasty. Twenty-five adult, male, New Zealand white rabbits were divided into 5 groups (n = 5/group). Groups 1 to 3 were controls: group 1, untreated; group 2, sham procedure; and group 3, burring the cortical surface. Group s 4 and 5 had augmentation of the parietal bones with particulate graft harvested from the frontal bone with a brace and bit. The particulate graft was placed on native parietal bone (group 4) or on parietal bone that had been abraded to punctuate bleeding with an electric burr (group 5). Volume maintenance and osseointegration of the grafts were determined by micro-computed tomography and histology. At 16 weeks postoperatively, the mean (SD) volumes of the parietal bones in control groups 1, 2, and 3 were 555.8 (29.2), 550.8 (36.8), and 539.0 (39.0) mm, respectively. Immediately after cranioplasty, the mean (SD) volumes of augmented parietal bone were 846.0 (10.8) mm for group 4 and 831.8 (11.8) mm for group 5. Sixteen weeks postoperatively, 100% of the group 4 grafts had resorbed (551.8 [SD, 24.0] mm), and parietal volume was no different from controls (P = 0.89). Group 5 maintained 54.2% of volume (695.6 [SD, 22.0] mm), which was greater than those of the controls (P < 0.0001). Particulate graft may be used for onlay cranioplasty if the recipient site is burred. Approximately one half of the onlay graft is resorbed, and its original shape is not maintained. PMID:21239926

  16. Ordinary and Activated Bone Grafts: Applied Classification and the Main Features

    PubMed Central

    Deev, R. V.; Drobyshev, A. Y.; Bozo, I. Y.; Isaev, A. A.

    2015-01-01

    Bone grafts are medical devices that are in high demand in clinical practice for substitution of bone defects and recovery of atrophic bone regions. Based on the analysis of the modern groups of bone grafts, the particularities of their composition, the mechanisms of their biological effects, and their therapeutic indications, applicable classification was proposed that separates the bone substitutes into “ordinary” and “activated.” The main differential criterion is the presence of biologically active components in the material that are standardized by qualitative and quantitative parameters: growth factors, cells, or gene constructions encoding growth factors. The pronounced osteoinductive and (or) osteogenic properties of activated osteoplastic materials allow drawing upon their efficacy in the substitution of large bone defects. PMID:26649300

  17. Secondary Alveolar Bone Grafting and Iliac Cancellous Bone Harvesting for Patients With Alveolar Cleft.

    PubMed

    Pan, Weiyi; Wu, Chenzhou; Yang, Zheng; Duan, Zexi; Su, Zhifei; Wang, Peiqi; Zheng, Qian; Li, Chunjie

    2016-06-01

    To assess the efficacy of present interventions optimizing the result of secondary alveolar bone grafting (SABG) and the interventions alleviating the donor site morbidity after iliac cancellous bone harvesting. Researches were identified by searching the electronic database of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Chinese BioMedical Literature Database, and the China National Knowledge Infrastructure. In addition, relevant journals and references of the included studies were searched manually. The Oxford 2011 Levels of Evidence were applied to assess the methodological quality of selected studies, and the best evidence synthesis system was applied afterward to measure the strength of evidence. As a result, 42 studies were considered eligible and included, among which 4 were of high quality while 38 were of low quality. Thirty lines of evidences were acquired after the synthesis, among which 13 were rated as moderate while 17 were rated as insufficient. As for the interventions optimizing the result of SABG, moderate evidence confirmed the efficacy of preoperative orthodontic treatment, the superiority of performing SABG before the eruption of canine, and the accuracy of cone beam computed tomography in preoperative estimation of the cleft volume. As for the interventions alleviating the morbidity of iliac cancellous bone harvesting, moderate evidence confirmed the treatment benefit of the interventions below: minimally invasive technique, including trephine and Shepard osteotomy; preemptive analgesia, including continuous bupivacaine infusion or transversus abdominis plane block. As for the rest interventions, only insufficient evidence was found. PMID:27244214

  18. Free bone graft reconstruction of irradiated facial tissue: Experimental effects of basic fibroblast growth factor stimulation

    SciTech Connect

    Eppley, B.L.; Connolly, D.T.; Winkelmann, T.; Sadove, A.M.; Heuvelman, D.; Feder, J. )

    1991-07-01

    A study was undertaken to evaluate the potential utility of basic fibroblast growth factor in the induction of angiogenesis and osseous healing in bone previously exposed to high doses of irradiation. Thirty New Zealand rabbits were evaluated by introducing basic fibroblast growth factor into irradiated mandibular resection sites either prior to or simultaneous with reconstruction by corticocancellous autografts harvested from the ilium. The fate of the free bone grafts was then evaluated at 90 days postoperatively by microangiographic, histologic, and fluorochrome bone-labeling techniques. Sequestration, necrosis, and failure to heal to recipient osseous margins was observed both clinically and histologically in all nontreated irradiated graft sites as well as those receiving simultaneous angiogenic stimulation at the time of graft placement. No fluorescent activity was seen in these graft groups. In the recipient sites pretreated with basic fibroblast growth factor prior to placement of the graft, healing and reestablishment of mandibular contour occurred in nearly 50 percent of the animals. Active bone formation was evident at cortical margins adjacent to the recipient sites but was absent in the more central cancellous regions of the grafts.

  19. The Volume Behavior of Autogenous Iliac Bone Grafts After Sinus Floor Elevation: A Clinical Pilot Study.

    PubMed

    Gerressen, Marcus; Riediger, Dieter; Hilgers, Ralf-Dieter; Hölzle, Frank; Noroozi, Nelson; Ghassemi, Alireza

    2015-06-01

    Iliac crest is still regarded as one of the most viable source of autogenous graft materials for extensive sinus floor elevation. Three-dimensional resorption behavior has to be taken into account in anticipation of the subsequent insertion of dental implants. We performed 3-dimensional volume measurements of the inserted bone transplants in 11 patients (6 women and 5 men; mean age = 2.3 years) who underwent bilateral sinus floor elevation with autogenous iliac crest grafts. In order to determine the respective bone graft volumes, cone-beam computerized tomography studies of the maxillary sinuses were carried out directly after the operation (T0), as well as 3 months (T1) and 6 months (T2) postoperatively. The acquired DICOM (Digital Imaging and Communications in Medicine) data sets were evaluated using suitable analysis software. We evaluated statistical significance of graft volumes changes using a linear mixed model with the grouping factors for time, age, side, and sex with a significance level of P = .05. 38.9% of the initial bone graft volume, which amounted to 4.2 cm(3), was resorbed until T1. At T2, the average volume again decreased significantly by 18.9 % to finally reach 1.8 cm(3). The results show neither age nor side dependency and apply equally to both sexes. Without functional load, iliac bone grafts feature low-volume stability in sinus-augmentation surgery. Further clinical and animal studies should be done to detect the optimal timing for implant placement. PMID:24303797

  20. Treatment of a two wall defect in a mandibular posterior tooth with autogenous bone graft obtained during ledge removal with a hand instrument

    PubMed Central

    Sam, George; Vadakkekuttical, Rosamma Joseph; Harikumar, Kanakkath; Amol, Nagrale Vijay

    2015-01-01

    Autogenous bone grafts have been considered the gold standard for bone grafting procedures. This case report describes the management of a two wall defect by utilizing the autogenous bone graft obtained during removal of ledges as a part of osteoplasty procedure. The bone was removed with a sickle scaler, and sufficient amounts of bone graft material were obtained to fill a two wall defect distal to left mandibular first molar. PMID:26392695

  1. Posterolateral spinal fusion in a rabbit model using a collagen–mineral composite bone graft substitute

    PubMed Central

    Vizesi, F.; Cornwall, G. B.; Bell, D.; Oliver, R.; Yu, Y.

    2009-01-01

    Choosing the appropriate graft material to participate in the healing process in posterolateral spinal fusion continues to be a challenge. Combining synthetic graft materials with bone marrow aspirate (BMA) and autograft is a reasonable treatment option for surgeons to potentially reduce or replace the need for autograft. FormaGraft, a bone graft material comprising 12% bovine-derived collagen and 88% ceramic in the form of hydroxyapatite (HAp) and beta tricalcium phosphate (β-TCP) was evaluated in three possible treatment modalities for posterior spinal fusion in a standard rabbit model. These three treatment groups were FormaGraft alone, FormaGraft soaked in autogenous BMA, and FormaGraft with BMA and iliac crest autograft. No statistically demonstrable benefits or adverse effects of the addition of BMA were found in the current study based on macroscopic, radiology or mechanical data. This may reflect, in part, the good to excellent results of the collagen HA/TCP composite material alone in a well healing bony bed. Histology did, however, reveal a benefit with the use of BMA. Combining FormaGraft with autograft and BMA achieved results equivalent to autograft alone. The mineral and organic nature of the material provided a material that facilitated fusion between the transverse processes in a standard preclinical posterolateral fusion model. PMID:19475437

  2. The use of autogeneous mandibular bone block grafts for reconstruction of alveolar defects

    PubMed Central

    Dolanmaz, Doğan; Esen, Alparslan; Yıldırım, Gülsün; İnan, Özgür

    2015-01-01

    Objective: Purpose of this retrospective study was to evaluate outcomes autogenous bone block grafts obtained from mandible for different indications. The healing of the donor and recipient sites in the postoperative period, morbidity and the resorption of the graft were investigated. Patients and Methods: Twenty-nine patients grafted with mandibular bone block graft were participated in the present study. Grafting was applied in these patients for three indications; reconstruction of alveolar cleft, lateral crest augmentation before dental implantation and sinus floor augmentation. All operations were performed under local anesthesia and in some cases sedation was used as well. Results: Minimal exposure of the block graft occurred in three alveolar cleft patients. Secondary epithelization was achieved in all cleft patients with no symptoms of infection. In one patient infection was seen in donor site 1-week after the operation. The region was curetted and antibiotics administrated again. Two patients showed an infection of recipient site, after 4 weeks the grafts were removed. In all the patients, as the screw head became apparent until 1 thread, amount of the resorption were considered <1.5 mm. Conclusion: The usage of mandibular block grafts is a simple and effective treatment modality for reconstruction of different types of alveolar defects and it also reduces cost of treatment. PMID:26389038

  3. Cyclooxygenase-2 inhibition does not impair block bone grafts healing in rabbit model.

    PubMed

    Moreschi, Eduardo; Biguetti, Claudia Cristina; Comparim, Eliston; De Andrade Holgado, Leandro; Ribeiro-Junior, Paulo Domingos; Nary-Filho, Hugo; Matsumoto, Mariza Akemi

    2013-12-01

    Success of alveolar reconstructions using onlay autogenous block bone grafts depends on their adequate integration to the recipient bed influenced by a number of local molecules. Considering the fundamental role of cyclooxygenase (COX-2) in bone repair, the aim of this study was to analyze the effect of its inhibition in the integration of endochondral (EC) iliac crest, and intramembranous (IM) calvaria bone grafts. Thirty-two rabbits were divided into 4 groups: Calvaria Control (CC) and Iliac Control--treated with oral 0.9 % saline solution, and Calvarial-NSAID (C-NSAID) and Iliac-NSAID (I-NSAID) groups--treated with oral 6 mg/Kg non-steroidal anti-inflammatory drug etoricoxib. After 7, 14, 30 and 60 days the animals were euthanized and the specimens removed for histological, histomorphometric and immunohistochemistry analysis. At day 60, a tight integration of IM blocks could be seen with the presence of remodeling bone, whereas integration of EC grafts was mainly observed at the edges of the grafts. A significant higher percentage of bone matrix in the interface region of the CC grafts in comparison to C-NSAID only at day 14, whereas no differences were detected comparing the EC grafts. No differences were observed in Runx-2 and vascular endothelial growth factor (VEGF) immunolabeling when comparing CC and C-NSAID groups, while a significant weaker Runx-2 and VEGF labeling was detected in I-NSAID group at day 60. Although some influence was detected in osteogenesis, it is concluded that drug induced inhibition of COX-2 does not impair onlay bone grafts' healing of both embryologic origins in rabbits. PMID:23783533

  4. Rare giant cell tumor involvement of the olecranon bone

    PubMed Central

    Yang, Chen; Gong, Yubao; Liu, Jianguo; Qi, Xin

    2014-01-01

    Giant cell tumor (GCT) of bone is a relatively common benign bone lesion and is usually located in long bones, but involvement of the olecranon is extremely rare. Here, we present a case of solitary GCT of bone in the olecranon that was confirmed by preoperative needle biopsy and postoperative histological examination. The treatment included intralesional curettage, allogeneic bone grafting, and plating. At 26 months follow-up, the patient had no local recurrence. PMID:25197303

  5. Synchrotron X-ray bio-imaging of natural and synthetic bone-graft materials in an aqueous environment

    NASA Astrophysics Data System (ADS)

    Kim, Yong-Gun; Bark, Chung Wung

    2014-11-01

    Bone-graft materials in dentistry have osteoinductive and osteoconductive abilities, which depend on their microstructural characteristics, such as their porosity, particle size, micro channels, and absorption. These characteristics have been observed using various imaging techniques, such as optical microscopy and scanning electron microscopy (SEM). However, most techniques cannot provide images in water, even though graft materials in vivo are invariably in contact with different water-based fluids. Synchrotron X-ray imaging allows sample microenvironments to be controlled as X-ray beams easily penetrate air and water. In this report, we used the synchrotron X-ray imaging technique to provide in-situ images of various bone-graft materials in aqueous environments. We observed internal microstructural images of bone-graft materials in real-time in 0.9% saline solution and interactions between bone-graft materials and saline, that is, hydration patterns and bone-graft expansion.

  6. A Novel Local Autologous Bone Graft Donor Site After Scalp Tissue Expansion in Aplasia Cutis Congenita.

    PubMed

    Hadad, Ivan; Meara, John G; Rogers-Vizena, Carolyn R

    2016-06-01

    Aplasia cutis congenita (ACC) is a rare condition often presenting as an absent area of cutaneous scalp. The calvarium and dura may also be affected. Scalp reconstruction with tissue expansion is often needed for large defects. Patients involving deficient calvarial bone present a dilemma for the reconstructive surgeon, because bone graft donor sites are limited in young children.A thick, bony rim has been noted to form around the periphery of scalp tissue expanders. The authors present a series of 3 patients with ACC for whom this bony hyperostosis was used as donor particulate bone graft at the time of scalp tissue expansion. There was 85 to 100% graft ossification on postoperative computed tomography scan. There were no bone graft-related complications.In conclusion, the hyperostotic rim that forms after scalp tissue expansion can be successfully used as particulate bone graft, decreasing the number of procedures needed for patient with ACC and obviating the need for other donor sites. PMID:27192637

  7. Durable Remission of Renal Cell Carcinoma in Conjuncture with Graft versus Host Disease following Allogeneic Stem Cell Transplantation and Donor Lymphocyte Infusion: Rule or Exception?

    PubMed Central

    van Bergen, Cornelis A. M.; Verdegaal, Elisabeth M. E.; Honders, M. Wilhelmina; Hoogstraten, Conny; Steijn-van Tol, A. Q. M. Jeanne; de Quartel, Linda; de Jong, Joan; Meyering, Maaike; Falkenburg, J. H. Frederik; Griffioen, Marieke; Osanto, Susanne

    2014-01-01

    Allogeneic stem cell transplantation (alloSCT) followed by donor lymphocyte infusion (DLI) can be applied as immunotherapeutic intervention to treat malignant diseases. Here, we describe a patient with progressive metastatic clear cell renal cell carcinoma (RCC) who was treated with T cell depleted non-myeloablative alloSCT and DLI resulting in disease regression accompanied by extensive graft versus host disease (GVHD). We characterized the specificity of this immune response, and detected a dominant T cell population recognizing a novel minor histocompatibility antigen (MiHA) designated LB-FUCA2-1V. T cells specific for LB-FUCA2-1V were shown to recognize RCC cell lines, supporting a dominant role in the graft versus tumor (GVT) reaction. However, coinciding with the gradual disappearance of chronic GVHD, the anti-tumor effect declined and 3 years after alloSCT the metastases became progressive again. To re-initiate the GVT reaction, escalating doses of DLI were given, but no immune response could be induced and the patient died of progressive disease 8.5 years after alloSCT. Gene expression studies illustrated that only a minimal number of genes shared expression between RCC and professional antigen presenting cells but were not expressed by non-malignant healthy tissues, indicating that in patients suffering from RCC, GVT reactivity after alloSCT may be unavoidably linked to GVHD. PMID:24454818

  8. The addition of sirolimus to the graft-versus-host disease prophylaxis regimen in reduced intensity allogeneic stem cell transplantation for lymphoma: a multicentre randomized trial.

    PubMed

    Armand, Philippe; Kim, Haesook T; Sainvil, Marie-Michele; Lange, Paulina B; Giardino, Angela A; Bachanova, Veronika; Devine, Steven M; Waller, Edmund K; Jagirdar, Neera; Herrera, Alex F; Cutler, Corey; Ho, Vincent T; Koreth, John; Alyea, Edwin P; McAfee, Steven L; Soiffer, Robert J; Chen, Yi-Bin; Antin, Joseph H

    2016-04-01

    Inhibition of the mechanistic target of rapamycin (mTOR) pathway has clinical activity in lymphoma. The mTOR inhibitor sirolimus has been used in the prevention and treatment of graft-versus-host disease (GVHD) after allogeneic haematopoietic stem cell transplantation (HSCT). A retrospective study suggested that patients with lymphoma undergoing reduced intensity conditioning (RIC) HSCT who received sirolimus as part of their GVHD prophylaxis regimen had a lower rate of relapse. We therefore performed a multicentre randomized trial comparing tacrolimus, sirolimus and methotrexate to standard regimens in adult patients undergoing RIC HSCT for lymphoma in order to assess the possible benefit of sirolimus on HSCT outcome. 139 patients were randomized. There was no difference overall in 2-year overall survival, progression-free survival, relapse, non-relapse mortality or chronic GVHD. However, the sirolimus-containing arm had a significantly lower incidence of grade II-IV acute GVHD (9% vs. 25%, P = 0·015), which was more marked for unrelated donor grafts. In conclusion, the addition of sirolimus for GVHD prophylaxis in RIC HSCT is associated with no increased overall toxicity and a lower risk of acute GVHD, although it does not improve survival; this regimen is an acceptable option for GVHD prevention in RIC HSCT. This trial is registered at clinicaltrials.gov (NCT00928018). PMID:26729448

  9. Graft-infiltrating cells expressing a CD200 transgene prolong allogeneic skin graft survival in association with local increases in Foxp3(+)Treg and mast cells.

    PubMed

    Gorczynski, Reginald M; Chen, Zhiqi; Khatri, Ismat; Yu, Kai

    2011-12-01

    Expression of the molecule CD200 has been reported to increase allograft survival by suppression of inflammation and acquired immunity. In previous studies we have shown that increased skin and cardiac allograft survival in transgenic mice over-expressing CD200 (CD200(tg)) occurs in association with increased intra-graft expression of mRNAs for genes associated with altered T cell subset differentiation. We investigated changes in graft-infiltrating cells, Treg and mast cells in skin grafts post transplantation into control or CD200(tg) mice, using focused gene array and real-time PCR to assess altered gene expression, and FACS, immunohistology and MLC to determine numbers/function of those cells. Graft-infiltrating cells isolated from CD200(tg) recipients suppressed induction of CTL from control lymph node cells in vitro, and contained increased numbers of infiltrating, non-degranulating, mast cells and Foxp3(+)Treg. Mast cells were also evident in graft tissue of control animals, but there these cells showed evidence for degranulation, and fewer Foxp3(+)Treg were present than was the case of CD200(tg) mice. The infusion of a competitive inhibitor of CD200:CD200R interactions, CD200(tr), at high concentrations (50μg/mouse iv) caused rapid rejection of grafts in CD200(tg) mice, mast cell degranulation within graft tissue, and a decrease in Treg infiltrates. These effects were attenuated by simultaneous infusion of the mast cell stabilizer, sodium cromoglycate. We conclude that CD200 expression contributes to graft prolongation through local suppression of mast cell degranulation, attraction/expansion of Treg, and attenuation of T cell effector activation. PMID:21801836

  10. Histological evaluation of an impacted bone graft substitute composed of a combination of mineralized and demineralized allograft in a sheep vertebral bone defect.

    PubMed

    Fujishiro, Takaaki; Bauer, Thomas W; Kobayashi, Naomi; Kobayashi, Hideo; Sunwoo, Moon Hae; Seim, Howard B; Turner, A Simon

    2007-09-01

    Demineralized bone matrix (DBMs) preparations are a potential alternative or supplement to autogenous bone graft, but many DBMs have not been adequately tested in clinically relevant animal models. The aim of current study was to compare the efficacy of a new bone graft substitute composed of a combination of mineralized and demineralized allograft, along with hyaluronic acid (AFT Bone Void Filler) with several other bone graft materials in a sheep vertebral bone void model. A drilled defect in the sheep vertebral body was filled with either the new DBM preparation, calcium sulfate (OsteoSet), autologous bone graft, or left empty. The sheep were euthanized after 6 or 12 weeks, and the defects were examined by histology and quantitative histomorphometry. The morphometry data were analyzed by one-way analysis of variance with the post hoc Tukey-Kramer test or the Student's t-test. All of the bone defects in the AFT DBM preparation group showed good new bone formation with variable amounts of residual DBM and mineralized bone graft. The DBM preparation group at 12 weeks contained significantly more new bone than the defects treated with calcium sulfate or left empty (respectively, p < 0.05, p < 0.01). There was no significant difference between the DBM and autograft groups. No adverse inflammatory reactions were associated with any of the three graft materials. The AFT preparation of a mixture of mineralized and demineralized allograft appears to be an effective autograft substitute as tested in this sheep vertebral bone void model. PMID:17309059

  11. The combined effect of parathyroid hormone and bone graft on implant fixation

    PubMed Central

    Daugaard, H.; Elmengaard, B.; Andreassen, T. T.; Baas, J.; Bechtold, J. E.; Søballe, K.

    2013-01-01

    Impaction allograft is an established method of securing initial stability of an implant in arthroplasty. Subsequent bone integration can be prolonged, and the volume of allograft may not be maintained. Intermittent administration of parathyroid hormone has an anabolic effect on bone and may therefore improve integration of an implant. Using a canine implant model we tested the hypothesis that administration of parathyroid hormone may improve osseo-integration of implants surrounded by bone graft. In 20 dogs a cylindrical porous-coated titanium alloy implant was inserted into normal cancellous bone in the proximal humerus and surrounded by a circumferential gap of 2.5 mm. Morsellised allograft was impacted around the implant. Half of the animals were given daily injections of human parathyroid hormone (1-34) 5 μg/kg for four weeks and half received control injections. The two groups were compared by mechanical testing and histomorphometry. We observed a significant increase in new bone formation within the bone graft in the parathyroid hormone group. There were no significant differences in the volume of allograft, bone-implant contact or in the mechanical parameters. These findings suggest that parathyroid hormone improves new bone formation in impacted morsellised allograft around an implant and retains the graft volume without significant resorption. Fixation of the implant was neither improved nor compromised at the final follow-up of four weeks. PMID:21196558

  12. Traumatic Periprosthetic Acetabular Fracture Treated with One-Stage Exchange and Bone Reconstruction Using a Synthetic Bone Graft Substitute

    PubMed Central

    2016-01-01

    A case of a traumatic periprosthetic acetabular fracture in an elderly patient, which was treated by one-stage hip exchange with implantation of an antiprotrusio cage and reconstruction of the acetabular bone loss with an injectable calcium sulphate/hydroxyapatite bone graft substitute, is reported. The paste-like bone graft substitute was injected through the holes of the antiprotrusio cage. After a setting time of 15 minutes, a low-profile cup was cemented onto the cage using polymethylmethacrylate and a new stem was inserted. The patient was encouraged to ambulate three days postoperatively weight-bearing as tolerated. At the one-year follow-up visit the patient was ambulatory and full weight-bearing without any walking aids. The follow-up radiographs demonstrated stable position and articulation of the revision hip arthroplasty with no signs of loosening of the antiprotrusio cage. However, the most interesting finding was that the bone graft substitute had remodelled to a great extent into bone. This calcium sulphate/hydroxyapatite composite shows high osteoconductive potential and can be used to regenerate bone stock in revision arthroplasty. PMID:27446621

  13. Traumatic Periprosthetic Acetabular Fracture Treated with One-Stage Exchange and Bone Reconstruction Using a Synthetic Bone Graft Substitute.

    PubMed

    Svacina, Jan

    2016-01-01

    A case of a traumatic periprosthetic acetabular fracture in an elderly patient, which was treated by one-stage hip exchange with implantation of an antiprotrusio cage and reconstruction of the acetabular bone loss with an injectable calcium sulphate/hydroxyapatite bone graft substitute, is reported. The paste-like bone graft substitute was injected through the holes of the antiprotrusio cage. After a setting time of 15 minutes, a low-profile cup was cemented onto the cage using polymethylmethacrylate and a new stem was inserted. The patient was encouraged to ambulate three days postoperatively weight-bearing as tolerated. At the one-year follow-up visit the patient was ambulatory and full weight-bearing without any walking aids. The follow-up radiographs demonstrated stable position and articulation of the revision hip arthroplasty with no signs of loosening of the antiprotrusio cage. However, the most interesting finding was that the bone graft substitute had remodelled to a great extent into bone. This calcium sulphate/hydroxyapatite composite shows high osteoconductive potential and can be used to regenerate bone stock in revision arthroplasty. PMID:27446621

  14. Mechanical characteristics of impacted morsellised bone grafts used in revision of total hip arthroplasty.

    PubMed

    Giesen, E B; Lamerigts, N M; Verdonschot, N; Buma, P; Schreurs, B W; Huiskes, R

    1999-11-01

    The use of impacted, morsellised bone grafts has become popular in revision total hip arthroplasty (THA). The initial stability of the reconstruction and the effectiveness of any subsequent process of revitalisation and incorporation will depend on the mechanical integrity of the graft. Our aim in this study was to document the time-dependent mechanical properties of the morsellised graft. This information is useful in clinical application of the graft, in studies of migration of the implant and in the design of the joint. We used 16 specimens of impacted, morsellised cancellous bone from the sternum of goats to assess the mechanical properties by confined compression creep tests. Consideration of the graft material as a porous, permeable solid, filled with fluid, allowed determination of the compressive modulus of the matrix, and its permeability to fluid flow. In all specimens the compression tests showed large, irreversible deformations, caused by flow-independent creep behaviour as a result of rolling and sliding of the bone chips. The mean permeability was 8.82 *10(-12) m4/Ns (SD 43%), and the compressive modulus was 38.7 MPa (SD 34%). No correlation was found between the apparent density and the permeability or between the apparent density and the compressive modulus. The irreversible deformations in the graft could be captured by a creep law, for which the parameters were quantified. We conclude that in clinical use the graft is bound to be subject to permanent deformation after operation. The permeability of the material is relatively high compared with, for example, human cartilage. The confined compression modulus is relatively low compared with cancellous bone of the same apparent density. Designs of prostheses used in revision surgery must accommodate the viscoelastic and permanent deformations in the graft without causing loosening at the interface. PMID:10615985

  15. Comparing Morbidities of Bone Graft Harvesting from the Olecranon Process and the Distal Radius

    PubMed Central

    Micev, Alan J.; Slikker, William; Ma, Madeleine; Richer, Ross J.; Cohen, Mark S.

    2016-01-01

    Background: The aim of this study is to compare donor-site morbidities between patients who underwent bone graft harvesting from either the olecranon process (OP) or the distal radius (DR). Methods: We evaluated 44 patients who underwent bone graft harvesting from the OP (25 cases) or the DR (19 cases) for various procedures in the ipsilateral upper extremity. Follow-up averaged 14 (OP group) and 19 months (DR group). Outcome measures included visual analog scales (VAS) for graft harvest-site pain and scar appearance, joint motion, and x-rays of the graft harvest and recipient sites. The VAS scores ranged from 0 to 10 with a low score reflecting no pain and excellent satisfaction and a high score reflecting severe pain and poor satisfaction. Results: The VAS scores for pain averaged 0.4 (OP) and 0.5 (DR), and the VAS scores for scar appearance averaged 0.3 (OP) and 0.7 (DR). These differences were not significant. Within each group, there were no significant differences between the operative and nonoperative limbs for elbow or wrist motion. Early graft harvest-site complications involved 1 superficial wound infection (OP) and 1 wound dehiscence (DR). A graft harvest-site defect was detected by x-ray in 84% of OP cases and in 67% of DR cases. Bone healing at the graft recipient sites was observed in more than 87% of cases in both groups. Conclusions: Bone graft harvesting from either the OP or the DR led to comparable patient- and evaluator-determined outcomes with low risks of complications. Surgeons can safely use either option. PMID:27014552

  16. Application of bioabsorbable screw fixation for anterior cervical decompression and bone grafting

    PubMed Central

    Zhao, Bo; Qiu, Xiaowen; Wang, Dong; Li, Haopeng; He, Xijing

    2016-01-01

    OBJECTIVES: To examine the application of bioabsorbable screws for anterior cervical decompression and bone grafting fixation and to study their clinical effects in the treatment of cervical spondylosis. METHODS: From March 2007 to September 2012, 56 patients, 36 males and 20 females (38-79 years old, average 58.3±9.47 years), underwent a novel operation. Grafts were fixed by bioabsorbable screws (PLLA, 2.7 mm in diameter) after anterior decompression. The bioabsorbable screws were inserted from the midline of the graft bone to the bone surface of the upper and lower vertebrae at 45 degree angles. Patients were evaluated post-operatively to observe the improvement of symptoms and evaluate the fusion of the bone. The Japanese Orthopaedic Association (JOA) score was used to evaluate the recovery of neurological functions. RESULTS: All screws were successfully inserted, with no broken screws. The rate of symptom improvement was 87.5%. All of the grafts fused well with no extrusion. The average time for graft fusion was 3.8±0.55 months (range 3-5 months). Three-dimensional reconstruction of CT scans demonstrated that the grafts fused with adjacent vertebrae well and that the screws were absorbed as predicted. The MRI findings showed that the cerebrospinal fluid was unobstructed. No obvious complications appeared in any of the follow-up evaluations. CONCLUSIONS: Cervical spondylosis with one- or two-level involvement can be effectively treated by anterior decompression and bone grafting with bioabsorbable screw fixation. This operative method is safe and can avoid the complications induced by metal implants. PMID:27438565

  17. A qualitative evaluation of scaphoid remodeling in bone-grafted scaphoid nonunions.

    PubMed

    Grewal, Ruby; Boyd, Kirsty U; Macdermid, Joy; McMurtry, Robert Y

    2010-12-01

    The purpose of this case series is to identify and illustrate the phenomenon of scaphoid remodeling in skeletally mature subjects following bone grafting for scaphoid nonunion. Nine patients with scaphoid nonunions were treated with interpositional bone grafting (with iliac crest bone graft) and K-wire fixation. The mean length of follow-up was 28.6 ± 9 months. Radiographs and CT scans were reviewed and assessed for degree of union and a qualitative assessment of scaphoid architecture. Following surgery, there was marked distortion of the scaphoid. Once healed, the contour of the scaphoid was still significantly distorted in all nine patients. Remodeling then became evident along the articular surfaces between 8 and 12 months. By 3 years, the scaphoid was completely recontoured and the normal architecture was completely restored in all nine patients. We conclude that the articular surface of the scaphoid remodels over time in skeletally mature subjects. PMID:22131928

  18. A current review of non-vascularized bone grafting in osteonecrosis of the femoral head.

    PubMed

    Pierce, Todd P; Elmallah, Randa K; Jauregui, Julio J; Poola, Shiva; Mont, Michael A; Delanois, Ronald E

    2015-09-01

    Over the past three decades, non-vascularized bone grafts have been demonstrated to be viable treatments for pre- and early post-collapse osteonecrosis of the femoral head; however, there are limited reviews on this topic. Therefore, the purposes of this review are to (1) provide a summary of the different surgical techniques and their respective clinical outcomes and (2) evaluate new adjunct therapies. Originally, non-vascularized bone grafting was performed using the Phemister technique with varying results. More recently, newer techniques such as the lightbulb and trapdoor are used to place non-vascularized bone grafts with excellent results. The addition of various biological agents has demonstrated positive results; however, further studies are needed to confirm the best appropriate indications and to elucidate long-term results. PMID:26009009

  19. Effects of a buried magnetic field on cranial bone reconstruction in rats

    PubMed Central

    de ABREU, Maíra Cavallet; PONZONI, Deise; LANGIE, Renan; ARTUZI, Felipe Ernesto; PURICELLI, Edela

    2016-01-01

    ABSTRACT The understanding of bone repair phenomena is a fundamental part of dentistry and maxillofacial surgery. Objective The present study aimed to evaluate the influence of buried magnetic field stimulation on bone repair in rat calvaria after reconstruction with autogenous bone grafts, synthetic powdered hydroxyapatite, or allogeneic cartilage grafts, with or without exposure to magnetic stimulation. Material and Methods Ninety male Wistar rats were divided into 18 groups of five animals each. Critical bone defects were created in the rats’ calvaria and immediately reconstructed with autogenous bone, powdered synthetic hydroxyapatite or allogeneic cartilage. Magnetic implants were also placed in half the animals. Rats were euthanized for analysis at 15, 30, and 60 postoperative days. Histomorphometric analyses of the quantity of bone repair were performed at all times. Results These analyses showed significant group by postoperative time interactions (p=0.008). Among the rats subjected to autogenous bone reconstruction, those exposed to magnetic stimulation had higher bone fill percentages than those without magnetic implants. Results also showed that the quality of bone repair remained higher in the former group as compared to the latter at 60 postoperative days. Conclusions After 60 postoperative days, bone repair was greater in the group treated with autogenous bone grafts and exposed to a magnetic field, and bone repair was most pronounced in animals treated with autogenous bone grafts, followed by those treated with powdered synthetic hydroxyapatite and allogeneic cartilage grafts. PMID:27119765

  20. Osteogenesis effect of guided bone regeneration combined with alveolar cleft grafting: assessment by cone beam computed tomography.

    PubMed

    Xiao, W-L; Zhang, D-Z; Chen, X-J; Yuan, C; Xue, L-F

    2016-06-01

    Cone beam computed tomography (CBCT) allows for a significantly lower radiation dose than conventional computed tomography (CT) scans and provides accurate images of the alveolar cleft area. The osteogenic effect of guided bone regeneration (GBR) vs. conventional alveolar bone grafting alone for alveolar cleft defects was evaluated in this study. Sixty alveolar cleft patients were divided randomly into two groups. One group underwent GBR using acellular dermal matrix film combined with alveolar bone grafting using iliac crest bone grafts (GBR group), while the other group underwent alveolar bone grafting only (non-GBR group). CBCT images were obtained at 1 week and at 3 months following the procedure. Using Simplant 11.04 software, the bone resorption rate was calculated and compared between the two groups. The bone resorption rate from 1 week to 3 months following bone grafting without the GBR technique was 36.50±5.04%, whereas the bone resorption rate using the GBR technique was 31.69±5.50% (P=0.017). The application of autogenous iliac bone combined with the GBR technique for alveolar bone grafting of alveolar cleft patients can reduce bone resorption and result in better osteogenesis. PMID:26876144

  1. Volumetric stability of autogenous bone graft with mandibular body bone: cone-beam computed tomography and three-dimensional reconstruction analysis

    PubMed Central

    Lee, Hyeong-Geun

    2015-01-01

    Objectives The purpose of this study was to estimate the volumetric change of augmented autobone harvested from mandibular body cortical bone, using cone-beam computed tomography (CBCT) and three-dimensional reconstruction. In addition, the clinical success of dental implants placed 4 to 6 months after bone grafting was also evaluated. Materials and Methods Ninety-five patients (48 men and 47 women) aged 19 to 72 years were included in this study. A total of 128 graft sites were evaluated. The graft sites were divided into three parts: anterior and both posterior regions of one jaw. All patients included in the study were scheduled for an onlay graft and implantation using a two-stage procedure. The dental implants were inserted 4 to 6 months after the bone graft. Volumetric stability was evaluated by serial CBCT images. Results No major complications were observed for the donor sites. A total of 128 block bones were used to augment severely resorbed alveolar bone. Only 1 of the 128 bone grafts was resorbed by more than half, and that was due to infection. In total, the average amount of residual grafted bone after resorption at the recipient sites was 74.6%±8.4%. Conclusion Volumetric stability of mandibular body autogenous block grafts is predictable. The procedure is satisfactory for patients who want dental implants regardless of atrophic alveolar bone. PMID:26568924

  2. Different bone regeneration patterns in periimplant circumferential gap defects grafted with two types of osteoconductive biomaterial.

    PubMed

    Lee, Jung-Seok; Sohn, Joo-Yeon; Lim, Hyun-Chang; Jung, Ui-Won; Choi, Seong-Ho

    2016-08-01

    This study aimed to determine healing patterns in periimplant gap defect grafted with demineralized bovine bone mineral (DBBM) and porous titanium granules (PTG), which are known to induce a minimal tissue reaction and to undergo minimal biodegradation in healing process. Experiments were performed using a standardized periimplant gap-defect model in dogs with two observational periods: 4 and 8 weeks. Circumferential defects were surgically induced around dental implants on unilateral mandibles in five dogs, and collagen barrier membranes were placed over the DBBM and PTG grafts at two experimental sites and over a nongrafted site. Four weeks later, the same procedures were performed on the contralateral mandible, and the animals allowed to heal for a further 4 weeks, after which they were sacrificed and their mandibles with graft/control sites harvested for histologic evaluation. Both types of grafted biomaterials significantly enhanced the defect fill with newly formed bone, but the bone-to-implant contact (BIC) was significantly increased only at sites that had been grafted with DBBM. The two experimental sites exhibited different healing patterns, with new bone formation being observed on the surface of the DBBM particles throughout the defect, while there was no de novo bone formation on the PTG surface, but rather appositional bone growth from the base and lateral walls of the defect. It has been suggested that gap-defect filling with DBBM around dental implants may enhance both BIC and defect fill; however, the present findings show that defect grafting with PTG enhances only defect fill and not BIC. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1202-1209, 2016. PMID:26087247

  3. Preparation, degradation, and calcification of biodegradable polyurethane foams for bone graft substitutes.

    PubMed

    Gorna, Katarzyna; Gogolewski, Sylwester

    2003-12-01

    Autogenous cancellous bone graft is used to heal critical-size segmental long bone defects and defects in the maxillofacial skeleton. Harvesting of bone graft is traumatic, causes morbidity of the donor site, and often results in complications. Thus, there is a need for new biologically functional bone graft substitutes that, instead of autogenous bone graft, could be used to facilitate bone regeneration in critical-size defects. Porous biodegradable elastomeric polyurethane scaffolds combined with the patient's own bone marrow could potentially be such bone substitutes. The elastomeric bone substitute prevents shear forces at the interface between bone and rigid, e.g., ceramic bone substitutes and establishes an intimate contact with the native bone ends, thus facilitating the proliferation of osteogenic cells and bone regeneration. Crosslinked 3D biodegradable polyurethane scaffolds (foams) with controlled hydrophilicity for bone graft substitutes were synthesized from biocompatible reactants. The scaffolds had hydrophilic-to-hydrophobic content ratios of 70:30, 50:50, and 30:70. The reactants used were hexamethylene diisocyanate, poly(ethylene oxide) diol (MW = 600) (hydrophilic component), and poly(epsilon-caprolactone) diol (M(w) = 2000), amine-based polyol (M(w) = 515) or sucrose-based polyol (M(w) = 445) (hydrophobic component), water as the chain extender and foaming agent, and stannous octoate, dibutyltin dilaurate, ferric acetylacetonate, and zinc octoate as catalysts. Citric acid was used as a calcium complexing agent, calcium carbonate, glycerol phosphate calcium salt, and hydroxyapatite were used as inorganic fillers, and lecithin or solutions of vitamin D(3) were used as surfactants. The scaffolds had an open-pore structure with pores whose size and geometry depended on the material's chemical composition. The compressive strengths of the scaffolds were in the range of 4-340 kPa and the compressive moduli in the range of 9-1960 kPa, the values of

  4. Effects of Gaps Induced Into the ACL Tendon Graft on Tendon-Bone Healing in a Rodent ACL Reconstruction Model

    PubMed Central

    Lovric, Vedran; Kanazawa, Tomonoshin; Nakamura, Yoshinari; Oliver, Rema A.; Yu, Yan; Walsh, William Robert

    2011-01-01

    Summary Graft necrosis following ACL reconstruction is often associated with the use of autologous grafts. Host cells rather than graft cells contribute to the repair of the tendon-bone interface and the remodeling of the autologous graft. The native tendon-bone interface is not recreated and the biomechanical properties are not restored back to native values. We examined the effects of introducing gaps within the tendon graft prior to ACL reconstruction in a rodent model. We hypothesised that gaps will make physical way for host cells to infiltrate and repopulate the graft and thus enhance healing. Animals were sacrificed at seven, fourteen, and twenty-eight days for biomechanical testing and histology. Our findings indicate that graft necrosis, usually observed in the initial two weeks of the healing process, is averted. Histological observations showed that tendon-bone healing stages were hastened however this didn’t translate into improved biomechanical properties. PMID:23738254

  5. [Grafting of preserved homogenous cancellous bone. Results of 90 operations (author's transl)].

    PubMed

    Ackermann, W; Taillard, W

    1977-10-01

    Description of a simple technique for the removal of homogeneous cancellous bone from heads of femur removed during replacement of the hip-joint. The material has been preserved for one year at -20 degrees C and can be used after simple washing. Results in 89 grafts are analysed: They all took perfectly at the site of grafting. There was no rejection, no local or general allergy. Risk of infection was not increased. The technique is simple and useful where much cancellous bone is needed. PMID:337707

  6. Do human leukocyte antigen E polymorphisms influence graft-versus-leukemia after allogeneic hematopoietic stem cell transplantation?

    PubMed

    Hosseini, Ehteramolsadat; Schwarer, Anthony P; Ghasemzadeh, Mehran

    2015-03-01

    Hematopoietic-stem-cell transplantation (HSCT) is complicated by histocompatibility-dependent immune responses such as graft-versus-host disease, relapse, and graft rejection. The severity of these common adverse effects is directly related to the degree of human leukocyte antigen (HLA) incompatibility. In addition to the key role of classic HLA matching in influencing HSCT outcome, several lines of evidence suggest an important role for nonclassic major histocompatibility complex class I molecule, HLA-E. The interaction of HLA-E with NKG2A, its main receptor on natural killer cells, modulates cell-mediated cytotoxicity and cytokine production, an important role in innate immune responses. In addition, the HLA-E molecule can present peptides to different subtypes of T cells that may either support graft-versus-leukemia effects or be involved in bridging innate and acquired immunity. To date, the role of HLA-E and its polymorphisms in HSCT outcomes such as graft-versus-host disease, transplant-related mortality, and improved survival has been published by a number of groups. In addition, these data suggest an association between HLA-E polymorphisms and relapse. Whether the engagement of the HLA-E molecule in the modulation of donor T cells is involved in the graft-versus-leukemia effect, or whether a different mechanism of HLA-E dependent reduction of relapse is involved, requires further investigation. PMID:25434712

  7. Evaluation of laser photobiomodulation on healing of bone defects grafted with bovine bone in diabetic rats

    NASA Astrophysics Data System (ADS)

    Paraguassú, Gardênia Matos; da Costa Lino, Maíra Doria Martinez; de Carvalho, Fabíola Bastos; Cangussu, Maria Cristina; Pinheiro, Antônio Luiz Barbosa; Ramalho, Luciana Maria Pedreira

    2012-09-01

    Previous studies have shown positive effects of Low Level Laser Therapy (LLLT) on the repair of bone defects, but there is a few that associates bone healing in the presence of a metabolic disorder such as Diabetes Mellitus, a systemic disorder associated to impair of the repair of different tissues. The aim of this study was to assess, histologically, the repair of surgical defects created in the femur of diabetic and non-diabetic rats treated or not with LLLT (λ780nm, 70mW, CW, o/˜0.4mm, 16J/cm2 per session) associated or not to the use of a biomaterial. Surgical tibial bone defects were created in 60 animals that were divided into 4 groups: Group B (non-diabetic + biomaterial); Group BL (non-diabetic + biomaterial + LLLT); Group BD (diabetic + biomaterial); Group BDL (diabetic + biomaterial + LLLT). The irradiated group received 16 J/cm2 per session divided into 4 points around the defect, being the first irradiation carried out immediately after surgery and repeated every 48h for 14 days. The animals were killed 15, 21 and 30 days after surgery. The specimens underwent a semi-quantitative analysis. The results showed inflammation more intense in the BD and BDL groups than in the B and BL groups in the period of 15 days (p = 0.02), however the cortical repair in the BDL group was below 25% in more than half of the specimens, while in the BD group, the repair was more than to 25% in all specimens. At 30 days, both osteoblastic activity and collagen deposition were significantly higher in the B group when compared to the BD group (p=0.04). Bone deposition was significantly higher in the BL group (p=0.023) than in BDL group. It is concluded that LLLT has a positive biomodulative effect in the early stages of the healing process of bone defects grafted with biomaterial in diabetic and non-diabetic rats.

  8. From bench to clinic and back: skeletal stem cells and impaction bone grafting for regeneration of bone defects.

    PubMed

    Aarvold, A; Smith, J O; Tayton, E R; Jones, A M H; Dawson, J I; Lanham, S; Briscoe, A; Dunlop, D G; Oreffo, R O C

    2014-10-01

    Tissue engineering offers enormous potential for bone regeneration. Despite extensive in vitro and in vivo work, few strategies translate into clinical practice. This paper describes the combination of skeletal stem cells (SSCs) and impaction bone grafting (IBG) for the treatment of patients with bone defects associated with avascular necrosis of the femoral head. SSCs and milled allograft were impacted into necrotic bone in the femoral heads of four patients. Three patients remained asymptomatic at 22-44 month follow-up, but one patient has required total hip replacement (both hips). This has allowed retrieval of the femoral heads, which were analysed structurally and functionally by μCT, histology and mechanical testing. A central channel of impacted bone was found in the femoral heads, which displayed a mature trabecular micro-architecture. The impacted bone was denser than the surrounding trabecular bone, as strong in compression and with histological micro-architecture comparable to that of trabecular bone. Analysis of the retrieved femoral head samples has demonstrated that this tissue-engineering strategy regenerates bone that is both structurally and functionally analogous to normal trabecular bone. SSCs, together with IBG, have proved an effective treatment for avascular necrosis of the femoral head and offer significant potential for the broader spectrum of bone defects. PMID:23038218

  9. USE OF CORTICAL STRUCTURAL HOMOLOGOUS BONE GRAFT IN FEMORAL RECONSTRUCTIVE SURGERY

    PubMed Central

    Roos, Milton Valdomiro; Roos, Bruno Dutra; Giora, Taís Stedile Busin; Taglietti, Thiago Martins

    2015-01-01

    To perform a clinical and radiographic assessment of patients undergoing surgical treatment using a cortical structural homologous bone graft for femoral reconstruction following mechanical failure of total hip arthroplasty and periprosthetic fractures. Methods: A retrospective study was conducted on 27 patients who underwent surgical treatment for femoral reconstruction following mechanical failure of total hip arthroplasty (12 cases) and periprosthetic fractures (15 cases), using a cortical structural homologous bone graft and cemented implants, between June 1999 and February 2008. Of these, 21 fulfilled all the criteria required for this study. The patients underwent pre and postoperative clinical assessments using the Harris Hip Score. Preoperative, immediate postoperative and late postoperative radiographs were also evaluated, with comparisons of fracture consolidation, radiographic signs of graft consolidation, changes to the bone stock and femoral bone quality, and femoral alignment. Results: Nine patients (42.9%) underwent femoral reconstruction following mechanical failure of total hip arthroplasty and 12 cases (57.1%) underwent femoral reconstruction following periprosthetic fracture. Regarding the postoperative clinical classification, the results were considered satisfactory in 85.7% of the cases and unsatisfactory in 14.3%. Radiographic signs of graft consolidation were seen in all cases. There was an increase in bone stock in 90.5% of the hip reconstructions, as measured by the cortical index. Furthermore, the changes to femoral bone quality were considered good in 66.7% of the cases. Conclusion: The use of cortical structural homologous bone grafts for both femoral reconstructive surgery on total hip arthroplasty and periprosthetic fractures is a good treatment option for selected cases, enabling satisfactory clinical and radiographic results. PMID:27026955

  10. Lesser toe salvage with external fixation and autogenous bone grafting: a case series.

    PubMed

    Roukis, Thomas S

    2010-06-01

    Lesser toe salvage secondary to soft tissue ulceration and underlying osteomyelitis is a challenge, and amputation is frequently the primary procedure recommended. The author presents an observational case series involving retrospective review of prospectively collected data of 4 lesser toe salvage procedures with external fixation and delayed autogenous bone grafting for the treatment of osteomyelitis in 4 consecutive patients. Each patient underwent initial resection of involved soft tissue ulceration and underlying osseous components of the lesser toe with application of external fixation and polymethylmethacrylate antibiotic-loaded bone cement spacer. Once eradication of osteomyelitis was confirmed clinically, the patient underwent delayed insertion of autogenous bone graft harvested from the ipsilateral calcaneus or osteocutaneous flap transfer from the fibular border of the ipsilateral great toe. There were 2 men and 2 women with a mean age of 56.5 years. Three patients had diabetes mellitus, and 1 had previous history of open fracture. There were 2 right feet and 2 left feet involved and 2 second, 1 third, and 1 fourth toe salvage procedures performed with a mean follow-up of 12 months. The external fixation device was maintained until complete osseous integration was verified, which occurred at a mean of 7.5 weeks. All procedures were deemed successful with complete osseous incorporation of the proximal and distal graft-host bone interfaces and no recurrent soft tissue ulcerations, osteomyelitis, toe deformity, or fracture about the bone graft sites. PMID:20508009

  11. Dental devices; reclassification of tricalcium phosphate granules and classification of other bone grafting material for dental bone repair. Final rule.

    PubMed

    2005-04-28

    The Food and Drug Administration (FDA) is reclassifying tricalcium phosphate (TCP) granules for dental bone repair from class III to class II (special controls), classifying into class II (special controls) other bone grafting material for dental indications, and revising the classification name and identification of the device type. Bone grafting materials that contain a drug that is a therapeutic biologic will remain in class III and continue to require a premarket approval application. The classification identification includes materials such as hydroxyapatite, tricalcium phosphate, polylactic and polyglycolic acids, or collagen. This action is being taken to establish sufficient regulatory controls that will provide reasonable assurance of the safety and effectiveness of these devices. Elsewhere in this issue of the Federal Register, FDA is announcing the availability of the guidance document that will serve as the special control for the class II devices. PMID:15858911

  12. The use of the free vascularised bone graft for nonunion of the scaphoid: a systematic review

    PubMed Central

    2014-01-01

    Background Fractures of the scaphoid are well known to be problematic especially when complicated by avascular necrosis, nonunion and carpal collapse. Fixation techniques have involved nonvascularised bone grafting; however, in the presence of avascular necrosis, generally poor union rates (47%) occur as identified by a meta-analysis performed by Merrell et al. The introduction of pedicled vascularised bone grafts showed further improvement; however, in the presence of carpal collapse, union rates as low as 50% have been reported by Chang et al. amongst others using the 1,2-intercompartmental supraretinacular artery pedicled graft. The difficulty lies in having a short pedicle with limited manoeuvrability to correct a humpback deformity and insert into the scaphoid cavity. Prior trauma to the soft tissues or distal radius may prohibit the use of pedicled grafts. The aim of this systematic review is to examine the published evidence for the use of free vascularised bone grafts in cases of scaphoid nonunion. Methods A systematic review was performed with the following defined search strategy on MEDLINE and Google Scholar: ((scaphoid nonunion) OR scaphoid pseudarthrosis) AND bone graft. Articles were reviewed and data compiled into tables for analysis. Statistical analysis was performed with determination of descriptive statistics, and differences between the groups were calculated using categorical variables and chi-square test. A p value of 0.05 or less was considered to be statistically significant. Results Two hundred and sixty-three articles were identified with a total of 12 articles meeting the inclusion criteria. Two hundred and forty-five cases of scaphoid nonunion were identified through the articles included in this systematic review. Fifty-six patients underwent free vascularised bone grafts from the medial femoral condyle with a 100% union rate and correction of humpback deformity, and 188 patients underwent free vascularised bone grafting from the iliac

  13. Pathology of the thymus after allogeneic bone marrow transplantation in man. A histologic immunohistochemical study of 36 patients.

    PubMed Central

    Müller-Hermelink, H. K.; Sale, G. E.; Borisch, B.; Storb, R.

    1987-01-01

    A major hypothesis to explain the immunodeficiency associated with bone marrow transplantation states that thymic epithelial damage due to graft-versus-host disease (GVHD) abrogates or delays the recovery of normal immunologic function. This study evaluated the thymus glands of 36 human bone marrow transplant recipients dying between 4 and 1742 days after transplant using histology, histochemistry, and immunohistology. The observations lead to a model of thymic damage by irradiation, chemotherapy, and GVHD in which early injury by all three of these agents results in profound thymic atrophy followed by long-delayed restitution. Patients undergoing total body irradiation showed more severe damage to thymic cortical and medullary epithelium than did patients undergoing chemotherapy alone as preparation for transplantation. Patients with GVHD showed additional damage in the form of individual thymic epithelial cell death and showed HLA-DR surface protein expression on thymic epithelium during GVHD. Longer-term survivors showed a profoundly delayed restitution of normal thymic epithelium and delayed evidence of restored lymphopoiesis. A few patients dying late after transplant showed evidence of reconstitution of normal thymic structure or nodules of lymphopoiesis in focal areas of epithelial-cell reconstitution. Evidence of such lymphopoiesis was seen at times ranging between 90 and 1742 days after grafting. The data are consistent with a model of long-standing thymic damage caused by GVHD which is reversible after the development of tolerance. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:3314529

  14. Vascularized Bone Grafts from the Dorsal Wrist for the Treatment of Kienböck Disease.

    PubMed

    Nakagawa, Makoto; Omokawa, Shohei; Kira, Tsutomu; Kawamura, Kenji; Tanaka, Yasuhito

    2016-05-01

    Purpose The objective of this article is to evaluate functional and radiological outcomes of vascularized bone grafts for stage 2 and 3 Kienböck disease. The outcomes of three different donor sites via dorsal approach of the wrist were compared. Pearls and pitfalls in surgical technique were discussed. Methods There were 28 patients who underwent vascularized bone grafts, including the extensor fourth and fifth compartmental artery graft of distal radius in 8 patients, the first and second supraretinacular intercompartmental artery graft of distal radius in 12 patients, and the second dorsal metacarpal neck graft in 8 patients. Average age was 32 years, and radiological grading according to Lichtman classification was stage 2 in 8 patients, stage 3A in 10 patients, and stage 3B in 10 patients. Temporary pinning fixing the midcarpal joint was conducted for 10 weeks postoperatively. Results Follow-up periods averaged 70 months. Pain reduced in 27 patients, and visual analog scale for pain of pre- and postoperative level averaged 59 and 18. Range of wrist flexion and extension motion improved from 87 to 117 degrees, and average grip strength improved from 21 kg preoperatively to 33 kg postoperatively. Carpal height ratio had almost no change from 0.52 to 0.53. Fragmentation of necrotic bone healed in 7 of the 14 cases. Comparative analyses of functional and radiological outcomes between three donor sites found no significant difference. Conclusion Three different vascularized bone grafts from the dorsal wrist and hand area demonstrated favorable and comparable functional outcomes. It was technically important to elevate vascular bundle with surrounding retinaculum or fascia, to include sufficient periosteum, and to insert the vascularized bone as the cortex aligned longitudinally. PMID:27104073

  15. Outcomes of Capitohamate Bone-Ligament-Bone Grafts for Scapholunate Injury.

    PubMed

    van Kampen, Robert J; Bayne, Christopher O; Moran, Steven L; Berger, Richard A

    2015-11-01

    Purpose In an attempt to restore natural carpal kinematics more closely, bone-ligament-bone (BLB) grafts have been described for treating scapholunate (SL) injury. In this article we report the long-term results of capitohamate BLB autograft for the treatment of SL dissociation. Methods The medical records of patients treated with capitohamate BLB grafts for SL dissociation were retrospectively reviewed. Twenty-three patients were available for evaluation. Patients were sent a Disabilities of the Arm, Shoulder, and Hand (DASH) and a Patient-Rated Wrist Evaluation (PRWE) questionnaire and returned for exam. Thirteen patients returned the questionnaire, and 12 wrists were examined. Range of motion, grip strength, pain, complications, return to work, and radiographic parameters were documented. Results The average length of follow-up evaluation was 9.2 years. The average SL gap was 4.5 mm preoperatively and 3.6 mm at final follow-up. The average SL angle was 70 degrees preoperatively and 73 degrees at final follow-up. There was no statistically significant difference in preoperative versus postoperative flexion, extension, radial deviation, ulnar deviation, or grip strength. The average postoperative visual analog scale (VAS) score was 1.25 at rest and 3.58 with activity. The average Mayo Wrist Score was 66.8 preoperatively and 70.9 postoperatively (p = 0.158). The average postoperative PRWE was 20.5, and average postoperative DASH was 15.1. At final follow-up, four patients had no radiographic evidence of arthritis. Two patients had evidence of early-stage radiocarpal arthritis, four had evidence of midcarpal arthritis, and two had radiographic evidence of mild scaphotrapeziotrapezoid arthritis. One patient required a salvage procedure with four-corner fusion. Discussion BLB reconstruction can be used to treat SL instability. At final follow-up, the majority of patients did not worsen clinically or functionally or require secondary salvage procedures

  16. Sequential expression of adhesion and costimulatory molecules in graft-versus-host disease target organs after murine bone marrow transplantation across minor histocompatibility antigen barriers.

    PubMed

    Eyrich, Matthias; Burger, Gudrun; Marquardt, Katja; Budach, Wilfried; Schilbach, Karin; Niethammer, Dietrich; Schlegel, Paul G

    2005-05-01

    Graft-versus-host disease (GVHD) is a potentially fatal complication after allogeneic bone marrow transplantation. However, few data exist thus far on the molecular signals governing leukocyte trafficking during the disease. We therefore investigated the sequential pattern of distinct adhesion, costimulatory, and apoptosis-related molecules in GVHD organs (ileum, colon, skin, and liver) after transplantation across minor histocompatibility barriers (B10.D2 --> BALB/c, both H-2d). To distinguish changes induced by the conditioning regimen from effects achieved by allogeneic cell transfer, syngeneic transplant recipients (BALB/c --> BALB/c) and irradiated nontransplanted mice were added as controls. Irradiation upregulated the expression of vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-l, and B7-2 in ileum, as well as VCAM-1 and B7-2 in colon, on day 3 in all animals. Whereas in syngeneic mice these effects were reversed from day 9 on, allogeneic recipients showed further upregulation of VCAM-1, ICAM-1, B7-1, and B7-2 in these organs on day 22, when GVHD became clinically evident. Infiltration of CD4+ and CD8+ donor T cells was noted on day 9 in skin and liver and on day 22 in ileum and colon. Surprisingly, the expression of several other adhesion molecules, such as ICAM-2, platelet-endothelial cell adhesion molecule 1, E-selectin, and mucosal addressin cell adhesion molecule 1, did not change. Proapoptotic and antiapoptotic markers were balanced in GVHD organs with the exception of spleen, in which a preferential expression of the proapoptotic Bax could be noted. Our results indicate that irradiation-induced upregulation of VCAM-1, ICAM-1, and B7-2 provides early costimulatory signals to incoming donor T cells in the intestine, followed by a cascade of proinflammatory signals in other organs once the alloresponse is established. PMID:15846291

  17. “Over-inlay” block graft and differential morphometry: a novel block graft model to study bone regeneration and host-to-graft interfaces in rats

    PubMed Central

    2016-01-01

    Purpose The aim of this study was to present new a model that allows the study of the bone healing process, with an emphasis on the biological behavior of different graft-to-host interfaces. A standardized “over-inlay” surgical technique combined with a differential histomorphometric analysis is presented in order to optimize the use of critical-size calvarial defects in pre-clinical testing. Methods Critical-size defects were created into the parietal bone of 8 male Wistar rats. Deproteinized bovine bone (DBBM) blocks were inserted into the defects, so that part of the block was included within the calvarial thickness and part exceeded the calvarial height (an “over-inlay” graft). All animals were sacrificed at 1 or 3 months. Histomorphometric and immunohistochemical evaluation was carried out within distinct regions of interest (ROIs): the areas adjacent to the native bone (BA), the periosteal area (PA) and the central area (CA). Results The animals healed without complications. Differential morphometry allowed the examination of the tissue composition within distinct regions: the BA presented consistent amounts of new bone formation (NB), which increased over time (24.53%±1.26% at 1 month; 37.73%±0.39% at 3 months), thus suggesting that this area makes a substantial contribution toward NB. The PA was mainly composed of fibrous tissue (71.16%±8.06% and 78.30%±2.67%, respectively), while the CA showed high amounts of DBBM at both time points (78.30%±2.67% and 74.68%±1.07%, respectively), demonstrating a slow remodeling process. Blood vessels revealed a progressive migration from the interface with native bone toward the central area of the graft. Osterix-positive cells observed at 1 month within the PA suggested that the periosteum was a source of osteoprogenitor elements. Alkaline phosphatase data on matrix deposition confirmed this observation. Conclusions The present model allowed for a standardized investigation of distinct graft

  18. Histometric analyses of cancellous and cortical interface in autogenous bone grafting

    PubMed Central

    Netto, Henrique Duque; Olate, Sergio; Klüppel, Leandro; do Carmo, Antonio Marcio Resende; Vásquez, Bélgica; Albergaria-Barbosa, Jose

    2013-01-01

    Surgical procedures involving the rehabilitation of the maxillofacial region frequently require bone grafts; the aim of this research was to evaluate the interface between recipient and graft with cortical or cancellous contact. 6 adult beagle dogs with 15 kg weight were included in the study. Under general anesthesia, an 8 mm diameter block was obtained from parietal bone of each animal and was put on the frontal bone with a 12 mm 1.5 screws. Was used the lag screw technique from better contact between the recipient and graft. 3-week and 6-week euthanized period were chosen for histometric evaluation. Hematoxylin-eosin was used in a histologic routine technique and histomorphometry was realized with IMAGEJ software. T test was used for data analyses with p<0.05 for statistical significance. The result show some differences in descriptive histology but non statistical differences in the interface between cortical or cancellous bone at 3 or 6 week; as natural, after 6 week of surgery, bone integration was better and statistically superior to 3-week analyses. We conclude that integration of cortical or cancellous bone can be usefully without differences. PMID:23923071

  19. Osteogenic Matrix Cell Sheet Transplantation Enhances Early Tendon Graft to Bone Tunnel Healing in Rabbits

    PubMed Central

    Uematsu, Kota; Akahane, Manabu; Morita, Yusuke; Ogawa, Munehiro; Ueha, Tomoyuki; Shimizu, Takamasa; Kura, Tomohiko; Kawate, Kenji; Tanaka, Yasuhito

    2013-01-01

    The objective of this study was to determine whether osteogenic matrix cell sheets (OMCS) could induce bone formation around grafted tendons, thereby enhancing early stage tendon to bone tunnel healing in skeletally mature male Japanese white rabbits. First, the osteogenic potential of rabbit OMCS was evaluated. Then, the OMCS were transplanted into the interface between the grafted tendon and the bone tunnel created at the tibia. Histological assessments and biomechanical tensile testing were performed after 3 weeks. The rabbit OMCS showed high alkaline phosphatase (ALP) activity, positive staining of ALP, and osteogenic potential when transplanted subcutaneously with beta tricalcium phosphate disks. Newly formed bony walls and positive collagen type I staining were seen around the grafted tendon with OMCS transplantation, whereas such bony walls were thinner or less frequent without OMCS transplantation. Micro-computed tomography images showed significantly higher bone volume in the OMCS transplantation group. The pullout strength was significantly higher with OMCS (0.74 ± 0.23 N/mm2) than without OMCS (0.58 ± 0.15 N/mm2). These results show that OMCS enhance early tendon to bone tunnel healing. This method can be applied to cases requiring early tendon to bone tunnel healing after ligament reconstruction surgery. PMID:24106718

  20. Norethisterone treatment, a major risk-factor for veno-occlusive disease in the liver after allogeneic bone marrow transplantation.

    PubMed

    Hägglund, H; Remberger, M; Klaesson, S; Lönnqvist, B; Ljungman, P; Ringdén, O

    1998-12-15

    In this single-center study, we retrospectively analyzed incidence and risk factors for hepatic veno-occlusive disease (VOD) in 249 consecutive patients who underwent allogeneic hematopoietic stem cell transplantation between January 1990 and June 1995. Twenty-four of the 249 transplanted patients developed VOD. The probabilities of developing VOD were 17% among women and 7% in men (P =.01). In women treated with norethisterone, the incidence was 27% compared with 3% in women without this treatment (P =.007). One-year survival rates were 17% and 73% in patients with (n = 24) or without VOD (n = 225), respectively. The use of heparin prophylaxis (100 IE/kg/24 hours for 1 month) did not alter the incidence or 1-year mortality of VOD. In multivariate analysis, the following risk factors were significant: norethisterone treatment (P <.001), bilirubin >26 micromol/L before bone marrow transplantation (BMT) (P =.002), one HLA-antigen mismatch (P =.003), previous abdominal irradiation (P =.02), and conditioning with busulphan (P =.02). Our conclusion is that norethisterone treatment should not be used in patients undergoing BMT and heparin prophylaxis did not affect the incidence or mortality of VOD. PMID:9845522

  1. Factors influencing the late phase of recovery after bone mineral density loss in allogeneic stem cell transplantation survivors.

    PubMed

    Anandi, P; Jain, N A; Tian, X; Wu, C O; Pophali, P A; Koklanaris, E; Ito, S; Savani, B N; Barrett, J; Battiwalla, M

    2016-08-01

    Accelerated bone mineral density loss (BMDL) occurs early after allogeneic stem cell transplantation (SCT) and is related to factors such as steroids and chronic GvHD. In order to understand the natural history of BMDL of SCT in the longer term, we evaluated a longitudinal cohort of 148 survivors with a median follow-up of 12 years (range 3-22 years). All women received hormone replacement therapy, and routine calcium/vitamin D supplementation was recommended but ∼50% of patients still had suboptimal vitamin D levels and bisphosphonates were rarely utilized. BMD significantly improved from 5 to 20+ years but the femoral neck and forearm remained vulnerable sites. Younger age, higher pretransplant body mass index (BMI) and increment in BMI post transplant were significantly associated with increased BMD and protected against osteopenia/osteoporosis. These findings support consideration of BMD loss in SCT survivors in two phases, an early phase of BMD loss (3-5 years) followed by a later phase of BMD recovery, with different protective and aggravating factors. Treatment- and transplant-related factors (such as steroids, immunosuppressives, chronic GvHD, vitamin D) are known to impact the early phase of BMD loss but age and BMI are more influential in the late phase of BMD recovery. PMID:27042843

  2. Engineered allogeneic chondrocyte pellet for reconstruction of fibrocartilage zone at bone-tendon junction--a preliminary histological observation.

    PubMed

    Wong, Margaret W N; Qin, Lin; Tai, Jenny K O; Lee, Simon K M; Leung, K S; Chan, K M

    2004-08-15

    This study examined histologically the potential of using allogeneic cultured chondrocyte pellet (CCP) in enhancing bone-tendon junction (BTJ) healing using a rabbit partial patellectomy model. Chondrocytes isolated from the cartilaginous ribs of 6-week-old New Zealand white rabbits were cultured for 14 days to form CCP. Partial patellectomy was performed on 30 18-week-old rabbits. After removal of the distal third patella, the BTJ gap was repaired surgically with or without CCP interposition. Four samples of patella-patellar tendon complexes (PPTC) for each group were harvested each at 8, 12, and 16 weeks; and two additional PPTC for each group were harvested at 2, 4, and 6 weeks for early observation of fibrocartilage zone regeneration, histologically. Results showed that CCP interposition demonstrated earlier structural integration at the BTJ after 8, 12, and 16 weeks of healing, and formation of a fibrocartilage zone like structure, compared with control specimens. In addition, no immune rejection was observed in CCP experimental group. The results suggested that CCP had a stimulatory effect on BTJ healing. This bioengineering approach might have potential clinical application in treatment of difficult BTJ healing. However, systemic histomorphometric, immunological tests, and biomechanical evaluations are needed before any clinical trials. PMID:15264320

  3. Comparison of Two Synthetic Bone Graft Products in a Rabbit Posterolateral Fusion Model

    PubMed Central

    Fredericks, Douglas; Petersen, Emily B.; Watson, Nicole; Grosland, Nicole; Gibson-Corley, Katherine; Smucker, Joseph

    2016-01-01

    Background The drawbacks of iliac crest autograft as graft material for spine fusion are well reported. Despite continued modifications to improve bone healing capacity, the efficacy of synthetic graft materials as stand-alone replacements remains uncertain. The rabbit posterolateral fusion model is an established environment for testing of fusion concepts. It offers the opportunity to obtain radiographic, biomechanical and histological data on novel fusion materials. The objective of this study was to compare the spine fusion capability of two synthetic bone graft products in an established rabbit posterolateral spine fusion (PLF) model: Signafuse® Bioactive Bone Graft Putty and Actifuse® ABX. Methods Bilateral intertransverse spine fusion was performed at the L5-L6 transverse processes (TPs) of New Zealand White rabbits using either Signafuse or Actifuse ABX as the bone graft material. Bone remodeling and spine fusion were assessed at 6 and 12 weeks using radiographic, biomechanical and histological endpoints. Results Fusion rate by manual palpation at 6 weeks was greater for Signafuse (33%) compared to Actifuse ABX (0%), and equivalent in both groups at 12 weeks (50%). Biomechanical fusion rate based on flexion-extension data was 80% in Signafuse group and 44% for Actifuse ABX. Histology revealed a normal healing response in both groups. MicroCT and histomorphometric data at 6 weeks showed greater new bone formation in the Signafuse group compared to Actifuse ABX (p <0.05), with no differences detected at 12 weeks. Histological fusion scores were greater in the Signafuse group at 6 and 12 weeks, indicated by higher degree structural remodeling and tendency towards complete bridging of the fusion bed compared to the Actifuse ABX group. Conclusion Confirmed by several metrics, Signafuse outperformed Actifuse ABX as a standalone synthetic bone graft in an established PLF model, demonstrating greater rates of bone remodeling and spine fusion. The combination of 45

  4. Intraosseous Ganglion Cyst of Scaphoid treated by Curettage and Bone Grafting: Case report and Review

    PubMed Central

    Jain, Saurabh; Jain, Anil Kumar; Dhammi, Ish Kumar; Mishra, Puneet; Modi, Prasant

    2011-01-01

    Introduction: Intraosseous ganglions, although share same pathology as the soft tissue ganglions are rare entities, further rare in carpals. Cases of intraosseous ganglions are reported in literature mostly in lower limbs and lunate among carpals, with treatment options ranging from curettage and grafting to calcium phosphate cement injection and finally to arthroscopic treatment. Case report: Here, we present a case of 2 years follow up of 40 years old female with nonspecific clinical finding of wrist and slight limitation of restriction of motion, diagnosed as intraosseous ganglion cyst of scaphoid. This case was treated with curettage and bone grafting having excellent results with visual and analog pain scores reduced from 68 to 11 and range of motion was 90° extension to 80° flexion and full grip strength. Conclusion: Intraosseous ganglion cyst should be considered in differential diagnosis of chronic dull wrist pain because they produce disabling symptoms which ceases once adequately treated by curettage and bone grafting.

  5. Arthroscopic Bone Grafting of Deep Acetabular Cysts Using a Curved Delivery Device

    PubMed Central

    Garabekyan, Tigran; Chadayammuri, Vivek; Pascual-Garrido, Cecilia; Mei-Dan, Omer

    2016-01-01

    Acetabular intraosseous cysts are frequently encountered in patients with dysplasia or femoroacetabular impingement. Small cysts are typically addressed by removing the cyst lining and stimulating healing via microfracture or abrasion chondroplasty. In contrast, larger cysts involving 1-3 cm3 frequently require additional fortification with bone graft material to facilitate osseous ingrowth and cyst healing. Previous arthroscopic reports have described the use of rim trimming to access the extra-articular side of the cyst, with subsequent use of straight metal cannulas for delivery of bone graft material. The downsides of this technique include the requirement for rim trimming, which may be ill advised in patients with normal coverage or dysplasia, as well as the creation of a second breach in the cyst wall, precluding pressurization of the bone graft material. We describe an arthroscopic technique using a curved delivery device allowing for deeper penetration into the cyst cavity through the articular side and greater delivery of bone graft material. PMID:27073770

  6. Autologous cranial particulate bone grafting reduces the frequency of osseous defects after cranial expansion.

    PubMed

    Gao, Lin Lin; Rogers, Gary F; Clune, James E; Proctor, Mark R; Meara, John G; Mulliken, John B; Greene, Arin K

    2010-03-01

    Primary autologous particulate bone grafting has been demonstrated to heal osseous defects after fronto-orbital advancement. We sought to determine if this technique was equally effective for larger defects resulting from major cranial expansion procedures. We studied children who underwent cranial expansion (other than fronto-orbital advancement) between 1989 and 2008. Defects either were left to heal spontaneously (group 1) or had autologous cranial particulate bone graft placed over dura at the time of cranial expansion (group 2). Particulate bone graft was harvested from the endocortical or ectocortical surface using a hand-driven brace and bit. Outcome variables were ossification and need for revision cranioplasty. The study included 53 children. Mean (SD) age at procedure was 12.2 (8.1) months (range, 1.0-36.0 months) for group 1 (n = 15) and 20.2 (15.1) months (range, 3.3-78.6 months) for group 2 (n = 38) (P = 0.06). There were palpable bony defects in 33.0% (n = 5) of group 1 patients versus 7.9% (n = 3) of group 2 patients (P = 0.03). Corrective cranioplasty was needed in 26.7% of group 1 patients and only 5.3% of those in group 2 (P = 0.04). Primary cranial particulate bone grafting significantly reduced the frequency of osseous defects and secondary cranioplasty following cranial remodeling. PMID:20186093

  7. Comparison of platelet rich plasma and synthetic graft material for bone regeneration after third molar extraction

    PubMed Central

    Nathani, Dipesh B.; Sequeira, Joyce; Rao, B. H. Sripathi

    2015-01-01

    Aims: To compare the efficacy of Platelet rich plasma and synthetic graft material for bone regeneration after bilateral third molar extraction. Material and Methods: This study was conducted in 10 patients visiting the outpatient department of Oral & Maxillofacial Surgery, Yenepoya Dental College & Hospital. Patients requiring extraction of bilateral mandibular third molars were taken for the study. Following extraction, PRP (Platelet Rich Plasma) was placed in one extraction socket and synthetic graft material in form granules [combination of Hydroxyapatite (HA) and Bioactive glass (BG)] in another extraction socket. The patients were assessed for postoperative pain and soft tissue healing. Radiological assessment of the extraction site was done at 8, 12 and 16 weeks interval to compare the change in bone density in both the sockets. Results: Pain was less on PRP site when compared to HA site. Soft tissue evaluation done using gingival healing index given by Landry et al showed better healing on PRP site when compared to HA site. The evaluation of bone density by radiological assessment showed the grey level values calculated at 4 months at the PRP site were comparatively higher than HA site. Conclusion: The study showed that the platelet rich plasma is a better graft material than synthetic graft material in terms of soft tissue and bone healing. However a more elaborate study with a larger number of clinical cases is very much essential to be more conclusive regarding the efficacy of both the materials. PMID:26981473

  8. Heterotopic implantation of autologous bone marrow in rock pigeons (Columba livia): possible applications in avian bone grafting.

    PubMed

    Sanaei, M Reza; Abu, Jalila; Nazari, Mojgan; Faiz, Nik Mohd; Bakar, Mohd Zuki Abu; Allaudin, Zeenathul N

    2011-12-01

    Autologous bone marrow, alone or as a composite marrow graft, has received much attention in various species. To assess the potential osteogenicity of autologous, extramedullary bone marrow implants in an avian model, 24 adult pigeons (Columba livia) were given intramuscular implantations of autologous marrow aspirated from the medial tibiotarsus. Birds were euthanatized at 1, 4, 6, 8, 10, and 12 weeks after surgery to evaluate whether ectopic bone had formed at the implant sites. Primary evaluations by in situ radiography and postmortem histologic examinations showed no evidence of bone formation. Further evaluation with histologic scores and histomorphometry revealed a significantly increased rate of angiogenesis at the implant sites by the sixth and tenth week postimplantation (P < .05). No significant differences between the treatment and control sites were present at any other endpoints. Results of this study show that, although autologous bone marrow lacks heterotopic osteogenic potentials in this avian model, it could still function as a useful adjunct to routine bone grafting techniques because of its unique capabilities to promote early angiogenesis. PMID:22458179

  9. Bone Repair on Fractures Treated with Osteosynthesis, ir Laser, Bone Graft and Guided Bone Regeneration: Histomorfometric Study

    NASA Astrophysics Data System (ADS)

    dos Santos Aciole, Jouber Mateus; dos Santos Aciole, Gilberth Tadeu; Soares, Luiz Guilherme Pinheiro; Barbosa, Artur Felipe Santos; Santos, Jean Nunes; Pinheiro, Antonio Luiz Barbosa

    2011-08-01

    The aim of this study was to evaluate, through the analysis of histomorfometric, the repair of complete tibial fracture in rabbits fixed with osteosynthesis, treated or not with infrared laser light (λ780 nm, 50 mW, CW) associated or not to the use of hydroxyapatite and guided bone regeneration (GBR). Surgical fractures were created, under general anesthesia (Ketamina 0,4 ml/Kg IP and Xilazina 0,2 ml/Kg IP), on the dorsum of 15 Oryctolagus rabbits that were divided into 5 groups and maintained on individual cages, at day/night cycle, fed with solid laboratory pelted diet and had water ad libidum. On groups II, III, IV and V the fracture was fixed with wire osteosynthesis. Animals of groups III and V were grafted with hydroxyapatite and GBR technique used. Animals of groups IV and V were irradiated at every other day during two weeks (16 J/cm2, 4×4 J/cm2). Observation time was that of 30 days. After animal death (overdose of general anesthetics) the specimes were routinely processed to wax and underwent histological analysis by light microscopy. The histomorfometric analysis showed an increased bone neoformation, increased collagen deposition, less reabsorption and inflammation when laser was associated to the HATCP. It is concluded that IR laser light was able to accelerate fracture healing and the association with HATCP and GBR resulted on increased deposition of CHA.

  10. Design and optimization of a tissue-engineered bone graft substitute

    NASA Astrophysics Data System (ADS)

    Shimko, Daniel Andrew

    2004-12-01

    In 2000, 3.1 million surgical procedures on the musculoskeletal system were reported in the United States. For many of these cases, bone grafting was essential for successful fracture stabilization. Current techniques use intact bone obtained either from the patient (autograft) or a cadaver (allograft) to repair large defects, however, neither source is optimal. Allografts suffer integration problems, and for autografts, the tissue supply is limited. Because of these shortcomings, and the high demand for graft tissues, alternatives are being explored. To successfully engineer a bone graft replacement, one must employ a three pronged research approach, addressing (1) the cells that will inhabit the new tissue, (2) the culture environment that these cells will be exposed to, and (3) the scaffold in which these cells will reside. The work herein examines each of these three aspects in great detail. Both adult and embryonic stem cells (ESCs) were considered for the tissue-engineered bone graft. Both exhibited desirable qualities, however, neither were optimal in all categories examined. In the end, the possibility of teratoma formation and ethical issues surrounding ESCs, made the use of adult marrow-derived stem cells in the remaining experiments obligatory. In subsequent experiments, the adult stem cells' ability to form bone was optimized. Basic fibroblast growth factor, fetal bovine serum, and extracellular calcium supplementation studies were all performed. Ultimately, adult stem cells cultured in alpha-MEM supplemented with 10% fetal bovine serum, 10mM beta-glycerophosphate, 10nM dexamethasone, 50mug/ml ascorbic acid, 1%(v/v) antibiotic/antimycotic, and 10.4mM CaCl2 performed the best, producing nearly four times more mineral than any other medium formulation. Several scaffolds were then investigated including those fabricated from poly(alpha-hydroxy esters), tantalum, and poly-methylmethacrylate. In the final study, the most appealing cell type, medium

  11. Demineralized Bone Matrix, as a Graft Enhancer of Auto-Local Bone in Posterior Lumbar Interbody Fusion

    PubMed Central

    Moon, Sang Ho; Kim, Tae Woo; Boo, Kyung Hwan; Hong, Sung Won

    2014-01-01

    Study Design A case controlled study with prospective data collection. Purpose To evaluate the early influence and the final consequence of demineralized bone matrix (DBM) on auto-local bone as a graft enhancer in posterior lumbar interbody fusion (PLIF). Overview of Literature DBM is known as an osteoinductive material; however, it has not been clearly recognized to enhance auto-local bone with a small amount. Methods Patients who had a PLIF were allocated into two groups. Group I (70 cases) used auto-local bone chips and group II (44 cases) used DBM as an additive to auto-local bone, 1 mL per a segment. Group selection was alternated. Early assessment was performed by computed tomography at 6 months and final assessment was done by simple radiography after 24 months at least. The degree of bone formation was assessed by 4 grade scale. Results The subjects of both groups were homogenous and had similar Oswestry Disability Index at final assessment. The ratio of auto-local bone chips and DBM was 6:1. The degree of bone formation at 6 months after surgery was superior in group II. However, there was no significant difference between the two groups at the final assessment. Conclusions DBM was not recognized to enhance auto-local bone with small amount. PMID:24761193

  12. Comparison of the Human Bone Matrix Gelatin (HBMG) with Autogenous Bone Graft in Reconstruction of the Parietal Bone Defects in Rat: A Histological and Radiographic Study

    PubMed Central

    Shahoon, Hossein; Azimi, Hamid Reza; Kianbakht, Camellia

    2009-01-01

    Background and aims Autogenous bone graft is commonly used for reconstruction of bone defects in routine surgical procedures. The complexity of producing bone grafts and their application has lead to the use of human bone matrix gelatin (HBMG). The present study was conducted to compare the efficacy of HBMG and autograft on the reconstruction of bone defects in rats. Materials and methods In this cross-sectional, experimental study, two defects were put on left and right sides of parietal bone of rats. HBMG was placed randomly on defects of one side and autograft in the defects of the other side. All specimens were assessed and compared with each other according to histological and radiographic characteristics. Other assessments included amount and the rate of bone formation, inflammation signs, fibrosis tissue and cartilage formation and also radio-graphic characteristics of grafts, assessed by digital and film-based methods. Mann-Whitney U test was used for statistical analysis. Results The results showed a reduction of inflammation and an increase in new bone formation in both groups in 7, 14, 28 and 60 days after surgery. Bone formation with HBMG on day 24 was more than autograft. However, there was no sig-nificant difference between the groups on day 60. Superiority of digital method to film-based method of imaging was also observed. Conclusion Although HBMG has the same efficacy as autograft, the rate of bone reconstruction with HBMG is higher. HBMG also induces focal, rather than peripheral, bone construction in the defect. PMID:23230480

  13. Risk Factors for Steroid-Refractory Acute Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation from Matched Related or Unrelated Donors.

    PubMed

    Calmettes, Claire; Vigouroux, Stéphane; Labopin, Myriam; Tabrizi, Reza; Turlure, Pascal; Lafarge, Xavier; Marit, Gérald; Pigneux, Arnaud; Leguay, Thibaut; Bouabdallah, Krimo; Dilhuydy, Marie-Sarah; Duclos, Cédric; Mohr, Catherine; Lascaux, Axelle; Dumas, Pierre-Yves; Dimicoli-Salazar, Sophie; Saint-Lézer, Arnaud; Milpied, Noël

    2015-05-01

    We performed a retrospective study to identify pretransplantation risk factors for steroid-refractory (SR) acute graft-versus host disease (aGVHD) after allogeneic stem cell transplantation from matched donors in 630 adult patients who underwent transplantation at our center between 2000 and 2012. The cumulative incidence (CI) of SR aGVHD was 11.3% ± 2.3%. The identified independent risk factors were matched unrelated donor (hazard ratio [HR], 2.52; P = .001), female donor for male recipient (HR, 1.84; P = .023) and absence of antithymocyte globulin (HR, 2.02; P = .005). Three risk groups were defined according to the presence of these risk factors. In the whole cohort, the CI of SR aGVHD was 3.5% ± 1.7% in the low-risk group (0 risk factor, n = 115), 9.3% ± 1.6% in the intermediate-risk group (1 risk factor, n = 323), and 19.3% ± 2.9% in the high-risk group (2 or 3 risk factors, n = 192). Our study suggests that pretransplantation characteristics might help identify patients at high risk for SR aGVHD. A risk adapted first-line treatment of aGVHD could be evaluated in those patients. PMID:25617807

  14. Pretransplant β2-Microglobulin Is Associated with the Risk of Acute Graft-versus-Host-Disease after Allogeneic Hematopoietic Cell Transplant.

    PubMed

    Costa-Lima, Carolina; Miranda, Eliana Cristina Martins; Colella, Marcos Paulo; Aranha, Francisco Jose Penteado; de Souza, Carmino Antonio; Vigorito, Afonso Celso; De Paula, Erich Vinicius

    2016-07-01

    The risk of acute graft-versus-host disease (aGVHD) can be reliably estimated by the hematopoietic cell transplantation-specific comorbidity index (HCT-CI), which can be further refined by the incorporation of pre-hematopoietic cell transplantation (HCT) serum levels of inflammatory biomarkers such as ferritin and albumin. β2-Microglobulin (β2-m) is a key component of the MHC class I complex, which is independently associated with mortality and frailty in the general population. We took advantage of our institutional protocol that includes measurement of pre-HCT β2-m serum levels in the most patients to investigate whether pre-transplant β2-m levels were associated with the risk of aGVHD. One hundred three consecutive patients submitted to allogeneic HCT, of which 26 developed grades II to IV aGVHD, were included in the analysis. β2-m was significantly associated with age and HCT-CI. Higher levels of β2-m were observed in patients who developed aGVHD (P = .008). In the multivariate Cox regression model, β2-m and HCT-CI remained independently associated with the risk of developing aGVHD. In conclusion, the association between β2-m and the occurrence of aGVHD suggests that the measurement of this protein before HCT might represent an additional element for risk stratification of aGVHD. PMID:27044906

  15. Rat CD8+ FOXP3+ T suppressor cells mediate tolerance to allogeneic heart transplants, inducing PIR-B in APC and rendering the graft invulnerable to rejection.

    PubMed

    Liu, Jiawang; Liu, Zhuoru; Witkowski, Piotr; Vlad, George; Manavalan, John S; Scotto, Luigi; Kim-Schulze, Seunghee; Cortesini, Raffaello; Hardy, Mark A; Suciu-Foca, Nicole

    2004-12-01

    Human CD8+ FOXP3+ T suppressor cells (TS) were previously shown to induce the expression of the inhibitory receptors, Immunoglobulin-like transcript (ILT) 3 and ILT4 on dendritic and endothelial cells, rendering them tolerogenic to allogeneic T cells. We have demonstrated the importance of CD8+ TS in a rat model of heart allo-transplantation. Tolerance was induced in ACI recipients by multiple transfusions of UVB-irradiated blood from Lewis heart donors. CD8+ T cells from tolerant ACI rats expressed FOXP3, transferred tolerance to naive secondary hosts and induced the upregulation of the inhibitory receptor, paired immunoglobulin-like receptor (PIR)-B, an ILT4 orthologue, in Lewis dendritic cells (DC) and heart endothelial cells (EC). When long-term surviving Lewis heart allografts with PIR-B+ EC were retransplanted from a primary to a secondary ACI recipient they did not elicit rejection. This study focuses attention on the need to develop agents that act directly on graft EC in order to achieve tolerance. PMID:15589736

  16. Dermoscopic Follow-Up of the Skin towards Acute Graft-versus-Host-Disease in Patients after Allogeneic Hematopoietic Stem Cell Transplantation

    PubMed Central

    Kaminska-Winciorek, Grazyna; Czerw, Tomasz; Kruzel, Tomasz; Giebel, Sebastian

    2016-01-01

    Background. Acute graft-versus-host disease (aGVHD) involving skin is one of the most frequent complications of allogeneic hematopoietic stem cell transplantation (alloHSCT), usually diagnosed based on clinical manifestations. So far, skin biopsy with histopathological evaluation is the only method to confirm the diagnosis. Objective. In this prospective study we monitored alloHSCT recipients by dermoscopy in order to assess its utility as an alternative noninvasive tool to early diagnose acute GVHD. Methods. Thirteen consecutive patients who received alloHSCT were examined clinically and dermoscopically towards aGVHD [days 28 (±7), 56 (±7), and 100 (±7)], as well as in each patient who developed cutaneous aGVHD diagnosed according to clinical criteria (Glucksberg scale). Results. Six patients (46%) developed symptoms of cutaneous acute GVHD (grade 1, n = 3; grade 2, n = 3). Dermoscopic evaluation revealed pinkish or reddish background and well-visible, multiple thin telangiectasias. Conclusion. To our knowledge, this is the first report on the use of dermoscopy to evaluate skin involvement in the course of acute GVHD suggesting its role as a diagnostic tool in follow-up of GVHD, which can be also used before clinical symptoms occur. PMID:27446950

  17. Impacts of graft-versus-host disease on outcomes after allogeneic hematopoietic stem cell transplantation for chronic myelomonocytic leukemia: A nationwide retrospective study.

    PubMed

    Itonaga, Hidehiro; Iwanaga, Masako; Aoki, Kazunari; Aoki, Jun; Ishiyama, Ken; Ishikawa, Takayuki; Sakura, Toru; Fukuda, Takahiro; Najima, Yuho; Yujiri, Toshiaki; Mori, Takehiko; Kurokawa, Mineo; Nawa, Yuichiro; Uchida, Naoyuki; Morishita, Yoshihisa; Hashimoto, Hisako; Eto, Tetsuya; Hirokawa, Makoto; Morishima, Yasuo; Nagamura-Inoue, Tokiko; Atsuta, Yoshiko; Miyazaki, Yasushi

    2016-02-01

    Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a therapeutic option that may lead to improved outcomes in patients with chronic myelomonocytic leukemia (CMML). However, few studies have examined the impact of the grade of graft-versus-host disease (GVHD) on post-transplant outcomes for CMML. We retrospectively analyzed the outcomes of 141 patients with CMML who underwent allo-HSCT between 1987 and 2010, and achieved neutrophil engraftment. The effects of acute GVHD (aGVHD) or chronic GVHD (cGVHD) on overall survival (OS), leukemia-associated mortality (LAM), and transplant-related mortality were evaluated by hazards regression models, in which the onset date of aGVHD or cGVHD was treated as a time-dependent covariate. Grade I aGVHD was associated with better OS and lower LAM (P=0.042, P=0.033, respectively) than no GVHD in univariate analyses, but not in the multivariate analyses. The multivariate analyses demonstrated that extensive cGVHD significantly associated with better OS (Hazard Ratio [HR] 0.35 [95% confidence intervals (CI), 0.16-0.74]; P=0.007) and lower LAM (HR 0.36 [95% CI, 0.14-0.92]; P=0.033) in patients who were not in complete remission at transplantation. In conclusion, the occurrence of cGVHD may be an important factor affecting the outcomes of CMML patients who received transplantation. PMID:26754557

  18. Umbilical cord blood-derived mesenchymal stem cells ameliorate graft-versus-host disease following allogeneic hematopoietic stem cell transplantation through multiple immunoregulations.

    PubMed

    Wu, Qiu-Ling; Liu, Xiao-Yun; Nie, Di-Min; Zhu, Xia-Xia; Fang, Jun; You, Yong; Zhong, Zhao-Dong; Xia, Ling-Hui; Hong, Mei

    2015-08-01

    Although mesenchymal stem cells (MSCs) are increasingly used to treat graft-versus-host disease (GVHD), their immune regulatory mechanism in the process is elusive. The present study aimed to investigate the curative effect of third-party umbilical cord blood-derived human MSCs (UCB-hMSCs) on GVHD patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and their immune regulatory mechanism. Twenty-four refractory GVHD patients after allo-HSCT were treated with UCB-hMSCs. Immune cells including T lymphocyte subsets, NK cells, Treg cells and dendritic cells (DCs) and cytokines including interleukin-17 (IL-17) and tumor necrosis factor-alpha (TNF-α) were monitored before and after MSCs transfusion. The results showed that the symptoms of GVHD were alleviated significantly without increased relapse of primary disease and transplant-related complications after MSCs transfusion. The number of CD3(+), CD3(+)CD4(+) and CD3(+)CD8(+) cells decreased significantly, and that of NK cells remained unchanged, whereas the number of CD4(+) and CD8(+) Tregs increased and reached a peak at 4 weeks; the number of mature DCs, and the levels of TNF-α and IL-17 decreased and reached a trough at 2 weeks. It was concluded that MSCs ameliorate GVHD and spare GVL effect via immunoregulations. PMID:26223913

  19. Efficacy of tacrolimus/mycophenolate mofetil as acute graft-versus-host disease prophylaxis and the impact of subtherapeutic tacrolimus levels in children after matched sibling donor allogeneic hematopoietic cell transplantation.

    PubMed

    Offer, Katharine; Kolb, Michelle; Jin, Zhezhen; Bhatia, Monica; Kung, Andrew L; George, Diane; Garvin, James H; Robinson, Chalitha; Sosna, Jean; Karamehmet, Esra; Satwani, Prakash

    2015-03-01

    Only a few studies in children have evaluated the efficacy of prophylactic regimens using tacrolimus on acute graft-versus-host disease (aGVHD). As a result, optimal tacrolimus levels in children after matched sibling donor allogeneic hematopoietic cell transplantation (alloHCT) are not well defined. We measured the association between subtherapeutic levels (<10 ng/mL) during weeks 1 to 4 after alloHCT and the cumulative incidence of grades II to IV aGVHD in children. Additionally, we identified optimal lower cutoff levels for tacrolimus. Sixty patients (median age, 8 years) received tacrolimus/mycophenolate mofetil between March 2003 and September 2012. Twenty-three had a malignant disease and 37 nonmalignant disorders. The stem cell source included peripheral blood stem cells (n = 12) and bone marrow or cord blood (n = 48). Conditioning regimen varied. Specifically, 38.3% received a myeloablative regimen, 36.7% receiving a reduced-toxicity regimen, and 25% receiving a reduced-intensity regimen. Tacrolimus was initiated at .03 mg/kg/day via continuous i.v. infusion or .12 mg/kg/day orally. The dose was adjusted to maintain daily steady state concentrations within a range of 10 to 20 ng/mL. The overall incidence of grades II to IV aGVHD was 33.3%. On multivariate analysis, a mean tacrolimus level < 10 ng/mL during week 3 (P = .042; 95% confidence interval, 1.051 to 14.28) was significantly associated with increased incidence of grades II to IV aGVHD. Using weekly receiver operator curves, the optimal lower cutoff for tacrolimus levels was 10 to 11.2 ng/mL. Further prospective studies are warranted to study the incidence of aGVHD comparing the conventional tacrolimus levels of 5 to 15 versus 10 to 15 ng/mL. PMID:25536217

  20. Preoperative implant planning considering alveolar bone grafting needs and complication prediction using panoramic versus CBCT images

    PubMed Central

    Guerrero, Maria Eugenia; Noriega, Jorge

    2014-01-01

    Purpose This study was performed to determine the efficacy of observers' prediction for the need of bone grafting and presence of perioperative complications on the basis of cone-beam computed tomography (CBCT) and panoramic radiographic (PAN) planning as compared to the surgical outcome. Materials and Methods One hundred and eight partially edentulous patients with a need for implant rehabilitation were referred for preoperative imaging. Imaging consisted of PAN and CBCT images. Four observers carried out implant planning using PAN image datasets, and at least one month later, using CBCT image datasets. Based on their own planning, the observers assessed the need for bone graft augmentation as well as complication prediction. The implant length and diameter, the need for bone graft augmentation, and the occurrence of anatomical complications during planning and implant placement were statistically compared. Results In the 108 patients, 365 implants were installed. Receiver operating characteristic analyses of both PAN and CBCT preoperative planning showed that CBCT performed better than PAN-based planning with respect to the need for bone graft augmentation and perioperative complications. The sensitivity and the specificity of CBCT for implant complications were 96.5% and 90.5%, respectively, and for bone graft augmentation, they were 95.2% and 96.3%, respectively. Significant differences were found between PAN-based planning and the surgery of posterior implant lengths. Conclusion Our findings indicated that CBCT-based preoperative implant planning enabled treatment planning with a higher degree of prediction and agreement as compared to the surgical standard. In PAN-based surgery, the prediction of implant length was poor. PMID:25279342

  1. Efficacy of guided bone regeneration using composite bone graft and resorbable collagen membrane in Seibert's Class I ridge defects: radiological evaluation.

    PubMed

    Saravanan, Pushparajan; Ramakrishnan, T; Ambalavanan, N; Emmadi, Pamela; John, Thomas Libby

    2013-08-01

    The purpose of the study was to evaluate radiologically the efficacy of guided bone regeneration using composite bone graft (autogenous bone graft and anorganic bovine bone graft [Bio-Oss]) along with resorbable collagen membrane (BioMend Extend) in the augmentation of Seibert's class I ridge defects in maxilla. Bone width was evaluated using computerized tomography at day 0 and at day 180 at 2 mm, 4 mm, and 6 mm from the crest. There was a statistically significant increase in bone width between day 0 and day 180 at 2 mm, 4 mm, and 6 mm from the crest. The results of the study demonstrated an increase in bone width of Seibert's class I ridge defects in the maxilla of the study patients. PMID:23964779

  2. A new Fe-Mn-Si alloplastic biomaterial as bone grafting material: In vivo study

    NASA Astrophysics Data System (ADS)

    Fântânariu, Mircea; Trincă, Lucia Carmen; Solcan, Carmen; Trofin, Alina; Strungaru, Ştefan; Şindilar, Eusebiu Viorel; Plăvan, Gabriel; Stanciu, Sergiu

    2015-10-01

    Designing substrates having suitable mechanical properties and targeted degradation behavior is the key's development of bio-materials for medical application. In orthopedics, graft material may be used to fill bony defects or to promote bone formation in osseous defects created by trauma or surgical intervention. Incorporation of Si may increase the bioactivity of implant locally, both by enhancing interactions at the graft-host interface and by having a potential endocrine like effect on osteoblasts. A Fe-Mn-Si alloy was obtained as alloplastic graft materials for bone implants that need long recovery time period. The surface morphology of the resulted specimens was investigated using scanning electrons microscopy (VegaTescan LMH II, SE detector, 30 kV), X-ray diffractions (X'Pert equipment) or X-ray dispersive energy analyze (Bruker EDS equipment). This study objective was to evaluate in vivo the mechanisms of degradation and the effects of its implantation over the main metabolic organs. Biochemical, histological, plain X radiography and computed tomography investigations showed good compatibility of the subcutaneous implants in the rat organism. The implantation of the Fe-Mn-Si alloy, in critical size bone (tibiae) defect rat model, did not induced adverse biological reactions and provided temporary mechanical support to the affected bone area. The biodegradation products were hydroxides layers which adhered to the substrate surface. Fe-Mn-Si alloy assured the mechanical integrity in rat tibiae defects during bone regeneration.

  3. Retrospective clinical study on sinus bone graft and tapered-body implant placement

    PubMed Central

    Kim, Jong-Hwa; Kim, Young-Kyun

    2013-01-01

    Objectives This study evaluated implant success rate, survival rate, marginal bone resorption of implants, and material resorption of sinus bone graft in cases wherein tapered body implants were installed. Materials and Methods From September 2003 to January 2006, 20 patients from Seoul National University Bundong Hospital, with a mean age of 54.7 years, were considered. The mean follow-up period was 19 months. This study covered 50 implants; 14 implants were placed in the maxillary premolar area, and 36 in the maxillary molar area; 24 sinuses were included. Results The success rate was 92%, and the survival rate was 96.0%. The mean amount of sinus augmentation was 12.35±3.27 mm. The bone graft resorption rate one year after surgery was 0.97±0.84 mm; that for the immediate implantation group was 0.91±0.86 mm, and that for the delayed implantation group was 1.16±0.77 mm. However, the difference was not statistically significant. The mean marginal bone resorption one year after restoration was 0.17±0.27 mm (immediate group: 0.12±0.23 mm; delayed group 0.40±0.33 mm); statistically significant difference was observed between the two groups. Conclusion Tapered body implant can be available in the maxillary posterior edentulous ridge which sinus bone graft is necessary. PMID:24471022

  4. Arthroscopic Posterior Shoulder Stabilization With an Iliac Bone Graft and Capsular Repair: A Novel Technique

    PubMed Central

    Smith, Tomas; Goede, Fabian; Struck, Melena; Wellmann, Mathias

    2012-01-01

    Several surgical approaches have been described for the treatment of recurrent posterior shoulder instability. Many authors have performed posterior bone block procedures with good results not only in the presence of glenoid bone loss or dysplasia but also in the case of capsular hyperlaxity and poor soft-tissue quality. Open techniques often require an extensive approach with the disadvantage of a poor cosmetic result and possible insufficiency of the deltoid muscle. Furthermore, the treatment of concomitant pathologies and the correct placement of the bone graft are difficult. Therefore we describe an all-arthroscopic posterior shoulder stabilization technique with an iliac bone graft and capsular repair that is intended to improve the pre-existing open procedure. The key steps of the operation are the precise placement and screw fixation of the bone block at the posterior glenoid under arthroscopic control and the subsequent posterior capsular refixation and plication using 2 suture anchors to create an extra-articular graft position. PMID:23766993

  5. Choice of Unmanipulated T Cell Replete Graft for Haploidentical Stem Cell Transplant and Posttransplant Cyclophosphamide in Hematologic Malignancies in Adults: Peripheral Blood or Bone Marrow—Review of Published Literature

    PubMed Central

    Farhan, Shatha; Peres, Edward; Janakiraman, Nalini

    2016-01-01

    Allogeneic hematopoietic stem cell transplantation (SCT) is often the only curative option for many patients with malignant and benign hematological stem cell disorders. However, some issues are still of concern regarding finding a donor like shrinking family sizes in many societies, underrepresentation of the ethnic minorities in the registries, genetic variability for some races, and significant delays in obtaining stem cells after starting the search. So there is a considerable need to develop alternate donor stem cell sources. The rapid and near universal availability of the haploidentical donor is an advantage of the haploidentical SCT and an opportunity that is being explored currently in many centers especially using T cell replete graft and posttransplant cyclophosphamide. This is probably because it does not require expertise in graft manipulation and because of the lower costs. However, there are still lots of unanswered questions, like the effect of use of bone marrow versus peripheral blood as the source of stem cells on graft-versus-host disease, graft versus tumor, overall survival, immune reconstitution, and quality of life. Here we review the available publications on bone marrow and peripheral blood experience in the haploidentical SCT setting. PMID:27118973

  6. A comprehensive flow-cytometric analysis of graft infiltrating lymphocytes, draining lymph nodes and serum during the rejection phase in a fully allogeneic rat cornea transplant model

    PubMed Central

    Maenz, Martin; Morcos, Mourice

    2011-01-01

    Purpose To establish a cornea transplant model in a pigmented rat strain and to define the immunologic reaction toward corneal allografts, by studying the cellular and humoral immune response after keratoplasty. Methods Full thickness penetrating keratoplasty was performed on Brown Norway (RT1n) recipients using fully major histocompatibility complex (MHC)-mismatched Piebald-Viral-Glaxo (PVG; RT1c) donors. Using multicolor flow cytometry (FACS) we quantified and compared the cellular composition of draining versus non-draining lymph nodes (LN). Furthermore, we developed an isolation method to release viable graft infiltrating lymphocytes (GIL) and subjected them to phenotypic analysis and screened serum from transplanted animals for allo-antibodies. Results Assessing ipsi-lateral submandibular LN we find ample evidence for post surgical inflammation such as elevated absolute numbers of cluster of differentiation (CD)4+, CD8+, B-cells, and differential expression of CD134. However, we could not unequivocally identify an allo-antigen-specific immune response. FACS analysis of lymphocytes isolated from collagenase digested rejected corneas revealed the following six distinct subpopulations: MHC-2+ cells, CD4+ T-cells, CD8+ T-cells, CD161dull large granular lymphocytes, CD3+ CD8+ CD161dull natural killer (NK)-T-cells and CD161high CD3- NK cells. At post-operation day (POD)-07 only CD161dull MHC-2neg large granular lymphocytes (LGLs) were detected in syngeneic and allo-grafts. In concordance with an increase in B-cell numbers we often detected copious amounts of allo-antibodies in serum of rejecting animals, in particular immunoglobulin (Ig) M (IgM), immunoglobulin (Ig) G1 (IgG1), and IgG2a. Conclusions Our results demonstrate that despite its immune privileged status and low-responder characteristics of the strain combination, allogeneic corneal grafts mount a full fledged T helper1 (Th1) and Th2 response. The presence of NK-T-cells and NK-cells in rejecting corneas

  7. Indications and results of vascularized pedicle iliac bone graft in avascular necrosis of the femoral head.

    PubMed

    Iwata, H; Torii, S; Hasegawa, Y; Itoh, H; Mizuno, M; Genda, E; Kataoka, Y

    1993-10-01

    Several reports describe methods of treatment for avascular necrosis of the femoral head (ANFH) involving 0 to 2 mm of collapse. Some cases of ANFH have good prognoses, requiring only non-weight-bearing treatment. Other cases rapidly progress to collapse and complete destruction with enlargement of the necrotic area. The progression of the necrotic area is related to the activity of the original disease, steroid treatment, and the size and location of the necrotic area in the early stages of the disorder. In this report, a vascularized pedicle bone graft was used to treat ANFH, particularly those cases identified as Stage II on the system established by the Japanese Investigation Committee. Surgery involved curettage of necrotic bone, implantation of spongy bone, and application of a vascularized pedicle bone graft. Grafts were taken from the ilium and included the superficial circumflex iliac artery (SCIA). A bony canal was made in the anterior femoral neck, from which the necrotic bone was curetted and to which the bone graft was applied. The deep circumflex iliac artery (DCIA) was also used in combination with the SCIA. The postoperative weight-bearing period was six months. Follow-up periods lasted one to six years. Seventeen of 23 Stage II joints (19 cases) achieved satisfactory results at a mean of three years after surgery. Three Stage II joints and three Stage III joints continue to have significant problems. One of these six has been converted to a dual-bearing type endoprosthesis. The unsuccessful results generally occurred in patients who were treated with steroids. PMID:8403663

  8. Hydroxyapatite-Based Biomaterials vs. Autologous Bone Graft in Spinal Fusion: An in Vivo Animal Study.

    PubMed

    Bròdano, Giovanni Barbanti; Giavaresi, Gianluca; Lolli, Francesco; Salamanna, Francesca; Parrilli, Annapaola; Martini, Lucia; Griffoni, Cristiana; Greggi, Tiziana; Arcangeli, Elena; Pressato, Daniele; Boriani, Stefano; Fini, Milena

    2014-04-01

    Study Design. An in vivo study was designed to compare the efficacy of biomimetic Magnesium-Hydroxyapatite (MgHA) and of human demineralised bone matrix (HDBM), both dispersed in a mixture of biomimetic Mg-HA nanoparticles, with that of an autologous bone graft.Objective. The objective of this study was to evaluate two new bone substitutes as alternatives to a bone autograft for spinal fusion, determining their osteoinductive and osteoconductive properties, and their capacity of remodeling, using a large animal model.Summary of Background Data. Spinal fusion is a common surgical procedure and it is performed for different conditions. A successful fusion requires potentially osteogenic, osteoinductive and osteoconductive biomaterials.Methods. A posterolateral spinal fusion model involved 18 sheep, bilaterally implanting test materials between the vertebral transverse processes. The animals were divided into two groups: one fusion level was treated with MgHA (Group 1) or with HDBM-MgHA (Group 2). The other fusion level received bone autografts in both groups.Results. Radiographic, histological and microtomographic results indicated good osteointegration between the spinous process and the vertebral foramen for both materials. Histomorphometry revealed no significant differences between MgHA and autologous bone for all the parameters examined while significantly lower values of bone volume were observed between HDBM-MgHA and autologous bone. Moreover, the normalisation of the histomorphometrical data with autologous bone revealed that MgHA showed a significantly higher value of bone volume and a lower value of trabecular number, more similar to autologous bone, in comparison to HDBM-MgHA.Conclusion. The study showed that the use of MgHA in an ovine model of spinal fusion led to the deposition of new bone tissue without qualitative and quantitative differences with respect to new bone formed with autologous bone while the HDBM-MgHA led to a reduced deposition of newly

  9. Nonmyeloablative allogeneic hematopoietic cell transplantation

    PubMed Central

    Storb, Rainer; Sandmaier, Brenda M.

    2016-01-01

    Most hematological malignancies occur in older patients. Until recently these patients and those with comorbidities were not candidates for treatment with allogeneic hematopoietic transplantation because they were unable to tolerate the heretofore used high-dose conditioning regimens. The finding that many of the cures achieved with allogeneic hematopoietic transplantation were due to graft-versus-tumor effects led to the development of less toxic and well-tolerated reduced intensity and nonmyeloablative regimens. These regimens enabled allogeneic engraftment, thereby setting the stage for graft-versus-tumor effects. This review summarizes the encouraging early results seen with the new regimens and discusses the two hurdles that need to be overcome for achieving even greater success, disease relapse and graft-versus-host disease. PMID:27132278

  10. TREATMENT OF SCAPHOID NONUNION WITH OLECRANON BONE GRAFT AND COMPRESSION SCREW

    PubMed Central

    NEDER, ANTONIO TUFI; FRANCESCHINI, EDUARDO TRALDI; PARDINI, ARLINDO GOMES; RIBERTO, MARCELO; MAZZER, NILTON

    2016-01-01

    ABSTRACT Objective: To evaluate the outcome of olecranon bone graft and compression screw for the treatment of nonunion of the Lichtman type I scaphoid. Method: We evaluated 15 patients of 32 who underwent surgical treatment for nonunion of the Lichtman type I scaphoid with olecranon bone graft and screw compression. Results: We obtained 100% consolidation in our sample. The mean flexion of the wrist on the affected side was 68° and 75° on the non-affected side. The average extension was 63° and 72°, respectively. The average grip strength was 35 kgf. This corresponds to 98% of the handgrip strength of the non-affected side, which was 37 kgf. The DASH score averaged 5 points. Conclusion: We believe that the use of bone graft obtained from the olecranon and secured with cannulated screw is a resolute technique for cases of linear nonunion of the Lichtmann type I scaphoid. It has the advantages of a new anesthesia for removal of the graft and the access is easy, providing a good exposure for removal and good aesthetic results. Level of evidence IV. Case series. PMID:27217819

  11. Antibiotic-Impregnated Bone Grafts in Orthopaedic and Trauma Surgery: A Systematic Review of the Literature

    PubMed Central

    Anagnostakos, Konstantinos; Schröder, Katrin

    2012-01-01

    There exist several options for local antibiotic therapy in orthopaedic and trauma surgery. Over the past years, the use of antibiotic-impregnated bone grafts (AIBGs) has become a popular procedure in the treatment of bone and joint infections. A major advantage of AIBGs involves the possibility of impregnation of various antibiotics depending on the sensitivity profile of the causative organism, whereas an additional surgery with removal of the antibiotic carrier is not necessary, as in the use of antibiotic-loaded bone cement. However, generalized conclusions cannot be clearly drawn from the existing literature due to differences of bone used, impregnation method, antibiotics, their doses, laboratory circumstances, or clinical indications. The present work reviews the literature regarding this topic and sheds some light onto the choice of bone and antibiotics, manufacturing details, and clinical experience. PMID:22899933

  12. The use of demineralized bone matrix in the repair of segmental defects. Augmentation with extracted matrix proteins and a comparison with autologous grafts.

    PubMed

    Bolander, M E; Balian, G

    1986-10-01

    A soluble protein component of bone, bone morphogenetic protein, and decalcified bone matrix have been shown to induce the formation of bone in extraosseous tissue. Clinical and animal studies investigating the use of these materials as bone grafts have shown radiographic and histological evidence of formation of bone, but the clinical usefulness of these grafts remains unknown. This study compared the healing processes when plasma-coated demineralized bone matrix and autologous cancellous bone were used to graft segmental defects of bone. A standard procedure was used to make a two-centimeter defect bilaterally in the ulna of forty-eight skeletally mature New Zealand White rabbits. In each rabbit, one ulnar defect was grafted with autologous citrated plasma-coated demineralized bone matrix while the other defect served as a control and was grafted with either autologous cancellous bone from the iliac crest, demineralized bone matrix, or demineralized bone matrix augmented with bone proteins that had been extracted with guanidinium hydrochloride. The ulnar defect was stabilized by the intact radius, and no supplemental device was necessary for fixation. To examine spontaneous healing in this model, one group of rabbits had a control defect that was not grafted. The grafts were periodically evaluated by radiographs, and twelve weeks after surgery the grafts were harvested and tested to failure in a standard torsion-test machine. The mechanical parameters were calculated, and histological examination of major fragments of the grafts was performed. The results of the radiographic and histological evaluation showed that all of the grafted ulnae healed, with fusion of the graft to the cut ends of the defect and reformation of approximately normal anatomy. No ungrafted ulnar defects healed. The results from the mechanical tests were evaluated by comparing the defect that was grafted with plasma-coated demineralized bone matrix with the control graft in each animal. These

  13. Evaluation of cranial bone transport distraction with and without adipose grafting.

    PubMed

    Koch, Felix P; Yuhasz, Mikell M; Travieso, Rob; Wong, Kenneth; Clune, James; Zhuang, Zhen W; Van Houten, Joshua; Steinbacher, Derek M

    2014-05-01

    Transport distraction osteogenesis (DO) can be used to autologously reconstitute calvarial defects. The purpose of this study is to histomorphologically interrogate osteogenic formation during cranial transport distraction using a novel device. We also evaluate the effect of fat grafting on the regenerate and soft-tissue stability during distraction. This study was approved by Yale IACUC. Ten male New Zealand white rabbits (3 mo; 3.5 kg) were used (8 treatment, 2 control). A 16 × 16 mm defect was created abutted by a 10 × 16 mm transport disc. The device was fixated anterioposteriorly. Four animals were fat-grafted using 2 mL of subdermal intrascapular fat deposited along the distraction site. Latency (1 d), active distraction (12-14 d) (1.5 mm/d), and consolidation (4 wk) followed. Calcein and xylene orange fluorochromes were injected subcutaneously during and post-distraction to mark sites of bone formation. Following sacrifice, osteogenesis was assessed using microCT, histology, and fluorescence. Treatment animals demonstrated regenerate bone between distracted segments on microCT. MicroCT analysis of non-fat-grafted and fat-grafted animals revealed a mean density of 2271.95 mgHA/ccm and 2254.27 mgHA/ccm (P = 0.967), respectively, and defect bone versus total volume (BV/TV) of 0.0999 and 0.0766 (P = 0.5979), respectively. Controls had minimal reossification. Histologically, mean densities measured 43.63% and 8.19%, respectively. Fluorescence revealed ossification from the callus as well as from dura and periosteum in the cranial defect. Transport distraction is effective to reconstruct critically sized rabbit calvarial defects. Regenerate bone arises predominantly from the callus with contribution from surrounding dura and periosteum. Adipose grafting is well tolerated but does not enhance osseous regeneration. PMID:24820707

  14. Alveolar ridge augmentation using chin bone graft, bovine bone mineral, and titanium mesh: Clinical, histological, and histomorphomtric study

    PubMed Central

    Khamees, Jihad; Darwiche, Mohammad Atef; Kochaji, Nabil

    2012-01-01

    Background: Resorption of the alveolar ridge often leaves insufficient bone volume. Very few studies have investigated the quantity and quality of bone formation in humans, following alveolar ridge augmentation, using autogenous bone and bovine bone mineral (BBM) under titanium mesh. Materials and Methods: Sixteen alveolar bone defects divided into two groups; control group with symphyseal autogenous bone covered by titanium mesh; and test group with symphyseal autogenous bone mixed with BBM in 1: 1 ratio and covered by titanium mesh. The outcomes were evaluated clinically, histologically, and histomorphometrically. Results: Clinical measurements showed that the horizontal bone gain was 3.44±0.54 mm and 2.88±0.57 mm, on average, for control group and test group, respectively. While graft absorption was 2.66±0.98 mm (43.62%) and 1.67±1.00 mm (36.65%), on average, for control group and test group, respectively. In the test group, BBM particles were still recognizable, on histologic analysis. They were surrounded completely or partly by newly formed bone. Clear signs of resorption of the BBM were found, with osteoclast cell noticed in the area. Histomorphometrically, the newly formed bone was 78.40%±13.97% and 65.58%±6.59%, whereas connective tissue constituted 21.60%±13.97% and 23.87%±4.79% for control group and test group, respectively. The remaining BBM particles occupied 10.55%±1.80%. All differences between the control and test groups were not significant (P>.05). Conclusion: This investigation suggests that horizonal ridge augmentation with titanium mesh and autogenous bone alone or mixed with BBM are predictable and ridges were augmented even if mesh exposure occurs. PMID:23055591

  15. Secondary alveolar bone grafting in cleft of the lip and palate patients

    PubMed Central

    Walia, Abhilashaa

    2011-01-01

    Aim: The aim was to restore the function and form of both arches with a proper occlusal relationship and eruption of tooth in the cleft area. Materials and Methods: Eleven patients were selected irrespective of sex and socio-economic status and whose age was within the mixed dentition period. Iliac crest is grafted in cleft area and subsequently evaluated for graft success using study models, and periapical and occlusal radiographs. Results: At the time of evaluation teeth were erupted in the area and good alveolar bone levels were present. Premaxilla becomes immobile with a good arch form and arch continuity. There are no major complications in terms of pain, infection, paraesthesia, hematoma formation at donor site without difficulty in walking. There is no complication in terms of pain, infection, exposure of graft, rejection of graft, and wound dehiscence at the recipient site. Discussion: It is evident that secondary alveolar grafting during the mixed dentition period is more beneficial for patients at the donor site as well as the recipient site. Conclusion: Long-term follow-up is required to achieve maximum advantage of secondary alveolar grafting; the age of the patient should be within the mixed dentition period, irrespective of sex, socio-economic status. It may be unilateral or bilateral. PMID:22090755

  16. Prostaglandin E2 Production and T Cell Function in Mouse Adenovirus Type 1 Infection following Allogeneic Bone Marrow Transplantation

    PubMed Central

    McCarthy, Mary K.; Procario, Megan C.; Wilke, Carol A.; Moore, Bethany B.; Weinberg, Jason B.

    2015-01-01

    Adenovirus infections are important complications of bone marrow transplantation (BMT). We demonstrate delayed clearance of mouse adenovirus type 1 (MAV-1) from lungs of mice following allogeneic BMT. Virus-induced prostaglandin E2 (PGE2) production was greater in BMT mice than in untransplanted controls, but BMT using PGE2-deficient donors or recipients failed to improve viral clearance, and treatment of untransplanted mice with the PGE2 analog misoprostol did not affect virus clearance. Lymphocyte recruitment to the lungs was not significantly affected by BMT. Intracellular cytokine staining of lung lymphocytes demonstrated impaired production of INF-γ and granzyme B by cells from BMT mice, and production of IFN-γ, IL-2, IL-4, and IL-17 following ex vivo stimulation was impaired in lymphocytes obtained from lungs of BMT mice. Viral clearance was not delayed in untransplanted INF-γ-deficient mice, suggesting that delayed viral clearance in BMT mice was not a direct consequence of impaired IFN-γ production. However, lung viral loads were higher in untransplanted CD8-deficient mice than in controls, suggesting that delayed MAV-1 clearance in BMT mice is due to defective CD8 T cell function. We did not detect significant induction of IFN-β expression in lungs of BMT mice or untransplanted controls, and viral clearance was not delayed in untransplanted type I IFN-unresponsive mice. We conclude that PGE2 overproduction in BMT mice is not directly responsible for delayed viral clearance. PGE2-independent effects on CD8 T cell function likely contribute to the inability of BMT mice to clear MAV-1 from the lungs. PMID:26407316

  17. Long-term observations of autoimmune-prone mice treated for autoimmune disease by allogeneic bone marrow transplantation

    SciTech Connect

    Ikehara, S.; Yasumizu, R.; Inaba, M.; Izui, S.; Hayakawa, K.; Sekita, K.; Toki, J.; Sugiura, K.; Iwai, H.; Nakamura, T. )

    1989-05-01

    Long-term effects of allogeneic bone marrow transplantation (ABMT) across major histocompatibility complex barriers were studied in (NZB x NZW)F1 (B/W), BXSB, and MRL/Mr-lpr-lpr (MRL/lpr) mice with established autoimmune disease at the time of ABMT. In the BXSB or B/W mice, ABMT cured all aspects of autoimmune disease. Glomerular damage, revealed by histological study was dramatically improved. Serological abnormalities and immunologic functions also were normalized. Correction of autoimmune disease and advanced renal disease in BXSB and B/W mice regularly lasted greater than 5-6 mo and even 1 yr after ABMT. In the MRL/lpr mice, however, autoimmune and renal disease at first improved but then recurred after ABMT, apparently because of intolerance of mice for high doses of irradiation and a high degree of resistance of recipient stem cells to irradiation. In this model, H-2 typing revealed that by the time of relapse, immunocompetent cells of the chimeric mice had been replaced by host (MRL/lpr; H-2k) cells. B220+ Ly-1+ cells, present in increased numbers in untreated MRL/lpr mice, initially returned to normal levels after ABMT but then reappeared in the MRL/lpr mice that had received marrow from donors having few such lymphocytes. Thus, our results show that MRL/lpr mice possess abnormal radioresistant stem cells and provide impressive evidence that the origin of autoimmune diseases in this strain, as in the several other strains studied, resids in abnormalities present in stem cells.

  18. Numerical impairment of nestin(+) bone marrow niches in acute GvHD after allogeneic hematopoietic stem cell transplantation for AML.

    PubMed

    Medinger, M; Krenger, W; Jakab, A; Halter, J; Buser, A; Bucher, C; Passweg, J; Tzankov, A

    2015-11-01

    The nestin(+) perivascular bone marrow (BM) stem cell niche (N(+)SCN) may be involved in GvHD. To investigate whether acute GvHD (aGvHD) reduces the number of N(+)SCN, we examined patients with AML who had undergone allogeneic hematopoietic stem cell transplantation. In the test cohort (n=8), the number of N(+)SCN per mm(2) in BM biopsies was significantly reduced in aGvHD patients at the time of aGvHD compared with patients who did not have aGvHD (1.2±0.78 versus 2.6±0.93, P=0.04). In the validation cohort (n=40), the number of N(+)SCN was reduced (1.9±0.99 versus 2.6±0.90 N(+)SCN/mm(2), P=0.05) in aGvHD patients. Receiver operating curves suggested that the cutoff score that best discriminated between patients with and without aGvHD was 2.29 N(+)SCN/mm(2). Applying this cutoff score, 9/11 patients with clinically relevant aGvHD (⩾grade 2) and 13/20 with any type of GvHD had decreased N(+)SCN numbers compared with only 10/29 patients without clinically relevant aGvHD (P=0.007) and 6/20 patients without any type of GvHD (P=0.028). In patients tracked over time, N(+)SCN density returned to normal after aGvHD resolved or remained stable in patients who did not have aGvHD. Our results show a decrease in the number of N(+)SCN in aGvHD. PMID:26301968

  19. Effects of Ischemic Preconditioning of Different Intraoperative Ischemic Times of Vascularized Bone Graft Rabbit Models

    PubMed Central

    Wan Ahmad Kamal, Wan Syazli Rodzaia; Noor, Norizal Mohd; Abdullah, Shafie

    2013-01-01

    Background Ischemic preconditioning has been shown to improve the outcomes of hypoxic tolerance of the heart, brain, lung, liver, jejunum, skin, and muscle tissues. However, to date, no report of ischemic preconditioning on vascularized bone grafts has been published. Methods Sixteen rabbits were divided into four groups with ischemic times of 2, 6, 14, and 18 hours. Half of the rabbits in each group underwent ischemic preconditioning. The osteomyocutaneous flaps consisted of the tibia bone, from which the overlying muscle and skin were raised. The technique of ischemic preconditioning involved applying a vascular clamp to the pedicle for 3 cycles of 10 minutes each. The rabbits then underwent serial plain radiography and computed tomography imaging on the first, second, fourth, and sixth postoperative weeks. Following this, all of the rabbits were sacrificed and histological examinations were performed. Results The results showed that for clinical analysis of the skin flaps and bone grafts, the preconditioned groups showed better survivability. In the plain radiographs, except for two non-preconditioned rabbits with intraoperative ischemic times of 6 hours, all began to show early callus formation at the fourth week. The computed tomography findings showed more callus formation in the preconditioned groups for all of the ischemic times except for the 18-hour group. The histological findings correlated with the radiological findings. There was no statistical significance in the difference between the two groups. Conclusions In conclusion, ischemic preconditioning improved the survivability of skin flaps and increased callus formation during the healing process of vascularized bone grafts. PMID:24286040

  20. Silver nanoparticle based antibacterial methacrylate hydrogels potential for bone graft applications

    PubMed Central

    González-Sánchez, M. Isabel; Perni, Stefano; Tommasi, Giacomo; Morris, Nathanael Glyn; Hawkins, Karl; López-Cabarcos, Enrique; Prokopovich, Polina

    2015-01-01

    Infections are frequent and very undesired occurrences after orthopedic procedures; furthermore, the growing concern caused by the rise in antibiotic resistance is progressively dwindling the efficacy of such drugs. Artificial bone graft materials could solve some of the problems associated with the gold standard use of natural bone graft such as limited bone material, pain at the donor site and rejections if donor tissue is used. We have previously described new acrylate base nanocomposite hydrogels as bone graft materials. In the present paper, we describe the integration of silver nanoparticles in the polymeric mineralized biomaterial to provide non-antibiotic antibacterial activity against Staphylococcus epidermidis and Methicillin-resistant Staphylococcus aureus. Two different crosslinking degrees were tested and the silver nanoparticles were integrated into the composite matrix by means of three different methods: entrapment in the polymeric hydrogel before the mineralization; diffusion during the process of calcium phosphate crystallization and adsorption post-mineralization. The latter being generally the most effective method of encapsulation; however, the adsorption of silver nanoparticles inside the pores of the biomaterial led to a decreasing antibacterial activity for adsorption time longer than 2 days. PMID:25746278

  1. Treatment of scaphoid nonunion with vascularised and nonvascularised dorsal bone grafting from the distal radius

    PubMed Central

    Medina, Carlos Eduardo Gonzalez; Mattar, Rames; Ulson, Heitor Jose Rizzardo; de Resende, Marcelo Rosa; Etchebehere, Mauricio

    2009-01-01

    We conducted a prospective randomised study comparing the clinical, functional and radiographic results of 46 patients treated for scaphoid nonunion using a vascularised bone graft from the dorsal and distal aspect of the radius (group I), relative to 40 patients treated by means of a conventional non-vascularised bone graft from the distal radius (group II). Surgical findings included 30 sclerotic, poorly-vascularised scaphoids in group I versus 20 in group II. Bone fusion was achieved in 89.1% of group I and 72.5% of group II patients (p = 0.024). Functional results were good to excellent in 72.0% of the patients in group I and 57.5% in group II. Considering only patients with sclerotic, poorly-vascularised scaphoids, the mean final outcome scores obtained were 7.5 and 6.0 for groups I and group II, respectively. We conclude that vascularised bone grafting yields superior results and is more efficient when there is a sclerotic, poorly-vascularised proximal pole in patients in scaphoid nonunion. PMID:19730861

  2. Silver nanoparticle based antibacterial methacrylate hydrogels potential for bone graft applications.

    PubMed

    González-Sánchez, M Isabel; Perni, Stefano; Tommasi, Giacomo; Morris, Nathanael Glyn; Hawkins, Karl; López-Cabarcos, Enrique; Prokopovich, Polina

    2015-05-01

    Infections are frequent and very undesired occurrences after orthopedic procedures; furthermore, the growing concern caused by the rise in antibiotic resistance is progressively dwindling the efficacy of such drugs. Artificial bone graft materials could solve some of the problems associated with the gold standard use of natural bone graft such as limited bone material, pain at the donor site and rejections if donor tissue is used. We have previously described new acrylate base nanocomposite hydrogels as bone graft materials. In the present paper, we describe the integration of silver nanoparticles in the polymeric mineralized biomaterial to provide non-antibiotic antibacterial activity against Staphylococcus epidermidis and Methicillin-resistant Staphylococcus aureus. Two different crosslinking degrees were tested and the silver nanoparticles were integrated into the composite matrix by means of three different methods: entrapment in the polymeric hydrogel before the mineralization; diffusion during the process of calcium phosphate crystallization and adsorption post-mineralization. The latter being generally the most effective method of encapsulation; however, the adsorption of silver nanoparticles inside the pores of the biomaterial led to a decreasing antibacterial activity for adsorption time longer than 2 days. PMID:25746278

  3. Structural mechanical properties of radiation-sterilized human Bone-Tendon-Bone grafts preserved by different methods.

    PubMed

    Gut, Grzegorz; Marowska, Joanna; Jastrzebska, Anna; Olender, Ewa; Kamiński, Artur

    2016-06-01

    To avoid the risk of infectious disease transmission from donor to recipient, allografts should be terminally sterilized. In the previous paper (Kaminski et al. in Cell Tissue Bank 10:215-219, 2009) we presented the effect of various methods of preservation (deep fresh freezing, glycerolization, lyophilization), followed by irradiation with different doses of electron beam (EB), on material (intrinsic) mechanical properties of human patellar tendons cut out as for anterior cruciate ligament reconstruction, obtained in failure tensile test. As structural mechanical properties are equally important to predict the behaviour of the graft as a whole functional unit, the purpose of the present paper was to show the results for failure load and elongation, obtained in the same experiment. Paired Bone-Tendon-Bone grafts (BTB) were prepared from cadaveric human patella tendons with both patellar and tibial attachments. They were preserved by deep freezing, glycerolization or lyophilization and subsequently EB-irradiated with the doses of 25, 35, 50 or 100 kGy (fresh-frozen grafts) or a single dose of 35 kGy (glycerolized and lyophilized grafts). Each experimental (irradiated) group was provided with control (non-irradiated), donor-matched group. The specimens from all groups were subjected to mechanical failure tensile test with the use of Instron system in order to measure their structural properties (failure load and elongation). All lyophilized grafts were rehydrated before mechanical testing. In our study we did not observe significant deterioration of structural mechanical properties of BTB grafts processed by fresh-freezing and then terminal sterilized with growing doses of EB up to 100 kGy. In contrast, BTB grafts processed by glycerolization or lyophilization and irradiated with 35 kGy showed significant decrease of failure load. Obtained results suggest that deep-frozen irradiated grafts retain their initial mechanical properties to an extent which does not

  4. Man as a Living Bioreactor: Prefabrication of a Custom Vascularized Bone Graft in the Gastrocolic Omentum.

    PubMed

    Wiltfang, Jörg; Rohnen, Michael; Egberts, Jan-Hendrik; Lützen, Ulf; Wieker, Henning; Açil, Yahya; Naujokat, Hendrik

    2016-08-01

    Reconstruction of critical-size jaw defects still remains challenging. The standard treatment today is transplantation of autologous bone grafts, which is associated with high donor-site morbidity and unsatisfactory outcomes. We aimed to reconstruct a mandibular discontinuity defect after ablative surgery using the gastrocolic omentum as a bioreactor for heterotopic ossification. Three-dimensional computed tomography data were used to produce an ideal virtual replacement for the mandibular defect. A titanium mesh cage was filled with bone mineral blocks, infiltrated with 12 mg of recombinant human bone morphogenetic protein 2, and enriched with bone marrow aspirate. The scaffold was implanted into the gastrocolic omentum, and 3 months later, a free flap was harvested to reconstruct the mandibular defect. In vivo single photon emission computed tomography/computed tomography revealed bone remodeling and mineralization inside the mandibular transplant during prefabrication and after transplantation. Reconstruction was possible without any further modifications of the graft. A histological evaluation revealed that large sections of the Bio-Oss material were covered with osteoid matrix 3 months after transplantation. The quality of life of the patient significantly increased with acquisition of the ability to masticate and the improvement in pronunciation and aesthetics. Heterotopic bone induction to form a mandibular replacement inside the gastrocolic omentum is possible in human subjects. Heterotopic prefabrication is associated with many advantages, like allowing a reduced operative burden compared with conventional techniques and good three-dimensional outcomes. PMID:27317022

  5. Bone grafting and one-stage revision of THR - biological reconstruction and effective antimicrobial treatment using antibiotic impregnated allograft bone.

    PubMed

    Winkler, Heinz

    2012-01-01

    Infection of a total hip replacement (THR) is considered one of the most serious complications in orthopaedic surgery. Problems derive from the presence of biofilms with inherent resistance to usual antibiotic treatment and bone defects resulting from infection induced osteolysis. Discussions on the choice of treatment mainly focus on the chance of eradicating the infection in either one or more stages. The advantages of only one operation with regard to patients' satisfaction, functional results and economical burden are evident. However, the fear of re-infection usually leads surgeons to multiple stage procedures, mostly using antibiotic loaded spacers in the interval. Spacers have no effect on biofilms and are associated with a high rate of complications such as breakage or dislocation. Cemented revisions show several disadvantages like reduction of biomechanical properties through added antibiotics, inferior long term results, difficulties of removal in case of recurrence etc. Uncemented implants appear more advantageous but are at risk of becoming colonised by remaining biofilm fragments. To overcome this risk higher local concentrations of antibiotics are needed. Allograft bone may be impregnated with high loads of antibiotics using special incubation techniques, resulting in an antibiotic bone compound (ABC). ABC provides local concentrations exceeding those of cement by more than a 100-fold and efficient release is prolonged for several weeks. At the same time it is likely to restore bone stock, which is usually compromised after removal of an infected endoprosthesis. Based on these considerations new protocols for one-stage exchange of infected THR have been established. Bone voids may be filled with ABC, uncemented implants may be fixed in original healthy bone. Recent studies indicate an overall success rate of more than 90% with one operation, without any adverse side effects. Incorporation of allografts appears as after grafting with unimpregnated bone

  6. Is nonstructural bone graft useful in surgical treatment of lumbar spinal tuberculosis?

    PubMed Central

    Liu, Jia-Ming; Chen, Xuan-Yin; Zhou, Yang; Long, Xin-Hua; Chen, Wen-Zhao; Liu, Zhi-Li; Huang, Shan-Hu; Yao, Hao-Qun

    2016-01-01

    Abstract Surgical intervention is an important option for treating spinal tuberculosis. Previous studies have reported different surgical procedures and bone grafts for it. To our knowledge, few studies demonstrated the clinical results of using nonstructural autogenous bone graft in surgical treatment of spinal tuberculosis. The purpose of this study is to compare the clinical outcomes of surgical management lumbar spinal tuberculosis by one-stage posterior debridement with nonstructural autogenous bone grafting and instrumentation versus anterior debridement, strut bone grafting combined with posterior instrumentation. A total of 58 consecutive patients who underwent surgical treatment due to lumbar spinal tuberculosis from January 2011 to December 2013 were included. A total of 22 patients underwent one-stage posterior debridement, nonstructural autogenous bone grafting, and instrumentation (group A), and 36 patients received anterior debridement, strut bone grafting combined with posterior instrumentation (group B). The operative duration, total blood loss, perioperative transfusion, length of hospital stay, hospitalization cost, and complications were recorded. The bony fusion of the graft was assessed by computed tomography scans. American Spinal Injury Association (ASIA) Impairment Scale was used to evaluate the neurological function of patients in the 2 groups. All the patients were followed up, with a mean follow-up duration of 21.6 ± 5.7 months in group A and 22.3 ± 6.2 months in group B (P = 0.47). The average operative duration was 257.5 ± 91.1 minutes in group A and 335.7 ± 91.0 minutes in group B (P = 0.002). The mean total blood loss was 769.6 ± 150.9 mL in group A and 1048.6 ± 556.9 mL in group B (P = 0.007). Also, significant differences were found between the 2 groups in perioperative transfusion volumes, length of hospital stay, and hospitalization cost (P < 0.05), which were less in group A

  7. THE EFFECT OF 2-BUTYL-CYANOACRYLATE ADHESIVE IN OSTEOTOMIES AND BONE GRAFTS IN RABBITS: MACROSCOPIC AND RADIOGRAPHIC CHARACTERISTICS

    PubMed Central

    Xavier, Mário Sérgio Viana; Leite, Vilnei Mattioli

    2015-01-01

    Objective: To evaluate the effect of butyl-2-cyanoacrylate tissue adhesive in osteotomies and bone grafts, with regard to macroscopic and radiographic characteristics. Methods: Forty-eight rabbits were used, randomly divided into four groups of 12 animals, with observation periods of two, four, eight and 16 weeks. Both thoracic limbs were operated in each animal and two osteotomies were performed in each of the radii, withdrawing a bone fragment (bone graft) of 1 cm in length. On one side, the bone graft was then replaced and a drop of adhesive was applied to each of the osteotomies. On the other side, the same procedure was performed without applying the adhesive. The rejection level for the nullity hypothesis was set at 0.05% or 5%. Results: Blue marks were present in all the surgical specimens in which adhesive was applied. From the fourth week onwards, there was absence of movement of the bone grafts with adhesive and control. In group A, in the proximal osteotomies with adhesive, there was less deviation of the bone graft (p = 0.02). In group C, the union (p = 0.03) and the integration of the bone graft (p = 0.02) were better in the proximal osteotomies with adhesive. Conclusions: The adhesive was not completely metabolized within 16 weeks. There was clinical consolidation of the osteotomies within four weeks. The adhesive stabilized the bone graft within the first weeks and did not interfere with the consolidation of the osteotomies, or the integration of the bone graft in radiographic observations. PMID:27047878

  8. Allogeneic hematopoietic stem cell transplantation for inherited bone marrow failure syndromes.

    PubMed

    Dalle, Jean-Hugues; Peffault de Latour, Régis

    2016-04-01

    Inherited bone marrow failure (IBMF) syndromes are a heterogeneous group of rare hematological disorders characterized by the impairment of hematopoiesis, which harbor specific clinical presentations and pathogenic mechanisms. Some of these syndromes may progress through clonal evolution, myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Most prominent are failures of DNA repair such as Fanconi Anemia and much rarer failure of ribosomal apparatus, e.g., Diamond Blackfan Anemia or of telomere elongation such as dyskeratosis congenita. In these congenital disorders, hematopoietic stem cell transplantation (HSCT) is often a consideration. However, HSCT will not correct the underlying disease and possible co-existing extra-medullary (multi)-organ defects, but will improve BMF. Indications as well as transplantation characteristics are most of the time controversial in this setting because of the rarity of reported cases. The present paper proposes a short overview of current practices. PMID:26872907

  9. Osteosynthesis of ununited femoral neck fracture by internal fixation combined with iliac crest bone chips and muscle pedicle bone grafting

    PubMed Central

    Baksi, D D; Pal, A K; Baksi, D P

    2016-01-01

    Background: Ununited femoral neck fracture is seen commonly in developing countries due to delayed presentation or failure of primary internal fixation. Such fractures, commonly present with partial or total absorption of femoral neck, osteonecrosis of femoral head in 8–30% cases with upward migration of trochanter posing problem for osteosynthesis, especially in younger individuals. Several techniques for treatment of such conditions are described like osteotomies or nonvascularied cortical or cancellous bone grafting provided varying degrees of success in terms of fracture union but unsatisfactory long term results occurred due to varying incidence of avascular necrosis (AVN) of femoral head. Moreover, in presence of AVN of femoral head neither free fibular graft nor cancellous bone graft is satisfactory. The vascularied bone grafting by deep circumflex iliac artery based on iliac crest bone grafting, free vascularied fibular grafting and muscle pedicle periosteal grafting showed high incidence of success rate. Osteosynthesis is the preferred treatment of choice in ununited femoral neck fracture in younger individuals. Materials and Methods: Of the 293 patients operated during the period from June 1977 to June 2009, 42 were lost to followup. Seven patients with gluteus medius muscle pedicle bone grafting (MPBG) were excluded. Thus, out of 244 patients, 208 (85.3%) untreated nonunion and 36 (14.7%) following failure of primary internal fixation were available for studies. Time interval between the date of injury and operation in untreated nonunion cases was mean 6.5 months and in failed internal fixation cases was mean 11.2 months. Ages of the patients varied from 16 to 55 years. Seventy patients had partial and 174 had subtotal absorption of the femoral neck. Evidence of avascular necrosis (AVN) femoral head was found histologically in 135 (54.3%) and radiologically in 48 (19.7%) patients. The patients were operated by open reduction of fracture, cannulated hip

  10. Expanding the utility of modified vascularized femoral periosteal bone-flaps: An analysis of its form and a comparison with a conventional-bone-graft

    PubMed Central

    Hamada, Yoshitaka; Hibino, Naohito; Kobayashi, Anna

    2014-01-01

    Background Vascularized medial femoral condyle (MFC) corticoperiosteal bone-flap is a well-accepted technique when dealing with tissue defects or infection. Its role in refractory conditions and in the possible use for options concerning modifications of this bone-flap compared to a conventional iliac bone graft (conventional-graft) are rarely discussed. Methods We reviewed 21 consecutive cases concerning alternatives with some modifications of original MFC bone-flap surgery used to treat refractory conditions with bone defects, necrosis, or infection in the extremities. We present our devised approaches for this boneflap, and especially modifications of the grafted bone (including strut bone, perforator to the vastus medialis muscle, and the use of one vascular pedicle for some bone flaps) as well as the combined use of artificial bone as hybrid bone transplantation. We also compared the clinical results of 21 cases that received a conventional-graft. Results and Conclusions Following flap placement, 100% of the nonunion sites healed in an average of 2 months, which was significantly shorter than 5.5 months for the conventional-graft. The results showed the expanding possibility for options with regard to the form and options of this bone-flap as well as the shortening the duration of treatment, especially at the site of an infected distal tibia, insertion of the Achilles tendon on the posterior aspect of calcaneal osteomyelitis, distal end of the clavicle, clavicle or forearm with a bone defect, small bones with refractory conditions, and a femur without implant failure. However, it was not efficient for treating a forearm without bone defect. PMID:25983463

  11. Influence of the volume of bone defect, bone grafting methods, and hook fixation on stress on the Kerboull-type plate and screw in total hip arthroplasty: three-dimensional finite element analysis.

    PubMed

    Kaku, Nobuhiro; Hara, Katsutoshi; Tabata, Tomonori; Tsumura, Hiroshi

    2015-02-01

    For total hip arthroplasty or revision surgery using acetabular reinforcement cross-plates, choosing between bulk and morselized bone grafts for filling acetabular defects is challenging. We used finite element model (FEM) analysis to clarify various stresses on the cross-plate based on bone defect size, bone graft type, and presence or absence of hook fixation to the bone. We constructed 12-pattern FEMs and calculated the maximum stress generated on the Kerboull-type (KT) plate and screw. Bone defects were classified into four patterns according to the volume. Regarding the bone graft type, bulk bone grafts were considered as cortical bone, and morselized bone grafts were considered to consist of cancellous bone. Models were compared based on whether hook fixation was used and whether a gap was present behind the plate. The upper surface of the host bone was fixed, and a 1,000-N load was imposed on the horizontal axis at 71°. Larger bone defects increased the stress on the KT plate and screws. This stress increased when no bone was grafted; it was lower when bulk cortical bone grafts were used for filling than when morselized cancellous bone grafts were used. For cortical bone grafts, the increased stress on the KT plate and screws was lowered with hook removal. Attaching the hook to the bone and filling the gap behind the KT plate with an adequate bone graft reduced the stress on the KT plate and screws, particularly for large bone defects filled by bulk bone grafting. PMID:24964969

  12. Bone marrow (stem cell) donation

    MedlinePlus

    Stem cell transplant; Allogeneic-donation ... There are two types of bone marrow donation: Autologous bone marrow transplant is when people donate their own bone marrow. "Auto" means self. Allogenic bone marrow transplant is when another person ...

  13. Primary Aneurysmal Bone Cyst in the Iliac Bone: A Case Report

    PubMed Central

    Kim, Chae Geun

    2014-01-01

    Symptomatic aneurysmal bone cysts with expansible lesions in the pelvis are rare in children. The management of an aggressive vascular lesion in a female child is challenging. The standard treatment for aneurysmal bone cysts is accompanied by a high risk of local recurrence. A 12-year-old female presented with a history of pelvic pain for 5 months. Plain radiographs and magnetic resonance imaging showed a very large expansile lytic lesion arising from the right iliac bone. Intralesional curettage, electric cauterization, chemical sclerotherapy and allogeneic bone graft were performed through the window of the iliac crest. At a follow-up consultation 3.5 years post-surgery, the child had painless full-range movement in the hip joint with no recurrence. Although many treatment options are described, our patient was treated successfully using curettage and allogeneic bone graft without recurrence.

  14. Calcium phosphate-hybridized tendon graft to enhance tendon-bone healing two years after ACL reconstruction in goats

    PubMed Central

    2011-01-01

    Background We developed a novel technique to improve tendon-bone attachment by hybridizing calcium phosphate (CaP) with a tendon graft using an alternate soaking process. However, the long-term result with regard to the interface between the tendon graft and the bone is unclear. Methods We analyzed bone tunnel enlargement by computed tomography and histological observation of the interface and the tendon graft with and without the CaP hybridization 2 years after anterior cruciate ligament (ACL) reconstruction in goats using EndoButton and the postscrew technique (CaP, n = 4; control, n = 4). Results The tibial bone tunnel enlargement rates in the CaP group were lower than those in the control group (p < 0.05). In the CaP group, in the femoral and tibial bone tunnels at the anterior and posterior of the joint aperture site, direct insertion-like formation that contained a cartilage layer without tidemarks was more observed at the tendon-bone interface than in the control group (p < 0.05). Moreover, the gap area between the tendon graft and the bone was more observed at the femoral bone tunnel of the joint aperture site in the control group than in the CaP group (p < 0.05). The maturation of the tendon grafts determined using the ligament tissue maturation index was similar in both groups. Conclusions The CaP-hybridized tendon graft enhanced the tendon-bone healing 2 years after ACL reconstruction in goats. The use of CaP-hybridized tendon grafts can reduce the bone tunnel enlargement and gap area associated with the direct insertion-like formation in the interface near the joint. PMID:22166674

  15. A comparison study between periosteum and resorbable collagen membrane on iliac block bone graft resorption in the rabbit calvarium

    PubMed Central

    2014-01-01

    Background To compare the different resorption patterns between resorbable membrane barrier and periosteum after iliac block bone grafting radiographically and histologically. Methods Eighteen mature male rabbits weighing from 2.0 to 2.5 kg were used. The recipient site was the rabbit skull, and autogenous iliac bone was used as the grafting material. The harvested iliac block bones were divided in the following groups: autogenous iliac block bone with preservation of the periosteum (the periosteum group), autogenous iliac block bone covered with a resorbable collagen membrane (Biomesh®, Samyang Co, Korea) after removing the periosteum (the collagen membrane group), and autogenous iliac block bones with removal of the periosteum (the control group). In each experimental group, periosteum or resorbable collagen membrane of the donor site was fixed directed to the periosteum of the recipient site. The specimens were examined macroscopically, radiographically, histologically, and histomorphometrically at every 2, 4, and 8 weeks. Results All groups presented excellent bone graft healing state without inflammation, dehiscence, or displacement. The radiolucency increased from mild to moderate in all groups over the experiment. The mean thickness of the upper end of the cortical iliac bone graft was statistically significantly different between the control group and the periosteum group, between the four-week and eight-week control group, and between the four- week and eight-week periosteum group (p & 0.05). Conclusion This study suggests that both the periosteum and the resorbable collagen membrane may help to prevent soft tissue infiltration into the bone graft and to reduce bone graft resorption compared to block graft alone. PMID:24886656

  16. [Reconstruction of defects of the anterior wall of the frontal sinus using autologous bone transplantation obtained by calvarian split graft].

    PubMed

    Fürst, G; Maurer, J; Mann, W

    1992-03-01

    We present the technique to gain free calvarian split bone grafts for reconstruction of the anterior wall of the frontal sinus. The indication for surgery, the surgical technique and the results in 12 patients are discussed. PMID:1596313

  17. Hydroxyapatite grafted carbon nanotubes and graphene nanosheets: Promising bone implant materials

    NASA Astrophysics Data System (ADS)

    Oyefusi, Adebola; Olanipekun, Opeyemi; Neelgund, Gururaj M.; Peterson, Deforest; Stone, Julia M.; Williams, Ebonee; Carson, Laura; Regisford, Gloria; Oki, Aderemi

    2014-11-01

    In the present study, hydroxyapatite (HA) was successfully grafted to carboxylated carbon nanotubes (CNTs) and graphene nanosheets. The HA grafted CNTs and HA-graphene nanosheets were characterized using FT-IR, TGA, SEM and X-ray diffraction. The HA grafted CNTs and graphene nanosheets (CNTs-HA and Gr-HA) were further used to examine the proliferation and differentiation rate of temperature-sensitive human fetal osteoblastic cell line (hFOB 1.19). Total protein assays and western blot analysis of osteocalcin expression were used as indicators of cell proliferation and differentiation. Results indicated that hFOB 1.19 cells proliferate and differentiate well in treatment media containing CNTs-HA and graphene-HA. Both CNTs-HA and graphene-HA could be promising nanomaterials for use as scaffolds in bone tissue engineering.

  18. Factors Predicting Graft-versus-Host Disease-Free, Relapse-Free Survival after Allogeneic Hematopoietic Cell Transplantation: Multivariable Analysis from a Single Center.

    PubMed

    Solh, Melhem; Zhang, Xu; Connor, Katelin; Brown, Stacey; Solomon, Scott R; Morris, Lawrence E; Holland, H Kent; Bashey, Asad

    2016-08-01

    The ideal outcome of allogeneic hematopoietic cell transplantation (allo-HCT) is based on survival that is free of morbidity. The most common causes of treatment failure and morbidity after HCT are relapse, graft-versus-host disease (GVHD), and nonrelapse death. A composite endpoint that measures survival free of clinically significant negative events may be a useful way to determine the success of allo-HCT. We assessed GVHD and relapse-free survival (GRFS) where the events were acute GVHD grades III to IV, chronic GVHD requiring immunosuppression, relapse, or death in 531 consecutive adult patients who received an allo-HCT between 2006 and 2014 at our center. Median follow-up of living patients was 46 months (range, 12 to 123). HLA matched related donor (MRD, n = 198, 37%), matched unrelated donor (MUD, n = 205, 39%), and haploidentical donor with post-transplant cyclophosphamide (HID, n = 128, 24%) were used. Thirty-six percent of patients had a high/very-high Dana Farber disease risk index (DRI). Estimated rates of GRFS at 1 and 2 years after MRD, MUD, and HID transplantations were 34% and 26%, 26% and 17%, and 33% and 31%, respectively, with MRD recipients having a better GRFS than MUD (P < .05). On multivariable analysis, peripheral blood stem cell source (HR, 1.34; P = .04), MUD (HR, 1.41; P = .003), and high/very high DRI (HR, 1.66; P = .001) were all associated with a worse GFRS post-HCT. These data suggest that GRFS can be predicted by patient disease risk, stem cell source, and donor type. Importantly, MUDs produce inferior GRFS to MRDs, whereas HIDs do not. PMID:27095692

  19. μCT-Based Measurement of Cortical Bone Graft-to-Host Union

    PubMed Central

    Reynolds, David G.; Shaikh, Saad; Papuga, Mark Owen; Lerner, Amy L.; O'Keefe, Regis J.; Schwarz, Edward M.; Awad, Hani A.

    2009-01-01

    Evaluation of structural bone grafts risk of failure requires noninvasive quantitative predictors of functional strength. We hypothesized that a quantitative graft-to-host union biometric would correlate significantly with biomechanical properties as a surrogate for the risk of fracture. To test this, we developed a novel algorithm to compute the union between host callus and graft, which was termed the union ratio. We compared the union ratio of live autografts to devitalized allografts implanted into the mid-diaphysis of mouse femurs for 6 and 9 wk. Surprisingly, the autograft union ratio decreased from 0.228 ± 0.029 at 6 wk to 0.15 ± 0.011 at 9 wk (p < 0.05) and did not correlate with the torsional properties of the autografts . The allograft union ratio was 0.105 ± 0.023 at 6 wk but increased to 0.224 ± 0.029 at 9 wk (p < 0.05). As a single variable, the union ratio correlated significantly with ultimate torque (R 2 = 0.58) and torsional rigidity (R 2 = 0.51) of the allografts. Multivariable regression analyses of allografts that included the union ratio, the graft bone volume, the maximum and minimum polar moment of inertia, and their first-order interaction terms with the union ratio as independent variables resulted in significant correlations with the ultimate torque and torsional rigidity (adjusted R 2 = 0.80 and 0.89, respectively). These results suggest that, unlike live autografts, the union between the devitalized allograft and host contributes significantly to the strength of grafted bone. The union ratio has important clinical implications as a novel biometric for noninvasive assessment of functional strength and failure risk. PMID:19063685

  20. Effect of body mass in children with hematologic malignancies undergoing allogeneic bone marrow transplantation

    PubMed Central

    Aplenc, Richard; Zhang, Mei-Jie; Sung, Lillian; Zhu, Xiaochun; Ho, Vincent T.; Cooke, Kenneth; Dvorak, Christopher; Hale, Gregory; Isola, Luis M.; Lazarus, Hillard M.; McCarthy, Philip L.; Olsson, Richard; Pulsipher, Michael; Bunin, Nancy

    2014-01-01

    The rising incidence of pediatric obesity may significantly affect bone marrow transplantation (BMT) outcomes. We analyzed outcomes in 3687 children worldwide who received cyclophosphamide-based BMT regimens for leukemias between 1990 and 2007. Recipients were classified according to age-adjusted body mass index (BMI) percentiles as underweight (UW), at risk of UW (RUW), normal, overweight (OW), or obese (OB). Median age and race were similar in all groups. Sixty-one percent of OB children were from the United States/Canada. Three-year relapse-free and overall survival ranged from 48% to 52% (P = .54) and 55% to 58% (P = .81) across BMI groups. Three-year leukemia relapses were 33%, 33%, 29%, 25%, and 21% in the UW, RUW, normal, OW, and OB groups, respectively (P < .001). Corresponding cumulative incidences for transplant-related mortality (TRM) were 18%, 19%, 21%, 22%, and 28% (P < .01). Multivariate analysis demonstrated a decreased risk of relapse compared with normal BMI (relative risk [RR] = 0.73; P < .01) and a trend toward higher TRM (RR = 1.28; P = .014). BMI in children is not significantly associated with different survival after BMT for hematologic malignancies. Obese children experience less relapse posttransplant compared with children with normal BMI; however, this benefit is offset by excess in TRM. PMID:24711663

  1. 8-10 year follow-up survival of dental implants in maxillae with or without autogenous bone graft reconstruction

    PubMed Central

    de Moraes, Paulo H; Olate, Sergio; Lauria, Andrezza; Asprino, Luciana; de Moraes, Márcio; de Albergaria-Barbosa, José Ricardo

    2015-01-01

    The aim of this research was to ascertain the survival of implants installed in the atrophic maxillae of patients treated with or without autogenous bone graft at 8 to 10 years of follow-up. A retrospective study was conducted using clinical and imaging analysis. 42 adult patients were selected, treated with osseointegrated implants in a fixed maxillary prosthesis model with suprastructure using 6 to 8 implants; of these, 22 underwent reconstruction with a bone graft taken from the anterior iliac crest and 20 were treated without any type of bone graft. The sequence of removal, installation and management of the grafts followed routine patterns, and the implant installation and prosthesis preparation also followed parameters established in previous publications. Variables of implant survival, stage of loss and bone stability of the implants were analyzed with the Wilcoxon signed-rank test, considering a value of P<0.05 to obtain statistical significance. After 8 to 10 years of follow-up the 306 implants installed in the 42 patients were evaluated. 162 implants were in the bone graft group, where 8.0% of implants were lost in the pre-loading stage, 3.7% in the post-loading stage and 88.7% had complete survival. In the group without bone graft, 6.17% were lost in the pre-loading stage, 1.85% in the post-loading stage and 90.97% had complete survival. There was no significant difference in the survival of the implants between the two groups (P=0.082). Cervical bone loss between the groups showed no significant differences either (P=0.241). The implants in grafted maxillae with cases of severe maxillary atrophy are just as efficient as implants installed in maxillae without bone graft. PMID:26770565

  2. Allogeneic cell-mediated immunotherapy for breast cancer after autologous stem cell transplantation: a clinical pilot study.

    PubMed

    Or, R; Ackerstein, A; Nagler, A; Kapelushnik, J; Naparstek, E; Samuel, S; Amar, A; Bruatbar, C; Slavin, S

    1998-03-01

    Allogeneic cell therapy (allo-CT) is emerging as an effective treatment for patients relapsing after allogeneic bone marrow transplantation (BMT), indicating that tumor cells resisting chemoradiotherapy may still respond to immunocompetent allogeneic lymphocytes. We investigated possible graft-versus-tumor (GVT) effects in six patients with metastatic breast cancer that would be comparable to the graft-versus-leukemia (GVL) phenomenon occurring after allogeneic BMT in hematologic malignancies. The patients were cytoreduced with high-dose chemotherapy and autologous stem cell transplantation (ASCT), and were treated ambulatory with allo-CT consisting of adoptive transfer of HLA-matched donor peripheral blood lymphocytes (PBL) activated in vivo with human recombinant interleukin-2 (rIL-2). If no graft-versus-host disease (GVHD) developed, allo-CT was augmented with infusion of donor PBL, preactivated in vitro with rIL-2. Treatment was well tolerated, with low therapy-related toxicity in all patients. Two patients developed signs and symptoms compatible with GVHD grade I-II, one of whom shows no evidence of disease at more than 34 months out. In the remaining patients, progression-free survival following allo-CT ranged between 7 and 13 months. Allogeneic cell-mediated, cytokine-activated immunotherapy might be utilized for induction of GVT in metastatic breast cancer. A search for techniques to boost chimerism without severe GVHD is indicated. PMID:9557210

  3. The crooked nose: the use of medial iliac crest bone graft as a supporting framework.

    PubMed

    Cil, Yakup; Ozturk, Serdar; Kocman, Atacan Emre; Isik, Selcuk; Sengezer, Mustafa

    2008-11-01

    The crooked nose is one that the vertical axis of the nose inclines from the midline. As a rule, a major septal deformity almost always accompanies to impairing breathing and aesthetic appearance. To achieve total straightening of the crooked nose, the septum must become the target of the treatment. To prevent redeviation, we used rigid bone grafts instead of flexible and relatively weak cartilage to maintain the support of the corrected deformity. Between February 2005 and July 2007, 9 patients (all male) with crooked noses underwent corrective surgery. The mean age of the patients was 21 years (range, 19-23 years). The source of the bone graft was medial side of iliac crest in all patients. The mean follow-up was 18 months, ranging from 10 to 26 months. All patients had both functional and cosmetic problems. Mean operation time was 4 hours. Airway patency was improved in all cases. The grafts did not shift in any case and did not develop unsightly irregularities over time. Absorption of the grafts was not seen in the follow-up. There were no cases of extrusion or infection. No donor site complication occurred. None of the patient required secondary surgery. A residual deviation can be obvious despite all attempts, which has no deleterious effect on patient satisfaction. This article introduces a novel technique for the correction of the crooked nose. PMID:19098567

  4. [Renal transplantation without maintenance immunosuppression. Identical twins and kidney transplantation following a successful bone marrow graft].

    PubMed

    Hadi, Riad Abdel; Thomé, Gustavo Gomes; Ribeiro, Adriana Reginato; Manfro, Roberto Ceratti

    2015-01-01

    Renal transplantation without maintenance immunosuppression has been sporadically reported in the literature. The cases include non-adherent patients who discontinued their immunosuppressive medications, transplantation between identical twins, kidney transplantation after a successful bone marrow graft from the same donor and simultaneous bone marrow and kidney transplantation for the treatment of multiple myeloma with associated renal failure. There are also ongoing clinical trials designed to induce donor specific transplant tolerance with infusion of hematopoietic cells from the same kidney donor. Here we describe two cases of renal transplantation without immunosuppression as examples of situations described above. PMID:26154652

  5. Increasing Incidence of Chronic Graft-versus-Host Disease in Allogeneic Transplantation – A Report from CIBMTR

    PubMed Central

    Arai, Sally; Arora, Mukta; Wang, Tao; Spellman, Stephen R.; He, Wensheng; Couriel, Daniel R.; Urbano-Ispizua, Alvaro; Cutler, Corey S.; Bacigalupo, Andrea A.; Battiwalla, Minoo; Flowers, Mary E.; Juckett, Mark B.; Lee, Stephanie J.; Loren, Alison W.; Klumpp, Thomas R.; Prockup, Susan E.; Ringdén, Olle T.H.; Savani, Bipin N.; Socié, Gérard; Schultz, Kirk R.; Spitzer, Thomas; Teshima, Takanori; Bredeson, Christopher N.; Jacobsohn, David A.; Hayashi, Robert J.; Drobyski, William R.; Frangoul, Haydar A.; Akpek, Görgün; Ho, Vincent T.; Lewis, Victor A.; Gale, Robert Peter; DSc(hon); Koreth, John; Chao, Nelson J.; Aljurf, Mahmoud D.; Cooper, Brenda W.; Laughlin, Mary J.; Hsu, Jack W.; Hematti, Peiman; Verdonck, Leo F.; Solh, Melhelm M.; Norkin, Maxim; Reddy, Vijay; Martino, Rodrigo; Gadalla, Shahinaz; Goldberg, Jenna D.; McCarthy, Philip L.; Pérez-Simón, José A.; Khera, Nandita; Lewis, Ian D.; Atsuta, Yoshiko; Olsson, Richard F.; Saber, Wael; Waller, Edmund K.; Blaise, Didier; Pidala, Joseph A.; Martin, Paul J.; Satwani, Prakash; Bornhäuser, Martin; Inamoto, Yoshihiro; Weisdorf, Daniel J.; Horowitz, Mary M.; Pavletic, Steven Z.

    2015-01-01

    Although transplant practices have changed over the last decades there is no information on trends in incidence and outcome of cGVHD over time. This study utilized the central database of the Center for International Blood and Marrow Transplant Research (CIBMTR) to describe the time trends for cGVHD incidence, non-relapse mortality, and the risk factors for cGVHD. The 12-year period was divided into three intervals: 1995-1999, 2000-2003, 2004-2007, and included 26,563 patients with acute leukemia, chronic myeloid leukemia and myelodysplastic syndrome. In the multivariate analysis, the incidence of cGVHD was shown to be increased in more recent years (odds ratio= 1.19, p<0.0001) and this trend was still seen when adjusting for donor type, graft type, or conditioning intensity. In patients with cGVHD, non-relapse mortality has decreased over time, but at 5-years there were no significant differences among different time periods. Risk factors for cGVHD were in line with previous studies. This is the first comprehensive characterization of the trends in cGVHD incidence and underscores the mounting need for addressing this major late complication of transplantation in future research. PMID:25445023

  6. Immunohistochemical characterization of wound healing at two different bone graft substitutes.

    PubMed

    Sager, M; Ferrari, D; Wieland, M; Dard, M; Becker, J; Schwarz, F

    2012-05-01

    The immunohistochemical characteristics of wound healing following application of a biphasic calcium phosphate or a collagen coated natural bone combined with a native collagen membrane in a dog model was assessed. Standardized buccal dehiscence-type defects were surgically created following implant bed preparation in 6 dogs. Following implant placement, defects were randomly filled with a collagen coated natural bone mineral (GBO), or a biphasic hydroxyapatite/beta tricalcium phosphate (SBC), and covered with a native collagen membrane. After 1, 4, and 9 weeks' submerged healing, dissected blocks were processed for immunohistochemical (collagen type I (CI), osteocalcin (OC), angiogenesis (TG)) analysis. At 1 week, GBO and SBC granules were homogeneously surrounded by a well vascularized, non-mineralized tissue (NMT). CI and OC antigen reactivity was commonly observed adjacent to both bone graft substitutes. At 4 and 9 weeks, SBC and GBO granules were completely integrated into a secondly formed network of spongiosa. At 9 weeks, dissolution of some granules was observed in the SBC group. Adjacent to these granules, NMT was significantly increased and revealed a pronounced CI, OC and TG antigen reactivity. The initial pattern of bone regeneration and graft integration was comparable in both groups; bone remodelling was more pronounced with SBC. PMID:22169169

  7. An Injectable Hydrogel as Bone Graft Material with Added Antimicrobial Properties

    PubMed Central

    Tommasi, Giacomo; Perni, Stefano

    2016-01-01

    Currently, the technique which provides the best chances for a successful bone graft, is the use of bone tissue from the same patient receiving it (autograft); the main limitations are the limited availability and the risks involved in removing living bone tissue, for example, explant site pain and morbidity. Allografts and xenografts may overcome these limitations; however, they increase the risk of rejection. For all these reasons the development of an artificial bone graft material is particularly important and hydrogels are a promising alternative for bone regeneration. Gels were prepared using 1,4-butanediol diacrylate as crosslinker and alpha tricalciumphosphate; ZnCl2 and SrCl2 were added to the aqueous phase. MTT results demonstrated that the addition of strontium had a beneficial effect on the osteoblast cells density on hydrogels, and zinc instead did not increase osteoblast proliferation. The amount of calcium produced by the osteoblast cells quantified through the Alizarin Red protocol revealed that both strontium and zinc positively influenced the formation of calcium; furthermore, their effect was synergistic. Rheology properties were used to mechanically characterize the hydrogels and especially the influence of crosslinker's concentration on them, showing the hydrogels presented had extremely good mechanical properties. Furthermore, the antimicrobial activity of strontium and zinc in the hydrogels against methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis was determined. PMID:27174392

  8. An Injectable Hydrogel as Bone Graft Material with Added Antimicrobial Properties.

    PubMed

    Tommasi, Giacomo; Perni, Stefano; Prokopovich, Polina

    2016-06-01

    Currently, the technique which provides the best chances for a successful bone graft, is the use of bone tissue from the same patient receiving it (autograft); the main limitations are the limited availability and the risks involved in removing living bone tissue, for example, explant site pain and morbidity. Allografts and xenografts may overcome these limitations; however, they increase the risk of rejection. For all these reasons the development of an artificial bone graft material is particularly important and hydrogels are a promising alternative for bone regeneration. Gels were prepared using 1,4-butanediol diacrylate as crosslinker and alpha tricalciumphosphate; ZnCl2 and SrCl2 were added to the aqueous phase. MTT results demonstrated that the addition of strontium had a beneficial effect on the osteoblast cells density on hydrogels, and zinc instead did not increase osteoblast proliferation. The amount of calcium produced by the osteoblast cells quantified through the Alizarin Red protocol revealed that both strontium and zinc positively influenced the formation of calcium; furthermore, their effect was synergistic. Rheology properties were used to mechanically characterize the hydrogels and especially the influence of crosslinker's concentration on them, showing the hydrogels presented had extremely good mechanical properties. Furthermore, the antimicrobial activity of strontium and zinc in the hydrogels against methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis was determined. PMID:27174392

  9. Hybrid Matrix Grafts to Favor Tissue Regeneration in Rabbit Femur Bone Lesions

    PubMed Central

    Goy, Dante Pascual; Gorosito, Emmanuel; Costa, Hermes S; Mortarino, Pablo; Pedemonte, Noelia Acosta; Toledo, Javier; Mansur, Herman S; Pereira, Marivalda M; Battaglino, Ricardo; Feldman, Sara

    2012-01-01

    At present, typical approaches employed to repair fractures and other bone lesions tend to use matrix grafts to promote tissue regeneration. These grafts act as templates, which promote cellular adhesion, growth and proliferation, osteoconduction, and even osteoinduction, which commonly results in de novo osteogenesis. The present work aimed to study the bone-repairing ability of hybrid matrixes (HM) prepared with polyvinyl alcohol (PVA) and bioactive glass in an experimental rabbit model. The HM were prepared by combining 30% bioactive glass (nominal composition of 58% SiO2 -33 % CaO - 9% P2O5) and 70% PVA. New Zealand rabbits were randomly divided into the control group (C group) and two groups with bone lesions, in which one received a matrix implant HM (Implant group), while the other did not (no Implant group). Clinical monitoring showed no altered parameters from either the Implant or the no Implant groups as compared to the control group, for the variables of diet grades, day and night temperatures and hemograms. In the Implant group, radiologic and tomographic studies showed implanted areas with clean edges in femoral non-articular direction, and radio-dense images that suggest incipient integration. Minimum signs of phlogosis could be observed, whereas no signs of rejection at this imaging level could be identified. Histological analysis showed evidence of osteo-integration, with the formation of a trabecular bone within the implant. Together, these results show that implants of hybrid matrixes of bioactive glass are capable of promoting bone regeneration. PMID:22848334

  10. Hyperfractionated total body irradiation for bone marrow transplantation. Results in seventy leukemia patients with allogeneic transplants

    SciTech Connect

    Shank, B.; Chu, F.C.H.; Dinsmore, R.; Kapoor, N.; Kirkpatrick, D.; Teitelbaum, H.; Reid, A.; Bonfiglio, P.; Simpson, L.; O'Reilly, R.J.

    1983-11-01

    From May, 1979 to March, 1981, 76 leukemia patients were prepared for bone marrow transplantation (BMT) with a new hyperfractionated total body irradiation (TBI) regimen (1320 cGy in 11 fractions, 3x/day), followed by cyclophosphamide, 60 mg/kg, for two days. Partial lung shielding was done on each treatment, with supplemental electron beam treatments of the chest wall to compensate, and of the testes, a sanctuary site. This regimen was initiated to potentially reduce fatal interstitial pneumonitis as well as decrease leukemic relapse. Overall actuarial survival at 1 year for acute non-lymphocytic leukemia (ANLL) patients is 63%, while relapse-free survival at 1 year is 53%. On the other hand, for acute lymphocytic leukemia (ALL) patients, there is no significant difference between relapse or remission patients with regard to overall survival or relapse-free survival, when relapse is defined as > 5% blasts in the marrow at the time of cytoreduction. Overall actuarial survival at 1 year for ALL is 61% and relapse-free survival is 45% at 1 year. Fatal interstitial pneumonitis has dropped to 18% compared with 50% in our previous single-dose TBI regimen (1000 cGy), in which the same doses of cyclophosphamide were given prior to TBI. In conclusion, not only has fatal interstitial pneumonitis been reduced by hyperfractionation and partial lung blocking, but there may be a survival advantage in ALL patients in relapse, who have a survival equal to that of remission patients. This may indicate a greater cell kill with the higher dose (1320 cGy) attained with this regimen, in these patients with a higher leukemic cell burden.

  11. Identification of a novel HLA-G+ regulatory population in blood: expansion after allogeneic transplantation and de novo HLA-G expression at graft-versus-host disease sites

    PubMed Central

    Lazana, Ioanna; Zoudiari, Anastasia; Kokkinou, Dimitra; Themeli, Maria; Liga, Maria; Papadaki, Helen; Papachristou, Dionysios; Spyridonidis, Alexandros

    2012-01-01

    Background The human leukocyte antigen-G (HLA-G) has been considered to be an important tolerogeneic molecule playing an essential role in maternal-fetal tolerance, which constitutes the perfect example of successful physiological immunotolerance of semi-allografts. In this context, we investigated the putative role of this molecule in the allogeneic hematopoietic cell transplantation setting. Design and Methods The percentage of HLA-G+ cells in peripheral blood of healthy donors and allo-transplanted patients was evaluated by flow cytometry. Their immunoregulatory and tolerogeneic properties were investigated in in vitro immunostimulatory and immunosuppression assays. Immunohistochemical analysis for HLA-G expression was performed in skin biopsies from allo-transplanted patients and correlated with the occurrence of graft-versus-host disease. Results We identified a CD14+HLA-Gpos population with an HLA-DRlow phenotype and decreased in vitro immunostimulatory capacity circulating in peripheral blood of healthy individuals. Naturally occurring CD14+HLA-Gpos cells suppressed T-cell responses and exerted an immunotolerogenic action on T cells by rendering them hyporesponsive and immunosuppressive in vitro. After allogeneic hematopoietic cell transplantation, HLA-Gpos cells increase in blood. Interestingly, besides an increase in CD14+HLA-Gpos cells, there was also a pronounced expansion of CD3+HLA-Gpos cells. Of note, CD3+HLA-Gpos and CD14+HLA-Gpos cells from transplanted patients were suppressive in in vitro lymphoproliferation assays. Furthermore, we found an upregulation of HLA-G expression in skin specimens from transplanted patients that correlated with graft-versus-host disease. Inflammatory cells infiltrating the dermis of transplanted patients were also HLA-Gpos. Conclusions We report the presence of naturally occurring HLA-Gpos monocytic cells with in vitro suppressive properties. HLA-G expressing regulatory blood cells were found in increased numbers after

  12. Effects of low-level laser therapy on autogenous bone graft stabilized with a new heterologous fibrin sealant.

    PubMed

    de Oliveira Gonçalves, Jéssica Barbosa; Buchaim, Daniela Vieira; de Souza Bueno, Cleuber Rodrigo; Pomini, Karina Torres; Barraviera, Benedito; Júnior, Rui Seabra Ferreira; Andreo, Jesus Carlos; de Castro Rodrigues, Antonio; Cestari, Tania Mary; Buchaim, Rogério Leone

    2016-09-01

    Autogenous bone grafts are used to repair bone defects, and the stabilization is needed for bone regeneration. Laser photobiomodulation is a modality of treatment in clinical practice for tissue regeneration, and it has therapeutic effects as an anti-inflammatory, analgesic and modulating cellular activity. The aim of the present study was to evaluate the effects of low-level laser therapy (LLLT) on an autogenous bone graft integration process stabilized with a new heterologous fibrin sealant. Forty rats were divided into two groups: Autogenous Fibrin Graft (AFG, n=20), in which a 5mm dome osteotomy was conducted in the right parietal bone and the graft was adhered to the left side using fibrin sealant; and Autogenous Fibrin Graft Laser (AFGL, n=20), which was subjected to the same procedures as AFG with the addition of LLLT. The treatment was performed immediately following surgery and then three times a week until euthanasia, using an 830nm laser (30mW, 6J/cm(2), 0.116cm(2), 258.6mW/cm(2), 2.9J). Five animals from each group were euthanized at 10, 20, 30 and 40days postoperative, and the samples were submitted to histomorphological and histomorphometric analysis. Partial bone regeneration occurred, with new bone tissue integrating the graft to the recipient bed and small areas of connective tissue. Comparative analysis of the groups at the same intervals revealed minor interfaces in group AFGL, with statistically significant differences (p<0.05) at all of the analyzed intervals (10days p=0.0087, 20days p=0.0012, 30days p<0.0001, 40days p=0.0142). In conclusion, low-level laser therapy stimulated bone regeneration and accelerated the process of integration of autogenous bone grafts. PMID:27497370

  13. Clinical Outcomes of Radial Shortening Osteotomy and Vascularized Bone Graft in Kienböck's Disease

    PubMed Central

    Dehghani, Mohammad; Nouraei, Mohammad Hadi; Dehghani, Shaghayegh; Gholshahi, Maryam

    2014-01-01

    The aim of this study was to compare two surgery methods including radial shortening and radial shortening combined with vascularized bone graft for treatment of stage II or IIIa of Kienböck's disease. It is a randomized, controlled clinical trial, which was carried out in 2011–2013. Twenty-four patients were assigned equally to radial shortening group (A) or radial shortening combined with vascularized bone graft group (B). The outcome was assessed by Mayo Wrist score before and 9 months after surgery. The mean Mayo Wrist score (SD) was 27.1 (15.4) and 32.5 (18.3) before surgery and 74.6 (5.4) and 85.8 (5.1) after surgery for groups A and B, respectively. The mean score increased in both groups, and it was higher in group B significantly. Radial shortening combined with vascularized bone graft is a valuable method which can be more effective than radial shortening alone, in early stages of Kienböck's disease. This trial is registered with IRCT201404127841N5.

  14. Operative treatment of isthmic spondylolisthesis with posterior stabilization and ALIF. Cages versus autogenous bone grafts.

    PubMed

    Pankowski, Rafal; Smoczynski, Andrzej; Roclawski, Marek; Ceynowa, Marcin; Kloc, Wojciech; Wasilewski, Wojciech; Jende, Piotr; Liczbik, Wieslaw; Beldzinski, Piotr; Libionka, Witold; Pierzak, Olaf; Adamski, Stanislaw; Niedbala, Miroslaw

    2012-01-01

    In the following study the use of cages and autogenous bone grafts were compared in the operative treatment of isthmic spondylolisthesis with the posterior stabilization and Anterior Lumbosacral Interbody Fusion (ALIF). 55 patients were divided into two groups. Autogenous bone grafts were used in the first group (34 patients) and titanium interbody implants (cages) in the second group (21 patients). The mean follow up period in the first group was 8.6 years and 3.4 years in the second group. The radiological outcome was based upon the evaluation of the degree of spondylolisthesis, the angle of the lumbar lordosis, the height of the interbody space and intervertebral foramen and the evaluation of the spinal fusion. The objective clinical outcome assessment was based on Oswestry Disability Index. Subjective clinical evaluation was performed with the use of Visual Analog Pain Score (VAS) and the two questions concerning the evaluation of success of the operative treatment and a possible agreement to the following operation if necessary. The use of autogenous bone grafts alone in ALIF was related to the significant loss of achieved segmental spine anatomy restoration. The implantation of the cages prevented the loss of slippage correction, permanently reconstructed the anatomical conditions in the area of the operated spinal segment. PMID:22744517

  15. Anterior debridement and bone grafting of spinal tuberculosis with one-stage instrumentation anteriorly or posteriorly

    PubMed Central

    Lian, Xiao Feng; Hou, Tie Sheng; Ma, Hui; Chen, Zhi Ming

    2006-01-01

    Between 2000 and 2004, 40 cases (average age 38, range 16–65 years) of spinal tuberculosis were treated with anterior debridement and iliac bone graft with one-stage anterior or posterior instrumentation in our unit. All patients received at least 2 weeks of regular antituberculous chemotherapy before surgery. We followed up all patients for 12–48 months (mean 22 months). Local symptoms of all patients were relieved significantly 1–3 weeks postoperatively; 23 of 25 cases (92%) with neurogical deficit had excellent or good clinical results. Erythrocyte sedimentation rates (ESR) returned from 51 mm/h to 32 mm/h (average) two weeks postoperatively. Kyphosis degrees were corrected by a mean of 16°. Fusion rate of the grafting bone was 72.5% one year postoperatively and 90% two years postoperatively. Severe complications did not occur. We therefore believe that patients undergoing anterior debridement and iliac bone grafting with one-stage anterior or posterior instrumentation achieve satisfactory clinical and radiographic outcomes. PMID:17061127

  16. The use of platelet-rich fibrin (PRF) and PRF-mixed particulated autogenous bone graft in the treatment of bone defects: An experimental and histomorphometrical study

    PubMed Central

    Kökdere, Nesligül Niyaz; Baykul, Timuçin; Findik, Yavuz

    2015-01-01

    Background: Various materials and techniques have been developed to facilitate bone healing process and reduce its healing period. In recent studies, it is pointed out that, platelet-rich fibrin (PRF) which is derived autogenously from the own blood of the individuals, increase regeneration and accelerate the healing of the wound, due to the consisting various growing factors. The aim of the experimental study is to evaluate the efficiency of PRF and PRF/autogenous graft combination on bone healing in different time intervals. Materials and Methods: A total of 24 skeletally mature New Zealand rabbits were used. Animals were divided randomly into two groups. Two bone defects with a diameter 3, 3 mm were created on the right and left tibia in all group animals. Only particulate autogeneous bone graft, only PRF, combination of PRF and autogeneous bone graft and empty bone cavity, were performed to all animals. The animals in the first experimental group were sacrificed after 30 days. The animals in the second experimental group were sacrificed after 60 days from the operation. Histomorphometrical and statistical analysis was performed. The data were analyzed using Tukey test (P < 0.05 for osteoblast number, P < 0.01 for osteoclast and new bone area values). Results: Histomorphometrical analyzes showed that either PRF used alone or used in conjuction with autogenous bone graft, PRF accelerated the healing of the bone defects. There were statistically significant differences in osteoblast, osteoblast and new bone area values in PRF alone and autogenous graft with PRF than the other groups. Conclusion: Our preliminary result demonstrated that PRF increase new bone formation and has a positive effect on early bone healing. PMID:26604954

  17. A randomized study of the prevention of acute graft-versus-host disease

    SciTech Connect

    Ramsay, N.K.C.; Kersey, J.H.; Robison, L.L.; McGlave, P.B.; Woods, W.G.; Krivit, W.; Kim, T.H.; Goldman, A.I.; Nesbit, M.E., Jr.

    1982-02-01

    Acute graft-versus-host disease is a major problem in allogeneic bone-marrow transplantation. We performed a randomized study to compare the effectiveness of two regimens in the prevention of acute graft-versus-host disease. Thirty-five patients received methotrexate alone, and 32 received methotrexate, antithymocyte globulin, and prednisone. Of the patients who received methotrexate alone, 48 percent had acute graft-versus-host disease, as compared with 21 per cent of those who received methotrexate, antithymocyte globulin, and prednisone (P = 0.01). The age of the recipient was a significant factor in the development of acute graft-versus-host disease: Older patients had a higher incidence of the disease (P = 0.001). We conclude that the combination of methotrexate, antithymocyte globulin, and prednisone significantly decreased the incidence of acute graft-versus-host disease and should be used to prevent this disorder in patients receiving allogeneic marrow transplants.

  18. Nanocomposites and bone regeneration

    NASA Astrophysics Data System (ADS)

    James, Roshan; Deng, Meng; Laurencin, Cato T.; Kumbar, Sangamesh G.

    2011-12-01

    This manuscript focuses on bone repair/regeneration using tissue engineering strategies, and highlights nanobiotechnology developments leading to novel nanocomposite systems. About 6.5 million fractures occur annually in USA, and about 550,000 of these individual cases required the application of a bone graft. Autogenous and allogenous bone have been most widely used for bone graft based therapies; however, there are significant problems such as donor shortage and risk of infection. Alternatives using synthetic and natural biomaterials have been developed, and some are commercially available for clinical applications requiring bone grafts. However, it remains a great challenge to design an ideal synthetic graft that very closely mimics the bone tissue structurally, and can modulate the desired function in osteoblast and progenitor cell populations. Nanobiomaterials, specifically nanocomposites composed of hydroxyapatite (HA) and/or collagen are extremely promising graft substitutes. The biocomposites can be fabricated to mimic the material composition of native bone tissue, and additionally, when using nano-HA (reduced grain size), one mimics the structural arrangement of native bone. A good understanding of bone biology and structure is critical to development of bone mimicking graft substitutes. HA and collagen exhibit excellent osteoconductive properties which can further modulate the regenerative/healing process following fracture injury. Combining with other polymeric biomaterials will reinforce the mechanical properties thus making the novel nano-HA based composites comparable to human bone. We report on recent studies using nanocomposites that have been fabricated as particles and nanofibers for regeneration of segmental bone defects. The research in nanocomposites, highlight a pivotal role in the future development of an ideal orthopaedic implant device, however further significant advancements are necessary to achieve clinical use.

  19. Increased serum IgE concentrations during infection and graft versus host disease after bone marrow transplantation.

    PubMed Central

    Walker, S A; Rogers, T R; Perry, D; Hobbs, J R; Riches, P G

    1984-01-01

    Serum IgE concentrations estimated in 25 bone marrow transplant recipients during episodes of infection or graft versus host disease, or both, were raised not only in some patients with acute graft versus host disease but also in many patients with infection. Raised values were not seen in chronic graft versus host disease. The routine estimation of serum IgE in bone marrow transplant recipients had minimal value because of the lack of specificity of the IgE response. PMID:6368605

  20. Treatment of the benign bone tumors including femoral neck lesion using compression hip screw and synthetic bone graft

    PubMed Central

    Nakamura, Tomoki; Matsumine, Akihiko; Asanuma, Kunihiro; Matsubara, Takao; Sudo, Akihiro

    2015-01-01

    Purpose: The proximal femur is one of the most common locations for benign bone tumors and tumor like conditions. We describe the clinical outcomes of the surgical treatment of benign lesions of the proximal femur including femoral neck using compression hip screw and synthetic bone graft. Methods: Thirteen patients with benign bone tumors or tumor like conditions of the proximal femur including femoral neck were surgically treated. Their average age at the time of presentation was 35 years and the average follow-up time was 76 months. Results: The average intraoperative blood loss was 1088 mL and intraoperative blood transfusion was required in eight patients. The average operative time was 167 minutes. All patients required one week and 12 weeks after surgery before full weight-bearing was allowed. All patients had regained full physical function without pain by the final follow-up. No patient sustained a pathological fracture of the femur following the procedure. All patients achieved partial or complete radiographic consolidation of the lesion within one year except one patient who developed a local tumor recurrence in 11 months. Post-operative superficial wound infection was observed in one patient, which resolved with intravenous antibiotics. Chronic hip pain was observed in one patient due to the irritation of tensor fascia lata muscle by the tube plate. Conclusion: We suggest that the treatment of benign bone lesion of the proximal femur using compression hip screw and synthetic bone graft is a safe and effective method. PMID:27163071

  1. Design, synthesis, and initial evaluation of D-glyceraldehyde crosslinked gelatin-hydroxyapatite as a potential bone graft substitute material

    NASA Astrophysics Data System (ADS)

    Florschutz, Anthony Vatroslav

    Utilization of bone grafts for the treatment of skeletal pathology is a common practice in orthopaedic, craniomaxillofacial, dental, and plastic surgery. Autogenous bone graft is the established archetype but has disadvantages including donor site morbidity, limited supply, and prolonging operative time. In order to avoid these and other issues, bone graft substitute materials are becoming increasingly prevalent among surgeons for reconstructing skeletal defects and arthrodesis applications. Bone graft substitutes are biomaterials, biologics, and guided tissue/bone regenerative devices that can be used alone or in combinations as supplements or alternatives to autogenous bone graft. There is a growing interest and trend to specialize graft substitutes for specific indications and although there is good rationale for this indication-specific approach, the development and utility of a more universal bone graft substitute may provide a better answer for patients and surgeons. The aim of the present research focuses on the design, synthesis, and initial evaluation of D-glyceraldehyde crosslinked gelatin-hydroxyapatite composites for potential use as a bone graft substitutes. After initial establishment of rational material design, gelatinhydroxyapatite scaffolds were fabricated with different gelatin:hydroxyapatite ratios and crosslinking concentrations. The synthesized scaffolds were subsequently evaluated on the basis of their swelling behavior, porosity, density, percent composition, mechanical properties, and morphology and further assessed with respect to cell-biomaterial interaction and biomineralization in vitro. Although none of the materials achieved mechanical properties suitable for structural graft applications, a reproducible material design and synthesis was achieved with properties recognized to facilitate bone formation. Select scaffold formulations as well as a subset of scaffolds loaded with recombinant human bone morphogenetic protein-2 were

  2. Tooth movement out of the bony wall using augmented corticotomy with nonautogenous graft materials for bone regeneration.

    PubMed

    Lee, Kye-Bok; Lee, Dong-Yeol; Ahn, Hyo-Won; Kim, Seong-Hun; Kim, Eun-Cheol; Roitman, Igor

    2014-01-01

    This prospective randomized split-mouth study was performed to compare the effects of augmented corticotomy with those of different nonautogenous bone graft materials combined with orthodontic tooth movement in dogs. Decortication was performed on the buccal bone surface of 6 male beagle dogs that were randomly assigned to receive grafts of deproteinized bovine bone mineral, irradiated cortical bone, or synthetic bone. Immediate orthodontic force was applied to the second and third premolars for buccal tipping for 6 weeks. The pocket depth and width of keratinized tissue (WKT) were measured. Histologic and histomorphometric analyses were performed. The probing depth, WKT, and ratio of the area of new bone to that of total bone on the buccal side were not significantly different between groups. All groups had considerable new bone formation on the pressure side. New bone formation on the buccal side and buccal plate formation in the coronal direction along the root surfaces were induced by the bone-derived and PDL-derived mesenchymal matrix, respectively. The angular change between groups was significantly different (P < 0.001). Augmented corticotomy using nonautogenous graft materials facilitated tooth movement without fenestrations and accelerated new bone formation on the pressure side. PMID:25247172

  3. Tooth Movement out of the Bony Wall Using Augmented Corticotomy with Nonautogenous Graft Materials for Bone Regeneration

    PubMed Central

    Kim, Seong-Hun; Kim, Eun-Cheol

    2014-01-01

    This prospective randomized split-mouth study was performed to compare the effects of augmented corticotomy with those of different nonautogenous bone graft materials combined with orthodontic tooth movement in dogs. Decortication was performed on the buccal bone surface of 6 male beagle dogs that were randomly assigned to receive grafts of deproteinized bovine bone mineral, irradiated cortical bone, or synthetic bone. Immediate orthodontic force was applied to the second and third premolars for buccal tipping for 6 weeks. The pocket depth and width of keratinized tissue (WKT) were measured. Histologic and histomorphometric analyses were performed. The probing depth, WKT, and ratio of the area of new bone to that of total bone on the buccal side were not significantly different between groups. All groups had considerable new bone formation on the pressure side. New bone formation on the buccal side and buccal plate formation in the coronal direction along the root surfaces were induced by the bone-derived and PDL-derived mesenchymal matrix, respectively. The angular change between groups was significantly different (P < 0.001). Augmented corticotomy using nonautogenous graft materials facilitated tooth movement without fenestrations and accelerated new bone formation on the pressure side. PMID:25247172

  4. Bone marrow transplant

    MedlinePlus

    Transplant - bone marrow; Stem cell transplant; Hematopoietic stem cell transplant; Reduced intensity nonmyeloablative transplant; Mini transplant; Allogenic bone marrow transplant; Autologous bone marrow transplant; ...

  5. Bone marrow transplant

    MedlinePlus

    Transplant - bone marrow; Stem cell transplant; Hematopoietic stem cell transplant; Reduced intensity, nonmyeloablative transplant; Mini transplant; Allogenic bone marrow transplant; Autologous bone marrow transplant; Umbilical ...

  6. Allogeneic human mesenchymal stem cell therapy (remestemcel-L, Prochymal) as a rescue agent for severe refractory acute graft-versus-host disease in pediatric patients.

    PubMed

    Kurtzberg, Joanne; Prockop, Susan; Teira, Pierre; Bittencourt, Henrique; Lewis, Victor; Chan, Ka Wah; Horn, Biljana; Yu, Lolie; Talano, Julie-An; Nemecek, Eneida; Mills, Charles R; Chaudhury, Sonali

    2014-02-01

    Severe steroid-refractory acute graft-versus-host disease (aGVHD) is related to significant mortality and morbidity after allogeneic stem cell transplantation. Early clinical trials of therapy with human mesenchymal stem cells (hMSCs) in pediatric patients with severe aGVHD resistant to multiple immunosuppressive agents showed promising results. In this study, we evaluated the risk/benefit profile of remestemcel-L (Prochymal), a third-party, off-the-shelf source of hMSCs, as a rescue agent for treatment-resistant aGVHD in pediatric patients. Children with grade B-D aGVHD failing steroids and, in most cases, other immunosuppressive agents were eligible for enrollment. Patients received 8 biweekly i.v. infusions of 2 × 10(6) hMSCs/kg for 4 weeks, with an additional 4 weekly infusions after day +28 for patients who achieved either a partial or mixed response. The enrolled patients compose a very challenging population with severe disease that was nonresponsive to the standard of care, with 88% of the patients experiencing severe aGVHD (grade C or D). Seventy-five patients (median age, 8 yr; 58.7% male; and 61.3% Caucasian) were treated in this study. Sixty-four patients (85.3%) had received an unrelated hematopoietic stem cell graft, and 28 patients (37.3%) had received a cord blood graft. At baseline, the distribution of aGVHD grades B, C, and D was 12.0%, 28.0%, and 60.0%, respectively. The median duration of aGVHD before enrollment was 30 d (range, 2 to 1639 d), and patients failed a median of 3 immunosuppressive agents. Organ involvement at baseline was 86.7% gastrointestinal, 54.7% skin, and 36.0% liver. Thirty-six patients (48.0%) had 2 organs involved, and 11 patients (14.7%) had all 3 organs involved. When stratified by aGVHD grade at baseline, the rate of overall response (complete and partial response) at day +28 was 66.7% for aGVHD grade B, 76.2% for grade C, and 53.3% for grade D. Overall response for individual organs at day +28 was 58.5% for

  7. ACL reconstruction using bone-tendon-bone graft engineered from the semitendinosus tendon by injection of recombinant BMP-2 in a rabbit model.

    PubMed

    Hashimoto, Yusuke; Naka, Yoshifumi; Fukunaga, Kenji; Nakamura, Hiroaki; Takaoka, Kunio

    2011-12-01

    We attempted to generate a bone-tendon-bone structure by injecting human-type recombinant human bone morphogenetic protein-2 (rhBMP-2) into the semitendinosus tendon, and an anterior cruciate ligament (ACL) defect was reconstructed by grafting the engineered bone-tendon-bone graft. Two ossicles with a separation distance of 1 cm were generated within the left semitendinosus tendon of a rabbit 6 weeks after the injection of rhBMP-2 (15 µg at each site). The engineered bone-tendon-bone graft was transplanted in order to reconstruct the ACL by passing the graft through the bone tunnels. In the control group, the ACL was reconstructed with the semitendinosus tendon without BMP-2 using the same methods as those used in the experimental group. The animals were harvested at 4 or 8 weeks after surgery and examined by radiographic, histological, and biomechanical methods. In the experimental group, ossicles in the bone-tendon-bone graft were successfully integrated into the host bone of the femur and tibia. Histological analysis revealed that characteristic features identical to the normal direct insertion morphology had been restored. Biomechanical pull-out testing showed that the ultimate failure load and stiffness of the reconstructed ACL in the experimental group were significantly higher than those in the control group at both 4 and 8 weeks (p < 0.05). These results indicate the potential of regenerative reconstruction of the ACL, and the reconstruction resulted in the restoration of morphology and function equivalent to those of the normal ACL. PMID:21557301

  8. Maxillary sinus grafting with fresh frozen allograft versus bovine bone mineral: A tomographic and histological study.

    PubMed

    Xavier, Samuel Porfirio; Santos, Thiago de Santana; Sehn, Felipe Perraro; Silva, Erick Ricardo; Garcez-Filho, João de Andrade; Martins-Filho, Paulo Ricardo Saquete

    2016-06-01

    We evaluated histologically and tomographically the effects of fresh frozen bone allograft (FFB) or bovine bone mineral (BBM) in maxillary sinus floor augmentations. In total, 30 maxillary sinuses from 30 patients (mean age = 51.17 ± 10.86 years) underwent sinus augmentation. Patients were divided in two test groups (15 sinuses each). The first group was grafted with allograft bone, and the second group received bovine bone mineral. After 6 months, bone samples from each group were collected for histological examination. Implant survival rates were 97.78% (FFB group) and 100% (BBM group) 6 months after functional loading. Median volumetric reductions of 31.2% (11.33-40.56) and 12.22% (9.91-20.59) were observed in the FFB and BBM groups, respectively. Comparisons between the groups for differences in initial and final volumes of bone (p = 0.015) and the rate of resorption (p = 0.009) showed statistically significant differences. The FFB group showed osteoblastic cells in close contact with osteoid matrix, connected through bridges between allograft bone particles and new bone formation. The BBM group showed BBM particles in close contact with new bone, with visible osteoid matrix bridges and osteoblastic cells surrounding it. None showed signs of acute or chronic inflammatory infiltrate. Despite better results with BBM, both FFB and BBM in maxillary sinus augmentation resulted in high percentages of new bone formation, and allowed implant placement with a low rate of failure of osseointegration at a 6-month follow-up. PMID:27107475

  9. Secure fixation of femoral bone plug with a suspensory button in anatomical anterior cruciate ligament reconstruction with bone-patellar tendon-bone graft

    PubMed Central

    TAKETOMI, SHUJI; INUI, HIROSHI; NAKAMURA, KENSUKE; YAMAGAMI, RYOTA; TAHARA, KEITARO; SANADA, TAKAKI; MASUDA, HIRONARI; TANAKA, SAKAE; NAKAGAWA, TAKUMI

    2015-01-01

    Purpose the efficacy and safety of using a suspensory button for femoral fixation in anatomical anterior cruciate ligament (ACL) reconstruction with bone-patellar tendon-bone (BPTB) graft have not been established. The purpose of the current study was to evaluate bone plug integration onto the femoral socket and migration of the bone plug and the EndoButton (EB) (Smith & Nephew, Andover, MA, USA) after rectangular tunnel ACL reconstruction with BPTB autograft. Methods thirty-four patients who underwent anatomical rectangular ACL reconstruction with BPTB graft using EB for femoral fixation and in whom three-dimensional (3D) computed tomography (CT) was performed one week and one year after surgery were included in this study. Bone plug integration onto the femoral socket, bone plug migration, soft tissue interposition, EB migration and EB rotation were evaluated on 3D CT. The clinical outcome was also assessed and correlated with the imaging outcomes. Results the bone plug was integrated onto the femoral socket in all cases. The incidence of bone plug migration, soft tissue interposition, EB migration and EB rotation was 15, 15, 9 and 56%, respectively. No significant association was observed between the imaging outcomes. The postoperative mean Lysholm score was 97.1 ± 5.0 points. The postoperative side-to-side difference, evaluated using a KT-2000 arthrometer, averaged 0.5 ± 1.3 mm. There were no complications associated with EB use. Imaging outcomes did not affect the postoperative KT side-to-side difference. Conclusions the EB is considered a reliable device for femoral fixation in anatomical rectangular tunnel ACL reconstruction with BPTB autograft. Level of evidence Level IV, therapeutic case series. PMID:26889465

  10. Sinus lift tissue engineering using autologous pulp micro-grafts: A case report of bone density evaluation

    PubMed Central

    Brunelli, Giorgio; Motroni, Alessandro; Graziano, Antonio; D’Aquino, Riccardo; Zollino, Ilaria; Carinci, Francesco

    2013-01-01

    Background: Although autografts are the standard procedure for bone grafting, the use of bone regeneration by means of dental pulp stem cell is an alternative that opens a new era in this field. Rigenera Protocol is a new technique able to provide the surgeon autologous pulp micro-grafts. Materials and Methods: At the Department of Oral Surgery, Don Orione Hospital, Bergamo, Italy, one patient underwent sinus lift elevation with pulp stem micro-grafts gentle poured onto collagen sponge. A CT scan control was performed after 4 months and DICOM data were processed with medical imaging software which gives the possibility to use a virtual probe to extract the bone density. Pearson's Chi-square test was used to investigate difference in bone density (BD) between native and newly formed bone. Results: BD in newly formed bone is about the double of native bone. Conclusion: This report demonstrated that micro-grafts derived from dental pulp poured onto collagen sponge are a useful method for bone regeneration in atrophic maxilla. PMID:24174760

  11. Development and validation of technique for in-vivo 3D analysis of cranial bone graft survival

    NASA Astrophysics Data System (ADS)

    Bernstein, Mark P.; Caldwell, Curtis B.; Antonyshyn, Oleh M.; Ma, Karen; Cooper, Perry W.; Ehrlich, Lisa E.

    1997-05-01

    Bone autografts are routinely employed in the reconstruction of facial deformities resulting from trauma, tumor ablation or congenital malformations. The combined use of post- operative 3D CT and SPECT imaging provides a means for quantitative in vivo evaluation of bone graft volume and osteoblastic activity. The specific objectives of this study were: (1) Determine the reliability and accuracy of interactive computer-assisted analysis of bone graft volumes based on 3D CT scans; (2) Determine the error in CT/SPECT multimodality image registration; (3) Determine the error in SPECT/SPECT image registration; and (4) Determine the reliability and accuracy of CT-guided SPECT uptake measurements in cranial bone grafts. Five human cadaver heads served as anthropomorphic models for all experiments. Four cranial defects were created in each specimen with inlay and onlay split skull bone grafts and reconstructed to skull and malar recipient sites. To acquire all images, each specimen was CT scanned and coated with Technetium doped paint. For purposes of validation, skulls were landmarked with 1/16-inch ball-bearings and Indium. This study provides a new technique relating anatomy and physiology for the analysis of cranial bone graft survival.

  12. Guided tissue regeneration and bone grafts in the treatment of furcation defects.

    PubMed

    Caffesse, R G; Nasjleti, C E; Plotzke, A E; Anderson, G B; Morrison, E C

    1993-11-01

    The present study evaluated the effects of guided tissue regeneration (GTR), with and without demineralized freeze-dried cortical bone grafts, in the treatment of furcation defects in 4 female beagle dogs with naturally occurring periodontal disease. The root surfaces were thoroughly debrided. Four weeks later, full thickness facial and lingual mucoperiosteal flaps were reflected using inverse bevel incisions on both sides of the mandible involving the 2nd, 3rd, and 4th premolar, and the 1st molar teeth. Following debridement, notches were placed on the roots at the level of supporting bone. Test quadrants were randomly selected and furcations were filled with reconstituted, demineralized, freeze-dried human cortical bone grafts. Following bone grafting, all defects were covered with an expanded polytetrafluoroethylene (ePTFE) membrane, which was sutured with 4-0 sutures. Afterward, interproximal sutures were placed through the flaps, assuring the flaps covered the membranes completely. The contralateral side, serving as control, was treated by debridement only and application of ePTFE membrane. All membranes were removed 6 weeks after surgery. Dogs were sacrificed at 4 months after surgery. Both mesio-distal and bucco-lingual histologic sections were evaluated by descriptive histology. Linear measurements and surface area determination of the furcal tissues were carried out using the microscope attached to a digitizer. Twelve to 20 nonserial sections were made of the mid-buccal aspects of each root of each treated tooth. Half of these sections were stained with Harris' hematoxylin and eosin (H&E) and the other half stained with Mallory's trichrome stain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8295103

  13. Evaluation of inorganic bovine bone graft in periodontal defects after third molar surgery

    PubMed Central

    de Melo, Daniela Guimaraes; de Santana Santos, Thiago; Sehn, Felipe Perraro; de Oliveira e Silva, Emanuel Dias; Martins-Filho, Paulo Ricardo Saquete; Dourado, Ana Cláudia Amorim Gomes

    2015-01-01

    Aim: This study evaluated the e cacy of inorganic bovine bone graft (IBB) in periodontal defect after mandibular third molar (3M) surgery. Methods: The authors conducted a split-mouth, prospective, randomized, blinded, placebo-controlled clinical trial involving 20 participants with a mean age of 21.60 ± 6.5 years who had symmetrical bilateral lower 3M randomly assigned to receive IBB or left empty (blooding clot). The clinical variables studied were probing depth and clinical attachment level (CAL) at preoperative and postoperative periods of 10, 30, and 60 days. Radiographic measures included the distance from the alveolar bone crest to the cementoenamel junction and the bone density at 30 and 60 days postsurgical procedure. For statistical analysis, we used the paired t-test at a level of signi cance of 5%. Results: It was observed a reduction in pocket depth and CAL in both groups, but IBB did not provide better results than blooding clot (P > 0.05). On the other hand, IBB group showed an increased in the bone density, and a decrease in the periodontal defect on the distal surface of second molar (2M) after 30 and 60 days of surgery compared to the control group (P < 0.05). Conclusion: The use of inorganic bone graft (GenOx) did not enhance the probing depth after 3M removal. Although the radiographic ndings have showed an increase in bone density and a decrease in the periodontal defect on the distal surface of the 2M, we cannot recommend the use of IBB as a treatment for periodontal defect prevention after 3M removal. PMID:26981470

  14. Engineering anatomically shaped vascularized bone grafts with hASCs and 3D-printed PCL scaffolds.

    PubMed

    Temple, Joshua P; Hutton, Daphne L; Hung, Ben P; Huri, Pinar Yilgor; Cook, Colin A; Kondragunta, Renu; Jia, Xiaofeng; Grayson, Warren L

    2014-12-01

    The treatment of large craniomaxillofacial bone defects is clinically challenging due to the limited availability of transplantable autologous bone grafts and the complex geometry of the bones. The ability to regenerate new bone tissues that faithfully replicate the anatomy would revolutionize treatment options. Advances in the field of bone tissue engineering over the past few decades offer promising new treatment alternatives using biocompatible scaffold materials and autologous cells. This approach combined with recent advances in three-dimensional (3D) printing technologies may soon allow the generation of large, bioartificial bone grafts with custom, patient-specific architecture. In this study, we use a custom-built 3D printer to develop anatomically shaped polycaprolactone (PCL) scaffolds with varying internal porosities. These scaffolds are assessed for their ability to support induction of human adipose-derived stem cells (hASCs) to form vasculature and bone, two essential components of functional bone tissue. The development of functional tissues is assessed in vitro and in vivo. Finally, we demonstrate the ability to print large mandibular and maxillary bone scaffolds that replicate fine details extracted from patient's computed tomography scans. The findings of this study illustrate the capabilities and potential of 3D printed scaffolds to be used for engineering autologous, anatomically shaped, vascularized bone grafts. PMID:24510413

  15. Biomechanical Comparison Between Bashti Bone Plug Technique and Biodegradable Screw for Fixation of Grafts in Ligament surgery

    PubMed Central

    Bashti, Kaveh; Tahmasebi, Mohammad N; Kaseb, Hasan; Farahmand, Farzam; Akbar, Mohammad; Mobini, Amir

    2015-01-01

    Background: Ligament reconstruction is a common procedure in orthopedic surgery. Although several popular techniques are currently in use, new methods are proposed for secure fixation of the tendon graft into the bone tunnel. Purposes: We sought to introduce our new technique of Bashti bone plug for fixation of soft tissue graft in anterior cruciate ligament (ACL) reconstruction and to compare its biomechanical features with conventional absorbable interference screw technique in a bovine model. Methods: Twenty pairs of bovine knees were harvested after death. Soft tissue was removed and the Achilles tendon was harvested to be used as an ACL graft. It was secured into the bone tunnel on the tibial side via two different methods: Bashti Bone Plug technique and conventional screw method. Biomechanical strength was measured using 200 N and 300 N cyclic loading on the graft. Pull out strength was also tested until the graft fails. Results: No graft failure was observed after 200 N and 300 N cyclic loading in either fixation methods. When testing for pull out failure, 21 tendons (53%) were torn and 19 tendons (48%) slipped out. No fixation failure occurred, which did not reveal a significant difference between the bone plug or interference screw group (P=0.11). The mean pull out force until failure of the graft was 496±66 N in the screw group and 503±67 N in the bone plug group (P=0.76). Conclusions: Our suggested fixation technique of Bashti bone plug is a native, cheap, and feasible method that provides comparable biomechanical strength with interference screw when soft tissue fixation was attempted in bovine model. PMID:25692166

  16. Cannabidiol for the Prevention of Graft-versus-Host-Disease after Allogeneic Hematopoietic Cell Transplantation: Results of a Phase II Study.

    PubMed

    Yeshurun, Moshe; Shpilberg, Ofer; Herscovici, Corina; Shargian, Liat; Dreyer, Juliet; Peck, Anat; Israeli, Moshe; Levy-Assaraf, Maly; Gruenewald, Tsipora; Mechoulam, Raphael; Raanani, Pia; Ram, Ron

    2015-10-01

    Graft-versus-host-disease (GVHD) is a major obstacle to successful allogeneic hematopoietic cell transplantation (alloHCT). Cannabidiol (CBD), a nonpsychotropic ingredient of Cannabis sativa, possesses potent anti-inflammatory and immunosuppressive properties. We hypothesized that CBD may decrease GVHD incidence and severity after alloHCT. We conducted a phase II study. GVHD prophylaxis consisted of cyclosporine and a short course of methotrexate. Patients transplanted from an unrelated donor were given low-dose anti-T cell globulin. CBD 300 mg/day was given orally starting 7 days before transplantation until day 30. Forty-eight consecutive adult patients undergoing alloHCT were enrolled. Thirty-eight patients (79%) had acute leukemia or myelodysplastic syndrome and 35 patients (73%) were given myeloablative conditioning. The donor was either an HLA-identical sibling (n = 28), a 10/10 matched unrelated donor (n = 16), or a 1-antigen-mismatched unrelated donor (n = 4). The median follow-up was 16 months (range, 7 to 23). No grades 3 to 4 toxicities were attributed to CBD. None of the patients developed acute GVHD while consuming CBD. In an intention-to-treat analysis, we found that the cumulative incidence rates of grades II to IV and grades III to IV acute GVHD by day 100 were 12.1% and 5%, respectively. Compared with 101 historical control subjects given standard GVHD prophylaxis, the hazard ratio of developing grades II to IV acute GVHD among subjects treated with CBD plus standard GVHD prophylaxis was .3 (P = .0002). Rates of nonrelapse mortality at 100 days and at 1 year after transplantation were 8.6% and 13.4%, respectively. Among patients surviving more than 100 days, the cumulative incidences of moderate-to-severe chronic GVHD at 12 and 18 months were 20% and 33%, respectively. The combination of CBD with standard GVHD prophylaxis is a safe and promising strategy to reduce the incidence of acute GVHD. A randomized double-blind controlled study is warranted

  17. Metagenomic Analysis of the Stool Microbiome in Patients Receiving Allogeneic Stem Cell Transplantation: Loss of Diversity Is Associated with Use of Systemic Antibiotics and More Pronounced in Gastrointestinal Graft-versus-Host Disease

    PubMed Central

    Holler, Ernst; Butzhammer, Peter; Schmid, Karin; Hundsrucker, Christian; Koestler, Josef; Peter, Katrin; Zhu, Wentao; Sporrer, Daniela; Hehlgans, Thomas; Kreutz, Marina; Holler, Barbara; Wolff, Daniel; Edinger, Matthias; Andreesen, Reinhard; Levine, John E.; Ferrara, James L.; Gessner, Andre; Spang, Rainer; Oefner, Peter J.

    2016-01-01

    Next-generation sequencing of the hypervariable V3 region of the 16s rRNA gene isolated from serial stool specimens collected from 31 patients receiving allogeneic stem cell transplantation (SCT) was performed to elucidate variations in the composition of the intestinal microbiome in the course of allogeneic SCT. Metagenomic analysis was complemented by strain-specific enterococcal PCR and indirect assessment of bacterial load by liquid chromatography-tandem mass spectrometry of urinary indoxyl sulfate. At the time of admission, patients showed a predominance of commensal bacteria. After transplantation, a relative shift toward enterococci was observed, which was more pronounced under antibiotic prophylaxis and treatment of neutropenic infections. The shift was particularly prominent in patients that developed subsequently or suffered from active gastrointestinal (GI) graft-versus-host disease (GVHD). The mean proportion of enterococci in post-transplant stool specimens was 21% in patients who did not develop GI GVHD as compared with 46% in those that subsequently developed GI GVHD and 74% at the time of active GVHD. Enterococcal PCR confirmed predominance of Enterococcus faecium or both E. faecium and Enterococcus faecalis in these specimens. As a consequence of the loss of bacterial diversity, mean urinary indoxyl sulfate levels dropped from 42.5 ± 11 µmol/L to 11.8 ± 2.8 µmol/L in all post-transplant samples and to 3.5 ± 3 µmol/L in samples from patients with active GVHD. Our study reveals major microbiome shifts in the course of allogeneic SCT that occur in the period of antibiotic treatment but are more prominent in association with GI GVHD. Our data indicate early microbiome shifts and a loss of diversity of the intestinal microbiome that may affect intestinal inflammation in the setting of allogeneic SCT. PMID:24492144

  18. Development of a Three-Dimensional (3D) Printed Biodegradable Cage to Convert Morselized Corticocancellous Bone Chips into a Structured Cortical Bone Graft.

    PubMed

    Chou, Ying-Chao; Lee, Demei; Chang, Tzu-Min; Hsu, Yung-Heng; Yu, Yi-Hsun; Liu, Shih-Jung; Ueng, Steve Wen-Neng

    2016-01-01

    This study aimed to develop a new biodegradable polymeric cage to convert corticocancellous bone chips into a structured strut graft for treating segmental bone defects. A total of 24 adult New Zealand white rabbits underwent a left femoral segmental bone defect creation. Twelve rabbits in group A underwent three-dimensional (3D) printed cage insertion, corticocancellous chips implantation, and Kirschner-wire (K-wire) fixation, while the other 12 rabbits in group B received bone chips implantation and K-wire fixation only. All rabbits received a one-week activity assessment and the initial image study at postoperative 1 week. The final image study was repeated at postoperative 12 or 24 weeks before the rabbit scarification procedure on schedule. After the animals were sacrificed, both femurs of all the rabbits were prepared for leg length ratios and 3-point bending tests. The rabbits in group A showed an increase of activities during the first week postoperatively and decreased anterior cortical disruptions in the postoperative image assessments. Additionally, higher leg length ratios and 3-point bending strengths demonstrated improved final bony ingrowths within the bone defects for rabbits in group A. In conclusion, through this bone graft converting technique, orthopedic surgeons can treat segmental bone defects by using bone chips but with imitate characters of structured cortical bone graft. PMID:27104525

  19. Development of a Three-Dimensional (3D) Printed Biodegradable Cage to Convert Morselized Corticocancellous Bone Chips into a Structured Cortical Bone Graft

    PubMed Central

    Chou, Ying-Chao; Lee, Demei; Chang, Tzu-Min; Hsu, Yung-Heng; Yu, Yi-Hsun; Liu, Shih-Jung; Ueng, Steve Wen-Neng

    2016-01-01

    This study aimed to develop a new biodegradable polymeric cage to convert corticocancellous bone chips into a structured strut graft for treating segmental bone defects. A total of 24 adult New Zealand white rabbits underwent a left femoral segmental bone defect creation. Twelve rabbits in group A underwent three-dimensional (3D) printed cage insertion, corticocancellous chips implantation, and Kirschner-wire (K-wire) fixation, while the other 12 rabbits in group B received bone chips implantation and K-wire fixation only. All rabbits received a one-week activity assessment and the initial image study at postoperative 1 week. The final image study was repeated at postoperative 12 or 24 weeks before the rabbit scarification procedure on schedule. After the animals were sacrificed, both femurs of all the rabbits were prepared for leg length ratios and 3-point bending tests. The rabbits in group A showed an increase of activities during the first week postoperatively and decreased anterior cortical disruptions in the postoperative image assessments. Additionally, higher leg length ratios and 3-point bending strengths demonstrated improved final bony ingrowths within the bone defects for rabbits in group A. In conclusion, through this bone graft converting technique, orthopedic surgeons can treat segmental bone defects by using bone chips but with imitate characters of structured cortical bone graft. PMID:27104525

  20. Saprochaete clavata invasive infection in a patient with severe aplastic anemia: Efficacy of voriconazole and liposomal amphotericin B with adjuvant granulocyte transfusions before neutrophil recovery following allogeneic bone marrow transplantation

    PubMed Central

    Favre, Simon; Rougeron, Amandine; Levoir, Laure; Pérard, Baptiste; Milpied, Noël; Accoceberry, Isabelle; Gabriel, Frédéric; Vigouroux, Stéphane

    2016-01-01

    We report a case of a 27-year old man with severe aplastic anemia who developed a Saprochaete clavata (Geotrichum clavatum) disseminated invasive infection shortly prior a scheduled allogeneic bone marrow transplantation. Treatment with a combination of voriconazole, liposomal amphotericin B and adjuvant granulocyte transfusions was successful before neutrophil recovery. PMID:27069848

  1. Saprochaete clavata invasive infection in a patient with severe aplastic anemia: Efficacy of voriconazole and liposomal amphotericin B with adjuvant granulocyte transfusions before neutrophil recovery following allogeneic bone marrow transplantation.

    PubMed

    Favre, Simon; Rougeron, Amandine; Levoir, Laure; Pérard, Baptiste; Milpied, Noël; Accoceberry, Isabelle; Gabriel, Frédéric; Vigouroux, Stéphane

    2016-03-01

    We report a case of a 27-year old man with severe aplastic anemia who developed a Saprochaete clavata (Geotrichum clavatum) disseminated invasive infection shortly prior a scheduled allogeneic bone marrow transplantation. Treatment with a combination of voriconazole, liposomal amphotericin B and adjuvant granulocyte transfusions was successful before neutrophil recovery. PMID:27069848

  2. Bone morphogenetic protein-2-encapsulated grafted-poly-lactic acid-polycaprolactone nanoparticles promote bone repair.

    PubMed

    Xu, Xiaojun; Yang, Jun; Ding, Lifeng; Li, Jianjun

    2015-01-01

    The aim of this study is to test the efficacy of a novel tissue-engineered bone in repairing bone defects, using poly-lactic-acid-polycaprolactone (PLA-PCL) scaffolding seeded with PEG-bone morphogenetic protein-2 (BMP-2)-transfected rBMSCs (rabbit bone marrow stromal cells). The rBMSCs were transfected with PEG/BMP-2 or liposome/BMP-2, and then implanted into a PLA-PCL tissue-engineered bone. The protein level of BMP-2 was assessed by Western blot analysis and immunohistochemistry. ELISA was used to measure the amount of BMP-2 secreted in the culture media. The mRNA level of BMP-2 and osteocalcin was assayed quantitatively by real-time PCR. The middle portion of the bilateral radius in New Zealand rabbits was excised and implanted with tissue-engineered bone, and the modified areas were monitored by X-ray, hematoxylin-eosin staining, and immunohistochemistry staining of BMP-2. PEG-BMP-2 nanoparticles (NPs) and BMP-2-loaded PEG-PLA-PCL tissue-engineered bones were successfully constructed. The novel PEG-PLA-PCL NPs/DNA complex was a superior option for transfecting BMP-2 in rBMSCs compared to normal liposomes Moreover, the mRNA level of osteocalcin and alkaline phosphatase activity was also elevated upon transfection of BMP-2-encapsulated NPs. In vivo implants with BMP-2-carried tissue-engineered bone exhibited dramatic augmentation of BMP-2 and effective bone formation in the rabbit ectopic model. The PEG-PLA-PCL NPs/BMP-2 complex had an advantageous effect on bone repair, which provided an important theoretic basis for potential clinical treatments. PMID:25158862

  3. Maxillary sinus augmentation using recombinant bone morphogenetic protein-2/acellular collagen sponge in combination with a mineralized bone replacement graft: a report of three cases.

    PubMed

    Tarnow, Dennis P; Wallace, Stephen S; Testori, Tiziano; Froum, Stuart J; Motroni, Alessandro; Prasad, Hari S

    2010-04-01

    The objective of the following case reports was to assess whether mineralized bone replacement grafts (eg, xenografts and allografts) could be added to recombinant human bone morphogenetic protein-2/acellular collagen sponge (rhBMP-2/ACS) in an effective manner that would: (1) reduce the graft shrinkage observed when using rhBMP-2/ACS alone, (2) reduce the volume and dose of rhBMP-2 required, and (3) preserve the osteoinductivity that rhBMP-2/ACS has shown when used alone. The primary outcome measures were histomorphometric analysis of vital bone production and analysis of serial computed tomographic scans to determine changes in bone graft density and stability. Over the 6-month course of this investigation, bone graft densities tended to increase (moreso with the xenograft than the allograft). The increased density in allograft cases was likely the result of both compression of the mineralized bone replacement graft and vital bone formation, seen histologically. Loss of volume was greater with the four-sponge dose than the two-sponge dose because of compression and resorption of the sponges. Vital bone formation in the allograft cases ranged from 36% to 53% but, because of the small sample size, it was not possible to determine any significant difference between the 5.6 mL (four-sponge) dose and the 2.8 mL (two-sponge) dose. Histology revealed robust new woven bone formation with only minimal traces of residual allograft, which appeared to have undergone accelerated remodeling or rhBMP-2-mediated resorption. PMID:20228973

  4. Computer-aided osteotomy design for harvesting autologous bone grafts in reconstructive surgery

    NASA Astrophysics Data System (ADS)

    Krol, Zdzislaw; Zerfass, Peter; von Rymon-Lipinski, Bartosz; Jansen, Thomas; Hauck, Wolfgang; Zeilhofer, Hans-Florian U.; Sader, Robert; Keeve, Erwin

    2001-05-01

    Autologous grafts serve as the standard grafting material in the treatment of maxillofacial bone tumors, traumatic defects or congenital malformations. The pre-selection of a donor site depends primarily on the morphological fit of the available bone mass and the shape of the part that has to be transplanted. To achieve sufficient incorporation of the autograft into the host bone, precise planning and simulation of the surgical intervention based on 3D CT studies is required. This paper presents a method to identify an optimal donor site by performing an optimization of appropriate similarity measures between donor region and a given transplant. At the initial stage the surgeon has to delineate the osteotomy border lines in the template CT data set and to define a set of constraints for the optimization of appropriate similarity measures between donor region and a given transplant. At the initial stage the surgeon has to delineate the osteotomy border lines in the template CT data set and to define a set of constraints for the optimization task in the donor site CT data set. The following fully automatic optimization stage delivers a set of sub-optimal and optimal donor sites for a given template. All generated solutions can be explored interactively on the computer display using an efficient graphical interface. Reconstructive operations supported by our system were performed on 28 patients. We found that the operation time can be considerably shortened by this approach.

  5. Orthotopic bone transplantation in mice. III. Methods of reducing the immune response and their effect on healing

    SciTech Connect

    Kliman, M.; Halloran, P.F.; Lee, E.; Esses, S.; Fortner, P.; Langer, F.

    1981-01-01

    Various methods of reducing the immune response to allogeneic bone grafts, either by pretreating the graft or by immunosuppressing the recipient, were compared. Tibial grafts from B10.D2 mice, either untreated or pretreated in various ways, were transplanted into B10 recipients. The antibody response was followed and the extent of bone healing at 4 months was assessed. Pretreatment of the graft by X-irradiation, freezing, or by incubation in alloantisera (either anti-H-2 or anti-Ia) reduced or abolished the immunogenicity of the graft. Immunosuppression of the recipient with methotrexate or antilymphocyte serum (ALS) also greatly depressed the antibody response. But when healing was assessed, none of these treatments except ALS improved the delayed healing of the bone allografts. The reason for this failure was probably that X-irradiation, freezing, alloantiserum pretreatment, and methotrexate all interfered with bone healing directly, whereas ALS did not. We conclude that many methods will reduce the immune response to allogeneic bone, but that only ALS will improve the healing of the allogeneic bone. Furthermore, as a corollary to the observation that pretreatment with anti-Ia serum markedly reduced the immunogenicity of bone allografts, we conclude that much of the immunogenicity of bone allografts is attributable to a population of Ia-positive cells.

  6. An association between human leucocyte antigen alleles and acute and chronic graft-versus-host disease after allogeneic haematopoietic stem cell transplantation.

    PubMed

    Remberger, Mats; Persson, Ulla; Hauzenberger, Dan; Ringdén, Olle

    2002-12-01

    The association between various human leucocyte antigen (HLA) alleles and the occurrence of acute and chronic graft-versus-host disease (GVHD) was evaluated in 493 haematopoietic stem-cell transplant (HSCT) patients with HLA identical sibling donors. There were 307 men and 186 women with a median age of 30 years (0.2-77). Most of the patients had a haematological malignancy and received total body irradiation or busulphan combined with cyclophosphamide as conditioning before transplantation. GVHD prophylaxis consisted of monotherapy with methotrexate (MTX) or cyclosporin (CsA) in 118 patients, MTX + CsA in 323, T-cell depletion in 28 and other combinations in 24. In total, 84 patients (17%) received a peripheral blood stem-cell graft, whereas the rest received bone marrow. The cumulative incidence of acute GVHD grades II-IV was 20%, and chronic GVHD 46%. In the multivariate analysis, HLA-A10 (OR 2.14, CI 1.04-4.41, P = 0.03) and HLA-B7 (OR 1.80, CI 1.04-3.12, P = 0.03) correlated with an increased risk of acute GVHD grades II-IV. We also found an association between HLA-B27 (RR 0.60, CI 0.37-0.95, P = 0.04) and a lower incidence of chronic GVHD. These HLA alleles were independent of other known risk factors for acute or chronic GVHD, as shown by multivariate analysis. These results show that major histocompatibility comlex (MHC) alleles may influence the incidence of GVHD in HSCT with HLA identical sibling donors. PMID:12437654

  7. Efficient natural defense mechanisms against Listeria monocytogenes in T and B cell-deficient allogeneic bone marrow radiation chimeras. Preactivated macrophages are the main effector cells in an early phase after bone marrow transfer

    SciTech Connect

    Roesler, J.; Groettrup, E.B.; Baccarini, M.; Lohmann-Mattes, M.L. )

    1989-09-01

    Radiation chimeras in the early phase after bone marrow transplantation are a good model to study the efficiency of the body's nonspecific defense system represented by macrophages (M phi), polymorphonuclear cells (PMN), and NK cells. These cell types are present in large numbers in spleen and liver at that time, whereas the specific immune system represented by T and B cells is functionally deficient. We previously reported enhanced activities in vitro of M phi (and PMN) from recipient animals in an early phase after allogeneic bone marrow transfer. We here demonstrate that these activities result in enhanced spontaneous resistance against Listeria monocytogenes in vivo: CFU of L. monocytogenes in spleen and liver 48 h after infection were about 1 or 2 to 4 log steps less than in untreated control mice of donor or host haplotype. This enhanced resistance decreased over the 4-mo period after marrow transfer. Preactivated M phi were identified as the most important effector cells. Isolated from spleen and peritoneal cavity, they performed enhanced killing of phagocytosed Listeria. Such preactivated M phi occurred in recipient animals after transfer of allogeneic but not of syngeneic bone marrow. The precise mechanism of M phi activation in the allogeneic radiation chimera in the complete absence of any detectable T cell function is not clear at present. However, these preactivated M phi display an important protective effect against L. monocytogenes: chimeras could eliminate Listeria without acquisition of positive delayed-type sensitivity when infected with 10(3) bacteria. An inoculum of 5 . 10(3) L. monocytogenes resulted either in prolonged survival compared with normal mice of the recipient haplotype or in definitive survival accompanied by a positive delayed-type sensitivity.

  8. Successful management of EBV-PTLD in allogeneic bone marrow transplant recipient by virological-immunological monitoring of EBV infection, prompt diagnosis and early treatment.

    PubMed

    Chiereghin, Angela; Bertuzzi, Clara; Piccirilli, Giulia; Gabrielli, Liliana; Squarzoni, Diego; Turello, Gabriele; Ferioli, Martina; Sessa, Mariarosaria; Bonifazi, Francesca; Zanoni, Lucia; Sabattini, Elena; Lazzarotto, Tiziana

    2016-02-01

    Epstein-Barr virus-related post-transplant lymphoproliferative disorder (EBV-PTLD) is an uncommon, but frequently fatal, complication after allogeneic hematopoietic stem cell transplant. Prospective post-transplant virological and immunological monitoring allowed to successfully manage a patient who developed both polymorphic and monomorphic, "diffuse large B-cell lymphoma like", as an EBV-PTLD, 65days after allogeneic bone marrow transplant. Early detection of significant increase in EBV DNA level in patient's peripheral blood (peak of viral load equal to 119,039copies/mL whole blood, +56day after transplant) led to administration of pre-emptive anti-CD20 monoclonal antibody (rituximab) and close clinical monitoring. After one week, physical exam revealed laterocervical adenopathy. Histopathologic features, immunohistochemical characterization and in situ hybridization study allowed to establish a diagnosis of EBV-related PTLD. Immunological monitoring showed no EBV-specific T-cell responses during EBV replication, thus potentially explaining the occurrence of high EBV load with subsequent PTLD development. A total of four doses of anti-CD20 monoclonal antibody were administered and at the end of the treatment, EBV infection was cleared and imaging technique showed complete disease remission. In conclusion, the early use of anti-CD20 monoclonal antibody proved to be a safe and effective treatment strategy for EBV-PTLD. Moreover, combined virological-immunological monitoring of EBV infection may more accurately assess patients at higher risk for EBV-PTLD. PMID:26687013

  9. Engraftment of allogeneic bone marrow following administration of anti-T cell monoclonal antibodies and low-dose irradiation

    SciTech Connect

    Sharabi, Y.; Sachs, D.H.

    1989-02-01

    A nonlethal conditioning regimen involving administration of mAb in vivo, low-dose WBI and 700 rads of thymic irradiation, permits engraftment of T cell-depleted allogeneic BM. Engraftment of class I + II disparate allogeneic BM after conditioning with this regimen required depletion of both L3T4 and Lyt2 host T cell subsets in vivo. Treatment with a combination of specific mAbs to each subset (GK1.5 plus 2.43) was more effective than treatment with an anti-Thy1 mAb (30-H12). The low incidence of engraftment after 30-H12 treatment is probably due to reduced efficiency of 30-H12 in depletion of host alloreactive cell populations rather than an effect of this mAb on a particular population of donor cells that are important for engraftment.

  10. Arresting rampant dental caries with silver diamine fluoride in a young teenager suffering from chronic oral graft versus host disease post-bone marrow transplantation: a case report

    PubMed Central

    2014-01-01

    Background Rampant caries is an advanced and severe dental disease that affects multiple teeth. This case describes the management of rampant caries in a young teenager suffering from chronic oral graft versus host disease after allogeneic bone marrow transplantation. Case presentation A 14-year-old Chinese boy suffering from β–thalassemia major was referred to the dental clinic for the management of rampant dental caries. An oral examination revealed pale conjunctiva, bruising of lips, and depapillation of tongue indicating an underlying condition of anemia. The poor oral condition due to topical and systemic immunosuppressants was seriously aggravated, and rampant caries developed rapidly, affecting all newly erupted, permanent teeth. The teeth were hypersensitive and halitosis was apparent. Strategies for oral health education and diet modification were given to the patient. Xylitol chewing gum was used to stimulate saliva flow to promote remineralization of teeth. Silver diamine fluoride was topically applied to arrest rampant caries and to relieve pain from hypersensitivity. Carious teeth with pulpal involvement were endodontically treated. Stainless steel crowns were provided on molars to restore chewing function, and polycarbonate crowns were placed on premolars, upper canines and incisors. Conclusion This case report demonstrates success in treating a young teenager with severe rampant dental decay by contemporary caries control and preventive strategy. PMID:24383434

  11. Curettage of benign bone tumors without grafts gives sufficient bone strength

    PubMed Central

    Watanabe, Hideomi; Shinozaki, Tetsuya; Takagishi, Kenji

    2009-01-01

    Background and purpose The defect that results after curettage of a bone tumor is usually filled in the same way. We report the outcome in patients with benign bone tumors that were treated with curettage but no filling. Patients and methods We retrospectively studied 78 patients (mean age at the time of operation was 27 (6–73) years, 44 men) who had had a benign bone tumor curetted with no filling of the defect. The commonest tumor types were giant cell tumor of bone (27), fibrous dysplasia (13), enchondroma (9), and simple bone cyst (7). The mean size of the lesions was 35 (2–196) cm3. Normal activities, including full weight bearing for lower extremity lesions, were allowed after 3 months or less. The patients were followed for an average of 10 (1.2–21) years. Results A postoperative fracture with a minor displacement occurred in 3 patients, in 2 of them because of local recurrence. All fractures healed. Local recurrence occurred in 9 patients; 7 of them had a giant cell tumor. Repeated local recurrences necessitated above-knee amputation in 1 patient. All other patients had unrestricted activities of daily living. Interpretation Routine filling of curetted bone lesions does not appear to be necessary from a mechanical point of view. PMID:19234882

  12. Correlations between initial cleft size and dental anomalies in unilateral cleft lip and palate patients after alveolar bone grafting.

    PubMed

    Jabbari, Fatima; Reiser, Erika; Thor, Andreas; Hakelius, Malin; Nowinski, Daniel

    2016-03-01

    Objective To determine in individuals with unilateral cleft lip and palate the correlation between initial cleft size and dental anomalies, and the outcome of alveolar bone grafting. Methods A total of 67 consecutive patients with non-syndromic unilateral complete cleft lip and palate (UCLP) were included from the cleft lip and palate-craniofacial center, Uppsala University Hospital, Sweden. All patients were operated by the same surgeon and treated according to the Uppsala protocol entailing: lip plasty at 3 months, soft palate closure at 6 months, closure of the residual cleft in the hard palate at 2 years of age, and secondary alveolar bone grafting (SABG) prior to the eruption of the permanent canine. Cleft size was measured on dental casts obtained at the time of primary lip plasty. Dental anomalies were registered on radiographs and dental casts obtained before bone grafting. Alveolar bone height was evaluated with the Modified Bergland Index (mBI) at 1 and 10-year follow-up. Results Anterior cleft width correlated positively with enamel hypoplasia and rotation of the central incisor adjacent to the cleft. There was, however, no correlation between initial cleft width and alveolar bone height at either 1 or 10 years follow-up. Conclusions Wider clefts did not seem to have an impact on the success of secondary alveolar bone grafting but appeared to be associated with a higher degree of some dental anomalies. This finding may have implications for patient counseling and treatment planning. PMID:26923345

  13. Use of mineralized collagen bone graft substitutes and dorsal locking plate in treatment of elder metaphyseal comminuted distal radius fracture

    NASA Astrophysics Data System (ADS)

    Liu, Ke-Bin; Huang, Kui; Teng, Yu; Qu, Yan-Zheng; Cui, Wei; Huang, Zhen-Fei; Sun, Ting-Fang; Guo, Xiao-Dong

    2014-03-01

    Bone graft may be needed to fill bone defect in elderly patients with a metaphyseal comminuted distal radius fracture. In this retrospective, nonrandomized, single-surgeon study, we evaluated the clinical and radiologic outcomes of using both dorsal locking plates with or without augmentation with mineralized collagen (MC) bone graft for elderly patients with dorsally metaphyseal comminuted radius fractures. Patients in group 1 ( n = 12) were treated with dorsal locking plates with MC bone graft application into the metaphyseal bone defect, and those in group 2 ( n = 12) only with dorsal locking plates. Clinical and radiologic parameters were determined at three and 12 months after surgery. At final follow-up, no significant difference was noted between the 2 groups in terms of palmar tilt and radial inclination ( p = 0.80); however, ulnar variance increased significantly in the group 2 treated with dorsal locking plates without augmentation ( p < 0.05). Functionally, there was no significant difference between the groups. Our preliminary study suggests that combination of MC as bone-graft substitutes and dorsal locking plates may be a usefully alternative for elderly patients with metaphyseal comminuted distal radius fracture.

  14. Correlations between initial cleft size and dental anomalies in unilateral cleft lip and palate patients after alveolar bone grafting

    PubMed Central

    Jabbari, Fatima; Reiser, Erika; Thor, Andreas; Hakelius, Malin; Nowinski, Daniel

    2016-01-01

    Objective To determine in individuals with unilateral cleft lip and palate the correlation between initial cleft size and dental anomalies, and the outcome of alveolar bone grafting. Methods A total of 67 consecutive patients with non-syndromic unilateral complete cleft lip and palate (UCLP) were included from the cleft lip and palate-craniofacial center, Uppsala University Hospital, Sweden. All patients were operated by the same surgeon and treated according to the Uppsala protocol entailing: lip plasty at 3 months, soft palate closure at 6 months, closure of the residual cleft in the hard palate at 2 years of age, and secondary alveolar bone grafting (SABG) prior to the eruption of the permanent canine. Cleft size was measured on dental casts obtained at the time of primary lip plasty. Dental anomalies were registered on radiographs and dental casts obtained before bone grafting. Alveolar bone height was evaluated with the Modified Bergland Index (mBI) at 1 and 10-year follow-up. Results Anterior cleft width correlated positively with enamel hypoplasia and rotation of the central incisor adjacent to the cleft. There was, however, no correlation between initial cleft width and alveolar bone height at either 1 or 10 years follow-up. Conclusions Wider clefts did not seem to have an impact on the success of secondary alveolar bone grafting but appeared to be associated with a higher degree of some dental anomalies. This finding may have implications for patient counseling and treatment planning. PMID:26923345

  15. BIOMECHANICAL STUDY OF TRANSCORTICAL OR TRANSTRABECULAR BONE FIXATION OF PATELLAR TENDON GRAFT WITH BIOABSORBABLE PINS IN ACL RECONSTRUCTION IN SHEEP

    PubMed Central

    Albano, Mauro Batista; Borges, Paulo César; Namba, Mario Massatomo; da Silva, João Luiz Vieira; de Assis Pereira Filho, Francisco; Filho, Edmar Stieven; Matias, Jorge Eduardo Fouto

    2015-01-01

    Objective: To determine the initial resistance of fixation using the Rigid Fix® system, and compare it with traditional fixation methods using metal interference screws; and to evaluate the resistance of the fixation with the rigid fix system when the rotational position of the bone block is altered in the interior of the femoral tunnel. Methods: forty ovine knee specimens (stifle joints) were submitted to anterior cruciate ligament reconstruction (ACL) using a bone-tendon-bone graft. In twenty specimens, the Rigid Fix method was used; this group was subdivided into two groups: ten knees the pins transfixed only the spongious area of the bone block, and ten for fixation passing through the layer of cortical bone. In the twenty remaining specimens, the graft was fixed with 9mm metal interference screws. Results: comparison of the RIGIDFIX® method with the metal interference screw fixation method did not show any statistically significant differences in terms of maximum load and rigidity; also, there were no statistically significant differences when the rotational position of the bone block was altered inside the femoral tunnel. For these evaluations, a level of significance of p < 0.017 was considered. Conclusion: fixation of the bone-tendon-bone graft with 2 bioabsorbable pines, regardless of the rotational position inside the femoral tunnel, gave a comparable fixation in terms of initial resistance to the metal interference screw, in this experimental model. PMID:27027081

  16. Failure load of patellar tendon grafts at the femoral side: 10- versus 20-mm-bone blocks.

    PubMed

    Meuffels, Duncan E; Niggebrugge, Marnix J N; Verhaar, Jan A N

    2009-02-01

    The aim of the study was to investigate whether use of short bone blocks is safe in anterior cruciate ligament (ACL) reconstruction. Our hypothesis was that the smaller 10-mm-length bone blocks will fail at lower loads than 20-mm-bone blocks. Ten paired human cadaver knees were randomly assigned to the 10- or 20-mm group (group 1 and 2) and underwent bone-patellar tendon-bone femoral fixation with interference screw. Tensile tests were performed using a tensile testing machine (Instron). Stiffness, failure load and failure mode were recorded. Median stiffness was 72 N/mm (16-103) for 10-mm-bone blocks and 91 N/mm (40-130) for 20-mm-bone blocks. Median failure loads were 402 N (87-546) for 10-mm-long bone block and 456 N (163-636) for 20-mm-bone blocks. There was no statistically significant difference between groups (P = 0.35). All bone-patellar tendon-bone grafts were pulled out of the femoral tunnel with interference screw, due to slippage. We concluded that a 10-mm-long bone block was not significantly weaker than a 20-mm-long bone block. Failure loads of a 10-mm-bone block exceeded loading values at passive and active extension of the knee under normal conditions. Ten millimetre bone blocks offered sufficient fixation strength in ACL reconstruction. PMID:18839146

  17. Assessment of bone repair following the use of anorganic bone graft and membrane associated or not to 830-nm laser light

    NASA Astrophysics Data System (ADS)

    de Assis Limeira, Francisco, Jr.; Barbosa Pinheiro, Antônio L.; Marquez de Martinez Gerbi, Marleny E.; Pedreira Ramalho, Luciana Maria; Marzola, Clovis; Carneiro Ponzi, Elizabeth A.; Soares, Andre O.; Bandeira de Carvalho, Lívia C.; Vieira Lima, Helena Cristina; Oliveira Gonçalves, Thais; Silva Meireles, Gyselle C.; Possa, Thaise R.

    2003-06-01

    The aim of this study was to assess the effect of LLLT (λ830nm, Thera lase, DMC Equipmentos, Sao Carlos, SP, Brazil, 40mW, CW, spot size 0.60mm, 16J/cm2 per session) on the repair of bone defects on the femur of Wistar albinus rats which were grafted with anorganic bovine bone associated or not to bovine bone membrane. Five randomized groups were studied: I (Control); II (anorganic bovine bone); III (anorganic bovine bone + LLLT); IV (anorganic bovine bone + bovine bone membrane) and V (anorganic bovine bone + bovine bone membrane + LLLT). The animals were irradiated at every 48h during 15 days, the first irradiation was performed immediately after the procedure. The animals were irradiated transcutaneuosly in four points around the defect. At each point a dose of 4J/cm2 was given (f~0,60mm, 40mW) totaling 16J/cm2 per session. The animals were sacrificed 15, 21 and 30 days after surgery. The specimens were routinely processed to wax and stained with H&E and Picrosírius stains and analyzed under light microscopy. The results showed evidence of a more advanced repair on the irradiated groups when compared to non-irradiated ones. The repair of irradiated groups was characterized by both increased bone formation and amount of collagen fibers around the graft within the cavity early, considering the osteoconductive capacity of the anorganic bovine bone and the increment of the cortical repair in specimens with membrane. It is concluded that LLLT had a positive effect on the repair of bone defect submitted the implantation of graft associated or not to the use of biological membrane.

  18. Iliac Crest Donor Site for Children With Cleft Lip and Palate Undergoing Alveolar Bone Grafting: A Long-term Assessment.

    PubMed

    Wheeler, Jonathan; Sanders, Megan; Loo, Stanley; Moaveni, Zac; Bartlett, Glenn; Keall, Heather; Pinkerton, Mark

    2016-05-01

    The authors aimed to accurately assess the donor site morbidity from iliac crest bone grafts for secondary bone grafting in patients with cleft lip and palate alveolar defects. Fifty patients between 3 months and 10 years following alveolar bone grafting for cleft lip and palate were entered into the study. Two-thirds of patients had no significant concerns about the donor site. The remaining third had some concerns about the appearance of their hips and less than 10% of patients expressing strong agreement with statements about concerns with shape, appearance, and self-consciousness about the iliac crest donor site. Examination findings showed the average length of scar being 5.4 cm and a third of patients having some minor palpable boney irregularities of the iliac crest. The authors found that the alveolar crest donor site is well tolerated by patients long term but has a measurable morbidity long term. PMID:27035602

  19. Allogeneic T cell responses are regulated by a specific miRNA-mRNA network

    PubMed Central

    Sun, Yaping; Tawara, Isao; Zhao, Meng; Qin, Zhaohui S.; Toubai, Tomomi; Mathewson, Nathan; Tamaki, Hiroya; Nieves, Evelyn; Chinnaiyan, Arul M.; Reddy, Pavan

    2013-01-01

    Donor T cells that respond to host alloantigens following allogeneic bone marrow transplantation (BMT) induce graft-versus-host (GVH) responses, but their molecular landscape is not well understood. MicroRNAs (miRNAs) regulate gene (mRNA) expression and fine-tune the molecular responses of T cells. We stimulated naive T cells with either allogeneic or nonspecific stimuli and used argonaute cross-linked immunoprecipitation (CLIP) with subsequent ChIP microarray analyses to profile miR responses and their direct mRNA targets. We identified a unique expression pattern of miRs and mRNAs following the allostimulation of T cells and a high correlation between the expression of the identified miRs and a reduction of their mRNA targets. miRs and mRNAs that were predicted to be differentially regulated in allogeneic T cells compared with nonspecifically stimulated T cells were validated in vitro. These analyses identified wings apart-like homolog (Wapal) and synaptojanin 1 (Synj1) as potential regulators of allogeneic T cell responses. The expression of these molecular targets in vivo was confirmed in MHC-mismatched experimental BMT. Targeted silencing of either Wapal or Synj1 prevented the development of GVH response, confirming a role for these regulators in allogeneic T cell responses. Thus, this genome-wide analysis of miRNA-mRNA interactions identifies previously unrecognized molecular regulators of T cell responses. PMID:24216511

  20. A facile magnesium-containing calcium carbonate biomaterial as potential bone graft.

    PubMed

    He, Fupo; Zhang, Jing; Tian, Xiumei; Wu, Shanghua; Chen, Xiaoming

    2015-12-01

    The calcium carbonate is the main composition of coral which has been widely used as bone graft in clinic. Herein, we readily prepared novel magnesium-containing calcium carbonate biomaterials (MCCs) under the low-temperature conditions based on the dissolution-recrystallization reaction between unstable amorphous calcium carbonate (ACC) and metastable vaterite-type calcium carbonate with water involved. The content of magnesium in MCCs was tailored by adjusting the proportion of ACC starting material that was prepared using magnesium as stabilizer. The phase composition of MCCs with various amounts of magnesium was composed of one, two or three kinds of calcium carbonates (calcite, aragonite, and/or magnesian calcite). The different MCCs differed in topography. The in vitro degradation of MCCs accelerated with increasing amount of introduced magnesium. The MCCs with a certain amount of magnesium not only acquired higher compressive strength, but also promoted in vitro cell proliferation and osteogenic differentiation. Taken together, the facile MCCs shed light on their potential as bone graft. PMID:26539810

  1. Delayed Union of a Sacral Fracture: Percutaneous Navigated Autologous Cancellous Bone Grafting and Screw Fixation

    SciTech Connect

    Huegli, R. W. Messmer, P.; Jacob, A. L.; Regazzoni, P.; Styger, S.; Gross, T.

    2003-09-15

    Delayed or non-union of a sacral fracture is a serious clinical condition that may include chronic pain, sitting discomfort, gait disturbances, neurological problems, and inability to work. It is also a difficult reconstruction problem. Late correction of the deformity is technically more demanding than the primary treatment of acute pelvic injuries. Open reduction, internal fixation (ORIF), excision of scar tissue, and bone grafting often in a multi-step approach are considered to be the treatment of choice in delayed unions of the pelvic ring. This procedure implies the risk of neurological and vascular injuries, infection, repeated failure of union, incomplete correction of the deformity, and incomplete pain relief as the most important complications. We report a new approach for minimally invasive treatment of a delayed union of the sacrum without vertical displacement. A patient who suffered a Malgaigne fracture (Tile C1.3) was initially treated with closed reduction and percutaneous screw fixation (CRPF) of the posterior pelvic ring under CT navigation and plating of the anterior pelvic ring. Three months after surgery he presented with increasing hip pain caused by a delayed union of the sacral fracture. The lesion was successfully treated percutaneously in a single step procedure using CT navigation for drilling of the delayed union, autologous bone grafting, and screw fixation.

  2. Raman study of the effect of LED light on grafted bone defects

    NASA Astrophysics Data System (ADS)

    Soares, Luiz G. G. P.; Aciole, Jouber M. S.; Aciole, Gilbeth T. S.; Barbosa, Artur F. S.; Silveira-Júnior, Landulfo; Pinheiro, Antônio L. B.

    2013-03-01

    Benefits of the isolated or combined use light and biomaterials on bone healing have been suggested. Our group has used several models to assess the effects of laser on bone. A Raman spectral analysis on surgical bone defects grafted or not with Hydroxyapatite (HA), treated or not with LED was carried out. 40 rats were divided into 4 groups. On Group I the defect was filled with the clot. On Group II, the defect was filled with the HA. On groups III the defect was