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Biomedical subjects

Ginger E Holt

Publications and source records attributed to Ginger E Holt.

11 recordsLinked to original sources
PubMed2006

The application of a murine bone bioreactor as a model of tumor: bone interaction.

A limited number of in vivo models that rapidly assess bone development or allow for the study of tumor progression in a closed in vivo environment exist. To address this, we have used bone tissue engineering techniques to generate a murine in vivo bone bioreactor. The bioreactor was created by implanting an osteoconductive hydroxyapatite scaffold pre-loaded with saline as a control or with bone morphogenetic protein-2 (BMP-2) to the murine femoral artery. Control and BMP-2 bioreactors were harvested and histologically assessed for vascularization and bone formation at 6 and 12 weeks post implantation. BMP-2 significantly enhanced the formation of osteoid within the bioreactor in comparison to the controls. To test the in vivo bone bioreactor as a model of tumor: bone interaction, FVB mice were implanted with control or BMP-2 treated bioreactors. After 6 weeks, an osteolytic inducing mammary tumor cell line tagged with luciferase (PyMT-Luc) derived from the polyoma virus middle T (PyMT) model of mammary tumorigenesis was delivered to the bioreactor via the femoral artery. Analysis of luciferase expression over time demonstrated that the presence of osteoid in the BMP-2 treated bioreactors significantly enhanced the growth rate of the PyMT-Luc cells in comparison to the control group. These data present a unique in vivo model of ectopic bone formation that can be manipulated to address molecular questions that pertain to bone development and tumor progression in a bone environment.

Animals↗
PubMed2006

Level-adjusted perioperative risk of sacral amputations.

BACKGROUND AND OBJECTIVES: Sacral amputations above the S2 body often involve increased surgical complexity leading to long-term morbidity. The purpose of this study was to determine whether proximal sacral amputations have substantially higher perioperative morbidity compared with more distal sacral amputations. METHODS: We evaluated the effect of sacral amputation level on perioperative outcomes within 90 days of surgery. Outcome measures included blood loss, intensive care unit (ICU) and hospital stay, hospital cost, and incidence of a major and minor morbidity. Survival analyses were adjusted for the level of resection and histological appearance. RESULTS: Thirteen proximal and 14 distal resections were performed. In comparing proximal versus distal resections, median estimated blood loss was 4 L versus 1 L (P < 0.001), ICU stay was 4 days versus 0 days (P = 0.012), hospital stay was 19 days versus 8 days (P = 0.001), hospital cost was 28,800 dollars versus 7,500 dollars (P = 0.003), with one or more major complications in 85% versus 29% (P = 0.011). Survival analysis demonstrated that the sacral resection level did not influence survival (P = 0.936), whereas the type of tumor did influence survival (P = 0.012). CONCLUSION: Tumor resections above S2 demonstrate increased perioperative morbidity, suggesting that proximal osteotomies be reserved for patients with a realistic cure potential.

Adenocarcinoma↗
PubMed2006

Multifocality and multifocal postradiation sarcomas.

UNLABELLED: Hypothetically, any site in a radiation portal has potential for late malignant transformation. Secondary malignant neoplasms may occur after almost any index cancer has been treated with radiation and/or chemotherapy. The incidence of secondary malignant neoplasms, histopathology, time delay, radiation dose, cytotoxic agents, age and type of initial malignancy, and outcome all negatively impact cancer survivors. We highlight the new concept of multifocality, defined as greater than two noncontiguous second malignant neoplasms that develop in a prior radiation port. We identified 48 patients with postradiation sarcomas from three prospectively collected databases. Fifteen of these patients (31%) had evidence of multifocal postradiation sarcomas. Five of 10 women had multifocal postradiation sarcomas after breast-conserving surgery for carcinoma. The longer the time interval between the index cancer and post-radiation sarcoma, the greater the likelihood of multifocal malignant transformation occurring. LEVEL OF EVIDENCE: Therapeutic study, level III.

Adult↗
PubMed2006

Prognosis of radiation-induced bone sarcoma is similar to primary osteosarcoma.

UNLABELLED: Radiation-induced sarcoma of bone (RISB) is thought to be associated with a poor prognosis. The purpose of this study was to determine disease-free and overall survival of patients treated for RISB, and whether there is a role for limb sparing surgery. Twenty-four patients had a mean latency of 16 years between radiation for their index cancer and RISB diagnosis. The most common tumor was osteosarcoma (n = 17). Ten patients with localized disease treated aggressively with chemotherapy and surgical resection had estimated 5-year disease-free and overall survival rates of 58% and 69% respectively. Patients treated by surgery alone or those with metastases at diagnosis had inferior outcomes. Patients who received a complete course of chemotherapy demonstrated better histologic tumor response and improved survival. There was no difference in survival between the limb sparing surgery (n = 12) or amputation (n = 8) groups. However, limb salvage patients had slightly higher rates of local tumor relapse and post-operative complications. Functional outcome following limb sparing surgery for 10 patients with RISB was similar to a matched cohort treated for primary osteosarcoma. An aggressive treatment approach for patients with RISB may provide similar rates of local recurrence and metastasis and functional outcomes compared to patients with primary osteosarcoma. LEVEL OF EVIDENCE: Therapeutic study, level IV-1.

Adolescent↗
PubMed2006

Proteomic profiling in musculoskeletal oncology by MALDI mass spectrometry.

UNLABELLED: Proteomics is the emerging technology that evaluates normal and abnormal protein expression in tissues. Tissue profiling by matrix assisted laser desorption ionization mass spectrometry (MALDI MS) is a proteomic tool that permits the rapid detection of proteins expressed in tissues and serum. To date, tissue profiling has been successfully utilized to detect proteins specific to various cancers, including those of non-small cell lung carcinoma and glioblastoma multiforme. The usefulness of histological analyses to predict soft tissue sarcoma (STS) behavior has plateaued, and a critical need exists to identify other means to objectively predict tumor grade and behavior. We describe tissue profiling as a tool for orthopaedic research, and review recent work utilizing the technology for detecting proteins that differentiate low grade from high grade STS. We used MALDI MS tissue profiling technology to detect differentially expressed proteins in high grade and low grade STS. LEVEL OF EVIDENCE: Level I, prognostic study.

Cell Cycle Proteins↗
PubMed2005

Fractures following radiotherapy and limb-salvage surgery for lower extremity soft-tissue sarcomas. A comparison of high-dose and low-dose radiotherapy.

BACKGROUND: The purpose of the present retrospective study was to determine the correlation between radiation therapy and the risk of postradiation fracture following combined therapy for the treatment of soft-tissue sarcomas of the lower extremity. METHODS: Three hundred and sixty-four patients with lower extremity sarcomas that had been treated with combined external beam radiation therapy and limb-salvage surgery were evaluated on the basis of a combined chart and data-base review. For the purposes of analysis, high-dose radiation was defined as 60 or 66 Gy and low-dose radiation was defined as 50 Gy. The timing of irradiation was defined as preoperative, postoperative, or preoperative followed by a postoperative boost. Univariate and multivariate analyses were used to determine which factors were associated with fracture risk. RESULTS: Twenty-seven fractures occurred in twenty-three patients. Twenty-four fractures occurred in twenty patients who had been managed with high-dose radiation. Seventeen of these patients had received postoperative radiation (with fifteen patients receiving 66 Gy and two receiving 60 Gy), and three had received preoperative radiation with a postoperative boost (total dose, 66 Gy). Three fractures occurred in three patients who had received preoperative, low-dose radiation (50 Gy). Of the twenty-three patients who sustained a pathologic fracture, eighteen were female and five were male. The crude median time to fracture was forty-three months. Most fractures occurred in the femoral shaft (thirteen) or the femoral neck (eight). High-dose radiation was associated with a greater risk of fracture when compared with low-dose radiation (p = 0.007). CONCLUSIONS: Women more than fifty-five years of age who are managed with removal of a thigh sarcoma combined with radiation therapy have a higher risk of pathologic fracture. The frequency of pathologic fractures associated with higher doses (60 or 66 Gy) of radiation is significantly higher than that associated with lower doses (50 Gy).

Adolescent↗
PubMed2004

Evolution of an in vivo bioreactor.

The ideal bone graft substitute requires osteoconductive, osteoinductive, and osteogenic components. This study introduces an "in vivo bioreactor," a model in which pluripotent cells are recruited from circulating blood to a vascularized coralline scaffold supplemented with bone morphogenetic protein-2 (BMP-2). The bioreactor generates new, ectopic host bone with the capability of vascularized tissue transfer. More importantly, bone is reproducibly formed in a closed and malleable environment. In a rat model, the superficial inferior epigastric vessels were isolated, ligated, and then threaded through a prefabricated coral cylinder (hydroxyapatite, ProOsteon 500). Experimental groups were characterized by the following variables: (1) with/without incorporation of vascular pedicle; (2) with/without addition of BMP-2 (0.02 mg/cm3). Scaffolds were harvested 6 weeks after implantation, embedded and sectioned. Tissue samples were decalcified, fixed, and stained with H&E, trichrome green, and CD31/PECAM-1 (a marker of endothelial cells). Vascularized coral scaffolds supplemented with BMP-2 presumably recruited circulating mesenchymal stem cells to generate bone. Bone formation was quantified through histological analysis, and reported as a percentage, area bone/area cross section scaffold x 100. Mean bone formation was 11.30%+/-1.19. All scaffolds supplied by the vascular pedicle, regardless of BMP-2 supplementation, demonstrated neo-vascular ingrowth. Scaffolds lacking a pedicle showed no evidence of vascular ingrowth or bone formation. This paper introduces a model of a novel "in vivo bioreactor" that has future clinical and research applications. The tissue engineering applications of the "bioreactor" include treatment of skeletal defects (nonunion, tumor post-resection reconstruction). The bioreactor also may serve as a unique model in which to study primary and metastatic cancers of bone.

Animals↗
PubMed2004

Use of custom triflanged acetabular components in revision total hip arthroplasty.

Difficulty persists in consistently treating massive acetabular defects in revision total hip arthroplasty. A relatively new treatment option for these complex cases is a custom triflanged acetabular component created from anatomic data derived from a computed tomography scan of the pelvis. The custom triflanged acetabular component achieves fixation on the remaining ilium, ischium, and pubis with multiple fixation screws while the acetabular defect is filled with cancellous allograft bone. A retrospective review was done of 26 hips (26 patients) with massive periacetabular bone loss (Paprosky Type 3B) reconstructed with a custom triflanged acetabular component. Twenty-three of 26 patients (88.5%) were considered clinically successful at short-term followup (average, 54 months; range, 24 to 85 months), with stable fixation and reconstruction of periacetabular bone. Three failures occurred from loss of ischial fixation in two patients with a preoperative pelvic discontinuity and one patient with severe osteopenia. These devices should be used with caution in patients with a preoperative pelvic discontinuity unless additional column plating is done.

Acetabulum↗
PubMed2003

Pelvic C-clamp in a pediatric patient.

The pelvic C-clamp was designed to provide posterior stability temporarily to pelvic ring injuries associated with massive venous hemorrhage in adult patients. Pediatric pelvic ring injuries are uncommon, but when unstable injuries occur they may be coupled with visceral injuries and lethal hemorrhage. 1, 2 Anterior external frame fixators have been described in the treatment of these injuries in pediatric patients with few adverse outcomes and good long-term results. Although they provide adequate fixation, anterior frame application is complicated, time-consuming, and cumbersome as an emergency application. The pelvic C-clamp eliminated these problems, while providing fixation points that do not violate areas of cartilage or physeal growth. We present a case demonstrating that the pelvic C-clamp is a safe form of temporary fixation in a skeletally immature patient with a posterior pelvic ring injury associated with massive hemorrhage.

Child↗
PubMed2003

The role of patellar resurfacing in total knee arthroplasty.

The ideal treatment of the patella in primary total knee arthroplasty (TKA) for osteoarthritis (OA) remains unclear. Although data exist in the literature to support either resurfacing or not resurfacing the patella, evidence continues to emerge that unresurfaced patellas deteriorate with time. Recent prospective, randomized studies also favor patellar resurfacing over retaining the native patella, reporting reoperation rates to convert unresurfaced to resurfaced patellas exceeding those for complications after patellar resurfacing. In addition, the incidence of residual patellofemoral pain after secondary resurfacing is substantially higher than when patellofemoral resurfacing is done primarily. Patient selection criteria are critical in the decision-making process. Patellofemoral complications, the greatest argument against resurfacing, have been diminished with improved surgical techniques and implant design.

Arthroplasty, Replacement, Knee↗