Biomedical subjects

Herbert S Schwartz

Publications and source records attributed to Herbert S Schwartz.

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

Clonality studies in sacral chordoma.

Chordomas are rare, slow-growing, primary malignant skeletal neoplasms. Chromosome analysis, telomere reduction and telomere activity, DNA microsatellite, and loss of heterozygosity studies have been performed on chordomas; however, the clonality status (monoclonal versus polyclonal proliferation) is unknown. The primary purpose of this study was to determine whether sacral chordoma is monoclonal or polyclonal in origin with the use of a polymorphic X-linked gene (AR; alias HUMARA) and X-chromosome inactivation studies. DNA was harvested from tumor and corresponding normal tissue from eight women (37-71 years) with chordoma. Clonality was determined using an X chromosome inactivation protocol and a polymorphic human androgen receptor gene (AR) located on the X chromosome. The procedure required a methylation-specific polymerase chain reaction (PCR) and determination of the ratio of active to inactive X chromosomes. Results were informative for seven of the eight women, with two separate X-linked alleles seen for the AR gene in the normal tissue. Expression of AR gene alleles from each of the two X chromosomes was present in the chordoma tumor, indicating a polyclonal proliferation in all seven women. Most solid tumors and skeletal neoplasms are polyclonal in nature. Our study indicates that chordoma is polyclonal in its pattern of proliferation.

Adult↗

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

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↗

PubMed2006

Soft tissue perineurioma in a patient with neurofibromatosis type 2: a tumor not previously associated with the NF2 syndrome.

Neoplasms that commonly affect patients with neurofibromatosis type 2 (NF2) include schwannomas, meningiomas, astrocytomas, ependymomas, and neurofibromas. Perineuriomas are rare tumors of the peripheral nerve sheath that share some characteristics with meningioma. As in both NF2-associated and sporadic cases of schwannoma and meningioma, perineuriomas often harbor mutations or deletions of the NF2 gene. However, perineuriomas have not previously been reported in the clinical setting of NF2. A 30-year-old man with a history of bilateral vestibular schwannomas, a parasagittal meningioma, an intraspinal ependymoma, and multiple other neoplasms involving both cranial and peripheral nerves (thereby fulfilling the diagnostic criteria for NF2) presented with an enlarging thigh mass. The diagnosis of cellular soft tissue perineurioma was confirmed by both immunohistochemical and ultrastructural analysis. This case represents the first report of a soft tissue perineurioma arising in the setting of NF2.

Adult↗

PubMed2005

Allograft ankle arthrodesis: a limb salvage technique for distal tibial tumors.

UNLABELLED: Allograft ankle arthrodesis using a retrograde intramedullary tibial nail is a new strategy in limb salvage for treatment of distal intraarticular tibial tumors. After tumor resection, the ankle is reconstructed using an intercalary allograft and retrograde intramedullary fixation. We retrospectively reviewed nine consecutive patients with intraarticular resection of distal tibial tumors who had allograft ankle arthrodesis reconstruction between April 1994 and August 2000. Patient charts were reviewed for: (1) local recurrence, new metastases, and survival; (2) Musculoskeletal Tumor Society score; and (3) complications or reoperations or both. Only one of nine patients had a local recurrence. Eight of nine patients achieved independent ambulation. Eight of nine patients had a Musculoskeletal Tumor Society score greater than 73%. Six of nine patients required nine additional operations. No patients required flap coverage. There were no superficial or deep infections. Allograft ankle arthrodesis is a new alternative in limb salvage for distal tibial tumors. It has oncologic outcomes (rate of local recurrence, new metastases, and survival from time of diagnosis) and functional outcomes (Musculoskeletal Tumor Society score and rates of reoperation) comparable to previously reported and accepted methods of limb salvage. LEVEL OF EVIDENCE: Therapeutic study, Level IV (case series). See the Guidelines for Authors for a complete description of levels of evidence.

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↗

PubMed2003

Publication rates of abstracts presented at annual musculoskeletal tumor society meetings.

Beware of the unpublished abstract! What is the publication rate of abstracts presented at Musculoskeletal Tumor Society meetings, and how does this compare with other orthopaedic and medical meetings? Three hundred thirty-six podium presentations from six annual meetings were identified and their publication was searched at a minimum of 3 years after the event. An effort was made to determine what percent of these abstracts eventually were published in a peer-reviewed journal. It was determined that 137 abstracts were published for a publication rate of 41%. The average time between presentation at the meeting and publication was 21.8 plus or minus 13.5 months. The published articles appeared in 48 peer-reviewed journals. The rate of publication and time until publication was similar to other orthopaedic meetings and to other medical disciplines. Changes to the cohort, title, or authors occurred in approximately (1/3) of the published articles compared with the abstracts. These results suggest that for various reasons the majority of presented material at Musculoskeletal Tumor Society meetings may not survive peer review and may not be scientifically valid.

Abstracting and Indexing↗

PubMed2003

Orthopaedic malpractice claims in the VA medical system.

This study was undertaken to delineate the outcome of orthopaedic malpractice claims in the Veterans Affairs Medical Center (VAMC) system compared with the private sector. All orthopaedic administrative tort (malpractice) claims handled by the Office of Regional Counsel in Nashville, Tennessee during the 5-year period (8/93-7/98) were analyzed. Attention was directed at: 1) the number and type of claims, 2) the disposition of the claims, 3) the average award or settlement and range in size of awards (indemnity), and 4) the length of time required to process and dispose of each claim. These data were compared to those compiled in that segment of the private sector represented in the database of Physician Insurers Association of America (PIAA) for a similar five years (1/90-12/94). Twenty-six claims were filed in the 5-year study period and 22 were adjudicated by December 1999. Fourteen of 22 (64%) were defended successfully and eight (36%) resulted in an award to the claimant plaintiff. In the private sector those figures were 69% and 31%, respectively. The VAMC average indemnity was 20,404 dollars (range, 3500-100,000 dollars) versus 145,200 dollars in the private sector. Approximately 1% of all awards in the private sector were greater than 1,000,000 dollars. The length of time required by the VAMC to process and dispose of each claim ranged from 6 to 59 months and averaged 15.2 months. The settlement rate of orthopaedic medical malpractice claims involving the VAMC and the private sector is similar. It appears that the average award is greater in the private sector. This may reflect more claims and lesser awards in the VAMC. In both systems, most claims do not result in an indemnity.

Arthroplasty↗

PubMed2002

Galectin-3: a biologic marker and diagnostic aid for chordoma.

Galectin-3 is a beta-galactoside binding protein. Its expression is quantitatively and qualitatively altered during self-proliferation, malignant transformation, and tumor progression. Galectin-3 is a lectin-related molecule. Lectins are proteins that bind specific carbohydrate structures. Although their precise biologic function is unclear, the general idea is that these molecules operate in modulating cell-to-cell and cell-to-matrix interactions. Galectins have been implicated in cell growth and differentiation and seem to play a role in malignant transformation and metastasis. Galectin-3 is expressed in primitive notochord. The purpose of the current investigation was to identify an immunohistochemical marker to help distinguish the pathologically overlapping entities of chordoma from myxoid low-grade chondrosarcoma. Twelve of 16 (75%) chordomas stained positive for Galectin-3 whereas only one of 12 low-grade myxoid chondrosarcomas stained positive. Galectin-3 chordoma staining is 75% sensitive and 92% specific.

Adult↗