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Biomedical subjects

H S Schwartz

Publications and source records attributed to H S Schwartz.

At least 19 recordsLinked to original sources
PubMed1996

Analysis of variables affecting wound healing after musculoskeletal sarcoma resections.

Adjuvant treatment modalities, nutritional parameters, and allogenic blood transfusions are investigated as possible contributing variables which may adversely affect wound healing after tumor resections for musculoskeletal sarcomas. Statistical analysis determined that preoperative chemotherapy, depressed preoperative hematocrit, and allogenic blood transfusions (probably immunosuppression mediated) were the only significant factors affecting wound healing outcome. Suggestions to improve postoperative infection rates are discussed.

Analysis of Variance↗
PubMed1996

Chromosome telomere integrity of human solid neoplasms.

Eukaryotic chromosomes contain specialized structures at the termini called telomeres. This region of DNA is required for replication and stability of the chromosome. Telomere reduction can contribute to genetic instability and has been described in certain malignancies (e.g., colon, leukemia, giant cell tumor of bone). To determine whether telomere reduction is a generalized phenomenon in malignancies, the telomere integrity of genomic DNA isolated from tumor cells was determined from 39 individuals with 15 different malignancies categorized as musculoskeletal, epithelial, cranial, or other, and peripheral blood leukocytes from the same patient, when possible, or age-matched controls. Significant telomere reduction occurred randomly across histopathologic groups including giant cell tumor of bone, glioblastoma, colon cancer, and Wilms' tumor while telomere elongation occurred in chordoma. The other remaining 10 malignancies do not show significant differences in telomere lengths compared with controls.

Adolescent↗
PubMed1996

Lack of microsatellite instability in giant cell tumor of bone.

Microsatellite instability was searched for at six different loci on chromosome arms 5q, 18q, 15q, 17p, 19q, and 11p in 22 patients (12 men and 10 women; average age of 31.8 years, range of 20-55 years) with giant cell tumor of bone (GCT). These loci were chosen because of their use in microsatellite instability studies in other tumors such as colorectal cancer (e.g., 5q, 18q, 17p) or because of the presence of chromosomal abnormalities such as telomeric associations commonly occurring at 19q and 11p termini (thus the reason for including the 19q and 11p termini microsatellites in our study of GCT). No microsatellite instability or loss of heterozygosity were detected when comparing normal and tumor cells from any of the GCT patients. Unlike several other tumors, our study indicates that microsatellite instability does not appear to play a role in the tumorigenesis of GCT although other abnormal cytogenetic, biochemical, and molecular genetics data do exist for this musculoskeletal tumor.

Adult↗
PubMed1996

Heterogeneous survival rates for isolated skeletal metastases from melanoma.

In this study, the authors examine the survivorship of individuals who constitute the small subset of patients with Stage IV melanoma who present with their first and only detectable metastasis to the skeleton. One thousand two hundred six patients were identified with primary melanoma at the authors' institution since 1962. There were 14 patients with isolated (solitary) skeletal metastases. Survival was calculated by Kaplan-Meier technique. The survival rate for any individual with an isolated metastasis to the axial skeleton was 0. Three of 8 patients with melanoma metastases to the appendicular skeleton are alive at 18, 25, and 52 months after Stage IV detection. A statistically significant prolonged latency period (initial diagnosis to Stage IV) in the appendicular group compared with the axial group contributed to their significant survival rate advantage. The melanoma literature strongly supports the complete resection of soft tissue metastatic foci. These data support this concept and extend it to include isolated skeletal metastases. The mechanisms by which axial and appendicular skeletal metastases occur are significantly different. This difference manifests itself as a survival advantage for the appendicular group and warrants an aggressive surgical approach for these individuals.

Adult↗
PubMed1996

Caveat arthroscopy: definition and guidelines for prevention.

Caveat arthroscopy is defined as an arthroscopy done with the intention of managing intra-articular nonneoplastic disease that suddenly escalates into the surgical treatment of an extra-articular neoplasm. The term caveat arthroscopy is used to describe a maloccurrence, not an act of negligence. The purpose of this retrospective review is to provide examples of this entity, examine its consequences, and suggest guidelines for prevention. We identified 13 individuals who had caveat arthroscopy over a 6-year period. All but one case involved the knee. Diagnoses included 5 soft tissue sarcomas, 5 benign bone tumors, 2 skeletal sarcomas, and 1 benign soft tissue tumor. In each case, there were complications related to prereferral biopsy (ie, biopsy done before definitive management at a tertiary institution). Every subject had at least one untoward event consisting of either compartment contamination, inaccurate diagnosis, or delay in diagnosis. The best way to avoid the complications of caveat arthroscopy is to avoid the tendency to biopsy extra-articular lesions. Instead, adequate imaging of a suspected neoplasm should be done, and referral before biopsy should be considered.

Adolescent↗
PubMed1995

Telomerase activity and oncogenesis in giant cell tumor of bone.

BACKGROUND: Benign giant cell tumor of bone (GCT) is a primary skeletal neoplasm with an unpredictable pattern of biologic aggressiveness and cytogenetic findings characterized by telomeric associations and telomeric reduction. The role of maintaining telomeric integrity is performed by telomerase. To determine if telomerase activity is present, cell extracts from fibroblasts and tumor cells from five patients with GCT were analyzed and compared with HeLa (a positive control cell line). METHODS: Telomerase activity was detected by visualizing the extension of radioactive telomeric repeats on DNA sequencing gels. Telomere reduction was assessed using southern blot analyses of the restriction enzyme Hinf I digested DNA with a radio-labeled telomere probe. RESULTS: Telomerase or telomerase-like activity was detected in the cell extracts from HeLa and tumor cells. However, GCT telomerase activity varied and was less than that observed in HeLa, but no activity was detected from fibroblasts. In addition, telomere reduction was seen in DNA isolated from both HeLa and GCT but not in fibroblasts or age-matched controls. CONCLUSION: Telomere reduction and telomerase activity may be oncogenic sustaining events required to maintain the transformed phenotype seen in GCT.

Adult↗
PubMed1995

Osteosarcoma oncogene expression detected by in situ hybridization.

Fifteen archival human osteosarcoma specimens were examined by in situ hybridization for the expression of human and mouse transforming growth factor-beta (isoforms 1, 2, and 3), c-fos, and metalloproteinase (stromelysin-3 and matrilysin). Osteosarcoma subtypes were confirmed by review of patients' radiographs, histopathology, and age at diagnosis. The outcome and method of treatment were documented. The subtypes of osteosarcoma consisted of nine conventional osteosarcomas and two each of fibroblastic, telangiectatic, and post-radiation osteosarcomas. Each specimen was histologically examined under light microscopy, and then adjacent paraffin sections were assayed with sense and anti-sense RNA probes by in situ hybridization. The probes localized to the neoplastic cells, confirming the methodology of the technique. Human transforming growth factor-beta 1 had the most uniform binding affinity to the osteosarcomas examined and was more specific in binding than mouse transforming growth factor-beta 1. Specific mRNA encoding for the transforming growth factor-beta s, c-fos, and metalloproteinases are detectable in patterns within osteosarcoma cells, and collectively, their expression parallels the different histopathologic subtypes. The less differentiated subtypes (telangiectatic and post-radiation osteosarcomas) expressed the fewest molecular markers. Osteosarcoma is a heterogeneous tumor. Differential expression of matrilysin in osteosarcoma is the first reported detection of metalloproteinase activity in human skeletal sarcoma.

Adult↗
PubMed1995

Cytogenetic, telomere, and telomerase studies in five surgically managed lumbosacral chordomas.

Lumbosacral chordomas are rare skeletal sarcomas of the spine that originate from the remnant notochord. The understanding of this human cancer is limited to observations of its clinical behavior and its embryonic link. Thus, we performed chromosome and molecular analyses from five surgically harvested chordomas in an effort to document genetic and biochemical abnormalities which might aid in understanding the tumor biology of this understudied neoplasm. Cytogenetic analysis of the five chordomas revealed normal results in four patients and random abnormalities in only one tumor cell in the 100 cells studied from the fifth patient. A repeat telomeric probe (TTAGGG)50 was hybridized to genomic DNA isolated from chordoma cells (and HeLa cells) and digested with HinfI. The tumor DNA was paired with leukocyte DNA from age-matched controls and revealed telomere elongation in four of the four chordoma patients studied with molecular genetic techniques. Conversely, telomere length reduction has been reported during in vitro senescence of human fibroblasts, giant cell tumor of bone, colon cancer, intracranial tumors, childhood leukemia, Wilms tumor, and in HeLa cells. Telomerase activity (telomerase is required to maintain telomere integrity) was also determined by visualizing the extension of radioactive telomeric repeats on DNA sequencing gels. The telomeric fragments were assembled during incubation of the cytoplasmic extract containing telomerase. Telomerase activity was observed in HeLa (positive control and commercially available cell line), giant cell tumor of bone (positive control tumor cells from living patients), and in chordoma cells from one of the two chordoma patients (but to a lesser degree compared with HeLa). As expected, the chordoma patients' fibroblasts exhibited no telomerase activity.

Adult↗
PubMed1995

Structural allografts for reconstruction of lower extremity open fractures with 10 centimeters or more of acute segmental defects.

Long-term results on the use of structural allografts (> or = 10 cm) to reconstruct large skeletal defects sustained during high-energy, open lower extremity fractures have not been reported. Eight patients are retrospectively reviewed at postallograft time periods ranging from 18 to 93 months. Two patients required reoperation for noninfectious causes, and each healed uneventfully. Four individuals developed infectious complications, but only one required complete allograft removal (amputation). The others remain infection free at follow-up. Using any of three different rating systems, excellent functional outcome results from this method of reconstruction in an otherwise exceptionally challenging extremity for limb salvage.

Adolescent↗
PubMed1994

Dosage and allelic restriction fragment studies and PCR analysis of the H-ras locus in giant cell tumor of bone.

Several studies have shown that giant cell tumor of bone frequently exhibits telomeric associations, commonly at chromosome 11p, which is also the location of the H-ras oncogene. In addition, rare H-ras alleles are more common among cancer patients than among healthy controls and point mutations of this oncogene have also been reported in several malignancies. These data led us to investigate gene dosage, restriction fragment-length size, and point mutations for H-ras in giant cell tumor of bone. Quantitative Southern blot analysis revealed no amplification of the H-ras oncogene in tumor DNA compared with DNA from peripheral blood in the same patient or from control subjects. In addition, no point mutations were detected in codons 12, 13, or 61 (mutations of these codons have been reported in other neoplasms) of the H-ras gene. No differences were noted in restriction fragment-length polymorphisms between tumor and peripheral blood in the same patient and no loss of heterozygosity was detected. In addition, there was no increased frequency of rare H-ras alleles (8% of alleles) in giant cell tumor patients compared to controls (21% of alleles) in our study. However, large allele sizes (> 8.5 kb) were significantly overrepresented in GCT patients compared with healthy controls. In our study, three of 12 alleles were found to be rare in the healthy controls but were common among GCT patients. Our data suggest that the H-ras oncogene is unlikely to be the site of a biologically significant primary lesion in GCT tumorigenesis.

Adult↗
PubMed1994

Primary lymphoma and Paget's disease of the femur.

Malignant neoplasms associated with Paget's disease of the bone are most commonly metastatic and rarely primary malignant transformations. Sarcomatous transformations, such as osteogenic sarcoma, predominant in Paget's disease. The authors discuss the synchronous and synostotic occurrence of a primary lymphoma of bone in association with Paget's disease. The simultaneous occurrence of isolated primary lymphoma of bone and its phenotype in association with Paget's disease in the femur, which had not been rigorously documented in the previous literature, is reported.

Bone Neoplasms↗
PubMed1993

In vitro photodynamic therapy of musculoskeletal neoplasms.

Photodynamic therapy is a tumoricidal modality that utilizes an inactive pharmacologic agent that becomes activated on exposure to visible light. Neoplasms selectively retain and accumulate photosensitizers at levels generally higher than surrounding non-neoplastic tissues. The purpose of this study was to establish a testing method for in vitro investigation of the effects of photodynamic therapy on human musculoskeletal neoplasms by examination of the sensitivity of these tumors to photoactivation. Three human musculoskeletal neoplasms were cultured, exposed to the photosensitizer Photofrin, and then studied for their response to photodynamic therapy after laser activation. Giant-cell tumor, dedifferentiated chondrosarcoma, and osteosarcoma were examined with use of strict experimental controls. The photoradiation conditions during photodynamic therapy were kept constant. Cell viability was determined as a function of energy dose. We concluded that the three musculoskeletal tumors were susceptible to in vitro photodynamic therapy and the test system was reproducible. The optimal in vitro nontoxic incubation concentration of Photofrin was 3 micrograms/ml. A differential cytotoxic response to photodynamic therapy was exhibited by the musculoskeletal neoplasms as a function of increased dosages of energy.

Animals↗
PubMed1993

Lumbosacral chordoma resection: image integration and surgical planning.

Clinical, radiographic, and functional outcome parameters were analyzed before and after treatment of eight individuals with lumbosacral chordomas studied over a 3-year period. Emphasis was placed upon correlation of multiplane images and the pathoanatomy of the gross specimen. Surgical resections achieving wide margins can be curative. Magnetic resonance imaging of lumbosacral chordomas has revolutionized the preoperative anatomic localization of these tumors. Therefore, it is critical that the operating surgeon scrutinize the three-dimensional location of the tumor and its spatial relationship to surrounding structures prior to surgical eradication. A systematic approach for the radiographic analysis of tumor extent in lumbosacral chordomas is presented. Four strategic areas of preoperative analysis are identified for sacral chordomas and two for lumbar neoplasms. Functional outcome after resection is predicted by Stener's work. Contamination-free surgery is facilitated by accurate preoperative radiographic interpretation of the pathoanatomy by the surgeon.

Adult↗
PubMed1993

Telomere reduction in giant cell tumor of bone and with aging.

Giant cell tumor of bone is a benign, primary skeletal neoplasm that has an unpredictable pattern of biologic aggressiveness, and cytogenetically demonstrates genetic instability by exhibiting telomeric associations. Molecular analysis of telomeres from giant cell tumor of bone demonstrated reduction of telomere length (average loss of 500 base pairs) in eight individuals when compared with their leukocyte DNA. Those tumors which exhibited telomeric associations were found to have a greater reduction in telomere length than tumors not exhibiting them. For comparison, eleven cytogenetically healthy control individuals (7 females and 4 males, age range 2 weeks to 70 years) were included in this study. They demonstrated loss of telomere size (average 40 base pairs per year) with advancing age and the greatest rate of telomere reduction was identified in the young. Thus, the functional consequences of telomere shortening in a neoplastic cell may prove fundamental to sustaining the transformed phenotype in giant cell tumor of bone.

Adolescent↗
PubMed1993

Molecular analysis of transforming growth factor beta in giant cell tumor of bone.

Giant cell tumor of bone (GCT) is a primary bone neoplasm with unique cytogenetic findings including telomeric associations. Elevated expression of message RNA for transforming growth factor beta (TGF beta), but not transforming growth factor alpha (TGF alpha), has been reported in this tumor. Further investigation of GCT was undertaken to determine whether genetic loci for TGF beta in GCT patients with and without chromosome abnormalities are altered. Due to the reported TGF beta overexpression in GCT, qualitative and quantitative Southern blot analyses with TGF beta 1 and TGF beta 2 and an internal control probe (p3-21) were performed with tumor DNA and DNA from normal tissue on ten patients with GCT and control individuals. No obvious TGF beta 1 or TGF beta 2 gene alterations were detected. Normal copy numbers were calculated when comparing tumor and normal DNA from GCT patients as well as DNA from control individuals. Abnormal chromosome findings, including telomeric associations, marker chromosome, double minutes, chromosome fragments, ring chromosomes (possibly representing intra-chromosome telomeric associations), and polyploid cells were observed in seven of the ten patients with GCT. Chromosomes 11, 16, 19, 20, and 21 were most commonly observed in telomeric associations, with the terminus of the long arm of chromosome 19 being the most frequent. We conclude that there are no TGF beta 1 or TGF beta 2 gene alterations detected in GCT with the methodologies described, and that telomeric associations are a reproducible cytogenetic characteristic of this neoplasm.

Adult↗
PubMed1992

Cytogenetic abnormalities in a rare case of giant cell osteogenic sarcoma.

The cytogenetic analysis of a rare, nonirradiated case of giant cell tumor of bone with osteogenic sarcoma transformation is presented for the first time in a 19-year-old female. Telomeric associations involving 4p, 8p, 11p, 14p, 17p, 17q, and 20q were observed. Additionally, monosomy 13, 11p abnormalities and marker chromosomes were identified in tumor cells. Chromosome 11 involvement, particularly 11p translocations and 11p telomeric associations, were frequently observed in the tumor cells obtained from our patient, which suggests that chromosome 11p may play a role in the development of giant cell osteogenic sarcoma.

Adolescent↗