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Biomedical subjects

H J Mankin

Publications and source records attributed to H J Mankin.

At least 19 recordsLinked to original sources
PubMed1995

Frequent incidence of extrapulmonary sites of initial metastasis in patients with liposarcoma.

BACKGROUND: The vast majority of soft tissue sarcomas spread initially to the lungs and then to other sites. The lung has been the most carefully monitored organ system during routine surveillance for a metastasis. Liposarcoma is one of the most common soft tissue sarcomas and has been noted to have extrapulmonary sites of initial metastasis. This study was undertaken to investigate both the frequency and distinguishing features of initial extrapulmonary metastasis in patients with liposarcoma. METHODS: A review of 60 patients with liposarcoma treated at the Massachusetts General Hospital (MGH) from 1971 to 1990 was performed. Survival and regression analyses were used to analyze disease free intervals and prognostic factors. RESULTS: Metastatic disease occurred in 37% of patients and local failure in 17%. Among the subset of patients who underwent primary definitive surgery at the MGH, the incidence of local failure was 3%. An unusually high incidence of extrapulmonary site of first metastasis was found. Isolated extrapulmonary disease was the site of initial metastasis in 59% of patients. In contrast to patients with an initial pulmonary metastasis, patients with an initial extrapulmonary metastasis had a statistically significant (P = 0.001) longer disease free interval from diagnosis to first metastasis. CONCLUSIONS: Liposarcoma, in comparison with other soft tissue sarcomas, has a different pattern of metastatic spread, with a tendency toward extrapulmonary sites. In addition, patients with extrapulmonary metastases have a longer disease free interval compared with patients with pulmonary metastasis.

Adolescent↗
PubMed1995

Transforming growth factor-beta: possible roles in Dupuytren's contracture.

Transforming growth factor-beta (TGF-beta) is a multifunctional polypeptide that stimulates extracellular matrix deposition and fibroblast proliferation. Because both these features characterize Dupuytren's contracture, we investigated a possible role for TGF-beta in the etiology of this disorder. We studied receptor expression for TGF-beta, effects of TGF-beta 1 on DNA-synthesis, and in vitro production of TGF-beta 1 and TGF-beta 2 in both normal and Dupuytren-derived fibroblasts. We also studied the effects of epidermal growth factor (EGF) on growth of the different cell types. TGF-beta receptor profiles were different between the two cell types, as were TGF-beta 1 and EGF-induced stimulation of cell growth. Both cell types secreted both active and latent TGF-beta. Our results suggest that growth factors such as TGF-beta and EGF may play a role in Dupuytren's contracture.

Adult↗
PubMed1995

Osteoid osteoma: percutaneous radio-frequency ablation.

PURPOSE: To evaluate a percutaneous technique for in situ destruction of osteoid osteoma. MATERIALS AND METHODS: Radio-frequency ablation was performed in 18 patients with osteoid osteoma (17 male, one female; age range, 8-42 years). Diagnosis was established by means of clinical and radiographic features and confirmed by means of needle biopsy findings. No attempt was made to remove the lesion. A small radio-frequency electrode introduced into the lesion through the biopsy track was used to produce thermal necrosis of a 1-cm sphere of tissue. RESULTS: Symptoms were completely relieved in 16 (89%) of 18 patients. In one patient, a second procedure was required for pain relief. All but two patients underwent treatment as outpatients: These two were hospitalized for 1 night only. All patients resumed normal daily activities immediately. No casts or external supports were required; there were no complications. Twelve patients were followed up for more than 1 year. There were no recurrences CONCLUSION: Radio-frequency ablation of osteoid osteoma is a promising alternative to surgery in selected patients.

Activities of Daily Living↗
PubMed1995

Role of surgical resection in pelvic Ewing's sarcoma.

PURPOSE: The improved survival in patients with Ewing's sarcoma over the past two decades has placed increased importance on achievement of local disease control. Ewing's sarcoma that arises in the pelvis has been recognized to have a worse prognosis than that in the appendicular skeleton, and the role of surgical resection in these cases remains controversial. The current study attempts to identify a benefit to surgical resection in these patients. METHODS: We retrospectively examined 39 patients who presented with Ewing's sarcoma in a pelvic location, all of whom were treated systemically with chemotherapy. Twenty patients received radiation only as a means of local control, and 19 underwent resection with or without radiation therapy. The patients were evaluated with end points of disease-free survival and overall survival for a minimum of 24 months and a mean of 58 months. RESULTS: There was an even distribution among patients who underwent surgical resection for local control as compared with those who received only radiation therapy with respect to age, site, date of treatment, and stage of disease. Despite uncontrolled biases including tumor size and response to chemotherapy that would be expected to favor patients who undergo resection, surgery in addition to or in substitution for radiation therapy did not result in a statistically significant increase in disease-free survival or overall survival. Local disease control was comparable between those who underwent resection and those who did not: three patients in each group developed a local recurrence. CONCLUSION: Currently, morbidity of surgical resection should be weighed against the efficacy and secondary complications of radiation therapy in the decision-making process for local disease control. The issue of whether overall survival and local disease control is improved in patients who undergo surgical resection remains controversial and may require a prospective randomized trial to be answered definitively.

Adolescent↗
PubMed1995

Enzyme replacement therapy for Gaucher disease: skeletal responses to macrophage-targeted glucocerebrosidase.

OBJECTIVES: Reversal of the hematologic and visceral abnormalities characteristic of Gaucher disease, the most common lipid storage disorder, with biweekly infusions of macrophage-targeted glucocerebrosidase (glucosylceramidase) is well documented. The extent to which the skeleton responds to enzyme replacement therapy has not been systematically investigated. METHODS: To assess the skeletal response to enzyme replacement therapy, we treated 12 patients with type 1 Gaucher disease, who had intact spleens, with macrophage-targeted glucocerebrosidase. The initial dose of enzyme was 60 U/kg body weight every 2 weeks for 24 months, followed by reduction in dosage to 30 and then 15 U/kg body weight every 2 weeks, each for 9 months. RESULTS: The lipid composition of bone marrow, determined by direct chemical analysis, began to improve after 6 months of treatment at a time when noninvasive imaging studies showed no significant changes. By 42 months, improvement in marrow composition was demonstrable on all noninvasive, quantitative imaging modalities (magnetic resonance score, quantitative xenon scintigraphy, and quantitative chemical shift imaging) used in this study. Quantitative chemical shift imaging, the most sensitive technique, demonstrated a dramatic normalization of the marrow fat content in all patients. Net increases in either cortical or trabecular bone mass, as assessed by combined cortical thickness measurements and dual-energy quantitative computed tomography, respectively, occurred in 10 patients. CONCLUSIONS: Prolonged treatment over 3 1/2 years with macrophage-targeted glucocerebrosidase produces objective reversal of disease in both the axial and appendicular skeleton in patients with Gaucher disease. Marked improvement occurs in marrow composition and bone mass in both children and adults.

Adolescent↗
PubMed1995

Flexural rigidity in partially demineralized diaphyseal bone grafts.

Control of biomechanical properties of demineralized diaphyseal bone allografts is required for their clinical application. Therefore, the changes in flexural rigidity in human fibulae were investigated as a function of the demineralization depth using a nondestructive bending test. Starting at the facies medialis, the flexural rigidity was determined in 24 planes at 15 degrees sequential angular increments, which allowed data collection around the circumference of the bone. Test bones included 4 pairs of left and right human fibulae and 15 single fibulae. The elliptical distribution of the flexural rigidity of left and right fibulae and single fibulae before and after demineralization was compared. The stiffness index and the area ratio were defined as parameters to describe the mechanical status of the test bones. Results show that the rigidity of diaphyseal bones is strongly dependent on the reduction of their cortical thickness by demineralization. A mathematical model allowing prediction of the reduction of the rigidity of diaphyseal bone grafts as a function of the demineralization depth is presented.

Adult↗
PubMed1995

Late development of a malignant fibrous histiocytoma at the site of a giant cell tumor.

A case of late development of a high grade malignant fibrous histiocytoma at the site of a previously surgically treated giant cell tumor is reported. The patient initially was treated for a benign giant cell tumor of the lateral condyle of the distal femur by curettage, implant of auto and allograft bone, but no radiation. Eighteen years later, he noted progressively increasing pain and disability. Radiographs showed some change, but magnetic resonance imaging clearly disclosed a tumor arising at the site and extending outside the bone. After chemotherapy, the tumor was resected and histologically showed no evidence of a recurrent giant cell tumor, only a high grade malignant fibrous histiocytoma.

Adult↗
PubMed1995

Calcific myonecrosis. A late sequela to compartment syndrome of the leg.

The clinicopathologic features of calcific myonecrosis are presented from results of an examination of 3 cases of this rare syndrome and review of the literature. Calcific myonecrosis is a painful, expansile, calcified mass that develops in muscle several decades after lower extremity trauma that typically has been associated with vascular injury. Plain radiographs show a well-defined and heavily calcified mass replacing the leg musculature. The calcifications are present in a thin, linear pattern and are organized around the periphery of the lesion. Smooth erosion of the adjacent bone may be present, whereas magnetic resonance imaging shows a heterogeneous signal with enhancement limited to the periphery of the mass. Pathologic features consist of a centrally cystic mass arising in muscle filled with friable, tan to dark red, soft debris. The cyst walls are firm and fibrous and contain many needle-like, elongated, calcified shards of necrotic tissue composed of hypocellular fibrous tissue with focal aggregates of hemosiderin-laden macrophages. The cyst contents are composed of necrotic skeletal muscle and acellular amorphous debris containing many cholesterol crystals, fibrin, and recent hemorrhage, including focal aggregates of organizing thrombus. The pathologic findings suggest that calcific myonecrosis might expand with time by virtue of recurrent intralesional hemorrhage into a chronic calcified mass that eventually becomes symptomatic. Surgical intervention is associated with a high rate of complication, particularly in cases in which intralesional procedures have been done.

Aged↗
PubMed1994

Expression of transforming growth factor-beta (TGF-beta) receptors, TGF-beta 1 and TGF-beta 2 production and autocrine growth control in osteosarcoma cells.

Transforming growth factor-beta (TGF-beta) is a polypeptide with multiple physiological functions. Isoforms of this growth factor have important roles in control of the cell cycle, in regulation of cell-cell interactions and in growth and development. Malignant transformation has been shown to be associated with increased expression of TGF-beta. Since bone is the largest storage site and producer of TGF-beta, we speculated on the existence of an autocrine mechanism in osteosarcoma, a malignant bone tumor. Expression of TGF-beta cell surface receptors, effects on growth of TGF-beta and TGF-beta antibodies and production of 2 TGF-beta isoforms were studied in a panel of 7 osteosarcoma cell lines. In contrast to most previous reports on the effects of TGF-beta on osteosarcoma cell growth, we found a mitogenic effect of TGF-beta 1 in 4 of 7 osteosarcoma cell lines. Receptor profiles for TGF-beta were aberrant in 5 of the 7 cell lines tested, and production of TGF-beta 1 and TGF-beta 2 varied among cell lines. Addition of anti-TGF-beta antagonized the effects of endogenous TGF-beta. Our results suggest a potential role of TGF-beta in autocrine growth control of osteosarcoma cells.

Antibodies↗
PubMed1994

An assay to measure adriamycin binding in osteosarcoma cells.

Adjuvant chemotherapy is currently employed in the treatment of patients with osteosarcoma, but the drug regimens, although effective in improving disease-free survival, are unsuccessful in 20-40% of patients and very toxic. It would be useful to know whether tumor cells are sensitive to a given drug prior to its use. To this end, we developed a method of assessing Adriamycin (doxorubicin) binding to tumor nuclei as a possible means of detecting sensitivity to the drug. Adriamycin-sensitive murine osteosarcoma cells were used to develop the assay. The in vitro conditions (drug concentration, duration of incubation, and temperature) were optimized with use of the murine osteosarcoma cells in culture. After the cells had been incubated with Adriamycin, cell viability was determined and Adriamycin fluorescence intensity was measured with a cytofluorometer. The optimal parameters for Adriamycin binding were found to be a 30-minute incubation in a 10 micrograms/ml concentration of Adriamycin at 37 degrees C; the frequency of cells that emitted Adriamycin fluorescence from the nucleus compared with the total number of living cells reached 100% under these conditions. In a murine leukemia cell line with known sensitivity to Adriamycin, the cells emitted red fluorescence from the nucleus and cytoplasm, whereas in a resistant line the cells emitted Adriamycin fluorescence from only the cytoplasm. We demonstrated that it is possible to differentiate nuclear from cytoplasmic concentration of Adriamycin in a tumor cell with use of a fluorescent microscope and that resistant cell lines can be distinguished from sensitive cell lines by this method.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Suramin inhibits growth and transforming growth factor-beta 1 (TGF-beta 1) binding in osteosarcoma cell lines.

Autocrine production of growth factors has been shown to be involved in the multistep process of tumorigenesis. The ability of suramin, a polyanionic anti-parasitic drug, to block growth factor-induced cell proliferation makes it a potential antineoplastic drug. We studied the effects of suramin on seven osteosarcoma cell lines. Using clinically achievable concentrations of suramin (50-400 micrograms/ml), we found a time- and dose-dependent inhibition of [3H]thymidine incorporation. We also showed that suramin is able, dose-dependently, to prevent binding of transforming growth factor (TGF)-beta 1 to its receptors. DNA synthesis inhibition by suramin was attenuated by TGF-beta 1 in some cell lines. Two cell lines that were inhibited by TGF-beta 1 were affected similarly by suramin as cell lines that were stimulated by TGF-beta 1. In conclusion, in five out of seven osteosarcoma cell lines, we showed a correlation between inhibition of growth factor-stimulated mitogenesis and binding of TGF-beta 1 to its receptor. Similar effects in TGF-beta 1-inhibited osteosarcoma cell lines suggest involvement of other mechanisms and/or growth factors. However, suramin proves to be a potent inhibitor of osteosarcoma cell proliferation in vitro.

Bone Neoplasms↗
PubMed1994

A complex bilateral polysyndactyly disease locus maps to chromosome 7q36.

We demonstrated that the gene responsible for a congenital limb deformity (polysyndactyly) maps to chromosome 7q36 in a large family. Pre- and postaxial anomalies of the extremities are inherited in this family as an autosomal dominant trait. The disease locus is closely linked to D7S550 (maximum lod score = 6.85, theta = 0). This region is homologous to a segment of mouse chromosome 5, where the mutations hammer toe (HM) and hemimelic extra toes (HX) have been mapped. These data suggest that human chromosome 7q36 and the homologous region of mouse chromosome 5 contain genes involved in limb pattern formation.

Base Sequence↗
PubMed1994

Osteoarticular allografts for reconstruction after resection of a musculoskeletal tumor in the proximal end of the tibia.

An osteoarticular allograft was used to reconstruct a skeletal deficiency in sixteen patients after resection of a tumor in the proximal end of the tibia. The status of each allograft and the condition of each involved limb were evaluated an average of nine years (range, six to fourteen years) postoperatively. The status of the allograft was evaluated according to the survival of the allograft and the occurrence of complications. Of the original sixteen allografts, seven were removed: six, between two and five years after the reconstruction and one, seven years after the reconstruction. A second reconstruction with use of an allograft was performed in five of the seven patients. Fifteen complications occurred in association with eleven of the original sixteen allografts. These included fracture of the allograft (five patients), subchondral collapse (five patients), infection (two patients), non-union (two patients), and instability of the joint (one patient). At the latest follow-up examination, nine patients had retained the original allograft, five had had a second allograft procedure, and two had had an above-the-knee amputation. The most recent result was rated excellent or good in eleven patients and fair or a failure in five, with use of the system of Mankin et al. It was rated good or excellent in nine patients and fair, poor, or a failure in six, and it was not rated in one patient who had died, according to the system of the Musculoskeletal Tumor Society.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Limb salvage compared with amputation for osteosarcoma of the distal end of the femur. A long-term oncological, functional, and quality-of-life study.

The outcome of treatment of nonmetastatic high-grade osteosarcoma in the distal part of the femur was studied in 227 patients from twenty-six institutions. Eight of the seventy-three patients who had had a limb-salvage procedure and nine of the 115 patients who had had an above-the-knee amputation had a local recurrence, but there was no local recurrence in the thirty-nine patients who had had a disarticulation at the hip. There were no significant differences in the rate of survival or in the duration of the postoperative disease-free period between the three groups. One hundred and nine patients (48 per cent) were alive at an average of eleven years after the operation, and ninety patients (40 per cent) remained continuously disease-free. An additional operation on the limb was necessary more often for patients who had had a limb-salvage procedure than for those who had had an amputation. Function in seventy-eight living patients was assessed with the system of the Musculoskeletal Tumor Society for evaluation of function and by the functional assessment portion of the 1989 scoring system of the Knee Society; the scores were higher for the patients who had had a limb-salvage procedure than for the two groups of patients who had had an amputation. No difference was identified between the groups with regard to the patient's acceptance of the postoperative state, the ability to walk, or the amount of pain. The quality of life was evaluated for twenty-nine patients with a series of complex questionnaires.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Psychological↗