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Biomedical subjects

J Makley

Publications and source records attributed to J Makley.

5 recordsLinked to original sources

Myositis ossificans-like lesion of nerve.

An unusual ossifying lesion arising within the median nerve of a young adult male is presented. While ectopic ossification has been described in a large number of sites, intraneural ossification is an uncommon event and usually occurs in association with a pre-existing intraneural neoplasm. This case, in contrast, bears striking histopathological resemblance to myositis ossificans with prominent zonation. We believe that this may represent the first example of a benign myositis ossificans-like lesion of nerve.

Adult↗

Treatment of osseous metastases secondary to renal cell carcinoma.

Osseous metastases occur in 25 to 50% of the patients with metastatic renal cell carcinoma. We retrospectively reviewed our experience with 14 patients who underwent 20 palliative orthopedic procedures for treatment of bony metastases secondary to renal cell carcinoma. Of the patients 6 presented after nephrectomy (group 1) and 8 presented initially with osseous metastases (group 2). Only 1 of the group 2 patients underwent adjunctive nephrectomy. Overall, 5 of 14 patients (36%) presented with fracture and 9 of 14 (64%) presented with impending fracture. Five patients required multiple procedures. A total of 7 lesions had been previously treated with external radiation. Of the 20 orthopedic procedures 17 (85%) resulted in significant functional improvement and 18 (90%) resulted in significant relief of pain. There were 4 major complications in the series, including 2 culminating in amputation. Average survival after palliative orthopedic procedures was 22 months (range 7 to 64 months) with a 1-year survival rate of 58%. Orthopedic palliation of osseous metastases from renal cell carcinoma is effective, and our experience indicates that the majority of renal cancer patients with bone metastases will survive long enough to benefit from palliative orthopedic procedures.

Adult↗

Localization of GD2-specific monoclonal antibody 3F8 in human osteosarcoma.

3F8 is a murine IgG3 monoclonal antibody specific for the antigen disialoganglioside GD2. Immunofluorescence staining showed strong binding of 3F8 to 15 of 17 human osteosarcomas, including primary and metastatic tumors. The targeting potentials of the native monoclonal antibody (3F8) and the F(ab')2 fragment (p-3F8) were tested in BALB/c athymic nude mice xenografted with human osteosarcomas. After radiolabeling with iodine using the chloramine T method, both 3F8 and p-3F8 retained immunoreactivities. The irrelevant IgG3 antibody TIB114 and its F(ab')2 fragment were used as negative controls. A Ewing's sarcoma xenograft, which was low in GD2 antigen, was also studied for comparison. Mice were sacrificed 1 day and 4 days after i.v. antibody injection. 3F8 and p-3F8 showed preferential accumulation in osteosarcoma over normal tissues with tumor:nontumor ratios of 2.7-58:1 and 1.4-82:1, respectively, on Day 1. These ratios improved to 10-163:1 and 6.0-75:1 on Day 4. The intact antibody 3F8 showed selective tumor uptake with a much higher percentage of injected dose per g than the fragment p-3F8 and exhibited a longer tissue half-life than p-3F8. These data indicate that anti-GD2 monoclonal antibodies may be useful for imaging and targeted therapy of human osteogenic sarcoma. The F(ab')2 fragment has the advantage of achieving favorable tumor:nontumor ratios sooner after antibody injection while the intact antibody shows better retention by tumor tissues.

Animals↗

A randomized study comparing high-dose methotrexate with moderate-dose methotrexate as components of adjuvant chemotherapy in childhood nonmetastatic osteosarcoma: a report from the Childrens Cancer Study Group.

Methotrexate (MTX) has demonstrated significant activity against relapsed and metastatic osteosarcoma. However, there is little published data to indicate the appropriate dose for MTX when given as a component of a multidrug regimen for the treatment of osteosarcoma. Therefore, the investigators at the Childrens Cancer Study Group undertook a randomized clinical trial that compared Adriamycin and vincristine given with either high-dose methotrexate or moderate-dose methotrexate as postoperation chemotherapy in the treatment of childhood osteosarcoma. We report here the results for 166 patients with completely resected nonmetastatic disease of an extremity. The two therapies demonstrated equivalent disease-free survival (DFS). Further, no therapy prejudices survival after relapse. Approximately 38% of patients remain disease free 4 years after diagnosis. Two relapses occurred in patients free of disease at least 36 months after initiation of treatment. Some factors found by other investigators to be prognostic of poorer DFS, namely, male sex, primary tumor in the humerus or femur, and larger primary tumors, demonstrated similar though not statistically significant trends. The presence of spontaneous necrosis in the tumor sample from the definitive surgery was associated with poor prognosis for DFS. We postulate that this feature represents rapidly growing tumors with increased potential for metastases.

Adolescent↗

Local recurrence, rate and sites of metastases, and time to relapse as a function of treatment regimen, size of primary and surgical history in 62 patients presenting with non-metastatic Ewing's sarcoma of the pelvic bones.

This report reviews the experience of 62 patients who presented between 1972 and 1978 with non-metastatic Ewing's sarcoma of the pelvis and were entered on IESS I. Seventeen patients (27%) developed a local recurrence, 38 patients (61%) demonstrated metastases and 21 (34%) neither. In the dose range 4000 rad to 6000 rad no dose response could be detected for local control of tumor. Forty-six patients (74%) had a biopsy or exploratory surgery only, 5 patients (8%) had an incomplete resection and 11 patients (18%) had a complete resection of their tumor. In the 46 patients having a biopsy only, 13 developed a local recurrence (28%) as compared to 2 of 11 patients undergoing a complete resection (18%). The most common sites for metastases were lung in 19 patients (31%) and bone in 23 patients (37%). No significant difference was noted in the frequency of overall metastases or metastases to any site between those patients receiving one of the three treatment regimens used in IESS I: VAC and Adriamycin (regimen I), VAC alone (regimen II) and VAC plus bilateral pulmonary irradiation (regimen III). At a median follow-up of 135 weeks no significant difference in median survival could be detected in patients with pelvic primaries between regimens I, II and III. The mean diameter of the pelvic primaries was comparable to the nonpelvic, however, one half of the pelvic cases were in the range 10-15 cm. The median time to relapse of the 241 non-pelvic patients on IESS I was 222 weeks as contrasted with the median time to relapse of 92 weeks in the 62 pelvic patients on the same study (p = 0.002). The possible reasons for the poor prognosis of pelvic primary patients are discussed together with treatment policies that might improve the survival of this group of patients.

Adolescent↗