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Biomedical subjects

J H Healey

Publications and source records attributed to J H Healey.

At least 19 recordsLinked to original sources
PubMed1995

Clinical reproducibility of dual energy x-ray absorptiometry.

Dual energy x-ray absorptiometry is a technique advocated for the measurement of bone mass throughout the skeleton, and recently it has been used to measure changes in periprosthetic bone mass after joint replacement. The accuracy and precision of the method in clinical patient populations have not been firmly established. This study sought to establish the short-term reproducibility of measurements made with dual energy x-ray absorptiometry of multiple sites in a large sample of elderly patients with rheumatic disease. Reproducibility was assessed in the lumbar spine and in three femoral sites in 69 patients participating in a longitudinal clinical trial. In each patient, absorptiometry was performed twice in the same day at as many as five time points over a 2-year period. The mean (+/- SD) baseline bone density was 0.783 +/- 0.128 g/cm2 for the femoral neck and 1.015 +/- 0.218 g/cm2 for the lumbar spine. The correlations between the duplicate baseline measurements of the spine were excellent (r = 0.9936, p < 0.001) and were stable over the 2-year period; the mean difference between the duplicate baseline measurements was 1.82 +/- 1.54% and the mean coefficient of variation was 1.29%. Measurements in the femur were much less precise; these values were 3.61 +/- 3.14% and 2.55% in the femoral neck, 3.66 +/- 4.35% and 2.59% in the greater trochanter, and 5.28 +/- 5.61% and 3.73% in Ward's triangle. This study evaluated the short-term reproducibility of dual energy x-ray absorptiometry in a clinical population.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1995

MDM2 and CDK4 gene amplification in Ewing's sarcoma.

Amplification of the MDM2 gene, which maps to chromosome band 12q13 and encodes a p53-binding protein, may result in functional inactivation of p53 and has been observed in various bone and soft tissue sarcomas. Published studies have included few cases of Ewing's sarcoma (ES) or peripheral neuroectodermal tumour (PNET), a tumour group in which alterations of the p53 pathway have so far not been extensively studied. We examined two ES cell lines, RD-ES and SK-ES-1, and 30 specimens from 27 patients (24 ES, 6 PNET; 19 primary, 4 local recurrence, 7 metastasis) for MDM2 gene amplification by Southern blot analysis. All 30 clinical specimens had been confirmed to contain sufficient ES/PNET DNA by the demonstration of a rearrangement of the t(11;22)-associated EWS gene using an EWS cDNA probe on the same blots. MDM2 gene amplification was detected in 3 of 30 specimens (10 per cent), including two ES and one PNET, but in neither of the cell lines. The three cases with amplification were morphologically typical primary tumours. Two of the three cases also showed co-amplification of the CDK4 gene, which encodes a cyclin-dependent kinase and also maps to band 12q13. Clinically, all three cases had metastatic disease at diagnosis, compared with only 1 of 15 MDM2-negative cases where the primary tumour was studied. The difference was statistically significant (P = 0.005), suggesting an association of MDM2 amplification with advanced stage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Giant cell tumor of the distal radius.

We compared the outcome of patients with giant cell tumor of the distal radius treated by curettage/cryosurgery and en bloc resection, evaluating oncologic success, functional results, and complications. Thirty consecutive cases of giant cell tumor of the distal radius were treated at our institution between 1958 and 1988. Twenty-six patients were available for follow-up examination, with a minimum follow-up period of 3 years and median follow-up period of 9 years. Primary curettage/cryosurgery had a local recurrence in 3 of 12, and repeat curettage/cryosurgery achieved local control in in 16 of 18 primary and recurrent cases. The major complications in this group included skin necrosis, transient nerve palsies, and fragmentation with carpal collapse. An average of 60% of contralateral range of wrist motion was preserved. Ten patients underwent en bloc excision and arthrodesis for either primary or recurrent tumor; none developed local recurrence. The main complication in this group was failure of internal fixation and non-union at the graft-radius junction. Resultant strength and function were similar in both groups. Intralesional excision with adjunctive cryosurgery is an effective alternative to en bloc excision with the advantage of preserving the distal radius and wrist joint function, but with a notable complication rate. En bloc excision with arthrodesis is more suitable for extensive local disease with poor residual bone stock and as salvage for failed intralesional excision.

Adolescent↗
PubMed1995

Very-high-dose short-term chemotherapy for poor-risk peripheral primitive neuroectodermal tumors, including Ewing's sarcoma, in children and young adults.

PURPOSE: To improve the prognosis of patients with poor-risk peripheral primitive neuroectodermal tumors (pPNETs; including peripheral neuroepithelioma and Ewing's sarcoma), while testing the feasibility of intensive use in adolescents and young adults of high-dose cyclophosphamide, doxorubicin, and vincristine (HD-CAV). PATIENTS AND METHODS: This report concerns previously untreated patients with newly diagnosed pPNET deemed poor-risk because of a tumor volume more than 100 cm3 or metastases to bone or bone marrow. The P6 protocol consists of seven courses of chemotherapy. Courses 1, 2, 3, and 6 include 6-hour infusions of cyclophosphamide on days 1 and 2 for a total of 4,200 mg/m2 per course (140 mg/kg per course for patients < 10 years old), plus 72-hour infusions of doxorubicin 75 mg/m2 and vincristine 2.0 mg/m2 beginning on day 1 (HD-CAV). Courses 4, 5, and 7 consist of 1-hour infusions of ifosfamide 1.8 g/m2/d and etoposide (VP-16) 100 mg/m2/d, for 5 days. Granulocyte colony-stimulating factor (G-CSF) and mesna are used. Courses start after neutrophil counts reach 500/microL and platelet counts reach 100,000/uL. Surgical resection follows course 3 and radiotherapy follows completion of all chemotherapy. RESULTS: Among the first 36 consecutive assessable patients (median age, 17 years), HD-CAV achieved excellent histopathologic or clinical responses in 34 patients and partial responses (PRs) in two patients. For 24 patients with locoregional disease, the 2-year event-free survival rate was 77%; adverse events were two locoregional relapses, one distant relapse, and one secondary leukemia. All six patients with metastatic disease limited to lungs achieved a complete response (CR) and did not relapse; one is in remission 36+ months from diagnosis, but the other patients are not assessable in terms of long-term efficacy of the P6 protocol because of short follow-up time (n = 3), additional systemic therapy (bone marrow transplantation), or septic death (autopsy showed no residual pPNET). All six patients with widespread metastases had major responses, including eradication of extensive bone marrow involvement, but distant relapses ensued. Myelosuppression was severe, but most patients received the first three courses of HD-CAV within 6 to 7 weeks. Major nonhematologic toxicities were mucositis and peripheral neuropathy. CONCLUSION: Excellent antitumor efficacy and manageable toxicity support the dose-intensive use of HD-CAV for pPNET in children, as well as in young adults. Consolidation of remissions of pPNET metastatic to bone and bone marrow remains a therapeutic challenge.

Adolescent↗
PubMed1995

Treatment of soft-tissue sarcomas of the hand.

We studied the clinical features, radiographic and pathological findings, treatment, and results for twenty-three patients who had been managed for a soft-tissue sarcoma of the hand between 1982 and 1990. The ages of the patients ranged from sixteen to seventy-six years (median age, thirty-one years). The most common clinical finding was a small, painless soft-tissue mass. Twenty of the tumors were high-grade, and eighteen were less than five centimeters in diameter. The most common diagnosis was synovial sarcoma, which was identified in eight patients. Leiomyosarcoma, rhabdomyosarcoma, and malignant fibrous histiocytoma developed in three patients each; epithelioid sarcoma, in two patients; and angiosarcoma, liposarcoma, neuroectodermal tumor, and clear-cell sarcoma, in one patient each. Curative wide excision or amputation was attempted in twenty-two patients; the margins were positive for tumor cells in eight, and local recurrence was seen in nine. Of the twenty-three patients, fourteen had survived, without evidence of disease, after a median duration of follow-up of forty-nine months, and nine had died of disease. The median rate of survival did not differ significantly on the basis of the size or grade of the tumor or the use of adjuvant treatment. However, the rate of survival of the patients who had a soft-tissue sarcoma of the hand that was less than five centimeters in diameter was significantly lower (p = 0.0008) than that of 152 patients who had a similar tumor at another site in an extremity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

A custom distal femoral prosthesis for reconstruction of large defects following wide excision for sarcoma: results and prognostic factors.

Between 1979 and 1986, 37 patients with sarcoma of the distal femur underwent limb salvage using a custom prosthetic knee replacement. Thirteen (35%) had early complications. Fourteen (38%) had late complications, which consisted of 6 aseptic femoral loosenings, 1 aseptic tibial loosening, 2 tibial fractures, 2 contractures, 1 femoral fracture, 1 prosthetic fracture, and 1 septic loosening. By 1988, nine patients died. Thirteen prostheses failed in 12 patients, resulting in 9 revisions, 2 above-knee amputations, and 2 Van Nes rotationplasties. The 2- and 5-year prosthetic survival rates were 82% and 57%, respectively. Twenty-two of the 26 survivors (85%) had successful limb salvage. Preventable factors were implicated in the loosening of six femoral components and in one femoral fracture. The mean Hospital for Special Surgery Knee Score was 69 (range: 62 to 86).

Adolescent↗
PubMed1995

The treatment of aneurysmal bone cyst.

Forty-four patients with aneurysmal bone cysts were treated with curettage with or without bone grafting, and in 26 (59%) recurrence developed. Of 11 patients treated with radiation, in only 1 (9%) the disease was not controlled. In 1 patient, radiation-induced sarcoma developed. Since the introduction of cryosurgery 27 years ago, 51 patients have been treated with cryosurgery. The patients had an average age of 13 years (range, 2-32 years). Thirty-four primary aneurysmal bone cysts and 17 secondary aneurysmal bone cysts occurred in association with 7 giant-cell tumors, 5 chondroblastomas, 2 fibromyxomas, 2 nonossifying fibromas, and 1 unicameral bone cyst. The tumors were classified as inactive in 9 patients, active in 31, and aggressive in 11. Treatment consisted of local intralesional excision followed by application of liquid nitrogen. The defect was either allowed to heal spontaneously (n = 26) or was reconstructed using an intramedullary rod (n = 2), bone grafts (n = 5), fibular strut grafts (n = 14), or polymethylmethacrylate with Steinmann pins (n = 4). At median followup of 85 months (range, 24-311 months), the overall cure rate was 82%. This was increased to 96% after a second, or repeat, cryosurgery. The disease in all patients eventually was controlled by cryosurgery. The mean functional rating was 90% (range, 63%-100%). Intralesional excision with adjunctive cryosurgery is an effective method for the treatment of aneurysmal bone cyst.

Adolescent↗
PubMed1994

Fibroblast activation protein: purification, epitope mapping and induction by growth factors.

The human fibroblast activation protein (FAP) defined by monoclonal antibody (MAb) F19 is a cell surface antigen expressed in reactive stromal fibroblasts of breast, colorectal, lung and other epithelial cancers. In contrast to its stroma-specific localization in epithelial neoplasms, FAP is expressed in the malignant mesenchymal cells of bone and soft tissue sarcomas. FAP is transiently expressed in some fetal mesenchymal tissues but is absent or expressed at low levels in most adult tissues. FAP is induced in cultured fibroblasts and, in these cells, consists of a M(r) 95,000 subunit (FAP alpha) carrying the F19 epitope and a non-covalently bound M(r) 105,000 subunit (FAP beta) lacking the F19 epitope. Using MAb F19 and 5 newly derived MAbs, we identify 3 distinct epitopes on FAP alpha and tentatively assign one epitope to FAP beta. Analysis of detergent extracts of a FAP alpha high beta- sarcoma cell line by size exclusion-high performance liquid chromatography (HPLC) revealed that FAP alpha does not elute as a M(r) 95,000 species but as part of a high-molecular weight complex (M(r) > 400,000) that dissociates into M(r) 95,000 subunits in SDS gels. Immunoaffinity purification of FAP alpha followed by tryptic digestion, reversed-phase HPLC and microsequencing identified 3 unique FAP alpha peptides, with 2 showing sequence similarity (23/38 identical amino acids) to segments of CD26, a T-cell activation antigen. CD26 is a membrane-bound enzyme (dipeptidyl aminopeptidase IV), but immunopurified FAP alpha has little if any dipeptidase activity with typical CD26 substrates. Finally, studies with FAPlow leptomeningeal fibroblasts revealed that transforming growth factor-beta, 12-O-tetradecanoyl phorbol-13-acetate and retinoids can upregulate FAP expression, whereas serum and several other factors had no or little effect on FAP levels. FAP and CD26 may belong to a family of structurally related but functionally distinct activation proteins that are expressed on different cell types and show unique modes of regulation in normal and malignant cells.

Amino Acid Sequence↗
PubMed1992

Identification of endosialin, a cell surface glycoprotein of vascular endothelial cells in human cancer.

Cell surface antigens of transformed cells are the traditional targets for antibody-guided detection and therapy of solid neoplasms. Alternative targets may be found in the tumor stroma, which contains newly formed blood vessels, reactive fibroblasts, and extracellular matrix proteins. The F19 cell surface glycoprotein of reactive fibroblasts is a prototypic stromal antigen since it is found in the stroma of > 90% of common epithelial cancers but is absent or expressed at low levels in normal tissues and benign epithelial tumors. In the present study, we define an additional tumor stromal antigen, FB5, that is selectively expressed in vascular endothelial cells of malignant tumors. Immunohistochemical analysis of 128 tumors identified FB5 in endothelial cells in 67% of the samples (including 41 of 61 sarcomas, 26 of 37 carcinomas, and 18 of 25 neuroectodermal tumors) whereas normal blood vessels and other adult tissues tested lacked FB5 expression. In vitro studies showed that FB5 is a M(r) 165,000 cell surface glycoprotein, comprised of a M(r) 95,000 core polypeptide and highly sialyated O-linked oligosaccharides but few if any N-linked sugars, and that the FB5 gene is located on chromosome 11q13-qter. The restricted tissue distribution of the FB5 protein, which we refer to as endosialin, suggests strategies for tumor imaging and therapy that are aimed primarily at the tumor vasculature.

Adult↗
PubMed1992

Soft-tissue management with prosthetic replacement for sarcomas around the knee.

The soft-tissue management was reviewed in 46 consecutive primary and nine revision segmental knee resections with prosthetic reconstruction performed for sarcomas around the knee. From January 1983 until August 1986, before the extensive use of free-tissue transfer in these patients, 20 primary segmental knee reconstructions were performed with five patients receiving gastrocnemius rotation flaps, and one patient receiving a late free flap (Group I). In this group, three patients were converted to an above-knee amputation because of wound problems. From August 1986 to August 1988, free-tissue transfer was available and extensively used in addition to rotation flaps to manage 26 primary (Group II) and nine revision (Group III) segmental knee reconstructions. In contrast to Group I, none of the patients in Groups II or III required amputation or conversion to a nonlimb-sparing procedure for soft-tissue management. None of the patients in this study received radiation therapy to their extremities. Chemotherapy protocols were similar in Groups I and II with 22 of 26 patients in Group I and 19 of 20 in Group II receiving treatment. The availability and expertise to perform free and rotational flaps at the time of initial excision provides greater selection and improved outcome for those patients whose wounds are closed primarily. The capability to perform free and rotation flaps at initial resection and for postoperative wound management is a major determinant of ultimate success in patients having reconstruction after excision of sarcomas about the knee.

Bone Neoplasms↗
PubMed1991

Multiple giant cell tumors and Paget disease of bone: radiographic and clinical correlations.

The clinical and radiographic findings of four patients with multicentric giant cell tumor (GCT) of bone and Paget disease were retrospectively reviewed. Three patients underwent magnetic resonance (MR) imaging evaluation; all patients underwent computed tomography (CT). The MR characteristics of the bone component in pagetic GCT appeared to reflect the pagetic phase; a sclerotic pattern was largely represented by hypointense marrow signal intensity on images obtained with both long and short repetition times (TRs) and echo times (TEs). Conversely, a tumor appearing in a mixed pagetic phase demonstrated more heterogeneous signal intensity with all pulse sequences. Extensive soft-tissue components, noted in all cases, showed largely intermediate signal intensity on short TR/TE images and foci of increased signal intensity on longer TR/TE images. In most cases, dramatic reduction in tumor bulk was noted with the use of steroids alone. An awareness of this entity is important because the appearance of lytic lesions with soft-tissue extension in patients with Paget disease does not necessarily imply a grave prognosis. Serial CT or MR imaging is helpful in monitoring the remissions and exacerbations that reflect response to therapy in Paget disease and GCT.

Aged↗
PubMed1991

Radiation and pagetic osteogenic sarcomas.

Radiation and pagetic osteogenic sarcomas should be distinguished from classical osteogenic sarcoma. Both occur in older patients with significantly greater comorbidity. Roentgenographically, radiation osteogenic sarcoma is typically sclerotic, whereas pagetic osteogenic sarcoma is lytic and associated with pathologic fracture. Radical resections give the best result, local control, and survival. Chemotherapy has not proven effective to date. Improvements in tumor imaging and more intensive chemotherapy regimens may permit limb-sparing surgery. Overall results remain poor, with approximately 15% five-year survival in each condition.

Adolescent↗
PubMed1991

The effect of chemotherapy on growth in the skeletally immature individual.

One hundred twenty-two children with nonmetastatic osteogenic or Ewing's sarcoma were studied to assess the effect of multiagent adjuvant chemotherapy on skeletal growth and final stature. No deviations from the height distributions of a normal population were noted at diagnosis. There was a marked retardation of linear growth during the year of intensive chemotherapy. Only 15% of the patients grew at the expected rate during that year. The distribution of nutritional status scores was significantly different at the end of the first year than at baseline. The distribution of ultimate height scores was significantly different than the baseline distribution. The overall final distribution was also significantly different from the normal population expectation. Any absolute difference in height, however, is likely to be small. The subgroups that were observed to full adult stature showed mean heights of 162 cm for girls and 176 cm for boys.

Adolescent↗
PubMed1991

Cardiac arrest during hip arthroplasty with a cemented long-stem component. A report of seven cases.

Seven patients had a cardiac arrest during hip arthroplasty with a cemented long-stem femoral component. Four patients died in the operating room, and three patients were successfully resuscitated. When the three survivors were eventually discharged from the hospital, they had no known permanent cardiac, pulmonary, or neurological sequelae. Factors that were common to all of the patients were advanced age, osteoporotic bone, a previously undisturbed intramedullary canal, and use of a long-stem femoral component and several batches of methylmethacrylate. Hip arthroplasty with a long-stem femoral component is associated with substantial risk in these patients. Excessive pressurization of cement should be avoided, and invasive hemodynamic monitoring should be used when the described conditions are present.

Aged↗
PubMed1991

Prosthetic arthroplasty of the knee after resection of a sarcoma in the proximal end of the tibia. A report of sixteen cases.

The results of a specific type of prosthetic reconstruction of the knee (total replacement arthroplasty) after resection of a sarcoma of the proximal part of the tibia in sixteen patients were retrospectively reviewed. The diagnosis was stage-IIB osteogenic sarcoma in nine patients, stage-IIB malignant fibrous histiocytoma in three patients, and stage-IB sarcoma of various types in four patients. The length of tibial resection ranged from 100 to 257 millimeters. Of the eleven patients who were available for functional examination (mean duration of follow-up, sixty-three months), three patients had an excellent result, seven had a good result, and one had a fair result. Of the five patients who were not available for functional testing, one who was doing well was lost to follow-up at eighty months, one had died of metastases at sixteen months, and three had had a secondary amputation for infection or for loosening of the prosthesis.

Adolescent↗
PubMed1990

31P NMR spectra of extremity sarcomas: diversity of metabolic profiles and changes in response to chemotherapy.

We have used 31P NMR spectroscopy to study 22 patients with suspected sarcomas prior to any treatment. The spectra are characterized by the same peaks noted in murine tumors. The mean pH was 7.14 +/- 0.08 and PCr/Pi was 1.18 +/- 0.83. Comparison of pH and PCr/Pi ratios in human and a murine tumor with a low hypoxic cell fraction revealed no significant differences. Six patients subsequently received chemotherapy and three responded to therapy (based on pathologic examination and/or tumor reduction greater than 50%). The three responding patients were noted to have significantly lower PDE/PME in their pretreatment spectra than the three nonresponding patients. The three responding patients with sarcomas also showed a rise of greater than 100% in PDE/PME during the first cycle of therapy. Two of the responding patients had an increase of 0.37 pH units during this interval, which was not detected in the nonresponding patients. These data suggest that 31P NMR spectroscopy may be a useful prognostic indicator in conjunction with other clinical parameters.

Animals↗
PubMed1990

Factors predictive of mortality in pediatric extremity rhabdomyosarcoma.

In order to examine factors predictive of fatal outcome in children presenting with histologically confirmed extremity rhabdomyosarcoma, we performed a retrospective analysis of our institutional experience from 1970 to 1985. Thirty-five patients were identified and staged according to international criteria (TNM). Variables evaluated for their predictive effect on fatal outcome included (1) tumor invasiveness, (2) tumor size, (3) anatomic location of the primary, (4) regional lymph node involvement, (5) distant metastases at presentation, (6) complete surgical resection, (7) use of amputation, and (8) alveolar histologic subtype. Significant predictors of mortality included (1) tumor invasiveness (P less than or equal to .0001), (2) regional node involvement (P less than or equal to .0002), (3) distant metastases at the time of presentation (P less than or equal to .001), (4) alveolar histology (P less than or equal to .001), (5) size of primary (P less than or equal to .007), and (6) completeness of surgical resection (P less than or equal to .05). In multivariate analysis, local tumor invasiveness was the most important predictor of fatal outcome with an associated relative risk of 18. We conclude that local tumor invasiveness is the most important determinant of clinical stage.

Adolescent↗