Search PubMedSearch

Biomedical subjects

J H Healey

Publications and source records attributed to J H Healey.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

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

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

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

Osteoarthrosis and congenital dysplasia of the hip in family members of children who have congenital dysplasia of the hip.

Four hundred and eight siblings, parents, and grandparents of seventy-eight children from the New England area who had congenital dysplasia of the hip were evaluated, by clinical examination and by measurements of the acetabulum on pelvic radiographs, for the signs and sequelae of congenital dysplasia of the hip. Six siblings and four mothers (representing seven of seventy-eight families) had been diagnosed with congenital dysplasia of the hip during childhood. The other ninety-one siblings were asymptomatic and had no radiographic evidence of dysplasia of the hip. In the adults in these families, acetabular coverage (as measured by the center-edge angle of Wiberg) was no different from that in the control subjects. There was no difference between the study group and the control subjects in the prevalence of osteoarthrosis of the hip or of osteoarthrosis that could be considered secondary to congenital dysplasia of the hip. The results indicate that children born to families that have a history of congenital dysplasia of the hip have a greater prevalence of this problem compared with the general population, but also that examinations of the hip in newborns are effective in detecting congenital dysplasia of the hip in such families. The greater prevalence of congenital disease of the hip among the siblings and mothers in these families is consistent with a multifactorial inheritance. The fact that acetabular development in the family members who did not have congenital dysplasia of the hip was no different from that in the control subjects suggests that acetabular dysplasia, rather than being an inherited abnormality, is secondary to subluxation or dislocation.

Acetabulum

The Van Nes tibial rotationplasty. A functionally viable reconstructive procedure in children who have a tumor of the distal end of the femur.

Twelve patients who had a malignant tumor of the distal end of the femur were treated with a Van Nes tibial rotationplasty. The survival rates were comparable with those for above-the-knee amputees and patients who had an endoprosthetic replacement. The results of functional testing showed that these patients performed as well as those who had endoprosthetic replacement and better than those who had above-the-knee amputation. Rotationplasty is therefore a favorable alternative to amputation or endoprosthetic replacement, either as a primary or as a salvage procedure.

Adolescent

Treatment of pathologic fractures of the distal femur with the Zickel supracondylar nail.

Thirteen patients with 14 pathologic, supracondylar, and distal femoral fractures were evaluated retrospectively. The Zickel supracondylar device was easy to use and applicable to a wide range of clinical problems. It provided good functional and symptomatic results in 11 of 14 cases. Two patients required a removal of metal implants due to soft-tissue irritation. Attention to the detail of insertion of the Zickel device may prevent complications.

Adult

Percutaneous bone marrow grafting of delayed union and nonunion in cancer patients.

Bone marrow is a source of osteoprogenitor cells that are key elements in the process of bone formation and fracture healing. Eight patients with primary sarcomas treated by extensive en bloc resections and reconstruction using internal fixation who developed delayed unions or nonunions were treated by injection of autogeneic bone marrow into the site of failed healing. Five of the eight patients received chemotherapy, with one patient receiving radiation therapy in addition. Bone formation was noted in seven patients after injection. Union was achieved in five of the patients. These results, obtained in difficult clinical circumstances, are encouraging and suggest that autogeneic bone marrow grafting is a useful technique in the treatment of delayed unions and nonunions and warrant further clinical studies.

Adolescent

Peak skeletal mass assessment in young adults with idiopathic scoliosis.

In 52 adult women with ages ranging from 20 to 35 years (mean age, 26.5 +/- 4.9 years) with scoliosis of the idiopathic type (mean, 44.7 +/- 17.4 Cobb degrees), bone density was assessed by conventional grading of the relative vertebral density (RVD) and the Singh trabecular index (STI). In vivo determinations of the bone mineral content (BMC) were performed in the radius, femur, and lumbar vertebrae by new noninvasive techniques of single (SPA)- and dual (DPA)-photon absorptiometry. Frequency distributions of scoliosis vs. control subjects with respect to RVD and STI grades showed interdependence to the P less than 0.01 level of significance. The mean BMC determinations of the radius (0.685 +/- 0.061 gm/sq cm) of the femur (0.947 +/- 0.110 gm/BA/sq cm) and of the vertebrae (1.091 +/- 0.105 gm/BA/sq cm) were markedly reduced compared with published control values (P less than 0.001). In comparison with the authors' institutional controls, mean BMC measurements were significantly lower for the radius (P less than 0.05) and for the femur (P less than 0.001). These results conclusively demonstrated that assessment of peak skeletal mass in a population of adult premenopausal women with idiopathic scoliosis showed significant decrease in average BMC measurements compared with control values. Maximal bone accretion was best evaluated at locations unaffected by deformity such as the radial diaphysis and the femoral neck.

Adult