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Biomedical subjects

J Tepper

Publications and source records attributed to J Tepper.

13 recordsLinked to original sources

Radiation-blocking shields to localize periarticular radiation precisely for prevention of heterotopic bone formation around uncemented total hip arthroplasties.

Sixteen patients (18 hips) were treated with localized radiation therapy limited to periarticular regions surrounding the femoral neck by shielding the prosthesis and the adjacent regions to prevent heterotopic bone formation around the uncemented prosthesis. All hips received 1500 rads. Eight of these hips were irradiated after excising severe heterotopic bone, five because they developed extensive heterotopic ossification in the opposite hip, and five others because they were considered to be at high risk for developing heterotopic ossification. Only two of the 18 hips developed a small amount of heterotopic bone after localized periarticular radiation. All wounds healed primarily. No progressive radiolucencies developed at the bone-prosthesis interface. There was only one trochanteric nonunion of six trochanteric osteotomies. Localized periarticular radiation therapy with precision shielding of the prosthetic components and adjacent skeletal structures is an effective means to prevent heterotopic bone formation around cementless total hip arthroplasties. It also has the advantage of not adversely affecting the healing of the trochanteric osteotomy.

Adult

Early B-lymphocyte precursor cells in mouse bone marrow: subosteal localization of B220+ cells during postirradiation regeneration.

The localization of early B-lymphocyte precursor cells in the bone marrow of young mice has been studied during recovery from sublethal whole body gamma-irradiation (150 rad). Initial studies by double immunofluorescence labeling of the B-lineage-associated cell surface glycoprotein, B220, and of mu heavy chains in bone marrow cell suspensions, demonstrated a sequential wave of regeneration of early B precursor cells, pre-B cells, and B cells. Early B precursor cells expressing B220 but not mu chains were enriched at 1-3 days following irradiation. After in vivo administration of 125I-labeled monoclonal antibody 14.8 to detect B220+ cells in situ, light and electron microscope radioautography of femoral bone marrow sections revealed concentrations of labeled B220+ cells located peripherally near the cortical bone at 1-3 days following irradiation, increasing in numbers in more central areas by 5-7 days. Proliferative B220+ precursor cells were found within layers of bone-lining cells and in a subosteal area characterized by a prominent electron-dense extracellular matrix, often associated with stromal reticular cells. The results demonstrate that the precursor cells that are active in the bone marrow early in the recovery of B lymphopoiesis after gamma-irradiation are located both within and near the endosteum of the surrounding bone. The distinctive extracellular matrix and stromal cell associations noted in this region may contribute to a supportive local microenvironment for early hemopoietic progenitor cells.

Animals

A comparative evaluation of rare earth screen-film systems. Free-response operating characteristic analysis and anatomic criteria analysis.

Diagnostic accuracy was evaluated in a signal detection experiment that used low-contrast acute lesions in a living dog model. At the high levels of certainty normally used by radiologists, rare earth screen-film systems provided accuracy comparable to that of a reference calcium tungstate screen-film system. Additionally subjective image quality evaluation for a given imaging task (clinical pediatric anterior-posterior chest films) based on visualization of anatomic landmarks and physical parameters has been conducted for several rare earth and one calcium tungstate screen-film system. The correspondence of subjective physical ranking with physical and psychophysical measurements was investigated. Evaluating the visualization of anatomic parameters can provide a clear and objective distinction among systems with comparable physical and psychophysical properties.

Animals

A randomized, prospective trial of adjuvant chemotherapy in adults with soft tissue sarcomas of the head and neck, breast, and trunk.

Since 1977, 31 patients were entered in a randomized, prospective study testing the efficacy of adjuvant chemotherapy after aggressive local treatment of high-grade sarcomas of the head, neck, breast, and trunk (excluding retroperitoneal sarcomas). All patients had complete resection of gross tumor and underwent postoperative radiotherapy (6000-6300 rads over 7-8 weeks). Seventeen patients received adjuvant chemotherapy consisting of doxorubicin (less than or equal to 550 mg/m2), cyclophosphamide (less than or equal to 5500 mg/m2), and methotrexate (less than or equal to 1000 mg/kg). Three-year actuarial disease-free survival in the chemotherapy arm was 77%, compared to 49% in the no-chemotherapy arm (P = 0.075). Three-year overall actuarial survivals in the two treatment arms, however, were 68% and 58%, respectively (P = 0.38). Considering only patients with tumors of the trunk (22 patients), 3-year actuarial disease-free survival in the chemotherapy arm was 92%, compared to 47% in the no-chemotherapy arm (P = 0.006). Actuarial 3-year overall survival in the chemotherapy arm was 82%, compared to 61% in the no-chemotherapy arm (P = 0.18). An additional 26 patients were treated in an identical fashion, but were not part of the randomized trial because of contraindications to chemotherapy, refusal to enter the randomized trial, or because they were treated before 1977 in a trial in which all patients received chemotherapy. Considering the entire group of 57 patients, follow-up ranged from 10 to 86 months (median, 35 months). Local control was achieved in 46 patients (81%); 3-year actuarial disease-free and overall survivals were 67% and 77%, respectively. A tendency toward improved disease-free survival was apparent among patients treated with chemotherapy (P = 0.018), but there was no statistically significant improvement in overall actuarial survival (P = 0.46). The subgroup of patients with sarcomas of the trunk (39 patients) demonstrated the greatest benefit from chemotherapy, with regard to disease-free survival (P less than or equal to 0.001). The most significant toxicity associated with chemotherapy was doxorubicin-induced cardiomyopathy, which resulted in clinically apparent congestive heart failure in five patients. Thus, the use of chemotherapy when combined with aggressive local measures appears to improve disease-free survival, but additional patients and longer follow-up are necessary to determine if improved overall survival will result.

Actuarial Analysis

Results of multimodality therapy of resectable soft-tissue sarcomas of the retroperitoneum.

Thirty-seven patients with resectable retroperitoneal sarcomas were studied prospectively to determine the efficacy of aggressive multimodality treatments. No patients was lost to follow-up, which ranged from 11 to 85 months (median 29 months). All patients received radiotherapy and some received postoperative chemotherapy (doxorubicin, cyclophosphamide, and high-dose methotrexate). A subset of 15 patients were entered into a prospective, randomized study testing the efficacy of adjuvant chemotherapy (eight received chemotherapy; seven did not). Two-year actuarial survival rates were inferior in the chemotherapy arm (100% versus 47%; p = 0.06), but the small number of patients precluded drawing definitive conclusions from this randomized study alone. Among the entire 37 patients (21 received chemotherapy; 16 did not) the actuarial 3-year survival rate was 43% and appeared unaffected by chemotherapy. Two patients suffered doxorubicin infiltration, three sustained cardiac toxicity, two developed cyclophosphamide-induced cystitis, and three withstood transient, severe bone marrow suppression. Eight patients suffered severe radiation enteritis, and one patient died after bowel resection for this problem. Thus the chemotherapy regimen we administered did not appear to improve survival but was associated with major morbidity. Radiotherapy was also associated with major complications, and since all patients received radiotherapy, it remains to be established if this modality is beneficial in improving survival.

Actuarial Analysis

Proton irradiation of malignant melanoma of the ciliary body.

This is our first case of malignant melanoma of the ciliary body treated with proton beam irradiation, a technique that we developed for irradiating choroidal melanomas. After 21 months of follow-up no growth of the tumour has been observed, and shrinkage of the tumour was noted on the follow-up photographs and by ultrasonography. The 32P uptake test, which was positive before treatment, turned negative 14 months after irradiation. The described technique of proton beam irradiation might offer an alternative for the treatment of ciliary body melanomas when the present techniques of iridocyclectomy cannot be applied because of the size of the lesion.

Ciliary Body

Cholinergic inhibition of methylphenidate-induced stereotypy: oxotremorine.

Lethality of orally administered oxotremorine for female mice required 250 times the dose that was effective for inhibiting methylphenidate-induced stereotypy. A number of lines of evidence indicate that increasing central cholinergic activity may be useful in various psychiatric syndromes and movement disorders. A relatively safe oral cholinomimetic would be clinically useful. Oxotremorine may be such an agent.

Animals

Proton irradiation of choroidal melanomas. Preliminary results.

Choroidal malignant melanomas in nine patients were treated with proton beam irradiation at the Harvard Cyclotron Laboratory, Cambridge, Mass. Each patient received five proton beam treatments in eight to ten days, totalling 4,730 to 8,570 rads at the tumor. No complications occurred during the treatment or follow-up period, which, at the time of this writing, ranges from one to 24 months, with an average of 12 months. No further growth of the tumor has been observed in any patient. Different signs of tumor regression have been noted. Resolution of the serous retinal detachments that accompanied some tumors is the earliest finding. Pigment changes over the surface of the tumor and adjacent pigment epithelium is a usual initial tumor response. Fluorescein angiography initially showed decreased leakage of dye; later, destruction of the tumor's vasculature and elimination of fluorescein leakage became evident. Only large choroidal vessels remained patient. Ultrasonography revealed decreased height of the tumors postirradiation, and the radioactive phosphorus (32P) uptake test, repeated in one patient, turned negative on postirradiation measurements.

Aged

Proton irradiation of small choroidal malignant melanomas.

Five patients with choroidal malignant melanomas were treated with proton irradiation with a cyclotron. We developed an accurate method of aiming the proton beam within the eye. Four to five tantalum rings, 2 mm in diameter, were sutured to the sclera at the edges of the tumor, which is localized by indirect ophthalmoscopy and transillumination. The rings were used as markers for stereotactic radiography to align precisely the tumors with the proton beam. The patients were given a total tumor dose of 4,730 to 6,670 rads, delivered in five equal fractions, over a period of eight to nine days. All patients tolerated the treatments well without any adverse effects. The tumor response to therapy could not be evaluated at the completion of treatment since there was no immediate observable reaction of the tumor or of the surrounding retina. Although there has been no definite regression in any patient, we observed a change in the "color" of the tumor in the first two patients and resolution of two serous retinal detachments.

Choroid Neoplasms

Carcinoma of the pancreas: review of MGH experience from 1963 to 1973. Analysis of surgical failure and implications for radiation therapy.

A retrospective study was done of all patients who were seen for definitive treatment of adenocarcinoma of the pancreas at the Massachusetts General Hospital from 1963 to 1973. There were a total of 145 patients. Thirty-one patients were treated with radical surgery, with a 16% operative mortality, a 5-year crude survival rate of 15%, and a local recurrence rate of 50%. Sixty-two patients were treated with biopsy alone, with no 5-year survivors. In addition, there were 35 patients who did not have a radical surgical procedure performed only because of the extent of the local disease. It is proposed that postoperative irradiation may reduce the incidence of local failure after radical surgery, and that preoperative radiation therapy or radiation therapy alone would be an appropriate treatment of those patients in whom the local extent of disease is initially too far advanced to perform radical surgery.

Adenocarcinoma

Explorotory study of proton radiation therapy using large field techniques and fractionated dose schedules.

Three patients have been treated with 160-MeV protons combined with high-energy photons to examine the advantages and difficulties associated with the clinical implementation of a program of large-field, fractionated-dose, protonradiation therapy. We havefound it necessary to 1) obtain an accurate three-dimensional determination of the treatment volume including the density of all tissues in the beam path; 2) construct an adequate bolus to compensate for tissue heterogeneities; 3) use much more precise and accurate immobilization and patient positioning devices than used in photon irradiation; 4) treat with both protons and photons so as to keep the skin dose within an acceptable level. IN TISSUES WITHOUT SIGNIFICANT INHOMOGENETIES DUE TO BONE AND AIR SPACES WE HAVE DELIVEREDA WELL-DEFINED DOSE TO INVOLVED TISSUES WHILE SPARING DISTAL SENSITIVE STRUCTURES. However, in those regions where there is much "fine structure" of tissue density, it has been difficult to compensate satisfactorily for the inhomogeneties.

Adult