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Biomedical subjects

J Tepper

Publications and source records attributed to J Tepper.

At least 37 records · Page 2Linked to original sources
PubMed1984

A simple open-loop vibrating system for variable amplitude and frequency sinusoidal stretching of muscles.

A device designed to provide controlled variable amplitude and frequency sinusoidal stretching of muscles is described. The constructed vibrator included a pivoted lever with one arm fixed and the other variable, and was driven by an electric motor. The use of a powerful motor ensured that the stimulation parameters would not be significantly affected with tension changes in the muscle during contraction, which enables operating the system in an open-loop mode. This device is simple, low cost, and may be used in a variety of neurophysiologic studies with only conventional grounding, shielding, and noise suppression.

Animals↗
PubMed1983

Prospective randomized evaluation of adjuvant chemotherapy in adults with soft tissue sarcomas of the extremities.

Sixty-five patients with high-grade soft tissue sarcomas of the extremities were treated in a prospective randomized trial evaluating the efficacy of adjuvant chemotherapy with doxorubicin, cyclophosphamide, and high-dose methotrexate. Local therapy was administered using either amputation or wide local resection plus radiation therapy and the chemotherapy was begun in the immediate postoperative period. Actuarial analysis with median follow-up of 653 days revealed an advantage in continuous disease-free and overall survival in the patient group receiving chemotherapy (P = 0.0008 and P = 0.04, respectively, one-sided Mantel-Haenszel test). The continuous disease-free survival at three years is 92% in the chemotherapy group compared to 60% in the no chemotherapy group. Overall survival is 95% and 74% in these two patient groups. Fifty-eight percent of patients had limb-sparing surgery plus radiation therapy and 42% underwent amputation. In both treatment subgroups analyzed separately, chemotherapy resulted in an improvement in disease-free survival compared to randomized controls not receiving chemotherapy (P = 0.006 and P = 0.04 for groups receiving amputation and limb sparing, respectively). There were no local failures in the patients receiving chemotherapy and two local failures in the no chemotherapy group. The results of this trial confirm the historically controlled pilot trial performed in 26 patients between 1975 and 1977. A current update of the patients in the pilot trial, with a minimum four-year follow-up, reveals an improvement in disease-free and overall survival due to chemotherapy (P less than 0.002). Analysis of the previous pilot trial indicates that only few recurrences are seen beyond three years. Thus, it appears that adjuvant chemotherapy should be a part of the treatment adult patients with soft tissue sarcomas of the extremities.

Adult↗
PubMed1983

Effects of intraoperative electron irradiation in the dog on cell turnover in intact and surgically-anastomosed aorta and intestine.

Adult dogs were subjected to laparotomy and intraoperative electron irradiation after division and reanastomosis of aorta or after construction of a blind loop of small intestine having a transverse suture line and an end-to-side anastomosis. Dogs received intraoperative irradiation of both intact and anastomosed aorta or intestine in doses of 0, 2000, 3000, or 4500 rad. Animals were sacrificed at seven days or three months following treatment. At 24 hours prior to sacrifice, dogs received 5 mCi tritiated thymidine intravenously. Irradiated and non-irradiated segments of aorta and small intestine, including intact and anastomotic regions, were analyzed for tritiated thymidine incorporation and were subjected to autoradiography. Incorporation studies showed diminution in tritiated thymidine uptake by irradiated portions of aorta and small intestine, in both intact and anastomotic regions. Autoradiograms revealed that irradiated areas of intact or anastomotic aorta or intestine had diminished labeling of stromal cells, suggesting a lowered cell proliferative capacity of irradiated tissue compared to non-irradiated portions. Inflammatory cells showed similar labeling indices in irradiated and non-irradiated tissues, both intact and surgically-manipulated, suggesting that irradiation does not significantly affect a subsequent local inflammatory response. Radiation-induced decreases in tritiated thymidine incorporation in irradiated aorta and small intestine were generally more marked at seven days than at three months following irradiation, suggesting that radiation-induced depression of cell turnover rates decreases with time. The presence of tritiated thymidine uptake after irradiation demonstrates the ability of intact and surgically-manipulated aorta and intestine to recover from radiation-induced damage.

Animals↗
PubMed1983

Extremity preservation by combined modality therapy in sarcomas of the hand and foot: an analysis of local control, disease free survival and functional result.

A primary tumor arising in the hand or foot represents an uncommon presentation for patients with Ewing's sarcoma (ES) or soft tissue sarcoma (STS). While there exists considerable literature on the treatment of extremity sarcomas, very little deals specifically with lesions of the hand or foot. It remains controversial whether these lesions can be successfully treated with combined modality therapy which preserves the extremity and maintains function. From 1972 to 1979, 10 patients with sarcomas arising in the hand or foot were treated with combined modality therapy at the National Cancer Institute. Seven patients with ES of bone received local irradiation to 5000 rad and combination chemotherapy following an incisional biopsy. Three patients with STS received a gross tumor excision and local irradiation to 6000 rad. One STS patient also received combination chemotherapy. Local control was achieved in nine patients (90%) with a follow-up of 30-119 months (median 56 months). These patients have complete or almost complete function of the treated extremity. Nine patients are alive with five patients remaining disease-free following the initial combined modality treatment. Two patients with Ewing's sarcoma relapsed (1 patient with both local and distant failure) at 26 and 58 months and were again rendered disease-free with surgery, total body irradiation and further chemotherapy. One patient relapsed for a second time, being disease-free from the first relapse for 30 months. We conclude that for selected patients with sarcomas arising in the hand or foot, combined modality therapy which leaves the extremity intact results in excellent local tumor control and preserves function. Careful treatment planning is an essential aspect of successful radiation therapy of a hand or foot primary. Our treatment recommendations are outlined. This approach is a viable alternative to amputation in these patients.

Adolescent↗
PubMed1983

Experimental and clinical studies with intraoperative radiotherapy.

Studies of normal tissue tolerance to intraoperative radiotherapy were done upon 65 dogs subjected to laparotomy and 11 million electron volt electron irradiation in doses ranging from zero to 5,000 rads. Results of studies indicated that intact aorta and vena cava tolerate up to 5,000 rads without loss of structural integrity. Ureteral fibrosis and stenosis develop at doses of 3,000 rads or more. Arterial anastomoses heal after doses of 4,500 rads, but fibrosis can lead to occlusion. Intestinal suture lines heal after doses of 4,500 rads. Bile duct fibrosis and stenosis develop at doses of 2,000 rads or more. Biliary-enteric anastomoses fail to heal at any dose level. A clinical trial of intraoperative radiotherapy combined with radical surgery was performed upon 20 patients with advanced malignant tumors which were considered unlikely to be cured by conventional therapies and which included carcinomas of the stomach, carcinomas of the pancreas, carcinomas involving the hilus of the liver, retroperitoneal sarcomas and osteosarcomas of the pelvis. All patients underwent resection of gross tumor, followed by intraoperative irradiation of the tumor bed and regional nodal basins. Some patients received additional postoperative external beam radiotherapy. Treatment mortality for combined operation and radiotherapy occurred in four of 20 patients. Postoperative complications occurred in four of the 16 surviving patients. Local tumor control was achieved in 11 of the 16 surviving patients, with an over-all median follow-up period of 18 months. The clinical trial suggested that intraoperative radiotherapy is a feasible adjunct to resection in locally advanced tumors, that the resulting mortality and morbidity is similar to that expected from operation alone and that local tumor control may be improved.

Abdominal Neoplasms↗
PubMed1982

Radiation therapy technique in soft tissue sarcomas of the extremity--policies of treatment at the National Cancer Institute.

We have formulated certain treatment techniques for soft sarcomas of the extremities in adults, based on the experience of treating 75 patients at the National Cancer Institute. Attaining a high likelihood of tumor control is heavily dependent on a variety of factors. These factors include a knowledge of the biological characteristics of the tumor, of the normal tissue anatomy and its relationship to the tumor and of the surgical techniques available and the details of the surgery already performed. Obtaining good long term function in the irradiated extremity is dependent on sparing a strip of soft tissue and using sophisticated radiation therapy techniques. These techniques include casting of the extremity for immobilization, using a variety of gantry and collimator angulations, using treatment planning for determining the necessity for wedges or compensating filters in the radiation field and utilizing secondary collimation. With this highly individualized approach to treatment of patients with soft tissue sarcomas, optimal results can be obtained.

Extremities↗
PubMed1982

The treatment of soft-tissue sarcomas of the extremities: prospective randomized evaluations of (1) limb-sparing surgery plus radiation therapy compared with amputation and (2) the role of adjuvant chemotherapy.

Between May 1975 and April 1981, 43 adult patients with high-grade soft tissue sarcomas of the extremities were prospectively randomized to receive either amputation at or above the joint proximal to the tumor, including all involved muscle groups, or to receive a limb-sparing resection plus adjuvant radiation therapy. The limb-sparing resection group received wide local excision followed by 5000 rads to the entire anatomic area at risk for local spread and 6000 to 7000 rads to the tumor bed. Both randomization groups received postoperative chemotherapy with doxorubicin (maximum cumulative dose 550 mg/m2), cyclophosphamide, and high-dose methotrexate. Twenty-seven patients randomized to receive limb-sparing resection and radiotherapy, and 16 received amputation (randomization was 2:1). There were four local recurrences in the limb-sparing group and none in the amputation group (p1 = 0.06 generalized Wilcoxon test). However, there were no differences in disease-free survival rates (71% and 78% at five years; p2 = 0.75) or overall survival rates (83% and 88% at five years; p2 = 0.99) between the limb-sparing group and the amputation treatment groups. Multivariate analysis indicated that the only correlate of local recurrence was the final margin of resection. Patients with positive margins of resection had a higher likelihood of local recurrence compared with those with negative margins (p1 less than 0.0001) even when postoperative radiotherapy was used. A simultaneous prospective randomized study of postoperative chemotherapy in 65 patients with high-grade soft-tissue sarcomas of the extremities revealed a marked advantage in patients receiving chemotherapy compared with those without chemotherapy in three-year continuous disease-free (92% vs. 60%; p1 = 0.0008) and overall survival (95% vs. 74%; p1 = 0.04). Thus limb-sparing surgery, radiation therapy, and adjuvant chemotherapy appear capable of successfully treating the great majority of adult patients with soft tissue sarcomas of the extremity.

Adolescent↗
PubMed1982

Tolerance of retroperitoneal structures to intraoperative radiation.

In conjunction with the clinical development of intraoperative radiotherapy, a study was undertaken in dogs to define the tolerance of normal anatomic structures in the retroperitoneum to radiation delivered during operation. Twenty adult dogs were subjected to laparotomy and intraoperative 11 MeV electron irradiation in single doses ranging from 0.to 5000 rad. Animals were followed regularly with clinical observation, blood count, serum chemistries, pyelography, and angiography. Animals were sacrificed and autopsied at regular intervals up to 12 months following treatment to assess radiation-induced complications or tissue damage. Irradiation field in all dogs consisted of a 4 X 15 cm rectangle extending inthe retroperitoneum from the level of the renal vessels to the bifurcation of aorta and vena cava. The field included aorta, vena cava, inferior portion of left kidney, and distal portion of left ureter. No complications or histologic changes occurred in any animal given doses of 2000 rad, with a follow-up in excess of 18 months. A dose of 3000 rad was well tolerated, except for left ureteral occlusion in one animal. Mild vascular fibrosis was present inthe aorta and vena cava, and significant ureteral fibrosis developed by six months after doses of 4000 or 5000 rad. All animals that received 5000 rad died of radiation-related complications, including ureteral obstruction and rectal perforation. It was concluded that major vessels tolerate intraoperative irradiation well up to and including 3000 rad and that no clinically significant vascular problems develop after 4000 and 5000 rad, although some fibrosis does occur. The ureter and kidney appear to be the most radiosensitive structures inthe retroperitoneum, showing progressive changes at 300 rad or greater and showing the potential for serious complications after doses of 4000 rad or more.

Animals↗
PubMed1982

Tolerance of bile duct to intraoperative irradiation.

In order to determine the effects of intraoperative radiation therapy of the bile duct and surrounding tissues, seven adult dogs were subjected to laparotomy and intraoperative irradiation with 11 MeV electrons. Two animals were treated at each dose level of 2000, 3000, and 4500 rads. A single dog which received a laparotomy and sham irradiation served as a control. The irradiation field consisted of a 5 cm diameter circle encompassing the extrahepatic bile duct, portal vein, hepatic artery, and lateral duodenal wall. The animals were followed clinically for mor than 18 months after treatment, and autopsies were performed on dogs that died to assess radiation-induced complications or tissue damage. All dogs developed fibrosis and mural thickening of the common duct, which appeared by 6 weeks following irradiation and which was dose-related, being mild at low doses and more severe at high doses. Hepatic changes were seen as early as 6 weeks after irradiation, consisting of periportal inflammation and fibrosis. The hepatic changes appeared earliest at the highest doses. Frank biliary cirrhosis eventually developed at all dose levels. Duodenal fibrosis appeared in the irradiation portal, being most severe at the highest doses and in some animals resulting in duodenal obstruction. No changes were observed in irradiated portions of portal vein and hepatic artery at any dose level. It was concluded that intraoperative radiation therapy delivered to the region of the common duct leads to ductal fibrosis, partial biliary obstruction with secondary hepatic changes, and duodenal fibrosis if bowel wall is included in the field. Clinical use of intraoperative radiation therapy to the bile duct in humans may require routine use of biliary and duodenal bypass to prevent obstructive complications.

Animals↗
PubMed1981

Clonogenic potential of human tumors. A hypothesis.

Conventional radiation therapy of medium-sized (2 to 5 cm diameter) squamous cell carcinomas of the head and neck has resulted in data which were pooled to produce a curve of local control versus dose. From this curve, estimates were made of the number of clonogenic cells in these tumors. These calculations demonstrate a much smaller number of clonogenic cells than is usually assumed for human tumors. It is postulated that a relatively small proportion of the cells in human tumors are clonogenic. The number of cells which need to be destroyed by radiation therapy or chemotherapy in order to produce tumor control may be much less than usually estimated.

Carcinoma, Squamous Cell↗
PubMed1980

Local control of Ewing's sarcoma of bone with radiotherapy and combination chemotherapy.

Between 1964 and 1977, 94 patients with Ewing's sarcoma of bone were treated at the National Cancer Institute. They received 5000 rad to the whole bone and progressively more aggressive chemotherapy protocols. The patients were divided according to site of primary lesion into central, proximal and distal lesions, with 19%, 33% and 57%, respectively, alive and well. Of 28 patients autopsied, 11 (39%) had had a pathologic documentation of local recurrence. An additional three patients had a biopsy-proven local recurrence, for a total pathologically proven rate of 14/94 (15%). A total of 16/94 (17%) patients had clinical evidence of local recurrence. The overall local recurrence rate (clinical plus pathologic) was 22/94 (23%). This rate varied according to the site of the primary and was 14/42 (33%) for central, 6/24 (25%) for proximal, and 2/28 (7%) for distal lesions. The local recurrence rate did not change significantly either with the more aggressive chemotherapy regimens or with the presence of metastases at presentation. The local control rate is high (93%), with good functional results in the distal lesions, and no changes are needed in radiation therapy dose or volume. Control is not as satisfactory for central and proximal lesions and efforts need to be made to increase control at these sites. We are at present attempting to define more accurately the extent of soft tissue disease, increasing the dose to 6000 rad for central lesions, and using a more aggressive chemotherapy program, in the hope of increasing the local control in these more aggressive tumors.

Antineoplastic Agents↗
PubMed1979

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↗
PubMed1978

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↗
PubMed1978

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↗
PubMed1977

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↗
PubMed1976

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↗
PubMed1975

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↗