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Biomedical subjects

S Hellman

Publications and source records attributed to S Hellman.

At least 145 records · Page 8Linked to original sources
PubMed1982

Differing stem cell self-renewal of lectin-separated murine bone marrow fractions.

The success of bone marrow transplantation depends not only on the engraftment of adequate numbers of hematopoietic stem cells but also on their self-renewal capacity, which must be sufficient to provide lifetime hematopoiesis. The lectin peanut agglutinin (PNA), when exposed to bone marrow, causes separation into two distinct fractions. The agglutinated fraction not only is enriched with colony-forming units--spleen but also is devoid of graft-versus-host (GVH) activity when injected into allogeneic lethally irradiated recipients, and therefore, it is considered to be an ideal source for bone marrow transplantation. The absence of GVH activity is presumably due to the separation of mature thymocytes into the nonagglutinated fraction and functionally immature thymocytes into the agglutinated fraction. Although there has been speculation that immature hematopoietic stem cells also selectively bind to PNA, other evidence suggests that the relationship of lectin binding specificity to level of maturity varies in different tissues. This study was performed to assess the self-renewal capacity of lectin-separated bone marrow stem cells. Results indicate that the self-renewal of the agglutinated fraction is significantly lower than that of the unfractionated bone marrow; such self-renewal of the nonagglutinated fraction is higher. This is further evidence for the heterogeneity of the stem cell pool. Stem cell enrichment should not be the goal in bone marrow transplantation; rather, the goal should be utilization of stem cells with the greatest self-renewal potential.

Animals↗
PubMed1982

Paradoxical effect of radiation on tumor incidence in the rat: implications for radiation therapy.

The high incidence of leukemia in the Fischer rat is reduced by radiation to an incidence below that seen spontaneously. Fractionating the radiation decreased this effect. In contrast, mammary tumors increased with dose until reaching a plateau at the highest doses. Fractionation had little effect. These results are consistent with a hypothesis suggesting that tumor incidence due to radiation is the result of competing processes of tumor induction and cell killing.

Animals↗
PubMed1982

Anatomic substages of stage IIIA Hodgkin's disease: followup of a collaborative study.

The clinical significance of anatomic substage was reassessed in a previously reported series of 130 patients with Hodgkin's disease in pathologic stage IIIA. For 100 patients, followup was greater than 8 years. By definition, stage III1 disease includes involvement of spleen or splenic, celiac, or portal nodes, or any combination of these; stage III2 disease includes involvement of para-aortic, iliac, or mesenteric nodes, with or without upper abdominal involvement. Both 8-year relapse-free survival (71% versus 40%) and 8-year overall survival (80% versus 54%) were better in stage III1A than in III2A patients (P less than 0.001). For stage III1A, relapse-free survival was better in patients receiving radiotherapy alone as initial treatment (92% versus 60%, P less than 0.002). However, 8 year overall survival rates in these two treatment groups were not significantly different (88% versus 76%, P = 0.20). For stage III2A, both relapse-free survival at 8 years (84% versus 19%, P less than 0.001) and overall survival at 8 years (84% versus 41%, P less than 0.01) were superior in patients receiving combined modality therapy. Anatomic substage is a critical prognostic variable, especially if standard total nodal radiotherapy is considered as one of the therapeutic options.

Adult↗
PubMed1982

Influence of mediastinal adenopathy on site and frequency of relapse in patients with Hodgkin's disease.

Between April 1969 and July 1979, 267 patients with surgically staged IA-IIB Hodgkin's disease and 31 with clinically staged IIE or IV Hodgkin's disease were treated; disease was limited to the area above the diaphragm. Three separate groups of patients with mediastinal adenopathy were identified. Patients with disease limited to the mediastinum had a favorable prognosis, and treatment with mantle followed by para-aortic irradiation has resulted in 85% relapse-free survival and 100% overall survival at 8 years. Surgically staged patients with large diameter mediastinal adenopathy (greater than 0.33 of the thoracic diameter) have a high relapse rate with radiation therapy alone. The use of combined modality therapy has reduced the risk of relapse in these patients, but the survival remains higher whether MOPP is used initially or at relapse. Clinically staged IIE patients or stage IV patients with extensive extranodal disease limited to the thoracic cavity were treated with chemotherapy and involved- or extended-field irradiation. These patients had a 5-year survival of 66% with large mediastinal adenopathy and 90% with lesser mediastinal disease.

Hodgkin Disease↗
PubMed1982

Role of radiation therapy in the treatment of Hodgkin's disease.

We reviewed the results of 10 years of experience in treating 105 patients with stage IA-IIIB Hodgkin's disease at the Joint Center for Radiation Therapy. It appears that "total nodal irradiation" may largely be avoided. For supradiaphragmatic stage I and IIA disease, mantle and para-aortic irradiation result in excellent relapse-free survival except in patients with large mediastinal masses. Stage IIB patients can be treated similarly to those in stage IIA. Stage IIIA patients treated with total nodal irradiation alone fare less well. Combined modality treatment improves survival markedly but may cause excessive complications. For stage III1A, we currently recommend that patients be treated with mantle and para-aortic nodal irradiation, with chemotherapy used only in those who fail. We treat stage III2A and IIIB patients with both chemotherapy and radiation.

Hodgkin Disease↗
PubMed1981

The characteristics of long-term survivors of lung cancer treated with radiation.

Between 1968 and 1974, 348 patients with lung cancer were primarily treated with radiation therapy. There were 66 such patients (19%) who survived a minimum of 18 months and are the subject of this report. Of this group, 30 patients have no evidence of disease from 18-96 months, with a median follow-up of 38 months. Thirty-three patients are dead of disease. The five-year actuarial survival of the total group of 348 patients was 5.6%. There were 14 stage I and II patients who survived a minimum of 18 months, of whom 11 had no evidence of disease. Of the 42 Stage III patients, 18 presently show no evidence of disease. There were 13 patients who failed with locally recurrent disease; in this group a dose-response relationship was demonstrated. A local failure rate of 50% (4/8) was observed for patients who received fewer than 5000 rad, 22% (6/27) for patients receiving 5000-5500 rad, 18% (2/11) in patients receiving 5500-5900 rad, and 5% (1/20) for patients who received more than 5900 rad. Radiotherapeutic technique was a significant variable in local failure. Forty-six percent (6/13) of those patient failures may have been eliminated with the use of careful treatment planning with simulation. A statistically significant difference in dose was noted for patients with central recurrence, mean dose 4725 rad, 1561 RET, 81 TDF, when compared with patients with control of gross disease with radiation, mean dose 5740, 1880 RET, 108 TDF. There were four patients with marked early complications (6%) and eight patients with late complications (12%). There were no deaths attributable to radiation. Although most patients with advanced lung carcinoma die of distant disease, a significant number of patients can achieve long-term survival when radically treated with high-dose radiation therapy.

Actuarial Analysis↗
PubMed1981

A follow-up of deinstitutionalized chronic patients four years after discharge.

Twenty-seven chronically ill mental patients were followed up four years after their discharge from a state hospital to the Massachusetts Mental Health Center. In interviews with the patients and their caregivers, data were gathered on the patients' current places of residence, mental status, time spent in the hospital since discharge, levels of functioning, and quality of life. The authors found that patients tended to move from hospital to community, with rehospitalization dropping dramatically once patients were placed in the community; that the group of patients living in the community had a better average mental status; that all but two patients preferred their current living situations to life at the state hospital; and that the best predictor of community residence was age at first admission (over 20). Two policy issues are discussed: the relationship (or lack of one) between restrictiveness and type of residence, and the importance to the findings of changes in psychiatric practice over the lifetime of the sample.

Adult↗
PubMed1981

Alternative to the back ward: the quarterway house.

The Quarterway House was founded in December 1978 to deinstitutionalize and provide rehabilitation services to a small group of long-term, seriously ill inpatients of the Massachusetts Mental Health Center. The purposes of the residential program are to provide a less institutional therapeutic environment and to develop a psychosocial treatment program that might enable some patients to move toward more independent settings in the community. In a randomized experimental study, with center inpatients as the control group, the effectiveness of the program was assessed by multiple outcome measures before the program began and at one year. Although neither group moved rapidly to more independent community living, Quarterway House patients showed improvement in general functioning and socialization-survival skills and decreased medication and seclusion. They did not show a decline in psychotic symptoms, obstreperousness, or antisocial behavior. Over-all, the findings suggest the program may prove useful for the long-term rehabilitation of severely ill patients.

Activities of Daily Living↗
PubMed1981

The complicated business of setting up residential alternatives.

To meet the housing needs of deinstitutionalized clients characterized by low incomes, isolation from their families, and inability to function independently, the Massachusetts Mental Health Center has developed a range of community residential settings. Among them are the independent living apartment program, partly supported by section 8 rent subsidies from the Department of Housing and Urban Development, and group homes for 12 to 18 clients. Factors that have contributed to the success of the program include diligent cultivation of relationships with housing developers, innovative support from the staff of the state housing and finance agency, clear delineation of rights and responsibilities of tenants and owners, and the center's system of backup services for clients. The center is currently developing additional housing under HUD's section 202 demonstration program for housing of the handicapped through rehabilitation of existing buildings.

Boston↗
PubMed1981

Differential effects of cytotoxic agents on hematopoietic progenitors.

In order to predict the effect of chemotherapeutic agents on the hematopoietic progenitor compartment, it is necessary to have a hypothesis concerning the dynamics of the cells within the compartment. By viewing this compartment as a continuum of cells with varying self-renewal capacity, one can assess the significance of the stem cell damage incurred following a single drug dose. Vinblastine, 5-fluorouracil, cyclophosphamide, busulfan, and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) were investigated. The acute toxicity of the drug-exposed marrow was studied by the colony-forming units-spleen (CFU-S) and agar diffusion chamber assay. Busulfan and BCNU were found to kill CFU-S preferentially. By following CFU-S recovery for 14 days post drug, different recovery patterns are noted. Busulfan and BCNU produce prolonged depression in CFU-S, whereas cyclophosphamide and 5-fluorouracil show relatively rapid recovery. If one determines the Rs (a measure of proliferative capacity) after drug, busulfan and, to a lesser extent, BCNU produce a prolonged depression without return to normal even 650 days post drug. No such depression is noted with the other drugs. The data from the recovery curves and Rs support the notion of stem cells being heterogeneous with regard to self-renewal capacity. The agar diffusion chamber and CFU-S acute survival curves would not have predicted which drugs cause significant proliferative damage. Only with the use of CFU-S recovery and ratio of CFU-S can prolonged marrow damage be ascertained.

Animals↗
PubMed1980

Radiation therapy of early carcinoma of the breast without mastectomy.

The results of the treatment of 176 patients with early breast cancer, using radiation therapy without mastectomy are reported. The likelihood of local recurrence was 5% for Stage I patients and 7% for Stage II patients. Local control was significantly greater in those patients receiving and iridium implant (1/73 vs. 10/111, P less than .05). The cumulative survival probability at five years is 96% for Stage I and 68% for Stage II. Local control with good cosmetic results is greatly influenced by surgical and radiotherapeutic technique. Gross tumor resection with careful reapproximation of the breast tissue and well-placed incisions facilitates the radiation therapy. Homogeneous external beam radiation to the breast and draining lymph nodes (4500--5000 rads) and supplemental local radiation to the sites of the primary lesion (in this series using interstitial implantation) are recommended.

Adult↗
PubMed1980

Lack of selective killing by steroids in normal and malignant cells.

Using a colony formation assay, the cytotoxic effects of steroids and an anti-steroid on an established human breast tumor line and two human diploid fibroblast strains were studied. Experiments involving 17 a-estradiol, 17 beta-estradiol, dexamethasone, cortisone, dihydrotestosterone, and the anti-estrogen Tamoxifen showed no killing at concentrations below 10(-7)M following a 24-hour exposure to these agents. A maximum of 80% killing was observed at 10(-5)M with dexamethasone in one fibroblast strain and at the same dose of 17 beta-estradiol in the breast tumor line. The extent of killing observed is insufficient to account for many of the clinical remissions observed with steroid therapy. The data also suggest that at therapeutic doses, there is no selective killing of malignant cells by these agents.

Breast Neoplasms↗