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Biomedical subjects

S Hellman

Publications and source records attributed to S Hellman.

At least 127 records · Page 7Linked to original sources
PubMed1984

Busulfan and total body irradiation as antihematopoietic stem cell agents in the preparation of patients with congenital bone marrow disorders for allogenic bone marrow transplantation.

The capacity of busulfan and total body irradiation to ablate hematopoietic stem cells as preparation for the allogeneic bone marrow transplantation of patients with congenital bone marrow disorders was studied. Fourteen patients received 18 transplants; busulfan was used in the preparatory regimen of eight transplants and total body irradiation in the regimens of six transplants. Sustained hematopoietic ablation was achieved in six of eight patients prepared with busulfan and in all six patients prepared with total body irradiation. Three patients prepared with total body irradiation died with idiopathic interstitial pneumonitis, whereas no patients receiving busulfan developed interstitial pneumonitis. The optimal antihematopoietic stem cell agent to be used for the preparation of patients with congenital bone marrow disorder for bone marrow transplantation is not certain.

Adolescent↗
PubMed1984

The morphology of hematopoietic layers in long-term cultures of mouse bone marrow.

Mouse bone marrow cells in long-term culture were examined with scanning electron microscopy during the first 10 days of growth and with phase contrast microscopy during the first 4 weeks. The development of stroma and hematopoiesis was studied, and phase microscopic observation was used in order to achieve positive cell identifications with scanning EM. We analyzed those cell populations that could not be washed away from the adherent culture layer. These adherent cells in 24-hour cultures contain the full potential of hematopoietic long-term production. Stromal cells started to spread almost immediately and by 5 days had established several layers. Although in early cultures hematopoietic cells were found resting on the surfaces of stromal cells, they were later packed between stromal layers. The blast cells, especially, were usually buried under and between thin sheets of reticulum cells. The study confirms the three-dimensional nature of bone marrow in culture and points to close correspondence with bone marrow structure as studied by others in vivo.

Animals↗
PubMed1983

Primary radiation therapy for early breast cancer.

Primary radiation therapy for early breast cancer is a combination of limited breast surgery for the removal of gross disease, and moderate doses of radiation for the control of residual subclinical disease. The results from retrospective studies using primary radiation therapy indicate that high levels of local tumor control with good cosmetic results can be achieved. Preliminary results from a prospective randomized clinical trial indicate that radical mastectomy and primary radiation therapy result in equivalent survival rates. Primary radiation therapy is a reasonable alternative to mastectomy when adequate surgical and radiotherapeutic expertise is available to deliver this treatment.

Brachytherapy↗
PubMed1983

Axillary sampling in the definitive treatment of breast cancer by radiation therapy and lumpectomy.

Between January, 1967 and July, 1980, 176 women who were referred to the Joint Center for Radiation Therapy (JCRT) for definitive breast irradiation underwent low axillary dissection. A typical operative technique is described. The dissection stops short of the axillary vein although the vein is usually visualized. One hundred thirty-two axillae were thought to be N0 or N1a. Forty-six axillae were felt to be N1b. Seventeen percent of the T1 N0 patients had pathologically positive nodes. Twenty-seven percent of the T2 N0 patients had positive nodes. When 5 or less nodes were removed at axillary sampling the incidence of nodal involvement was very low. There were no differences in nodal positivity when comparing upper quadrant to lower or central lesions. Lateral lesions appeared to have higher positivity rates compared with either medial or central lesions. Ninety-four percent of axillae with N1b lesions were pathologically confirmed. The complication rate for this procedure was low. There were 5 transient non-surgical complications and 1 cellulitis resulting in a frozen shoulder, which required corrective surgery. There were no cases of moderate or severe arm edema. Axillary sampling is compared to axillary dissection as a diagnostic procedure. Axillary sampling may underestimate the true pathologic positive rate, but diagnostic accuracy appears excellent if level 1 and 2 nodes are sampled.

Axilla↗
PubMed1983

Management of locally advanced carcinoma of the breast by primary radiation therapy.

We performed a retrospective review of 137 patients with locally advanced breast cancer, but without distant metastases, who were treated with radical radiation therapy. Ninety percent of patients had an initial complete response to their radiation therapy. The 5 year rates of local tumor control, survival free of distant failure, and overall survival were 54%, 28% and 30%, respectively. Multivariate analysis revealed that the following features were associated with improved local tumor control: clinically negative axillary nodes, excisional biopsy, radiation dose greater than 6000 rad, and the use of adjuvant systemic therapy. Improved freedom from distant relapse was seen in patients with small primaries and non-inflammatory carcinoma, as well as clinically negative axillary nodes, excisional biopsy, radiation dose greater than 6000 rad, and the use of adjuvant systemic therapy. The results suggest that adequate levels of radiation therapy can provide local tumor control in a significant proportion of patients with locally advanced-breast cancer and that adjuvant systemic therapy is useful in improving both local tumor control and freedom from distant relapse in these patients.

Adult↗
PubMed1983

Clinical-pathologic study of early breast cancer treated by primary radiation therapy.

We performed a clinical-pathologic review of 231 patients with early breast cancer treated by primary radiation therapy. There were 27 patients with infiltrating ductal carcinoma treated with excisional biopsy whose tumors showed a constellation of histologic features: moderate or marked intraductal carcinoma in the tumor, intraductal carcinoma in the adjacent tissue, and high nuclear grade. These patients had a 5-yr local tumor control rate of 61% compared to 96% for similar patients whose tumors did not show all three features. Radiation dose to the primary tumor area influenced the likelihood of local recurrence in these 27 patients: 15 of these patients received 6000 rads or more to the primary tumor area and had a 5-yr local tumor control rate of 84%, compared to 48% for the 12 patients who received less than 6000 rads. These results indicate that a subgroup of breast cancer patients can be identified that has a high risk of local recurrence when an insufficient radiation dose (i.e., less than 6000 rads) is delivered to the primary tumor area.

Actuarial Analysis↗
PubMed1983

Functional organization of the hematopoietic stem cell compartment: implications for cancer and its therapy.

Recent discoveries indicate that hematopoietic stem cells have limits on their proliferative capacity and are unable to divide indefinitely. There is great heterogeneity within the compartment as to the extent of this proliferative limitation. At any given time it appears that hematopoiesis is maintained by the progeny of only a few stem cells. When these are exhausted the progeny from other stem cells take their place. The observations of proliferative limitation, heterogeneity, and clonal succession must be incorporated into any model of stem cell organization. These new discoveries and the models incorporating them have important clinical implications. They may explain the inability of normal tissues to develop drug resistance and they also offer a mechanism by which cell renewal systems decrease the development of malignancies. In the selection of chemotherapeutic agents not only the effectiveness of the drug upon the tumor must be considered, but also how specific agents affect the stem cell compartment. These data have important implications in the use of bone marrow transplantation for both malignant and nonmalignant disease.

Age Factors↗
PubMed1983

Circulating lymphocyte populations in Hodgkin's disease after mantle and paraaortic irradiation.

The effect of mantle and paraaortic radiation on peripheral blood lymphocytes was studied in 11 previously untreated patients with early stage Hodgkin's disease using a series of monoclonal antibodies defining immunoregulatory lymphoid cells. Immediately following the completion of radiotherapy, there was a significant reduction in the number of lymphocytes and the percent of circulating T cells. This acute decrease in T cells was due to a marked diminution in the number of inducer T cells, while the fraction of suppressor T cells remained constant. These changes persisted for up to 12 mo and were accompanied by a later increase in the fraction of circulating B lymphocytes and cells bearing surface Ia. It thus appears that mantle and paraaortic radiotherapy causes a relatively selective reduction in the inducer T-cell population. The implications of a change in the ratio of inducer to suppressor T cells is discussed.

Antibodies, Monoclonal↗
PubMed1982

Proliferative capacity of murine hematopoietic stem cells in vitro.

Large numbers of granulocytes can be collected repeatedly from the supernatant medium of long-term cultures of mouse bone marrow cells. A constant relationship was found between the number of adherent hematopoietic stem cells and the lifetime cell production per culture. The data indicate that there is a limit to the proliferative capacity of normal and of irradiated stem cells. A similar limitation was found in the production of marked granulocytes from clonal cultures of "beige" C57 (bg/bgJ) stem cells placed in limiting dilutions into stromal culture layers.

Animals↗
PubMed1982

Residual radiation injury exhibited in long-term bone marrow cultures.

Residual radiation injury was demonstrated in long-term primary cultures of mouse bone marrow. Control cultures underwent three phases of hematopoietic activity as distinguished by initial establishment, steady high (plateau) production of granulocytes, and gradual decline. Irradiation with 50, 300, or 550 rads, given at the end of the initial phase, did not prevent any culture flasks from entering the plateau phase. However, actual production levels and the time they were maintained varied inversely with the radiation dose so that the accumulated postradiation cell production corresponded to an exponential dose-response relationship at any time after treatment. The accumulated cell productions were found to be similar in all groups when expressed by the number of stem cell doublings necessary to produce them. The findings cannot be explained by reproductive cell death and are consistent with the notion of a limited division capacity in hematopoietic stem cells.

Animals↗
PubMed1982

The current status of primary radiation therapy in the treatment of early breast cancer.

Primary radiation therapy, usually with limited surgery, is being used increasingly as an alternative to mastectomy in patients with early breast cancer. Results so far appear similar in terms of local control and overall survival. Current questions on patient selection, extent of surgery, radiation therapy technique, possible long-term complications, and the role of axillary dissection and of adjuvant therapy are reviewed. Though many questions remain, it is hoped that this alternative will contribute to improved survival along with breast preservation for improved quality of life.

Adult↗
PubMed1982

The effect of dose rate and adriamycin on the tolerance of thoracic radiation in mice.

Radiation damage to the lung may be a predisposing factor in the development of interstitial pneumonitis in patients undergoing total body radiation and subsequent bone marrow transplantation in the treatment of leukemia. Adriamycin has been used in conjunction with bone marrow transplantation, and has also been shown to interact with radiation. This experiment was designed to study the effects of pre-administration of adriamycin on the radiation tolerance of the lung and esophagus. Since total body radiation is usually administered at low dose rates in order to spare the gastrointestinal tract preferentially as compared to the bone marrow, we investigated whether such a dose rate effect was present for the lung and if so, whether this pulmonary and esophageal dose rate effect would be ameliorated by pre-treatment with adriamycin. Mice were irradiated at 5 rad; 15 rad or 70 rad per minute to the upper body, 24 hours or 7 days after adriamycin. Oral esophageal death occurred within one month; thus deaths within 30 days were ascribed to this mechanism. In comparison, deaths because of pulmonary toxicity occurred later. Those between 30 and 160 days were ascribed to this mechanism. In the absence of adriamycin, a dose rate effect was found for the lung and confirmed for the upper gastrointestinal tract. The dose of radiation necessary to give pulmonary and gastrointestinal toxicity was markedly reduced when adriamycin was administered 24 hours before radiation. If seven days were allowed between adriamycin and radiation there was still an effect seen only at the high dose rate for the esophagus while for the lung at the high dose rate and for both systems at low dose rate no significant drug effects were noted. The dose rate effect is still seen after the drug, but it is reduced. These studies indicate that adriamycin given shortly before can significantly increase the oral esophageal and pulmonary toxicity of radiation and can practically abrogate the sparing effect of dose rate. This must be considered when clinically using total body radiation and adriamycin in preparation for bone marrow transplantation.

Animals↗
PubMed1982

Cell types associated with fibronectin in long-term mouse bone marrow cultures.

The formation of fibronectin matrix was studied in long-term mouse bone marrow cultures. Stromal and hematopoietic cells were observed in situ under phase contrast optics and quantified according to their staining characteristics on smear preparations. Surface fibronectin was demonstrated by indirect immunofluorescence. While only stromal and no hematopoietic cells participated, various stromal cell types differed in their expression of cell surface fibronectin: Reticulum cells contributed the major portion of fibronectin matrix. Elongated, meshwork-forming histiocytes expressed some surface fibronectin, while the flattened, macrophagic histiocytes remained fibronectin negative. These findings were recapitulated during regeneration of scrape wounds in the adherent layers. Isolated fibronectin matrix did not support hematopoietic cell adherence or maintenance, although it had marked effects on stromal cells.

Adipose Tissue↗