PubMed Health⌕ Search

Biomedical subjects

R A Steeves

Publications and source records attributed to R A Steeves.

At least 37 records · Page 2Linked to original sources
PubMed1989

Augmentation of helper virus replication in the presence of defective retrovirus.

The interaction between defective spleen focus-forming virus (SFFV) and helper virus(es) in Friend virus (FV) complex has been assumed to be one-way, with the helper virus complementing SFFV by supplying necessary virion components. To test this assumption the expression of both SFFV and helper virus in partially congenic mice which differ at the Fv-2 locus, a gene that specifically controls susceptibility to SFFV, was analysed. When the mice were infected with LLV (a strain of Friend SFFV-free helper virus), there was no detectable effect of Fv-2 genotype on LLV expression as tested by virus infectivity in the XC plaque assay or by quantitative viral antigen analysis in an immunoprecipitation assay. However, after infection with FV complex there was an amplification of LLV (as well as SFFV) synthesis in Fv-2s as compared with Fv-2r hosts. To determine whether the increased LLV synthesis in Fv-2s mice was due to an increased population of susceptible target cells as a result of SFFV infection and/or transformation, the ratios of LLV-infected cells in the spleens of LLV- and FV-infected Fv-2s hosts in an infectious centre assay, were compared. Since the percentage of LLV-infected cells was equivalent in both instances, the higher rate of LLV synthesis after infection with FV complex was presumably due to intrinsic properties of SFFV-infected erythroid cells.

Animals↗
PubMed1989

Clinical considerations in the use of external microwaves for local hyperthermia.

This article focuses on the clinical indications for local microwave hyperthermia, on the equipment and techniques involved in treatment planning, and on some of the controversies yet to be solved with regard to prescribing a course of hyperthermia treatments. Clinical results reviewed are restricted to three similar trials with microwave heating devices in patients with multiple superficial neoplasms. Matched-pair analysis of the responses of these lesions provides convincing evidence for the efficacy of local hyperthermia. In conclusion, the need for better equipment and new clinical protocols is stressed.

Clinical Trials as Topic↗
PubMed1988

A hyperthermia study of differential sensitivity and thermotolerance in AKR murine leukemia and normal bone marrow cells.

It has been previously demonstrated that AKR leukemia (lymphoma) cells are more sensitive than normal bone marrow cells to hyperthermic killing at 41.8 degrees C and 42.5 degrees C in vitro. This differential heat sensitivity might be explained by a greater ability to induce thermotolerance (TT) in normal versus neoplastic hematopoetic cells. We tested this hypothesis using the spleen colony methodology in the AKR murine model. A greater heat sensitivity of leukemia in comparison to normal bone marrow cells was observed at 42.5 degrees C; this observation agrees with previous reports. However, using a preincubation temperature of 40.0 degrees C for 120 min did not result in the induction of TT in either normal bone marrow (AKR) cells or AKR leukemia cells. The rationale for the choice of preincubation temperatures and times, as well as the clinical implications of these results are discussed.

Adaptation, Physiological↗
PubMed1988

A pilot study of whole body hyperthermia and local irradiation for advanced non-small cell lung cancer confined to the thorax.

Six patients with Stage III non-small cell lung cancer completed therapy which consisted of 4 whole body hyperthermia (WBH) treatments during the first 2 weeks of a 6 week course of radiotherapy (60 Gy). A radiant heat system was used to deliver the 41.8 degree C WBH. To reduce the danger of transverse myelitis, the spinal cord (and therefore part of the mediastinum and contralateral hilar region) was not irradiated during the first 2 weeks of radiotherapy and concurrent WBH. Subsequent treatments (weeks 3-6) included conventional irradiation to the primary tumor, mediastinal lymph nodes and spinal cord. Areas of gross disease responded to therapy in 5/6 patients. No radiation pneumonitis was observed. In 2/6 patients, relapse (after 10 months and 6 months, respectively) occurred with malignant pericardial effusions. The mediastinum in these patients was not an area of bulky disease involvement initially. To eliminate such WBH-radiation sanctuary zones, the protocol was modified to include greater combined WBH-radiation treatment. This is accomplished by having one WBH treatment "sandwiched" between 2 radiation fractions. The preclinical basis for the revised protocol is presented.

Adult↗
PubMed1987

Intermittent central nervous system irradiation and intrathecal chemotherapy for central nervous system leukemia in children.

Between 1979 and 1985, nine children with recurrent CNS leukemia who had previous radiation of more than 1800 cGy to the brain were treated with intermittent central nervous system irradiation and intrathecal chemotherapy (IIIC). There was no isolated CNS recurrence. Three patients died; one from generalized recurrent disease, two from complications associated with bone marrow transplantation. Six patients are alive without evidence of disease between 9 years and 2 4/12 years from the diagnosis of recurrent CNS leukemia. This experience suggests that IIIC may be an effective treatment for preventing the recurrence of CNS leukemia with minimal side effects.

Adolescent↗
PubMed1987

Interaction of whole-body hyperthermia and irradiation in the treatment of AKR mouse leukemia.

Whole-body hyperthermia (WBH) to 41-42 degrees C combined with fractionated total-body irradiation (TBI) was studied in mice with transplanted AKR leukemia. Mice treated with both TBI and WBH survived longer than mice treated with either modality alone. From other groups of similarly treated mice the spleens were removed, weighed, and assayed for their content of leukemic colony-forming units (CFU) by injecting single-cell suspensions into normal syngeneic recipients. Using this methodology it was determined that the thermal enhancement ratio for WBH combined with TBI was 1.6, and that enhanced killing of leukemia cells occurred irrespective of the sequence of WBH and TBI. Data are presented which relate variables, such as duration of WBH or heating time to target temperature, to the response of neoplastic disease. The implications of these preclinical findings to clinical trials are discussed.

Animals↗
PubMed1985

Chronic response of normal porcine fat and muscle to focused ultrasound hyperthermia.

Annular focused ultrasound (1.13 MHz) hyperthermia was used to evaluate chronic histologic effects of a range of high thermal dosages on normal porcine tissues. The effects of three peak temperatures (45, 47, and 49 degrees C) at a focal depth of 2 cm in thirty 4-cm-diameter sites were studied as a function of exposure time (10-60 min). Relative fat and muscle damage were histologically graded 1 month post-treatment. Unlike reports of radiofrequency hyperthermia, no necrosis or abscess formation was observed, even at 49 degrees C for 40 min. Fat sustained a greater percentage maximal tissue damage than muscle, although less than 4% of sections evaluated had histologic evidence of severe injury. Focused ultrasound provides a relatively uniform heat distribution in normal tissues. It should therefore be possible to raise normal tissues surrounding tumors to high temperatures using focused ultrasound, potentiating tumoricidal effects with minimal associated complications.

Adipose Tissue↗
PubMed1984

Potentiation of differential hyperthermic sensitivity of AKR leukemia and normal bone marrow cells by lidocaine or thiopental.

Previous work has utilized spleen colony formation to evaluate the fractional survival of AKR leukemia and normal bone marrow cells after in vitro heat exposure. An inherently greater sensitivity of neoplastic cells to thermal killing, as compared to normal syngeneic stem cells, has been established both at 41.8 degrees C and 42.5 degrees C. Normal bone marrow colony-forming units were assayed in lethally irradiated (750 cGy) mice. Leukemic colony-forming units were assayed in nonirradiated mice. Using this methodology, the authors demonstrated that the differential effect of hyperthermia on AKR murine leukemia and AKR bone marrow cells can be further enhanced by the addition of lidocaine or thiopental to incubation mixtures. These findings may have application to autologous bone marrow transplantation in humans.

Animals↗
PubMed1984

Versatility of distributed focus ultrasound in treatment of superficial lesions.

In order to study the efficacy of hyperthermia as a cancer treatment modality, it is important to be able to define the specific volume being raised to hyperthermic temperatures corresponding to the selected method of heating. Measurements have been made of temperature distributions in rat mammary tumors during steady state heating with annular focused ultrasound (2.0 MHz). Biological response in terms of growth inhibition is compared with uniformity of induced temperature throughout the tumors as a function of annular focusing dimensions.

Animals↗
PubMed1984

Effect of whole body hyperthermia and BCNU on the development of radiation myelitis in the rat.

A radiant heat device was used to study the interaction of 41.8 degrees C whole body hyperthermia (WBH), radiation (40 Gy) and the lipophilic anti-neoplastic agent BCNU in the development of myelitis in the rat spinal cord. The addition of WBH and BCNU neither precipitated myelitis acutely nor shortened the latency before the onset of neurological signs in irradiated animals.

Animals↗
PubMed1984

Aggressive combined modality therapy for advanced local-regional breast carcinoma.

Thirty-two women with advanced local regional breast carcinoma, including nine patients with histologically diagnosed inflammatory cancer, were entered on a prospective pilot study. They were treated aggressively with initial surgery, two courses of induction chemotherapy with cyclophosphamide, methotrexate, 5-fluorouracil, +/- prednisone, +/- tamoxifen (CMF [P] [T]), local-regional radiotherapy, and then maintenance chemotherapy with CMF(P) (T) alternating with doxorubicin, vincristine, +/- tamoxifen (AV[T]). The patients have been followed for 19-70 months from the time of mastectomy and their actuarial three-year survival is 65% with a median survival that has not yet been reached. Median disease-free survival (time to progression) is currently 29.5 months. Women whose gross disease could not be totally resected surgically had shorter disease-free survivals than those rendered surgically free of disease (p = 0.01). Clinically evident cardiotoxicity was seen in 25% of the patients and was felt to be primarily due to the combination of doxorubicin and radiation therapy. It was significantly more common (Plt less than 0.05) in patients with left chest irradiation (seven of 18 women) as opposed to those with right-sided irradiation (one of 14).

Adult↗
PubMed1984

A proposal for the addition of hyperthermia to treatment regimens for acute and chronic leukemia.

The application of hyperthermia to the treatment of neoplastic disease has focused on solid tumors. Human leukemias, both acute and chronic, may represent a unique category of diseases for which hyperthermia should be used in combination with other modalities with curative intent. Three clinical approaches to include hyperthermia are proposed. These are hyperthermia in combination with therapeutic low-dose whole-body irradiation, ablative high-dose total body irradiation, and bone marrow transplantation with the in vitro use of hyperthermia to purge remission bone marrow of abnormal cells. Current preclinical research further supporting these clinical applications of hyperthermia to leukemia therapy is presented.

Animals↗
PubMed1983

Differential sensitivity of AKR murine leukemia and normal bone marrow cells to hyperthermia.

To determine if there is a differential effect of hyperthermia on AKR murine leukemia and AKR normal bone marrow cells incubated in vitro, the fractional survival of leukemic and of normal cells with proliferative potential as a function of heating exposure was estimated by evaluating spleen colony formation. Normal bone marrow colony-forming units were assayed in lethally irradiated (750 centigrays) mice; leukemic colony-forming units were assayed in nonirradiated mice. Electron micrographic studies of leukemic cells treated with 41.8 degrees hyperthermia found that structural damage to the cell, i.e., changes in the Golgi apparatus, was associated with the lack of ability to form colonies. AKR leukemia cells were more sensitive than normal cells to hyperthermic killing at 41.8 degrees and at 42.5 degrees. This differential was found whether cells of each type were heated separately or when mixed together. This model system demonstrates an inherently greater sensitivity of neoplastic cells, as compared to normal syngeneic stem cells, to thermal killing. This finding may have relevance to autologous bone marrow transplantation in humans.

Animals↗
PubMed1982

EMIT theophylline assay at reduced cost.

An experiment was designed to determine if a new EMIT theophylline method that reduces reagent costs can maintain the standard EMIT method's high degree of accuracy and precision. Eight known theophylline concentrations ranging from 1.5 to 75 micrograms/ml were analyzed by both methods. Two hundred five assays were performed on study patients using the new method. During 4 months of clinical service, 51 assays, ranging from 0 to 51 micrograms/ml, were performed by the standard method, and during the following 12 months 213 clinical service assays, ranging from 0 to 35.6 micrograms/ml, were performed by the new method. A strong correlation (r = 0.997) was demonstrated between the new and standard EMIT methods. Both methods had similar variance and curve stability. A 56% reduction in reagent expenses was realized with the new method over a 12-month period.

Adult↗