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Biomedical subjects

H I Robins

Publications and source records attributed to H I Robins.

At least 91 records · Page 5Linked to original sources
PubMed1985

A nontoxic system for 41.8 degrees C whole-body hyperthermia: results of a Phase I study using a radiant heat device.

A Phase I study of whole-body hyperthermia (WBH) (52 treatments/12 patients) was completed with no significant clinical toxicity. The study incorporated a thermal dose escalation scheme from 39.5 degrees-41.8 degrees C for up to 151 min. A radiant-heat device was utilized for producing WBH. During WBH, patients were sedated; endotracheal intubation was not required. No changes in cardiovascular, respiratory, hematological, or biochemical indices requiring clinical intervention occurred during the study. We conclude the radiant-heat device coupled with a defined pharmacological approach to WBH with appropriate patient screening yields a system for 41.8 degrees C WBH which is safe and efficient, is not labor intensive, and does not require general anesthesia and endotracheal intubation. This system is appropriate for a multimodality approach to various systemic cancers.

Adolescent↗
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

Late recurrences of histiocytic lymphoma after treatment.

Disease-free intervals of 2 to 3 years after treatment of histiocytic lymphoma are generally thought to represent cures; flat survival curves beyond 3 years in several studies support this notion. Four case reports of histiocytic lymphoma recurrences 25, 10, 9 and 6 years, respectively, after the initial diagnosis are presented. Histologic confirmation comparing primary and recurrent disease is presented. The potential biological significance of such patient reports is discussed.

Adult↗
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

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↗
PubMed1984

Role of whole-body hyperthermia in the treatment of neoplastic disease: its current status and future prospects.

Modern cancer therapy has included surgery, radiotherapy, chemotherapy, and most recently, immunotherapy and hyperthermia. As neoplastic diseases are heterogeneous in regard to each cell subpopulation's response to a given therapy, a multimodality treatment approach should enhance the changes of all subpopulations of cells being killed. The potential of hyperthermia as a treatment modality for cancer was first predicted following observations that several types of cancer cells were more sensitive to temperatures in excess of 41 degrees than were their normal cell counterparts. Beyond these studies, there now is preclinical evidence as well as the clinical suggestion that hyperthermia potentiates radiation and/or drugs for the treatment of cancer. As most cancers refractory to conventional therapy are systemic diseases, the proposal that whole-body hyperthermia in combination with other therapies be used to treat metastatic disease is an inherently attractive approach. The basis and the practicality of this proposal is presented here with suggestions for its application to current preclinical and clinical research.

Body Temperature↗
PubMed1984

Augmented antiproliferative effects of interferons at elevated temperatures against human bladder carcinoma cell lines.

The in vitro antiproliferative effects of interferons (IFN) against the human bladder carcinoma cell lines T24, RT4, HT1197, and 647V were evaluated at temperatures ranging from 37-41 degrees. At 37 degrees, the antiproliferative activities of IFN, either naturally produced or produced by recombinant DNA technology, were different against different cell lines. An increase in temperature markedly enhanced the antimitotic effect of IFN for all cells. For example, T24 cells grown at 37 degrees and treated with 200 units naturally produced IFN-alpha or IFN-beta per ml for 7 days were inhibited 50 to 60%. No change in cell proliferation occurred in untreated T24 cells grown at 39.5 degrees. Treatment with 200 units IFN-alpha or IFN-beta per ml at 39.5 degrees inhibited these cells 80 to 90%. Similar results were obtained with IFN produced by recombinant DNA technology and purified to homogeneity. Colony formation by the RT4 cell line, at 37 degrees, was decreased less than 10% with 200 units IFN-alpha per ml and 63% by 200 units IFN-beta per ml. At 39.5 degrees, colony formation by untreated RT4 cells was inhibited 48%. Treatment with IFN-beta at 39.5 degrees did not result in an enhancement of the antiproliferative effect; however, treatment with IFN-alpha enhanced the inhibition from less than 10% to 98%. These results suggest that a supraadditive relationship exists between antiproliferative effects of IFN and temperature elevation. The differences seen between IFN-alpha and IFN-beta may be due to the different stabilities of these two molecules. In order to probe the mechanism of the enhanced antiproliferative effect, activity of an IFN-induced enzyme, 2'-5'-oligoadenylate synthetase, was measured. IFN-alpha treatment resulted in significantly greater 2'-5'-oligoadenylate synthetase induction at 39.5 degrees than at 37 degrees. Thus, two cellular effects resulting from IFN were augmented by increased temperature.

2',5'-Oligoadenylate Synthetase↗
PubMed1983

Whole body hyperthermia with a microwave regional boost: unexpected toxicity in the pig.

An animal model was used to investigate the potential for delivering a regional temperature boost using microwave energy after whole body hyperthermia had been induced in a pig using low density, radiant heat. Thermal profiles and an unexpected toxicity in the region of the microwave energy deposition, which included the heart and liver, are reported.

Animals↗
PubMed1983

Heated lymphocytes express HLA-DR antigens despite their inability to stimulate in MLC.

We have utilized serological techniques and mixed lymphocyte culture (MLC) reactions to examine HLA-DR and HLA-D expression by heated (45 degrees C for 1 h) lymphocytes in order to study the functional relationship of these antigens. Heated lymphocytes do not stimulate proliferation of allogeneic lymphocytes in MLC, yet they express HLA-DR antigens. The fraction of peripheral blood lymphocytes (PBL) expressing DR is not altered by heating, nor is the staining intensity altered as detected by fluorescence microscopy. Alloantisera to "B cell alloantigens" recognize HLA-DR determinants on heated cells without any detectable change in either specificity or quantitative cytotoxic effects. Flow cytometry with monoclonal antibody demonstrates only minimal decrease in HLA-DR expression after heating. Thus stimulation in MLC requires more of the stimulating cell than the mere expression of HLA-DR.

B-Lymphocytes↗
PubMed1983

Structural changes in murine cancer associated with hyperthermia and lidocaine.

Hyperthermia alone and hyperthermia with lidocaine cause changes in the fine structure of the CA755 tumor cell as well as the breakdown of the tumor vasculature. The first structural change, observed immediately after termination of hyperthermia of 43.5 degrees for 1 hr, is the vesiculation of the Golgi apparatus. Other structural changes occur later but with variable times of onset. The changes appear to be unrelated to the presence of lidocaine. Vascular breakdown results in hemorrhaging within the tumor, and its onset and intensity appear to vary directly with the size of the tumor. Breakdown of the tumor cell plasmalemma and degenerative changes of the cytoplasm and nucleoplasm are seen more frequently in large tumors and in the interior of small tumors at any given time after the end of hyperthermia. The vesiculation of the Golgi persists in treated cells for as long as 30 hr. This modification may represent an intensification in the function of the Golgi apparatus; however, it closely corresponds to that found in a variety of other cells treated with a class of compounds, including lidocaine, that specifically inhibits the function of the Golgi apparatus. The effect of these compounds is rapidly reversible, unlike hyperthermia. Since the Golgi apparatus probably is crucial in repairing any deleterious effects of hyperthermia, any impairment of its normal function would place most treated tumor cells in a difficult position. The rate of tumor destruction may ultimately depend on the breakdown of the tumor vasculature following hyperthermia and lidocaine.

Adenocarcinoma↗
PubMed1983

Preclinical trial of a radiant heat device for whole-body hyperthermia using a porcine model.

After review of the published clinical experience with systemic hypothermia, we concluded that a simple system which controls radiant heat balance to supplement metabolic heat might provide several advantages, including: (a) decreased morbidity; (b) elimination of the requirement for general anesthesia; (c) improved patient comfort; (d) favorable cost-benefit considerations. We have tested a prototype radiant heat device for whole-body hyperthermia (WBH) in patients with disseminated cancer. From preclinical evaluation of this device, the lightly anesthetized pig was found to be an ideal model for WBH. This species has physiological characteristics closely resembling those of humans. The pig's core, pulmonary artery, liver, rectal, and esophageal temperatures were raised to 41.8 degrees in 80 to 90 min. The air temperatures near the chamber wall never exceeded 65 degrees while the air temperature adjacent to the animal was 46 degrees. Skin temperatures were approximately 42.5 degrees at a core temperature of 41.8 degrees. Once the core temperature is raised to 41.8 degrees, this temperature is maintainable for approximately 3.5 hr without additional external heating if evaporative losses are controlled. Prolonged WBH was accomplished with light sedation and without the requirement for endotracheal intubation. No significant acute toxicity was encountered in a series of 6 pigs undergoing 9 separate exposures to WBH. From these results, we conclude that our radiant heat apparatus is feasible for clinical trials. Additionally, the use of the pig as an appropriate animal model for further physiological and pharmacological WBH studies is strongly recommended.

Animals↗
PubMed1983

Systemic lidocaine enhancement of hyperthermia-induced tumor regression in transplantable murine tumor models.

Previously, we reported that local lidocaine infusion of a CA 755 mammary adenocarcinoma growing in C57BL X DBA/2 F1 mice, when combined with local heating for 1 hr in a 43.5 degrees water bath, significantly increased survival and inhibited tumor growth more than heating alone. Because of its clinical implications, systemic lidocaine was tested in the above model system and in a murine fibrosarcoma tumor model. An equivalent supraadditive, tumor-inhibitory effect of heat and lidocaine was obtained with both systemically and intratumor-administered lidocaine. The serum levels of lidocaine necessary to achieve tumor regression were within the therapeutic range for the control of arrhythmia in humans. Several treatment schedules, varying the mode of drug delivery, were evaluated. The effects of treatment on tumor growth characteristics were analyzed using an extension of the Cox survival model.

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↗
PubMed1981

Vindesine. A phase II trial in advanced breast cancer patients.

A phase II trial of vindesine (VDS), a new vinca alkaloid, has been carried out in 40 patients with metastatic breast cancer. Patients entered in the study had been previously treated with an average of two chemotherapy regimens. Treatment was given as a weekly I.V. bolus of VDS at 3 mg/m2. The response rate in 31 evaluable patients was 19%, i.e., one complete response (CR), four partial responses, and one improvement in osseous disease (IMP). In 36 patients evaluable for toxicity, neurological and hematological toxicity was most significant. Half the patients treated had received previous vincristine therapy; this factor did not appear significant with regard to toxicity or response to VDS.

Adult↗