Biomedical subjects
J Overgaard
Publications and source records attributed to J Overgaard.
Treatment of early carcinoma of the breast.
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[New aspects in radiotherapy. II. Hyperthermia and irradation].
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[New aspects of radiotherapy. I. Significance of hypoxia in irradiation of solid tumors].
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Synergistic cell cycle kinetic effect of low doses of hyperthermia and radiation on tumour cells.
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Effect of local hyperthermia on the acute toxicity of misonidazole in mice.
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Hyperthermic radiosensitization of thermotolerant tumour cells in vitro.
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Lack of radiation protective effect of orgotein in normal and malignant mammalian cells.
The potential radiation protective effect of orgotein, a metalloprotein with superoxide dismutase activity, was investigated in L1A2 tumour cells in vitro, jejunal crypt cells and C3H mouse mammary carcinoma in vivo. No effect of orgotein, given either 2 hours before irradiation or 30 min after, was observed compared to the effect of irradiation alone. Thus, it was concluded that orgotein did not influence the primary radiation response in air in mammalian cells.
Effect of extracellular pH on thermotolerance and recovery of hyperthermic damage in vitro.
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Time-temperature relationship th hyperthermic treatment of malignant and normal tissue in vivo.
The effect of hyperthermia on normal and tumor tissue was studied following water bath heating of a methylcholanthrene-induced fibrosarcoma (FSaI) isotransplanted into the feet of C3H mice. The time-temperature relation for the 50% tumor control dose over the temperature range of 41.5--45.5 degrees showed a log linear relationship which followed a biphasically modified Arrhenius plot. At temperatures above 43 degrees, there was a 50% reduction in heating time to obtain the 50% tumor control dose for each 1 degree increase in temperature, corresponding to an activation energy of 140 kcal/mol. At temperatures below 43 degrees, the curve was steeper, with a tendency to double the treatment time for each 0.5 degree reduction in temperature (activation energy, approximately 230kcal/mol). Normal tissue damage in the tumor-bearing foot was estimated at two levels with a 50% response dose assay. Severe normal tissue damage showed a time-temperature relationship similar to the tumor response, thus indicating no variation in therapeutic ratio at different temperatures. However, for slight tissue damage, the therapeutic ratio increased with decreasing temperatures, yielding a better therapeutic ratio at lower temperatures. The time-temperature relationship obtained in the FSaI fibrosarcoma is supported by other studies and points to a general time-temperature relationship for hyperthermic tumor destruction.
[Radiotherapy of colo-rectal cancer].
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Althesin in neurosurgical patients: effects on cerebral hemodynamics and metabolism.
The effect of althesin 0.5 ml/10 kg on arterial blood pressure, intracranial pressure, cerebral blood flow and oxygen uptake was studied on 19 occasions in 16 patients with varied cerebral pathology. Cerebral blood flow (CBF) was measured using the intracarotid 133xenon method and a 35-channel scintillation detector after cannulation of the internal carotid artery, the internal jugular bulb and the lateral cerebral ventricle. Arterial and intracranial pressures were recorded continuously. Blood gas tensions were measured in simultaneously drawn samples from the internal carotid artery and the jugular bulb. Cerebral oxygen uptake was calculated from the product of CBF and arteriovenous oxygen content difference. Control values were obtained with the patients under a basic general anesthesia, consisting of N2O/O2 pancuronium. The effect of a bolus injection of althesin was then studied 1 and 20 min after the injection. A significant reduction in intracranial pressure, cerebral blood flow and metabolism at 1 min was found to have essentially subsided 20 min after the injection. In patients with focal brain damage, regional flow analysis revealed a paradoxical increase in flow after althesin in the areas corresponding to the focus.
Chroma-Memo-Flow technique for rapid sequential analysis of regional cerebral blood flow (rCBF) responses.
This is the first report of a method of sequential regional cerebral blood flow (rCBF) analysis, called Croma-Memo-Flow. This technique is a computerized modification of the initial slope method of regional cerebral blood flow (rCBF init.), allowing temporal resolution of the flow pattern by calculation of the slopes of sequential segments of the initial 1-2 minutes of the Xenon-133 washout curve. The same theoretical analysis applies to this method as to the rCBF init. method. Each flow calculation is based on the slope of a discrete 16 second segment of the initial washout; and each second the segment is advanced by one second. A new flow calculation is made each second and is displayed as a color coded map on a TV screen. Each map is labelled, indicating the time in seconds following Xenon injection, and sequential rCBF changes during the clearance period can be immediately visualized. This allows for almost instantaneous analysis and display of rapid or transient rCBF responses to activation and deactivation of the cerebral cortices. The data is stored in a 35 channel memory for deliberate replay, photography, and analysis. Functional tests may be applied during the initial washout period and both the magnitude and chronological relationships of the evoked regional cerebrovascular responses observed. A clinical study is presented to illustrate the possibilities of applying the technique to assess cortical reactivity.
Primary leiomyosarcoma of bone.
A case of primary leiomyosarcoma of bone in the femur of an 18-year-old girl is described. Light and electron microscopy showed characteristic changes with cytoplasmic myofilaments, dense bodies, pinocytic vesicles and basal lamina fragments. Clinically, the patient is well and without evidence of tumor 9 months after the femur amputation without further treatment.
Effect of hyperthermia on malignant cells in vivo. A review and a hypothesis.
The relevant literature is reviewed in an attempt to clarify the mechanism of heat-dependent tumor cell destruction in vivo. Malignant cells in vivo appear to be selectively destroyed by hyperthermia in the range of 41-43 degrees C. Heat evidently affects nuclear function, expressed by an inhibited RNA, DNA and protein synthesis and characteristic arrest or delay of cells in certain locations of the cell cycle. However, as these effects appear to be reversible and are observed in normal cells as well as malignant cells, they probably do not explain the hyperthermic induced selective in vivo destruction of malignant cells. Heat-induced cytoplasmic damage appears to be of more importance. Increased lysosomal activation is observed, and is further intensified by a relatively increased anaerobic glycolysis which develops selectively in tumor cells. A hypothesis is proposed and discussed which explains the marked and selective in vivo tumor cell destruction as a consequence of the enhancing effect on the cytoplasmic damage of certain environmental factors (e.g. increased acidity, hypoxia and insufficient nutrition.
Effect of hyperthermia and environmental acidity on the proteolytic activity in murine ascites tumor cells.
The influence of hyperthermia and environmental pH on proteolytic activity was studied in murine ascites tumor cells in vitro. PNJ ascites tumor cells were incubated with [125I]cytochrome c at 42.5 or 37 degrees C in a modified Krebs-Ringer buffer adjusted to pH 7.2 or 6.4. Incubation at normal temperature at pH 6.4 and 7.2 or at 42.5 degrees C and pH 7.2 resulted in identical protein digestion. However, hyperthermic incubation at pH 6.4 resulted in a significant increased activity. This was also observed after only 1 hour of hyperthermic incubation followed by subsequent incubation in an acidic environment at normal temperature. The increased proteolytic activity following hyperthermic treatment under acidic conditions may support the hypothesis that increased lysosomal activity is of primary importance in the hyperthermic tumor-cell destruction in vivo.
The influence of hypoxia and acidity on the hyperthermic response of malignant cells in vitro.
Colony formation of JB-1-E tumor cells was studied after hyperthermic treatment (42.5 degrees C) at a pH of 6.4 or 7.2 under hypoxic and euoxic conditions. At a pH of 7.2 and normal oxygen tension, there was a moderate decrease in colony formation with increasing duration of hyperthermic treatment (To = 65 min.). This effect was slightly enhanced under hypoxic conditions (To = 36 min.). The hyperthermic effect was enhanced to a considerably greater degree when treatment was performed at a pH of 6.4 (To = 19 min.), with no observable difference between hypoxia and euoxia. These findings indicate that environmental acidity is a determining factor in the hyperthermic effect. The hypoxic effect at a pH of 7.2 is probably due to a slight decrease in the intracellular pH caused by increased production of lactic acid.
The effect of sequence and time intervals of combined hyperthermia and radiation treatment.
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