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Biomedical subjects

J Overgaard

Publications and source records attributed to J Overgaard.

At least 307 records · Page 17Linked to original sources
PubMed1979

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.

Animals↗
PubMed1978

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.

Adolescent↗
PubMed1978

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.

Adult↗
PubMed1977

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.

Adolescent↗
PubMed1977

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.

Animals↗
PubMed1977

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.

Animals↗
PubMed1977

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.

Animals↗
PubMed1977

Hyperthermic tumour-cell devitalization in vivo.

A review of the morphologic, biochemical and clinical effects of hyperthermia on malignant cells indicates the presence of two principally different heat-induced alterations. (1) A 'destructive' lysosomal dependent cytoplasmic reaction dominates the tumour-cell devitalization in vivo, probably influenced by the characteristic tumour cell environment. (2) 'Repressive' nuclear abnormalities may be observed, but seem to be secondary in the in vivo reaction. However, under certain conditions (combined treatment modalities) this nuclear effect may be of importance.

Animals↗
PubMed1976

Occurrence of paired cisternae in the cytoplasm of interphase murine mammary carcinoma cells.

The presence of paired cisternae in the cytoplasm interphase murine mammary carcinoma cells is described. The paired cisternae are composed of about 65A thin trilaminated membranes, about 65A in thickness, with ribosomes attached to the outer membranes, but with smooth adjacent membranes between the cisternae. The function and origin of these structures were not clarified, but it is suggested that they represent surplus fragments of nuclear envelope material.

Animals↗
PubMed1976

Cerebral blood flow in patients with intracranial pressure elevation due to traumatic brain edema.

The object of this study was to determine if traumatic brain edema (BE) and increased intracranial pressure (ICP) reduce cerebral blood flow (CBF). Two groups of patients were studied, one with slight BE and ICP less than 20 mm Hg., the other with pronounced BE and ICP over 20 mm Hg. Although ICP was higher and cerebral perfusion pressure lower in pronounced edema there was only a small and non-significant reduction in CBF and no difference in cerebro-vascular resistance. Since traumatic BE does not increase resistance to blood flow through the brain, cerebral perfusion can be maintained if an adequate perfusion pressure is established. This in turn, demands the monitoring and control of ICP.

Blood Pressure↗
PubMed1976

Influence of extracellular pH on the viability and morphology of tumor cells exposed to hyperthermia.

The influence of hyperthermia (42.5 degrees C) on the viability and morphology of L1A2 ascites cells incubated at various pH levels (6.4-7.2) was studied. In contrast to unheated cells, increased extracellular acidity in hyperthermically treated tumor cells was associated with markedly reduced viability of the tumor cells exposed to hyperthermia. The cells heated at neutral pH underwent ultrastructural nuclear changes; the most prominent were the appearance of filamentous bundles and increased perichromatin granules. The cells heated under more acid conditions had an increased lysosomal activity and intense cell lysis resulting in lethal damage to the entire cell population within 6 hours after treatment. The active mechanism was not clear, but cell membrane lesions combined with the increased lysosome activity seemed of major importance in the mechanism of heat-induced damage to tumor cells kept in an acid milieu.

Animals↗
PubMed1976

Cerebral circulation after head injury. Part 2: The effects of traumatic brain edema.

The authors have assessed the effects of subacute traumatic brain edema (BE) on cerebral circulation and metabolism, and on clinical outcome. Fifty-five severely injured, comatose, young patients who survived for more than 24 hours were studied on 78 occasions within 30 days of injury. After hematomas had been surgically evacuated, BE was diagnosed by radiological evidence of brain swelling, demonstrated by cerebral angiograms and ventriculograms. At identical levels of carbon dioxide pressure, intracranial pressure was significantly elevated in the Edema Group to twice the value in the No Edema Group (27.1 vs 14.1 torr). There were, however, no significant differences in cerebral perfusion pressure cerebral blood flow, resistance to blood flow, cerebral metabolic oxygen rate, ventricular cerebrospinal fluid acid-base, lactate, K+ or Na+ concentrations, or in clinical outcome. It is concluded that this type of subacute traumatic BE, which is significantly associated with surgical lesions, is not of major hemodynamic or clinical significance in intensively treated patients, and does not cause cerebral ischemia. Patient outcome is determined more by the severity of the initial diffuse cortical and subcortical injury than by the presence or absence of subacute BE.

Adolescent↗
PubMed1976

Ultrastructure of a murine mammary carcinoma exposed to hyperthermia in vivo.

The ultrastructural changes following local hyperthermic therapy was studied in a solid murine mammary carcinoma. A few hr after treatment, a pronounced lysosomal activity was observed in the cytoplasm of the tumor cells, together with mitochondrial destruction and disaggregation of the polyribosomes. Later, more destructive changes with intense cell shrinkage and cytoplasmic lysis occurred, and within 24 hr the entire cytoplasm of all the tumor cells was completely destroyed. In the nuclei shrinkage and condensation of heterochromatin were early features. The nucleoli were gradually degranulated, but with preservation of the fibrillary component. However, here, too, complete destruction occurred within the first few days after treatment. Cells in mitosis were also arrested and destroyed in the same way. The nonmalignant cells of the tumor tissue presented only minor reversible morphological changes, and within a few days the tumor area was replaced by ingrowth of fibroblasts and macrophages. The morphological changes are discussed in the light of our present knowledge of the hyperthermic effect on tumor cells. As regards the mechanism of hyperthermic destruction of solid tumors in vivo, the hypothesis is advanced that a primary, lysosomally conditioned, selective destruction of the malignant cells occurs and that this reaction is intensified by a high acidity in the tumor milieu.

Acid Phosphatase↗
PubMed1976

Combined adriamycin and hyperthermia treatment of a murine mammary carcinoma in vivo.

A study was made of the effect of combined adriamycin and hyperthermic treatment in a solid mouse mammary carcinoma in vivo. This study demonstrated: (a) that, when given separately, adriamycin and hyperthermia enhance the destruction of a solid mouse mammary carcinoma in vivo; hyperthermia (40.5-42.5 degreesy greatly increases tumor destruction and, in a number of cases, caused initial and long-time regression; (c) that whole-body hyperthermia in combination with adriamycin gives a significant delay in tumor growth as compared with the controls, but not to the same degree as the local combined therapy; and (d) that treatment with local hyperthermia and adriamycin gives a pronounced decrease in the lethal toxicitity of adriamycin. The effect of adriamycin and heat treatment may be due to hyperthermic cell destruction in the central area of the solid tumor, together with a synergistic effect of heat and adriamycin on the proliferating peripheral tumor cells. Furthermore, local heat application may increase the adriamycin concentration in the heated tumor area, which causes a high destructive effect and a less toxic influence on the nonheated normal tissue.

Animals↗