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At least 19 records

Prostacyclin-induced hyperthermia - Implication of a protein mediator

The mechanism of the prostacyclin-linked hyperthermia is studied in rabbits. Results show that intracerebroventricular administration of prostacyclin (PGI2) induces dose-related hyperthermia at room temperature (21 C), as well as at low (4 C) and high (30 C) ambient temperatures. It is found that this PGI2-induced hyperthermia is not mediated by its stable metabolite 6-keto prostaglandin F-1(alpha). Only one of the three anion transport systems, the liver transport system, appears to be important to the central inactivation of pyrogen, prostaglandin E2, and PGI2. Phenoxybenzamine and pimozide have no thermolytic effect on PGI2-induced hyperthermia, while PGI2 still induces hyperthermia after norepinephrine (NE) and dopamine levels are depleted by 6-hydroxydopamine. Indomethacin and SC-19220 (a PG antagonist) do not antagonize PGI2 induced hyperthermia, while theophylline does not accentuate the PGI2-induced hyperthermia. However, the hyperthermic response to PGI2 is attenuated by central administration of the protein synthesis inhibitor, anisomycin. It is concluded that PGI2-induced hyperthermia is not induced by NE, dopamine, or cyclic AMP, but rather that a protein mediator is implicated in the induction of fever by PG12.

Kandasamy, S. B.↗

Numerical modeling for an electric-field hyperthermia applicator

Hyperthermia, in conjunction with radiation and chemotherapy for treatment of cancers, is an area of current concern. Experiments have shown that hyperthermia can increase the potency of many chemotherapy drugs and the effectiveness of radiation for treating cancer. A combination of whole body or regional hyperthermia with chemotherapy or radiation should improve treatment results. Conventional methods for inducing whole body hyperthermia, such as exposing a patient in a radiant cabinet or under a hot water blanket, conduct heat very slowly from the skin to the body core. Thus a more efficient system, such as the three-plate electric-field hyperthermia applicator (EHA), is developed. This three-plate EHA has one top plate over and two lower plates beneath the patient. It is driven at 27.12 MHz with 500 Watts through a matching circuit. Using this applicator, a 50 kg pig was successfully heated to 42 C within 45 minutes. However, phantom and animal studies have indicated non-uniform heating near the side of the body. In addition, changes in the size and distance between the electrode plates can affect the heating (or electromagnetic field) pattern. Therefore, numerical models using the method of moments (MOM) or the finite difference time domain (FDTD) technique are developed to optimize the heating pattern of this EHA before it is used for human trials. The accuracy of the numerical modeling has been achieved by the good agreement between the MOM and FDTD results for the three-plate EHA without a biological body. The versatile FDTD technique is then applied to optimize the EHA design with a human body. Both the numerical and measured data in phantom blocks will be presented. The results of this study will be used to design an optimized system for whole body or regional hyperthermia.

Wu, Te-Kao↗

Hyperthermia in the treatment of cancer: A review of the radiobiological basis

Temperatures in the range 41.5 C to 43.5 C tend to be more damaging to malignant than nonmalignant cells. Where local hyperthermia (41.5 C to 43.5 C) is combined with ionizing radiation, a significant therapeutic ratio may be realized. Total body hyperthermia, alone or combined with other therapeutic modalities, can provide palliation for some systemic malignancies but may not be as effective as local hyperthermia for treating local disease. The influence of hyperthermia on immune mechanisms and the risk of metastatic spread of potential tumor growth stimulation need further investigation. Among other questions needing elucidation before hyperthermia can be considered a standard treatment modality are the time-dose (for heating) relationships to produce an optimal therapeutic ratio and whether the late sequela of combined heat and ionizing radiation may result in an unacceptable risk of patient morbidity.

Baker, D. G.↗

Peptide and non-peptide opioid-induced hyperthermia in rabbits

The intracerebroventricular administration of prototype nonpeptide opioid receptor (mu, kappa, and sigma) agonists, morphine, ketocyclazocine, and N-allyl-normetazocine was found to induce hyperthermia in rabbits. The similar administration of peptide opioids like beta-endorphin (BE), methionine-enkephalin (ME), and its synthetic analogue D-ala2-methionine-enkephalinamide (DAME) was also found to cause hyperthermia. Results indicate that only the liver-like transport system is important to the ventricular inactivation of BE and DAME. Prostaglandins and norepinephrine were determined not to be involved in peptide and nonpeptide opioid-induced hyperthermia. In addition, cAMP was not required since a phosphodiesterase inhibitor, theophylline, did not accentuate the hyperthermia due to peptide and nonpeptide opioids. Naloxone-sensitive receptors were found to be involved in the induction of hyperthermia by morphine, BE, ME, and DAME since naloxone attenuated them. However, the hyperthermic response to ketocyclazocine and N-allyl-normetazocine was not antagonized by naloxone.

Kandasamy, S. B.↗

Temperature distribution in the human body under various conditions of induced hyperthermia

A mathematical model based on heat balance equations was developed for studying temperature distribution in the human body under deep hyperthermia which is often induced in the treatment of malignant tumors. The model yields results which are in satisfactory agreement with experimental data. The distribution of temperature under various conditions of induced hyperthermia, i.e. as a function of water temperature and supply rate, is examined on the basis of temperature distribution curves in various body zones.

Korobko, O. V.↗

The effect of hyperthermia on the radiation response of crypt cells in mouse jejunum

The effect of hyperthermia and/or gamma-radiation on the survival of intestinal crypt cells was studied in BDF sub 1 mice using a microcolony assay. Hyperthermia treatments, which in themselves caused no detectable cell lethality, inhibited the capacity of crypt cells to repair sublethal radiation damage. In addition, heat applied either before or after single radiation exposures potentiated lethal damage to crypt cells; the degree of enhancement was dependent on the time interval between treatments. At the levels of heating employed, DNA synthesis in the intestinal epithelium was significantly reduced immediately following exposure, but returned rapidly to normal levels. No further disturbances in cellular kinetics were observed for up to 10 days after heating.

Wilson, J. D.↗

A microangiographic study of the effect of hyperthermia on the rabbit bladder

A model was used to study the effect of hyperthermia on a normal tissue. The model selected was the rabbit bladder and the end point measured was the changes in the micro-vasculature of the bladder wall. It was already demonstrated clinically that hot water bladder infusions produce regression in bladder tumors.

Hietala, S. O.↗

Hyperthermia and exercise

The paper emphasizes fluid and electrolyte parameters that affect the hyperthermia of physical exercise (metabolic heat production). The major hypothesis discussed is that fluid and electrolyte changes influence thermal regulation within the fine control boundaries. A second working hypothesis is that the elevation of core temperature during exercise is a regulated phenomenon that is beneficial to the organism in terms of efficiency and potential for survival and is not merely a failure of the thermoregulatory control system. The central thermoregulatory mechanism seems more responsive to the hypothermic effect of calcium than to the hyperthermic effect of sodium. The mechanisms controlling plasma fluid-electrolyte shifts, particularly during exercise and recovery from exercise, may play an important part in exercise thermoregulation.

Greenleaf, J. E.↗

Temperature controller for hyperthermia devices

Temperature controller monitors and controls temperature in local region of tumor. Medical grade thermocouples are inserted in or near tumor, controller pulse modulates radio frequency diathermy power source to maintain temperature within 0.2 C. System may be extended to control diathermy of more than one tumor or patient.

Couch, R. H.↗

Hyperthermia heating apparatus

Electromagnetic energy is delivered to a localized area of a patient's body in a hyperthermic treatment so that it provides a uniform distribution of electromagnetic flux lines within the localized area of the patient's body and produces a uniform and localized heating gradient. An electrode array includes a number of electrodes which are arranged in pair, with the electrodes in each pair being spaced a particular distance apart. The array is driven by a balanced line system which is electromagnetically coupled to each pair of electrodes and which is shielded by a ground coaxial shield which itself is ground to the body of the patient. Each electrode is embedded in a Teflon stand-off in order to move the region of strong field, from the body, produced by rapidly changing potentials. The two pairs of electrodes forming a cross-like geometry are used with the balanced line systems. The electrical power is either multiplexed among the electrodes or the second pair is driven by a potential which is sinusoidal and which is 90% out of phase with the first balanced line system which is also sinusoidal.

Gammell, P. M.↗

Exercise hyperthermia as a factor limiting physical performance - Temperature effect on muscle metabolism

The effect of trunk cooling on the muscle contents of ATP, ADP, AMP, creatine phosphate (CrP), and creatine, as well as of glycogen, some glycolytic intermediates, pyruvate, and lactate were assessed in 11 fasted dogs exercised at 20 C on treadmill to exhaustion. Without cooling, dogs were able to run 57 min, and their rectal (Tre) and muscle (Tm) temperatures increased to 41.8 and 43.0 C, respectively. Cooling with ice packs prolonged the ability to run by 45 percent, and resulted in lower Tre (by 1.1 C) and Tm (by 1.2 C). Depletion of muscle content of total high-energy phosphates (ATP + CrP) and glycogen, and increases in contents of AMP, pyruvate, and lactate were lower in cooled dogs than in non-cooled dogs. The muscle content of lactiate correlated positively with TM. These results indicate that hypothermia accelerates glycolysis, and shifts the equilibrium between high- and low-energy phosphates in favor of the latter. The adverse effect of hypothermia on muscle metabolism may be relevant to the limitation of endurance.

Kozlowski, S.↗

Magnetic Microspheres for Therapeutical Applications

Hyperthermia is a well known cancer therapy and consists of heating a tumor region to the elevated temperatures in the range of 40-45 C for an extended period of time (2-8 hours). This leads to thermal inactivation of cell regulatory and growth processes with resulting widespread necrosis, carbonization and coagulation. Moreover, heat boosts the tumor response to other treatments such as radiation, chemotherapy or immunotherapy. Of particular importance is careful control of generated heat in the treated region and keeping it localized. Higher heating, to about 56 C can lead to tissue thermo-ablation. With accurate temperature control, hyperthermia has the advantage of having minimal side effects. Several heating techniques are utilized for this purpose, such as whole body hyperthermia, radio-frequency (RF) hyperthermia, ultrasound technique, inductive microwave antenna hyperthermia, inductive needles (thermoseeds), and magnetic fluid hyperthermia (MFH).MFH offers many advantages as targeting capability by applying magnets. However, this technology still suffers significant inefficiencies due to lack of thermal control. This paper will provide a review of the topic and outline the ongoing work in this area. The main emphasis is in devising ways to overcome the technical difficulty in hyperthermia therapy of achieving a uniform therapeutic temperature over the required region of the body and holding it steady. The basic obstacle of the present heating methods are non-uniform thermal properties of the tissue. Our approach is to develop a novel class of magnetic fluids which have inherent thermoregulating properties. We have identified a few magnetic alloys which can serve as a suitable nano-particle material. The objective is to synthesize, characterize and evaluate the efficacy of TRMF for hyperthermia therapy.

Mazuruk, K.↗

Magnetic Microspheres and Tissue Model Studies for Therapeutical Applications

Hyperthermia is a well known cancer therapy and consists of heating a tumor region to the elevated temperatures in the range of 40-45 C for an extended period of time (2-8 hours). This leads to thermal inactivation of cell regulatory and growth processes with resulting widespread necrosis, carbonization and coagulation. Moreover, heat boosts the tumor response to other treatments such as radiation, chemotherapy or immunotherapy. Of particular importance is careful control of generated heat in the treated region and keeping it localized. Higher heating, to about 56 C can lead to tissue thermo-ablation. With accurate temperature control, hyperthermia has the advantage of having minimal side effects. Several heating techniques are utilized for this purpose, such as whole body hyperthermia, radio-frequency (RF) hyperthermia, ultrasound technique, inductive microwave antenna hyperthermia, inductive needles (thermoseeds), and magnetic fluid hyperthermia (MFH).MFH offers many advantages as targeting capability by applying magnets. However, this technology still suffers significant inefficiencies due to lack of thermal control. This paper will provide a review of the topic and outline the ongoing work in this area. The main emphasis is in devising ways to overcome the technical difficulty in hyperthermia breast therapy of achieving a uniform therapeutic temperature over the required region of the body and holding it steady for an extended period (2-3 hours). The basic shortcomings of the presently utilized heating methods stem from the non-uniform thermal properties of the tissue and the point heating characteristics of the techniques without any thermal control. Our approach is to develop a novel class of magnetic fluids, which have inherent thermoregulating properties. We have identified a few magnetic alloys which can serve as suitable nano to micron-size particle material. The objective is to synthesize, characterize and evaluate the efficacy of Thermo Regulating Magnetic Fluids (TRMF) for hyperthermia therapy. The development of a tissue model and testing the fluid dynamics of particle motion, settling, distribution in the tissue matrix and heat generation will be discussed.

Ramachandran, N.↗