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Biomedical subjects

J A McDougall

Publications and source records attributed to J A McDougall.

At least 19 recordsLinked to original sources
PubMed2001

Variations of dose and electrode spacing for rat breast cancer electrochemical treatment.

Electrochemical treatment (EChT) with direct current delivered through implanted electrodes has been used for local control of solid tumors in humans. This study tested the hypothesis that rat breast cancer responses to EChT are dependent on electrode spacing and dose, and explored suitable parameters for treating breast cancers with EChT. Rat breast cancers were initiated by injecting 1 x 10(6) MTF-7 cells to the right mammary gland fat pad of Fisher 344 female rats. The rats were randomly divided into designated experimental groups when the tumors grew to approximately 2 x 2 x 2 cm. One hundred and thirty rats were used for a survival study and 129 for a pathology study. A 4-channel EChT machine was used to administer coulometric doses. The survival study indicated that local tumor control rate is less than 40% in the 40 coulomb (C) and 60 C groups and more than 70% in the 80 and 100 C groups. Sixty six rats died of primary tumors, including all 10 rats in the control group. Once a rat's primary tumor was controlled, no recurrence was found. The main reason for terminating the primary tumor-free rats (51) was lymph node metastasis. Thirteen tumor-free rats survived for more than 6 months. The pathology study showed a significant dose effect on EChT induced tumor necrosis. At 10, 20, 40, and 80 C, the fraction showing necrosis were 39.7, 52.3, 62, and 77.7%, respectively (P </= 0.001). Electrodes spacing was not an important factor within a given range. At 5, 10, and 15 mm spacing, the fraction showing the necrosis were 54.1, 60.4, and 59.2%, respectively (P = 0.552). The overlap rate of necroses was similar in the 5 and 10 mm groups (82.5 and 85%) and lower in the 15 mm group (65%). We conclude that the tumor responses to EChT, local control, survival rates, and necrosis percentages were significantly increased with increasing dose. The changes in electrode spacing (3, 5, and 10 mm) did not significantly affect the tumor responses to EChT within the same dose. For a diameter of 2.0-2.5 cm rat breast cancer, EChT should be applied with 5-10 mm spacing and a minimum dosage of 80 C.

Animals↗
PubMed1999

A quarter century of in vitro research: a new look at exposure methods.

The specific absorption rate (SAR) distributions in radio frequency-exposed solutions containing suspended or plated cells in vessels used for in vitro research were calculated by the finite-difference-time-domain method, graphed in color, and statistically analyzed in terms of uniformity for application to research on safety of wireless devices. The uniformity of SAR was quantified by visual inspection of colored plots, histograms, means, standard deviations, and maximums for the cell suspensions exposed in test tubes, Petri dishes, and rectangular flasks. Exposure sources included plane waves, transverse electromagnetic (TEM) cells, and striplines used at frequencies of 837, 2450, or 3,000 MHz. The results demonstrated that the most nonuniform SARs for plated or suspended cells in solution occurred for exposures of test tubes and rectangular flasks with plane waves, polarized for maximal absorption. The most uniform SARs for a layer of cells occurred for exposure of Petri dishes oriented for weakest coupling to the fields in a TEM cell. Additional improvement in uniformity was found to be possible by restricting the edge of the layer of cells from being too near the edges of the dish. It was not possible to achieve satisfactory uniformity in the SAR in cell suspensions exposed in standard vessels to any of the sources. The best but not satisfactory SAR uniformity was observed for cells suspended in the lowest 1-ml volume of the liquid contained in a test tube exposed at the bottom in a TEM cell. Experimental measurements of average SAR by temperature change for this case varied from 18% higher to 26% lower than finite difference time domain-derived values. The most uniform SAR distribution for cell suspensions in nonstandard containers was found for a rectangular slab configuration exposed in a stripline with the plates separated from the media by a thin layer of insulation. It is possible to experimentally implement this model by placing a fluid-filled thin-wall rectangular container tightly between the plates of a stripline.

Absorption↗
PubMed1999

Development of a rat head exposure system for simulating human exposure to RF fields from handheld wireless telephones.

The aim of this project was to develop an animal exposure system for the biological effect studies of radio frequency fields from handheld wireless telephones, with energy deposition in animal brains comparable to those in humans. The finite-difference time-domain (FDTD) method was initially used to compute specific absorption rate (SAR) in an ellipsoidal rat model exposed with various size loop antennas at different distances from the model. A 3 x 1 cm rectangular loop produced acceptable SAR patterns. A numerical rat model based on CT images was developed by curve-fitting Hounsfield Units of CT image pixels to tissue dielectric properties and densities. To design a loop for operating at high power levels, energy coupling and impedance matching were optimized using capacitively coupled feed lines embedded in a Teflon rod. Sprague Dawley rats were exposed with the 3 x 1 cm loop antennas, tuned to 837 or 1957 MHz for thermographically determined SAR distributions. Point SARs in brains of restrained rats were also determined thermometrically using fiberoptic probes. Calculated and measured SAR patterns and results from the various exposure configurations are in general agreement. The FDTD computed average brain SAR and ratio of head to whole body absorption were 23.8 W/kg/W and 62% at 837 MHz, and 22.6 W/kg/W and 89% at 1957 MHz. The average brain to whole body SAR ratio was 20 to 1 for both frequencies. At 837 MHz, the maximum measured SAR in the restrained rat brains was 51 W/kg/W in the cerebellum and 40 W/kg/W at the top of the cerebrum. An exposure system operating at 837 MHz is ready for in vivo biological effect studies of radio frequency fields from portable cellular telephones. Two-tenths of a watt input power to the loop antenna will produce 10 W/kg maximum SAR, and an estimated 4.8 W/kg average brain SAR in a 300 g medium size rat.

Animals↗
PubMed1999

TP53 tumor suppressor protein in normal human fibroblasts does not respond to 837 MHz microwave exposure.

The TP53 tumor suppressor protein (formerly known as p53) responds to a wide variety of environmental insults. To evaluate the safety of cellular telephones, TP53 responses in human fibroblast cells were studied after exposure to 837 MHz microwaves. Cells were exposed in a temperature-controlled transverse electromagnetic (TEM) chamber to a specific absorption rate (SAR) of 0.9 or 9.0 W/kg at 837 MHz continuous-wave (CW) microwave irradiation for 2 h. The TP53 protein levels were measured by Western blot at 2, 8, 24 and 48 h after treatment. The TP53 protein levels in microwave-treated cells, sham-treated cells, and untreated cells remained unchanged relative to each other at all times tested (Fisher test and Student-Newman-Keuls test, P > 0.05). No morphological alterations were observed in microwave-treated cells compared to sham-treated cells. We conclude that TP53 protein expression levels in cultured human fibroblast cells do not change significantly during a 48-h period after exposure to 837 MHz continuous microwaves for 2 h at SAR levels of 0.9 or 9.0 W/kg.

Cells, Cultured↗
PubMed1997

Mice lacking dopamine D4 receptors are supersensitive to ethanol, cocaine, and methamphetamine.

The human dopamine D4 receptor (D4R) has received considerable attention because of its high affinity for the atypical antipsychotic clozapine and the unusually polymorphic nature of its gene. To clarify the in vivo role of the D4R, we produced and analyzed mutant mice (D4R-/-) lacking this protein. Although less active in open field tests, D4R-/- mice outperformed wild-type mice on the rotarod and displayed locomotor supersensitivity to ethanol, cocaine, and methamphetamine. Biochemical analyses revealed that dopamine synthesis and its conversion to DOPAC were elevated in the dorsal striatum from D4R-/- mice. Based on these findings, we propose that the D4R modulates normal, coordinated and drug-stimulated motor behaviors as well as the activity of nigrostriatal dopamine neurons.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1997

RF heating of implanted spinal fusion stimulator during magnetic resonance imaging.

Radio frequency (RF) heating of an implanted spinal fusion stimulator (SpF) during magnetic resonance imaging (MRI) was studied on a full-size human phantom. Heating during MRI scans (GE Signa 4X, 1.5 T) was measured with RF-transparent fiberoptic sensors. With the implant correctly connected, the maximum temperature rises were less than 2 degrees C during the 26 min that the scans were at maximum RF power. At the tip of a broken stimulator lead (connecting the SpF generator and its electrodes), the maximum temperature rise was 11-14 degrees C. Regular 4-min scans of the spinal cord produced similar temperature rises at the broken tip. After the generator and the leads were removed, heating at the electrode connector tip was less than 1.5 degrees C. The control temperature rises at the same locations, without the stimulator, were less than 0.5 degree C. This study shows that spinal fusion stimulator heating is within the Food and Drug Administration safety guideline of 2 degrees C. However, if a lead wire is broken, it is unsafe during MRI scans. Radiological examinations will be necessary to ensure the integrity of the implant.

Electric Stimulation↗
PubMed1997

Electrochemical treatment of mouse and rat fibrosarcomas with direct current.

Electrochemical treatment (ECT) of cancer utilizes direct current to produce chemical changes in tumors. ECT has been suggested as an effective alternative local cancer therapy. However, a methodology is not established, and mechanisms are not well studied. In vivo studies were conducted to evaluate the effectiveness of ECT on animal tumor models. Radiation-induced fibrosarcomas were implanted subcutaneously in 157 female C3H/HeJ mice. Larger rat fibrosarcomas were implanted on 34 female Fisher 344 rats. When the spheroidal tumors reached 10 mm in the mice, two to five platinum electrodes were inserted into the tumors at various spacings and orientations. Ten rats in a pilot group were treated when their ellipsoidal tumors were about 25 mm long; electrode insertion was similar to the later part of the mouse study, i.e., two at the base and two at the center. A second group of 24 rats was treated with six or seven electrodes when their tumors were about 20 mm long; all electrodes were inserted at the tumor base. Of the 24 rats, 12 of these were treated once, 10 were treated twice. and 2 were treated thrice. All treated tumors showed necrosis and regression for both mice and rats; however, later tumor recurrence reduced long-term survival. When multiple treatments were implemented, the best 3 month mouse tumor cure rate was 59.3%, and the best 6 month rat tumor cure rate was 75.0%. These preliminary results indicate that ECT is effective on the radiation-induced fibrosarcoma (RIF-1) mouse tumor and rat fibrosarcoma. The effectiveness is dependent on electrode placement and dosage.

Animals↗
PubMed1995

Oral administration of dihydroartemisinin and ferrous sulfate retarded implanted fibrosarcoma growth in the rat.

In the presence of iron, dihydroartemisinin forms free radicals and causes cell death. Since most cancer cells have high rates of iron intake, dihydroartemisinin would have selective cytotoxic effect on cancer cells. The present experiment was designed to study the effect of dihydroartemisinin and ferrous sulfate on the growth of implanted fibrosarcoma in the rat. We found that the growth rate of the tumor was significantly retarded by daily oral administration of ferrous sulfate followed by dihydroartemisinin. No significant tumor growth retardation effect was observed in rats treated with either dihydroartemisinin or ferrous sulfate alone. The drug treatment did not significantly affect body weight compared with untreated tumor-implanted animals and no apparent toxic effect was observed after drug treatment. An artemisinin analog-ferrous salt combination may provide a novel approach for cancer therapy.

Administration, Oral↗
PubMed1995

Absence of radiofrequency heating from auditory implants during magnetic resonance imaging.

The possibility of tissue heating due to an auditory brainstem implant (ABI) or a modified cochlear implant (CI) during magnetic resonance imaging (MRI) of the head was tested on a full-sized human phantom using a realistic phantom head consisting of simulated skull, brain, and muscle. Dielectric properties of the brain, muscle, and bone materials were similar to those of human tissues at 64 MHz. The body consisted of homogeneous phantom muscle enclosed in a human-shaped fiberglass shell. Thermographic and fiber-optic temperature measurements were conducted to reveal any heating. Thermograms of sagittal, frontal, and horizontal planes of the head with the ABI and CI electrodes were taken immediately before and after a 26 min MRI scan. The MRI sequence was set at 94 excitations and 25 ms echo time to induce maximum radiofrequency heating, as suggested by the General Electric Company. The difference of these two thermograms gives the heating results. In two uncut phantom heads. Teflon tubes were placed along the implanted ABI and CI, and temperature data were recorded via fiber-optic probes before, during, and after the MRI. Results showed no observable heating associated with the ABI and the modified CI during worst-case MRI of the head.

Brain↗
PubMed1992

An eccentrically coated asymmetric antenna applicator for intracavitary hyperthermia treatment of cancer.

In this paper a model based on transmission line theory is used to predict the behavior of an eccentrically coated asymmetric antenna applicator for use in intracavitary hyperthermia. Theoretical results for the heating rate (HR) of the applicators are compared to experimental results. The experimental results were obtained at City of Hope National Medical Center using four different 915-MHz applicators, each with a different antenna size and eccentricity of the coating. A parameter delta is defined where delta << 1.0 is a thin wire approximation; delta is primarily a function of the eccentricity of the coating, the antenna diameter, and the coating diameter. It is found that when delta approximately less than 0.5, the theoretical model works well. In particular, it predicts the directivity due to the eccentricity of the coating. However, as this eccentricity is increased or as the antenna diameter is increased (delta approximately greater than 0.6), the model no longer accurately predicts directivity. Thus, the model that can be used to predict the HR profiles for an eccentrically coated asymmetric antenna only when delta approximately less than 0.5.

Computer Simulation↗
PubMed1990

Effects of fat thickness on heating patterns of the microwave applicator MA-151 at 631 and 915 MHz.

Previous studies showed that the surface heating patterns of the MA-151 applicator on a 2 cm fat and 10 cm thick muscle phantom had center heating at 581 and 930 MHz and two hot spots near the edges of the applicator at 657 and 779 MHz. The hot spots at 657 MHz were consistent with two blisters on a patient's thigh. Since the heating patterns on muscle only showed good center elliptical heating at all frequencies, in this study we have investigated the effects of fat thickness on the heating patterns. Thermograms of fat and muscle surfaces were taken on phantoms with 0, 0.25, 0.5, 1, and 2 cm thick fat exposed to 631 or 915 MHz energy. The 631 MHz was selected to provide reasonable energy coupling for all phantoms. At 631 MHz, two hot spots were evident on all fat surfaces. The pattern on the muscle surface under the 0.25 cm fat did not show two hot spots, but the heating was elongated in the E-field direction. At 915 MHz, the heating was elongated on the surface of the 0.25 and 2 cm fat, and two hot spots were observed on the 0.5 and 1 cm fat surfaces. However, the muscle heating was elliptical in all cases. The ratio of muscle to fat heating decreased as the fat thickness increased. At 0.5 cm fat the ratio was about 1. These results indicate that fat thickness influences heating in muscle. During treatment with this applicator, surface temperature probes should be placed over potential hot spots. Surface cooling is desirable for heating tumors beneath the fat.

Adipose Tissue↗
PubMed1988

Intracatheter hyperthermia and iridium-192 radiotherapy in the treatment of bile duct carcinoma.

We report a case of a patient with locally advanced bile duct carcinoma treated with 4500 cGy external beam radiotherapy, followed 3 weeks later by intracatheter 915 MHz microwave hyperthermia and radiotherapy delivered through a biliary U-tube placed at the time of surgery. Heating was to 43-45 degrees C for 1 hour followed immediately by intracatheter Iridium-192 seeds to deliver 5000 cGy over a 72 hour period. Prior to treatment, a thermal dosimetry study in phanton was conducted, using the same type of U-tube catheter tubing as in the patient. Orthogonal X rays of the patient's porta hepatis region were used to reconstruct the catheter geometry in the phantom. Proper insertion depth was determined thermographically to obtain maximum heating at the center of the tumor. The maximum SAR was 8.8 watts per kilogram per watt input. During the treatment, the average power applied was 30 W. Six months after therapy, the patient is asymptomatic. Although alkaline phosphatase, SGOT and SGPT have remained elevated, bilirubin has returned to normal and computerized tomographic scans and cholangiograms remain stable. A duodenal ulcer developed after therapy and is healing well with conservative medical management. This case demonstrates that hyperthermia applied through biliary drainage catheters is technically feasible and clinically tolerated. We believe the use of intracatheter hyperthermia in conjunction with external and/or intracatheter radiotherapy in selected patients with unresectable bile duct carcinomas warrants further study.

Alanine Transaminase↗
PubMed1985

Specific absorption rate in rats exposed to 2,450-MHz microwaves under seven exposure conditions.

Both positive and negative biological effects of microwaves on drug actions in rats exposed to 1-mW/cm2, 2,450-MHz microwaves have been reported by several investigators. We conducted dosimetry studies for seven different exposure conditions to determine whether these different results could be due to the rats having been exposed differently. They included anterior and posterior exposures in a circular waveguide, near field, far field with E- or H-field parallel to the long axis of the body and dorsal exposure in a miniature anechoic chamber with E- or H-field parallel to the long axis of the body. The average specific absorption rates (SARs) in the head, tail, and body of the exposed rats were measured by means of a calorimetry system. The local SARs at eight locations in the brain were determined by temperature measurement with Vitek probes. Intensive coupling of energy to the tail when it was exposed parallel to the E-field was shown by thermography. For the same average incident power density, the average SARs in the heads of rats were about two times higher in the circular waveguide than for other exposures. The local SARs in the brain varied for different exposure conditions. Statistical comparisons of SARs under the different exposure conditions are presented.

Animals↗
PubMed1983

Electrical discontinuity of tissue substitute models at 27.12 MHz.

Tissue-substitute models consisting of layers of synthetic, electrically equivalent subcutaneous fat, muscle, and bone shaped in conformation with the normal anatomy are used for rapid determination of distribution of temperature and specific absorption rate throughout the tissues when exposed to electromagnetic radiation. The surfaces of the bisected models are approximated during a short exposure period, then separated and scanned with a thermograph. A method was developed to eliminate the electrical discontinuity at the bisected surfaces while allowing separation and subsequent thermographic scanning. A thin layer of silk screen wetted with propylene glycol saturated with sodium chloride was used at the fat interface and a 0.9% sodium chloride solution was used to wet the screen at the muscle interface to eliminate electrical discontinuity during exposure to 27.12-MHz diathermy. Tests showed that in the presence of an electrical discontinuity the heating pattern was grossly distorted. With the method used, the electrical discontinuity is minimized and the subsequent thermographic scanning reveals that the heating pattern is equivalent to that of an intact model.

Adipose Tissue↗
PubMed1983

Heating patterns produced by shortwave diathermy applicators in tissue substitute models.

To be a deep-heating modality, shortwave diathermy applicators have to heat the musculature more than the subcutaneous fat. In this study, commercially available and prototype shortwave diathermy applicators were tested using tissue substitute models which allow rapid thermographic scanning of the initial linear transient temperature rise in the subcutaneous fat and muscle. The specific absorption rates (SAR) of the electromagnetic radiation were calculated throughout the tissues. Great differences were found in the deep-heating capability of these applicators. Some of the applicators heated the subcutaneous fat more than the muscle, while others were more efficient in heating the musculature.

Adipose Tissue↗
PubMed1978

MCQ assessment of introductory clinical course for fourth year medical students.

A 60-item MCQ as administered to 46 fourth year medical students at the beginning, half-way, and at the end of a five week introductory clinical course. The stated goals were achieved: (1) a baseline measure was provided, indicating abilities brought by newly-arriving students; (2) data gave opportunity for "mid-course" corrections by students in their study and by tutors in their teaching; (3) overall student change was assessed, offering a measure of the educational effectiveness of the course, and (4) tutors were made aware of individual students requiring particular attention. Such assessment techniques provide an effective monitoring and motivating instrument at this level of medical education.

Education, Medical, Undergraduate↗