Differences in the diagnosis and management of systemic lupus erythematosus by primary care and specialist providers in the American Indian/Alaska Native population.

Objectives The objective of this study is to investigate differences in the diagnosis and management of systemic lupus erythematosus (SLE) by primary care and specialist physicians in a population-based registry. Methods This study includes individuals from the 2009 Indian Health Service lupus registry population with a diagnosis of SLE documented by either a primary care provider or specialist. SLE classification criteria, laboratory testing, and medication use at any time during the course of disease were determined by medical record abstraction. Results Of the 320 individuals with a diagnosis of SLE, 249 had the diagnosis documented by a specialist, with 71 documented by primary care. Individuals with a specialist diagnosis of SLE were more likely to have medical record documentation of meeting criteria for SLE by all criteria sets (American College of Rheumatology, 79% vs 22%; Boston Weighted, 82% vs 32%; and Systemic Lupus International Collaborating Clinics, 83% vs 35%; p < 0.001 for all comparisons). In addition, specialist diagnosis was associated with documentation of ever having been tested for anti-double-stranded DNA antibody and complement 3 and complement 4 ( p < 0.001). Documentation of ever receiving hydroxychloroquine was also more common with specialist diagnosis (86% vs 64%, p < 0.001). Conclusions Within the population studied, specialist diagnosis of SLE was associated with a higher likelihood of having SLE classification criteria documented, being tested for biomarkers of disease, and ever receiving treatment with hydroxychloroquine. These data support efforts both to increase specialist access for patients with suspected SLE and to provide lupus education to primary care providers.

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

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.

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.

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.

A pilot study of intracavitary hyperthermia combined with radiation in the treatment of oesophageal carcinoma.

Twenty-five patients with primary squamous cell carcinoma of the oesophagus were treated with intracavitary hyperthermia combined with external beam radiation and intraluminal radiation at Nanjing Jinling Hospital, China. External beam radiation was given with a 6-MV X-ray; 1.8-2.0 Gy per fraction and five fractions per week; this brought the total dose to 60 Gy. Two weeks later, hyperthermia was applied with 915 MHz microwave intracavitary applicators, which were designed at the City of Hope. Temperature measurements were obtained while moving fibreoptic temperature sensors at 1.0 cm intervals in each of the six peripheral channels of the applicator. Hyperthermia was applied for 1 h before and after the intraluminal radiation. Intraluminal radiation was provided by low dose-rate iridium-192 ribbons in the same intracavitary applicator, giving 30 Gy at 0.75 cm from the applicator surface. The 3-month post-treatment responses showing complete response, partial response, no change and progressive disease were 60% (15/25), 24% (6/25), 8% (2/25) and 8% (2/25) respectively. The median follow-up time was 17 months (range 4-29 months). The 1- and 2-year overall survival rates were 72% (18/25) and 32% (8/25) respectively, and disease-free survival rates were 47 and 30% respectively. The median overall survival and disease-free survival periods were 17 and 10 months respectively. Fourteen patients had local recurrence (either at the primary site or in the lymph node) or had local progression, and five developed metastases. The median duration of the onset of local recurrence or of local progression was 9.5 months (range 0-20 months); the median of distant metastases was 8 months (range 2-16 months). Seventeen patients died. Of these, 15 died of cancer: six with local recurrence alone, four with local progression primary cancer alone, three with distant metastases alone, and two with both local and distant failure. Two patients with complete response of the primary disease died of other diseases. The toxicity was mild. According to the mucous reaction scoring criteria of the Radiation Therapy Oncology Group, the acute toxicity grades I, II, III and IV were 0% (0/25), 20% (5/25), 48% (12/25) and 32% (8/25) respectively. The major late complication was a mild oesophagus fibrosis and difficult swallowing. No serious side effects (grade IV), fistulas or perforations were seen. These results indicate that this method is safe and feasible for treating oesophageal carcinoma.

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.

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.

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.

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.

FDTD simulations of Clini-Therm applicators on inhomogeneous planar tissue models.

A finite-difference time-domain (FDTD) algorithm was used to compute SAR distributions in planar fat-muscle phantom exposed to the Clini-Therm microwave applicators. The models consisted of a 30 X 30 X 7.5 cm phantom and a 15 X 15 cm, 10 X 10 cm or 7.5 X 7.5 cm aperture dielectric slab loaded applicator. The phantom was either filled with muscle material or with 1.0 cm fat on 6.5 cm muscle. A mineral oil bolus was placed on the fat-muscle model with its integrated water channels parallel to the electric or magnetic field. The FDTD resolution was 3 mm and the applicators were excited with a Gaussian pulse. The computations required 6000-8000 time steps to reach steady state, with 45-48 Mwords on a Cray Y-MP C-90 in 1000-1200 CPU seconds. The electric field components at 915 MHz were obtained by summing the Fourier coefficients at each grid point during each time step and SAR was determined. The results were qualitatively compared to existing and published thermographic heating patterns with good agreement. The computed electric field distributions had provided a three dimensional view into the problem space to investigate and understand wave propagation phenomena in complex inhomogeneous configurations that were not feasible with experimental models.

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.

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.

Heating patterns of microwave applicators in inhomogeneous arm and thigh phantoms.

Heating rate (HR) patterns in cylindrical structures were studied with inhomogeneous limb phantoms. These phantoms, arm and thigh models consisting of fat, bone, and muscle material, were heated with Clini-Therm L, M, and MS applicators at 915 MHz. The thigh model is 18 cm in diameter with 2.65-cm-thick fat on the outside and a 4-cm-diam bone in the center. The arm model is 9 cm in diameter with 1.35-cm-thick fat and 2-cm-diam bone. All models are 29 cm long with phantom muscle in the space between fat and bone and were heated with their long axes parallel or perpendicular to the E field. HR patterns in the transverse and longitudinal planes were obtained thermographically. A large water bolus, with the water channels parallel to the E field, was used in every case. In the thigh model, maximum heating was in the muscle for both L and M applicators when the E field was parallel to the long axis. When it was perpendicular, the maximum heating occurred in the fat layer. However, the peak HR in the fat remained about the same for both E field orientations. For the small applicator, heating was mostly in the fat, and the two field orientations did not cause much difference in the heating pattern. In the arm model, the maximum heating of all three applicators occurred mostly in the muscle for both E-field orientations. However, the maximum HR was reduced by a factor of 2 to 3 when the E field was perpendicular rather than parallel to the long axis.(ABSTRACT TRUNCATED AT 250 WORDS)

Design of intracavitary microwave applicators for the treatment of uterine cervix carcinoma.

A 915 MHz intracavitary applicator was designed to heat tumours in the cervical and upper vaginal regions. The applicator has a 3.5-turn helical coil wound around the distal 19 mm of a dielectric rod 43 mm long and 30 mm in diameter. For treating uterine cancer, a 2450 MHz, 4 mm diameter helical applicator was made by replacing 6 cm of the outer conductor of a coaxial cable with six turns of copper wire soldered to the outer conductor. The heating patterns were determined thermographically in a muscle phantom. The maximum heating rates were 0.42 and 0.83 degrees C/W-min, respectively, for the 915 and 2450 MHz applicators. Intracavitary temperature distributions in the upper vagina, cervix and uterus were measured at the surface of the applicators with thermocouples. The average temperature was 46.0 +/- 2.1 degrees C (S.D.) at mid-tumour and 44.5 +/- 0.8 degrees C at the tumour periphery. The maximum temperature, up to 51.5 degrees C, was measured at the surface of the cervical applicator. The majority of the patients (28/30) tolerated the investigational treatment without burns or pain. Rectal temperatures were also monitored. The location of the hot-spot (40.7 degrees C) in the rectum, 5-7 cm above the anus, corresponded to the tip of the cervical applicator (47.1 degrees C).

Intracavitary hyperthermia applicators for treating nasopharyngeal and cervical cancers.

Many intracavitary microwave applicators have been designed to heat tissues along the side of an antenna. For tumours in nearly closed-end cavities such as the nasopharynx and cervix, heating near the tip of the applicators is necessary for effective treatment. A nasopharyngeal applicator made of Micro Coax UT-250A and a cervical applicator made of RG-9/U cables were designed to provide heating at the tip. Return losses of 8-12 dB were obtained at 915 MHz by varying the size of two metal sleeves and adjusting the distance between these sleeves and the reflectors at the applicator tips. Heating patterns were evaluated on a muscle phantom with a thermograph. At 915 MHz, maximum heating rates of 1.3 and 0.85 degrees C/W-min, respectively, were observed near the tip of the nasopharyngeal applicator and at its first sleeve opening. When operated at 915 MHz the cervical applicator has a maximum heating rate of 0.25 degrees C/W-min at the tip. Clinically, both applicators require a maximum power of 30 W to provide effective heating. This makes it possible to provide intracavitary hyperthermia at rural hospitals and small clinics with a small portable system.

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.

Evaluation of captive bolus applicators.

Three square (L, M, MS) and one rectangular (HN) applicators with captive boluses were provided by the Clini-Therm Corporation for evaluation. Surface cooling is achieved by attaching a mineral oil captive bolus to the built in water-circulating tubes at the aperture of the applicators. These applicators were tested on a phantom with a 2-cm fat slab over 10-cm-thick muscle. Surface and sagittal heating patterns were obtained using a thermograph. All captive-bolus applicators have heating patterns similar to that of the regular Clini-Therm applicators. Due to hot spots at the edges of the applicators where the E fields terminate, these modified applicators should not be placed in direct contact with patients when boluses are not used. Tests with Clini-Therm regular water bolus instead of the captive oil bolus indicated that the orientation of water flow should be parallel to the E field to minimize perturbation of the heating patterns. Thermal conduction studies showed that the captive bolus reacts too slowly for skin temperature control. The modified captive bolus applicators did not improve the performance of the system.

Changes in heating patterns of interstitial microwave antenna arrays at different insertion depths.

The changes in heating patterns of interstitial microwave antennas at different insertion depths were investigated in a static phantom at 915 MHz. Antennas for the Clini-Therm Mark VI system were inserted 5-15 cm into muscle-equivalent material, through nylon catheters. The phantom was heated with arrays of antennas at 2 cm spacings for 60 s at 15 W per antenna. Midplane and transverse heating patterns were determined thermographically with the antennas inserted parallel or perpendicular to the split of the phantom. Hot spots, independent of heating near the junction plane, were observed in the midplane of the 2 x 2 and 2 x 4 arrays at 2.8 cm from the insertion end. The magnitudes of these hot spots were reduced by 40-45 per cent as insertion depth was increased from 7 to 10.5 cm. With insertion depths of more than 11.5 cm the hot spots gradually diminished and heating occurred mostly near the junction plane. The observed heating patterns were caused by changes in impedance of the antenna arrays at different insertion depths. The impedance mismatch had resulted in different wave propagation within the tissue material which produced different radiation patterns. During treatments, because heating varies with insertion depth, great care must be exercised in monitoring temperatures.