iMRS 2000 - PEMF Publications
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PEMF Publications

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701

Magnetic field guided endoscopic dissection through a burr hole may avoid more invasive craniotomies. A preliminary report

The neuroendoscope, coupled with radiofrequency or laser dissecting tools, can effectively resect obstructing membranes, biopsy and debulk tumor, and evacuate hematomas when the pathology is within the ventricular system. This less invasive approach through a burr hole usually avoids craniotomies. When the abnormal condition is within parenchyma or in the presence of opacifying bloody fluid, landmarks are not recognizable and the neurosurgeon quickly becomes disoriented. A more extensive craniotomy or a stereotaxic-guided procedure is then necessary. We describe our preliminary experience with a geographic intracranial navigation system using realtime measurement of electromagnetic field strength in multiple planes to precisely indicate the position of the tip of the endoscope. A transmitting antenna is positioned beneath the patient's head. A 1.5 centimeter cubic antenna receiver is mounted upon a lenscope with instrument channel. The scope is guided into the surgical field after insertion through a burr hole. A square wave pulsed electromagnetic field measurement is made 140 times per second with correction for the earth's magnetic field once per second. Intracranial position data for the dissecting tip in regard to X, Y, Z, pitch, roll and yaw are output to a digitized computer map of the patient's MRI or CT scan. Also displayed on the computer screen is the video image from the endoscope. The neurosurgeon thus has simultaneous realtime geographic and near-field localization as he dissects. Electromagnetic field guided accuracy is within 2.0 mm inside the allowable 24 inch working sphere about the patient's head. Coupled with near-field video precision, accuracy is within 1 mm of recognizable dissection planes.(ABSTRACT TRUNCATED AT 250 WORDS)

702

Magnetic field inhibits isolated lymphocytes' proliferative response to mitogen stimulation

We aimed to find out how the exposure of isolated lymphocytes to a pulsed magnetic field (MF) affected their in vitro proliferative response to mitogenic stimulation. Cells were exposed to MF of various intensities (0.3, 0.6, and 1.2 T) at a constant frequency of 30 Hz, for a period of 60, 180, and 330 s. Then, the proliferative response of splenocytes was induced by optimal concentrations of concanavalin A (Con A; mitogenic toward T cells), bacterial lipopolysaccharide (LPS; mitogenic toward B cells), or pokeweed mitogen (PWM; mitogenic toward both populations). We found that the exposure of lymphocytes to the MF profoundly inhibited their proliferative response to mitogens. The suppressive action of the MF on B and T cell proliferation was intensified when a cooperative response of those two lymphocyte populations was simultaneously induced by PWM. The inhibitory effect of MF depended on the exposure time and MF intensity. Prolonged exposure and/or a stronger intensity of the MF weakened its inhibitory influence on the response of lymphocyte to mitogenic stimulation. The data show that an exposure to MF may influence the activity of lymphocytes in their response to mitogenic stimuli.

703

Magnetic field therapy for epilepsy

Attempts to control seizures in animal models and in humans with magnetic fields are in early stages of development. Devices that produce fields ranging from static to high frequency and with flux densities from well below geomagnetic intensities (nano-Tesla) to several Tesla have been tested with variable results. Fundamental cellular mechanisms of interaction and transduction of magnetic fields have not been adequately elucidated for systematic hypothesis-driven experimentation. However, indications of efficacy are sufficient to warrant further investigation at the basic and clinical levels.

704

Magnetic Field Therapy: A Review

There is increasing interest in using permanent magnets for therapeutic purposes encouraged by basic science publications and clinical reports. Magnetotherapy provides a non invasive, safe, and easy method to directly treat the site of injury, the source of pain and inflammation, and other types of disease. The physiological bases for the use of magnetic fields for tissue repair as well as physical principles of dosimetry and application of various magnetic fields are subjects of this review. Analysis of the magnetic and electromagnetic stimulation is followed by a discussion of the advantage of magnetic field stimulation compared with electric current and electric field stimulation.

705

Magnetic field therapy: a review

There is increasing interest in using permanent magnets for therapeutic purposes encouraged by basic science publications and clinical reports. Magnetotherapy provides a non invasive, safe, and easy method to directly treat the site of injury, the source of pain and inflammation, and other types of disease. The physiological bases for the use of magnetic fields for tissue repair as well as physical principles of dosimetry and application of various magnetic fields are subjects of this review. Analysis of the magnetic and electromagnetic stimulation is followed by a discussion of the advantage of magnetic field stimulation compared with electric current and electric field stimulation.

706

Magnetic field visualization in applications to pulsed electromagnetic field stimulation of tissues

Electromagnetic field visualization is important in multidisciplinary research on the molecular basis of therapeutic effects of pulsed electromagnetic fields (PEMF). We have compared classic PEMF representations by two-dimensional field lines and field magnitude contour plots with a field representation using three-dimensional field isosurfaces. Field simulations were performed for a clinically approved Spinal-Stim Lite system (Orthofix Inc., McKinney, TX). The relatively simple coil system geometry and the predominantly dielectric properties of the surrounding medium (air and human connective tissue) allowed us to develop analytical expressions for the field. The field model was validated by comparison with experimentally measured field values, and with values calculated using a commercial finite-element analysis software package. Two-dimensional field representations by field lines and field contour plots were less intuitive than three-dimensional field isosurface representations to members of the group without an engineering background. Field isosurfaces, represented as three-dimensional solids, allowed for direct visualization of PEMF targeting of individual organs (lumbar spine), the extent of the therapeutic field value, and the directional field characteristics. The dynamic characteristic of the field was well illustrated by a sequence of field isosurfaces corresponding to the evolution with time of the electric current waveform (sawtooth) powering the coils. The isosurface representation of the field can be extended to any three-dimensional coil system geometry using plotting capabilities of current computer algebra software packages.

707

Magnetic fields after translation in Escherichia coli

Quantitative two-dimensional gel electrophoresis of proteins in E. coli exposed for 60 min to weak, pulsed magnetic fields (1.5 mT peak) show that numerous proteins are both increased and decreased by a factor of 2 or more. An increase in the levels of two proteins, the a subunit of DNA-dependent RNA polymerase and NusA, was confirmed by Western blot analysis.

708

Magnetic fields alter the circadian periodicity of seizures

We have recently reported that application of external, weak magnetic fields attenuated seizures in epileptic patients (Anninos et al., 1991). However, the mechanisms by which magnetic stimulation reduces seizure activity are unknown. We present four non-selected epileptic patients the first to be rated by the senior author, in whom treatment with magnetic fields attenuated the severity of seizures and also altered the circadian occurrence of seizures. The first patient, a 27-year old woman, had generalized tonic-clonic seizures which occurred almost exclusively at night. Following treatment with magnetic fields she experienced attenuation of seizures which then occurred only after waking up in the morning. The second patient, a 42-year old man, had generalized tonic-clonic seizures which occurred randomly during the day and night. Treatment with magnetic fields resulted in disappearance of nocturnal seizures with seizures now occurring exclusively during the day. The third patient, a 21-year old woman had generalized tonic-clonic seizures which occurred randomly during the day. After treatment with magnetic fields she was free of seizures for 7 months, but recently experienced one attack in the morning hours while sleeping. The fourth patient, a 39-year old woman had secondary generalized seizures since the age of 12. Prior to treatment with magnetic fields she had 8-10 seizures daily which occurred randomly during the day and night hours. Magnetic treatment resulted in attenuation in seizure frequency (1-2/day) with seizures now occurring only during the day. We propose, therefore, that since the pineal gland is a magnetosensitive organ which "transduces" environmental information of the light-dark cycle and of the earth's magnetic field into an endocrine message mediated via the circadian release of melatonin, and since it is recognized that melatonin attenuates seizure activity, artificial magnetic fields attenuate seizure activity by altering the functions of the pineal gland.

709

Magnetic fields and cancer: animal and cellular evidence--an overview

A few animal studies on the possible carcinogenic effect of magnetic fields have been published. They have been designed to reveal a possible tumor promotion obtained by applying continuous or pulsed alternating fields at flux densities varying between 0.5 microT and 30 mT on mice or rats initiated with different initiators. One study with 2 mT applied on DMBA-initiated mice may suggest a copromotive effect together with the promoter TPA. Another study on rats suggests an inhibitory effect by a magnetic field on rat liver foci formation, induced with DENA. Cell studies show that magnetic fields at some frequencies, amplitudes, and wave forms interact with biological systems. Thus effects have been seen, e.g., on enzymes related to growth regulation, on calcium balance in the cell, on gene expression, and on pineal metabolism and its excretion of the oncostatic melatonin. Cellular and physiologic studies thus suggest effects that may be related to cell multiplication and tumor promotion.

710

Magnetic fields and seasonality of affective illness: implications for therapy

Seasonal affective disorder is characterized by recurrent winter depression associated with hypersomnia, overeating, and carbohydrate craving. The severe form of winter depression affects about 5% of the general population and is believed to be caused by light deficiency. About 70%-80% of patients with winter depression experience attenuation of symptoms when exposed to bright light therapy. Hypotheses pertaining to the pathogenesis of winter depression implicate the effects of light on different characteristics of circadian rhythms. One of the environmental factors which may be implicated, in addition to light, in the pathophysiology of winter depression is the geomagnetic field. There is strong indication that the pineal gland is a magnetosensitive system and that changes in the ambient magnetic field alter melatonin secretion and synchronize the circadian rhythms. In man, shielding of the ambient magnetic field significantly desynchronizes circadian rhythms which could be gradually resynchronized after application of magnetic fields. The strength of the environmental magnetic field diminishes during the winter months, leading to increased susceptibility for desynchronization of circadian rhythms. Thus, since the acute application of magnetic fields in experimental animals resembles that of acute exposure to light with respect to melatonin secretion (i.e., suppression of melatonin secretion), magnetic treatment might be beneficial for patients with winter depression. In addition, since the environmental light and magnetic fields, which undergo diurnal and seasonal variations, influence the activity of the pineal gland, we propose that a synergistic effect of light and magnetic therapy in patients with winter depression would be more physiological and, therefore, superior to phototherapy alone.(ABSTRACT TRUNCATED AT 250 WORDS)

712

Magnetic fields and time dependent effects on development

Pulsed, extremely-low-frequency electromagnetic fields caused a significant increase in abnormalities in the developing chick embryo. The effect was observed when the field was presented during the first 24 h of incubation; no significant effect was observed with exposure from 24 to 48 h of incubation.

713

Magnetic fields in the therapy of parkinsonism

In a recent Editorial published in this Journal, I presented a new and revolutionary method for the treatment of Parkinson's disease (PD). I reported that extracranial treatment with picoTesla magnetic fields (MF) is a highly effective, safe, and revolutionary modality in the symptomatic management of PD. My conclusion was based on experience gained following the successful treatment of over 20 Parkinsonian patients, two of whom had levodopa-induced dyskinesias. None of the patients developed side effects during a several month period of follow-up. In the present communication, I present two reports. The first concerns four Parkinsonian patients in whom picoTesla MF produced a remarkable and sustained improvement in disability. Three of the patients had idiopathic PD and the fourth patient developed a Parkinsonian syndrome following an anoxic episode. In all patients, treatment with MF was applied as an adjunct to antiParkinsonian medication. The improvement noted in these patients attests to the efficacy of picoTesla MF as an additional, noninvasive modality in the therapy of the disease. The second report concerns two demented Parkinsonian patients in whom treatment with picoTesla MF rapidly reversed visuospatial impairment as demonstrated by the Clock Drawing Test. These findings demonstrate, for the first time, the efficacy of these MF in the amelioration of cognitive deficits in Parkinson's disease. Since Alzheimer's pathology frequently coexists with the dementia of Parkinsonism, these observations underscore the potential efficacy of picoTesla MF in the treatment of dementias of various etiologies.

714

Magnetic fields in the treatment of Parkinson's disease

Levodopa-induced dyskinesias are a common complication of chronic dopaminergic therapy in patients with Parkinson's disease (PD). The overall prevalence of levodopa-induced dyskinesias ranges from 40%-90% and is related to the underlying disease process, pharmacologic factors, and to the duration of high dose levodopa therapy. The mechanisms underlying the emergence of levodopa-induced dyskinesias are unknown, although most investigators favor the theory that striatal dopamine receptor supersensitivity is directly responsible for the development of these abnormal movements. In laboratory animals, the pineal hormone melatonin has been shown to regulate striatal dopaminergic activity and block levodopa-induced dyskinesias (Cotzias et al., 1971). Since the pineal gland is known to be a magnetosensitive organ and as application of external magnetic fields has been shown to alter melatonin secretion, we studied the effects of application of external artificial weak magnetic fields in a Parkinsonian patient with severe levodopa-induced dyskinesias ("on-off"). Application of weak magnetic fields with a frequency of 2 Hz and intensity of 7.5 picotesla (pT) for a 6 minute period resulted in a rapid and dramatic attenuation of Parkinsonian disability and an almost complete resolution of the dyskinesias. This effect persisted for about 72 hours after which the patient regressed to his pretreatment state. To ascertain if the responses elicited in the laboratory were reproducible, the patient was instructed to apply magnetic fields of the same characteristics daily at home. These subsequent treatments paralleled the initial response with a sustained improvement being maintained during an observation period lasting at least one month. This case demonstrates the efficacy of weak magnetic fields in the treatment of Parkinsonism and motor complications of chronic levodopa therapy.

715

Magnetic fields mimic the behavioral effects of REM sleep deprivation in humans

The discovery of rapid eye movement (REM) sleep by Aserinsky and Kleitman in 1953 initiated the impetus for sleep research and specifically the investigations of the effects of REM sleep deprivation (RSD) on animal and human behavior. The behavioral effects of RSD include the enhancement of motivational and "drive"-related behaviors. In laboratory animals, RSD has been reported to increase appetite, sexual behavior, aggressiveness, and locomotor activity. Moreover, RSD reportedly improves mood in patients with endogenous depression and heightens appetite and sexual interest in normal subjects. Since "drive"-related behaviors are thought to involve activation of limbic dopaminergic reward sites, RSD may enhance motivational behaviors through an action on limbic dopaminergic functions. In the present communication, we present two patients (one with multiple sclerosis and the other with Parkinson's disease) in whom treatment with magnetic fields produced behavioral effects which paralleled those observed in REM-sleep-deprived animals and humans. We propose, therefore, that the behavioral and mental effects of treatment with magnetic fields may be mediated via RSD and, by inference, involve activation of limbic dopaminergic reward sites.

716

Magnetic fields normalize visual evoked potentials and brainstem auditory evoked potentials in multiple sclerosis

The present communication concerns a 46 year old woman with a 10 year history of chronic progressive multiple sclerosis (MS) in whom external application of magnetic fields (MF) (7.5 picoTesla; 5 Hz) during a period of remission resulted in a rapid and dramatic improvement in symptoms including vision, cerebellar symptomatology (ataxia and dysarthria), mood, sleep, bowel and bladder functions as well as fatigue. Improvement in the patient's symptoms was associated with normalization of the pretreatment latencies of the visual evoked potentials and brainstem auditory evoked potential responses within a week after initiation of magnetic treatment. This report demonstrates that treatment with picoTesla MF is an effective, nonpharmacological modality in the management of MS and for the first time documents reversal of abnormal evoked potential responses by this treatment. The pineal gland is a magnetosensor. As MF affect the release of the pineal gland's principal hormone, melatonin, it is hypothesized that the effects of picoTesla MF in MS are partly mediated by the pineal gland which has recently been implicated in the pathogenesis of MS (Sandyk, 1992 a; b).

717

Magnetic necklace: its therapeutic effectiveness on neck and shoulder pain

The effect of the magnetic necklace on chronic neck and shoulder pain was studied on 101 volunteers, 46 males and 55 females. A double-blind method was applied on 4 divided groups (with pain vs without pain matched with magnetic vs nonmagnetic necklace). All the subjects wore the necklace 24 hours per day for 3 weeks. Subjective evaluation from the subjects with pain, either with magnetic or nonmagnetic treatment, was performed before and 3 weeks after the necklace treatment, and revealed a significant placebo effect in terms of decrease in intensity or frequency of pain. The objective tests with electrodiagnostic procedures were done before the treatment and at 3 weekly intervals. The proximal conduction time of the ulnar nerve was significantly reduced by magnetic treatment in the subjects without pain but was not changed in the subjects with pain. There was no significant change in the excitation threshold of the suprascapular nerve in all subjects. The possible mechanism of magnetic effects on pain and the prospect of magnetotherapy for pain relief in physical medicine are discussed.

718

Magnetic pulse treatment for knee osteoarthritis: a randomised, double-blind, placebo-controlled study

We assessed the efficacy and tolerability of low-frequency pulsed electromagnetic fields (PEMF) therapy in patients with clinically symptomatic knee osteoarthritis (OA) in a randomised, placebo-controlled, double-blind study of six weeks' duration. Patients with radiographic evidence and symptoms of OA (incompletely relieved by conventional treatments), according to the criteria of the American College of Rheumatology, were recruited from a single tertiary referral centre. 75 patients fulfilling the above criteria were randomised to receive active PEMF treatment by unipolar magnetic devices (Medicur) manufactured by Snowden Healthcare (Nottingham, UK) or placebo. Six patients failed to attend after the screening and were excluded from analysis. The primary outcome measure was reduction in overall pain assessed on a four-point Likert scale ranging from nil to severe. Secondary outcome measures included the WOMAC Osteoarthritis Index (Likert scale) and the EuroQol (Euro-Quality of Life, EQ-5D). Baseline assessments showed that the treatment groups were equally matched. Although there were no significant differences between active and sham treatment groups in respect of any outcome measure after treatment, paired analysis of the follow-up observations on each patient showed significant improvements in the actively treated group in the WOMAC global score (p = 0.018), WOMAC pain score (p = 0.065), WOMAC disability score (p = 0.019) and EuroQol score (p = 0.001) at study end compared to baseline. In contrast, there were no improvements in any variable in the placebo-treated group. There were no clinically relevant adverse effects attributable to active treatment. These results suggest that the Medicur unipolar magnetic devices are beneficial in reducing pain and disability in patients with knee OA resistant to conventional treatment in the absence of significant side-effects. Further studies using different types of magnetic devices, treatment protocols and patient populations are warranted to confirm the general efficacy of PEMF therapy in OA and other conditions.

719

Magnetic resonance imaging of electroconvection in a polar organic solvent

Molecular motion in the polar organic solvent nitrobenzene induced by an electric field is studied by magnetic resonance imaging. Rf pulse sequences that correlate images obtained at two different times under conditions of both continuous and pulsed electric fields are introduced. The resultant image correlation spectra indicate that the time scale of motion in a 9.6 kV/cm electric field is tens of milliseconds. Comparison of the results to an analytic solution for the Fokker-Planck probability function for one-dimensional bounded diffusion yields an electric field dependent effective diffusion coefficient for perdeuterated nitrobenzene of D = 1.08 x 10(-5) cm(2)/s + (3.33 x 10(-3) cm(4)/kV(2)s) E(2) at room temperature. Characteristics of this electroconvection and its consequences for combining multidimensional nuclear magnetic resonance with electrical orientation are also discussed.

720

Magnetic resonance imaging of the manipulation of a chemical wave using an inhomogeneous magnetic field

The effects of applied magnetic fields on the traveling wave formed by the reaction of (ethylenediaminetetraacetato)cobalt(II) (Co(II)EDTA2-) and hydrogen peroxide have been studied using magnetic resonance imaging (MRI) . It was found that the wave could be manipulated by applying pulsed magnetic field gradients to a sample contained in a vertical cylindrical tube in the 7.0 T magnetic field of the spectrometer. Transverse field gradients decelerated the propagation of the wave down the high-field side of the tube and accelerated it down the low-field side. This control of the wave propagation eventually promoted the formation of a finger on the low-field side of the tube and allowed the wave to be maneuvered within the sample tube. The origin of these effects is rationalized by considering the Maxwell stress arising from the combined homogeneous and inhomogeneous magnetic fields and the magnetic susceptibility gradient across the wave front.

721

Magnetic resonance imaging with T1 dispersion contrast

Prepolarized MRI uses pulsed magnetic fields to produce MR images by polarizing the sample at one field strength (approximately 0.5 T) before imaging at a much lower field (approximately 50 mT). Contrast reflecting the T(1) of the sample at an intermediate field strength is achieved by polarizing the sample and then allowing the magnetization to decay at a chosen "evolution" field before imaging. For tissues whose T(1) varies with field strength (T(1) dispersion), the difference between two images collected with different evolution fields yields an image with contrast reflecting the slope of the T(1) dispersion curve between those fields. Tissues with high protein content, such as muscle, exhibit rapid changes in their T(1) dispersion curves at 49 and 65 mT due to cross-relaxation with nitrogen nuclei in protein backbones. Tissues without protein, such as fat, have fairly constant T(1) over this range; subtracting images with two different evolution fields eliminates signal from flat T(1) dispersion species. T(1) dispersion protein-content images of the human wrist and foot are presented, showing clear differentiation between muscle and fat. This technique may prove useful for delineating regions of muscle tissue in the extremities of patients with diseases affecting muscle viability, such as diabetic neuropathy, and for visualizing the protein content of tissues in vivo.

722

Magnetic resonance studies of laryngeal tumors implanted in nude mice: effect of treatment with bleomycin and electroporation

Recently, a new type of cancer treatment has been introduced that combines pulsed electric fields (PEF) with anticancer drugs. The proposed mode of action is that PEF create transient pores in the membranes which allow entry of drugs into the cells. This method increases cytotoxicity of some anticancer drugs like bleomycin (BLM) by 2-3 orders of magnitude, which, in turn, reduces systemic drug dosage without decreasing efficacy. In the present study, magnetic resonance imaging (MRI) was used to determine changes in apparent water self-diffusion coefficients (ADC) and spin-lattice (T(1)) and spin-spin (T(2)) relaxation times that occur in an animal laryngeal tumor (HEp-2 cells) model with BLM delivered by PEF. A Bruker 14 Tesla (600 MHz) wide-bore spectrometer with micro-imaging capability was used to generate all the data. Mice carrying approximately 8 mm tumors were treated with several combinations of drug and PEF. All measurements were made on tumor samples excised from mice 24 and 48 hours after treatment with (i) saline, intratumor injection (i.t.), (ii) BLM, i.t., (iii) saline with PEF, and (iv) BLM, i.t., followed by PEF. Although T(1) does not differ between the controls (i, ii, and iii) and full treatment (iv) 6.72 +/- 0.20 s vs. 6.31 +/- 1.7 s, T(2) for (iv) at 24 hours is significantly different from the controls 52.4 +/- 0.91 ms vs. 46.5 +/- 1.54 ms. T(2) differences between treatment and controls disappear at 48 hours. ADC increases significantly from 24 to 48 hours (7.31 +/- 0.16 x 10(-6) to 8.28 +/- 0.28 x 10(-6) cm(2)/sec, p = 0.05). Longer T(2) values may reflect early apoptosis and tumor death when the tumor is structurally less dense. Higher ADC's, associated with the periphery of the tumors and the central region, may indicate loose structural organization and necrosis resulting from the combination treatment.

723

Magnetic stimulation of human peripheral nerve and brain: response enhancement by combined magnetoelectrical technique

The authors describe the technique of magnetic stimulation from a pulsed induction coil (4.0 T) and the enhanced (5-fold) electromyogram response from hyperthenar muscles obtained when electric and magnetic stimuli are applied simultaneously. The enhancement results have been confirmed for central brain vertex stimulation using the Sheffield magnet. Results obtained with slow (1 to 6 seconds) depth electrode stimulation and recording in humans are compared and are used to predict probable developments in the magnetic field. Because magnetic and magnetoelectrical techniques are painless, noninvasive, and noninjurious, it is believed that they are an important advance in both research and clinical applications of instrumental modification of brain circuits and behavior. There are many diagnostic and therapeutic uses at peripheral and central levels, and some ethical problems need consideration.

724

Magnetic stimulation of the facial nerve

Electrical testing of the facial nerve has evolved into an important means of assessing neural injury. However, the inability to stimulate the intratemporal facial nerve electrically results in a delay in diagnosis, because axonal degeneration must progress distal to the stylomastoid foramen before testing can be meaningful. To circumvent this problem, we began an investigation of magnetic stimulation of the facial nerve, because pulsed magnetic fields can pass unattenuated through all body structures, including bone. Normal volunteers and one patient with acute facial paralysis were studied with both magnetic and electric stimulation of the facial nerve. The results indicate that (1) magnetic stimulation was more comfortable because high current levels were not required at the skin surface to assure indepth stimulation, (2) magnetic and electric stimulation of the extratemporal facial nerve resulted in nearly identical compound muscle action potentials, indicating that the sites and mechanisms of neural depolarization are similar, and (3) transtemporal magnetic stimulation appears to allow depolarization of the proximal intratemporal nerve. These preliminary results are encouraging and indicate that magnetic stimulation of the facial nerve warrants further investigation.

725

Magnetic-field induced transition to the 1/2 magnetization plateau state in the geometrically frustrated magnet CdCr2O4

The magnetization of the geometrically frustrated spinel CdCr2O4 was measured in pulsed fields of up to 47 T. We found a metamagnetic transition to a very wide magnetization plateau state with one half of the full moment of S=3/2 Cr3+ at 28 T, independent of the field direction. This is the first observation of magnetization plateau state realized in Heisenberg pyrochlore magnet. The plateau state can be ascribed to a collinear spin configuration with three-up and one-down spins out of four spins of each Cr tetrahedron. A large magnetostriction is observed at the transition in spite of the negligible spin-orbit couplings. We argue that spin frustration plays a vital role in this large spin-lattice coupling.

726

Magnetic-field-induced band-structure change in CeBiPt

We report on a field-induced change of the electronic band structure of CeBiPt as evidenced by electrical-transport measurements in pulsed magnetic fields. Above approximately 25 T, the charge-carrier concentration increases nearly 30% with a concomitant disappearance of the Shubnikov-de Haas signal. These features are intimately related to the Ce 4f electrons since for the non-4f compound LaBiPt the Fermi surface remains unaffected. Electronic band-structure calculations point to a 4f-polarization-induced change of the Fermi-surface topology.

728

Magnetization of a warm plasma by the nonstationary ponderomotive force of an electromagnetic wave

It is shown that magnetic fields can be generated in a warm plasma by the nonstationary ponderomotive force of a large-amplitude electromagnetic wave. In the present Brief Report, we derive simple and explicit results that can be useful for understanding the origin of the magnetic fields that are produced in intense laser-plasma interaction experiments.

735

Management of a delayed-union sesamoid fracture in a dancer

BACKGROUND: Misdiagnosed o sesamoid bone pathology in dancers may result in prolonged pain, disability, and career limitation. A thorough understanding of sesamoid disorders and appropriate treatment facilitates timely recovery. The potential loss of hallux plantar flexion strength consequent to sesamoidectomy is a major consideration for dancers. CASE DESCRIPTION: An 18-year-old dance student sustained a delayed-union fracture of her lateral (fibular) sesamoid. Treatment included an inductive coupling external bone stimulator with pulsed electromagnetic field, activity, and weight-bearing restrictions, protective padding, strengthening, functional retraining, and progressive return to dance. OUTCOME: Following use of an external bone stimulator for 12 months, the dancer successfully returned to her previous level of dancing. Repeated SF-36 and Dance Functional Outcome System scores confirmed this improvement. DISCUSSION: Loss of hallux plantar flexion strength with sesamoid resection can be devastating to a dancer who requires push-off strength for multiple turns and jumps. Treatment with bone stimulation was therefore selected over more invasive measures. The dancer was compliant with systematic functional progression. Improvement, as seen on radiographs and outcome scores, accompanied her full functional recovery.

736

Manipulating the loss in electromagnetic cloaks for perfect wave absorption

We examine several ways to manipulate the loss in electro-magnetic cloaks, based on transformation electromagnetics. It is found that, by utilizing inherent electric and magnetic losses of metamaterials, perfect wave absorption can be achieved based on several popular designs of electromagnetic cloaks. A practical implementation of the absorber, consisting of ten discrete layers of metamaterials, is proposed. The new devices demonstrate super-absorptivity over a moderate wideband range, suitable for both microwave and optical applications. It is corroborated that the device is functional with a subwavelength thickness and, hence, advantageous compared to the conventional absorbers.

737

Mapping transcranial magnetic stimulation (TMS) fields in vivo with MRI

Transcranial magnetic stimulation (TMS) is a non-invasive technique for investigating brain function that uses pulsed magnetic fields created by special coils to induce localized neuronal depolarization. Despite the technique's expanding application, the exact magnetic field produced by TMS coils have never been directly measured in human subjects. Using a standard 1.5T MR scanner and TMS coils constructed from non magnetic materials, we have obtained 3D maps of the magnetic field created by TMS coils in human volunteers. Further, we mapped the combined field of two coils and demonstrated that combinations of coils might be used to focus the magnetic field to achieve improved stimulation patterns and, perhaps, reach areas out of reach of single coils.

738

Maximum pulsed electromagnetic field limits based on peripheral nerve stimulation: application to IEEE/ANSI C95.1 electromagnetic field standards

This communication proposes a rationale for maximum pulsed magnetic field limits in the electromagnetic-field standards of IEEE/ANSI C95.1. The peak limits, intended to protect against peripheral nerve excitation by pulsed fields, are adapted from existing standards for patient exposure in magnetic resonance imaging (MRI) examinations.

739

Measurement of low frequency magnetic fields from digital cellular telephones

Digital cellular telephones using the GSM (Global System for Mobile Communication) transmit information in bursts of microwaves. This pulsed transmitting mode causes the battery current and currents in the electronics of the apparatus to be pulsed. These pulsed currents produce corresponding pulsed magnetic fields near the phones. A study to determine the magnitude of these fields involved two models of digital telephones. The highest value of the magnetic flux density was 1.8 microT (rms).

740

Measurement of visual evoked potential during and after periods of pulsed magnetic field exposure

PURPOSE: To study the effect of switched magnetic fields used in MR scanners on the visual evoked potential (VEP) in human subjects. MATERIALS AND METHODS: We have used an MRI gradient coil, remote from an MRI magnet to produce a time-varying magnetic field (0.5 kHz, peak field approximately 8.7 T/second) in the human brain without the confounding effects of static field exposure or accompanying acoustic noise. The VEP response to a 2-Hz reversal, 8 x 8 checkerboard, occupying 20 degrees of the visual field was recorded from occipital locations O1 and O2. VEP recordings were made every five minutes before, during, and after a 10-minute magnetic field exposure period for seven subjects. RESULTS: In contradiction to studies previously reported in the literature for fields of 50 Hz and 60 mT, no significant effects on the peak amplitude or latency of the VEP P100 O1 and O2 responses were found. CONCLUSION: Switched magnetic fields of a level and frequency comparable to those used in MRI do not have a significant effect on primary retinal or visual processing.

741

Mechanical characterization of protein L in the low-force regime by electromagnetic tweezers/evanescent nanometry

Mechanical manipulation at the single molecule level of proteins exhibiting mechanical stability poses a technical challenge that has been almost exclusively approached by atomic force microscopy (AFM) techniques. However, due to mechanical drift limitations, AFM techniques are restricted to experimental recordings that last less than a minute in the high-force regime. Here we demonstrate a novel combination of electromagnetic tweezers and evanescent nanometry that readily captures the forced unfolding trajectories of protein L at pulling forces as low as 10-15 pN. Using this approach, we monitor unfolding and refolding cycles of the same polyprotein for a period of time longer than 30 min. From such long-lasting recordings, we obtain ensemble averages of unfolding step sizes and rates that are consistent with single-molecule AFM data obtained at higher stretching forces. The unfolding kinetics of protein L at low stretching forces confirms and extends the observations that the mechanical unfolding rate is exponentially dependent on the pulling force within a wide range of stretching forces spanning from 13 pN up to 120 pN. Our experiments demonstrate a novel approach for the mechanical manipulation of single proteins for extended periods of time in the low-force regime.

742

Mechanism for action of electromagnetic fields on cells

A biophysical model for the action of oscillating electric fields on cells, presented by us before [Biochem. Biophys. Res. Commun. 272(3) (2000) 634-640], is extended now to include oscillating magnetic fields as well, extended to include the most active biological conditions, and also to explain why pulsed electromagnetic fields can be more active biologically than continuous ones. According to the present theory, the low frequency fields are the most bioactive ones. The basic mechanism is the forced-vibration of all the free ions on the surface of a cell's plasma membrane, caused by an external oscillating field. We have shown that this coherent vibration of electric charge is able to irregularly gate electrosensitive channels on the plasma membrane and thus cause disruption of the cell's electrochemical balance and function [Biochem. Biophys. Res. Commun. 272(3) (2000) 634-640]. It seems that this simple idea can be easily extended now and looks very likely to be able to give a realistic basis for the explanation of a wide range of electromagnetic field bioeffects.

743

Megagauss sensors

Magnetic fields change the way that electrons move through solids. The nature of these changes reveals information about the electronic structure of a material and, in auspicious circumstances, can be harnessed for applications. The silver chalcogenides, Ag2Se and Ag2Te, are non-magnetic materials, but their electrical resistance can be made very sensitive to magnetic field by adding small amounts--just 1 part in 10,000--of excess silver. Here we show that the resistance of Ag2Se displays a large, nearly linear increase with applied magnetic field without saturation to the highest fields available, 600,000 gauss, more than a million times the Earth's magnetic field. These characteristics of large (thousands of per cent) and near-linear response over a large field range make the silver chalcogenides attractive as magnetic-field sensors, especially in physically tiny megagauss (10(6) G) pulsed magnets where large fields have been produced but accurate calibration has proved elusive. High-field studies at low temperatures reveal both oscillations in the magnetoresistance and a universal scaling form that point to a quantum origin for this material's unprecedented behaviour.

744

Melatonin and a spin-trap compound block radiofrequency electromagnetic radiation-induced DNA strand breaks in rat brain cells

Effects of in vivo microwave exposure on DNA strand breaks, a form of DNA damage, were investigated in rat brain cells. In previous research, we have found that acute (2 hours) exposure to pulsed (2 microseconds pulses, 500 pps) 2450-MHz radiofrequency electromagnetic radiation (RFR) (power density 2 mW/cm2, average whole body specific absorption rate 1.2 W/kg) caused an increase in DNA single- and double-strand breaks in brain cells of the rat when assayed 4 hours post exposure using a microgel electrophoresis assay. In the present study, we found that treatment of rats immediately before and after RFR exposure with either melatonin (1 mg/kg/injection, SC) or the spin-trap compound N-tert-butyl-alpha-phenylnitrone (PBN) (100 mg/kg/injection, i.p.) blocks this effects of RFR. Since both melatonin and PBN are efficient free radical scavengers it is hypothesized that free radicals are involved in RFR-induced DNA damage in the brain cells of rats. Since cumulated DNA strand breaks in brain cells can lead to neurodegenerative diseases and cancer and an excess of free radicals in cells has been suggested to be the cause of various human diseases, data from this study could have important implications for the health effects of RFR exposure.

746

Melatonin suppression by static and extremely low frequency electromagnetic fields: relationship to the reported increased incidence of cancer

An increased cancer incidence has been reported in individuals living and/or working in an environment in which they are exposed to higher than normal artificial electromagnetic fields. One of the most uniform changes associated with the exposure of animals to either pulsed static geomagnetic fields or to sinusoidal extremely low frequency magnetic fields has been a reduction in high night-time levels of melatonin. Melatonin is a hormone produced especially at night in the pineal gland, a pea-sized organ near the center of the human brain. The high nocturnal production of melatonin leads to elevated blood melatonin levels at night as well. The exposure of humans or animals to light (visible electromagnetic radiation) at night rapidly depresses pineal melatonin production and blood melatonin levels. Likewise, the exposure of animals to various pulsed static and extremely low frequency magnetic fields also reduces melatonin levels. Melatonin is a potent oncostatic agent and it prevents both the initiation and promotion of cancer. Reduction of melatonin, at night, by any means, increases cells' vulnerability to alteration by carcinogenic agents. Thus, if in fact artificial electromagnetic field exposure increases the incidence of cancer in humans, a plausible mechanism could involve a reduction in melatonin which is the consequence of such exposures.

747

Membrane potential and currents of isolated heart muscle cells exposed to pulsed radio frequency fields

The influence of radio frequency (RF) fields of 180, 900, and 1800 MHz on the membrane potential, action potential, L-type Ca(2+) current and potassium currents of isolated ventricular myocytes was tested. The study is based on 90 guinea-pig myocytes and 20 rat myocytes. The fields were applied in rectangular waveguides (1800 MHz at 80, 480, 600, 720, or 880 mW/kg and 900 MHz, 250 mW/kg) or in a TEM-cell (180 MHz, 80 mW/kg and 900 MHz, 15 mW/kg). Fields of 1800 and 900 MHz were pulsed according to the GSM-standard of cellular phones. The specific absorption rates were determined from computer simulations of the electromagnetic fields inside the exposure devices by considering the structure of the physiological test arrangement. The electrical membrane parameters were measured by whole cell patch-clamp. None of the tested electrophysiological parameters was changed significantly by exposure to RF fields. Another physical stimulus, lowering the temperature from 36 degrees C to 24 degrees C, decreased the current amplitude almost 50% and shifted the voltage dependence of the steady state activation parameter d(infinity) and inactivation parameter f(infinity) of L-type Ca(2+) current by about 5 mV. However, at this lower temperature RF effects (900 MHz, 250 mW/kg; 1800 MHz, 480 mW/kg) on L-type Ca(2+) current were also not detected.

748

Meta-analysis of the efficacy of non-steroidal anti-inflammatory drugs vs. opioids for SWL using modern electromagnetic lithotripters

PURPOSE: Clinical studies produce conflicting results on pain relief for shock wave lithotripsy (SWL). We performed a systematic review and meta-analysis to compare non-steroidal anti-inflammatory drugs (NSAIDs) and opioids in pain relief for SWL powered by an electromagnetic generator. MATERIAL AND METHODS: A search of MEDLINE and EMBASE was performed and all randomized controlled trials comparing NSAIDs and opioids in pain relief for SWL using modern electromagnetic lithotripters were included in the analysis. Data from 3 trials (244 patients) were pooled. The primary outcome measure was adequate analgesia, defined as "if no additional pain relief was used". The difference in the proportion of patients with adequate anesthesia was compared between the NSAIDs and opioids groups as an odds ratio and odds ratio were pooled across the 3 trials with a fixed effects model. RESULTS: There was no statistically significant difference between using NSAIDs and opioids for pain relief during SWL using modern electromagnetic lithotripters (odds ratio 0.886, 95% CI 0.446-1,760, p = 0.730). CONCLUSIONS: Our analysis shows that in relieving pain during SWL using modern electromagnetic lithotripters NSAIDs are as effective as opioids.

749

Metabolic Effects of Static Magnetic Fields on Streptococcus Pyogenes

This study aimed to develop a simple experimental system utilising bacterial cells to investigate the dose responses resulting from exposures to static magnetic flux densities ranging from 0.05 to 0.5 Ton viability, bacterial metabolism and levels of DNA damage in Streptococcus pyogenes. Exposure of S. pyogenes to a field of 0.3 Tat 24 8C under anaerobic conditions resulted in a significant (P<0.05) decrease in growth rate, with an increased mean generation time of 199!6 min compared to the control cells at 165!6 min (P<0.05). Conversely, exposure to magnetic fields of 0.5 T significantly accelerated the growth rate at 24 8C compared to control cells, with a decreased mean generation time of 147!4 min (P<0.05). The patterns of metabolite release from cells incubated in phosphate buffered saline (PBS) at 24 8C and exposed to different magnetic flux densities (0.05–0.5 T) were significantly (P<0.05) altered, compared to non-exposed controls. Concentrations of metabolites, with the exception of aspartic acid (r¼0.44), were not linearly correlated with magnetic flux density, with all other r<0.20. Instead, ‘‘window’’ effects were observed, with 0.25–0.3 T eliciting the maximal release of the majority of metabolites, suggesting that magnetic fields of these strengths had significant impacts on metabolic homeostasis in S. pyogenes. The exposure of cells to 0.3 T was also found to significantly reduce the yield of 8-hydroxyguanine in extracted DNA compared to controls, suggesting some possible anti-oxidant protection to S. pyogenes at this field strength.

750

Metal-to-insulator crossover in the low-temperature normal state of Bi(2)Sr(2-x)La(x)CuO(6+delta)

We measure the normal-state in-plane resistivity of Bi(2)Sr(2-x)La(x)CuO(6+delta) single crystals at low temperatures by suppressing superconductivity with 60 T pulsed magnetic fields. With decreasing hole doping, we observe a crossover from a metallic to an insulating behavior in the low-temperature normal state. This crossover is estimated to occur near 1/8 doping, well inside the underdoped regime, and not at optimum doping as reported for other cuprates. The insulating regime is marked by a logarithmic temperature dependence of the resistivity over two decades of temperature, suggesting that a peculiar charge localization is common to the cuprates.

751

Methotrexate cytotoxicity on MCF-7 breast cancer cells is not altered by exposure to 25 Hz, 1.5 mT magnetic field and iron (III) chloride hexahydrate

The action of electromagnetic fields (EMF) on different pathways related to cell physiology, proliferation, toxicity of chemicals, gene expression, etc., are currently being investigated although the results are still not conclusive and even conflicting. In laboratory and animal studies, EMF has been found to produce a great variety of effects such as: increase in ornithine decarboxylase activity in breast, increase in beta-galactosidase gene expression and oncogene transcription after exposure to 50/60 Hz. Animal studies have shown that the use of EMF can enhance drug delivery across biological barriers (rat abdominal skin), using benzoic acid as the drug candidate. It has been reported by different authors that pulsed EMF (PEMF) can produce alterations in antineoplastic drugs potency. In the present study, we investigated the effects of PEMF on methotrexate cytotoxicity in MCF-7 breast cancer cells and the effects with simultaneous exposure to FeCl3. The data presented in the current report indicate that PEMF (25 Hz, 1.5 mT) do not induce modulation of the action of methotrexate (with and without iron-III) in MCF-7 cells when they are exposed to PEMF for 2 h/day during 3 days.

752

Micro-morphologic changes around biophysically-stimulated titanium implants in ovariectomized rats

BACKGROUND: Osteoporosis may present a risk factor in achievement of osseointegration because of its impact on bone remodeling properties of skeletal phsiology. The purpose of this study was to evaluate micro-morphological changes in bone around titanium implants exposed to mechanical and electrical-energy in osteoporotic rats. METHODS: Fifteen 12-week old sprague-dowley rats were ovariectomized to develop osteoporosis. After 8 weeks of healing period, two titanium implants were bilaterally placed in the proximal metaphyses of tibia. The animals were randomly divided into a control group and biophysically-stimulated two test groups with five animals in each group. In the first test group, a pulsed electromagnetic field (PEMF) stimulation was administrated at a 0.2 mT 4 h/day, whereas the second group received low-magnitude high-frequency mechanical vibration (MECHVIB) at 50 Hz 14 min/day. Following completion of two week treatment period, all animals were sacrificed. Bone sites including implants were sectioned, removed en bloc and analyzed using a microCT unit. Relative bone volume and bone micro-structural parameters were evaluated for 144 mum wide peri-implant volume of interest (VOI). RESULTS: Mean relative bone volume in the peri-implant VOI around implants PEMF and MECHVIB was significantly higher than of those in control (P < .05). Differences in trabecular-thickness and -separation around implants in all groups were similar (P > .05) while the difference in trabecular-number among test and control groups was significant in all VOIs (P < .05). CONCLUSION: Biophysical stimulation remarkably enhances bone volume around titanium implants placed in osteoporotic rats. Low-magnitude high-frequency MECHVIB is more effective than PEMF on bone healing in terms of relative bone volume.

753

Microcirculatory effects of pulsed electromagnetic fields

PURPOSE: Pulsed electromagnetic fields (PEMF) are used clinically to expedite healing of fracture non-unions, however, the mechanism of action by which PEMF stimulation is effective is unknown. The current study examined the acute effects of PEMF stimulation on arteriolar microvessel diameters in the rat cremaster muscle. The study hypothesis was that PEMF would increase arteriolar diameters, a potential mechanism involved in the healing process. METHODS: Local PEMF stimulation/sham stimulation of 2 or 60 min duration was delivered to the cremaster muscle of anesthetized rats. Arteriolar diameters were measured before and after stimulation/sham stimulation using intravital microscopy. Systemic hemodynamics also were monitored during PEMF stimulation. RESULTS: Local PEMF stimulation produced significant (p<0.001) vasodilation, compared to pre-stimulation values, in cremasteric arterioles in anesthetized rats (n=24). This dilation occurred after 2 min of stimulation (9% diameter increase) and after 1 h of stimulation (8.7% diameter increase). Rats receiving "sham" stimulation (n=15) demonstrated no statistically significant change in arteriolar diameter following either "sham" stimulation period. PEMF stimulation of the cremaster (n=4 rats) did not affect systemic arterial pressure or heart rate, nor was it associated with a change in tissue environmental temperature. CONCLUSIONS: These results support the hypothesis that local application of a specific PEMF waveform can elicit significant arteriolar vasodilation. Systemic hemodynamics and environmental temperature could not account for the observed microvascular responses.

754

Micromechanical "Trampoline" magnetometers for use in large pulsed magnetic fields

A silicon micromechanical magnetometer was constructed and successfully used in 60-tesla pulsed magnetic fields of less than 100-millisecond duration. The device is small, inexpensive to fabricate, and easy to use. It features a fast mechanical response (up to 50,000 hertz) and extremely high sensitivity yet is relatively robust against electrical and mechanical noise. Quantum oscillations in the magnetization of a 1-microgram sample of an organic superconductor, kappa-[bis(ethylenedithio)tetrathiafulvalene]2Cu(NCS)2, have been observed with this device.

755

Miniature pulsed magnet system for synchrotron x-ray measurements

We have developed a versatile experimental apparatus for synchrotron x-ray measurements in pulsed high magnetic fields. The apparatus consists of a double cryostat incorporating a liquid nitrogen bath to cool the miniature pulsed coil and an independent helium flow cryostat allowing sample temperatures from 4 up to 250 K. The high duty cycle miniature pulsed coils can generate up to 38 T. During experiments at 30 T a repetition rate of 6 pulsesmin was routinely reached. Using a 4 kJ power supply, the pulse duration was between 500 mus and 1 ms. The setup was used for nuclear forward scattering measurements on (57)Fe up to 25 T on the ESRF beamline ID18. In another experiment, x-ray magnetic circular dichroism was measured up to 30 T on the ESRF energy dispersive beamline ID24.

756

Mitogen dose-dependent effect of weak pulsed electromagnetic field on lymphocyte blastogenesis

The effects of pulsed extremely low frequency electromagnetic fields on human peripheral blood lymphocyte mitogenesis induced by phytohaemoagglutinin, concanavalin A or calcium ionophore A23187 were studied. The dependence of the field effect on mitogen concentrations was investigated. Field exposure produced strong inhibition of DNA synthesis when optimal doses of mitogens were used, confirming our previous findings. Opposite effects were observed at suboptimal concentration of mitogens. Experiments performed by exposing cell cultures to the field for short periods indicated that a field application of at least 6 h is needed to influence irreversibly lymphocyte blastogenesis.

757

Mobile phones modulate response patterns of human brain activity

Mobile phones emit a pulsed high-frequency electromagnetic field (PEMF) which may penetrate the scalp and the skull. Increasingly, there is an interest in the interaction of this pulsed microwave radiation with the human brain. Our investigations show that these electromagnetic fields alter distinct aspects of the brain's electrical response to acoustic stimuli. More precisely, our results demonstrate that aspects of the induced but not the evoked brain activity during PEMF exposure can be different from those not influenced by PEMF radiation. This effect appears in higher frequency bands when subjects process task-relevant target stimuli but was not present for irrelevant standard stimuli. As the induced brain activity in higher frequency bands has been proposed to be a correlate of coherent high-frequency neuronal activity, PEMF exposure may provide means to systematically alter the pattern fluctuations in neural mass activity.

758

Modelling the internal field distribution in human erythrocytes exposed to MW radiation

This paper studies the internal electric field distribution in human erythrocytes exposed to MW radiation. For this purpose, an erythrocyte cell model is exposed to linearly polarized electromagnetic (EM) plane waves of frequency 900 MHz and the electric field within the cell is calculated by using a finite element (FE) technique with adaptive meshing. The results obtained show the dependence of the induced electric field distribution on the main modelling parameters, i.e., the electrical properties (permittivity and conductivity) of the membrane and cytoplasm and the orientation of the cell with respect to the applied field. It is found that for certain orientations, the field amplification within the membrane of the erythrocyte shape cell can be higher than the one observed in an equivalent simple spheroidal geometry cell, commonly used in bioelectromagnetism. The present work shows that a better insight of the interaction of electromagnetic fields with basic biological structures is obtained when the most possible realistic cell shape is used.

759

Modification of activation and evaluation properties of narratives by weak complex magnetic field patterns that simulate limbic burst firing

In two separate experiments a total of 71 volunteers were asked to generate spontaneous narratives that were scored automatically by the Whissell Dictionary of Affect. During the narratives, weak (1 microT; 10 mG) magnetic fields were applied briefly through the temporal planes. In Experiment I, subjects who were exposed to simple sine wave or pulsed fields generated more scorable words that indicated lower activation and evaluation than sham-field conditions. In Experiment II subjects exposed to a computer-generated wave form, designed to simulate neuronal burst firing, generated narratives dominated by more pleasantness and less activation than a reference group. The possibility that this approach could be utilized to study the affective dimension of language selection was indicated.

761

Modification of osteoarthritis by pulsed electromagnetic field--a morphological study

OBJECTIVE: Hartley guinea pigs spontaneously develop arthritis that bears morphological, biochemical, and immunohistochemical similarities to human osteoarthritis. It is characterized by the appearance of superficial fibrillation by 12 months of age and severe cartilage lesions and eburnation by 18 months of age. This study examines the effect of treatment with a pulsed electromagnetic field (PEMF) upon the morphological progression of osteoarthritis in this animal model. DESIGN: Hartley guinea pigs were exposed to a specific PEMF for 1h/day for 6 months, beginning at 12 months of age. Control animals were treated identically, but without PEMF exposure. Tibial articular cartilage was examined with histological/histochemical grading of the severity of arthritis, by immunohistochemistry for cartilage neoepitopes, 3B3(-) and BC-13, reflecting enzymatic cleavage of aggrecan, and by immunoreactivity to collagenase (MMP-13) and stromelysin (MMP-3). Immunoreactivity to TGFbeta, interleukin (IL)-1beta, and IL receptor antagonist protein (IRAP) antibodies was examined to suggest possible mechanisms of PEMF activity. RESULTS: PEMF treatment preserves the morphology of articular cartilage and retards the development of osteoarthritic lesions. This observation is supported by a reduction in the cartilage neoepitopes, 3B3(-) and BC-13, and suppression of the matrix-degrading enzymes, collagenase and stromelysin. Cells immunopositive to IL-1 are decreased in number, while IRAP-positive cells are increased in response to treatment. PEMF treatment markedly increases the number of cells immunopositive to TGFbeta. CONCLUSIONS: Treatment with PEMF appears to be disease-modifying in this model of osteoarthritis. Since TGFbeta is believed to upregulate gene expression for aggrecan, downregulate matrix metalloprotease and IL-1 activity, and upregulate inhibitors of matrix metalloprotease, the stimulation of TGFbeta may be a mechanism through which PEMF favorably affects cartilage homeostasis.

762

Modification of the synaptic glutamate turnover in the hippocampal tissue exposed to low-frequency, pulsed magnetic fields

The influence of pulsed magnetic fields (PMF) on the release and uptake of glutamate was investigated. While the release was examined using hippocampal slices, synaptosomes were chosen to characterize the uptake process. (3)H-D-aspartate was used as a marker of glutamergic transmission. The pulsed magnetic fields (9-15 mT) applied according to the pattern which induced epileptic discharges in hippocampus amplified and attenuated the release and uptake of glutamate, respectively. However, the magnetic fields which induced an increase in neuronal excitability without concomitant seizures amplified both processes. These results confirm our previous reports and indicate that the glutamergic synapses are the target of magnetic fields action.

763

Modulation of bone loss during disuse by pulsed electromagnetic fields

The effect of pulsed electromagnetic fields (PEMFs) on bone loss associated with disuse was investigated by applying 1.5 Hz repetitions of 30 ms bursts of asymmetric pulses, varying from +2.5 to -135 mV, to bones deprived of their normal functional loading. The proximal portion of one fibula in each of a group of ovariectomised adult female beagle dogs was isolated from functional loading in vivo by proximal and distal osteotomies. Comparison of these prepared bones with their intact contralateral controls after 12 weeks, showed a 23% reduction in cross-sectional area. In similarly prepared bones exposed to PEMFs for 1 h per day, 5 days per week, this bone loss was substantially and significantly reduced to 9% (p = 0.029). There was no evidence of any new bone formation on the periosteal surface of prepared fibulae in treated or untreated situations. PEMF treatment was not associated with any significant change in number of osteons per mm2 formed within the cortex of the bones, their radial closure rate, or their degree of closure. The modulation in loss of bone area associated with exposure to PEMFs can, therefore, be inferred to be due to a reduction in resorption on the bone surface.

764

Modulation of collagen production in cultured fibroblasts by a low-frequency, pulsed magnetic field

Primary cultures of chicken tendon fibroblasts have been exposed for various periods to a low-frequency, pulsed magnetic field, and the effects on protein and collagen synthesis have been examined by radioisotopic incorporation. Total protein synthesis was increased in confluent cells treated with a pulsed magnetic field for the last 24 h of culture as well as in cells treated for a total of 6 days. However, in 6 day-treated cultures, collagen accumulation was specifically enhanced as compared to total protein, whereas after short-term exposure, collagen production was increased only to the same extent as total protein. Levels of cyclic AMP were significantly decreased after 6-day pulsed magnetic field treatment, probably as a consequence of diminished adenylate cyclase activity. Exposure to pulsed magnetic field had no effect on cell proliferation or collagen phenotype. These results indicate that a pulsed magnetic field can specifically increase production of collagen, the major differentiated function of fibroblasts, possibly by altering cyclic-AMP metabolism.

765

Modulation of tendon fibroplasia by exogenous electric currents

A chicken tendon explant model system has been developed to investigate the effects of extremely-low-frequency (ELF), low-amplitude, unipolar, square wave pulsed electric fields on fibroplasia in vitro. An electric field parameter set consisting of 1-Hz, 1-ms duration pulses, with a time-averaged current density of 7 mA/m2 (peak current density 7 A/m2) induced maximal (32%) increase in fibroblast proliferation in tendon explants exposed for 4 days. Exposure to the same field at an average current density of 1.8 mA/m2 had no effect on fibroblast proliferation, whereas exposure to current densities on greater than 10 mA/m2 inhibited proliferation and relative collagen synthesis, without affecting noncollagen protein synthesis. Fibroplasia was significantly increased in explants oriented parallel to applied electric fields having current densities of 3.5 or 7 mA/m2, but there was no detectable effect on explants oriented perpendicular to the same electric field. Fibroblast proliferation and relative collagen synthesis were inversely proportional to donor age for chickens in the 3- to 16-week age group used in this study. For these dependent variables (proliferation and relative collagen synthesis), there was no interaction between donor age and ELF electric field exposure.

766

Molecular diffusion and DNP enhancement in aqueous char suspensions

The heterogeneous 1H dynamic nuclear polarization (DNP) effect is studied at low magnetic fields for a system consisting of several newly synthesized carbon chars suspended in water. By using Fourier Transform pulsed-field-gradient spin-echo NMR spectroscopy, several different self-diffusion coefficients have been observed in aqueous char suspensions, corresponding to regions of differing water mobility in the porous structure. Proton spin-lattice relaxation data generally confirm the results of molecular diffusion measurements. Through utilization of the Torrey model, the influence of "cage effects" on DNP enhancement in porous media is discussed. Results suggest that short-range nuclear-electronic interactions in pores have a dominant effect on DNP enhancement in char suspensions.

767

Molecular dynamics of polystyrene solutions in microwave fields

Equilibrium and nonequilibrium molecular dynamics simulation techniques were used to assess the influence of an applied microwave field on the dynamics of methylamine-methanol and methylamine-dimethylformamide (DMF) solutions bound within atactic polystyrene over a range of polymer densities from 35 to 96 wt % polymer. Atomistically detailed systems were studied, ranging from 3000 to 10 644 particles, using previously established potential models. Structural and dynamical properties were determined in the canonical (NVT) ensemble at 298 K. The simulated DMF self-diffusion coefficients in polystyrene solutions were compared with the zero-field experimental results established with pulsed-gradient spin-echo NMR spectrometry. A simulated external microwave field, with a rms electric field intensity of 0.1 VA, was applied to these systems and the simulated dynamical results over field frequencies up to 10(4) GHz were compared with the zero-field values. Simulated evidence of athermal effects on the diffusive characteristics of these mixtures is reported.

768

Morphological evaluation of MRC-5 fibroblasts after stimulation with static magnetic field and pulsating electromagnetic field

The quality of tissue repair and the speed with which that repair can be accomplished are the two major variables in the healing of any injury. Today, magnetic field exposure to traumatized areas has shown to be a promising tool in the healing process. The exact mode of action by which radiating and unchanging magnetic fields still has to be elucidated. The objective of this study was to evaluate the morphology of MRC-5 fibro-blasts after stimulation with static and pulsating magnetic fields. Under sterile environment, a total of 24 wells were loaded with 50,000 MRC-5 cells each and further divided into three groups. Groups 1 and 2 were exposed to magnetic fields, static and pulsating respectively. Group 3 wells were unexposed and served as the control group. The cells were monitored at 0, 24, 48, and 72 hours and representative views were captured using digital analysis techniques. The live cells were screened for cellular mobility, cell distribution, and cellular morphology (size, shape, lysis, and background). After 72 hours, the supernatants and cells of all three groups were collected and MDA analysis was performed to determine possible cellular damage. Group 1 cells continued to grow at a reasonable rate, but there was substantial cell membrane damage (high MDA levels, p < 0.05). Group 2 cells appeared to be very stressed under these conditions especially at the initial phase (24 hours). In conclusion, the use of pulsating magnetic stimulation can be beneficial in the healing process of soft tissues.

769

MRI gradient fields increase brain mannitol space

Following nephrectomy and intravenous injection of tritiated mannitol, adult male rats were exposed to magnetic resonance imaging (MRI) procedures at 1.5 T, 0.5 T, and 0.3 T. Compared to rats similarly handled but not exposed to MRI procedures, brain mannitol concentration, expressed as a percentage of mean body concentration, was significantly increased at 0.3 T and 0.5 T but not at 1.5 T. At 0.3 T, exposure to gradient-field fluctuations used for imaging increased brain mannitol concentration, but exposures to static main field and pulsed radiofrequency energies did not. Increased brain mannitol associated with gradient-field flux may reflect increased blood-brain barrier permeability or blood volume in brain. MRI effects on brain mannitol space are of uncertain clinical significance, but are consistent with prior evidence of an MRI-induced increase of brain capillary endothelial cell transport observed with horseradish peroxidase. Further studies are needed to confirm these findings and to explore the processes underlying changes in mannitol distribution related to MRI.

770

Multi-echo imaging in highly inhomogeneous magnetic fields

A new pulsed field gradient multi-echo imaging technique to encode position in the phase of every echo generated by a CPMG sequence in the presence of a strongly inhomogeneous static magnetic field is presented. It was applied to improve the sensitivity in an imaging experiment by adding the echo train acquired during the CPMG sequence and to spatially resolve relaxation times of inhomogeneous specimens using single-sided probes. The sequence was implemented in a new bar-magnet MOUSE equipped with a gradient coil system to apply a pulsed magnetic field with a constant gradient along one spatial coordinate. An important reduction by a factor larger than two orders of magnitude in the acquisition time was obtained compared to the previously published single-point imaging technique.

771

Multiferroic BaTiO3-CoFe2O4 Nanostructures

We report on the coupling between ferroelectric and magnetic order parameters in a nanostructured BaTiO3-CoFe2O4 ferroelectromagnet. This facilitates the interconversion of energies stored in electric and magnetic fields and plays an important role in many devices, including transducers, field sensors, etc. Such nanostructures were deposited on single-crystal SrTiO3 (001) substrates by pulsed laser deposition from a single Ba-Ti-Co-Fe-oxide target. The films are epitaxial in-plane as well as out-of-plane with self-assembled hexagonal arrays of CoFe2O4 nanopillars embedded in a BaTiO3 matrix. The CoFe2O4 nanopillars have uniform size and average spacing of 20 to 30 nanometers. Temperature-dependent magnetic measurements illustrate the coupling between the two order parameters, which is manifested as a change in magnetization at the ferroelectric Curie temperature. Thermodynamic analyses show that the magnetoelectric coupling in such a nanostructure can be understood on the basis of the strong elastic interactions between the two phases.

772

Multiple sclerosis: improvement of visuoperceptive functions by picoTesla range magnetic fields

The occurrence of cognitive deficits in multiple sclerosis (MS) has been recognized since 1877 when Charcot first observed "enfeeblement of memory" in his patients. Recent studies employing standardized neuropsychological tests have confirmed the high incidence of cognitive deficits in MS patients particularly those with a chronic progressive course of the disease. Visuoperceptive and visuomotor deficits commonly occur in MS patients and are thought to reflect damage to attentional systems due to interruption by demyelinating plaques of nerve conduction along the ascending projections from the brainstem reticular formation to the cortex. Impairment of synaptic conductivity due to serotoninergic depletion (5-HT) may contribute to the emergence of cognitive deficits in MS. The present communication concerns a 36 year old patient with MS in whom external application of picoTesla range magnetic fields (MF) resulted in rapid improvement of symptoms including visuoperceptive functions as demonstrated on various drawing tasks. The report confirms the efficacy of picoTesla range MF in the treatment of MS and demonstrates beneficial effects on cognitive functions as well.

773

Multiple sclerosis: the role of puberty and the pineal gland in its pathogenesis

Epidemiological studies demonstrate that the incidence of multiple sclerosis (MS) is age-dependent being rare prior to age 10, unusual prior to age 15, with a peak in the mid 20s. It has been suggested that the manifestation of MS is dependent upon having passed through the pubertal period. In the present communication, I propose that critical changes in pineal melatonin secretion, which occur in temporal relationship to the onset of puberty, are intimately related to the timing of onset of the clinical manifestations of MS. Specifically, it is suggested that the fall in melatonin secretion during the prepubertal period, which may disrupt pineal-mediated immunomodulation, may stimulate either the reactivation of the infective agent or increase the susceptibility to infection during the pubertal period. Similarly, the rapid fall in melatonin secretion just prior to delivery may account for the frequent occurrence of relapse in MS patients during the postpartum period. In contrast, pregnancy, which is associated with high melatonin concentrations, is often accompanied by remission of symptoms. Thus, the presence of high melatonin levels may provide a protective effect, while a decline in melatonin secretion may increase the risk for the development and exacerbation of the disease. The melatonin hypothesis of MS may explain other epidemiological and clinical phenomena associated with the disease such as the low incidence of MS in the black African and American populations, the inverse correlation with sun light and geomagnetic field exposure, the occurrence of relapses in relation to seasonal changes and fluctuations in mood, and the association of MS with affective illness and malignant disease. Therapeutically, this hypothesis implies that application of bright light therapy or the use of other major synchronizers of circadian rhythms such as sleep deprivation or application of external weak magnetic fields may be beneficial in the treatment and/or prophylaxis of relapses in the disease.

774

Myosin Light Chain Modification Depending on Magnetic Fields: II. Experimental

Recent experiments have revealed that Ca2+ -calmodulin dependent myosin light chain phosphorylation in a cell-free preparation exhibits unexpectedly high sensitivity to weak magnetic fields. This enzyme system is a well-studied biochemical system, which appears to depend upon ion binding. A previous article in this journal discussed the theoretical background of myosin phosphorylation and the ion-dependent interactions of EMF with soft tissues. Because of the electromagnetic field (EMF) sensitivity of this cell-free system, experiments were designed to test the effect of a pulsed radio frequency (PRF) field, pulsating magnetic fields (TEMF), gradient magnetic fields (Magnabloc), and homogeneous static magnetic fields (in Helmholtz arrangement) designed for clinical application. It is concluded that these various magnetic fields affect this cell-free enzyme system by modulating ion-protein interactions.

775

Naltrexone attenuates the antiparkinsonian effects of picoTesla range magnetic fields

Extracranial treatment with magnetic fields (MF) in the picoTesla range has been shown an efficacious treatment modality in the management of Parkinsonism. The mechanisms by which such extremely weak MF improve Parkinsonian symptoms are unknown. As the pineal gland has been shown to function as a "magnetosensor" and since exposure to various intensities of MF disrupts melatonin secretion, it has been proposed that the beneficial effects of MF in Parkinsonism are partly mediated through the actions of pineal melatonin. Animal studies indicate that externally applied MF also influence the activity of the opioid peptides which have been implicated in a broad range of pathological conditions including Parkinsonism. To explore whether the beneficial effects of MF in Parkinsonism involve the mediation of the opioid systems and following informed consent, we administered the opiate receptor antagonist naltrexone (50 mg, P.O.) to a Parkinsonian patient after he showed improvement of symptoms with application of MF. Results of the trial showed that naltrexone partially reversed the antiparkinsonian effects of MF thus suggesting that opioid peptides are involved in mediating the clinical effects of these extremely weak MF in Parkinsonism. These results also suggest that intact opioid systems may be required for a full expression of the antiparkinsonian effect of picoTesla range MF.

776

Nanoelectropulse-driven membrane perturbation and small molecule permeabilization

BACKGROUND: Nanosecond, megavolt-per-meter pulsed electric fields scramble membrane phospholipids, release intracellular calcium, and induce apoptosis. Flow cytometric and fluorescence microscopy evidence has associated phospholipid rearrangement directly with nanoelectropulse exposure and supports the hypothesis that the potential that develops across the lipid bilayer during an electric pulse drives phosphatidylserine (PS) externalization. RESULTS: In this work we extend observations of cells exposed to electric pulses with 30 ns and 7 ns durations to still narrower pulse widths, and we find that even 3 ns pulses are sufficient to produce responses similar to those reported previously. We show here that in contrast to unipolar pulses, which perturb membrane phospholipid order, tracked with FM1-43 fluorescence, only at the anode side of the cell, bipolar pulses redistribute phospholipids at both the anode and cathode poles, consistent with migration of the anionic PS head group in the transmembrane field. In addition, we demonstrate that, as predicted by the membrane charging hypothesis, a train of shorter pulses requires higher fields to produce phospholipid scrambling comparable to that produced by a time-equivalent train of longer pulses (for a given applied field, 30, 4 ns pulses produce a weaker response than 4, 30 ns pulses). Finally, we show that influx of YO-PRO-1, a fluorescent dye used to detect early apoptosis and activation of the purinergic P2X7 receptor channels, is observed after exposure of Jurkat T lymphoblasts to sufficiently large numbers of pulses, suggesting that membrane poration occurs even with nanosecond pulses when the electric field is high enough. Propidium iodide entry, a traditional indicator of electroporation, occurs with even higher pulse counts. CONCLUSION: Megavolt-per-meter electric pulses as short as 3 ns alter the structure of the plasma membrane and permeabilize the cell to small molecules. The dose responses of cells to unipolar and bipolar pulses ranging from 3 ns to 30 ns duration support the hypothesis that a field-driven charging of the membrane dielectric causes the formation of pores on a nanosecond time scale, and that the anionic phospholipid PS migrates electrophoretically along the wall of these pores to the external face of the membrane.

777

Nanoelectropulse-induced phosphatidylserine translocation

Nanosecond, megavolt-per-meter, pulsed electric fields induce phosphatidylserine (PS) externalization, intracellular calcium redistribution, and apoptosis in Jurkat T-lymphoblasts, without causing immediately apparent physical damage to the cells. Intracellular calcium mobilization occurs within milliseconds of pulse exposure, and membrane phospholipid translocation is observed within minutes. Pulsed cells maintain cytoplasmic membrane integrity, blocking propidium iodide and Trypan blue. Indicators of apoptosis-caspase activation and loss of mitochondrial membrane potential-appear in nanoelectropulsed cells at later times. Although a theoretical framework has been established, specific mechanisms through which external nanosecond pulsed electric fields trigger intracellular responses in actively growing cells have not yet been experimentally characterized. This report focuses on the membrane phospholipid rearrangement that appears after ultrashort pulse exposure. We present evidence that the minimum field strength required for PS externalization in actively metabolizing Jurkat cells with 7-ns pulses produces transmembrane potentials associated with increased membrane conductance when pulse widths are microseconds rather than nanoseconds. We also show that nanoelectropulse trains delivered at repetition rates from 2 to 2000 Hz have similar effects, that nanoelectropulse-induced PS externalization does not require calcium in the external medium, and that the pulse regimens used in these experiments do not cause significant intra- or extracellular Joule heating.

778

Nanosecond electric pulses penetrate the nucleus and enhance speckle formation

Nanosecond electric pulses generate nanopores in the interior membranes of cells and modulate cellular functions. Here, we used confocal microscopy and flow cytometry to observe Smith antigen antibody (Y12) binding to nuclear speckles, known as small nuclear ribonucleoprotein particles (snRNPs) or intrachromatin granule clusters (IGCs), in Jurkat cells following one or five 10ns, 150kV/cm pulses. Using confocal microscopy and flow cytometry, we observed changes in nuclear speckle labeling that suggested a disruption of pre-messenger RNA splicing mechanisms. Pulse exposure increased the nuclear speckled substructures by approximately 2.5-fold above basal levels while the propidium iodide (PI) uptake in pulsed cells was unchanged. The resulting nuclear speckle changes were also cell cycle dependent. These findings suggest that 10ns pulses directly influenced nuclear processes, such as the changes in the nuclear RNA-protein complexes.

779

Nanosecond pulse electric field (nanopulse): a novel non-ligand agonist for platelet activation

Nanosecond pulse stimulation of a variety of cells produces a wide range of physiological responses (e.g., apoptosis, stimulation of calcium (Ca2+) fluxes, changes in membrane potential). In this study, we investigated the effect of nanosecond pulses, which generate intense electric fields (nsPEFs), on human platelet aggregation, intracellular free Ca2+ ion concentration ([Ca2+]i) and platelet-derived growth factor release. When platelet rich plasma was pulsed with one 300ns pulse with an electric field of 30kV/cm, platelets aggregated and a platelet gel was produced. Platelet aggregation was observed with pulses as low as 7kV/cm with maximum effects seen with approximately 30kV/cm. The increases in intracellular Ca2+ release and Ca2+ influx were dose dependent on the electrical energy density and were maximally stimulated with approximately 30kV/cm. The increases in [Ca2+]i induced by nsPEF were similar to those seen with thapsigargin but not thrombin. We postulate that nsPEF caused Ca2+ to leak out of intracellular Ca2+ stores by a process involving the formation of nanopores in organelle membranes and also caused Ca2+ influx through plasma membrane nanopores. We conclude that nsPEFs dose-dependently cause platelets to rapidly aggregate, like other platelet agonists, and this is most likely initiated by the nsPEFs increasing [Ca2+]i, however by a different mechanism.

780

Nanosecond pulsed electric field generators for the study of subcellular effects

Modeling and experimental studies have shown that pulsed electric fields of nanosecond duration and megavolt per meter amplitude affect subcellular structures but do not lead to the formation of large pores in the outer membrane. This "intracellular electromanipulation" requires the use of pulse generators which provide extremely high power but low energy pulses. In this study, we describe the concept of the required pulsed power sources, their design, operation, and the necessary diagnostics. Two types of pulse generators based on the Blumlein line principle have been developed and are described here. One system is designed to treat a large number of cells in cuvettes holding volumes from 0.1 to 0.8 ml. Pulses of up to 40 kV amplitude, with a duration of 10 ns and a rise time close to 1 ns can be applied to the cuvette. For an electrode gap of 1 mm this voltage corresponds to an average electric field of 40 MV/m. The second system allows for real time observation of individual cells under a microscope. It generates pulses of 10-300 ns duration with a rise time of 3.5 ns and voltage amplitudes up to 1 kV. Connected to a microreactor with an electrode gap of 100 microm, electric fields up to 10 MV/m are applied.

781

Nanosecond pulsed electric fields (nsPEF) induce direct electric field effects and biological effects on human colon carcinoma cells

Nanosecond pulsed electric fields (nsPEFs) are ultrashort pulses with high electric field intensity (kV/cm) and high power (megawatts), but low energy density (mJ/cc). To determine roles for p53 in response to nsPEFs, HCT116 cells (p53+/+ and p53-/-) were exposed to nsPEF and analyzed for membrane integrity, phosphatidylserine externalization, caspase activation, and cell survival. Decreasing plasma membrane effects were observed in both HCT116p53+/+ and p53-/- cells with decreasing pulse durations and/or decreasing electric fields. However, addition of ethidium homodimer-1 and Annexin-V-FITC post-pulse demonstrated greater fluorescence in p53-/- versus p53+/+ cells, suggesting a postpulse p53-dependent biological effect at the plasma membrane. Caspase activity was significantly higher than nonpulsed cells only in the p53-/- cells. HCT116 cells exhibited greater survival in response to nsPEFs than HL-60 and Jurkat cells, but survival was more evident for HCT116p53+/+ cells than for HCT116p53-/- cells. These results indicate that nsPEF effects on HCT116 cells include (1) apparent direct electric field effects, (2) biological effects that are p53-dependent and p53-independent, (3) actions on mechanisms that originate at the plasma membranes and at intracellular structures, and (4) an apparent p53 protective effect. NsPEF applications provide a means to explore intracellular structures and functions that can reveal mechanisms in health and disease.

782

Nanosecond pulsed electric fields cause melanomas to self-destruct

We have discovered a new, drug-free therapy for treating solid skin tumors. Pulsed electric fields greater than 20 kV/cm with rise times of 30 ns and durations of 300 ns penetrate into the interior of tumor cells and cause tumor cell nuclei to rapidly shrink and tumor blood flow to stop. Melanomas shrink by 90% within two weeks following a cumulative field exposure time of 120 micros. A second treatment at this time can result in complete remission. This new technique provides a highly localized targeting of tumor cells with only minor effects on overlying skin. Each pulse deposits 0.2 J and 100 pulses increase the temperature of the treated region by only 3 degrees C, ten degrees lower than the minimum temperature for hyperthermia effects.

783

Nanosecond pulsed electric fields induce apoptosis in p53-wildtype and p53-null HCT116 colon carcinoma cells

Non-ionizing radiation produced by nanosecond pulsed electric fields (nsPEFs) is an alternative to ionizing radiation for cancer treatment. NsPEFs are high power, low energy (non-thermal) pulses that, unlike plasma membrane electroporation, modulate intracellular structures and functions. To determine functions for p53 in nsPEF-induced apoptosis, HCT116p53(+/+) and HCT116p53(-/-) colon carcinoma cells were exposed to multiple pulses of 60 kV/cm with either 60 ns or 300 ns durations and analyzed for apoptotic markers. Several apoptosis markers were observed including cell shrinkage and increased percentages of cells positive for cytochrome c, active caspases, fragmented DNA, and Bax, but not Bcl-2. Unlike nsPEF-induced apoptosis in Jurkat cells (Beebe et al. 2003a) active caspases were observed before increases in cytochrome c, which occurred in the presence and absence of Bax. Cell shrinkage occurred only in cells with increased levels of Bax or cytochrome c. NsPEFs induced apoptosis equally in HCT116p53(+/+) and HCT116p53(-/-) cells. These results demonstrate that non-ionizing radiation produced by nsPEFs can act as a non-ligand agonist with therapeutic potential to induce apoptosis utilizing mitochondrial-independent mechanisms in HCT116 cells that lead to caspase activation and cell death in the presence or absence of p-53 and Bax.

784

Nanosecond pulsed electric fields modulate cell function through intracellular signal transduction mechanisms

These studies describe the effects of nanosecond (10-300 ns) pulsed electric fields (nsPEF) on mammalian cell structure and function. As the pulse durations decrease, effects on the plasma membrane (PM) decrease and effects on intracellular signal transduction mechanisms increase. When nsPEF-induced PM electroporation effects occur, they are distinct from classical PM electroporation effects, suggesting unique, nsPEF-induced PM modulations. In HL-60 cells, nsPEF that are well below the threshold for PM electroporation and apoptosis induction induce effects that are similar to purinergic agonistmediated calcium release from intracellular stores, which secondarily initiate capacitive calcium influx through store-operated calcium channels in the PM. NsPEF with durations and electric field intensities that do or do not cause PM electroporation, induce apoptosis in mammalian cells with a well-characterized phenotype typified by externalization of phosphatidylserine on the outer PM and activation of caspase proteases. Treatment of mouse fibrosarcoma tumors with nsPEF also results in apoptosis induction. When Jurkat cells were transfected by electroporation and then treated with nsPEF, green fluorescent protein expression was enhanced compared to electroporation alone. The results indicate that nsPEF activate intracellular mechanisms that can determine cell function and fate, providing an important new tool for probing signal transduction mechanisms that modulate cell structure and function and for potential therapeutic applications for cancer and gene therapy.

785

Negative intrinsic resistivity of an individual domain wall in epitaxial (Ga,Mn)As microdevices

Magnetic domains, and the boundaries that separate them (domain walls, DWs), play a central role in the science of magnetism. Understanding and controlling domains is important for many technological applications in spintronics, and may lead to new devices. Although theoretical efforts have elucidated several mechanisms underlying the resistance of a single DW, various experiments report conflicting results, even for the overall sign of the DW resistance. The question of whether an individual DW gives rise to an increase or decrease of the resistance therefore remains open. Here we report an approach to DW studies in a class of ferromagnetic semiconductors (as opposed to metals) that offer promise for spintronics. These experiments involve microdevices patterned from monocrystalline (Ga,Mn)As epitaxial layers. The giant planar Hall effect that we previously observed in this material enables direct, real-time observation of the propagation of an individual magnetic DW along multiprobe devices. We apply steady and pulsed magnetic fields, to trap and carefully position an individual DW within each separate device studied. This protocol reproducibly enables high-resolution magnetoresistance measurements across an individual wall. We consistently observe negative intrinsic DW resistance that scales with channel width. This appears to originate from sizeable quantum corrections to the magnetoresistance.

786

Nerve cell damage in mammalian brain after exposure to microwaves from GSM mobile phones

The possible risks of radio-frequency electromagnetic fields for the human body is a growing concern for our society. We have previously shown that weak pulsed microwaves give rise to a significant leakage of albumin through the blood-brain barrier. In this study we investigated whether a pathologic leakage across the blood-brain barrier might be combined with damage to the neurons. Three groups each of eight rats were exposed for 2 hr to Global System for Mobile Communications (GSM) mobile phone electromagnetic fields of different strengths. We found highly significant (p< 0.002) evidence for neuronal damage in the cortex, hippocampus, and basal ganglia in the brains of exposed rats.

787

Neurobiological effects of extensive transcranial electromagnetic stimulation in an animal model

The effects of transcranial electromagnetic stimulation (TEMS) on the cellular morphology of the cortex, cerebellum, and brain-stem were systematically investigated in rabbits exposed to 1000 pulsed stimuli at 100% maximum stimulation level (2.0 Tesla at the skull) over a 12 month period with a 5 cm circular magnetic coil positioned over the cranium. Also, the acute effects of TEMS on heart rate and respiration were examined. (1) T1 and T2 weighted magnetic resonance images (MRI) of 1-3 mm sections in both sagittal and axial planes revealed no evidence of gross morphological changes or subtler tissue damage to the cerebrum, cerebellum, or brain-stem. (2) Light microscopic examination of 60 microns hematoxylin-eosin/Cresyl Violet Luxol Fast Blue stained sections of the brain-stem, cerebellum, and cerebral cortex showed no TEMS-related changes in cellular organization or histological damage. (3) Autonomic activity as reflected by heart rate was also unaffected by high intensity TEMS. Normal heart rate was maintained during repeated TEMS at 100% of maximum. (4) Respiration rate was briefly altered at the time of the stimulus, but returned to normal immediately after the stimulus. These findings in experimental animals revealed no biohazardous effects on the brain following extensive exposure to high intensity, low frequency time-varying magnetic field stimulation from the coil of a clinical instrument.

788

Neuroelectric mechanisms applied to low frequency electric and magnetic field exposure guidelines--part II: non sinusoidal waveforms

Standards for human exposure to electromagnetic fields typically express maximum permissible exposure limits as a function of frequency. Often, these limits have been derived from experiments or theoretical models involving sinusoidal waveforms. In many practical situations, however, the relevant waveforms of interest may not be sinusoidal, such as with waveforms having harmonic distortion, or with pulsed waveforms. This paper evaluates methods for applying sinusoidal exposure standards to non-sinusoidal waveforms in the frequency regime below a few MHz where electrostimulation is the dominant mechanism. Waveforms treated include those of a pulsed or mixed frequency variety. We evaluate acceptance criteria for mixed frequency exposure using summation formulae cited by IEEE C95.1, ICNIRP, and NRPB. This is carried out using a Fourier synthesis of various waveshapes. Also evaluated is an acceptance criterion based on the peak of the exposure waveform. Excitation thresholds are evaluated using a myelinated nerve model that accounts for the nonlinear electrodynamics of the neural membrane. It is shown that a method based on the peak and phase duration of the in situ field waveform provides a typically conservative test for compliance with non sinusoidal waveforms. An alternate method, based on amplitude summation of the Fourier components of the applied waveforms, can also provide a meaningful test, albeit a more conservative one.

789

New technique for treating pseudocyst of the auricle

Although pseudocyst of the auricle is a common disease in China, its cause and mechanism are still not clear. Several methods of treatment have been advocated: repeated aspirations combined with physiotherapy, and incision and drainage with contour pressure dressing, magnetotherapy etc. In recent years, a new technique with a drainage tube inserted into the pseudocyst using a guide needle has been used in our hospital in the treatment of this condition. We report 45 cases treated by this method, none of whom had the condition previously.

790

New technologies in electron spin resonance

New electron spin resonance (ESR) technologies have been developed, which have led to new and improved applications. (a) The development of two-dimensional Fourier transform (FT) ESR required spectrometers providing intense pi/2 microwave pulses of very short (3-5 ns) duration, wide bandwidths, and very short dead times. It has enabled studies that resolve sophisticated details of molecular dynamics in complex fluids. (b) Methods that produce multiple quantum coherences by pulsed ESR now enable accurate measurements of large distances (>12A). (c) One of the most important advances has been the extension of ESR to high magnetic fields and high frequencies. This has benefited from the utilization of quasi-optical methods, especially above 150 GHz. The greatly improved orientational resolution and the faster "snapshot" of motions that are provided by ESR at high frequencies enhance studies of molecular dynamics. The use of both high and lower frequencies enables one to unravel faster and slower modes from the complex dynamics of fluids and macromolecules. (d) The development of FT-ESR imaging required substantial pulsed field gradients lasting only 50-100 ns. ESR imaging is effective in studying diffusion in fluids. Areas for further development are also described.

791

Nitric oxide mediates the effects of pulsed electromagnetic field stimulation on the osteoblast proliferation and differentiation

The purpose of this research was to investigate whether the effects of pulsed electromagnetic field (PEMF) stimulation on the osteoblast proliferation and differentiation are mediated by the increase in the nitric oxide (NO, nitrogen monoxide) synthesis. The osteoblasts (MC3T3-E1 cell line) were cultured in the absence (-NMMA group) or in the presence (+NMMA group) of the NO synthase inhibitor L-NMMA. First, osteoblasts were subjected to PEMF stimulation (15 Hz and 0.6 mT) up to 15 days. The DNA content and the NO concentration in the conditioned medium were determined on the 3rd, 7th, and 15th days of culture. Following, osteoblasts were stimulated in the proliferation (P-NMMA and P+NMMA groups) or in the differentiation (D-NMMA and D+NMMA groups) stages of maturation, and the alkaline phosphatase (AlPase) activity was determined on the 15th day of culture for all groups. PEMF stimulation increased significantly the nitrite concentration in the -NMMA group on the 3rd, 7th, and 15th days of culture. However, this effect was partially blocked in the +NMMA group. The DNA content in the -NMMA group, but not in the +NMMA group, increased significantly on the 3rd and 7th days of culture. The AlPase activity in the P-NMMA and D-NMMA groups, but not in the P+NMMA and D+NMMA groups, also increased significantly. In conclusion, the PEMF stimulatory effects on the osteoblasts proliferation and differentiation were mediated by the increase in the NO synthesis.

792

NMR probes for measuring magnetic fields and field dynamics in MR systems

High-resolution magnetic field probes based on pulsed liquid-state NMR are presented. Static field measurements with an error of 10 nanotesla or less at 3 tesla are readily obtained in 100 ms. The further ability to measure dynamic magnetic fields results from using small ( approximately 1 microL) droplets of MR-active liquid surrounded by susceptibility-matched materials. The consequent high field homogeneity allows free induction decay signals lasting 100 ms or more to be readily achieved. The small droplet dimensions allow the magnetic field to be measured even in the presence of large gradients. Highly sensitive detection yields sufficient SNR to follow the relevant field evolution without signal averaging and at bandwidths up to hundreds of kHz. Transient, nonreproducible effects and drifts are thus readily monitored. The typical application of k-space trajectory mapping has been demonstrated. Potential further applications include characterization, tuning, and maintenance of gradient systems as well as the mapping of the static field distribution of MRI magnets. Connection of the probes to a standard MR spectrometer is similar to that used for imaging coils.

793

No effect of pulsed electromagnetic fields on PC12 and HL-60 cells

The effect of pulsed electromagnetic fields (PEMF) similar to those used in transcranial magnetic stimulation (TMS) on two tumour cell lines, the human promyelocytic leukaemia cell line (HL-60) and the rat pheochromocytoma cell line (PC12), was investigated. The two cell lines were exposed to non-homogeneous pulsed electromagnetic fields (about 0.25-4.5 T peak magnetic field strength; 1-8 exponential pulses, 0.25 Hz) at different positions on the coil (2x25 mm). After exposure with various intensities, various numbers of pulses and at different coil positions, cell viability and the intracellular cyclic AMP content were determined in the two cell lines. Additionally, in HL-60 cells the intracellular Hsp72 content and in PC12 cells the release of the neurotransmitters dopamine, noradrenaline and acetylcholine were measured after PEMF treatment. The results of these analyses do not hint at alterations in the cell viability or in the content of cAMP, Hsp72, dopamine, noradrenaline, and acetylcholine in the two tumour cell lines after PEMF exposure under various conditions.

794

No effect of pulsed magnetic stimulation on the blood-brain barrier in rats

The impact of transcranial pulsed magnetic stimulation on blood-brain barrier permeability was studied in rats. An integral uptake technique was used to asses the blood-brain barrier permeability to the tracers [3H]sucrose, [14C]urea, and 36Cl-. From the arterial plasma concentration-time curve-integral the permeability surface-area products were calculated. A Dantec magnetic stimulator delivering a peak magnetic field of 1.9 T with a rise-time of 160 microseconds was used for transcranial stimulation of the rats. One group of rats had about 50-60 stimulations during the 15-min infusion of the tracers while another group was exposed to 50 magnetic stimulations a day for one week. A third group comprised the controls. No differences in permeability surface-area product were found for any of the three tracers in the rats exposed to magnetic stimulation as compared with the controls. It is concluded that with regard to blood-barrier integrity, pulsed magnetic stimulation of the brain can be regarded as safe.

795

No effects of mobile phone electromagnetic field on auditory brainstem response

The present study investigated the possible effects of the electromagnetic field (EMF) emitted by an ordinary GSM mobile phone (902.4 MHz pulsed at 217 Hz) on brainstem auditory processing. Auditory brainstem responses (ABR) were recorded in 17 healthy young adults, without a mobile phone at baseline, and then with a mobile phone on the ear under EMF-off and EMF-on conditions. The amplitudes, latencies, and interwave intervals of the main ABR components (waves I, III, V) were compared among the three conditions. ABR waveforms showed no significant differences due to exposure, suggesting that short-term exposure to mobile phone EMF did not affect the transmission of sensory stimuli from the cochlea up to the midbrain along the auditory nerve and brainstem auditory pathways. Bioelectromagnetics, 2009. (c) 2009 Wiley-Liss, Inc.

796

No effects of pulsed high-frequency electromagnetic fields on heart rate variability during human sleep

The influence of pulsed high-frequency electromagnetic fields emitted by digital mobile radio telephones on heart rate during sleep in healthy humans was investigated. Beside mean RR interval and total variability of RR intervals based on calculation of the standard deviation, heart rate variability was assessed in the frequency domain by spectral power analysis providing information about the balance between the two branches of the autonomic nervous system. For most parameters, significant differences between different sleep stages were found. In particular, slow-wave sleep was characterized by a low ratio of low- and high-frequency components, indicating a predominance of the parasympathetic over the sympathetic tone. In contrast, during REM sleep the autonomic balance was shifted in favor of the sympathetic activity. For all heart rate parameters, no significant effects were detected under exposure to the field compared to placebo condition. Thus, under the given experimental conditions, autonomic control of heart rate was not affected by weak-pulsed high-frequency electromagnetic fields.

797

No effects of pulsed radio frequency electromagnetic fields on melatonin, cortisol, and selected markers of the immune system in man

There is growing public concern that radio frequency electromagnetic fields may have adverse biological effects. In the present study eight healthy male students were tested to see whether or not radio frequency electromagnetic fields as used in modern digital wireless telecommunication (GSM standard) have noticeable effects on salivary melatonin, cortisol, neopterin, and immunoglobulin A (sIgA) levels during and several hours after exposure. In a specifically designed, shielded experimental chamber, the circularly polarized electromagnetic field applied was transmitted by an antenna positioned 10 cm behind the head of upright sitting test persons. The carrier frequency of 900 MHz was pulsed with 217 Hz (average power flux density 1 W/m2). In double blind trials, each test person underwent a total of 20 randomly allotted 4 hour periods of exposure and sham exposure, equally distributed at day and night. The results obtained show that the salivary concentrations of melatonin, cortisol, neopterin and sIgA did not differ significantly between exposure and sham exposure.

798

No influence of magnetic fields on cell cycle progression using conditions relevant for patients during MRI

The purpose of this study was to examine whether exposure to magnetic fields (MFs) relevant for magnetic resonance imaging (MRI) in clinical routine influences cell cycle progression in two tumor cell lines in vitro. HL60 and EA2 cells were exposed to four types of MFs: (i) static MF of 1.5 and 7.05 T, (ii) extremely low frequency magnetic gradient fields (ELFMGFs) with +/- 10 mT/m and 100 Hz, as well as +/- 100 mT/m and 100 Hz, (iii) pulsed high frequency MF in the radiofrequency (RF) range (63.6 MHz, 5.8 microT), and (iv) a combination of (i-iii). Exposure periods ranged from 1 to 24 h. Cell cycle distribution (G(0)/G(1), S, and G(2)/M phases) was analyzed by flow cytometry. Cell cycle analysis did not reveal differences between the exposed and the control cells. As expected, positive controls with irradiated (8 Gy) HL60 and EA2 cells showed a strong G(2)/M arrest. Using conditions that are relevant for patients during MRI, no influence of MFs on cell cycle progression was observed in these cell lines. Care was taken to control secondary parameters of influence, such as vibration by the MR scanner or temperature to avoid false positive results.

799

No short-term effects of digital mobile radio telephone on the awake human electroencephalogram

A recent study reported the results of an exploratory study of alterations of the quantitative sleep profile due to the effects of a digital mobile radio telephone. Rapid eye movement (REM) was suppressed, and the spectral power density in the 8-13 Hz frequency range during REM sleep was altered. The aim of the present study was to illuminate the influence of digital mobile radio telephone on the awake electroencephalogram (EEG) of healthy subjects. For this purpose, we investigated 34 male subjects in a single-blind cross-over design experiment by measuring spontaneous EEGs under closed-eyes condition from scalp positions C3 and C4 and comparing the effects of an active (0.05 mW/cm2) and an inactive digital mobile radio telephone (GSM) system. During exposure of nearly 3.5 min to the 900 MHz electromagnetic field pulsed at a frequency of 217 Hz and with a pulse width of 580 microseconds, we could not detect any difference in the awake EEGs in terms of spectral power density measures.

800

No short-term effects of high-frequency electromagnetic fields on the mammalian pineal gland

There is ample experimental evidence that changes of earth-strength static magnetic fields, pulsed magnetic fields, or alternating electric fields (60 Hz) depress the nocturnally enhanced melatonin synthesis of the pineal gland of certain mammals. No data on the effects of high-frequency electromagnetic fields on melatonin synthesis is available. In the present study, exposure to 900 MHz electromagnetic fields [0.1 to 0.6 mW/cm2, approximately 0.06 to 0.36 W/kg specific absorption rate (SAR) in rats and 0.04 W/kg in Djungarian hamsters; both continuous and/or pulsed at 217 Hz, for 15 min to 6 h] at day or night had no notable short-term effect on pineal melatonin synthesis in male and female Sprague-Dawley rats and Djungarian hamsters. Pineal synaptic ribbon profile numbers (studied in rats only) were likewise not affected. The 900 MHz electromagnetic fields, unpulsed or pulsed at 217 Hz, as applied in the present study, have no short-term effect on the mammalian pineal gland.

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