iMRS 2000 - PEMF Publications
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PEMF Publications

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901

Pulsed electromagnetic field treatments enhance the healing of fibular osteotomies

This study tested the hypothesis that pulsed electromagnetic field (PEMF) treatments augment and accelerate the healing of bone trauma. It utilized micro-computed tomography imaging of live rats that had received bilateral 0.2 mm fibular osteotomies (approximately 0.5% acute bone loss) as a means to assess the in vivo rate dynamics of hard callus formation and overall callus volume. Starting 5 days post-surgery, osteotomized right hind limbs were exposed 3 h daily to Physio-Stim PEMF, 7 days a week for up to 5 weeks of treatment. The contralateral hind limbs served as sham-treated, within-animal internal controls. Although both PEMF- and sham-treatment groups exhibited similar onset of hard callus at approximately 9 days after surgery, a 2-fold faster rate of hard callus formation was observed thereafter in PEMF-treated limbs, yielding a 2-fold increase in callus volume by 13-20 days after surgery. The quantity of the new woven bone tissue within the osteotomy sites was significantly better in PEMF-treated versus sham-treated fibulae as assessed via hard tissue histology. The apparent modulus of each callus was assessed via a cantilever bend test and indicated a 2-fold increase in callus stiffness in the PEMF-treated over sham-treated fibulae. PEMF-treated fibulae exhibited an apparent modulus at the end of 5-weeks that was approximately 80% that of unoperated fibulae. Overall, these data indicate that Physio-Stim PEMF treatment improved osteotomy repair. These beneficial effects on bone healing were not observed when a different PEMF waveform, Osteo-Stim, was used. This latter observation demonstrates the specificity in the relationship between waveform characteristics and biological outcomes.

904

Pulsed electromagnetic fields accelerate apoptotic rate in osteoclasts

Selective control of cell function by applying specifically configured, low-energy, time-varying electromagnetic fields (EMF) has added a new, exciting dimension to biology and medicine. However, the mechanism involved is less clear. In our study, we investigated the effect of pulsed electromagnetic fields (PEMF) on induction of osteoclasts apoptosis. A statistically significant increase of apoptotic rate in osteoclasts (48 hr after isolation) was found when exposed to 7.5 Hz PEMF with induced electric fields intensity of 3.0 muv/cm for 8 (105%, p < 0.001) and 16 hr (30%, p < 0.05). However, exposure of osteoclasts to PEMF for only 1 hr showed no statistically significant differences. These findings suggest that PEMF have the ability to speed up apoptosis of osteoclasts derived from primary osteoblasts and bone marrow cells cocultures. This in vitro study, therefore, could be considered as groundwork for in vivo PEMF applications on some osteoclasts-associated bone diseases such as osteoporosis.

905

Pulsed electromagnetic fields accelerate normal and diabetic wound healing by increasing endogenous FGF-2 release

BACKGROUND: Chronic wounds, particularly in diabetics, result in significant morbidity and mortality and have a profound economic impact. The authors demonstrate that pulsed electromagnetic fields significantly improve both diabetic and normal wound healing in 66 mice through up-regulation of fibroblast growth factor (FGF)-2 and are able to prevent tissue necrosis in diabetic tissue after an ischemic insult. METHODS: Db/db and C57BL6 mice were wounded and exposed to pulsed electromagnetic fields. Gross closure, cell proliferation, and vascularity were assessed. Cultured medium from human umbilical vein endothelial cells exposed to pulsed electromagnetic fields was analyzed for FGF-2 and applied topically to wounds. Skin flaps were created on streptozocin-induced diabetic mice and exposed to pulsed electromagnetic fields. Percentage necrosis, oxygen tension, and vascularity were determined. RESULTS: Pulsed electromagnetic fields accelerated wound closure in diabetic and normal mice. Cell proliferation and CD31 density were significantly increased in pulsed electromagnetic field-treated groups. Cultured medium from human umbilical vein endothelial cells in pulsed electromagnetic fields exhibited a three-fold increase in FGF-2, which facilitated healing when applied to wounds. Skin on diabetic mice exposed to pulsed electromagnetic fields did not exhibit tissue necrosis and demonstrated oxygen tensions and vascularity comparable to those in normal animals. CONCLUSIONS: This study demonstrates that pulsed electromagnetic fields are able to accelerate wound healing under diabetic and normal conditions by up-regulation of FGF-2-mediated angiogenesis. They also prevented tissue necrosis in response to a standardized ischemic insult, suggesting that noninvasive angiogenic stimulation by pulsed electromagnetic fields may be useful to prevent ulcer formation, necrosis, and amputation in diabetic patients.

906

Pulsed electromagnetic fields affect osteoblast proliferation and differentiation in bone tissue engineering

Bone tissue engineering is an interdisciplinary field involving both engineers and cell biologists, whose main purpose is to repair bone anatomical defects and maintain its functions. A novel system that integrates pulsed electromagnetic fields (PEMFs) and bioreactors was applied to bone tissue engineering for regulating osteoblast proliferation and differentiation in'vitro. Osteoblasts were acquired from the calvaria of newborn Wistar rats and isolated after sequential digestion. Poly(DL-lactic-co-glycolic acid) (PLGA) scaffolds were made by the solvent merging/particulate leaching method. Osteoblasts were seeded into porous PLGA scaffolds with 85% porosity and cultured in bioreactors for the 18-day culture period. Cells were exposed to PEMF pulsed stimulation with average (rms) amplitudes of either 0.13, 0.24, or 0.32 mT amplitude. The resulting induced electric field waveform consisted of single, narrow 300 micros quasi-rectangular pulses with a repetition rate of 7.5'Hz. The results showed that PEMF stimulation for 2 and 8 h at .13 mT increased the cell number on days 6 and 12, followed by a decrease on day 18 using 8 h stimulation. However, ALP activity was decreased and then increased on days 12 and 18, respectively. On the other hand, PEMF-treated groups (irrespective of the stimulation time) at 0.32 mT inhibited cell proliferation but enhanced ALP activity during the culture period. These findings suggested that PEMF stimulation with specific parameters had an effect on regulating the osteoblast proliferation and differentiation. This novel integrated system may have potential in bone tissue engineering.

907

Pulsed electromagnetic fields affect phenotype and connexin 43 protein expression in MLO-Y4 osteocyte-like cells and ROS 17/2.8 osteoblast-like cells

Osteocytes, the predominant cells in bone, are postulated to be responsible for sensing mechanical and electrical stimuli, transducing signals via gap junctions. Osteocytes respond to induced shear by increasing connexin 43 (Cx43) levels, suggesting that they might be sensitive to physical stimuli like low-frequency electromagnetic fields (EMF). Immature osteoblasts exhibit decreased intercellular communication in response to EMF but no change in Cx43. Here, we examined long term effects of pulsed EMF (PEMF) on MLO-Y4 osteocyte-like cells and ROS 17/2.8 osteoblast-like cells. In MLO-Y4 cell cultures, PEMF for 8 h/day for one, two or four days increased alkaline phosphatase activity but had no effect on cell number or osteocalcin. Transforming growth factor beta-1 (TGF-beta 1) and prostaglandin E(2) were increased, and NO(2-) was altered. PEMFs effect on TGF-beta1 was via a prostaglandin-dependent mechanism involving Cox-1 but not Cox-2. In ROS 17/2.8 cells, PEMF for 24, 48 or 72 h did not affect cell number, osteocalcin mRNA or osteocalcin protein. PEMF reduced Cx43 protein in both cells. Longer exposures decreased Cx43 mRNA. This indicates that cells in the osteoblast lineage, including well-differentiated osteoblast-like ROS 17/2.8 cells and terminally differentiated osteocyte-like MLO-Y4 cells, respond to PEMF with changes in local factor production and reduced Cx43, suggesting decreased gap junctional signaling.

908

Pulsed electromagnetic fields affect the intracellular calcium concentrations in human astrocytoma cells

Experiments assessed whether long term exposure to 50 Hz pulsed electromagnetic fields with a peak magnetic field of 3 mT can alter the dynamics of intracellular calcium in human astrocytoma U-373 MG cells. Pretreatment of cells with 1.2 microM substance P significantly increased the [Ca(2+)](i). The same effect was also observed when [Ca(2+)](i) was evaluated in the presence of 20 mM caffeine. After exposure to electromagnetic fields the basal [Ca(2+)](i) levels increased significantly from 143 +/- 46 nM to 278 +/- 125 nM. The increase was also evident after caffeine addition, but in cells treated with substance P and substance P + caffeine we observed a [Ca(2+)](i) decrease after exposure. When we substituted calcium-free medium for normal medium immediately before the [Ca(2+)](i) measurements, the [Ca(2+)](i) was similar to that measured in the presence of Ca(2+). In this case, after EMFs exposure of cells treated with substance P, the [Ca(2+)](i), measured without and with addition of caffeine, declined from 824 +/- 425 to 38 +/- 13 nM and from 1369 +/- 700 to 11 +/- 4 nM, respectively, indicating that electromagnetic fields act either on intracellular Ca(2+) stores or on the plasma membrane. Moreover the electromagnetic fields that affected [Ca(2+)](i) did not cause cell proliferation or cell death and the proliferation indexes remained unchanged after exposure.

909

Pulsed electromagnetic fields after arthroscopic treatment for osteochondral defects of the talus: double-blind randomized controlled multicenter trial

BACKGROUND: Osteochondral talar defects usually affect athletic patients. The primary surgical treatment consists of arthroscopic debridement and microfracturing. Although this is mostly successful, early sport resumption is difficult to achieve, and it can take up to one year to obtain clinical improvement. Pulsed electromagnetic fields (PEMFs) may be effective for talar defects after arthroscopic treatment by promoting tissue healing, suppressing inflammation, and relieving pain. We hypothesize that PEMF-treatment compared to sham-treatment after arthroscopy will lead to earlier resumption of sports, and aim at 25% increase in patients that resume sports. METHODS/DESIGN: A prospective, double-blind, randomized, placebo-controlled trial (RCT) will be conducted in five centers throughout the Netherlands and Belgium. 68 patients will be randomized to either active PEMF-treatment or sham-treatment for 60 days, four hours daily. They will be followed-up for one year. The combined primary outcome measures are (a) the percentage of patients that resume and maintain sports, and (b) the time to resumption of sports, defined by the Ankle Activity Score. Secondary outcome measures include resumption of work, subjective and objective scoring systems (American Orthopaedic Foot and Ankle Society--Ankle-Hindfoot Scale, Foot Ankle Outcome Score, Numeric Rating Scales of pain and satisfaction, EuroQol-5D), and computed tomography. Time to resumption of sports will be analyzed using Kaplan-Meier curves and log-rank tests. DISCUSSION: This trial will provide level-1 evidence on the effectiveness of PEMFs in the management of osteochondral ankle lesions after arthroscopy. TRIAL REGISTRATION: Netherlands Trial Register (NTR1636).

910

Pulsed electromagnetic fields alter phenotypic expression in chondroblasts in tissue culture

We hypothesize that pulsed electromagnetic fields (PEMF) alter phenotypic expression of chondroblasts by promoting the production of alkaline phosphatase (AP) and altering the structure of proteoglycans. Chondroblasts from the hypertrophic zone of tibial epiphyses (HC), sternum (SC), and skin fibroblasts (F) were cultured from 16 day chick embryos. Cultures were randomly designated control (C) or experimental (E). E received PEMF for 24 h in a 6 h on, 6 h rest sequence. The controls were in the same incubator shielded by Mu metal. Assays for AP activity were performed and normalized to protein content. Proteoglycan synthesis assay involved labeling with 35S fractionating in a 5% to 20% surcrose gradient determining total protein and chondroitin sulfate content. PEMF showed no change of AP activity on F. A high AP basal activity was found in HC, but was not increased above the control. PEMF increased AP in the SC samples (E/C ratio). The sucrose gradient data showed a shift in peaks for SC only altering the ratio of carbohydrate to protein for the SC. Analysis of carbohydrate and protein indicated that the effect was decreased synthesis or degradation of protein. We conclude that PEMF alters the phenotypic expression of sternal chondroblasts in our in vitro system.

912

Pulsed electromagnetic fields enhance BMP-2 dependent osteoblastic differentiation of human mesenchymal stem cells

Mesenchymal stem cells (MSCs) express an osteoblastic phenotype when treated with BMP-2, and BMP-2 is used clinically to induce bone formation although high doses are required. Pulsed electromagnetic fields (PEMF) also promote osteogenesis in vivo, in part through direct action on osteoblasts. We tested the hypothesis that PEMF enhances osteogenesis of MSCs in the presence of an inductive stimulus like BMP-2. Confluent cultures of human MSCs were grown on calcium phosphate disks and were treated with osteogenic media (OM), OM containing 40 ng/mL rhBMP-2, OM + PEMF (8 h/day), or OM + BMP-2 + PEMF. MSCs demonstrated minor increases in alkaline phosphatase (ALP) during 24 days in culture and no change in osteocalcin. OM increased ALP and osteocalcin by day 6, but PEMF had no additional effect at any time. BMP-2 was stimulatory over OM, and PEMF + BMP-2 synergistically increased ALP and osteocalcin. PEMF also enhanced the effects of BMP-2 on PGE2, latent and active TGF-beta1, and osteoprotegerin. Effects of PEMF on BMP-2-treated cells were greatest at days 12 to 20. These results demonstrate that PEMF enhances osteogenic effects of BMP-2 on MSCs cultured on calcium phosphate substrates, suggesting that PEMF will improve MSC response to BMP-2 in vivo in a bone environment.

913

Pulsed electromagnetic fields enhance the induction of cytokines by peripheral blood mononuclear cells challenged with phytohemagglutinin

We evaluated the effects of a 50-Hz pulsed electromagnetic field on the production of cytokines by both resting and mitogen-treated peripheral blood mononuclear cells. Our results demonstrate that after exposure of normal cells to EMFs for 12 h, the levels of neither interleukin-1beta, nor interleukin-2 were increased. Indeed, the concentration of tumor necrosis factor alpha decreased significantly immediately after the exposure period. The results were, however, markedly different when cells were stimulated with phytohemagglutinin immediately before the exposure to EMFs. In this case the levels of cytokines, measured 24 and 48 h after the treatment, were 630 +/- 440 pg/ml and 910 +/- 530 pg/ml for interleukin-1beta, 530 +/- 330 pg/ml, and 860 +/- 560 pg/ml for tumor necrosis factor alpha, respectively. These values were significantly higher (P < 0.05) when compared with the controls. Interleukin-2 levels were significantly higher at the end of the EMF exposure only in supernatants of phytohemagglutinin-stimulated cells and, as a consequence of this increase, the proliferation indexes also were significantly increased 48 h after the EMFs' treatment. The comparison between biological activity and the cytokine antigen present in our samples indicated that the amount of antigen was paralleled by an equal recovery of biological activity. This suggests either the absence of qualitative differences in these proteins or the impairment of both the transcriptional and translational processes.

914

Pulsed electromagnetic fields for the treatment of bone fractures

The effectiveness of electrical stimulation and Pulsed Electro Magnetic Field (PEMF) stimulation for enhancement of bone healing has been reported by many workers. The mechanism of osteogenesis is not clear, therefore, studies look for empirical evidence. The present study involved a clinical trial using low amplitude PEMF on 19 patients with non-union or delayed union of the long bones. The pulse system used was similar in shape to Bassett's single pulse system where the electric voltage pulse was 0.3 mSec wide repeating every 12 mSec making a frequency of about 80 Hz. The peak magnetic fields were of the order of 0.01 to 0.1 m Tesla, hundred to thousand times smaller than that of Bassett. Among the 13 who completed this treatment schedule the history of non-union was an average of 41.3 weeks. Within an average treatment period of 14 weeks, 11 of the 13 patients had successful bone healing. The two unsuccessful cases had bone gaps greater than 1 cm following removal of dead bone after infection. However, use of such a low field negates Bassett's claim for a narrow window for shape and amplitude of wave form, and justifies further experimental study and an attempt to understand the underlying mechanism.

915

Pulsed electromagnetic fields in experimental cutaneous wound healing in rats

Electromagnetic fields are now being used in many diseases such as osseous, ligamental, cartilaginous, or nervous reparation, diabetes, and myocardial or cerebral ischemia. Although many publications show the usefulness of magneto-therapy, discrepancies exist about the utility of electromagnetic fields in skin wound healing. The objective of this work was to study the effect of pulsed electromagnetic fields on wound healing in rats. Twenty-two male Wistar rats were used; a circular lesion was made in the back of each animal. They were divided into three groups: group C (control) with sham treatment (n = 8), group NF, treated with topical nitrofurazone solution (n = 7), and group PEMF, treated with pulsed electromagnetic fields of 20 mT (n = 7). The treatments were 35 minutes twice a day. The absolute and relative values of the area and perimeter of the wounds showed significantly lower values in the PEMF group at days 7, 14, and 21 compared with those in group C (p < 0.01, analysis of variance), whereas the PEMF group showed significantly lower values at day 21 only compared with the NF group (p < 0.01, analysis of variance). The results suggest a significant beneficial stimulation in the wound healing process in rats treated with PEMF, which could lead to the development of a practical tool for research and clinical use.

916

Pulsed electromagnetic fields increase growth factor release by nonunion cells

The mechanisms involved in pulsed electromagnetic field stimulation of nonunions are not known. Animal and cell culture models suggest endochondral ossification is stimulated by increasing cartilage mass and production of transforming growth factor-beta 1. For the current study, the effect of pulsed electromagnetic field stimulation on cells from human hypertrophic (n = 3) and atrophic (n = 4) nonunion tissues was examined. Cultures were placed between Helmholtz coils, and an electromagnetic field (4.5-ms bursts of 20 pulses repeating at 15 Hz) was applied to 1/2 of them 8 hours per day for 1, 2, or 4 days. There was a time-dependent increase in transforming growth factor-beta 1 in the conditioned media of treated hypertrophic nonunion cells by Day 2 and of atrophic nonunion cells by Day 4. There was no effect on cell number, [3H]-thymidine incorporation, alkaline phosphatase activity, collagen synthesis, or prostaglandin E2 and osteocalcin production. This indicates that human nonunion cells respond to pulsed electromagnetic fields in culture and that transforming growth factor-beta 1 production is an early event. The delayed response of hypertrophic and atrophic nonunion cells (> 24 hours) suggests that a cascade of regulatory events is stimulated, culminating in growth factor synthesis and release.

917

Pulsed electromagnetic fields increase the rate of rat liver regeneration after partial hepatectomy

Pulsed extremely low-frequency electromagnetic fields interact with rat liver regeneration following partial hepatectomy when delivered to the rats immediately after the operation and every 12 hr thereafter. This interaction results first in an increased ornithine decarboxylase activity, an enzyme used as an early marker of cell growth. The rate of labeled thymidine incorporation into DNA is also increased by the treatments with magnetic fields during the early phases of liver regeneration. Glycogen depletion and lipid accumulation, two well-known early peculiar phenomena of liver regeneration following partial hepatectomy, are quantitatively decreased by the treatments with electromagnetic fields. The recovery to normal glycogen and lipid contents is completed within 5 days after surgery, instead of 7 days as found in control rats.

918

Pulsed electromagnetic fields induce peripheral nerve regeneration and endplate enzymatic changes

An experimental study was carried out in rats with the purpose of demonstrating the capacity of pulsed electromagnetic fields (PEMFs) to stimulate regeneration of the peripheral nervous system (PNS). Wistar and Brown Norway (BN) rats were used. Direct sciatic nerve anastomoses were performed after section or allograft interposition. Treatment groups then received 4 weeks of PEMFs. Control groups received no stimulation. The evaluation of the results was carried out by quantitative morphometric analysis, demonstrating a statistically significant increase in regeneration indices (P < 0.05) in the stimulated groups (9000 +/- 5000 and 4000 +/- 6000) compared to the non-stimulated groups (2000 +/- 4000 and 700 +/- 200). An increase of NAD specific isocitrate dehydrogenase (IDH) activity was found along with an increase in the activity of acetyl cholinesterase at the motor plate. The present study might lead to the search for new alternatives in the stimulation of axonal regenerative processes in the PNS and other possible clinical applications.

919

Pulsed electromagnetic fields induced femoral metaphyseal bone thickness changes in the rat

The effect of 1 Hz, 30 mT pulsed magnetic fields on young adult rat femoral metaphyseal bone thickness was assessed. Ten same litter, female Wistar rats were studied; five of them underwent 30 min magnetic stimulation sessions for 20 consecutive days. The anterior and posterior cortical, as well as trabecular bone transverse thicknesses were measured. The results obtained under clear field microscopy in stimulated and control histological cuts were (in microm) 398 +/- 32 versus 260 +/- 22 (P = 0.002), 380 +/- 68 versus 252 +/- 21 (P = 0.03), and 168 +/- 11 versus 112 +/- 11 (P = 0.002), respectively. The transcranial magnetic stimulation system, approved for human therapy, generates pulsed electromagnetic fields, which induce a significant thickness increase in cortical and trabecular in vivo stimulated bone tissues. This is the first time this effect in healthy animals is shown.

920

Pulsed electromagnetic fields influence hyaline cartilage extracellular matrix composition without affecting molecular structure

Pulsed electromagnetic fields (PEMF) influence the extracellular matrix metabolism of a diverse range of skeletal tissues. This study focuses upon the effect of PEMF on the composition and molecular structure of cartilage proteoglycans. Sixteen-day-old embryonic chick sterna were explanted to culture and exposed to a PEMF for 3 h/day for 48 h. PEMF treatment did not affect the DNA content of explants but stimulated elevation of glycosaminoglycan content in the explant and conserved the tissue's histological integrity. The glycosaminoglycans in sterna exposed to PEMF were indistinguishable from those in controls in their composition of chondroitin sulfate resulting from chondroitinase ABC digestion. Specific examination with [35S]-sulfate labels showed that PEMF treatment significantly suppressed both the degradation of pre-existing glycosaminoglycans biosynthetically labeled in ovo and the synthesis of new [35S]-sulfated glycosaminoglycans. The average size and aggregating ability of pre-existing and newly synthesized [35S]-sulfated proteoglycans extracted with 4 M guanidinium chloride from PEMF-treated cartilage explants were identical to controls. The chain length and degree of sulfation of [35S]-sulfated glycosaminoglycans also were identical in control and PEMF-treated cultures. PEMF treatment also reduced the amount of both unlabeled glycosaminoglycans and labeled pre-existing and newly synthesized [35S]-sulfated glycosaminoglycans recovered from the nutrient media. [35S]-Sulfated proteoglycans released to the media of both control and PEMF-treated cultures were mostly degradation products although their glycosaminoglycan chain size was unchanged. These results demonstrate that exposure of embryonic chick cartilage explants to PEMF for 3 h/day maintains a balanced proteoglycan composition by down-regulating its turnover without affecting either molecular structure or function.

921

Pulsed electromagnetic fields preserve proteoglycan composition of extracellular matrix in embryonic chick sternal cartilage

The influence of pulsed electromagnetic fields (PEMF) on proteoglycan composition in cartilage extracellular matrix has been investigated. Day 16 embryonic chick sternal cartilage was explanted to culture and exposed for 3 h per day for 2 days to a repetitive single-pulse PEMF with frequency of 15 Hz and peak magnetic field of 1.25 G. PEMF treatment did not affect cell proliferation, as indicated by [3H]thymidine incorporation, but significantly stimulated the retention of glycosaminoglycans in the explants and reduced the release of glycosaminoglycans into the media. Determination of incorporation of [35S]sulfate and [3H]N-acetylglucosamine into proteoglycans in vitro and breakdown of in ovo labelled [35S]sulfated proteoglycans in vitro showed that PEMF treatment significantly suppressed the synthesis of proteoglycans and the degradation of both newly synthesized and pre-existing proteoglycans. Sepharose CL-2B chromatography demonstrated that PEMF did not affect either the size distribution of newly synthesized and pre-existing [35S]sulfated proteoglycans or their ability to aggregate with hyaluronate. Sepharose CL-6B chromatography followed by cellulose acetate electrophoresis revealed that the chain length and degree of sulfation of [35S]sulfated glycosaminoglycans were identical in control and PEMF-treated cultures. It is concluded that PEMF treatment preserved extracellular matrix integrity of cultured cartilage explants by down-regulating proteoglycan synthesis and degradation in a co-ordinated manner without affecting their gross structural nature.

922

Pulsed electromagnetic fields prevent osteoporosis in an ovariectomized female rat model: a prostaglandin E2-associated process

With the use of Helmholtz coils and pulsed electromagnetic field (PEMF) stimulators to generate uniform time varying electromagnetic fields, the effects of extremely low frequency electromagnetic fields on osteoporosis and serum prostaglandin E(2) (PGE(2)) concentration were investigated in bilaterally ovariectomized rats. Thirty-five 3 month old female Sprague-Dawley rats were randomly divided into five different groups: intact (INT), ovariectomy (OVX), aspirin treated (ASP), PEMF stimulation (PEMF + OVX), and PEMF stimulation with aspirin (PEMF + ASP) groups. All rats were subjected to bilateral ovariectomy except those in INT group. Histomorphometric analyses showed that PEMF stimulation augmented and restored proximal tibial metaphyseal trabecular bone mass (increased hard tissue percentage, bone volume percentage, and trabecular number) and architecture (increased trabecular perimeter, trabecular thickness, and decreased trabecular separation) in both PEMF + OVX and PEMF + ASP. Trabecular bone mass of PEMF + OVX rats after PEMF stimulation for 30 days was restored to levels of age matched INT rats. PEMF exposure also attenuated the higher serum PGE(2) concentrations of OVX rats and restored it to levels of INT rats. These experiments demonstrated that extremely low intensity, low frequency, single pulse electromagnetic fields significantly suppressed the trabecular bone loss and restored the trabecular bone structure in bilateral ovariectomized rats. We, therefore, conclude that PEMF may be useful in the prevention of osteoporosis resulting from ovariectomy and that PGE(2) might relate to these preventive effects.

923

Pulsed electromagnetic fields promote bone formation around dental implants inserted into the femur of rabbits

The present study examined the effect of applying a pulsed electromagnetic field (PEMF) on bone formation around a rough-surfaced dental implant. A dental implant was inserted into the femur of Japanese white rabbits bilaterally. A PEMF with a pulse width of 25 microseconds and a pulse frequency of 100 Hz was applied. PEMF stimulation was applied for 4 h or 8 h per day, at a magnetic intensity of 0.2 mT, 0.3 mT or 0.8 mT. The animals were sacrificed 1, 2 or 4 weeks after implantation. After staining the resin sections with 2% basic fuchsin and 0.1% methylene blue, newly formed bone around the implant on tissue sections was evaluated by computer image analysis. The bone contact ratios of the PEMF-treated femurs were significantly larger than those of the control groups. Both the bone contact ratio and bone area ratio of the 0.2 mT- and 0.3 mT-treated femurs were significantly larger than the respective value of the 0.8 mT-treated femurs (P < 0.001). No significant difference in bone contact ratio or bone area ratio was observed whether PEMF was applied for 4 h/day or 8 h/day. Although a significantly greater amount of bone had formed around the implant of the 2-week treated femurs than the 1-week treated femurs, no significant difference was observed between the 2-week and 4-week treated femurs. These results suggest that PEMF stimulation may be useful for promoting bone formation around rough-surfaced dental implants. It is important to select the proper magnetic intensity, duration per day, and length of treatment.

924

Pulsed electromagnetic fields promote collagen production in bone marrow fibroblasts via athermal mechanisms

Primary and passaged cultures of fibroblasts (RBMFs) raised from the bone marrow stroma of young rabbits were treated with pulsed electromagnetic fields (PEMFs) from the start of each culture until 1 week after they became confluent. the PEMF treatment had no effect on cell proliferation, estimated by phase contrast microscopy, by 3H-thymidine incorporation into DNA, or by total DNA assay. Collagen production, estimated by conversion of 3H-proline to 3H-hydroxyproline in nondialyzable material was markedly elevated in postconfluent cultures, but not in cultures that had only just reached confluence. About 65 of 3H-hydroxyproline was in low molecular weight form, and a correlation between collagen breakdown and cyclic AMP (cAMP) levels in RBMFs was demonstrated by adding dibutyryl cAMP or prostaglandin E3 (PGE2) to the culture medium concurrently with 3H-proline. The PEMF apparatus caused an insufficient temperature rise (less than 0.1 degree C) to account for these results. We propose that the rise in collagen production is consistent with the hypothesis that PEMFs act by reducing cAMP levels in RBMFs, and that thermal effects are insignificant.

925

Pulsed electromagnetic fields rapidly modulate intracellular signaling events in osteoblastic cells: comparison to parathyroid hormone and insulin

Pulsed electromagnetic field (PEMF) devices are approved for the healing of bone nonunions, but there is a lack of understanding as to their mechanism of action at the cell and molecular level. Intermittent parathyroid hormone (PTH) therapy is currently utilized for treatment of osteoporosis, and is also being investigated for the purpose of augmenting fracture healing. Insulin and IGF-1 are also thought to play important anabolic roles in osteogenesis. In this report, signaling pathways activated by acute PTH or insulin treatments were compared to those activated by PEMF treatment in osteoblast-like cells. Some signaling molecules like the extracellular response kinases 1/2 (Erk1/2) and the cAMP response element binding protein (CREB) were activated by insulin and PTH, respectively, but not by PEMF treatment. Other signaling molecules like the insulin receptor substrate-1 (IRS-1), the S6 ribosomal subunit kinase, and the endothelial nitric oxide synthase (eNOS) were phosphorylated by PTH, insulin, and PEMF to the same relative extent and within the same time frame. IRS-1, eNOS, and S6 have been implicated in bone anabolism, and our results suggest that the anabolic effects of PEMF may be mediated, in part, through the activation of these proteins.

926

Pulsed electromagnetic fields reduce knee osteoarthritic lesion progression in the aged Dunkin Hartley guinea pig

An experimental in vivo study was performed to test if the effect of Pulsed Electromagnetic Fields (PEMFs) on chondrocyte metabolism and adenosine A2a agonist activity could have a chondroprotective effect on the knee of Dunkin Hartley guinea-pigs of 12 months with spontaneously developed osteoarthritis (OA). After a pilot study, 10 animals were randomly divided into two groups: PEMF-treated group (6 h/day for 3 months) and Sham-treated group. Microradiography and histomorphometry were performed on the entire articular surface of knee joints used in evaluating chondropathy severity, cartilage thickness (CT), cartilage surface Fibrillation Index (FI), subchondral bone plate thickness (SBT) and histomorphometric characteristics of trabecular epiphyseal bone. The PEMF-treated animals showed a significant reduction of chondropathy progression in all knee examined areas (p<0.05). CT was significantly higher (p<0.001) in the medial tibia plateaus of the PEMF-treated group when compared to the Sham-treated group. The highest value of FI was observed in the medial tibia plateau of the Sham-treated group (p<0.05). Significant lower values were observed in SBT of PEMF-treated group in comparison to Sham-treated group in all knee examined areas (p<0.05). The present study results show that PEMFs preserve the morphology of articular cartilage and slower the progression of OA lesions in the knee of aged osteoarthritic guinea pigs. The chondroprotective effect of PEMFs was demonstrated not only in the medial tibial plateau but also on the entire articular surface of the knee.

927

Pulsed electromagnetic fields simultaneously induce osteogenesis and upregulate transcription of bone morphogenetic proteins 2 and 4 in rat osteoblasts in vitro

Pulsed electromagnetic fields (PEMF) are successfully employed in the treatment of a variety of orthopaedic conditions, particularly delayed and nonunion fractures. In this study, we examined PEMF effects on in vitro osteogenesis by bone nodule formation and on mRNA expression of bone morphogenetic proteins 2 and 4 by reverse-transcriptase polymerase chain reaction (RT-PCR) in cultured rat calvarial osteoblasts. PEMF exposure induced a significant increase in both the number (39% over unexposed controls) and size (70% larger compared to unexposed controls) of bone-like nodules formed. PEMF also induced an increase in the levels of BMP-2 and BMP-4 mRNA in comparison to controls. This effect was directly related to the duration of PEMF exposure. This study shows that clinically applied PEMF have a reproducible osteogenic effect in vitro and simultaneously induce BMP-2 and -4 mRNA transcription. This supports the concept that the two effects are related.

928

Pulsed electromagnetic fields stimulation affects BMD and local factor production of rats with disuse osteoporosis

Pulsed electromagnetic fields (PEMF) have been used widely to treat nonunion fractures and related problems in bone healing, as a biological and physical method. With the use of Helmholtz coils and PEMF stimulators to generate uniform time-varying electromagnetic fields, the effects of extremely low frequency electromagnetic fields on bone mineral density (BMD) and local factor production in disuse osteoporosis (DOP) rats were investigated. Eighty 4-month-old female Sprague Dawley (SD) rats were randomly divided into intact (INT) group, DOP group, calcitonin-treated (CT) group, and PEMF stimulation group. The right hindlimbs of all the rats were immobilized by tibia-tail fixation except for those rats in the INT group. Rats in the CT group were injected with calcitonin (2 IU/kg, i.p., once a day) and rats in the PEMF group were irradiated with PEMF immediately postoperative. The BMD, serum transforming growth factor-beta 1 (TGF-beta1), and interleukin-6 (IL-6) concentration of the proximal femur were measured 1, 2, 4, and 8 weeks after treatment. Compared with the CT and DOP groups, the BMD and serum TGF-beta1 concentration in the PEMF group increased significantly after 8 weeks. The IL-6 concentration in the DOP group was elevated significantly after operation. The PEMF group showed significantly lower IL-6 level than the DOP group. The results found demonstrate that PEMF stimulation can efficiently suppress bone mass loss. We, therefore, conclude that PEMF may affect bone remodeling process through promoting TGF-beta1 secretion and inhibiting IL-6 expression. Bioelectromagnetics, 2009. (c) 2009 Wiley-Liss, Inc.

929

Pulsed electromagnetic fields stimulation affects osteoclast formation by modulation of osteoprotegerin, RANK ligand and macrophage colony-stimulating factor

Electromagnetic stimulation has been documented to treat recalcitrant problems of musculoskeletal system. Yet, the underlying mechanisms are not completely understood. In this study, we investigated effect of pulsed electromagnetic fields (PEMF) with parameters modified from clinical bone growth stimulator on osteoclast formation, bone resorption, and cytokines associated with osteoclastogenesis. Marrow cells were harvested from both femora and tibiae of 6 week-old mice and cultured in 8-well chamber slides or 16-well calcium phosphate apatite-coated multitest slides. After 1-day incubation, marrow cells were exposed to PEMF at different electric field intensities for 2h/day and continued for 9 days. Osteoprotegerin (OPG), receptor activator of NFkappaB-ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) concentrations of each group were determined after PEMF stimulation. Osteoclast identity was confirmed by both tartrate resistant acid phosphatase (TRAP) stain and bone resorption assay. A statistically significant increase and decrease of osteoclastogenesis and bone resorption areas were found when exposed to PEMF with different intensities. Besides, consistent correlations among OPG, RANKL, M-CSF, osteoclast numbers, and bone resorption after exposure to different intensities of PEMF were observed. These data demonstrated that PEMF with different intensities could regulate osteoclastogenesis, bone resorption, OPG, RANKL, and M-CSF concentrations in marrow culture system.

930

Pulsed electromagnetic fields to reduce diabetic neuropathic pain and stimulate neuronal repair: a randomized controlled trial

OBJECTIVE: To determine whether repetitive and cumulative exposure to low-frequency pulsed electromagnetic fields (PEMF) targeting painful feet can reduce neuropathic pain (NP), influence sleep in symptomatic diabetic peripheral neuropathy (DPN), and influence nerve regeneration. DESIGN: Randomized, double-blind, placebo-controlled parallel study. SETTING: Sixteen academic and clinical sites in 13 states. PARTICIPANTS: Subjects (N=225) with DPN stage II or III were randomly assigned to use identical devices generating PEMF or sham (placebo) 2 h/d to feet for 3 months. INTERVENTIONS: Nerve conduction testing was performed serially. MAIN OUTCOME MEASURES: Pain reduction scores using a visual analog scale (VAS), the Neuropathy Pain Scale (NPS), and the Patient's Global Impression of Change (PGIC). A subset of subjects underwent serial 3-mm punch skin biopsies from 3 standard lower limb sites for epidermal nerve fiber density (ENFD) quantification. RESULTS: Subjects (N=225) were randomized with a dropout rate of 13.8%. There was a trend toward reductions in DPN symptoms on the PGIC, favoring the PEMF group (44% vs 31%; P=.04). There were no significant differences between PEMF and sham groups in the NP intensity on NPS or VAS. Twenty-seven subjects completed serial biopsies. Twenty-nine percent of PEMF subjects had an increase in distal leg ENFD of at least 0.5 SDs, while none did in the sham group (P=.04). Increases in distal thigh ENFD were significantly correlated with decreases in pain scores. CONCLUSIONS: PEMF at this dosimetry was noneffective in reducing NP. However neurobiological effects on ENFD, PGIC and reduced itching scores suggest future studies are indicated with higher dosimetry (3000-5000 G), longer duration of exposure, and larger biopsy cohort.

931

Pulsed field gradients in simulations of one- and two-dimensional NMR spectra

A method for the inclusion of the effects of z-axis pulsed field gradients in computer simulations of an arbitrary pulsed NMR experiment with spin (1/2) nuclei is described. Recognizing that the phase acquired by a coherence following the application of a z-axis pulsed field gradient bears a fixed relation to its order and the spatial position of the spins in the sample tube, the sample is regarded as a collection of volume elements, each phase-encoded by a characteristic, spatially dependent precession frequency. The evolution of the sample's density matrix is thus obtained by computing the evolution of the density matrix for each volume element. Following the last gradient pulse, these density matrices are combined to form a composite density matrix which evolves through the rest of the experiment to yield the observable signal. This approach is implemented in a program which includes capabilities for rigorous inclusion of spin relaxation by dipole-dipole, chemical shift anisotropy, and random field mechanisms, plus the effects of arbitrary RF fields. Mathematical procedures for accelerating these calculations are described. The approach is illustrated by simulations of representative one- and two-dimensional NMR experiments.

932

Pulsed high-frequency electromagnetic field affects human sleep and sleep electroencephalogram

To investigate whether the electromagnetic field (EMF) emitted by digital radiotelephone handsets affects the brain, healthy, young subjects were exposed during an entire night-time sleep episode to an intermittent radiation schedule (900 MHz; maximum specific absorption rate 1 W/kg) consisting of alternating 15-min on-15-min off intervals. Compared with a control night with sham exposure, the amount of waking after sleep onset was reduced from 18 to 12 min. Spectral power of the electroencephalogram in non-rapid eye movement sleep was increased. The maximum rise occurred in the 10-11 Hz and 13.5-14 Hz bands during the initial part of sleep and then subsided. The results demonstrate that pulsed high-frequency EMF in the range of radiotelephones may promote sleep and modify the sleep EEG.

933

Pulsed ion cyclotron resonance mass spectrometer for studying ion-molecule reactions

A pulsed ion cyclotron resonance mass spectrometer utilizes the cyclotron resonance principle for mass analysis of ions trapped at low pressures by electric and magnetic fields. Both mass analysis and ion trapping are accomplished in a one-region device called a trapped ion analyzer cell. A pulsing sequence is described which allows for generation of ions by electron impact, reaction with added gases, and mass analysis of the products of ion-molecule reactions. Methods are described for measuring rate constants and equilibrium constants for ion-molecule reactions. The high ion trapping efficiency and open geometry of the analyzer cell make it well suited for studying the interaction of laser radiation with gaseous ions and may also be useful for high-accuracy isotope ration mass spectrometry.

934

Pulsed magnetic and electromagnetic fields in experimental achilles tendonitis in the rat: a prospective randomized study

OBJECTIVE: To investigate the effects of pulsed magnetic fields (PMF) and pulsed electromagnetic fields (PEMF) on healing in experimental Achilles tendon inflammation in the rat. DESIGN: Prospective randomized trial. SETTING: University medical school. METHODS: Exposure of the Achilles tendon and injury by a weight of 98.24 g falling from a height of 35cm in 180 male Sprague-Dawley rats. INTERVENTION: A daily 15-minute session with PMF of 17Hz or 50Hz, or PEMF of 15Hz or 46Hz, or a sham session. OUTCOME MEASURES: Random sacrifice 2 hours after the operation, and at 1, 3, 7, 14, or 28 days. Assessment of water content, weight, and histological appearance of the tendons. RESULTS: The time from injury and the various treatment modalities exerted a significant influence on the water content of the tendon after the injury (two-way ANOVA, p = .02). At day 3, the water content of the PEMF 46Hz group was significantly higher than in the other groups, decreasing sharply by day 7, and being similar to the other groups thereafter. By the end of the experiment, the PEMF 15Hz group was not significantly different from the control group. At day 7, the PMF 50Hz group showed significantly lower water content than the control group (p = .03), but at 14 days the PMF 50Hz group was not significantly different from the control group. PMF 50Hz suppressed the extravascular edema during early inflammation. PMF 17Hz showed a similar initial trend, producing a consistent lower water content throughout the experiment, reaching statistical significance by the end of treatment. By the end of the experiment, the collagen fibers had nearly regained their normal alignment in all groups, with a more physiological alignment seen in the PEMF 17Hz group. CONCLUSIONS: The tendon returned to histological normality in all groups, but the PMF 17Hz group showed better collagen alignment by the end of the study. PMF 17Hz resulted in a greater reduction of inflammation, with a better return of the tendon to histological normality. Different PMF and PEMF could be applied according to when treatment is started after the injury. If there is no delay between injury and beginning of pulsed magnetic treatment, PMF 17 should be used.

935

Pulsed magnetic field effects on calcium signaling in lymphocytes: dependence on cell status and field intensity

The effect of 3-Hz, monopolar, quasi-rectangular magnetic field pulses on 45Ca2+ uptake in resting and mitogen-treated rat thymic lymphocytes was evaluated. A 30-min, non-thermal exposure to the pulsed magnetic field (Bpeak = 6.5 mT, Emax = 0.69 mV/cm, Jmax = 2.6 microA/cm2) reduced Concanavalin A-induced 45Ca2+ uptake by 45%. It was observed that (i) the induction of the 3-Hz field response depended on Ca2+ signal transduction activation; (ii) the response direction (stimulation or inhibition) depended on the level of lymphocyte mitogen responsiveness, and (iii) the field response magnitude increased with increasing magnetic field flux densities (Bpeak = 0, 1.6, 6.5 and 28 mT). Our results demonstrate field effects at Bmax nearly 10(4) greater than that of the average human environment for low-frequency magnetic fields and they are consistent with the independent results from other 3-Hz pulsed magnetic field studies with lymphocytes.

936

Pulsed magnetic field exposure during pregnancy and implications for NMR foetal imaging: a study with mice

Following the recent progress in NMR imaging of the foetus in utero an investigation has been made of the effect of exposure to strong pulsed magnetic fields on the pregnancy of mice and the post natal development of their litters. 23 pregnant mice received exposures ranging from 3.5-12kT/s with pulse periods in the range 0.33-0.56ms at various times during gestation. A similar number of pregnant mice served as controls. No adverse effect was observed on the pregnancy. There was no significant difference between the litter numbers and growth rates of the exposed litters compared with controls. The implications of these results are discussed with regard to the safety of NMR imaging during pregnancy.

937

Pulsed magnetic field from video display terminals enhances teratogenic effects of cytosine arabinoside in mice

Eighty-nine Swiss Webster mice were randomly divided into four groups: a control group, a pulsed magnetic field (PMF) group, a cytosine arabinoside (ara-C, a teratogen) group, and a combined PMF + ara-C group. Mice in the PMF and PMF + ara-C groups were irradiated with a PMF (a sawtooth waveform with 52 microseconds rise time, 12 microseconds decay time, and 15.6 kHz frequency) at a peak magnetic flux density of 40 microT for 4 hours daily on days 6-17 of gestation. The mice in the ara-C and the PMF + ara-C groups were injected intraperitoneally on day 9 of gestation with 10 mg/kg of ara-C. The incidence of resorption and dead fetuses was not affected by PMF but was increased by ara-C injection. The malformation incidence of cleft palate (CP) and/or cleft lip (CL) was significantly higher in all three of the treated groups than in the control group (P < 0.05). If, however, statistical analyses had been done on litters rather than on individual fetuses, they would show that the incidence of CP and/or CL in the PMF group is not significantly greater than that in the control group. A significantly higher incidence of CP and/or CL was found in the PMF + ara-C group (49%) than the ara-C alone group (26.1%). These data suggest that PMF might enhance the development of ara-C-induced CP and/or CL. The incidence of minor variations in skeletal development, including reduction of skeletal calcification and loss of skeleton, was not statistically significant in the PMF group.(ABSTRACT TRUNCATED AT 250 WORDS)

938

Pulsed magnetic field induced "analgesia" in the land snail, Cepaea nemoralis, and the effects of mu, delta, and kappa opioid receptor agonists/antagonists

A brief exposure to a pulsed magnetic field (Cnp: patent pending) had significant antinociceptive or "analgesic" effects in the land snail, Cepaea nemoralis, as evidenced by an increase in the latency of response to a warmed (40 degrees C) surface. This analgesia was in part opioid mediated being significantly reduced, but not eliminated: by the prototypic opiate antagonist, naloxone; the mu (mu) opioid receptor directed antagonists, naloxazine or beta-funaltrexamine, and the delta (delta) opioid receptor directed antagonists, naltrindole-5'-isothiocyanate or ICI 174,864. However the Cnp induced analgesia was unaffected by the kappa (kappa) opioid receptor directed antagonist, nor-binaltorphimine. The delta 1 and delta 2 opioid receptor directed agonists, (DPDPE, [D-Pen2,D-Pen5]enkephalin), (deltorphin, [D-Ala2,Glu4]), respectively, also had significant differential analgesic effects, supporting a functional delta opioid receptor mediated enkephalinergic mechanism in Cepaea. These results suggest that this specific pulsed magnetic field (Cnp) elicits significant analgesic effects through mechanisms that, in part, involve delta and, to a lesser extent mu opioid receptors.

940

Pulsed magnetic field therapy for osteoarthritis of the knee--a double-blind sham-controlled trial

BACKGROUND AND METHODS: Pulsed magnetic field therapy is frequently used to treat the symptoms of osteoarthritis, although its efficacy has not been proven. We conducted a randomized, double-blind comparison of pulsed magnetic field and sham therapy in patients with symptomatic osteoarthritis of the knee. Patients were assigned to receive 84 sessions, each with a duration of 30 minutes, of either pulsed magnetic field or sham treatment. Patients administered the treatment on their own at home, twice a day for six weeks. RESULTS: According to a sample size estimation, 36 consecutive patients were enrolled. 34 patients completed the study, two of whom had to be excluded from the statistical analysis, as they had not applied the PMF sufficiently. Thus, 15 verum and 17 sham-treated patients were enrolled in the statistical analysis. After six weeks of treatment the WOMAC Osteoarthritis Index was reduced in the pulsed magnetic field-group from 84.1 (+/- 45.1) to 49.7 (+/- 31.6), and from 73.7 (+/- 43.3) to 66.9 (+/- 52.9) in the sham-treated group (p = 0.03). The following secondary parameters improved in the pulsed magnetic field group more than they did in the sham group: gait speed at fast walking [+6.0 meters per minute (1.6 to 10.4) vs. -3.2 (-8.5 to 2.2)], stride length at fast walking [+6.9 cm (0.2 to 13.7) vs. -2.9 (-8.8 to 2.9)], and acceleration time in the isokinetic dynamometry strength tests [-7.0% (-15.2 to 1.3) vs. 10.1% (-0.3 to 20.6)]. CONCLUSION: In patients with symptomatic osteoarthritis of the knee, PMF treatment can reduce impairment in activities of daily life and improve knee function.

942

Pulsed magnetic field therapy for tibial non-union. Interim results of a double-blind trial

Patients with tibial fractures which had remained un-united for at least 52 weeks were randomly allocated to either active or dummy pulsed magnetic field stimulators and treated in full leg plasters for 24 weeks with a non-weightbearing conservative regimen, as is usual with such techniques. Fractures in 5 of the 9 patients with working machines united and fractures in 5 of the 7 patients with dummy machines also united. These early results of this double-blind trial are compatible with a difference in success rate at 24 weeks on active treatment of + 33% to -61% (95% confidence limits) compared with the success rate on the dummy stimulators. The high proportion of fractures uniting in the control group suggests that conservative management of non-union is effective and this may explain much of the success attributed to pulsed magnetic field therapy.

943

Pulsed magnetic field therapy in refractory neuropathic pain secondary to peripheral neuropathy: electrodiagnostic parameters--pilot study

CONTEXT: Neuropathic pain (NP) from peripheral neuropathy (PN) arises from ectopic firing of unmyelinated C-fibers with accumulation of sodium and calcium channels. Because pulsed electromagnetic fields (PEMF) safely induce extremely low frequency (ELF) quasirectangular currents that can depolarize, repolarize, and hyperpolarize neurons, it was hypothesized that directing this energy into the sole of one foot could potentially modulate neuropathic pain. OBJECTIVE: To determine if 9 consecutive 1-h treatments in physician's office (excluding weekends) of a pulsed signal therapy can reduce NP scores in refractory feet with PN. DESIGN/SETTING/PATIENTS: 24 consecutive patients with refractory and symptomatic PN from diabetes, chronic inflammatory demyelinating polyneuropathy (CIDP), pernicious anemia, mercury poisoning, paraneoplastic syndrome, tarsal tunnel, and idiopathic sensory neuropathy were enrolled in this nonplacebo pilot study. The most symptomatic foot received therapy. Primary endpoints were comparison of VAS scores at the end of 9 days and the end of 30 days follow-up compared to baseline pain scores. Additionally, Patients' Global Impression of Change (PGIC) questionnaire was tabulated describing response to treatment. Subgroup analysis of nerve conduction scores, quantified sensory testing (QST), and serial examination changes were also tabulated. Subgroup classification of pain (Serlin) was utilized to determine if there were disproportionate responses. INTERVENTION: Noninvasive pulsed signal therapy generates a unidirectional quasirectangular waveform with strength about 20 gauss and a frequency about 30 Hz into the soles of the feet for 9 consecutive 1-h treatments (excluding weekends). The most symptomatic foot of each patient was treated. RESULTS: All 24 feet completed 9 days of treatment. 15/24 completed follow-up (62%) with mean pain scores decreasing 21% from baseline to end of treatment (P=0.19) but with 49% reduction of pain scores from baseline to end of follow-up (P<0.01). Of this group, self-reported PGIC was improved 67% (n=10) and no change was 33% (n=5). An intent-to-treat analysis based on all 24 feet demonstrated a 19% reduction in pain scores from baseline to end of treatment (P=0.10) and a 37% decrease from baseline to end of follow-up (P<0.01). Subgroup analysis revealed 5 patients with mild pain with nonsignificant reduction at end of follow-up. Of the 19 feet with moderate to severe pain, there was a 28% reduction from baseline to end of treatment (P<0.05) and a 39% decrease from baseline to end of follow-up (P<0.01). Benefit was better in those patients with axonal changes and advanced CPT baseline scores. The clinical examination did not change. There were no adverse events or safety issues. CONCLUSIONS: These pilot data demonstrate that directing PEMF to refractory feet can provide unexpected shortterm analgesic effects in more than 50% of individuals. The role of placebo is not known and was not tested. The precise mechanism is unclear yet suggests that severe and advanced cases are more magnetically sensitive. Future studies are needed with randomized placebo-controlled design and longer treatment periods.

944

Pulsed magnetic field therapy increases tensile strength in a rat Achilles' tendon repair model

PURPOSE: To examine the effect of pulsing electromagnetic fields on the biomechanic strength of rat Achilles' tendons at 3 weeks after transection and repair. METHODS: This noninvasive modality was tested in a prospective, randomized, double-blinded, placebo-controlled study to evaluate the effect of a specific noninvasive radiofrequency pulsed electromagnetic field signal on tendon tensile strength at 21 days post transection in a rat model. RESULTS: In the animals receiving PMF exposure, an increase in tensile strength of up to 69% was noted at the repair site of the rat Achilles' tendon at 3 weeks after transection and repair compared with nonstimulated control animals. CONCLUSIONS: The application of electromagnetic fields, configured to enhance Ca(2+) binding in the growth factor cascades involved in tissue healing, achieved a marked increase of tensile strength at the repair site in this animal model. If similar effects occur in humans, rehabilitation could begin earlier and the risk of developing adhesions or rupturing the tendon in the early postoperative period could be reduced.

945

Pulsed magnetic fields accelerate cutaneous wound healing in rats

BACKGROUND: Previous studies of pulsed magnetic fields have reported enhanced fracture and chronic wound healing, endothelial cell growth, and angiogenesis. This study characterizes the biomechanical changes that occur when standard cutaneous wounds are exposed to radiofrequency pulsed magnetic fields with specific dosage parameters, in an attempt to determine whether return to functional tensile strength could be accelerated in wound healing. METHODS: There were two study phases and a total of 100 rats. In phase 1, wounds were exposed to a 1.0-G pulsed magnetic field signal in clinical use for wound repair for 30 minutes twice daily for 21 or 60 days. Phase 2 was a prospective, placebo-controlled, double-blind trial in which rats were treated for 30 minutes twice daily with three different low-amplitude signals (0.02 to 0.05 G), configured assuming a Ca binding transduction pathway, for 21 days. A midline, 8-cm, linear skin incision was made on the rat dorsum. Tensile strength was determined by measuring the point of rupture of the wound on a standard tensiometer loaded at 0.45 mm/second. RESULTS: The mean tensile strength of treated groups in phase 1 was 48 percent (p < 0.001) greater than that of controls at 21 days; there was no significant difference at 60 days. In phase 2, the treated groups showed 18 percent (not significant), 44 percent, and 59 percent (p < 0.001) increases in tensile strength over controls at 21 days. CONCLUSION: The authors successfully demonstrated that exposing wounds to pulsed magnetic fields of very specific configurations accelerated early wound healing in this animal model, as evidenced by significantly increased wound tensile strength at 21 days after wounding.

947

Pulsed magnetic fields alter the cell surface

Pulsed magnetic fields (PMFS) are routinely used in the medical community to facilitate bone repair in clinical cases of non-union or pseudarthoses [(1984) Orth. Clin. No. Am. 15, 61-87]. Although this therapeutic regimen appears to be reasonably effective, the mechanism of action between specific PMFs and the target tissue remains unknown. Adding urgency to the need to understand the mechanism are a wide number of reports that have appeared which demonstrate that PMFs similar to those in clinical use can alter many basic physiological functions. We report that a 24 h exposure to PMFs alters the cell surface of Physarum polycephalum amoebae. Further, using the technique of aqueous two-phase partitioning, we present evidence for individual magnetic and electric field, cell surface effects.

948

Pulsed magnetic fields applied to a transferred arterial loop support the rat groin composite flap

Pulsed magnetic fields have been shown to stimulate neovascularization in the authors' laboratory. The rat groin composite flap was used to create a prospective randomized trial to test the effectiveness of these pulsed magnetic fields. The skin paddle to this flap is highly consistent, and the authors proposed using the flap to study how pulsed magnetic fields affect composite flap survival when the dominant vessel to the flap is divided and flap survival becomes dependent on a transferred vessel loop. Forty-three rats had the tail artery microsurgically anastomosed to the femoral artery and placed between the groin musculature and the abdominal skin. Pulsed magnetic energy of 1 gauss was applied for 8 (n = 14) or 12 (n = 8) weeks to the experimental groups. Control groups were treated in a comparable manner for 8 (n = 16) or 12 (n = 5) weeks. After the 8 or 12 weeks, all groups had an 8 x 4-cm skin flap raised, and the superficial epigastric artery, the main feeding vessel, was ligated. After 5 days, the total area of the flap and the area of necrosis were traced onto velum paper for each rat. The percent survival was calculated per rat, and a mean survival percentage was calculated per group. The experimental animals treated with pulsed magnetic fields for 8 weeks had statistically significant improved flap survival over the control animals. The study provides evidence that pulsed magnetic energy stimulates angiogenesis and suggests a possible use of this modality to create island vascular flaps in otherwise random vascular territories.

949

Pulsed magnetic fields enhance nitric oxide synthase activity in rat cerebellum

The effect of pulsed magnetic fields on nitric oxide synthase (NOS) activity in the rat brain was investigated. Sprague-Dawley rats (male, 200-250 g body weight) brain were dissected regionally, and the crude enzyme solutions were treated with pulsed DC, AC or static DC magnetic fields at 0 degrees C for 1 h. After exposure, NOS activity was measured as nitrite and nitrate levels generated from incubation with arginine, CaCl(2) and beta-nicotinamide adenine dinucleotide phosphate. Under these experimental conditions, neither AC nor static DC field treatment showed any significant change in NOS activity. A significant increase in NOS activity was observed in the cerebellum (111.2+/-2.0%, P<0.05, five separate experiments) for a 1 Gauss (0.1 mT) pulsed DC field. Under the same experimental condition, only a slight change or no effect was observed in the hippocampus, cortex, medulla oblongata, hypothalamus, striatum and midbrain. These studies suggest that pulsed magnetic fields result in a different effect on NOS activity in the cerebellum of the rats.

951

Pulsed magnetic fields improve osteoblast activity during the repair of an experimental osseous defect

The influence of pulsed low-frequency electromagnetic fields (PEMFs) on bone formation was investigated in studies of the healing process of transcortical holes, bored at the diaphyseal region of metacarpal bones of six adult horses, exposed for 30 days to PEMFs (28 G peak amplitude, 1.3 ms rise time, and 75 Hz repetition rate). A pair of Helmholtz coils, continuously powered by a pulse generator, was applied for 30 days to the left metacarpal bone, through which two holes, of equal diameter and depth, had been bored at the diaphyseal region. Two equal holes, bored at the same level in the right metacarpal and surrounded by an inactive pair of Helmholtz coils, were used as controls. All horses were given an intravenous injection of 25-30 mg/kg of tetracycline chloride on the 15th and again on the 25th day after the operation and were killed 5 days later. The histomorphometric analysis indicated that both the amount of bone formed during 30 days and the mineral apposition rate during 10 days (deduced from the interval between the two tetracycline labels) were significantly greater (p < 0.01 and p < 0.0001, respectively) in the PEMF-treated holes than in the controls. As did a previous investigation, these preliminary findings indicate that PEMFs at low frequency not only stimulate bone repair but also seem to improve the osteogenic phase of the healing process, at least in our experimental conditions.

952

Pulsed magnetization transfer imaging with body coil transmission at 3 Tesla: feasibility and application

Pulsed magnetization transfer (MT) imaging has been applied to quantitatively assess brain pathology in several diseases, especially multiple sclerosis (MS). To date, however, because of the high power deposition associated with the use of short, rapidly repeating MT prepulses, clinical application has been limited to lower field strengths. The contrast-to-noise ratio (CNR) of MT is limited, and this method would greatly benefit from the use of higher magnetic fields and phased-array coil reception. However, power deposition is proportional to the square of the magnetic field and scales with coil size, and MT experiments are already close to the SAR limit at 1.5T even when smaller transmit coils are used instead of the body coil. Here we show that these seemingly great obstacles can be ameliorated by the increased T(1) of tissue water at higher field, which allows for longer maintenance of sufficiently high saturation levels while using a reduced duty cycle. This enables a fast (5-6 min) high-resolution (1.5 mm isotropic) whole-brain MT acquisition with excellent anatomical visualization of gray matter (GM) and white matter (WM) structures, and even substructures. The method is demonstrated in nine normal volunteers and five patients with relapsing remitting MS (RRMS), and the results show a clear delineation of heterogeneous lesions.

953

Pulsed magnetotherapy in Czechoslovakia--a review

Pulsed magnetotherapy has been used in Czechoslovakia for more than one decade. It has been proved that this type of physical therapy is very efficient mainly in rheumatic diseases, in paediatrics (sinusitis, enuresis), and in balneological care of patients suffering from ischaemic disorders of lower extremities. Promising results have also been obtained in neurological diseases (multiple sclerosis, spastic conditions) and in ophthalmology, in degenerative diseases of the retina.

954

Pulsed nuclear magnetic resonance study of 39K in frog striated muscle

Samples of 1 M KCl solution and 10 samples of intact frog striated muscle were studied at 4-7 degrees C and/or at 21-22 degrees C. Field inhomogeneity was minimized by using small sample volumes and by using a superconducting magnet designed specifically to provide highly homogeneous fields. In the present experiments, magnetic field inhomogeneity was measured to contribute less than 15% to the free induction decay observed for intracellular 39K. The signal-to-noise ratio of the measurements was enhanced by means of extensive time-averaging. The rates of nuclear relaxation for 39K in aqueous solution were 22 +/- 3 (mean +/- 95% confidence limits) s-1 at 4-7 degrees C and 15 +/- 2 s-1 at 21-22 degrees C. For intracellular 39K, (1/T2) was measured to be 327 +/- 22 s-1 and 229 +/- 10 s-1 at the lower and higher temperatures, respectively. The corresponding values for (1/T1) in the same muscle samples were 198 +/- 31 s-1 and 79 +/- 15 s-1 at 4-7 degrees C and at 21-22 degrees C, respectively. These results for 39K are similar to those previously obtained for intracellular 23Na. Since less than 1% of the intracellular 23Na has been estimated to be immobilized, fractional immobilization of intracellular 39K is also likely to be insubstantial.

955

Pulsed radio frequency radiation affects cognitive performance and the waking electroencephalogram

We investigated the effects of radio frequency electromagnetic fields on brain physiology. Twenty-four healthy young men were exposed for 30 min to pulse-modulated or continuous-wave radio frequency electromagnetic fields (900 MHz; peak specific absorption rate 1 W/kg), or sham exposed. During exposure, participants performed cognitive tasks. Waking electroencephalogram was recorded during baseline, immediately after, and 30 and 60 min after exposure. Pulse-modulated radio frequency electromagnetic field exposure reduced reaction speed and increased accuracy in a working-memory task. It also increased spectral power in the waking electroencephalogram in the 10.5-11 Hz range 30 min after exposure. No effects were observed for continuous-wave radio frequency electromagnetic fields. These findings provide further evidence for a nonthermal biological effect of pulsed radio frequency electromagnetic fields.

956

Pulsed radio-frequency electromagnetic fields: dose-dependent effects on sleep, the sleep EEG and cognitive performance

To establish a dose-response relationship between the strength of electromagnetic fields (EMF) and previously reported effects on the brain, we investigated the influence of EMF exposure by varying the signal intensity in three experimental sessions. The head of 15 healthy male subjects was unilaterally exposed for 30 min prior to sleep to a pulse-modulated EMF (GSM handset like signal) with a 10 g-averaged peak spatial specific absorption rate of (1) 0.2 W kg(-1), (2) 5 W kg(-1), or (3) sham exposed in a double-blind, crossover design. During exposure, subjects performed two series of three computerized cognitive tasks, each presented in a fixed order [simple reaction time task, two-choice reaction time task (CRT), 1-, 2-, 3-back task]. Immediately after exposure, night-time sleep was polysomnographically recorded for 8 h. Sleep architecture was not affected by EMF exposure. Analysis of the sleep electroencephalogram (EEG) revealed a dose-dependent increase of power in the spindle frequency range in non-REM sleep. Reaction speed decelerated with increasing field intensity in the 1-back task, while accuracy in the CRT and N-back task were not affected in a dose-dependent manner. In summary, this study reveals first indications of a dose-response relationship between EMF field intensity and its effects on brain physiology as demonstrated by changes in the sleep EEG and in cognitive performance.

958

Pulsed radiofrequency for the treatment of chronic ilioinguinal neuropathy

BACKGROUND: Ilioinguinal neuropathy is a rare but disabling condition. The condition may arise spontaneously or in the setting of pelvic surgery. To date, most therapeutic options have been limited to neuropathic pain medications, anti-inflammatory medications, nerve blocks with local anesthetics, or neurectomy. Long-term results of non-surgical interventions are fair at best. We present a case of chronic ilioinguinal neuropathy treated with pulsed radiofrequency. OBJECTIVE: To examine the efficacy of pulsed radiofrequency (PRF) lesioning on pain in ilioinguinal neuropathy. METHOD: A 58-year old man with chronic ilioinguinal neuropathy was treated with PRF and was followed for 3 months. RESULTS: The patient had significant pain relief at 3 months follow up. CONCLUSION: Pulsed radiofrequency lesioning may be a good treatment for chronic ilioinguinal neuropathy in cases refractory to conservative management.

959

Pulsed radiofrequency for the treatment of ilioinguinal neuralgia after inguinal herniorrhaphy

BACKGROUND AND PURPOSE: Ilioinguinal neuralgia secondary to inguinal hernia repair is frequently a chronic, debilitating pain. It is most often due to destruction or entrapment of nerve tissue from staples, sutures, or direct surgical trauma. Treatment modalities, including oral analgesics, nerve blocks, mesh excision, and surgical neurectomy, have varied success rates. Pulsed radiofrequency (PRF) has recently been described as a successful method of treating chronic groin pain. Unlike conventional radiofrequency, PRF is non-neurodestructive and therefore less painful and without the potential complications of neuritis-like reactions and neuroma formation. Although the mechanism is unknown, it appears that the interaction of an electromagnetic field and c-fos proteins may alter normal transmission of painful impulses. Our study examines five patients treated with PRF for ilioinguinal neuralgia secondary to inguinal herniorrhaphy. METHOD: Five patients were diagnosed with chronic ilioinguinal neuralgia secondary to inguinal hernia repair at our institution. Each patient was treated at vertebral T12, L1, and L2 with root PRF at 42 degrees C for 120 seconds per level. RESULTS: Four out of five patients reported pain relief lasting from four to nine months on follow-up visits. Only one patient reported no pain relief whatsoever. CONCLUSION: Ilioinguinal neuralgia is challenging to treat. We have demonstrated the successful use of PRF for four out of five patients seen in our office.

960

Pulsed static magnetic field effects on in-vitro pineal indoleamine metabolism

In-vitro rat pineal glands stimulated with the beta-adrenergic receptor agonist isoproterenol to induce melatonin synthesis and exposed for 1 h to a pulsed 0.4-G static magnetic field demonstrated significant inhibition of serotonin-N-acetyltransferase activity and melatonin content. 2-h exposure to pulsed magnetic field also resulted in a significant reduction in isoproterenol-induced serotonin-N-acetyltransferase activity. These results support the idea that the cultured pineal gland can be affected directly by artificially generated weak magnetic fields.

961

Pulsed subcutaneous electrical stimulation in spinal cord injury: preliminary results

The treatment of long-term, stable para- and quadriplegics with pulsed electrical stimulation for pain control resulted in, anecdotally, a significant number of these individuals showing increased motor function as well as sensory awareness. This small pilot study was conducted in order to assess the hypothesis that pulsed electrical fields can effect diseased neurological function. Thirteen para- and quadriplegic subjects with 18 months of stable neurological signs and symptoms were exposed daily to pulsed electrical stimulation for a 6-month period and assessed for any improvement in motor function or sensory perception. The hypothesis is that pulsed electromagnetic fields can normalize viable but dysfunctional neuronal structures. Results were encouraging.

963

Quality and safety aspects of PEF application in milk and milk products

The articles published to date on the possibilities of applying the new PEF technology to milk and milk products are summarized in a review that presents them in chronological order and grouped on the basis of the factor studied (microorganism, enzyme, quality parameter, or shelf-life). An accompanying table shows details of the equipment and process corresponding to each article in chronological order.

964

Quality assurance for clinical implementation of an electromagnetic tracking system

The Calypso Medical 4D localization system utilizes alternating current electromagnetics for accurate, real-time tumor tracking. A quality assurance program to clinically implement this system is described here. Testing of the continuous electromagnetic tracking system (Calypso Medical Technologies, Seattle, WA) was performed using an in-house developed four-dimensional stage and a quality assurance fixture containing three radiofrequency transponders at independently measured locations. The following tests were performed to validate the Calypso system: (a) Localization and tracking accuracy, (b) system reproducibility, (c) measurement of the latency of the tracking system, and (d) measurement of transmission through the Calypso table overlay and the electromagnetic array. The translational and rotational localization accuracies were found to be within 0.01 cm and 1.0 degree, respectively. The reproducibility was within 0.1 cm. The average system latency was measured to be within 303 ms. The attenuation by the Calypso overlay was measured to be 1.0% for both 6 and 18 MV photons. The attenuations by the Calypso array were measured to be 2% and 1.5% for 6 and 18 MV photons, respectively. For oblique angles, the transmission was measured to be 3% for 6 MV, while it was 2% for 18 MV photons. A quality assurance process has been developed for the clinical implementation of an electromagnetic tracking system in radiation therapy.

965

Quantification of electroporative uptake kinetics and electric field heterogeneity effects in cells

We have conducted experiments quantitatively investigating electroporative uptake kinetics of a fluorescent plasma membrane integrity indicator, propidium iodide (PI), in HL60 human leukemia cells resulting from exposure to 40 mus pulsed electric fields (PEFs). These experiments were possible through the use of calibrated, real-time fluorescence microscopy and the development of a microcuvette: a specialized device designed for exposing cell cultures to intense PEFs while carrying out real-time microscopy. A finite-element electrostatic simulation was carried out to assess the degree of electric field heterogeneity between the microcuvette's electrodes allowing us to correlate trends in electroporative response to electric field distribution. Analysis of experimental data identified two distinctive electroporative uptake signatures: one characterized by low-level, decelerating uptake beginning immediately after PEF exposure and the other by high-level, accelerating fluorescence that is manifested sometimes hundreds of seconds after PEF exposure. The qualitative nature of these fluorescence signatures was used to isolate the conditions required to induce exclusively transient electroporation and to discuss electropore stability and persistence. A range of electric field strengths resulting in transient electroporation was identified for HL60s under our experimental conditions existing between 1.6 and 2 kV/cm. Quantitative analysis was used to determine that HL60s experiencing transient electroporation internalized between 50 and 125 million nucleic acid-bound PI molecules per cell. Finally, we show that electric field heterogeneity may be used to elicit asymmetric electroporative PI uptake within cell cultures and within individual cells.

966

Quantitative characterization of rat tendinitis to evaluate the efficacy of therapeutic interventions

Tendinitis is a painful soft tissue pathology that accounts for almost half of all occupational injuries in the United States. It is often caused by repeated movements and may result in loss of work and income. Current treatments for tendinitis are aimed at reducing inflammation, the major cause of the pain. Although anti-inflammatory drugs and various alternative therapies are capable of improving tendinitis, there are no quantitative scientific data available regarding their impact on inflammation. The objective of this study is to determine the time course for healing of rat tendinitis without intervention to be able to assess the efficacy of tendinitis treatments. We are interested in evaluating the therapeutic use of pulsed electromagnetic fields (PEMFs), a therapeutic modality that has been found to be beneficial for healing soft tissue injuries. Tendinitis was induced in Harlan Sprague Dawley rats by collagenase injections into the Achilles tendon, and tendons were collected for four weeks post-injury. To determine the amount of edema, we used caliper measurements of the rat ankles and quantified the tendon water content. To determine the extent of inflammation, we estimated the number of inflammatory cells on histological sections applying stereological methods. The data reveal that edema is maximal 24 hours after injury accompanied by a massive infiltration of inflammatory cells. Inflammatory cells are then gradually replaced by fibroblasts, which are responsible for correcting damage to the extracellular matrix. This natural time course of tendon healing will be used to evaluate the use of PEMFs as a possible therapeutic modality.

967

Quantization of the Hall conductivity well beyond the adiabatic limit in pulsed magnetic fields

We measure the Hall conductivity, sigma(xy), on a Corbino geometry sample of a high-mobility AlGaAs/GaAs heterostructure in a pulsed magnetic field. At a bath temperature about 80 mK, we observe well expressed plateaux in sigma(xy) at integer filling factors. In the pulsed magnetic field, the Laughlin condition of the phase coherence of the electron wave functions is strongly violated and, hence, is not crucial for sigma(xy) quantization.

968

Quantum oscillations in the underdoped cuprate YBa2Cu4O8

We report the observation of quantum oscillations in the underdoped cuprate superconductor YBa2Cu4O8 using a tunnel-diode oscillator technique in pulsed magnetic fields up to 85 T. There is a clear signal, periodic in inverse field, with frequency 660+/-15 T and possible evidence for the presence of two components of slightly different frequency. The quasiparticle mass is m(*)=3.0+/-0.3m(e). In conjunction with the results of Doiron-Leyraud et al. for YBa2Cu3O6.5, the present measurements suggest that Fermi surface pockets are a general feature of underdoped copper oxide planes and provide information about the doping dependence of the Fermi surface.

969

Radial wave crystals: radially periodic structures from anisotropic metamaterials for engineering acoustic or electromagnetic waves

We demonstrate that metamaterials with anisotropic properties can be used to develop a new class of periodic structures that has been named radial wave crystals. They can be sonic or photonic, and wave propagation along the radial directions is obtained through Bloch states like in usual sonic or photonic crystals. The band structure of the proposed structures can be tailored in a large amount to get exciting novel wave phenomena. For example, it is shown that acoustical cavities based on radial sonic crystals can be employed as passive devices for beam forming or dynamically orientated antennas for sound localization.

970

Radiation characteristics of electromagnetic eigenmodes at the corrugated interface of a left-handed material

We study the radiation characteristics of electromagnetic surface waves at a periodically corrugated interface between a conventional and a negatively refracting (or left-handed) material. In this case, and contrary to the surface plasmon polariton in a metallic grating, surface plasmon polaritons may radiate on both sides of the rough interface along which they propagate. We find novel radiation regimes which provide an indirect demonstration of other unusual phenomena characteristic of electromagnetic wave propagation in left-handed materials, such as negative refraction or backward wave propagation.

971

Radio frequency electromagnetic radiation (RF-EMR) from GSM (0.9/1.8GHz) mobile phones induces oxidative stress and reduces sperm motility in rats

INTRODUCTION: Mobile phones have become indispensable in the daily lives of men and women around the globe. As cell phone use has become more widespread, concerns have mounted regarding the potentially harmful effects of RF-EMR from these devices. OBJECTIVE: The present study was designed to evaluate the effects of RF-EMR from mobile phones on free radical metabolism and sperm quality. MATERIALS AND METHODS: Male albino Wistar rats (10-12 weeks old) were exposed to RF-EMR from an active GSM (0.9/1.8 GHz) mobile phone for 1 hour continuously per day for 28 days. Controls were exposed to a mobile phone without a battery for the same period. The phone was kept in a cage with a wooden bottom in order to address concerns that the effects of exposure to the phone could be due to heat emitted by the phone rather than to RF-EMR alone. Animals were sacrificed 24 hours after the last exposure and tissues of interest were harvested. RESULTS: One hour of exposure to the phone did not significantly change facial temperature in either group of rats. No significant difference was observed in total sperm count between controls and RF-EMR exposed groups. However, rats exposed to RF-EMR exhibited a significantly reduced percentage of motile sperm. Moreover, RF-EMR exposure resulted in a significant increase in lipid peroxidation and low GSH content in the testis and epididymis. CONCLUSION: Given the results of the present study, we speculate that RF-EMR from mobile phones negatively affects semen quality and may impair male fertility.

972

Radiological workers sensitivity to 50 Hz pulsed magnetic fields: preliminary results

In the present study the effect of extremely low frequency pulsed magnetic fields (PMF) was evaluated in lymphocyte cultures from 12 subjects occupationally exposed to low doses of ionising radiations. The PMF signal characteristics were repetition frequency 50 Hz, triangular shape, rise time about 1.2 ms and peak intensity 2.5 mT. The cytokinesis-block technique was employed to evaluate genotoxicity and cytotoxicity in terms of micronucleus frequency and cell proliferation, respectively. When PMF-exposed cultures were compared with their respective controls, a slight but statistically significant increase was detected in both the biological parameters investigated ( p<0.05). The results obtained suggest a possible role of specific employments involving exposure to ionising radiation, in the risk associated with electromagnetic field exposure.

973

Randomized, prospective, and controlled clinical trial of pulsed electromagnetic field stimulation for cervical fusion

BACKGROUND CONTEXT: Multilevel fusions, the use of allograft bone, and smoking have been associated with an increased risk of nonunion after anterior cervical discectomy and fusion (ACDF) procedures. Pulsed electromagnetic field (PEMF) stimulation has been shown to increase arthrodesis rates after lumbar spine fusion surgery, but there are minimal data concerning the effect of PEMF stimulation on cervical spine fusion. PURPOSE: To determine the efficacy and safety of PEMF stimulation as an adjunct to arthrodesis after ACDF in patients with potential risk factors for nonunion. STUDY DESIGN: A randomized, controlled, prospective multicenter clinical trial. PATIENT SAMPLE: Three hundred and twenty-three patients with radiographic evidence (computed tomography-myelogram [CT-myelo] or magnetic resonance imaging [MRI]) of a compressed cervical nerve root and symptomatic radiculopathy appropriate to the compressed root that had failed to respond to nonoperative management were enrolled in the study. The patients were either smokers (more than one pack per day) and/or were undergoing multilevel fusions. All patients underwent ACDF using the Smith-Robinson technique. Allograft bone and an anterior cervical plate were used in all cases. OUTCOME MEASURES: Measurements were obtained preoperatively and at each postoperative interval and included neurologic assessment, visual analog scale (VAS) scores for shoulder/arm pain at rest and with activity, SF-12 scores, the neck disability index (NDI), and radiographs (anteroposterior, lateral, and flexion-extension views). Two orthopedic surgeons not otherwise affiliated with the study and blinded to treatment group evaluated the radiographs, as did a blinded radiologist. Adverse events were reported by all patients throughout the study to determine device safety. METHODS: Patients were randomly assigned to one of two groups: those receiving PEMF stimulation after surgery (PEMF group, 163 patients) and those not receiving PEMF stimulation (control group, 160 patients). Postoperative care was otherwise identical. Follow-up was carried out at 1, 2, 3, 6, and 12 months postoperatively. RESULTS: The PEMF and control groups were comparable with regard to age, gender, race, past medical history, smoking status, and litigation status. Both groups were also comparable in terms of baseline diagnosis (herniated disc, spondylosis, or both) and number of levels operated (one, two, three, or four). At 6 months postoperatively, the PEMF group had a significantly higher fusion rate than the control group (83.6% vs. 68.6%, p=.0065). At 12 months after surgery, the stimulated group had a fusion rate of 92.8% compared with 86.7% for the control group (p=.1129). There were no significant differences between the PEMF and control groups with regard to VAS pain scores, NDI, or SF-12 scores at 6 or 12 months. No significant differences were found in the incidence of adverse events in the groups. CONCLUSIONS: This is the first randomized, controlled trial that analyzes the effects of PEMF stimulation on cervical spine fusion. PEMF stimulation significantly improved the fusion rate at 6 months postoperatively in patients undergoing ACDF with an allograft and an anterior cervical plate, the eligibility criteria being patients who were smokers or had undergone multilevel cervical fusion. At 12 months postoperatively, however, the fusion rate for PEMF patients was not significantly different from that of the control group. There were no differences in the incidence of adverse events in the two groups, indicating that the use of PEMF stimulation is safe in this clinical setting.

974

Rapid improvement of visuoperceptive functions by picoTesla range magnetic fields in patients with Parkinson's disease

Impairment in perceptual motor or visuospatial tasks is among the most frequently encountered abnormality in neuropsychological testing of patients with Parkinson's disease, being present in up to 90% of cases. Visuoperceptive deficits can result from cortical and subcortical lesions involving the right hemisphere, thalamus, and basal ganglia and are thought to reflect a defect in attentional-arousal mechanisms induced by lesions that interrupt a cortical-limbic-reticular activating loop. Clinically, the presence of visuoperceptive impairment may not be noted by Parkinsonian patients but may contribute to various disabilities including difficulty driving a vehicle and difficulties performing daily tasks which require intact visuospatial abilities (i.e., walking, dressing, drawing and copying designs). The present communication concerns two fully medicated Parkinsonian patients who responded to extracranial treatment with picoTesla range magnetic fields (MF), behaviorally and also demonstrated rapidly and dramatically enhanced visuoperceptive functions as demonstrated on various drawing tasks. These findings demonstrate the efficacy of extremely weak MF in enhancing cognitive functions in patients with Parkinson's disease.

975

Rapid normalization of visual evoked potentials by picoTesla range magnetic fields in chronic progressive multiple sclerosis

This communication concerns a 55 year old woman with a 5 year history of chronic progressive multiple sclerosis (MS) in whom a single external application of extremely low magnetic fields (MF) (7.5 picoTesla; 5 Hz frequency) of 20 minutes duration resulted in a rapid improvement in symptoms including vision, cerebellar symptomatology (ataxia and dysarthria), bladder functions, mood, sleep, cognitive functions and fatigue. Improvement in the patient's symptoms was associated with normalization of the pretreatment abnormal visual evoked potential (VEP) latencies within 24 hours after magnetic treatment. The rapid normalization of the VEP latencies suggests that recovery did not occur as a result of remyelination but probably was related to enhancement of neurotransmitter functions. MF have been shown to alter cellular calcium metabolism which may facilitate axonal conduction in demyelinating plaques. Furthermore, as MF affects the release of the pineal gland's principal hormone, melatonin, which influences the release of monoamines, it is also 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).

976

Rapid rise time pulsed magnetic field circuit for pump-probe field effect studies

Here we describe an electronic circuit capable of producing rapidly switched dc magnetic fields of up to 20 mT with a rise time of 10 ns and a pulse length variable from 50 ns to more than 10 micros, suitable for use in the study of magnetic field effects on radical pair (RP) reactions. This corresponds to switching the field on a time scale short relative to the lifetime of typical RPs and maintaining it well beyond their lifetimes. Previous experiments have involved discharging a capacitor through a low inductance coil for a limited time using a switching circuit. These suffer from decaying field strength over the duration of the pulse given primarily by the ratio of the pulse width to the RC constant of the circuit. We describe here a simple yet elegant solution that completely eliminates this difficulty by employing a feedback loop. This allows a constant field to be maintained over the entire length of the pulse.

977

Rapid ventricular pacing in a pacemaker patient undergoing magnetic resonance imaging

Magnetic resonance imaging (MRI) generates potent electromagnetic forces in the form of a static, gradient, or pulsed radiofrequency magnetic field that can result in pacemaker malfunction. This report documents a case of rapid cardiac pacing during MRI in a patient with a dual chamber pacemaker. Although the mechanism of rapid cardiac pacing is unclear, it was directly related to radiofrequency pulsing. We postulated that the lead acts as an antenna for radiofrequency energy that interacts with the pacemaker's output circuit, thus, causing cardiac pacing at a cycle length representing a multiple of the repetition time; or perhaps rapid pacing is related to induced currents generated between the MRI unit and the pacing lead.

979

Real-time control of neutrophil metabolism by very weak ultra-low frequency pulsed magnetic fields

In adherent and motile neutrophils NAD(P)H concentration, flavoprotein redox potential, and production of reactive oxygen species and nitric oxide, are all periodic and exhibit defined phase relationships to an underlying metabolic oscillation of approximately 20 s. Utilizing fluorescence microscopy, we have shown in real-time, on the single cell level, that the system is sensitive to externally applied periodically pulsed weak magnetic fields matched in frequency to the metabolic oscillation. Depending upon the phase relationship of the magnetic pulses to the metabolic oscillation, the magnetic pulses serve to either increase the amplitude of the NAD(P)H and flavoprotein oscillations, and the rate of production of reactive oxygen species and nitric oxide or, alternatively, collapse the metabolic oscillations and curtail production of reactive oxygen species and nitric oxide. Significantly, we demonstrate that the cells do not directly respond to the magnetic fields, but instead are sensitive to the electric fields which the pulsed magnetic fields induce. These weak electric fields likely tap into an endogenous signaling pathway involving calcium channels in the plasma membrane. We estimate that the threshold which induced electric fields must attain to influence cell metabolism is of the order of 10(-4) V/m.

980

Real-time movie imaging from a single cardiac cycle by NMR

Using a 1-m-bore superconductive magnet at 0.1 T, whole-body transverse images through adult humans have been obtained at repetition times of 57 ms. The techniques used were minor variations of echo-planar imaging (EPI) employing large pulsed gradients to provide complete coverage of the plane in phase space, and low-angle RF excitation sequences allowing rapid repetition of the experiment. In addition active magnetic screening of the gradient coils was implemented to protect the surrounding magnet from the eddy currents induced by the necessarily fast switching of the large gradient fields.

981

Reduction of postherpetic neuralgia in herpes zoster.

BACKGROUND: Persons 50 years of age and older are not only at increased risk of developing herpes zoster, they are also more likely to suffer the long-term morbidity of postherpetic neuralgia (PHN). PHN is pain persisting after the rash of herpes zoster has healed. PHN affects at least 40% of all herpes zoster patients over age 50 and over 75% of herpes zoster patients over age 75; PHN is the single most common neurologic condition in elderly patients. OBJECTIVE: The objective of this review is to evaluate interventions that may reduce or even eliminate PHN. No single therapy has been consistently effective for PHN. The most effective approach appears to be with the use of antiviral therapy early in the course of herpes zoster. The goals of ongoing studies in herpes zoster are to develop interventions that will further reduce the symptoms of PHN and/or to eliminate PHN by prophylaxis using the varicella vaccine. CONCLUSIONS: Reduction of PHN can best be achieved with the use of antiviral medication early in the course of herpes zoster; other classes of drugs are minimally effective in treating established PHN. Widespread use of the varicella vaccine may lead to secondary reductions in PHN in the distant future.

982

Reentrant hidden order at a metamagnetic quantum critical end point

Magnetization measurements of URu2Si2 in pulsed magnetic fields of 44 T reveal that the hidden order phase is destroyed before appearing in the form of a reentrant phase between approximately 36 and 39 T. Evidence for conventional itinerant electron metamagnetism at higher temperatures suggests that the reentrant phase is created in the vicinity of a quantum critical end point.

983

Reformulation of Maxwell's Equations to Incorporate Near-Solute Solvent Structure

Maxwell's equations, which treat electromagnetic interactions between macroscopic charged objects in materials, have explained many phenomena and contributed to many applications in our lives. Derived in 1861 when no methods were available to determine the atomic structure of macromolecules, Maxwell's equations assume the solvent to be a structureless continuum. However, near-solute solvent molecules are highly structured, unlike far-solute bulk solvent molecules. Current methods cannot treat both the near-solute solvent structure and time-dependent electromagnetic interactions in a macroscopic system. Here, we derive "microscopic" electrodynamics equations that can treat macroscopic time-dependent electromagnetic field problems like Maxwell's equations and reproduce the solvent molecular and dipole density distributions observed in molecular dynamics simulations. These equations greatly reduce computational expense by not having to include explicit solvent molecules, yet they treat the solvent electrostatic and van der Waals effects more accurately than continuum models. They provide a foundation to study electromagnetic interactions between molecules in a macroscopic system that are ubiquitous in biology, bioelectromagnetism, and nanotechnology. The general strategy presented herein to incorporate the near-solute solvent structure would enable studies on how complex cellular protein-ligand interactions are affected by electromagnetic radiation, which could help to prevent harmful electromagnetic spectra or find potential therapeutic applications.

984

Regenerative effects of pulsed magnetic field on injured peripheral nerves

Previous studies confirm that pulsed magnetic field (PMF) accelerates functional recovery after a nerve crush lesion. The contention that PMF enhances the regeneration is still controversial, however. The influence of a new PMF application protocol (trained PMF) on nerve regeneration was studied in a model of crush injury of the sciatic nerve of rats. To determine if exposure to PMF influences regeneration, we used electrophysiological recordings and ultrastructural examinations. After the measurements of conduction velocity, the sucrose-gap method was used to record compound action potentials (CAPs) from sciatic nerves. PMF treatment during the 38 days following the crush injury enhanced the regeneration. Although the axonal ultrastructures were generally normal, slight to moderate myelin sheath degeneration was noted at the lesion site. PMF application for 38 days accelerated nerve conduction velocity, increased CAP amplitude and decreased the time to peak of the CAP. Furthermore, corrective effects of PMF on. the abnormal characteristics of sensory nerve fibers were determined. Consequently, long-periodic trained-PMF may promote both morphological and electrophysiological properties of the injured nerves. In addition, corrective effects of PMF on sensory fibers may be considered an important finding for neuropathic pain therapy.

985

Rehabilitation for distal radial fractures in adults

BACKGROUND: Fracture of the distal radius is a common clinical problem, particularly in older white women with osteoporosis. OBJECTIVES: To examine the effects of rehabilitation interventions in adults with conservatively or surgically treated distal radial fractures. SEARCH STRATEGY: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (December 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2005), MEDLINE, EMBASE, CINAHL, AMED, PEDro, OTseeker and other databases, conference proceedings and reference lists of articles. No language restrictions were applied. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials evaluating rehabilitation as part of the management of fractures of the distal radius sustained by adults. Rehabilitation interventions such as active and passive mobilisation exercises, and training for activities of daily living, could be used on their own or in combination, and be applied in various ways by various clinicians. DATA COLLECTION AND ANALYSIS: The authors independently selected and reviewed trials. Study authors were contacted for additional information. No data pooling was done. MAIN RESULTS: Fifteen trials, involving 746 mainly female and older patients, were included. Initial treatment was conservative, involving plaster cast immobilisation, in all but 27 participants whose fractures were fixed surgically. Though some trials were well conducted, others were methodologically compromised.For interventions started during immobilisation, there was weak evidence of improved hand function for hand therapy in the days after plaster cast removal, with some beneficial effects continuing one month later (one trial). There was weak evidence of improved hand function in the short term, but not in the longer term (three months), for early occupational therapy (one trial), and of a lack of differences in outcome between supervised and unsupervised exercises (one trial).For interventions started post-immobilisation, there was weak evidence of a lack of clinically significant differences in outcome in patients receiving formal rehabilitation therapy (four trials), passive mobilisation (two trials), ice or pulsed electromagnetic field (one trial), or whirlpool immersion (one trial) compared with no intervention. There was weak evidence of a short-term benefit of continuous passive motion (post external fixation) (one trial), intermittent pneumatic compression (one trial) and ultrasound (one trial). There was weak evidence of better short-term hand function in participants given physiotherapy than in those given instructions for home exercises by a surgeon (one trial). AUTHORS' CONCLUSIONS: The available evidence from randomised controlled trials is insufficient to establish the relative effectiveness of the various interventions used in the rehabilitation of adults with fractures of the distal radius.

986

Rehabilitation for patients with lateral epicondylitis: a systematic review

The purpose of this systematic review was to determine the effectiveness of conservative treatments for lateral epicondylitis and to provide recommendations based on this evidence. Five reviewers searched computerized bibliographic databases for articles on the conservative treatment of lateral epicondylitis from the years 1983 to 2003. A total of 209 studies were located; however, only 31 of these met the study inclusion criteria. Each of the articles was randomly allocated to reviewers and critically appraised using a structured critical appraisal tool with 23 items. Treatment recommendations were based on this rating and Sackett's Level of Evidence. This review has determined, with at least level 2b evidence, that a number of treatments, including acupuncture, exercise therapy, manipulations and mobilizations, ultrasound, phonophoresis, Rebox, and ionization with diclofenac all show positive effects in the reduction of pain or improvement in function for patients with lateral epicondylitis. There is also at least level 2b evidence showing laser therapy and pulsed electromagnetic field therapy to be ineffective in the management of this condition. Practitioners should use the treatment techniques that have strongest evidence and ensure that studies findings are generalized to patients who are similar to those reported in primary research studies in terms of patient demographics and injury presentation.

987

Relationship between heart rate variability and cognitive function during threat of shock.

The aim of the present study was to investigate the relationship between resting heart rate variability (HRV) and cognitive functions during threat of shock. A Continuous Performance Task and a Working Memory Task were used to measure cognitive functions. Sixty-five male participants from the Royal Norwegian Navy participated. HRV was measured during baseline, test conditions and recovery. Participants were randomly assigned into non-threat and threat groups. Based on the median split of the high frequency (HF) spectral power, groups were divided into two additional groups. Overall, the high HRV participants showed superior performance on cognitive tasks independent of non-threat or threat conditions. During threat condition the low HRV group showed improved performance. Thus, individuals with high HRV were more stress tolerant and resilient in the face of environmental changes. The results from the study might have implications with regard to performance in operational settings, but also for other fields of psychological research such as individual differences, anxiety and coping.

988

Relationship between sublethal injury and inactivation of yeast cells by the combination of sorbic acid and pulsed electric fields

The objective of this study was to investigate the occurrence of sublethal injury after the pulsed-electric-field (PEF) treatment of two yeasts, Dekkera bruxellensis and Saccharomyces cerevisiae, as well as the relation of sublethal injury to the inactivating effect of the combination of PEF and sorbic acid. PEF caused sublethal injury in both yeasts: more than 90% of surviving D. bruxellensis cells and 99% of surviving S. cerevisiae cells were sublethally injured after 50 pulses at 12 kV/cm in buffer at pHs of both 7.0 and 4.0. The proportion of sublethally injured cells reached a maximum after 50 pulses at 12.0 kV/cm (S. cerevisiae) or 16.5 kV/cm (D. bruxellensis), and it kept constant or progressively decreased at greater electric field strengths and with longer PEF treatments. Sublethally PEF-injured cells showed sensitivity to the presence of sorbic acid at a concentration of 2,000 ppm. A synergistic inactivating effect of the combination of PEF and sorbic acid was observed. Survivors of the PEF treatment were progressively inactivated in the presence of 2,000 ppm of sorbic acid at pH 3.8, with the combined treatments achieving more than log10 5 cycles of dead cells under the conditions investigated. This study has demonstrated the occurrence of sublethal injury after exposure to PEF, so yeast inactivation by PEF is not an all-or-nothing event. The combination of PEF and sorbic acid has proven to be an effective method to achieve a higher level of yeast inactivation. This work contributes to the knowledge of the mechanism of microbial inactivation by PEF, and it may be useful for improving food preservation by PEF technology.

990

Repairing large bone fractures with low frequency electromagnetic fields

The healing effects of low frequency pulse electromagnetic field (EMF) on bone fractures larger than 1 cm are unsatisfactory. Three- dimensional chitosan scaffolds are designed to fill in larger bone fractures and have been shown to be osteogenic. We hypothesized that EMF could accelerate the repair process of larger bone fractures with the use of chitosan scaffolds. Chitosan (96% deacetylation) films and lyophilized scaffolds, with and without osteoblast cells, were exposed to EMF (18-30 Gauss, 75 Hz) for 2 h a day for 3 weeks. Each week, the growth and phenotype expressions of osteoblasts and properties of chitosan were examined. The hydrophilicity, Young's modulus, and biodegradability of chitosan were not altered by EMF exposure. EMF osteoblasts showed 37% higher cell proliferation, 15% lower alkaline phosphatase activity, and 74% more calcium deposition than the controls. Based on SEM photomicrographs, EMF- treated cells appeared to produce more collagen fibrils, matrix vesicles, and calcium in the extracellular matrix than the controls. In conclusion, EMF was capable of enhancing the proliferation and mineralization of osteoblasts cultured on chitosan scaffolds. (c) 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

991

Repetitive 50 Hz pulsed electromagnetic field ameliorates the diabetes-induced impairments in the relaxation response of rat thoracic aorta rings

PURPOSE: To evaluate the characteristic features of mechanical responses and the membrane potential changes induced by repetitive pulsed electromagnetic field (PEMF, 50 Hz, 5 mT) in thoracic aorta rings obtained from streptozotocin-induced diabetic and healthy control rats to determine if PEMF could ameliorate problems associated with diabetes. METHODS: Sixty male Wistar rats weighing 250-290 g were randomly divided into two experimental groups, each containing 30 animals. Streptozotocin was given via tail vein to produce diabetes mellitus (DM) in the first group rats. The second group rats were treated only with % 0.9 saline and considered as non-DM group. Both groups were also divided into two subgroups as DM + PEMF, DM + sham, PEMF and sham, each containing 15 animals. Although the DM + PEMF and PEMF groups were treated, the DM + sham and sham groups were not treated with PEMF. The PEMF treatment occurred four times daily for 30 min at 15-min intervals repeated daily for 30 days. Thoracic aorta rings from both DM and non-DM rats exposed to PEMF were evaluated for contraction and relaxation responses and membrane potential changes in the presence or absence of chemical agents that were selected to test various modes of action. RESULTS: Relaxation response of thoracic aorta rings was significantly reduced in DM than non-DM group. PEMF treatment significantly increased the relaxation response of the diabetic rings to acetylcholine, and reduced the concentration response to phenylephrine. Resting membrane potential was significantly higher in DM than in non-DM group. Inhibitors of nitric oxide (NO), both nitro-L-arginine (L-NO-ARG) and L-NO-ARG + indometacin combination, produced a significant transient hyperpolarisation in all groups. Inhibitors of potassium channel activity, charybdotoxin or apamine, produced a membrane depolarisation. However, PEMF did not induce any significant effect on the membrane potential in DM group. CONCLUSIONS: Diabetes reduced the relaxation response of thoracic aorta rings. It also affected the membrane potentials of the rings. Treatment with PEMF ameliorated the diabetes-induced impairments in the relaxation response of these rings.

992

Repetitive pulsed-train "off" duration mitigates reductions in root growth rates of Pisum sativum L. induced by 60-Hz electric field

An investigation was undertaken to define a 60-Hz electric field exposure system which would affect a eukaryotic cell system while mitigating a potential thermal rise. The biological effectiveness of pulsed 60-Hz electric fields on a cell system of defined sensitivity to continuous-wave 60-Hz electric fields was sought. Roots of garden pea (Pisum sativum L.) were exposed to pulsed trains of 60-Hz, 430 V/m electric fields. The "on" time was constant at 1 s and the "off" time varied. The repetitive on:off regimens used were 1:20, 1:50, 1:100, 1:130, 1:200, and 1:300. With continuous or 1:20 pulsed fields the growth response was equivalent (representing a 60% depression in root growth rate). The severity of the growth effect diminished as the off time increased; for the 1:100 regimen, the relative growth rate was depressed by about 30%; for the 1:300 regimen, the relative growth rate was equal to that of the controls.

993

Repetitive transcranial magnetic stimulation of the motor cortex ameliorates spasticity in multiple sclerosis.

OBJECTIVE: To investigate whether repetitive transcranial magnetic stimulation (rTMS) can modify spasticity. METHODS: We used high-frequency (5 Hz) and low-frequency (1 Hz) rTMS protocols in 19 remitting patients with relapsing-remitting multiple sclerosis and lower limb spasticity. RESULTS: A single session of 1 Hz rTMS over the leg primary motor cortex increased H/M amplitude ratio of the soleus H reflex, a reliable neurophysiologic measure of stretch reflex. Five hertz rTMS decreased H/M amplitude ratio of the soleus H reflex and increased corticospinal excitability. Single sessions did not induce any effect on spasticity. A significant improvement of lower limb spasticity was observed when rTMS applications were repeated during a 2-week period. Clinical improvement was long-lasting (at least 7 days after the end of treatment) when the patients underwent 5 Hz rTMS treatment during a 2-week protocol. No effect was obtained after a 2-week sham stimulation. CONCLUSIONS: Repetitive transcranial magnetic stimulation may improve spasticity in multiple sclerosis.

994

Resolution of dysarthria in multiple sclerosis by treatment with weak electromagnetic fields

It has been reported that 50% or more of patients diagnosed with multiple sclerosis (MS) exhibit speech impairment (dysarthria) which in some cases can be exceedingly disabling. Currently there is no effective medical treatment for the dysarthria of MS which occurs as a result of lesions to the cerebellum and its outflow tracts. It was reported recently that extracranial application of brief AC pulsed electromagnetic fields (EMFs) in the picotesla (pT) range intensity produced in patients with MS sustained improvement in motor functions including cerebellar symptomatology. This communication concerns two MS patients with a chronic progressive course who exhibited severe dysarthria which improved already during the initial treatment with pulsed EMFs and which resolved completely 3-4 weeks later. Since application of EMFs has been shown to alter: (a) the resting membrane potential and synaptic neurotransmitter release through an effect involving changes in transmembrane calcium flux; and (b) the secretion of pineal melatonin which in turn influences the synthesis and release of serotonin (5-HT) and gamma-amino butyric acid (GABA) in the cerebellum, it is suggested that the immediate improvement of the dysarthria occurred as a result of changes in cerebellar neurotransmitter functions particularly 5-HT and GABA rather than from remyelination.

995

Resolution of dysarthria in multiple sclerosis by treatment with weak electromagnetic fields.

It has been reported that 50% or more of patients diagnosed with multiple sclerosis (MS) exhibit speech impairment (dysarthria) which in some cases can be exceedingly disabling. Currently there is no effective medical treatment for the dysarthria of MS which occurs as a result of lesions to the cerebellum and its outflow tracts. It was reported recently that extracranial application of brief AC pulsed electromagnetic fields (EMFs) in the picotesla (pT) range intensity produced in patients with MS sustained improvement in motor functions including cerebellar symptomatology. This communication concerns two MS patients with a chronic progressive course who exhibited severe dysarthria which improved already during the initial treatment with pulsed EMFs and which resolved completely 3-4 weeks later. Since application of EMFs has been shown to alter: (a) the resting membrane potential and synaptic neurotransmitter release through an effect involving changes in transmembrane calcium flux; and (b) the secretion of pineal melatonin which in turn influences the synthesis and release of serotonin (5-HT) and gamma-amino butyric acid (GABA) in the cerebellum, it is suggested that the immediate improvement of the dysarthria occurred as a result of changes in cerebellar neurotransmitter functions particularly 5-HT and GABA rather than from remyelination.

996

Resolution of Lhermitte's sign in multiple sclerosis by treatment with weak electromagnetic fields

PicoTesla EMFs successfully manage MS patients with Lhermitte's sign: an electrical sensation passing down the back of the legs on flexion.

997

Resolution of Lhermitte's sign in multiple sclerosis by treatment with weak electromagnetic fields

Lhermitte's sign, the occurrence of an electrical sensation passing down the back to the legs on flexion of the neck is a common and characteristic feature of multiple sclerosis (MS) which is related to spinal cord lesions affecting the posterior columns and cervical nerve roots. The Lhermitte's sign, which has been reported to occur at some time in up to 25% of MS patients, is seldom painful but is often a cause of distress to the patient and usually a marker of increased disease activity. Treatment with extracranial picotesla range pulsed electromagnetic fields (EMFs) has been found efficacious in the management of various MS symptoms including pain syndromes. The present communication concerns three MS patients in whom two brief applications of EMFs resulted in resolution of the Lhermitte's sign which emerged during a period of exacerbation of symptoms in one patient and during a prolonged phase of symptom deterioration in the other two patients. As the cause of the Lhermitte's sign is thought to result from the spread of ectopic excitation in demyelinated plaques in the cervical and thoracic regions of the spinal cord, it is hypothesized that the effects of EMFs are related to the reduction of axonal excitability via a mechanism involving changes in ionic membrane permeability. A systemic effect on pain control systems is also postulated to occur secondary to the effects of EMFs on neurotransmitter activity and pineal melatonin functions. This report underscores the efficacy of picotesla EMFs in the management of paroxysmal pain symptoms in MS.

998

Resolution of Long-standing symptoms of multiple sclerosis by application of picoTesla range magnetic fields

this report attests to to the unique efficacy of extremely weak magnetic fields in the symptomatic treatment of patients with MS including those patients with a chronic progressive course of the disease and supports the hypothesis that dysfunction of synaptic conductivity due to neurotransmitter deficiency (specifically of serotonin) rather than demyelination underlies the neurologic deficits of the disease.

999

Resolution of longstanding symptoms of multiple sclerosis by application of picoTesla range magnetic fields

Recent clinical reports have suggested that treatment with extremely weak magnetic fields (MF) in the picoTesla range is an efficacious modality for the symptomatic therapy in patients with multiple sclerosis (MS) during the remission and exacerbation periods of the disease. The present communication concerns a 64 year old woman with a 22 year history of MS of the chronic-progressive type who presented with a longstanding history of ataxia of gait, weakness in the legs, difficulties with swallowing, loss of bladder control, blurred vision, diplopia, chronic fatigue, and cognitive impairment. In this patient two 30 minute treatments with MF on two separate days resulted in a dramatic improvement of symptoms. Specifically, the patient experienced marked improvement in balance and gait as well as increased strength in the legs to the extent that she was able to abandon the use of a walker within 48 hours after initiation of magnetic treatment. In addition, there was complete resolution of diplopia, bladder dysfunction, and fatigue with improvement in mood and cognitive functions. The report attests to the unique efficacy of extremely weak MF in the symptomatic treatment of patients with MS including those patients with a chronic progressive course of the disease and supports the hypothesis that dysfunction of synaptic conductivity due to neurotransmitter deficiency specifically of serotonin rather than demyelination underlies the neurologic deficits of the disease.

1000

Resolution of partial cataplexy in multiple sclerosis by treatment with weak electromagnetic fields

Cataplexy, an ancillary symptom of narcolepsy, involves the sudden loss of muscle tone without altered consciousness usually brought on by sudden excitement or emotional influence and extreme exertions (Guilleminault et al., 1974; Parks et al., 1974; Guilleminault, 1976; Aldrich, 1992; 1993; Scrima, 1981; Baker, 1985). Attacks of generalized cataplexy produce complete atonic, areflexic partial or complete paralysis of striated muscles commonly involving the leg muscles resulting in collapse of the knees and falling while milder forms often termed partial cataplexy may manifest by sagging of the face, eyelid, or jaw, dysarthria, blurred vision, drooping of the head, weakness of an arm or leg, buckling at the knees, or simply a momentary sensation of weakness that is imperceptible to observers (Guilleminault, 1976; Aldrich, 1993). The duration of cataplexy is usually a few seconds, although severe episodes can last several minutes and rarely several hours or days in the case of "status cataplecticus" (Parkes et al., 1974; Guilleminault, 1976; Billiard & Cadilhac, 1985; Aldrich, 1992; 1993). This report concerns a 51 year old man with chronic progressive multiple sclerosis who exhibited daily episodes of partial cataplexy which resolved within 3 weeks after he received treatment with picotesla electromagnetic fields.

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