iMRS 2000 - PEMF Publications
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PEMF Publications

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801

Noise performance of a precision pulsed electromagnet power supply for magnetic resonance imaging

Prepolarized magnetic resonance imaging (PMRI) uses two pulsed electromagnets to achieve high-field image quality with the benefits of low-field data acquisition. The principal challenge with all resistive MRI systems is the implementation of a highly precise magnet current supply. The noise current through the magnet is fundamentally limited by the current transducer used to provide feedback and the voltage reference used to generate the demand signal. Field instability in the main field magnet can both corrupt the received data and degrade the robustness of Carr inverted question markPurcell inverted question markMeiboom inverted question markGill (CPMG) echo trains, which are paramount to efficient imaging in PMRI. In this work, we present the magnet control system that achieved sufficient field stability for PMRI at $0.5/0.13$ T, identify the dominant sources of noise in the control system, examine the imaging artifacts that can occur if the field stability is insufficient, and identify how the design can be improved for better field stability, should it be required for future implementations of PMRI.

802

Non-invasive treatment of ununited fractures of the tibia using electrical stimulation

A non-invasive method of electrical stimulation of healing in ununited fractures of the tibia by pulsed magnetic fileds has been evaluated. In a series of 17 patients all but two of the fractures united within 4 to 10 months, with an average time of just under six months. The method is sufficiently promising to merit further clinical investigation.

803

Noninvasive Electromagnetic Fields on Keratinocyte Growth and Migration

BACKGROUND: Although evidence has shown that very small electrical currents produce a beneficial therapeutic result for wounds, noninvasive electromagnetic field (EMF) therapy has consisted mostly of anecdotal clinical reports, with very few well-controlled laboratory mechanistic studies. In this study, we evaluate the effects and potential mechanisms of a noninvasive EMF device on skin wound repair. MATERIALS AND METHODS: The effects of noninvasive EMF on keratinocytes and fibroblasts were assessed via proliferation and incisional wound model migration assays. cDNA microarray and RT-PCR were utilized to assess genetic expression changes in keratinocytes after noninvasive EMF treatment. RESULTS: In vitro analyses with human skin keratinocyte cultures demonstrated that noninvasive EMFs have a strong effect on accelerating keratinocyte migration and a relatively weaker effect on promoting keratinocyte proliferation. The positive effects of noninvasive EMFs on cell migration and proliferation seem keratinocyte-specific without such effects seen on dermal fibroblasts. cDNA microarray and RT-PCR performed revealed increased expression of CRK7 and HOXC8 genes in treated keratinocytes. CONCLUSIONS: This study suggests that a noninvasive EMF accelerates wound re-epithelialization through a mechanism of promoting keratinocyte migration and proliferation, possibly due to upregulation of CRK7 and HOXC8 genes.

804

Noninvasive inductive stent heating: alternative approach to prevent instent restenosis?

RATIONALE AND OBJECTIVES: To test noninvasive inductive heating of implanted vascular stents as an alternative approach for reduction or prevention of neointimal hyperplasia. METHODS: Calorimetric pretests were performed to get an orientation on the different parameters of influence for inductive heating of stents. The field strength was set to a maximum of 90 kA/m within a frequency range from 80 kHz to 320 kHz. The electromagnetic field was emitted by a custom-made water-cooled copper winding antenna. A flow model for stent heating was set up to assess the increase in temperature of an expanded 316L stainless steel stent with typical coronary stent dimensions of 3.5 mm diameter and 14.5 mm in length, and in a second setup with 4.5 mm diameter and 13 mm in length, respectively. The stent was located in a bioartificial artery, simulated by a fibrinogen matrix with a defined number of vital cells. The system was exposed to a pulsating perfusion and to an electromagnetic field of 200 kHz over a period of 20 minutes and in a second setup to an electromagnetic field of 300 kHz and increasing intensity up to maximum power-output. Afterward, the artificial vessel was sliced and examined by fluorescence microscopy to evaluate the number and location of damaged cells. RESULTS: The calorimetric tests show an exponential correlation of energy uptake in the stent with an increase in frequency and a constant generator output. At a frequency of 80 kHz, the power uptake accounts for 0.1 W (250 kHz 1.0 W; 320 kHz 1.9 W, respectively). The flow tests confirmed feasibility to elevate the stent temperature from 37 degrees C body temperature to 44 degrees C at 200 kHz within 55 seconds. The temperature increase of the fluid passing the heated vessel region was only marginal (maximum of 0.5 degrees C). Cell necrosis after 20 minutes of treatment was not observed. In a second set-up with 4.5 mm stent diameter, a frequency of 300 kHz and with maximum power output, the stent temperature was increased to 80 degrees C and there was extensive necrosis area around the stent. Treatment time and stent temperature were optimized in further tests. CONCLUSION: Selective noninvasive energy transfer to coronary stainless steel stents by inductive heating is possible within a wide range of power. By thermal conduction, vital cells close to the stent struts can be affected. The frequency of 200 kHz turned out to be favorable. There is still room for further optimization of energy dosage with regard to material and stent design, to induce controlled cell death. The method has potential to serve as an alternative approach for prevention of instent restenosis.

805

Nonpharmacologic management of osteoarthritis

Several nonpharmacologic interventions for osteoarthritis are in different stages of development, investigation, and application. Such interventions capitalize on current knowledge of the causes of symptoms, disease progression, and disability in patients with osteoarthritis. Many nonpharmacologic interventions are low in cost and incorporate self-management approaches or home-based activities and, as such, may ultimately have substantial public health impact. Recent studies and reviews of exercise, weight loss, education, inserts, footwear, bracing, therapeutic ultrasound, acupuncture, and pulsed electromagnetic field therapy will be highlighted in this review. For many of these interventions, further investigation will be necessary to define their place in the management of osteoarthritis.

806

Nonunion treatment with pulsed electromagnetic fields

Noninvasive, pulsed electromagnetic field treatment, when properly employed, was effective in securing healing of ununited fractures in 64.4% of 149 patients. The effectiveness of this modality can be ascertained after three months of intensive use in more than 85% of patients, thus enabling the clinician to decide to terminate treatment, continue electrostimulation, or abandon it in favor of another treatment modality. The success of treatment is dependent upon certain variables. Anatomic location of the nonunion is important. Higher healing rates were noted in the tibia than in the femur or humerus. In some conditions, combined electrostimulation and bone grafting was more effective than either measure alone. Young patients healed more rapidly than older patients. Electrostimulation is more effective when instituted within two years of the original fracture than when started at longer intervals after the injury. Infection, either quiescent or actively draining, does not seem to affect the overall results. Of greatest importance is patient adherence to the treatment protocol as outlined, with emphasis placed on adequate immobilization of the fracture and absolute nonweight-bearing during treatment. Considering these factors and in light of the very rare frequency of short-term side effects, the use of pulsed electromagnetic fields appears to be a reasonable choice of treatment in the management of ununited fractures.

808

Novel electromagnetic lithotriptor for upper tract stones with and without a ureteral stent

PURPOSE: We compared the treatment efficacy and safety of the novel Lithoskop electromagnetic extracorporeal shock wave lithotriptor for upper urinary tract stones with and without prior ureteral stent placement. MATERIALS AND METHODS: A total of 665 consecutive patients harboring single renal or ureteral stones underwent shock wave lithotripsy between August 2006 and July 2008. In 75 and 46 patients with renal and ureteral stones, respectively, stents were placed before the first shock wave lithotripsy session. Treatment outcome was assessed in relation to stent placement. All data were derived from a prospectively maintained database. RESULTS: The mean size of nonstented vs stented renal and ureteral stones was 8.6 vs 12.5 mm (p <0.0001) and 7.1 vs 7.3 mm (p = 0.6), respectively. The stone-free rate in nonstented vs stented renal and ureteral stone cases was 76.3% vs 77.3% and 91.4% vs 93.5%, respectively (each p >0.99). The total energy applied per stone was 110 +/- 83 vs 150 +/- 89 J (p <0.0001) and 183 +/- 131 vs 209 +/- 125 J (p = 0.1), respectively. Auxiliary measures were required after shock wave lithotripsy for renal and ureteral stones in 5.4% and 10.8% of nonstented, and in 1.3% and 4.3% of stented cases, respectively. No complications were detected in stented renal and ureteral stone cases compared to 2.9% and 6.9% in nonstented cases, respectively. CONCLUSIONS: A high success rate and a low complication rate were achieved in renal and ureteral stone cases with and without prior ureteral stent placement. Total energy needed to achieve a stone-free state did not differ between stented and nonstented ureteral cases, suggesting the absence of a significant influence of the stent. Overall stents decreased complications necessitating hospitalization and auxiliary invasive measures.

809

Novel pulsed switched power supply for a fast field cycling NMR spectrometer

In this paper, we outline the operating principles of a pulsed switched power supply for a fast field-cycling nuclear magnetic resonance spectrometer. The power supply uses a variant of a four-quadrant chopper with a duty cycle that defines the average output current. With this topology only two semiconductors are necessary to drive hundreds of amperes with an output power of several kilowatts. The output current ripple has a well-defined shape that can be reduced to acceptable values by a careful design of the semiconductors' controlling circuits and drivers. A power supply prototype was tested with a home build air-core magnet operating with fields between 0 and 0.21 T. The system is computer controlled using pulse generator and data acquisition PC cards, and specific user-friendly home-developed software. A comparative proton relaxometry study in two well-known liquid crystal compounds 5CB and MBBA was performed to check the reproducibility of the T1 measurements.

810

Nuclear translocation and DNA-binding activity of NFKB (NF-kappaB) after exposure of human monocytes to pulsed ultra-wideband electromagnetic fields (1 kV/cm) fails to transactivate kappaB-dependent gene expression

The objective of this study was to investigate whether exposure of human monocytes to a pulsed ultra-wideband electromagnetic field (EMF) of 1 kV/cm average peak power triggers a signaling pathway responsible for the transcriptional regulation of NFKB (NF-kappaB)-dependent gene expression. Human Mono Mac 6 (MM6) cells were exposed intermittently to EMF pulses for a total of 90 min. The pulse width was 0.79+/-0.01 ns and the pulse repetition rate was 250 pps. The temperature of the medium was maintained at 37 degrees C in both sham- and EMF-exposed flasks. Total NFKB DNA-binding activity was measured in the nuclear extracts by the electrophoretic mobility shift assay. Cells exposed to the EMFs and incubated for 24 h postexposure showed a 3.5+/-0.2-fold increase in the NFKB DNA-binding activity. Since activation of NFKB was observed, the possibility of kappaB-dependent gene expression in response to exposure to the EMFs was investigated using NFKB signal-specific gene arrays. The results revealed no difference in the NFKB-dependent gene expression profiles at 8 or 24 h postexposure, indicating that activated NFKB does not lead to the differential expression of kappaB-dependent target genes. To determine whether the absence of the kappaB-dependent gene expression was due to compromised transcriptional regulation of NFKB, the functional activity of NFKB was examined in cells transiently transfected with Mercury Pathway constructs containing 4x NFKB binding sites associated either with the luciferase reporter system or a control vector. Pulsed EMF exposure did not induce NFKB-driven luciferase activity in these cells, indicating that the activation of NFKB at 24 h after the 1 kV/cm EMF exposure is functionally inactive. From these results, it is clear that the EMF-induced NFKB activation is only a transient response, with minimal or no downstream effect.

811

Null orbital frustration at the pseudogap boundary in a layered cuprate superconductor

We assess the relative importance of orbital frustration at the pseudogap closing field H(pg). Using interlayer tunneling transport in pulsed magnetic fields nearly up to 60 T, we track the field-temperature (H-T) phase diagram for fields parallel ( parallel ab) and normal ( parallel c) to the layered structure of Bi(2)Sr(2)CaCu(2)O(8+y). In contrast to large orientational anisotropy of the superconducting state related to the orbital motion of Cooper pairs, we find anisotropy of H(pg) temperature independent and small, due solely to the g factor. The obtained Zeeman relation with the pseudogap temperature T small star, filled, g( parallel c)micro(B)H( parallel c)(pg)=g( parallel ab)micro(B)H( parallel ab)(pg) approximately k(B)T small star, filled, is fully consistent with the correlations only in the spin channel.

812

Numerical evaluation of radio frequency power deposition in human models during MRI

Concerns have been expressed about safety of MRI examination of two groups of people, namely pregnant mothers and cardiac pacemaker bearers. The main uncertainty relates to excessive heating by pulsed radio frequency (RF) fields. To address these issues, numerical evaluations of the power deposition are performed for a 27-week old fetus in a simplified model of the mother, and a realistic model of a human torso with an in situ pacemaker including its leads. The evaluations are supplemented with organ dosimetry for a realistic model of the human torso. An ideal non-resonant and two resonant birdcage coils operating at 64 MHz (corresponding to 1.5 T MRI) are evaluated. All simulations are performed with the finite difference time domain (FDTD) method.

813

Numerical field evaluation of healthcare workers when bending towards high-field MRI magnets

In MRI, healthcare workers may be exposed to strong static and dynamic magnetic fields outside of the imager. Body motion through the strong, non-uniform static magnetic field generated by the main superconducting magnet and exposure to gradient-pulsed magnetic fields can result in the induction of electric fields and current densities in the tissue. The interaction of these fields and occupational workers has attracted an increasing awareness. To protect occupational workers from overexposure, the member states of the European Union are required to incorporate the Physical Agents Directive (PAD) 2004/40/EC into their legislation. This study presents numerical evaluations of electric fields and current densities in anatomically equivalent male and female human models (healthcare workers) as they lean towards the bores of three superconducting magnet models (1.5, 4, and 7 T) and x-, y-, and z- gradient coils. The combined effect of the 1.5 T superconducting magnet and the three gradient coils on the body models is compared with the contributions of the magnet and gradient coils in separation. The simulation results indicate that it is possible to induce field quantities of physiological significance, especially when the MRI operator is bending close towards the main magnet and all three gradient coils are switched simultaneously.

814

Numerical simulation of thermal disposition with induction heating used for oncological hyperthermic treatment

Hyperthermia plays an important role in oncological therapies, most often being used in combination with radiotherapy, chemotherapy and immunotherapy. The success of this therapy is strongly dependent on the precision and control of thermal deposition. Hyperthermia based on induction heating, with thermally self-regulating thermoseeds inserted into the tumorous mass, is used for interstitial treatment. The technique was the subject of the numerical study presented in the paper. The analysis was carried out using coupled electromagnetic heating and thermo-fluid dynamic FEM simulations. During thermal deposition by induction heating of inserted seeds, the simulations estimated the thermal field inside and outside the tumour, as well as the sensitivity of the thermal field to variations regarding seed temperature, configuration and proximity to vessels. The method, for which accurate anatomical patient's information is essential, is suitable for providing useful qualitative and quantitative information about thermal transients and power density distribution for hyperthermic treatment. Several grid steps were analysed and compared. A 1 cm seed grid was resulted in good homogeneity and effectiveness of the thermal deposition. The cold spot effect caused by large vessels was demonstrated and quantified. Simulations of the heating of a tumorous mass in the liver showed that an indcutor generator operating at 200 kHz frequency and 500 A current, producing a pulsating magnetic field of H = 60 A cm(-1), was adequate for the treatment. The seeds that perform best among those tested (Nicu (28% Cu), PdNi (27.2% Ni), PdCo (6.15% Co) and ferrite core) were the PdNi (1 mm radius, 10 mm length), as they have a low Curie temperature (52 degrees C), which is the closest to the desired treatment temperature and thus reduces the risk of hot spots.

815

Observations of electromagnetic fields and plasma flow in hohlraums with proton radiography

We report on the first proton radiography of laser-irradiated hohlraums. This experiment, with vacuum gold (Au) hohlraums, resulted in observations of self-generated magnetic fields with peak values approximately 10;{6} G. Time-gated radiographs of monoenergetic protons with discrete energies (15.0 and 3.3 MeV) reveal dynamic pictures of field structures and plasma flow. Near the end of the 1-ns laser drive, a stagnating Au plasma (approximately 10 mg cm;{-3}) forms at the center of the hohlraum. This is a consequence of supersonic, radially directed Au jets (approximately 1000 microm ns;{-1}, approximately Mach 4) that arise from the interaction of laser-driven plasma bubbles expanding into one another.

816

Occupational exposure to ambient electromagnetic fields of technical operational personnel working for a mobile telephone operator

In order to investigate the exposure of operational personnel to radiofrequency electromagnetic fields when working for a mobile telephone operator, exposimeters were used to make individual records on 23 Technical Operations personnel (mobile telephone maintenance staff) and also on 22 Other Workers. The exposure densities, to which each of the 45 subjects was subjected, were quantified using 229 exposure indicators. Cluster analysis techniques were applied to the data, in an attempt to show that they would re-emerge as belonging to one of the two groups, i.e. the Technical Operational Personnel group or the Other Workers group. This exploratory investigation has shown that the cluster analysis does not reveal a sufficiently reliable emergence of the two groups, even though certain exposure indicators were significantly different for the two groups. In addition, the use of a Learning Group method does not lead to the discovery of a predictive law that could identify the Technical Operational Personnel as a sub-group within the overall group.

817

On Cu(II)-Cu(II) distance measurements using pulsed electron electron double resonance

The effects of orientational selectivity on the 4-pulse electron electron double resonance (PELDOR) ESR spectra of coupled Cu(II)-Cu(II) spins are presented. The data were collected at four magnetic fields on a poly-proline peptide containing two Cu(II) centers. The Cu(II)-PELDOR spectra of this peptide do not change appreciably with magnetic field at X-band. The data were analyzed by adapting the theory of Maryasov, Tsvetkov, and Raap [A.G. Maryasov, Y.D. Tsvetkov, J. Raap, Weakly coupled radical pairs in solids:ELDOR in ESE structure studies, Appl. Magn. Reson. 14 (1998) 101-113]. Simulations indicate that orientational effects are important for Cu(II)-PELDOR. Based on simulations, the field-independence of the PELDOR data for this peptide is likely due to two effects. First, for this peptide, the Cu(II) g-tensor(s) are in a very specific orientation with respect to the interspin vector. Second, the flexibility of the peptide washes out the orientation effects. These effects reduce the suitability of the poly-proline based peptide as a good model system to experimentally probe orientational effects in such experiments. An average Cu(II)-Cu(II) distance of 2.1-2.2 nm was determined, which is consistent with earlier double quantum coherence ESR results.

818

Optical pulsations from the anomalous X-ray pulsar 4U0142+61

Anomalous X-ray pulsars (AXPs) differ from ordinary radio pulsars in that their X-ray luminosity is orders of magnitude greater than their rate of rotational energy loss, and so they require an additional energy source. One possibility is that AXPs are highly magnetized neuron stars or 'magnetars' having surface magnetic fields greater than 10(14) G. This would make them similar to the soft gamma-ray repeaters (SGRs), but alternative models that do not require extreme magnetic fields also exist. An optical counterpart to the AXP 4U0142+61 was recently discovered, consistent with emission from a magnetar, but also from a magnetized hot white dwarf, or an accreting isolated neutron star. Here we report the detection of optical pulsations from 4U0142+61. The pulsed fraction of optical light (27 per cent) is five to ten times greater than that of soft X-rays, from which we conclude that 4U0142+61 is a magnetar. Although this establishes a direct relationship between AXPs and the soft gamma-ray repeaters, the evolutionary connection between AXPs, SGRs and radio pulsars remains controversial.

819

Optical pump-probe measurements of local nuclear spin coherence in semiconductor quantum wells

We demonstrate local manipulation and detection of nuclear spin coherence in semiconductor quantum wells by an optical pump-probe technique combined with pulse rf NMR. The Larmor precession of photoexcited electron spins is monitored by time-resolved Kerr rotation (TRKR) as a measure of nuclear magnetic field. Under the irradiation of resonant pulsed rf magnetic fields, Rabi oscillations of nuclear spins are traced by TRKR signals. The intrinsic coherence time evaluated by a spin-echo technique reveals the dependence on the orientation of the magnetic field with respect to the crystalline axis as expected by the nearest neighbor dipole-dipole interaction.

820

Optimization of electric field parameters for the control of bone remodeling: exploitation of an indigenous mechanism for the prevention of osteopenia

The discovery of piezoelectric potentials in loaded bone was instrumental in developing a plausible mechanism by which functional activity could intrinsically influence the tissue's cellular environment and thus affect skeletal mass and morphology. Using an in vivo model of osteopenia, we have demonstrated that the bone resorption that normally parallels disuse can be prevented or even reversed by the exogenous induction of electric fields. Importantly, the manner of the response (i.e., formation, turnover, resorption) is exceedingly sensitive to subtle changes in electric field parameters. Fields below 10 microV/cm, when induced at frequencies between 50 and 150 Hz for 1 h/day, were sufficient to maintain bone mass even in the absence of function. Reducing the frequency to 15 Hz made the field extremely osteogenic. Indeed, this frequency-specific sinusoidal field initiated more new bone formation than a more complex pulsed electromagnetic field (PEMF), though inducing only 0.1% of the electrical energy of the PEMF. The frequencies and field intensities most effective in the exogenous stimulation of bone formation are similar to those produced by normal functional activity. This lends strong support to the hypothesis that endogenous electric fields serve as a critical regulatory factor in both bone modeling and remodeling processes. Delineation of the field parameters most effective in retaining or promoting bone mass will accelerate the development of electricity as a unique and site-specific prophylaxis for osteopenia. Because fields of these frequencies and intensities are indigenous to bone tissue, it further suggests that such exogenous treatment can promote bone quantity and quality with minimal risk or consequence.

821

Optimization of pulsed electromagnetic field therapy for management of arthritis in rats

Studies were undertaken to find out the effects of low frequency pulsed electromagnetic field (PEMF) in adjuvant induced arthritis (AIA) in rats, a widely used model for screening potential therapies for rheumatoid arthritis (RA). AIA was induced by an intradermal injection of a suspension of heat killed Mycobacterium tuberculosis (500 mug/0.1 ml) into the right hind paw of male Wistar rats. This resulted in swelling, loss of body weight, increase in paw volume as well as the activity of lysosomal enzymes viz., acid phosphatase, cathepsin D, and beta-glucuronidase and significant radiological and histological changes. PEMF therapy for arthritis involved optimization of three significant factors, viz., frequency, intensity, and duration; and the waveform used is sinusoidal. The use of factorial design in lieu of conventional method resulted in the development of an ideal combination of these factors. PEMF was applied using a Fransleau-Braunbeck coil system. A magnetic field of 5 Hz x 4 muT x 90 min was found to be optimal in lowering the paw edema volume and decreasing the activity of lysosomal enzymes. Soft tissue swelling was shown to be reduced as evidenced by radiology. Histological studies confirmed reduction in inflammatory cells infiltration, hyperplasia, and hypertrophy of cells lining synovial membrane. PEMF was also shown to have a membrane stabilizing action by significantly inhibiting the rate of release of beta-glucuronidase from lysosomal rich and sub-cellular fractions. The results indicated that PEMF could be developed as a potential therapy in the treatment of arthritis in humans.

822

Optimizing the hyperpolarizability tensor using external electromagnetic fields and nuclear placement

We investigate the effects of an external electric and magnetic field on the first hyperpolarizability tensor of a quantum system, such as a molecule or nanoparticle, whose nonlinear response is well below the fundamental limit. We find that the intrinsic hyperpolarizability is optimized when the applied electric and magnetic fields are comparable to the internal molecular fields. Indeed, the nonlinear response is just as large for an electron in the presence of the external field without the nuclei as it is for an electron bound to a molecule and in the presence of the applied field. We find that all combinations of fields and molecular structures that optimize the largest diagonal component of the intrinsic hyperpolarizability share the same universal properties: The three-level ansatz is obeyed, the normalized transition moment to the dominant state is about 0.76, the ratio of the two dominant excited state energies is about 0.48, the electron density tends toward being one-dimensional, and the intrinsic hyperpolarizability is less than 0.71. Thus, strategies for optimizing the hyperpolarizability should focus on ways to achieve these universal properties. On the other hand, when beta(xxy) is optimized, the three level ansatz appears to hold for a pair of degenerate states. In this case, the energy ratio between the pairs of degenerate states is 0.42 and the normalized transition moment to the pair of dominant states is 0.87. Most importantly, the intrinsic hyperpolarizability is 0.9, the largest ever calculated for a system described by a potential energy function.

823

Orientation of the catfish in uniform and nonuniform electric fields

The ability of the catfish to orient itself according to the direction and density gradient of current was studied in behavioral experiments. The catfish was shown to possess directional sensitivity of up to 20 degrees in orientation according to the direction of an electric field. The orientational behavior was manifested at a current density of 1.5 X 10(-11) A/mm2 and a specific resistance of the water equal to 15 omega . m and is maintained on replacement of a constant current by pulsed current. In a nonuniform field, the fish were shown to be capable of orienting themselves according to the gradient of current density with a threshold value of 3.6 X 10(-12) per mm. The functional significance of the electrosensory system of the catfish is discussed.

824

Orthopedic prosthesis fixation

The fixation of orthopedic implants has been one of the most difficult and challenging problems. The fixation can be achieved via: (a) direct mechanical fixation using screws, pins, wires, etc.; (b) passive or interference mechanical fixation where the implants are allowed to move or merely positioned onto the tissue surfaces; (c) bone cement fixation which is actually a grouting material; (d) biological fixation by allowing tissues to grow into the interstices of pores or textured surfaces of implants; (e) direct chemical bonding between implant and tissues; or (f) any combination of the above techniques. This article is concerned with various fixation techniques including the potential use of electrical, pulsed electromagnetic field, chemical stimulation using calcium phosphates for the enhancement of tissue ingrowth, direct bonding with bone by glass-ceramics and resorbable particle impregnated bone cement to take advantages of both the immediate fixation offered by the bone cement and long term fixation due to tissue ingrowth.

825

Osteonecrosis of the femoral head treated by pulsed electromagnetic fields (PEMFs): a preliminary report

This has been a preliminary report with a short-term follow-up of a small number of observations (28 hips of 24 patients). The follow-ups ranged from 6 to 36 months, with an average of 17.8 months. Only eleven hips (in eleven patients) were followed an average of 8 months after cessation of the treatment. It should be emphasized that this was a "pilot" study, in which no control series was used to determine the natural course of the disease in a comparable clinical setting. Of note was the pain relief, in 19 of 23 patients with moderate to severe pretreatment pain. Also there was an improved function, which suggests that at least in approximately two thirds of the patients there was some clinical benefit from this mode of treatment. In eight hips, clinical conditions did not change; and in two they worsened, requiring further treatment. Eighteen remaining hips were thought to have been benefited by the treatment. Six femoral heads that had already developed varying degrees of collapse (Ficat Type III) collapsed further (1 to 2 mm), and two round heads (Ficat II) progressed to off-round (Ficat III). This preliminary study suggests that further exploration of pulsed electromagnetic fields (PEMFs) is warranted in the treatment of osteonecrosis of the femoral head.

826

Outcomes after posterolateral lumbar fusion with instrumentation in patients treated with adjunctive pulsed electromagnetic field stimulation

Fusion success and clinical outcome were determined in 48 high-risk patients who underwent posterolateral lumbar fusions with internal fixation and were treated with adjunctive pulsed electromagnetic field (PEMF) stimulation postoperatively. An independent radiographic assessment demonstrated a success rate of 97.9%. Following treatment, 59% of the working patients returned to their employment. Overall clinical assessment was excellent in 4.2% of patients, good in 79.2%, and fair in 16.7%; no patient had a poor clinical assessment.

827

Outlook for the use of focused shock waves and pulsed electric fields in the complex treatment of malignant neoplasms

The experimental studies the synchronous action of electric field microsecond range with amplitude within the range of 1-7 kV/sm and shock waves with pressure before 100 MPa on cells membrane permeability of the mouse's ascitic tumors in vitro have shown the intensification the efficiency of the forming the irreversible pores under synchronous action. Thereby, enabling the electric field in the compression phase of shock wave pulse which can essentially reduce the electric field intensity required for breakdown cell membrane. In usual condition at amplitude of electric field, specified above, electric breakdown membrane carries basically reversible nature. At the same time in the pressure field tension phase of shock-wave pulse reversible pores, created by electric field, can grow before sizes, under which wholeness membrane is not restored. Under simultaneous action on cellular suspension the shock wave and electric field with moderate intensity cells survival is reduced in 5 once in contrast with occuring at different time's action, and in 10 once in contrast with checking. The most sensitive to influence by under study fields are cells in phase of the syntheses DNA, preparation to fission and in phase of the mitosis. Thereby, continuation of the studies on use synchronous action shock waves and pulsed electric fields in complex treatment of the tumors introduces perspective.

828

Overcoming electromagnetic interference by LVADs on ICD function by shielding the ICD programmer wand and extension cable

Patients with end-stage cardiomyopathy and congestive heart failure are increasingly undergoing implantation with left ventricular assist devices (LVADs). In addition, implantable cardioverter-defibrillator (ICD) therapy has been proven to be an important part of the treatment for cardiomyopathy/congestive heart failure. Previous reports have noted a potential and dramatic electromagnetic interference from LVADs on ICDs that cause impaired telemetry communication between the ICD and ICD programmer. Such interference has necessitated explantation and generator replacement in order to resume communication between the ICD and programmer. We report two patients with advanced congestive heart failure and ICD programming impairment caused by a HeartMate II LVAD (Thoratec Corporation, Pleasanton, CA, USA) that was overcome by placing aluminum shielding around the ICD programmer wand and steel shielding around the extension cable during ICD interrogation.

830

Parkinsonian micrographia reversed by treatment with weak electromagnetic fields

Micrographia is one of the characteristic clinical signs of Parkinson's disease (PD) which is linked to striatal dopaminergic deficiency. It has been reported recently that external application of weak electromagnetic fields (EMFs) in the picotesla (pT) range and of low frequency produced dramatic improvements in motor symptoms in Parkinsonian patients indicating that a specific range of electromagnetic energy increases, among others, striatal dopaminergic neurotransmission. In the present communication, I present two fully mediated Parkinsonian patients who, prior to the application of EMFs, drew lilliputian sized figures reflecting the micrographia of the disease. In both patients a series of treatments with pT EMFs produced, in addition to improvement in motor symptoms, a dramatic increase in the size of their drawings with reversal of their micrographia. Since both patients were maintained on dopaminergic medications prior to and during treatment with EMFs it is suggested that Parkinsonian micrographia is related also to abnormalities of nondopaminergic systems which are affected by weak EMFs. This report corroborates previous observations demonstrating the powerful antiParkinsonian effect of pT range EMFs and highlights the unique efficacy of this treatment modality in Parkinsonism.

831

Paroxysmal itching in multiple sclerosis during treatment with external magnetic fields

Paroxysmal attacks of itching constitute a rare sensory symptom of multiple sclerosis (MS). It is generally thought that paroxysmal itching, a form of subthreshold pain sensation, is caused by transversely spreading ephaptic activation (i.e., activation via an artificial synapse) of axons within a partially demyelinated lesion in fiber tracts in the CNS, most commonly in the spinal cord. In MS, attacks of paroxysmal itching have been reported to occur either as the initial symptom of the disease or at the onset of an acute relapse. I present two female MS patients aged 36 and 40 years in whom paroxysmal itching was a prominent sensory symptom which occurred at the onset of treatment with external picoTesla range magnetic fields (MF) and coincident with the process of neurologic recovery. This report suggests that picoTesla range MF may cause activation of neuronal transmission along partially demyelinated axons of pain conduction in the spinal cord. The occurrence of rapid neurologic recovery with initiation of treatment with MF supports the notion that impaired synaptic conductivity rather than demyelination underlies some of the neurologic deficits of MS.

832

Partial-body exposure of human volunteers to 2450 MHz pulsed or CW fields provokes similar thermoregulatory responses

Many reports describe data showing that continuous wave (CW) and pulsed (PW) radiofrequency (RF) fields, at the same frequency and average power density (PD), yield similar response changes in the exposed organism. During whole-body exposure of squirrel monkeys at 2450 MHz CW and PW fields, heat production and heat loss responses were nearly identical. To explore this question in humans, we exposed two different groups of volunteers to 2450 MHz CW (two females, five males) and PW (65 micros pulse width, 10(4) pps; three females, three males) RF fields. We measured thermophysiological responses of heat production and heat loss (esophageal and six skin temperatures, metabolic heat production, local skin blood flow, and local sweat rate) under a standardized protocol (30 min baseline, 45 min RF or sham exposure, 10 min baseline), conducted in three ambient temperatures (T(a) = 24, 28, and 31 degrees C). At each T(a), average PDs studied were 0, 27, and 35 mW/cm2 (Specific absorption rate (SAR) = 0, 5.94, and 7.7 W/kg). Mean data for each group showed minimal changes in core temperature and metabolic heat production for all test conditions and no reliable differences between CW and PW exposure. Local skin temperatures showed similar trends for CW and PW exposure that were PD-dependent; only the skin temperature of the upper back (facing the antenna) showed a reliably greater increase (P =.005) during PW exposure than during CW exposure. Local sweat rate and skin blood flow were both T(a)- and PD-dependent and showed greater variability than other measures between CW and PW exposures; this variability was attributable primarily to the characteristics of the two subject groups. With one noted exception, no clear evidence for a differential response to CW and PW fields was found.

833

PEMF as treatment for delayed healing of foot and ankle arthrodesis

BACKGROUND: Arthrodesis is the most common surgical treatment for foot and ankle arthritis. In adults, these procedures are associated with a 5% to 10% rate of nonunion. Pulsed electromagnetic field (PEMF) stimulation was approved by the Federal Drug Administration (FDA) for treatment of delayed unions after long-bone fractures and joint arthrodesis. The purpose of this study was to examine the results of PEMF treatment for delayed healing after foot and ankle arthrodesis. METHODS: Three hundred and thirty-four foot and ankle arthrodeses were done. Nineteen resulted in delayed unions that were treated with a protocol of immobilization, limited weightbearing, and PEMF stimulation for a median of 7 (range 5 to 27) months. All patients were followed clinically and radiographically. RESULTS: The use of PEMF, immobilization, and limited weightbearing to treat delayed union after foot and ankle arthrodesis was successful in 5 of 19 (26%) patients. Of the other 14 patients with nonunions, nine had revision surgery with autogenous grafting, continued immobilization, and PEMF stimulation. Seven of these eventually healed at a median of 5.5 (range 2 to 26) months and two did not heal. One patient had a below-knee amputation, and four refused further treatment. CONCLUSIONS: The protocol of PEMF, immobilization, and limited weightbearing had a relatively low success rate in this group of patients. We no longer use this protocol alone to treat delayed union after foot and ankle arthrodesis.

834

Perception of the electromagnetic field emitted by a mobile phone

Electromagnetic sensibility refers to the ability to perceive the electromagnetic field (EMF) without necessarily developing health symptoms attributed to EMF exposure. A large sample of young healthy adults (n = 84) performed two forced-choice tasks on the perception of the GSM mobile phone EMF (902 MHz pulsed at 217 Hz), "Was the field on?" and "Did the field change?" (3 conditions x 100 trials for each task, n = 600 trials in total). A monetary prize was announced for good performance (correct response rate > or =75%, n = 600 trials). The performance was no better than expected by chance, and thus none of the participants won the prize. Two participants showed extraordinary performance in one of the task conditions ("Was the field on?", n = 100 trials), with correct response rates of 97% (P = 1.28 x 10(-25)) and 94% (P = 9.40 x 10(-22)), but they failed to replicate the result in the retest of six blocks of the same condition 1 month later. Six participants had reported being able to perceive the mobile phone EMF in the preliminary inquiry, but they performed no better than the others. This study provides empirical evidence against the existence of electromagnetic sensibility to the mobile phone EMF, demonstrating the necessity for replication in EMF studies.

835

Peripheral nerve stimulation by induced electric currents: exposure to time-varying magnetic fields

The review evaluates thresholds of peripheral nerve stimulation by complex current waveforms. A neuroelectric model employing Frankenhaeuser-Huxley membrane nonlinearities is used to derive excitation thresholds for monophasic and biphasic pulse sequences, as well as sinusoidal stimuli. The model, along with principles of magnetic field induction, is used to derive criteria of acceptability for exposure to time-varying magnetic fields. Applications to pulsed gradient fields from magnetic resonance imaging devices are discussed.

836

Phenomenological local field enhancement factor distributions around electromagnetic hot spots

We propose a general phenomenological description of the enhancement factor distribution for surface-enhanced Raman scattering (SERS) and other related phenomena exploiting large local field enhancements at hot spots. This description extends naturally the particular case of a single (fixed) hot spot, and it is expected to be "universal" for many classes of common SERS substrates containing a collection of electromagnetic hot spots with varying geometrical parameters. We further justify it from calculations with generalized Mie theory. The description studied here provides a useful starting point for a qualitative (and semiquantitative) understanding of experimental data and, in particular, the analysis of the statistics of single-molecule SERS events.

837

Phenotypic comparison between mesothelial and microvascular endothelial cell lineages using conventional endothelial cell markers, cytoskeletal protein markers and in vitro assays of angiogenic potential

Endothelial and mesothelial cells are mesodermally derived simple squamous epithelial cells. A controversy concerning the ontogenetic origin of neoplasms derived from these cell types, commonly cited in the literature, is whether Kaposi's sarcoma is a mesothelioma or an angioma. To assess the similarities and differences between these cell types, pulmonary microvascular endothelial cells (PMVEC) and pericardial mesothelial cells (PMC) were cultured in vitro. PMVEC and PMC were found to be difficult to distinguish from one another by histological criteria alone. Both cell types formed contact-inhibited, and 'cobblestone', monolayers typical of simple epithelial cells. PMVEC and PMC demonstrated positive immunoreactivity to Factor VIII-related antigen and angiotensin-converting enzyme (ACE) antigen. They also showed uptake of 1,1'-dioctacecyl-1,3,3,3',3-tetramethyl-indocarbocyanine perchlorate acetylated low density lipoprotein (DiI-Ac-LDL) in 4 h. Both PMVEC and PMC expressed low ACE activities when compared to macrovessel endothelial cells. PMVEC and PMC shared similar isoform profiles for vimentin and actin. Both cell types expressed the simple epithelial keratins, cytokeratins 8 and 19, though PMC contained 50% more cytokeratins than PMVEC. Additionally, PMC contained cytokeratin 18, an intermediate filament protein not detectable in PMVEC. PMC formed 15 times as many epithelial ringlets or "stomata" as PMVEC. PMVEC but not PMC could be induced in vitro to differentiate into branching tube-like structures in response to their culture environment. Reorganization of PMVEC into vessel-like structures was more rapid and complete than PMC when embedded in three-dimensional collagen I lattices, cultured on Matrigel or exposed to a shaped-pulsed electromagnetic field. The angiogenic response of PMVEC to specialized culture conditions in vitro may reflect their phenotypic differentiation state characterized by anastomosing vascular structures in vivo, whereas PMC remain differentiated into monolayer sheet-like structures.

838

Photodynamic effect on cancer cells influenced by electromagnetic fields

The synergism of low-frequency electromagnetic field treatment and photodynamic effect on killing of human cancer cells is presented. The weak pulsating electromagnetic field (PEMF) generated by Helmholtz coils in the mT range influences the permeability of cell membranes for photosensitizers. Several types of sensitizers were excited by visible light during incorporation without and with two kinds of PEMF treatment. In the first part suitable photosensitizers were selected in the absorption range between 400 and 700 nm against human myeloid leukaemia K562 and human histiocytic lymphoma U937 cells by treatment of PEMF consisting of rectangular pulse groups. In the second part amplitude and frequency dependencies were measured using sinuous PEMF and white light with the result that after 12 min the PEMF treatment enhanced photodynamic effectivity by more than 40% over the control value. Taking into account the influence of many parameters, an additional optimization will be possible by photodynamic PEMF synergism for an increased drug delivery in general.

839

Physical and physiological specification of magnetic pulse stimuli that produce cortical damage in rats

The effects of transcranial magnetic pulse stimuli on the brain tissue of rats were examined. In Experiment I, 52 male albino rats received pulsed magnetic stimulation of the head. Stimulus intensity, number of stimulations, stimulated sites, and interval between last stimulation and sacrifice for neuropathological examination were varied. High stimulus intensity (2.8 T) and 100 or more stimulations produced clearly defined microvacuolar changes in the neuropil portion of cortical layers 2-6 (especially layers 3 and 4) in 12 of 24 animals. Fewer stimulations and lower intensities produced no such effects in 28 rats given that stimulation. Midline stimulation and stimulation over the left hemisphere produced similar results. No other brain, ocular, or spinal structures manifested such changes. Lesions were present in animals that had intervals up to 30 days between the last stimulation and perfusion. In Experiment II with 18 animals, compound motor action potentials (CMAPs) evoked by magnetic stimulation of the cortical motor area and recorded from the right lower extremity were examined. The electromyographic threshold was 0.83 T. Further increases in stimulus intensity produced increases in CMAP amplitude, up to approximately 1.9 T. It was noted that the lesion-producing intensity (2.8 T) was 0.9 T greater than the intensity needed for near-asymptotic reactions and was 3.4 times the CMAP threshold value.

840

Physical source realization of complex source pulsed beams

Complex source pulsed beams (CSPB) are exact wave-packet solutions of the time-dependent wave equation that are modeled mathematically in terms of radiation from a pulsed point source located at a complex space-time coordinate. In the present paper, the physical source realization of the CSPB is explored. This is done in the framework of the acoustic field, as a concrete physical example, but a similar analysis can be applied for electromagnetic CSPB. The physical realization of the CSPB is addressed by deriving exact expressions for the acoustic source distribution in the real coordinate space that generates the CSPB, and by exploring the power and energy flux near these sources. The exact source distribution is of finite support. Special emphasis is placed on deriving simplified source functions and parametrization for the special case where the CSPB are well collimated.

841

Physician perceptions of the value of physical modalities in the treatment of musculoskeletal disease

We randomly surveyed 100 specialists in rehabilitation medicine and 100 rheumatologists concerning their perceptions of the value of 11 different physical modalities--cold, active and passive exercise, interferential current, laser, magnetotherapy, microwave, shortwave diathermy, traction, ultrasound and transcutaneous nerve stimulation in the treatment of seven different musculoskeletal conditions--acute arthritis, joint contracture, neck pain, back pain, tendinitis, reflex sympathetic dystrophy and frozen shoulder. There were significant differences in the perceived benefits of modalities which varied by modality and condition. Overall, rehabilitation medicine specialists regarded modalities to be helpful more often than rheumatologists (P < 0.001).

842

Physics models of centriole replication

Our previous pre-clinic experimental results have showed that the epithelialization can be enhanced by the externally applied rectangular pulsed electrical current stimulation (RPECS). The results are clinically significant for patients, especially for those difficult patients whose skin wounds need long periods to heal. However, the results also raise questions: How does the RPECS accelerate the epithelium cell proliferation? To answer these questions, we have previously developed several models for animal cells, in a view of physics, to explain mechanisms of mitosis and cytokinesis at a cellular level, and separation of nucleotide sequences and the unwinding of a double helix during DNA replication at a bio-molecular level. In this paper, we further model the mechanism of centriole replication during a natural and normal mitosis and cytokinesis to explore the mechanism of epithelialization enhanced with the externally applied RPECS at a bio-molecular level. Our models suggest: (1) Centriole replication is an information flowing. The direction of the information flowing is from centrioles to centrioles based on a cylindrical template of 9 x 3 protein microtubules (MTs) pattern. (2) A spontaneous and strong electromagnetic field (EMF) force is a pushing force that separates a mother and a daughter centrioles in centrosomes or in cells, while a pulling force of interacting fibers and pericentriolar materials delivers new babies. The newly born babies inherit the pattern information from their mother(s) and grow using microtubule fragments that come through the centrosome pores. A daughter centriole is always born and grows along stronger EMF. The EMF mostly determines centrioles positions and plays key role in centriole replication. We also hypothesize that the normal centriole replication could not been disturbed in centrosome in the epithelium cells by our RPECS, because the centrioles have two non-conducting envelope (cell and centrosome membranes), that protect the normal duplication. The induced electric field by externally applied RPECS could be mild compared with the spontaneous and natural electric field of the centrioles. Therefore, the centriole replication during the epithelium cellular proliferation may be directly, as well as indirectly (e.g., somatic reflex) accelerated by the RPECS.

843

Physiologic effects of intense MR imaging gradient fields

The strength duration relationship for peripheral nerve stimulation by MR imaging pulsed gradient magnetic fields was measured in 84 human subjects. The data were fitted to the hyperbolic strength-duration relationship: dB/dt=b(1 + c/d), where b is rheobase, c is chronaxie, and d is duration, and dB/dt is reported as the maximal value on the axis of the bore. For sensation threshold, average (b,c) (15 T/s, 0.37 ms) for the y-gradient and (26 T/s, 0.38 ms) for the z-gradient coil. The dB/dt intensity to induce a sensation which the subject described as uncomfortable was about 50% above the sensation threshold. Experiments with dogs showed that the cardiac stimulation by pulsed magnetic gradient fields is exceedingly unlikely.

844

Physiotherapy interventions for shoulder pain

BACKGROUND: The prevalence of shoulder disorders has been reported to range from seven to 36% of the population (Lundberg 1969) accounting for 1.2% of all General Practitioner encounters in Australia (Bridges Webb 1992). Substantial disability and significant morbidity can result from shoulder disorders. While many treatments have been employed in the treatment of shoulder disorders, few have been proven in randomised controlled trials. Physiotherapy is often the first line of management for shoulder pain and to date its efficacy has not been established. This review is one in a series of reviews of varying interventions for shoulder disorders, updated from an earlier Cochrane review of all interventions for shoulder disorder. OBJECTIVES: To determine the efficacy of physiotherapy interventions for disorders resulting in pain, stiffness and/or disability of the shoulder. SEARCH STRATEGY: MEDLINE, EMBASE, the Cochrane Clinical Trials Regiter and CINAHL were searched 1966 to June 2002. The Cochrane Musculoskeletal Review Group's search strategy was used and key words gained from previous reviews and all relevant articles were used as text terms in the search. SELECTION CRITERIA: Each identified study was assessed for possible inclusion by two independent reviewers. The determinants for inclusion were that the trial be of an intervention generally delivered by a physiotherapist, that treatment allocation was randomised; and that the study population be suffering from a shoulder disorder, excluding trauma and systemic inflammatory diseases such as rheumatoid arthritis. DATA COLLECTION AND ANALYSIS: The methodological quality of the included trials was assessed by two independent reviewers according to a list of predetermined criteria, which were based on the PEDro scale specifically designed for the assessment of validity of trials of physiotherapy interventions. Outcome data was extracted and entered into Revman 4.1. Means and standard deviations for continuous outcomes and number of events for binary outcomes were extracted where available from the published reports. All standard errors of the mean were converted to standard deviation. For trials where the required data was not reported or not able to be calculated, further details were requested from first authors. If no further details were provided, the trial was included in the review and fully described, but not included in the meta-analysis. Results were presented for each diagnostic sub group (rotator cuff disease, adhesive capsulitis, anterior instability etc) and, where possible, combined in meta-analysis to give a treatment effect across all trials. MAIN RESULTS: Twenty six trials met inclusion criteria. Methodological quality was variable and trial populations were generally small (median sample size = 48, range 14 to 180). Exercise was demonstrated to be effective in terms of short term recovery in rotator cuff disease (RR 7.74 (1.97, 30.32), and longer term benefit with respect to function (RR 2.45 (1.24, 4.86). Combining mobilisation with exercise resulted in additional benefit when compared to exercise alone for rotator cuff disease. Laser therapy was demonstrated to be more effective than placebo (RR 3.71 (1.89, 7.28) for adhesive capsulitis but not for rotator cuff tendinitis. Both ultrasound and pulsed electromagnetic field therapy resulted in improvement compared to placebo in pain in calcific tendinitis (RR 1.81 (1.26, 2.60) and RR 19 (1.16, 12.43) respectively). There is no evidence of the effect of ultrasound in shoulder pain (mixed diagnosis), adhesive capsulitis or rotator cuff tendinitis. When compared to exercises, ultrasound is of no additional benefit over and above exercise alone. There is some evidence that for rotator cuff disease, corticosteroid injections are superior to physiotherapy and no evidence that physiotherapy alone is of benefit for Adhesive Capsulitis REVIEWER'S CONCLUSIONS: The small sample sizes, variable methodological quality and heterogeneity in terms of population studied, physiotherapy intervention employed and length of follow up of randomised controlled trials of physiotherapy interventions results in little overall evidence to guide treatment. There is evidence to support the use of some interventions in specific and circumscribed cases. There is a need for trials of physiotherapy interventions for specific clinical conditions associated with shoulder pain, for shoulder pain where combinations of physiotherapy interventions, as well as, physiotherapy interventions as an adjunct to other, non physiotherapy interventions are compared. This is more reflective of current clinical practice. Trials should be adequately powered and address key methodological criteria such as allocation concealment and blinding of outcome assessor.

845

Pineal sensitivity to pulsed static magnetic fields changes during the photoperiod

The effect of pulsed static magnetic fields on the rat pineal melatonin synthesis was studied at different times of the photoperiod. Exposure to magnetic fields during mid- or late dark phase significantly suppressed pineal N-acetyltransferase activity, the rate-limiting enzyme in melatonin synthesis, as well as the melatonin content in the pineal gland. These parameters were not influenced by magnetic fields when the exposure occurred early in the dark phase or during the day. These results suggest that the responsiveness of the pineal gland to magnetic field perturbations changes throughout the photoperiod.

846

Pineal-hypothalamic tract mediation of picotesla magnetic fields in the treatment of neurological disorders

The objective of this study is analysis of the clinical efficacy of picotesla magnetic fields in the treatment of epilepsy, Parkinson's disease and multiple sclerosis. The method utilized involved the exogenous application of physiologic, very weak magnetic fields to the brain by Sandyk, Anninos, Derpapas and Tsagas. The magnetic device produced a magnetic field ranging from about 5 x 10(-8) gauss to about 2.5 x 10(-7) gauss at frequencies of 2 to 7 Hertz. The wave form was sinusoidal and the device was positioned about the posterior portion of the corpus callosum most specifically to influence the pineal gland. Direct correlation of melatonin production with magnetic field stimulation was established. Amelioration or palliation of the neurological conditions was observed over an extended period of time in most cases. It appeared that a resonance situation was established between the magnetic field and melatonin which could be explained with Jacobson Resonance. These studies begin to point to the explanation of the mechanism of interaction between non-ionizing electromagnetic radiation and biological systems. Furthermore, the evaluation of the pineal gland as an magneto-sensitive gland may help us understand fundamental conditions in magneto-receptors of biological systems in terms of their piezoelectric nature.

847

Pivotal steps towards quantification of molecular diffusion coefficients by NMR

Using nuclear magnetic resonance (NMR) spectroscopy with a pair of pulsed field gradients (PFGs), Stajeskal and Tanner successfully measured molecular diffusion coefficients in solution in 1965. This method has since been used extensively in various applications, especially after the PFG was implemented in commercial NMR probes. Due to the nonuniformity of the PFG and radio frequency (RF) fields, molecules distributed throughout the sample experience different PFG and RF fields and contribute unevenly to the measured diffusion coefficients, resulting in considerable errors in conventional NMR diffusion experiments. By selective excitation of a central sample region with an offset-independent adiabatic inversion pulse and a PFG, a uniform RF field can be assumed, and the PFG can be represented as a linear approximation. Under these conditions, the molecules diffuse as if they were all experiencing the same effective gradient g(e), leading to a Gaussian signal decay as a function of the PFG strength. Quantitative measurement of molecular diffusion coefficients is therefore made possible. From the diffusion coefficient of a 90 % H(2)O/10 % D(2)O sample, it is convenient to calibrate g(e) with a Java program. In a similar way the nonlinearity of the PFG can be corrected.

848

Plasma membrane voltage changes during nanosecond pulsed electric field exposure

The change in the membrane potential of Jurkat cells in response to nanosecond pulsed electric fields was studied for pulses with a duration of 60 ns and maximum field strengths of approximately 100 kV/cm (100 V/cell diameter). Membranes of Jurkat cells were stained with a fast voltage-sensitive dye, ANNINE-6, which has a subnanosecond voltage response time. A temporal resolution of 5 ns was achieved by the excitation of this dye with a tunable laser pulse. The laser pulse was synchronized with the applied electric field to record images at times before, during, and after exposure. When exposing the Jurkat cells to a pulse, the voltage across the membrane at the anodic pole of the cell reached values of 1.6 V after 15 ns, almost twice the voltage level generally required for electroporation. Voltages across the membrane on the side facing the cathode reached values of only 0.6 V in the same time period, indicating a strong asymmetry in conduction mechanisms in the membranes of the two opposite cell hemispheres. This small voltage drop of 0.6-1.6 V across the plasma membrane demonstrates that nearly the entire imposed electric field of 10 V/mum penetrates into the interior of the cell and every organelle.

849

Plasmid DNA and low-frequency electromagnetic fields

Physico-chemical and biological properties were studied in recombinant plasmids exposed to electric and magnetic fields (EMFs). The absence of slow-migrating DNA species and failure to identify induced DNA conformers, suggests that EMFs do not have any obvious genotoxic effect in any of the experimentally tested conditions.

850

Possible health hazards from exposure to power-frequency electric and magnetic fields--a COMAR Technical Information Statement

In recent years concerns have been raised about the biological effects of exposure to electric and magnetic fields at extremely low frequencies (ELF), particularly those associated with the distribution and utilization of electric power. In 1989, the Institute of Electrical and Electronics Engineers (IEEE) issued an "Entity Position Statement" which stated that "there is not enough relevant scientific data to establish whether common exposure to power-frequency fields should be considered a health hazard" and that "there is general agreement that more research is needed to define safe limits of human exposure to power-frequency fields." After examination of relevant research reports published during the last ten years, COMAR concludes that it is highly unlikely that health problems can be associated with average 24-hour field exposure to power frequency magnetic fields of less than 1 microT (10 mG). Good laboratory evidence shows that magnetic fields 100 to 10,000 times higher than this level, either ELF sinusoidal or pulsed, can induce a variety of biological effects, including beneficial health effects such as bone or tissue healing. Many of the reports of effects of weaker fields should be considered preliminary, as some observations have not been reproduced in different laboratories, while others, observed in cells, have not been clearly connected to effects in intact animals. Also, the means of interaction of low-level ELF fields with cells, tissues or laboratory animals is not fully understood; therefore the health impacts of such weak fields on intact animals and humans, if any, cannot be predicted or explained. Further research is needed to confirm or negate reports of effects of weak fields, and to determine mechanisms and relevance of these effects to actual health hazards. Continued study in this complicated area will enhance our understanding of biological systems, as well as help identify levels and types of ELF exposure that may be deleterious to human health.

851

Potentials of radio-frequency field gradient NMR microscopy in environmental science

An understanding of transport, flow, diffusivity and mass transfer processes is of central importance in many fields of environmental biotechnology such as biofilm, bioreactor and membrane engineering, soil and groundwater bioremediation, and wastewater treatment. Owing to its remarkable sensitivity to molecular displacements and to its noninvasive and nondestructive character, pulsed field gradient (PFG) nuclear magnetic resonance (NMR) can be a valuable tool for investigating such processes. In conventional NMR microscopy, spatial encoding is achieved by using static magnetic field gradients (B(0) gradients). However, an interesting alternative is to use radio-frequency magnetic field gradients (RF or B(1) gradients). Although the latter are less versatile than the former, RF field gradient microscopy is particularly suitable for dealing with heterogeneous systems such as porous media because of its quasi-immunity to background static magnetic field gradients arising from magnetic susceptibility inhomogeneities, unlike the B(0) gradients microscopy. Here, we present an overview of basic principles and the main features of this technique, which is still relatively unused. Different examples of diffusion imaging illustrate the potentialities of the method in both micro-imaging and the measurement of global or local diffusion coefficients within membranes and at liquid-solid interfaces. These examples suggest that a number of environmental problems could benefit from this technique. Different future prospects of application of B(1) gradient NMR microscopy in environmental biotechnology are considered.

852

Power frequency fields promote cell differentiation coincident with an increase in transforming growth factor-beta(1) expression

Recent information from several laboratories suggest that power frequency fields may stimulate cell differentiation in a number of model systems. In this way, they may be similar to pulsed electromagnetic fields, which have been used therapeutically. However, the effects of power frequency fields on phenotypic or genotypic expression have not been explained. This study describes the ability of power frequency fields to accelerate cell differentiation in vivo and describes dose relationships in terms of both amplitude and exposure duration. No change in proliferation or cell content were observed. A clear dose relationship, in terms of both amplitude and duration of exposure, was determined with the maximal biological response occurring at 0.1 mT and 7-9 h/day. Because this study was designed to explore biological activity at environmental exposure levels, this exposure range does not necessarily define optimal dosing conditions from the therapeutic point of view. This study reports the stimulation by power frequency fields of transforming growth factor-beta, an important signalling cytokine known to regulate cell differentiation. The hypothesis is raised that the stimulation of regulatory cytokines by electromagnetic fields may be an intermediary mechanism by which these fields have their biological activity.

853

Power increases within the gamma range over the frontal and occipital regions during acute exposures to cerebrally counterclockwise rotating magnetic fields with specific derivatives of change

A total of 11 men and women were exposed for 5 min each to six different temporal configurations of pulsed magnetic fields that were delivered through serial activation of 8 solenoids in a counterclockwise direction around the head within the horizontal plane above the ears. Twenty-second samples of quantitative electroencephalographic activity within the delta, theta, lower alpha, upper alpha, beta, and gamma regions were collected after each configuration had been activated for 2.5 min. Only the circumcerebral presentation of the first pulse for 25 ms followed by an acceleration of +2 ms to each of the other 7 solenoids (the last duration = 11 ms) resulted in a significant increase in power within the gamma range (35 Hz to 45 Hz) over both frontal and occipital lobes but not over the parietal or temporal lobes. These results suggest topical application of specific spatial-temporal configurations of magnetic fields may affect the recursive creation of the rostral-caudal waves of cohesive fields that might produce consciousness.

854

Practice of Magnetic Field Therapy

Page 241 deals with Vegetative/Autonomic Dystonia

855

Preliminary evaluation of nanoscale biogenic magnetite-based ferromagnetic transduction mechanisms for mobile phone bioeffects

Ferromagnetic transduction models have been proposed as a potential mechanism for mobile phone bioeffects. These models are based on the coupling of RF and pulsed electromagnetic emissions to biogenic magnetite (Fe3O4) present in the human brain via either ferromagnetic resonance or mechanical activation of cellular ion channels. We have tested these models experimentally for the first time using a bacterial analogue (Magnetospirillum magnetotacticum) which produces intracellular biogenic magnetite similar to that present in the human brain. Experimental evaluation revealed that exposure to mobile phone emissions resulted in a consistent and significantly higher proportion of cell death in exposed cultures versus sham exposure (p = 0.037). Though there appears to be a repeatable trend toward higher cell mortality in magnetite-producing bacteria exposed to mobile phone emissions, it is not yet clear that this would extrapolate to a deleterious health effect in humans.

856

Preliminary report: modification of cardiac contraction rate by pulsed magnetic fields

Isolated rat hearts and excised canine cardiac tissues were subjected to pulsed magnetic fields. The fields excited in coils by tandem pairings of sinusoidal pulses were presented at various inter-pair delays and repetition rates. The waveform of the magnetic field was a single or multiple sinusoid followed after a variable delay by another single or multiple sinusoid. Small but reliable increases in the beating rate of rat heart were observed. Similar increases occurred in contraction rates of canine tissues. Both preparations exhibited a contraction-rate dependency on the repetition rate of the paired magnetic pulses: 4.5-6 rep/s for canine tissue, and 20-25 and 40-55 reps/s for rat heart. Flux-density thresholds for both preparations approximated 10 mT (100 gauss) rms.

857

Preliminary study of quantitative aspects and the effect of pulsed electromagnetic field treatment on the incorporation of equine cancellous bone grafts

The quantitative aspects of equine cancellous bone graft incorporation and the possibility of influencing graft incorporation by daily exposure to a pulsed electromagnetic field (PEMF) was studied in eight yearling ponies. In order to be able to quantify formative aspects of graft remodelling, a double and treble tetracycline intravital labelling technique was used. Intravital radiographs were obtained at regular intervals throughout the trial, but were found to be of little assistance in assessing any differences between stimulated and non-stimulated grafts. The ponies were humanely destroyed at regular intervals between nine and 241 days after installation of the graft. Light microscopy and fluorescent light microscopy were used to evaluate quantitative aspects of graft incorporation and to compare PEMF-stimulated grafts with control grafts. There was a small but statistically significant effect of PEMF-stimulation on cancellous bone graft incorporation. In view of this, these observations can only be considered as indicative of a possible trend, but should encourage further studies using different signal modalities.

858

Premenstrual exacerbation of symptoms in multiple sclerosis is attenuated by treatment with weak electromagnetic fields

It has been suspected that hormonal factors contribute to the etiology and pathogenesis of multiple sclerosis (MS). A direct relationship between MS and endocrine functions is suggested by changes in disease activity during the phases of the menstrual cycle. A subset of women with MS experience premenstrual worsening of symptoms which improve dramatically with the onset of menstruation. The biological mechanisms underlying these changes in disease activity are unexplained but may be related to cyclical fluctuations in gonadal sex steroid hormones, abrupt changes in the activity of the endogenous opioid peptides and fluctuations in plasma melatonin levels which affect neuronal excitability and immune functions. Extracerebral application of weak electromagnetic fields (EMFs) in the picotesla range intensity has been reported efficacious in the treatment of MS with patients experiencing sustained improvement in motor, sensory, autonomic, affective and cognitive functions. The present report concerns two women with chronic progressive stage MS who experienced, coincident with increasing functional disability, regular worsening of their symptoms beginning about a week before menstruation and abating with the onset of menstruation. These symptoms resolved two months after the initiation of treatment with EMFs. The report supports the association between the endocrine system and MS and indicates that brief, extracranial applications of these magnetic fields modifies the activity of neuroendocrine systems which precipitate worsening of MS symptoms premenstrually.

859

Prenatal exposure to a low-frequency electromagnetic field demasculinizes adult scent marking behavior and increases accessory sex organ weights in rats

Pregnant Sprague-Dawley dams were exposed to a low-level, low-frequency pulsed electromagnetic (EM) field (15 Hz, 0.3 msec duration, peak intensity 8 gauss) for 15 min twice a day from day 15 through day 20 of gestation, a period in development that is critical for sexual differentiation of the male rat brain. No differences in litter size, number of stillborns, or body weight were observed in offspring from field-exposed dams. At 120 days of age, field-exposed male offspring exhibited significantly less scent marking behavior than controls. Accessory sex organ weights, including epididymis, seminal vesicles, and prostate, were significantly higher in field-exposed subjects at this age. However, circulating levels of testosterone, luteinizing hormone, and follicle-stimulating hormone, as well as epididymal sperm counts, were normal. These data indicate that brief, intermittent exposure to low-frequency EM fields during the critical prenatal period for neurobehavioral sex differentiation can demasculinize male scent marking behavior and increase accessory sex organ weights in adulthood.

860

Pretraining exposure to physiologically patterned electromagnetic stimulation attenuates fear-conditioned analgesia

The effect of weak electromagnetic stimulation on the emergence of conditioned analgesia was examined in the adult rat. Subjects were conditioned to associate a continuous 20 kHz ultrasonic tone (CS) with 0.2 mA footshock (UCS-) over five successive days. For 30 min either before or after conditioning sessions, rats were exposed to sham or pulsed (primed burst potentiation) magnetic fields (500 nT). At the end of the conditioning phase, all animals were evaluated for anticipatory analgesia following CS presentation using a hotplate analgesiometer. Data analysis suggested a statistically significant attenuation of fear-conditioned analgesia in rats exposed to electromagnetic stimulation prior to conditioning, whereas post-conditioning exposure potentiated the reduction in pain sensitivity compared to baseline measures. The present results suggest that the emergence of fear-conditioned responses is sensitive to whole body exposure to a magnetic field pattern that has been shown to induce long-term potentiation in hippocampal slices.

861

Pretraining Exposure to Physiologically Patterned Electromagnetic Stimulation Attenuates Fear-Conditioned Analgesia

The effect of weak electromagnetic stimulation on the emergence of conditioned analgesia was examined in the adult rat. Subjects were conditioned to associate a continuous 20 kHz ultrasonic tone (CS) with 0.2 mA footshock (UCS(-) ) over five successive days. For 30 min either before or after conditioning sessions, rats were exposed to sham or pulsed (primed burst potentiation) magnetic fields (500 nT). At the end of the conditioning phase, all animals were evaluated for anticipatory analgesia following CS presentation using a hotplate analgesiometer. Data analysis suggested a statistically significant attenuation of fear-conditioned analgesia in rats exposed to electromagnetic stimulation prior to conditioning, whereas post-conditioning exposure potentiated the reduction in pain sensitivity compared to baseline measures. The present results suggest that the emergence of fear-conditioned responses is sensitive to whole body exposure to a magnetic field pattern that has been shown to induce long-term potentiation in hippocampal slices.

862

Pretreatment of rats with pulsed electromagnetic fields enhances regeneration of the sciatic nerve

Regeneration of the sciatic nerve was studied in rats pretreated in a pulsed electromagnetic field (PEMF). The rats were exposed between a pair of Helmholtz coils at a pulse repetition rate of 2 pps at a field density of 60 or 300 microT. The PEMF treatment was then discontinued. After an interval of recovery, regeneration of the sciatic nerve was initiated by a crush lesion. Regeneration of sensory fibers was measured by the "pinch test" after an additional 3-6 days. A variety of PEMF pretreatments including 4 h/day for 1-4 days or exposure for 15 min/day during 2 days resulted in an increased regeneration distance, measured 3 days after the crush lesion. This effect could be demonstrated even after a 14-day recovery period. In contrast, pretreatment for 4 h/day for 2 days at 60 microT did not affect the regeneration distance. The results showed that PEMF pretreatment conditioned the rat sciatic nerve in a manner similar to that which occurs after a crush lesion, which indicates that PEMF affects the neuronal cell body. However, the mechanism of this effect remains obscure.

863

Prevalence of Pain in Patients With Cancer: A Systematic Review of the Past 40 Years

Pooled prevalence of pain was > 50% in all cancer types with the highest prevalence in head/neck cancer patients (70%; 95% CI 51% to 88%).

864

Prevalence of postherpetic neuralgia after a first episode of herpes zoster: a prospective study with long-term follow-up.

OBJECTIVE: To estimate the frequency, duration, and clinical importance of postherpetic neuralgia after a single episode of herpes zoster. DESIGN: Prospective cohort study with long term follow up. SETTING: Primary health care in Iceland. PARTICIPANTS: 421 patients with a single episode of herpes zoster. MAIN OUTCOME MEASURES: Age and sex distribution of patients with herpes zoster, point prevalence of postherpetic neuralgia, and severity of pain at 1, 3, 6, and 12 months and up to 7.6 years after the outbreak of zoster. RESULTS: Among patients younger than 60 years, the risk of postherpetic neuralgia three months after the start of the zoster rash was 1.8% (95% confidence interval 0.59% to 4.18%) and pain was mild in all cases. In patients 60 years and older, the risk of postherpetic neuralgia increased but the pain was usually mild or moderate. After three months severe pain was recorded in two patients older than 60 years (1.7%, 2.14% to 6.15%). After 12 months no patient reported severe pain and 14 patients (3.3%) had mild or moderate pain. Seven of these became pain free within two to seven years, and five reported mild pain and one moderate pain after 7.6 years of follow up. Sex was not a predictor of postherpetic neuralgia. Possible immunomodulating comorbidity (such as malignancy, systemic steroid use, diabetes) was present in 17 patients. CONCLUSIONS: The probability of longstanding pain of clinical importance after herpes zoster is low in an unselected population of primary care patients essentially untreated with antiviral drugs.

865

Prevention of osteoporosis by pulsed electromagnetic fields

Using an animal model we examined the use of pulsed electromagnetic fields, induced at a physiological frequency and intensity, to prevent osteoporosis that is concomitant with disuse. By protecting the left ulnae of turkeys from functional loading, WE NOTED A LOSS OF BONE OF 13% COMPARED WITH THE INTACT CONTRALATERAL CONTROL ULNAE over an eight week experimental period. Using a treat a regimen of one hour per day of pulsed electromagnetic fields, we observed an osteogenic dose-response to induced electrical power, with a maximum cost eugenic effect between 0.01 and 0.04 Tesla(squared) per second. Pulse power levels of more or less than these levels were less effective. The maximum osteogenic response was obtained by a decrease in the level of intra-cortical remodeling, inhibition of endosteal resorption, and stimulation of both periosteal and endosteal new bone formation. These data suggest that short daily periods of exposure to appropriate electromagnetic fields can beneficially influence the behavior of the cell populations that are responsible for bone remodeling, and that there is an effective window of induced electrical power in which bone mass can be controlled in the absence of mechanical loading.

866

Prevention of osteoporosis by pulsed electromagnetic fields

Using an animal model, we examined the use of pulsed electromagnetic fields, induced at a physiological frequency and intensity, to prevent the osteoporosis that is concomitant with disuse. By protecting the left ulnae of turkeys from functional loading, we noted a loss of bone of 13.0 per cent compared with the intact contralateral control ulnae over an eight-week experimental period. Using a treatment regimen of one hour per day of pulsed electromagnetic fields, we observed an osteogenic dose-response to induced electrical power, with a maximum osteogenic effect between 0.01 and 0.04 tesla per second. Pulse power levels of more or less than these levels were less effective. The maximum osteogenic response was obtained by a decrease in the level of intracortical remodeling, inhibition of endosteal resorption, and stimulation of both periosteal and endosteal new-bone formation. These data suggest that short daily periods of exposure to appropriate electromagnetic fields can beneficially influence the behavior of the cell populations that are responsible for bone-remodeling, and that there is an effective window of induced electrical power in which bone mass can be controlled in the absence of mechanical loading.

867

Progressive cognitive improvement in multiple sclerosis from treatment with electromagnetic fields

It has long been recognized that cognitive impairment occurs in patients with multiple sclerosis (MS) particularly among patients with a chronic progressive course. MS is considered a type of "subcortical dementia" in which cognitive and behavioral abnormalities resemble those observed in patients with a frontal lobe syndrome. The Bicycle Drawing Test is employed for the neuropsychological assessment of cognitive impairment specifically that of mechanical reasoning and visuographic functioning. It also provides clues concerning the patient's organizational skills which are subserved by the frontal lobes. Extracerebral pulsed applications of picotesla flux intensity electromagnetic fields (EMFs) have been shown to improve cognitive functions in patients with MS. I present three patients with long standing symptoms of MS who, on the initial baseline, pretreatment Bicycle Drawing Test, exhibited cognitive impairment manifested by omissions of essential details and deficient organizational skills. All patients demonstrated progressive improvement in their performance during treatment with EMFs lasting from 6-18 months. The improvement in cognitive functions, which occurred during the initial phases of the treatment, was striking for the changes in organizational skills reflecting frontal lobe functions. These findings demonstrate that progressive recovery of cognitive functions in MS patients are observed over time through continued administration of picotesla flux intensity EMFs. It is believed that the beneficial cognitive effects of these EMFs are related to increased synaptic neurotransmission and that the progressive cognitive improvement noted in these patients is associated with slow recovery of synaptic functions in monoaminergic neurons of the frontal lobe or its projections from subcortical areas.

868

Propagation of an electromagnetic wave in an absorbing anisotropic medium and infrared transmission of liquid crystals: Comparison with experiments

The theory of the absorbance of a semi-infinite medium characterized by a second-rank dielectric tensor for the entire electromagnetic spectrum, as given by Scaife and Vij [J. Chem. Phys. 122, 174901 (2005)], is extended to include molecules of prolate spheriodal shape with longitudinal and transverse polarizabilities and to cover the case of elliptically polarized incident radiation. The theory is applied to the infrared transmission experiments of biaxial liquid crystals. It is found that the formula for the dependence on frequency and on angle of polarization of the absorbance A(omega,theta)=-log_{10}[10;{A(omega,0)} cos;{2} theta+(10;{-A(omega,pi/2)} sin;{2} theta)] is unaffected by the anisotropy of the molecules and by the elliptical polarization of the incident radiation. A small (+/-5%) discrepancy between theory and experiment has been found for bands with high absorbances. It is found that this discrepancy does not depend on birefringence of the sample but may depend on the precise method of absorbance measurement and on effects at the surface of the cell containing the liquid crystal under test.

869

Prospective comparison of the effect of direct current electrical stimulation and pulsed electromagnetic fields on instrumented posterolateral lumbar arthrodesis

The purpose of this prospective study was to compare the effect of adjunctive direct current (DC) electrical stimulation and pulsed electromagnetic field therapy (PEMF) on augmentation of instrumented lumbar fusion. Sixty-one patients undergoing lumbar spine fusion were enrolled in the study and randomized to one of three treatment protocols: 1) adjunctive PEMF group (n = 22) fitted with Spinal-Stim model 8212(AME) within 30 days of surgery; 2) DC group (n = 17) had a SpF-2T stimulator(EBI) implanted at the time of surgery; or 3) control group (n = 22). The fusion mass bone mineral density (BMD) assessment was performed on 3-month and 1-year radiographs for each patient. Lateral flexion-extension and anteroposterior radiographs were evaluated at 1 year to determine the presence of fusion. Clinical outcome patient analyses were performed at 1 year. At 1-year follow-up, radiographic fusion and fusion mass bone density were not significantly different among the groups. In the nonstimulated group, there were 43% excellent, 43% good, and 14% fair results. In the PEMF group, there were 35% excellent, 50% good, 10% fair, and 5% poor results. In the DC group, there were 32% excellent, 37% good, and 31% fair results. The results of the current study suggest that electrical stimulation does not significantly enhance fusion rate in instrumented lumbar arthrodesis, although we observed a statistically insignificant trend toward increased fusion mass BMD in the electrically stimulated groups. The significance of increased BMD remains unknown.

870

Prospects on clinical applications of electrical stimulation for nerve regeneration

Regenerative capability is limited in higher vertebrates but present in organ systems such as skin, liver, bone, and to some extent, the nervous system. Peripheral nerves in particular have a relatively high potential for regeneration following injury. However, delay in regrowth or growth, blockage, or misdirection at the injury site, and growth to inappropriate end organs may compromise successful regeneration, leading to poor clinical results. Recent studies indicate that low-intensity electrical stimulation is equivalent to various growth factors, offering avenues to improve these outcomes. We present a review of studies using electric and electromagnetic fields that provide evidence for the enhancement of regeneration following nerve injury. Electric and electromagnetic fields (EMFs) have been used to heal fracture non-unions. This technology emerged as a consequence of basic studies [Yasuda, 1953; Fukada and Yasuda, 1957] demonstrating the piezoelectric properties of (dry) bone. The principle for using electrical stimulation for bone healing originated from the work of Bassett and Becker [1962], who described asymmetric voltage waveforms from mechanically deformed live bone. These changes were presumed to occur in bone during normal physical activity as a result of mechanical forces, and it was postulated that these forces were linked to modifications in bone structure. Endogenous currents present in normal tissue and those that occur after injury were proposed to modify bone structure [Bassett, 1989]. These investigators proposed that tissue integrity and function could be restored by applying electrical and/or mechanical energy to the area of injury. They successfully applied electrical currents to nonhealing fractures (using surgically implanted electrodes or pulsed currents using surface electrodes) to aid endogenous currents in the healing process.(ABSTRACT TRUNCATED AT 250 WORDS)

871

Protection against focal cerebral ischemia following exposure to a pulsed electromagnetic field

There is evidence that electromagnetic stimulation may accelerate the healing of tissue damage following ischemia. We undertook this study to investigate the effects of low frequency pulsed electromagnetic field (PEMF) exposure on cerebral injury in a rabbit model of transient focal ischemia (2 h occlusion followed by 4 h of reperfusion). PEMF exposure (280 V, 75 Hz, IGEA Stimulator) was initiated 10 min after the onset of ischemia and continued throughout reperfusion (six exposed, six controls). Magnetic resonance imaging (MRI) and histology were used to measure the degree of ischemic injury. Exposure to pulsed electromagnetic field attenuated cortical ischemia edema on MRI at the most anterior coronal level by 65% (P < 0.001). On histologic examination, PEMF exposure reduced ischemic neuronal damage in this same cortical area by 69% (P < 0.01) and by 43% (P < 0.05) in the striatum. Preliminary data suggest that exposure to a PEMF of short duration may have implications for the treatment of acute stroke.

872

Proteoglycan synthesis in bovine articular cartilage explants exposed to different low-frequency low-energy pulsed electromagnetic fields

OBJECTIVE: To investigate the role of pulsed electromagnetic field (PEMF) exposure parameters (exposure length, magnetic field peak amplitude, pulse frequency) in the regulation of proteoglycan (PG) synthesis of bovine articular cartilage explants. METHODS: Bovine articular cartilage explants were exposed to a PEMF (75 Hz; 2 mT) for different time periods: 1, 4, 9, 24 h. Then, cartilage explants were exposed for 24 h to PEMFs of different magnetic field peak amplitudes (0.5, 1, 1.5, 2 mT) and different frequencies (2, 37, 75, 110 Hz). PG synthesis of control and exposed explants was determined by Na2-35SO4 incorporation. RESULTS: PEMF exposure significantly increased PG synthesis ranging from 12% at 4 h to 17% at 24 h of exposure. At all the magnetic field peak amplitude values, a significant PG synthesis increase was measured in PEMF-exposed explants compared to controls, with maximal effect at 1.5 mT. No effect of pulse frequency was observed on PG synthesis stimulation. CONCLUSIONS: The results of this study show the range of exposure length, PEMF amplitude, pulse frequency which can stimulate cartilage PG synthesis, and suggest optimal exposure parameters which may be useful for cartilage repair in in vivo experiments and clinical application.

873

Proton positions in the Mn(2+) binding site of concanavalin A as determined by single-crystal high-field ENDOR spectroscopy

High-field (95 GHz) pulsed EPR and electron-nuclear double resonance (ENDOR) techniques have been used for the first time to determine coordinates of ligand protons of a high-spin metal center in a protein single crystal. The protein concanavalin A contains a Mn(2+) ion which is coordinated to two water molecules, a histidine residue, and three carboxylates. Single crystals of concanavalin A were grown in H(2)O and in D(2)O to distinguish the exchangeable water protons from the nonexchangeable protons of the imidazole group. Distinct EPR transitions were selected by performing the ENDOR measurements at different magnetic fields within the EPR spectrum. This selection, combined with the large thermal polarization achieved at 4.5 K and a magnetic field of approximately 3.4 T allowed us to assign the ENDOR signals to their respective M(S) manifolds, thus providing the signs of the hyperfine couplings. Rotation patterns were acquired in the ac and ab crystallographic planes. Two distinct crystallographic sites were identified in each plane, and the hyperfine tensors of two of the imidazole protons and the four water protons were determined by simulations of the rotation patterns. All protons have axially symmetric hyperfine tensors and, by applying the point-dipole approximation, the positions of the various protons relative to the Mn(2+) ion were determined. Likewise, the water protons involved in H-bonding to neighboring residues were identified using the published, ultrahigh-resolution X-ray crystallographic coordinates of the protein (Deacon et al. J. Chem. Soc., Faraday Trans. 1997, 93(24), 4305-4312).

874

Proton radiography of inertial fusion implosions

A distinctive way of quantitatively imaging inertial fusion implosions has resulted in the characterization of two different types of electromagnetic configurations and in the measurement of the temporal evolution of capsule size and areal density. Radiography with a pulsed, monoenergetic, isotropic proton source reveals field structures through deflection of proton trajectories, and areal densities are quantified through the energy lost by protons while traversing the plasma. The two field structures consist of (i) many radial filaments with complex striations and bifurcations, permeating the entire field of view, of magnetic field magnitude 60 tesla and (ii) a coherent, centrally directed electric field of order 10(9) volts per meter, seen in proximity to the capsule surface. Although the mechanism for generating these fields is unclear, their effect on implosion dynamics is potentially consequential.

875

Pseudarthrosis after lumbar spine fusion: nonoperative salvage with pulsed electromagnetic fields

We studied 100 patients in whom symptomatic pseudarthrosis had been established at more than 9 months after lumbar spine fusion. All patients were treated with a pulsed electromagnetic field device worn consistently 2 hours a day for at least 90 days. Solid fusion was achieved in 67% of patients. Effectiveness was not statistically significantly different for patients with risk factors such as smoking, use of allograft, absence of fixation, or multilevel fusions. Treatment was equally effective for posterolateral fusions (66%) as with interbody fusions (69%). For patients with symptomatic pseudarthrosis after lumbar spine fusion, pulsed electromagnetic field stimulation is an effective nonoperative salvage approach to achieving fusion.

876

Psychosomatic disorders and autonomic dystonia.

Autonomic dystonia is one of the psychosomatic diseases, characterized by unstable multi-organic complaints, abnormal function of the autonomic nervous system, and is affected by psychological events. It is considered to be identical with somatoform autonomic dysfunction in ICD-10 (F 45.3). Many physicians and researchers both Occidental and Oriental, have taken a great interest in this disease, including Eppinger & Hess, Bergmann, Okinaka, Abe and others. The Autogenic Training one of the the most important therapies of psychosomatic disease, was established by Schultz & Luthe and introduced to Japan by Ikemi and Sasaki. "Zen" in Buddhism provides a efficacious treatment for the allied dysfunction so called "Zen disease". In 1711, Buddhist Hakuin was suffered from Zen disease. He used three techniques of "Naikan-ho", "Nanso-noho" and "ana-pana-sati" (Buddha's breathing). He lay in supine position, relaxed the upper half of the body, energized the lower half of it, breathed a slow and calm breath, and had the image that warm creamy fluid flew slowly in the whole body. Repeating this again and again every day, he finally recovered from the disease. There are somethings in common between the "Hakuin's Zen" method and the Autogenic Training. I would like to emphasize that the traditional "Hakuin's Zen" method should be reappraised and applied to treating autonomic dystonia and stress-related ilness as well as to promoting health. (author abst.)

877

Pulsating electromagnetic field induces apoptosis of rat's bowel Cajal's cells

We previously have shown that pulsating electromagnetic field (PEMF) reduce expression of interstitial cells of Cajal (ICCs) in the rat gastrointestinal tract. Aim of present study was to determine whether diminished expression of ICCs in the rat's bowel after PEMF exposure was related to apoptosis and to PEMF dose. Methods: rats were divided into two groups (n= 32). First group (n = 16) was exposed to four rising doses of PEMF from one dose 12.5 x 10(3) A(2) x h/m(2) to four doses 50 x 10(3) A(2) x h/m(2). Second group (n = 16) served as a control. Tissue samples of the rat duodenum and colon from exposed to PEMF and control animals were fixed and paraffin embedded and cryostat frozen. The tangential paraffin bowel sections were stained with anti c-Kit antibody. C-Kit positive cells were assessed by image analysis. Apoptosis detection in rat's tissues was performed with rabbit polyclonal anti-Bax antibody. Results: the surface of c-Kit immunopositive cells decreased in the duodenum and colon of rats stimulated with PEMF in a dose dependent manner with increase in expression of pro-apoptotic Bax protein in c-Kit immunopositive myenteric cells. The apoptosis - inducing action of PEMF on the c-Kit immunoreactivity of Cajal's cells suggests a possible therapeutical implications in diseases associated with overactive smooth muscles dysfunction. Pulsating electromagnetic field (PEMF) induced changed immunoreactivity in rat's myenteric Cajal cells. C-Kit diminished reactivity of ICCs was proved to be caused by triggering of apoptotic pathwa in ICCs upon PEMF stimulation. PEMF generated apoptosis was dependant on applied dose of PEMF and detected by immunostaining with antibody against proapoptic protein Bax.

878

Pulsating electromagnetic field stimulates mRNA expression of bone morphogenetic protein-2 and -4

The effects of a pulsating electromagnetic field on mRNA expression of bone morphogenetic protein-2 and -4 in chick embryonic calvaria were examined. From the onset of embryogenesis (Day 0), chick embryos were incubated in a continuously generated pulsating electromagnetic field with a peak of 3.5 milli-Tesla (mean: 2 milli-Tesla) and vibration at 15 Hz. Control chicks were incubated in a normal magnetic field. Northern-blot analysis showed that the mRNAs of bone morphogenetic protein-2 and -4 were expressed in the calvaria. Quantitative analysis of the mRNA expressions was done by means of slot-blot hybridization. The magnetic field enhanced the expressions of both mRNAs. The enhancements were more pronounced in younger chick embryos (Day 15 > Day 17), and no significant change was observed in the 19-day-old embryos. These results indicate that osteo-inductive effects of the magnetic field were mediated at least in part by bone morphogenetic protein-2 and -4.

879

Pulsating electromagnetic fields in the treatment of delayed and non-union of fractures: results from a district general hospital

Pulsating electromagnetic fields (PEMFs) have been used to treat delayed and non-union of fractures at the Royal Berkshire Hospital since 1982. Thirteen patients started treatment during the first 2 years and their progress has been reviewed. It is concluded that the PEMFs produced a beneficial effect in only a small percentage of cases.

880

Pulse shape of magnetic fields influences chick embryogenesis

A total of 295 chick embryos was exposed during the first 48 hours of development to pulsed electromagnetic fields of 100 Hz and 0.4 to 104 microTeslas (micro T), and findings were compared with those in 364 control embryos. General morphology was analysed and supplemented by light microscopy studies. Exposure to electromagnetic fields with a pulse rise time of 100 microseconds produced teratogenic changes when intensities of 1.0 and 13.9 micro T were used but not with lower or higher intensities, demonstrating a 'window' effect and ruling out the possible influence of a rise in internal embryonic temperature. Exposure to an electromagnetic field of 1.0 micro T specifically altered organogenesis of the truncal nervous system and drastically reduced the alcian blue-stained components, whereas with an intensity of 13.9 micro T, there were abnormalities in the circulatory system and foregut, altering cell-to-cell contacts in the walls of developing vessels. When embryos were exposed to intensities of 0.4 and 1.0 micro T with 2.0 and 42 microseconds pulse rise times, teratogenic effects were greater and alterations involved all developing systems. The most powerful effects were obtained with 1.0 micro T and 42 microseconds rise time. The findings confirm the sensitivity of chick embryos to electromagnetic fields of extremely low frequency and intensity and indicate that pulse shape may be a decisive parameter determining strong, slight, or no modification of embryonic development. Mechanisms of action of electromagnetic fields are still unclear, but induced alterations in extracellular glycosaminoglycans could be a causal factor in the observed malformations.

881

Pulsed 180-GHz EPR/ENDOR/PELDOR spectroscopy

Within this review, we describe a home-built pulsed electron paramagnetic resonance (EPR) spectrometer operating at 180 GHz as well as the incorporation of two double resonance techniques, electron nuclear double resonance (ENDOR) and pulsed electron double resonance (PELDOR), along with first applications. Hahn-echo decays on a TEMPO/polystyrene sample are presented, demonstrating that the observation of anisotropic librational motions is possible in a very precise manner at high magnetic fields. Bisdiphenylene-phenyl-allyl is used as a model system to illustrate the performance of the setup for 1H-ENDOR using the Mims as well as the Davies sequence. Furthermore, first 1H-Mims and Davies ENDOR spectra on a biological sample, the wild-type Ras*Mn2+*GDP protein, are reported. The capability of the 180-GHz PELDOR setup is demonstrated using the three-pulse ELDOR sequence on the protein ribonucleotide reductase (RNR) subunit R2 from Escherichia coli, which contains two tyrosyl radicals at a 33 angstroms distance. At 180 GHz, orientation selectivity is observed and the modulation frequency is found to be in good agreement with theoretical predictions.

883

Pulsed and continuous wave mobile phone exposure over left versus right hemisphere: effects on human cognitive function

The possible effects of continuous wave (CW) and pulse modulated (PM) electromagnetic field (EMF) on human cognition was studied in 36 healthy male subjects. They performed cognitive tasks while exposed to CW, PM, and sham EMF. The subjects performed the same tasks twice during each session; once with left-sided and once with right-sided exposure. The EMF conditions were spread across three testing sessions, each session separated by 1 week. The exposed hemisphere, EMF condition, and test order were counterbalanced over all subjects. We employed a double-blind design: both the subject and the experimenter were unaware of the EMF condition. The EMF was created with a signal generator connected via amplifier to a dummy phone antenna, creating a power output distribution similar to the original commercial mobile phone. The EMF had either a continuous power output of 0.25 W (CW) or pulsed power output with a mean of 0.25 W. An additional control group of 16 healthy male volunteers performed the same tasks without any exposure equipment to see if mere presence of the equipment could have affected the subjects' performance. No effects were found between the different EMF conditions, separate hemisphere exposures, or between the control and experimental group. In conclusion, the current results indicate that normal mobile phones have no discernible effect on human cognitive function as measured by behavioral tests.

884

Pulsed DC electric fields couple to natural NAD(P)H oscillations in HT-1080 fibrosarcoma cells

Previously, we have demonstrated that NAD(P)H levels in neutrophils and macrophages are oscillatory. We have also found that weak ultra low frequency AC or pulsed DC electric fields can resonate with, and increase the amplitude of, NAD(P)H oscillations in these cells. For these cells, increased NAD(P)H amplitudes directly signal changes in behavior in the absence of cytokines or chemotactic factors. Here, we have studied the effect of pulsed DC electric fields on HT-1080 fibrosarcoma cells. As in neutrophils and macrophages, NAD(P)H levels oscillate. We find that weak (approximately 10(-5) V/m), but properly phased DC (pulsed) electric fields, resonate with NAD(P)H oscillations in polarized and migratory, but not spherical, HT-1080 cells. In this instance, electric field resonance signals an increase in HT-1080 pericellular proteolytic activity. Electric field resonance also triggers an immediate increase in the production of reactive oxygen metabolites. Under resonance conditions, we find evidence of DNA damage in HT-1080 cells in as little as 5 minutes. Thus the ability of external electric fields to effect cell function and physiology by acting on NAD(P)H oscillations is not restricted to cells of the hematopoietic lineage, but may be a universal property of many, if not all polarized and migratory eukaryotic cells.

885

Pulsed electric field exposure of insulin induces anti-proliferative effects on human hepatocytes

The purpose of this study was to examine the effects and the mechanism of a pulsed electric field (PEF) on insulin and its subsequent mediation of proliferative changes in human hepatocytes in vitro. The PEF, the electric field intensity coupled into the culture medium, was about 0.7 V/m with a repeating frequency of 50 Hz. Insulin solution was exposed to PEF for 20 min and added to the culture medium of human hepatocytes. Combining fluorescence spectroscopy, immunocytochemistry, microarrays, RT-PCR and MTT, several important events of the insulin signaling pathways were investigated, including ligand-receptor binding capacity, intracellular tyrosine phosphorylation level, gene transcription, and cell proliferation. PEF produced a conformational change of insulin molecule. The binding capacity of insulin to its receptors was reduced to 87% of the control level after PEF treatment, and the average intracellular tyrosine phosphorylation level decreased by 11%. The expression of 55 of 12,000 genes examined was modified, including an increase in the expression of human tyrosine phosphatase and the small GTP-binding protein. Based on these results, a mechanism is proposed to explain the bio-effects of PEF on hepatic cell proliferation through the insulin signaling pathway.

886

Pulsed electric field reduces the permeability of potato cell wall

The effect of the application of pulsed electric fields to potato tissue on the diffusion of the fluorescent dye FM1-43 through the cell wall was studied. Potato tissue was subjected to field strengths ranging from 30 to 500 V/cm, with one 1 ms rectangular pulse, before application of FM1-43 and microscopic examination. Our results show a slower diffusion of FM1-43 in the electropulsed tissue when compared with that in the non-pulsed tissue, suggesting that the electric field decreased the cell wall permeability. This is a fast response that is already detected within 30 s after the delivery of the electric field. This response was mimicked by exogenous H2O2 and blocked by sodium azide, an inhibitor of the production of H2O2 by peroxidases.

887

Pulsed electric field stimulates plant secondary metabolism in suspension cultures of Taxus chinensis

The effects of pulsed electric field (PEF) on growth and secondary metabolite production by plant cell culture were investigated by using suspension cultures of Taxus chinensis as a model system. Cultured cells in different growth phases were exposed to a PEF (50 Hz, 10 V/m) for various periods of time. A significant increase in intracellular accumulation of taxuyunnanine C (Tc), a bioactive secondary metabolite, was observed by exposing the cells in the early exponential growth phase to a 30-min PEF. The Tc content (i.e., the specific production based on dry cell weight) was increased by 30% after exposure to PEF, without loss of biomass, compared with the control. The combination of PEF treatment and sucrose feeding proved useful for improving secondary metabolite formation. Production levels of reactive oxygen species, extracellular Tc, and phenolics were all increased, whereas cell capacitance was decreased with PEF treatment. The results show that PEF induced a defense response of plant cells and may have altered the cell/membrane's dielectric properties. PEF, an external stimulus or stress, is proposed as a promising new abiotic elicitor for stimulating secondary metabolite biosynthesis in plant cell cultures.

888

Pulsed electric fields versus thermal treatment: equivalent processes to obtain equally acceptable citrus juices

Pulsed electric field treatment has been claimed to produce more acceptable chilled citrus juices than those obtained by conventional thermal treatment. The pectin methylesterase activity and the acceptability of nine juices obtained from Clementine mandarins, Valencia oranges, and Ortanique fruits (hybrid of mandarin and orange), untreated, pasteurized (85 degrees C for 10 s), and treated by pulsed electric fields (25 kV/cm for 330 micros), were evaluated. The treatments, selected to reach a similar level of pectin methylesterase inactivation, produced juices that did not differ in acceptability from each other for the three varieties and in all cases were less acceptable than the untreated juice.

889

Pulsed electrical stimulation for control of vasculature: temporary vasoconstriction and permanent thrombosis

A variety of medical procedures is aimed to selectively compromise or destroy vascular function. Such procedures include cancer therapies, treatments of cutaneous vascular disorders, and temporary hemostasis during surgery. Currently, technologies such as lasers, cryosurgery and radio frequency coagulation, produce significant collateral damage due to the thermal nature of these interactions and corresponding heat exchange with surrounding tissues.We describe a non-thermal method of inducing temporary vasoconstriction and permanent thrombosis using short pulse (microseconds) electrical stimulation. The current density required for vasoconstriction increases with decreasing pulse duration approximately as t!0.25. The threshold of electroporation has a steeper dependence on pulse duration—exceeding t!0.5. At pulse durations shorter than 5 ms, damage threshold exceeds the vasoconstriction threshold, thus allowing for temporary hemostasis without direct damage to surrounding tissue.With a pulse repetition rate of 0.1 Hz, vasoconstriction is achieved approximately 1 min after the beginning of treatment in both arteries and veins. Thrombosis occurs at higher electric fields, and its threshold increases with vessel diameter. Histology demonstrated a lack of tissue damage during vasoconstriction, but vascular endothelium was damaged during thrombosis. The temperature increase does not exceed 0.1 8C during these treatments. Bioelectromagnetics 29:100–107, 2008. ! 2007 Wiley-Liss, Inc.

890

Pulsed electromagnetic energy treatment offers no clinical benefit in reducing the pain of knee osteoarthritis: a systematic review

BACKGROUND: The rehabilitation of knee osteoarthritis often includes electrotherapeutic modalities as well as advice and exercise. One commonly used modality is pulsed electromagnetic field therapy (PEMF). PEMF uses electro magnetically generated fields to promote tissue repair and healing rates. Its equivocal benefit over placebo treatment has been previously suggested however recently a number of randomised controlled trials have been published that have allowed a systematic review to be conducted. METHODS: A systematic review of the literature from 1966 to 2005 was undertaken. Relevant computerised bibliographic databases were searched and papers reviewed independently by two reviewers for quality using validated criteria for assessment. The key outcomes of pain and functional disability were analysed with weighted and standardised mean differences being calculated. RESULTS: Five randomised controlled trials comparing PEMF with placebo were identified. The weighted mean differences of the five papers for improvement in pain and function, were small and their 95% confidence intervals included the null. CONCLUSION: This systematic review provides further evidence that PEMF has little value in the management of knee osteoarthritis. There appears to be clear evidence for the recommendation that PEMF does not significantly reduce the pain of knee osteoarthritis.

891

Pulsed electromagnetic field at 9.71GHz increase free radical production in yeast (Saccharomyces cerevisiae)

Potential human health hazards have been reported after exposure to electromagnetic fields at low power density. Increased oxidative stress has been suggested as a potential mechanism involved in long-term effect of such exposure. In the present work, yeast cultures were exposed for 20min to a 9.71GHz pulsed electromagnetic field at specific absorption rates (SAR) from 0.5W/kg to 16W/kg. Oxidative perturbations were investigated using ESR spin trapping experiments and their impacts on membrane fluidity were assessed using spin label five nitroxide stearate. The experiments using the water-soluble spin trap alpha-(4-pyridyl-1-oxide)-N-t-butylnitrone and the lipid-soluble N-tert-Butyl-alpha-phenylnitrone showed an increase of spin adduct production both in low power density exposure (SAR<4W/kg) and in thermal conditions (SAR>4W/kg). The membrane fluidity diminutions after exposure in all the conditions were consistent with lipid peroxidation. The overall results suggest an increase of the free radical production in the intra cellular compartment; however no effect on the yeast vitality was found.

893

Pulsed electromagnetic field stimulation of bone marrow cells derived from ovariectomized rats affects osteoclast formation and local factor production

This study examined the effects of a specific pulsed electromagnetic field (PEMF) stimulation on osteoclast formation in bone marrow cells from ovariectomized rats and to determine if the signal modulates the production of cytokines associated with osteoclast formation. Adult female Wistar rats were subjected to bilateral or sham ovariectomy, and primary bone marrow cells were harvested at 4 days (Subgroup I) and 7 days (Subgroup II) after surgery. Primary bone marrow cells were subsequently placed in chamber slides and set inside solenoids powered by a pulse generator (300 micros, 7.5 Hz) for 1 h per day for 9 days (OVX + PEMF group). Others (INT, SHAM, and OVX groups) were cultured under identical conditions, but no signal was applied. Recruitment and authentication of osteoclast-like cells were evaluated by determining multinuclear, tartrate-resistant acid phosphatase (TRAP) positive cells on day 10 of culture and by pit formation assay, respectively. The PEMF signal caused significant reductions in osteoclast formation in both Subgroups I (-55%) and II (-43%). Tumor necrosis factor-alpha (TNF-alpha), interleukin 1beta (IL-1beta), and interleukin 6 (IL-6) in OVX + PEMF group of Subgroup I were significantly reduced at 5, 7, and 9 days as compared to OVX group. The results found in this study suggest that osteoclastogenesis can be inhibited by PEMF stimulation, putatively due to a concomitant decrease in local factor production. Bioelectromagnetics 25:134-141, 2004.

894

Pulsed electromagnetic field stimulation of MG63 osteoblast-like cells affects differentiation and local factor production

Pulsed electromagnetic field stimulation has been used to promote the healing of chronic nonunions and fractures with delayed healing, but relatively little is known about its effects on osteogenic cells or the mechanisms involved. The purpose of this study was to examine the response of osteoblast-like cells to a pulsed electromagnetic field signal used clinically and to determine if the signal modulates the production of autocrine factors associated with differentiation. Confluent cultures of MG63 human osteoblast-like cells were placed between Helmholtz coils and exposed to a pulsed electromagnetic signal consisting of a burst of 20 pulses repeating at 15 Hz for 8 hours per day for 1, 2, or 4 days. Controls were cultured under identical conditions, but no signal was applied. Treated and control cultures were alternated between two comparable incubators and, therefore, between active coils; measurement of the temperature of the incubators and the culture medium indicated that application of the signal did not generate heat above the level found in the control incubator or culture medium. The pulsed electromagnetic signal caused a reduction in cell proliferation on the basis of cell number and [3H]thymidine incorporation. Cellular alkaline phosphatase-specific activity increased in the cultures exposed to the signal, with maximum effects at day 1. In contrast, enzyme activity in the cell-layer lysates, which included alkaline phosphatase-enriched extracellular matrix vesicles, continued to increase with the time of exposure to the signal. After 1 and 2 days of exposure, collagen synthesis and osteocalcin production were greater than in the control cultures. Prostaglandin E2 in the treated cultures was significantly reduced at 1 and 2 days, whereas transforming growth factor-beta1 was increased; at 4 days of treatment, however, the levels of both local factors were similar to those in the controls. The results indicate enhanced differentiation as the net effect of pulsed electromagnetic fields on osteoblasts, as evidenced by decreased proliferation and increased alkaline phosphatase-specific activity, osteocalcin synthesis, and collagen production. Pulsed electromagnetic field stimulation appears to promote the production of matrix vesicles on the basis of higher levels of alkaline phosphatase at 4 days in the cell layers than in the isolated cells, commensurate with osteogenic differentiation in response to transforming growth factor-beta1. The results indicate that osteoblasts are sensitive to pulsed electromagnetic field stimulation, which alters cell activity through changes in local factor production.

895

Pulsed electromagnetic field stimulation on posterior spinal fusions: a histological study in rats

This study reports the histological data relative to the effect of pulsed electromagnetic fields (PEMFs) on the evolution of posterior arthrodesis induced in the lumbar vertebrae of 12 adult male Sprague-Dawley rats. After the operation, one group of six rats was stimulated with PEMFs for 18 h per day, by means of a pair of coils fixed to the outside of the cage. A control group of six rats was given no stimulation after surgery. In the groups stimulated with PEMFs an acceleration of the process of bone callus organization was already observed after 4 weeks, and even more so after 8: An early replacement was in fact observed of the newly formed cartilage tissue with primary bone (at 4 weeks) and subsequently with secondary bone (after 8 weeks).

897

Pulsed electromagnetic field therapy of persistent rotator cuff tendinitis. A double-blind controlled assessment

The value of pulsed electromagnetic fields (PEMF) for the treatment of persistent rotator cuff tendinitis was tested in a double-blind controlled study in 29 patients whose symptoms were refractory to steroid injection and other conventional conservative measures. The treated group (15 patients) had a significant benefit compared with the control group (14 patients) during the first 4 weeks of the study, when the control group received a placebo. In the second 4 weeks, when all patients were on active coils, no significant differences were noted between the groups. This lack of difference persisted over the third phase, when neither group received any treatment for 8 weeks. At the end of the study 19 (65%) of the 29 patients were symptomless and 5 others much improved. PEMF therapy may thus be useful in the treatment of severe and persistent rotator cuff and possibly other chronic tendon lesions.

898

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

Authors conclude that PEMF may be useful in the prevention of osteoporosis resulting from ovariectomy and that PGE2 might relate to these preventive effects. 35 three-month-old female Sprague-Dawley rats were randomly divided into five different groups. Changes in trabecular bone perimeter, trabecular thickness and decreased trabecular separation were measured across the five groups. The restoration of trabecular bone structure was greatest in ovariectomized rats exposed to PEMF stimulation.

899

Pulsed electromagnetic field treatment failure in radius non-united fracture healing

Pulsed electromagnetic field (PEMF) treatment is a non-invasive technique which has wide use in promoting healing of delayed union and non-union of bone. According to reports in the literature, PEMF has a 'success' of about 70%, but with no clear-cut reason to explain the failures. Our tests were carried out on 11 patients with radius non-unions and delayed unions; the results suggest that PEMF failure is associated with implanted metallic plates. In our view, this can be explained because the conducting plates create a uniform bone biopotential around the fracture and thus prevent the negative polarization which stimulates callus formation. Although further controlled and randomized clinical tests are needed, our results indicate that it may be necessary to remove the plates before PEMF application.

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