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Stationary headband for clinical time-of-flight optical imaging at the bedside.

Conventional brain-imaging modalities may be limited by high cost, difficulty of bedside use, noncontinuous operation, invasiveness or an inability to obtain measurements of tissue function, such as oxygenation during stroke. Our goal was to develop a bedside clinical device able to generate continuous, noninvasive, tomographic images of the brain using low-power nonionizing optical radiation. We modified an existing stage-based time-of-flight optical tomography system to allow imaging of patients under clinical conditions. First, a stationary head-band consisting of thin, flexible optical fibers was constructed. The headband was then calibrated and tested, including an assessment of fiber lengths, the existing system software was modified to collect headband data and to perform simultaneous collection of data and image reconstruction, and the existing hardware was modified to scan optically using this headband. The headband was tested on resin models and allowed for the generation of tomographic images in vitro; the headband was tested on critically ill infants and allowed for optical tomographic images of the neonatal brain to be obtained in vivo.

Brain↗

[Health Council Report 'Radiofrequency electromagnetic fields (300 Hz-300 GHz). The Health Council of the Netherlands].

The Health Council of the Netherlands in 1997 issued a report updating the guidelines for maximum acceptable exposure to radiofrequency electromagnetic fields formulated in 1975. The new recommendations are based on thermal effects for frequencies over 10 MHz. The committee considers the results of studies indicating non-thermal effects such as direct damage to DNA, not reliable enough to be used in setting exposure limits. Electromagnetic interference by electromagnetic fields generated by hand-held telephones may indirectly result in threats to health if vital medical equipment is affected. The committee advises people wearing an implanted pacemaker not to carry a portable telephone that is in stand-by mode in close proximity to the pacemaker; a minimum distance of 15 cm should be observed.

Body Temperature Regulation↗

[No increase in cancer incidence due to high-voltage cables in Odijk].

OBJECTIVE: To determine the incidence of cancer in Odijk and the connection if any of the occurrence of cancer with the presence of a high-voltage cable constructed there in the fifties. DESIGN: Descriptive. SETTING: Public Health Services, South-East Utrecht, the Netherlands. METHOD: Data on the numbers of new cancer patients in Odijk over the period 1985/'96 were obtained from general practitioners, from the Integral Cancer Centre Mid-Netherlands (IKMN) and from the Foundation Dutch Study Group Leukaemia in Children. The classifications were according to age and to distance from the home to the high-voltage cable. The electric and magnetic field strengths in dwellings situated less than 28 m from the cable were calculated. RESULTS: Cancer was diagnosed in 131 patients in the period 1985/'96, 127 adults and four children. The cases in 3 of 4 children occurred in the period 1993/'96. Over the period 1990-1994, the registered cancer incidence did not deviate from the expected incidence in the IKMN region, nor from the mean incidence in the Netherlands. Neither for adults nor for children was a relationship found between cancer and living in the vicinity of the high-voltage cable. The exposure to the electric field of persons living in houses near the cable was maximally 7%, and exposure to the magnetic field maximally 6.5% of the maximal liminal values applied in the Netherlands on recommendation of the Health Council. CONCLUSION: No relationship existed between development of cancer and the presence of a high-voltage cable.

Adolescent↗

Effects of millimeter waves on ionic currents of Lymnaea neurons.

The effects of mm-waves 60.22-62.22 GHz and 75 GHz on A-type K+ currents and the effects of 61.22 GHz on Ca2+ currents of Lymnaea neurons were investigated using a whole-cell voltage-clamp technique. The open end of a rectangular waveguide covered with a thin Teflon film served as a radiator. Specific absorption rates at the waveguide outlet, inserted into physiological solution, were in the range of 0-2400 W/kg. Millimeter wave irradiation increased the peak amplitudes, activation rates, and inactivation rates of both ion currents. The changes in A-type K+ current were not dependent on the irradiation frequency. It was shown that the changes in the amplitudes and kinetics of both currents resulted from the temperature rise produced by irradiation. No additional effects of irradiation on A-type K+ current other than thermal were found when tested at the phase transition temperature or in the presence of ethanol. Ethanol reduced the thermal effect of irradiation. Millimeter waves had no effect on the steady-state activation and inactivation curves, suggesting that the membrane surface charge and binding of calcium ions to the membrane in the area of channel locations did not change.

Absorption↗

[The limit of the modifiability of cellular radiosensitivity in sequential exposure to ionizing radiation and physical factors of a nonionizing nature].

The application of a mathematical model of synergism in describing the consecutive combined actions of ionizing radiation and other physical agents has been considered. Using various cell systems it has been shown that the model permits to predict the highest dose modifying factor and conditions in which it can be achieved.

Animals↗

Calicivirus inactivation by nonionizing (253.7-nanometer-wavelength [UV]) and ionizing (gamma) radiation.

Noroviruses (previously Norwalk-like viruses) are the most common viral agents associated with food- and waterborne outbreaks of gastroenteritis. In the absence of culture methods for noroviruses, animal caliciviruses were used as model viruses to study inactivation by nonionizing (253.7-nm-wavelength [UV]) and ionizing (gamma) radiation. Here, we studied the respiratory feline calicivirus (FeCV) and the presumed enteric canine calicivirus (CaCV) and compared them with the well-studied bacteriophage MS2. When UV irradiation was used, a 3-log(10) reduction was observed at a fluence of 120 J/m(2) in the FeCV suspension and at a fluence of 200 J/m(2) for CaCV; for the more resistant phage MS2 there was a 3-log(10) reduction at a fluence of 650 J/m(2). Few or no differences were observed between levels of UV inactivation in high- and low-protein-content virus stocks. In contrast, ionizing radiation could readily inactivate MS2 in water, and there was a 3-log(10) reduction at a dose of 100 Gy, although this did not occur when the phage was diluted in high-protein-content stocks of CaCV or FeCV. The low-protein-content stocks showed 3-log(10) reductions at a dose of 500 Gy for FeCV and at a dose of 300 for CaCV. The inactivation rates for both caliciviruses with ionizing and nonionizing radiation were comparable but different from the inactivation rates for MS2. Although most FeCV and CaCV characteristics, such as overall particle and genome size and structure, are similar, the capsid sequences differ significantly, making it difficult to predict human norovirus inactivation. Adequate management of UV and gamma radiation processes for virus inactivation should limit public health risks.

Animals↗

High-frequency electromagnetic radiation injury to the upper extremity: local and systemic effects.

Industrial use of radiofrequency and microwave energy sources (nonionizing, high-frequency electromagnetic radiation) is a growing and widespread phenomenon, with projected risks of exposure to more than 20 million workers in the United States. A description of the nature of this form of electromagnetic energy is given, with emphasis on the variability of energy absorption by humans. The current state of biological research is reviewed, and a summary of the known effects of radiofrequency and microwave radiation exposure on animals and humans provided. These known effects appear to be principally thermal, similar to conventional electrical burn injuries, but with some unique systemic expression. Derangements of cardiovascular, gastrointestinal, endocrine, hematological, ophthalmological, and behavioral functions are well described in animal experimentation. Two patients are presented--one a young woman exposed to a high-density radiofrequency field in an industrial setting, leading to necrosis of the entire hand and wrist as well as to a constellation of systemic effects, and one an older woman exposed to excessive microwave radiation from a malfunctioning microwave oven, leading to chronic hand pain and paresthesias resembling median nerve entrapment at the carpus. The prevalence of potential exposure in certain industries is noted and recommendations for follow-up care of workers exposed to this form of trauma are delineated.

Accidents, Occupational↗

Increase in radiation-induced HPRT gene mutation frequency after nonthermal exposure to nonionizing 60 Hz electromagnetic fields.

It is widely accepted that moderate levels of nonionizing electric or magnetic fields, for example 50/60 Hz magnetic fields of about 1 mT, are not mutagenic. However, it is not known whether such fields can enhance the action of known mutagens. To explore this question, a stringent experimental protocol, which included blinding and systematic negative controls, was implemented, minimizing the possibility of observer bias or experimental artifacts. As a model system, we chose to measure mutation frequencies induced by 2 Gy gamma rays in the redox-sensitive hypoxanthine-guanine phosphoribosyl transferase (HPRT) gene in Chinese hamster ovary cells. We tested whether a 12-h exposure to a 60 Hz sinusoidally oscillating magnetic-flux density (Brms = 0.7 mT) could affect the mutagenic effects of ionizing radiation on the HPRT gene locus. We determined that the magnetic-field exposure induced an approximate 1.8-fold increase in HPRT mutation frequency. Additional experiments at Brms = 0.23 and 0.47 mT revealed that the effect was reduced at lower flux densities. The field exposure did not enhance radiation-induced cytotoxicity or mutation frequencies in cells not exposed to ionizing radiation. These results suggest that moderate-strength, oscillating magnetic fields may act as an enhancer of mutagenesis in mammalian cells.

Animals↗

Heating of tissues by microwaves: a model analysis.

We consider the thermal response times for heating of tissue subject to nonionizing (microwave or infrared) radiation. The analysis is based on a dimensionless form of the bioheat equation. The thermal response is governed by two time constants: one (tau1) pertains to heat convection by blood flow, and is of the order of 20-30 min for physiologically normal perfusion rates; the second (tau2) characterizes heat conduction and varies as the square of a distance that characterizes the spatial extent of the heating. Two idealized cases are examined. The first is a tissue block with an insulated surface, subject to irradiation with an exponentially decreasing specific absorption rate, which models a large surface area of tissue exposed to microwaves. The second is a hemispherical region of tissue exposed at a spatially uniform specific absorption rate, which models localized exposure. In both cases, the steady-state temperature increase can be written as the product of the incident power density and an effective time constant tau(eff), which is defined for each geometry as an appropriate function of tau1 and tau2. In appropriate limits of the ratio of these time constants, the local temperature rise is dominated by conductive or convective heat transport. Predictions of the block model agree well with recent data for the thresholds for perception of warmth or pain from exposure to microwave energy. Using these concepts, we developed a thermal averaging time that might be used in standards for human exposure to microwave radiation, to limit the temperature rise in tissue from radiation by pulsed sources. We compare the ANSI exposure standards for microwaves and infrared laser radiation with respect to the maximal increase in tissue temperature that would be allowed at the maximal permissible exposures. A historical appendix presents the origin of the 6-min averaging time used in the microwave standard.

Heating↗

Radiation exposure, socioeconomic status, and brain tumor risk in the US Air Force: a nested case-control study.

A nested case-control study was used to investigate the relation between a range of electromagnetic field exposures and brain tumor risk in the US Air Force. Cumulative extremely low frequency and radiofrequency/microwave electromagnetic field potential exposures were estimated from a job-exposure matrix developed for this study. Ionizing radiation exposures were obtained from personal dosimetry records. Men who were exposed to nonionizing electromagnetic fields had a small excess risk for developing brain tumors, with the extremely low frequency and radiofrequency/microwave age-race-senior military rank-adjusted odds ratios being 1.28 (95% confidence interval (Cl) 0.95-1.74) and 1.39 (95% Cl 1.01-1.90), respectively. By contrast, men who were exposed to ionizing radiation had an age-race-senior military rank-adjusted odds ratio of 0.58 (95% Cl 0.22-1.52). These results support a small association between extremely low frequency and radiofrequency/microwave electromagnetic field exposure and no association between ionizing radiation exposure and brain tumors in the US Air Force population. Military rank was consistently associated with brain tumor risk. Officers were more likely than enlisted men to develop brain tumors (age-race-adjusted odds ratio (OR) = 2.11, 95% Cl 1.48-3.01), and senior officers were at increased risk compared with all other US Air Force members (age-race-adjusted OR = 3.30, 95% Cl 1.99-5.45).

Adult↗

The challenge of biophysics to dynamic dermatology.

Dermatologic biophysics has much to offer both clinical and investigative dermatology. For the clinician, the radiation biophysicist can provide accurate measurements of ionizing and nonionizing outputs, including those for PUVA, and critical evaluation of radiation safety measures. In optics, there is a need for accurate measurements of skin color and examination of the skin at moderate magnification. The biophysicist, with the biomedical engineer, can improve all the physical modality instrumentation used in practice. In investigative dermatology, there is the cellular biophysics of radiation. Doppler techniques for skin circulation, spectroscopy of living cells, and many other applications are suggested for current and future studies.

Biophysical Phenomena↗

Nonionizing electromagnetic fields and cancer: a review.

Low-frequency electromagnetic radiation had previously been thought to cause human injury only by generation of excess heat or by shock from direct contact with electric current. Information accumulating over the past few decades, however, suggests that nonionizing electric and magnetic fields associated with this radiation may be an environmental etiology in human disease. Human beings are affected not only by natural background nonionizing electromagnetic fields produced by the Earth, but also by a host of manmade sources. Of the diseases believed related to these fields, cancer and participation of these fields in the carcinogenic process have received considerable attention. This paper is a review of the basic science that points to this possible association.

Animals↗

Environment and the skin.

The skin is an important organ of defense adaptation and a portal of entry for xenobiotics. It is vulnerable to physical, chemical, and biologic agents and capable of expressing responses to these agents in a variety of pathologic patterns. These patterns are characterized by morphologic and functional features which are elicited by careful examination and test procedures. Cutaneous cancer may result from exposure to nonionizing as well as ionizing radiation, to specific identifiable chemical hazards, and may be enhanced by trauma. Cutaneous hazards of chemical sources are largely found in the workplace and among consumer products, including drugs and toilet goods. Environmental skin diseases and injuries are preventable. Prior to use assessment for safety and for possible risks from exposure to an agent, product, or process is of primary importance in the prevention and control of environmental skin disease and injury.

Dermatitis, Occupational↗

[The effect of microwaves on the bioelectric brain activity].

The experiments on rats have shown that the effect of millimeter range electromagnetic radiation on the bioelectric brain activity is dependent on the initial functional state of central nervous system. Microwaves are able to cause a nonspecific electroencephalographic reaction of synchronization and probably the lower the bioelectric brain process dynamics of active rats. Enrichment of electrocorticograms with high-frequency rhythms and increase in degree of bioelectric brain dynamics can be observed in narcosis conditions. The appearance of biological resonance in the brain of narcotized rats preliminary injected aminazin by pulse-modulated microwaves is noted. This is expressed as epileptiform convulsive activity in electrocorticogram. It has been shown that the nonlinear dynamics method may provide a reliable characterization of changing bioelectric brain activity under of nonionized electromagnetic fields. It is possible to modulate the bioelectric brain activity by microwaves to change the functional state of central nervous system and probably of the whole organism.

Alpha Rhythm↗

Role of endogenous nitric oxide generation in the regulation of vascular tone and reactivity in small vessels as investigated in transgenic mice using synchrotron radiation microangiography.

Nitric oxide (NO) produced by endothelial NO synthase (eNOS) plays a central role in regulation of vascular tone and reactivity. The purpose of this study is to clarify the basal tone and microvascular reactivity in eNOS-overexpressing transgenic (Tg) mice in vivo with a microangiography system using monochromatic synchrotron radiation (SR). The mouse femoral artery was cannulated, nonionic contrast media was injected, and microangiography was performed in hindlimbs of mice. Serial images of the small blood vessels (diameter <200 microm) were recorded by the SR microangiography system. At basal conditions, the diameter of tibial arteries in eNOS-Tg mice was larger than that of wild-type mice (179 +/- 8 versus 132 +/- 8 microm; P < 0.01). l-NAME treatment decreased the vessel diameter and canceled the difference in vessel diameters between two genotypes. Acetylcholine- and sodium nitroprusside-induced relaxations of small vessels were significantly reduced in Tg mice compared with wild-type mice (35.0 +/- 9.4 versus 61.6 +/- 6.7%, 85.0 +/- 10.2 versus 97.3 +/- 6.7% of the maximum relaxation, respectively). Our data provide the evidence that overproduced NO from endothelium reduces vascular tone and plays a pivotal role in regulation of vascular tone in small vessels. Furthermore, the reduced NO-mediated relaxation in small vessels of eNOS-Tg mice is demonstrated for the first time in vivo. SR microangiography allows us to evaluate the reactivity in small-sized vessels and appears to be a powerful tool for assessing the microvascular circulation in vivo.

Angiography↗

Structural change of jack bean urease induced by addition of surfactants studied with synchrotron-radiation small-angle X-ray scattering.

Both the quaternary and subunit structures of jack bean urease in solutions with ionic and nonionic surfactants have been studied by small-angle X-ray scattering using a synchrotron-radiation source. The effects of those surfactants on the enzyme activity of urease have also been investigated in the same kind of solvent systems as those used for the scattering experiments. The present results show that the quaternary structure of urease in solution is fairly elongate and that by the relatively minor binding of SDS (SDS/protein = 0.23/1) the native urease molecule is dissociated into six identical subunits with nearly spherical structures. In addition the enzyme activity of urease was mostly retained under every solvent condition investigated, indicating that the subunit found in the present scattering experiments is the fundamental monomeric unit for both the quaternary-structure formation and enzyme function of urease.

Fabaceae↗

Surfactant sealing of membranes permeabilized by ionizing radiation.

Acute tissue injury and subsequent inflammation, including tissue edema and erythema, can be caused by sufficiently high levels of exposure to gamma radiation. The mechanism of this tissue injury is related to the generation of reactive oxygen intermediates (ROI) which chemically alter biological molecules and cell physiology. Cell membrane lipids are vulnerable to ROI-mediated lipid peroxidation that then leads to many of the acute tissue effects. We hypothesize that increased cell membrane permeability leading to osmotic swelling and vascular transudation is one of these effects. Thus we used adult postmitotic rhabdomyocytes in culture and microscopic fluorescence techniques to quantify radiation-induced changes in cell membrane permeability. Based on time-resolved dye flux measurements, a characteristic lag time of 34 +/- 3 min was determined between exposure to 160 Gy of gamma radiation and the decrease in membrane permeability. Administration of 0.1 mM nonionic surfactant Poloxamer 188 added to the cell medium after irradiation completely inhibited the dye loss over the time course of 2 h. Thus a reproducible model was developed for studying the mechanism of acute radiation injury and the efficacy of membrane-sealing agents. As only supportive measures now exist for treating the acute, nonlethal injuries from high-dose radiation exposure, agents that can restore cell membrane function after radiation damage may offer an important tool for therapy.

Animals↗

DNA damage from oxidants: influence of lesion complexity and chromatin organization.

DNA damage by reactive oxygen species results in a spectrum of DNA lesions including single-strand breaks (ssb) and double-strand breaks (dsb). However, most damage is not lethal, and the location and nature of the DNA damage, in addition to total number of breaks, are likely to be critical in determining ultimate survival. Generally associated only with ionizing radiation, multiply damaged sites (i.e., complex lesions and clusters of complex lesions in DNA) are more likely to be lethal because they are less easily repaired. We examined five drugs known to cause DNA adducts, strand breaks, and reactive oxygen species for their ability to produce complex lesions: 4-nitroquinoline-1-oxide (4NQO), H2O2, doxorubicin, Tirapazamine, and etoposide. As indicators of lesion complexity we compared 1) the ratio of ssb to dsb, 2) the rate of rejoining of single-strand breaks, 3) the relative lethality of the breaks (number of breaks per mean lethal dose), and 4) the ability to produce complex lesions. Tirapazamine, etoposide, and doxorubicin gave dsb/ssb ratios similar to that for X-rays, whereas 4NQO and H2O2 showed dsb/ssb ratios of 200 and 3250, respectively. The number of dsb per LD50 varied from 2.5 to 500 for different drugs. There was no apparent relation between ssb rejoining half-time (3.5-85 min) and relative lethality or lesion complexity. A modified (nonionic detergent) filter elution method confirmed that tirapazamine, like ionizing radiation, produced multiple dsb within single chromatin domains. These data indicate that complex lesions can be produced by a number of different chemicals and suggest that the damage that results in killing by these drugs may be related to production of multiply damaged sites in DNA.

Animals↗