Current state and implications of research on biological effects of millimeter waves: a review of the literature
Bioelectromagnetics 19:393 – 413 (1998) Current State and Implications of Research on Biological Effects of Millimeter Waves: Andrei G. Pakhomov,1* Yahya Akyel,1 Olga N. Pakhomova,1 Bruce E. Stuck,2 and Michael R. Murphy3 1McKesson BioServices, Brooks Air Force Base, San Antonio, Texas2U.S. Army Medical Research Detachment of the Walter Reed Army Instituteof Research, Brooks Air Force Base, San Antonio, Texas3Directed Energy Bioeffects Division, Human Effectiveness Directorate, Air ForceResearch Laboratory, Brooks Air Force Base, San Antonio, Texas
In recent years, research into biological and medical effects of millimeter waves (MMW) has expandedgreatly. This paper analyzes general trends in the area and briefly reviews the most significantpublications, proceeding from cell-free systems, dosimetry, and spectroscopy issues through culturedcells and isolated organs to animals and humans. The studies reviewed demonstrate effects of low-intensity MMW (10 mW/cm2 and less) on cell growth and proliferation, activity of enzymes, stateof cell genetic apparatus, function of excitable membranes, peripheral receptors, and other biologicalsystems. In animals and humans, local MMW exposure stimulated tissue repair and regeneration,alleviated stress reactions, and facilitated recovery in a wide range of diseases (MMW therapy). Manyreported MMW effects could not be readily explained by temperature changes during irradiation. Thepaper outlines some problems and uncertainties in the MMW research area, identifies tasks for futurestudies, and discusses possible implications for development of exposure safety criteria and guidelines. Bioelectromagnetics 19:393 – 413, 1998. Key words: electromagnetic fields; bioeffects; mm wave band; millimeter waves, review INTRODUCTION
penetrating less than 1 mm into biological tissues. Anumber of theoretical models have been set forth to
The term ‘‘millimeter waves’’ (MMW) refers to
explain peculiarities and primary mechanisms of
extremely high-frequency (30 – 300 GHz) electromag-
MMW biological action [Fro¨hlich 1980, 1988; Golant,
netic oscillations. Coherent oscillations of this range
1989; Grundler and Kaiser, 1992; Belyaev et al.,
are virtually absent from the natural electromagnetic
environment. This absence might have had important
One of the most remarkable events in contempo-
consequences. First, living organisms could not havedeveloped adaptation to MMW during the course of
Contract grant sponsor: U.S. Army Medical Research and Materiel Com-
evolution on Earth. Second, some specific features of
mand; Contract grant sponsor: U.S. Air Force Armstrong Laboratory;
MMW radiation and the absence of external ‘‘noise’’
Contract grant number: U.S. Army contract DAMD17-94-C-4069 (to
might have made this band convenient for communica-
tions within and between living cells [Golant, 1989;
*Correspondence to: Andrei G. Pakhomov, USA-MCMR, McKesson
Betzky, 1992]. These arguments, although not ade-
BioServices, 8308 Hawks Road, Building 1168, Brooks Air Force Base,
quately proven, are often used to explain the high sensi-
San Antonio, TX 78235-5324. E-mail: [email protected]. af.mil
tivity to MMW of biological subjects. Indeed, MMWhave been reported to produce a variety of bioeffects,
Received for review 21 October 1997; final revision received 30 January
many of which are quite unexpected from a radiation
᭧ 1998 Wiley-Liss, Inc. Pakhomov et al.
(0.5%) in 1989 – 1990. Concurrently, MMW researchin the FSU expanded greatly: Both the count of publi-cations (up to 120 in 1995 – 1996) and their portion inthe FSU bioelectromagnetic research (20 to 30%) farexceeded these numbers for non-FSU publications.
Aside from the number of studies, there are im-
portant qualitative differences. Western (non-FSU) re-search was largely driven by concerns for public safety. However, safety issues occupy a relatively small por-tion of the FSU research, whereas far more studiesare related to medical applications of MMW. Over50 diseases and conditions have been claimed to besuccessfully treated with MMW alone or in combina-tion with other means. Lebedeva and Betskii [1995]have reported more than a thousand MMW therapycenters in the FSU and over 3 million people whoreceived this therapy. Naturally, the extensive medical
Fig. 1. Absolute numbers and percentages of publications on
use of MMW has stimulated basic research as well.
topics related to biological action of millimeter waves vs. years
Nowadays, MMW technologies are increasingly
of publication. The graph is based on counts of citations in the
being used in practical applications (e.g., wireless com-
EMF Database version 3.0, 1997. Studies by the former Soviet
munication, traffic and military radar systems), making
Union (FSU) scientists and by all other (non-FSU) were countedseparately. Vertical scale is the number of published MMW stud-
it imperative that bioeffects data be available for health
ies per 2-year time intervals (abscissa). Numbers next to the
hazard evaluation and restoring the interest to MMW
datapoints indicate the weight (%) of MMW studies in the FSU
biological research in the West. The number of non-
and non-FSU bioelectromagnetic research (i.e., the percentage
FSU publications on this topic is again increasing. A
of MMW studies relative to the total number of studies included
specialized MMW session appeared at the 1996 meet-
in the EMF database for the respective time periods).
ing of the Bioelectromagnetics Society and the 1997Second World Congress on Electricity and Magnetismin Biology and Medicine, and the first Infrared Lasers
rary electromagnetic biology is a surge in interest in
and MMW Workshop was held at Brooks Air Force
MMW biological and medical effects in the countries
Base, Texas in 1997. Unfortunately, the FSU research,
of the former Soviet Union (FSU). A striking differ-
a rich source of MMW bioeffects data, is not readily
ence in the FSU and ‘‘non-FSU’’ research activity in
available in the West and is scarcely known by Western
this area can be seen from counts of related publica-
tions. For example, the EMF Database1 version 3.0
The present paper is intended to fill in this gap
(1997) lists a total of 463 FSU publications on MMW-
by reviewing recent research in the MMW field, from
related topics, and only 261 such publications from the
molecules and cells to MMW therapy. We have ana-
rest of the world. Although these numbers should not
lyzed over 300 original FSU publications and about 50
be taken as exact (the Database includes most but cer-
non-FSU papers and selected those which appeared
tainly not all relevant citations), the situation in general
more interesting and credible. This review is primarily
is portrayed correctly and is particularly explicit in a
focused on experimental and clinical findings reported
historic perspective (Fig. 1). The non-FSU production
during the last decade. Therefore, it includes only a
reached its peak of 52 papers (including meeting ab-
few essential citations of earlier publications and does
stracts) in 1983 – 1984, when MMW titles were 3.3%
not cover such topics as theoretical modeling of possi-
of all non-FSU publications in the bioelectromagnetics
ble interaction mechanisms. Interested readers should
area. Then it gradually declined to only seven papers
see other reviews for additional information [Fro¨chlich,1980, 1988 (ed.); Gandhi, 1983; Grundler, 1983;
1The EMF Database is produced by Information Ventures, Inc. (Phila-
Postow and Swicord, 1986; Belyaev, 1992].
delphia, PA) and covers topics related to biological effects of electro-magnetic fields, from DC to submillimeter wavelengths. The Database
PHYSICOCHEMICAL EFFECTS, MMW
contains over 20,000 citations of relevant publications from varioussources, including peer-reviewed journals, books, proceedings, and
ABSORPTION, AND SPECTROSCOPY
meeting abstracts. Available citations are assimilated in the Databasewithout any preselection based on the language, affiliation of the authors,
A number of independent studies have shown
or relevance to a particular EMF frequency range.
specific MMW effects in the absence of living subjects,
Bioeffects of Millimeter Waves
i.e., in solutions of biomolecules and even in pure wa-
samples to particular radiation wavelengths strongly
ter. Fesenko and Gluvstein [1995] analyzed MMW ef-
varied from one blood donor to another.
fects on periodic voltage oscillations during discharge
Khizhnyak and Ziskin [1996] analyzed peculiari-
of a water capacitor. The capacitor, which was a dis-
ties of MMW heating and convection phenomena in
tilled water sample in a 1-mm capillary, was charged
water solutions. Besides the most expected reaction
by 18 V, 1-ms-wide unipolar rectangular pulses. The
(gradual temperature rise), irradiation could induce ei-
capacitor discharged within 500 – 600 ms after a pulse.
ther temperature oscillations and a decrease in average
The discharge curve contained periodic voltage oscilla-
temperature or a biphasic response in which the tem-
tions reaching 10 – 15 mV. The Fourier spectrum of
perature initially rises and then decreases. These anom-
these oscillations included two strong peaks, at 5.25
alous effects resulted from convective processes, i.e.,
and 46.8 Hz, and these peaks did not change during at
the formation of a toroidal vortex. When the vortex
least 2 h of experimentation. The water sample was
became stable, the temperature decreased after the ini-tial rise phase, although the irradiation was constantly
exposed at 36 GHz from an open-ended waveguide
maintained. The local temperature could decrease with
(7.2 1 3.4 mm cross-section). Irradiation at 50 mW
increasing power density, and, in biological systems,
output power greatly reduced the 46.8 Hz peak in
this would appear as an effect opposite to heating.
1 min and virtually eliminated it in 10 min; the 5.25 Hz
Probably, this phenomena could explain some of re-
peak shifted to 6.75 Hz. These changes showed little
ported ‘‘nonthermal’’ MMW effects. If irradiation con-
or no recovery within 2 – 60 min after cessation of a
tinued for a long time (30 – 40 min), the convection
10-min exposure. Irradiation at 5 mW output power
phenomena disappeared and could not be reintroduced,
produced similar changes, but, unexpectedly, was far
even after restoration of the initial temperature. This
less effective: the changes developed more slowly, and
observation suggested that some irreversible process
the original peaks were restored more quickly. Mecha-
had occurred in the liquid, which resembles findings
nisms of the phenomenon itself, its anomalous power
of the water ‘‘memory’’ cited above.
sensitivity, and the long-lasting ‘‘memory’’ of water
The supposed role of water as a primary target
were not understood. The authors suggested that
for MMW radiation motivated Zavizion et al. [1994]
MMW-induced changes in water properties could un-
and Kudryashova et al. [1995] to study how MMW
absorption at the wavelengths of 2.0, 5.84, and 7.12 mm
Direct MMW effects on pure water properties
is affected by the presence of other substances, namely
were also observed by holographic interferometry [Be-
a-amino acids (0.25–2.5 mol/l). Because MMW ab-
rezhinskii et al., 1993; Litvinov et al., 1994]. Refraction
sorption by amino acid molecules is negligible, the
of light in fluid was determined from the width and
absorption of solutions in most cases decreased propor-
number of interference bands formed by a He-Ne laser
tionally to the amino acid concentration. This differ-
beam (630 nm) passing through the fluid and a referent
ence in absorption by pure water and solutions, called
beam. Irradiation of distilled water at 10 mW output
‘‘absorption deficit,’’ increased with increasing length
power for 5 – 7 min caused no effect at 41.5 GHz, but
of the hydrophobic radical in a series of homologous
decreased the number of the interference bands from
amino acids (glycine, alanine, GABA, valine). Para-
6 to 5 at 51.5 GHz; the distance between the bands
doxically, the absorption deficit was negative for sar-
increased 1.2 times. These changes developed faster
cosine at 5.84 mm and 7.12 mm and for glycine at all
and were more profound in a 2% human blood plasma
the wavelengths, meaning that these two amino acids
solution. The effect reached saturation in 6 – 7 min and
can increase MMW absorption by water molecules.
was completely reversible. Both theoretical calcula-
A detailed theoretical analysis of MMW absorp-
tions and direct measurements established that maxi-
tion in flat structures with high water content was per-
mal MMW heating was about 1 ЊC. MMW-induced
formed by Ryakovskaya and Shtemler [1983]. The au-
changes in the light refraction coefficient were almost
thors produced dependencies of the specific absorption
an order of magnitude greater than produced by con-
rate (SAR) on the radiation frequency, temperature,
ventional heating by 1 ЊC and, therefore, were attrib-
thickness of the absorptive medium, and presence of
dielectric layer(s) above and/or underneath. This work
Other properties of blood plasma, such as dielec-
modeled most common biological setups, such as irra-
tric permittivity and absorption coefficient, could be
diation of cell suspensions in Petri dishes, cuvettes, etc.
altered by MMW irradiation as well [Belyakov et al.,
The wavelength in the medium, reflection coefficients,
1989]. Changes of only 0.05 – 0.5% in these parameters
depth of penetration, and SAR at the surface of a semi-
were measured but were well beyond the limits of
infinite absorptive medium were calculated for wave-
the method used (0.01%). The sensitivity of plasma
lengths from 1 to 10 mm, using 1-mm steps. For exam-
Pakhomov et al.
ple, the depth of penetration for 1- and 10-mm wave-
growth rate and bud formation in the culture of S.
lengths at 20 ЊC equals 0.195 mm and 0.56 mm, respec-
cerevisiae can be induced by 0.03 mW/cm2, 46 GHz
tively, and the respective surface SARs are 79.4 and
irradiation for 50 min. This effect was claimed to per-
15.5 mW/cm3 per 1 mW/cm2. Exposure through a thin
sist for over 20 cell generations. Periodicity of bud
dielectric layer (e.g., bottom of a Petri dish) may de-
formation was observed in control samples as well, but
crease reflection and further increase SAR by up to 2.5
it was less pronounced and had a different time dura-
times. SAR in thin absorptive films (0.1 – 0.01 mm)
tion (60 min vs. 80 min after MMW exposure).
increases greatly and may exceed SAR at the surface
Synchronizing effects of MMW were also ob-
of a semi-infinite medium more than 10-fold. Further-
served in higher plant specimens (Shestopalova et al.,
more, presence of a dielectric above or below the thin
1995). Barley seeds were exposed for 20 min at
absorptive film may increase SAR in the film by as
0.1 mW/cm2 (61.5 GHz), and then the exposed and
much as 20-fold. Apparently, the possibility of reach-
control seeds (150 seeds per group) were put into an
ing very high SAR levels and of local heating cannot
incubator for sprouting. The incubator was maintained
be underestimated, even for the incident power levels
at either 28 ЊC or 8 ЊC. Cytologic examination estab-
that are often regarded as nonthermal (0.1 – 1 mW/cm2).
lished that the degree of synchronization of cell divi-sion in MMW-exposed sprouts increased by 36%(28 ЊC) and 50% (8 ЊC) over the respective control
MMW EFFECTS AT SUBCELLULAR, CELLULAR, AND TISSUE LEVELS
Levina et al. [1989] studied MMW effects on the
development of a protozoan Spirostum sp. cell popula-
Growth Rate Effects
tion. The population was begun in a saline medium
Debates about resonance growth rate effects of
with beer yeast (550 mg/l) as food by adding of 5 – 6
MMW have been going on for over 20 years, and this
protozoan cells/ml. The culture was exposed once for
problem was widely discussed in earlier reviews. In
30 min at 1.5 mW/cm2 (7.1-mm wavelength), between
brief, Grundler and coauthors [1977, 1982, 1988] re-
days 2 and 11 of growth. Unexposed cultures grew
ported that the growth rate of the yeast Saccharomyces
exponentially up to a density of 100 cells/ml on day
cerevisiae may be either increased by up to 15% or
11, then rapidly died without reaching stationary phase,
decreased by up to 29% by certain frequencies of
obviously due to poisoning by waste products. Expo-
MMW within a 41.8 – 42.0 GHz band. The effect was
sures on days 2, 4, or 7 caused the populations to enter
established by different methods, both in suspended
the stationary phase on or around day 9. Exposures on
cells and in monolayer. According to recent observa-
day 9 or 11 postponed the population death by 5 days,
tions [Grundler and Kaiser, 1992], an effect of about
and the final cell content increased to 115–135 cells/ml
the same magnitude is produced by field intensities
on day 14. Irradiation on day 2 also increased the prolifer-
from 5 pW/cm2 to 10 mW/cm2 (8 kHz modulation).
ation rate, and by day 7 the cell density was nearly twice
The width of the resonance peaks increased with the
as high as in control samples. In another series of experi-
intensity from about 5 MHz to 12 – 15 MHz over the
ments, the population began with an initial concentration
above intensity range. However, thorough independent
of 1-2 protozoan cells/ml and stabilized in 8–10 days
attempts to replicate these findings were not successful
at 12–13 cells/ml. In these cultures, MMW exposure
[Furia et al., 1986; Gos et al., 1997], suggesting that
suppressed proliferation, and the final cell density was
these MMW effects could be dependent on (or even
only 6–10 cells/ml. This study indicated that irradiation
produced by) some as yet unidentified and uncontrolled
affects the population’s own growth control mechanisms
and that the effect depends on the stage and other particu-
Dardanoni and coauthors [1985] observed fre-
quency- and modulation-dependent effects on the
Exposure for 30 min at 2.2 mW/cm2, 7.1-mm
growth of yeast Candida albicans. MMW modulated
wavelength enhanced the growth of a blue-green algae
at 1 kHz reduced the growth rate by about 15% at
Spirulina platensis by 50% [Tambiev et al., 1989],
72 GHz, but not at 71.8 or 72.2 GHz. A 3-h continuous
whereas 8.34-mm wavelength produced no changes
wave (CW) irradiation at 72 GHz had the opposite
compared with sham control. The alga growth rate
effect, i.e., the growth rate increased by about 25% over
more than doubled when a 30-min irradiation at
the sham-irradiated control. Remarkable variability of
7.1 mm was immediately followed by exposure to
the results was noted, which could be a result of cell
high-peak power microwave pulses (15 pulses, 10-nspulse width, 6-min pause, 3-cm wavelength, 200 kW/cm2
subpopulations with different sensitivity.
Golant and coauthors [1994] reported that a
peak incident power density). Concurrently, photosyn-
marked synchronicity of periodic fluctuations in the
thetic oxygen evolution increased about 1.5 times. The
Bioeffects of Millimeter Waves
observed stimulatory effects are of considerable prom-
changes have not yet been convincingly defined. A
ise in biotechnology, in which S. platensis is used for
discussion is continuing as to whether super-low radia-
production of food protein and biologically active com-
tion intensities in these studies were measured correctly
[Osepchuk and Petersen, 1997a, 1997b; and a reply by
Other publications by the same authors [Tambiev
Belyaev et al., 1997]. Supposedly, some power at a
and Kirikova, 1992] and independent investigators [Re-
harmonic frequency might be transmitted to the sample
brova, 1992; Shub et al., 1995] presented MMW effects
despite large attenuation at the fundamental frequency.
on the growth rate of several species of bacteria, Cyan-
Whether this was the case or not, consistent observa-
obacteria, algae, yeasts, and higher plants (fennel, let-
tions of resonance effects represent an important find-
tuce, tomato). For example, in the yeasts S. cerevisiae
ing, which requires understanding and independent rep-
and S. carlsbergensis MMW shortened the phases of
culture growth 2.3 – 6.0 times and could increase the
MMW-induced visible changes in giant chromo-
biomass production rate by up to 253%. Effects on
somes of salivary glands of the midge AcricotopusEscherichia coli growth could be either stimulatory or
lucidus [Kremer et al., 1988]. A certain puff, the Balbi-
inhibitory, depending on the wavelength (6.0- to
ani ring BR1 in the chromosome II, reduced in size
6.7-mm band, ° 1 mW/cm2 for 30 min). However, all
after irradiation at 67.2 { 0.1 GHz or 68.2 { 0.1 GHz
three papers were summaries of the authors’ multiyear
(5 mW/cm2), and this effect seemed to be unrelated to
experiences with studying these and other MMW ef-
heating. Numerous alterations in the giant chromosome
fects and did not provide enough detail for full evalua-
morphology were also independently found in Chiro-nomus plumosus (Diptera) after a 15-min exposure at1 mW/cm2 [Brill’ et al., 1993]. Chromosome Alterations and Genetic Effects
Exposure of ultraviolet (UV)-treated E. coli cul-
ture to MMW at 61 { 2.1 GHz, 1 mW/cm2 increased
Absence of mutagenic or recombinagenic effects
cell survival [Rojavin and Ziskin, 1995]. The most
of MMW radiation was clearly demonstrated in the
likely mechanism of this effect was either direct or
late 1970s [Dardalhon et al., 1979, 1981], and later
indirect activation of the dark repair system. No sur-
investigations were consistent with this conclusion. At
vival effects were found if the sequence of exposures
the same time, a number of studies indicated that
was reversed, i.e., when UV irradiation was performed
MMW could affect the fine chromosome structure and
immediately after a 10- to 30-min MMW exposure.
function, cell tolerance to standard mutagens, and le-
Genetic effects of 61.02-61.42 GHz radiations
were studied in the D7 strain of the yeast S. cerevisiae
Best known is the recent work by Belyaev and
[Pakhomova et al., 1997]. MMW exposures lasted for
coauthors [1993a, b, 1994, 1996], who discovered
30 min at 0.13 mW/cm2, and were followed in 60 min
sharp frequency resonances by using an anomalous
by a 100 J/m2 dose of 254 nm UV radiation. Compared
viscosity time dependence (AVTD) technique. This
with the parallel control, the MMW pretreatment did
technique is supposed to reflect fine changes in DNA
not affect cell survival or the rate of reverse mutations,
conformation and DNA-protein bonds. At a resonance
but significantly increased the incidence of gene con-
frequency, biological changes could be produced by
versions. Sham-exposed samples showed no differ-
field intensities as low as 10019 W/cm2. The magnitude
ences from respective parallel control groups. The data
of changes gradually increased with the field intensity
suggested that MMW did not alter the UV-induced
and reached a plateau between 10017 and 1008 W/cm2,
mutagenesis, but might facilitate UV-induced recombi-
depending on cell density in exposed samples. Reso-
nagenic processes. A thermal mechanism for this effect
nance peaks for E. coli cells were found at 51.76 and
was improbable, but could not be ruled out entirely.
41.34 GHz; these values decreased in strains with in-
Excitable Tissues and Membranes
creased haploid genome length. These results pointedto the chromosomal DNA as a target for resonance
Along with the genetic apparatus, the cell mem-
interaction between living cells and MMW. The width
brane is another site suspected to be a primary target for
of the resonances increased from units to tens of mega-
MMW radiation. Many of the works discussed below
hertz by increasing the incident power, and this depen-
established profound MMW effects; however, only a
dence is in notable agreement with the one reported for
few attempts have been made to replicate them.
cell growth rate effects [Grundler and Kaiser, 1992].
Brovkovich et al. [1991] reported that 61 GHz,
However, the AVTD test is not a conventional
4 mW/cm2 radiation significantly activates the Ca//
technique in cell biology. Interpretation of AVTD data
pump in the sarcoplasmic reticulum (SR) of skeletal
is uncertain and functional consequences of AVTD
and heart muscles of the rat. The rate of Ca// uptake
Pakhomov et al.
by SR membranes was measured by an ion-selective
nylboron anions changed proportionally to MMW heat-
electrode in an ATP-containing medium. An intermit-
ing, regardless of the frequency (53 – 78 GHz range)
tent MMW treatment (5-min exposure, 15-min pause,
or modulation used. Irradiation of snail neurons at
3 cycles) of skeletal muscle SR increased the rate of
75 GHz (600 – 4200 W/kg) produced biphasic alter-
Ca// uptake by 23%, and this increased level was
ations of their firing rate, which were similar to those
retained for 1 h after the exposure. Uninterrupted
caused by equivalent conventional heating.
MMW irradiation had no effect in 10 min, but in-
Burachas and Mascoliunas [1989] studied MMW
creased Ca// uptake by 27% in 20 min; and the effect
effects on the compound action potential (CAP) in iso-
reached maximum (48%) in 40 min. In heart muscle
lated frog sciatic nerve. CAP decreased exponentially
SR, even a 5-min exposure enhanced Ca// uptake
and fell 10-fold within 50-110 min of exposure at
77.7 GHz, 10 mW/cm2. CAP restored entirely soon
Geletyuk and coauthors [1995] used patch-clamp
after the exposure, but the nerve became far more sensi-
(inside-out mode) to study 42.25 GHz radiation effects
tive to MMW: CAP suppression due to the next expo-
on single Ca//-activated K/ channels in cultured
sures became increasingly steep and finally took only
kidney cells (Vero). Exposure for 20 – 30 min at
10 – 15 min. This sensitized state persisted for at least
0.1 mW/cm2, CW, greatly modified the activation char-
16 h. In addition to this ‘‘slow’’ response, switching
acteristics of the channels, particularly the open state
the field on increased CAP amplitude instantly by
probability. The field increased the activity of channels
5 – 7%, and switching it off caused the opposite reac-
with a low initial activity and inhibited channels with
tion. These effects were found in ‘‘winter’’ frogs, but
initially high activity. In a subsequent study [Fesenko
weakened and finally disappeared in spring.
et al., 1995], these effects were reproduced without
A different effect in the isolated frog nerve was
direct irradiation of the membrane, just by applying
described by Chernyakov and coauthors [1989]. The
bathing solution pre-exposed for 30 min at 2 mW/cm2,
exposures lasted for 2-3 h, either with a regular fre-
42.25 GHz. Irradiation of the solution did not alter its
quency change by 1 GHz every 8 – 9 min or with a
pH or Ca// concentration, and the nature of the MMW-
random frequency change every 1-4 min (53 – 78 GHz
introduced channel-modifying properties of the solu-
band, 0.1-0.2 mW/cm2). The latter regimen induced an
tion is not understood. The solution retained its biologi-
abrupt CAP ‘‘rearrangement’’ in 11 of 12 exposed
cal efficacy for at least 10-20 min after cessation of
preparations: the position, magnitude, and polarity of
CAP peaks (the initial CAP was polyphasic) drastically
Kataev and coauthors [1993] used a voltage clamp
changed in an unforeseeable manner. The other expo-
to study membrane currents in giant alga cells (Nitellopsis
sure regimen altered the amplitude and duration of late
obtusa, Characea). Irradiation for 30–60 min at 41 GHz,
CAP components in 30-40 min. The authors supposed
5 mW/cm2 suppressed the chloride current to zero with
that MMW increased CAP conduction velocity in fast
no recovery for 10–14 h. Marked inhibitory effects were
nerve fibers and decreased it in slow fibers.
also found at 50 and 71 GHz, whereas most of other
Neither of these effects on CAP conduction was
frequencies tested in the 38–78 GHz range enhanced the
observed by Pakhomov et al. [1997a]. Irradiation for
chloride current up to 200–400% (49, 70, 76 GHz). This
10 – 60 min, either at various constant frequencies or
activation was reversible, and recovery to the initial value
with a stepwise frequency change did not alter CAP at
took 30–40 min. Moreover, ‘‘activating’’ frequencies
0.2 – 1 mW/cm2. At 2.0 – 2.8 mW/cm2, it produced mi-
could restore the chloride current after its complete and
nor changes, which were independent from the fre-
normally irreversible suppression by ‘‘inhibitory’’ fre-
quency and matched the effect of heating. At the same
quencies. MMW heating did not exceed 1 ЊC, and neither
time, a different MMW effect was revealed using a
activating nor inhibitory effects were related to or could
high-rate nerve stimulation test. MMW attenuated the
be explained by it. Calcium current also changed during
stimulation-induced CAP decrease in a frequency-
irradiation, but this effect was not frequency dependent
dependent manner. The effect reached maximum at
and could be adequately explained by heating. The au-
41.34 GHz [Pakhomov, 1997b], and at this frequency
thors noted that algae collected in the fall of 1990 and
the magnitude of changes was the same (20 – 25%) at
stored over the winter had entirely lost MMW sensitivity
0.02, 0.1, and 2.6 mW/cm2 [Pakhomov et al., 1997c].
A 100 MHz deviation from 41.34 GHz (to 41.24 or
Experiments with artificial bilayer membranes
41.44 GHz) reduced the effect about twofold, and a
and snail neurons did not reveal any frequency-specific
200 MHz deviation eliminated it. The field distribution
effects of MMW [Alekseev and Ziskin, 1995; Alekseev
over the preparation at these frequencies was virtually
et al., 1997]. The capacitance of artificial membranes,
the same, so different MMW absorption or heating
ionic channel currents, and the transport of tetraphe-
patterns could not account for the frequency specificity
Bioeffects of Millimeter Waves
of the effect. Interestingly, the most effective frequency
group), but not with inhibitors of cell wall synthesis
in these experiments happened to be the same as the
(penicillin group), of DNA-dependent RNA synthesis
resonance frequency in the cell genome studies of
(actinomycin D), of the RNA polymerase and RNA
synthesis (heliomycin), or protein biosynthesis inhibi-
Low-intensity MMW radiation effectively changed
tors (neomycin, tetracycline, etc.). Irradiation either in-
membrane functions in striated muscle and cardiac
creased or decreased the antibiotic sensitivity, and the
pacemaker cells [Chernyakov et al., 1989]. Exposure
probability of these opposite effects depended on the
at 0.1-0.15 mW/cm2 for 90 s or less (frequencies be-
antibiotic concentration. MMW could induce sensitiv-
tween 54 and 78 GHz) decelerated the natural loss of
ity to subbactericidal antibiotic concentrations, which
transmembrane potential in myocytes, or even in-
normally would not affect the cell growth. Within stud-
creased it by 5 – 20 mV. Exposure reduced the over-
ied limits, the effect showed no clear dependence on
shoot voltage, action potential amplitude, and conduc-
the radiation intensity or frequency. The data suggested
tion velocity. This effect was observed in 80% of expo-
that some membrane processes might be a target for
sures, with no clear dependence on the radiation
the MMW effect. The authors also noted that MMW
frequency. MMW influence on pacemaker activity was
treatment can reveal (or even induce) the heterogeneity
analyzed in 990 experiments with 80 tissue strip prepa-
of the sensitivity of a cell population to certain antibi-
rations from the frog heart sinoatrial area. In most
cases, irradiation immediately decreased the interspike
Rebrova [1992] reviewed various MMW effects
interval, often in less than 2 s. The maximal effect was
on cell metabolism, synthesis of enzymes, and other
reached within 30 s. The changes linearly increased
processes in unicellular organisms, e.g., frequency-de-
with the incident power increase in the range from 20 –
pendent enhancement and suppression of colicin syn-
30 to 500 mW/cm2. The frequency dependence of the
thesis in E. coli, stimulation of synthesis of fibrinolytic
effect was individual, with at least four maximums in
enzymes in Bacillus firmus, increasing of the contents
the studied range. Maximal preparation heating after a
of peptides, DNA, and RNA in B. mucilaginous, and
2 s exposure at 1 mW/cm2 was calculated as 0.005 ЊC.
suppression of tolerance to antibiotics in S. aureus. The
With a physiologic response latency of less than 2 s,
maximal magnitude of MMW-induced changes ranged
this response could not be thermal. Exposure to infra-
from 20 to 90%, depending on the wavelength and the
red light (4 to 6 mm wavelength) often evoked the
initial condition of the strain. In contrast to bacteria,
same effects as MMW, but the threshold intensity was
reproduction rate and biosynthetic properties of fungi
Aspergillus sp., Endomyces fibuliger, and Dacthilyum
In other experiments described in the same paper,
dendraides changed only after repeated exposures (10
low-intensity MMW synchronized firing of urinary
times). Certain MMW frequencies increased alpha am-
bladder mechanoreceptors, suppressed and altered the
ylase activity in A. orizae by 67% and suppressed glu-
T-peak on electrocardiography of in situ exposed myo-
coamylase by 30%; others had the opposite effect. In
cardium, enhanced respiration, altered membrane cal-
yeast species, MMW accelerated maltose fermentation
cium binding, and reduced the contractility of cardio-
by 73%, whereas synthesis of diacetil and aldehydes
myocytes. Summarizing their results, the authors stated
decreased by 20%. New biosynthetic culture properties
that the dependence of bioeffects upon radiation fre-
introduced by exposure persisted in at least 100 (S.
quency is not monotonic. Peaks of this dependence are
carlsbergensis) and 300 (S. cerevisiae) cell genera-
individual and are not fixed at particular frequencies,
tions. The selective stimulation of production of some
and they become smoother with increased complexity
enzymes and suppression of others is promising for
of physiologic control mechanisms involved.
An unusual ‘‘double-resonance’’ effect of MMW
Other In Vitro Effects
was described by Gapeev et al. [1994]. Spontaneous
Bulgakova et al. [1996] studied how MMW expo-
locomotor activity of the protozoan Paramecium cau-
sure of Staphylococcus aureus affects its sensitivity to
datum was not affected by irradiation unless both the
antibiotics with different mechanisms of action. Irradi-
radiation frequency and modulation were tuned to
ations lasted from 1.5 to 60 min (54 or 42.195 GHz,
‘‘resonance’’ values. These values were 42.25 GHz
or 66-78 GHz band with 1 GHz steps, 10 mW/cm2).
and 0.0956 Hz, respectively (0.5 duty ratio). At these
MMW heating did not exceed 1.5 ЊC. Over 1000 exper-
parameters, the threshold field intensity was about
iments with 14 antibiotics were completed. A differ-
0.02 mW/cm2. The effect reached maximum (about
ence in the growth of exposed cells compared with
20%) at 0.1 mW/cm2, and remained at this level at
control cells was most often observed with polypeptide
intensities up to 50 mW/cm2, despite increasing heat
antibiotics, which affect the cell membrane (gramicidin
production (0.1 – 0.2 ЊC at 5 mW/cm2). CW irradiation
Pakhomov et al.
or modulation rates of 16, 8, 1, 0.5, 0.25, or 0.05 Hz
its probability. The data suggested a reflex mechanism
produced no effect, regardless of the field intensity or
of the MMW action, maybe involving certain periph-
heating. At the resonance modulation frequency, a shift
of the carrying frequency to 42.0 or 42.5 GHz elimi-
These data are in agreement with later findings
nated the reaction. No effects were observed with heat-
by Potekhina et al. [1992]. Certain frequencies from
ing of samples by other means, e.g., infrared light
the 53 – 78 GHz band (CW) effectively changed the
modulated at 0.0956 Hz. Locomotor activity changes
natural heart rate variability in anesthetized rats. The
similar to the MMW effect could be evoked by increas-
radiation was applied to the upper thoracic vertebrae
ing the level of intracellular calcium, pointing to a
for 20 min at 10 mW/cm2 or less. The frequencies of
possible mechanism of the MMW action. However,
55 and 73 GHz caused pronounced arrhythmia: the
reasons for the ‘‘double-resonance’’ dependence of this
variation coefficient of the R-R interval increased four
to five times. Exposure at 61 or 75 GHz had no effect,
More reported MMW effects in various in vitro
and other tested frequencies caused intermediate
changes. Skin and whole-body temperature of the ani-mals remained unchanged. Similar frequency depen-dence was observed in additional experiments with
ANIMAL AND HUMAN STUDIES
3-h exposures; however, about 25% of experimentswere interrupted because of sudden animal death
MMW Effects on Peripheral Receptors
that occurred after 2.5 h of exposure at 51, 61, and
Abundant evidence for MMW effects in speci-
73 GHz. A possible role for receptor structures and
mens directly exposed in vitro neither explains nor
neural pathways in the development of the MMW-
predicts possible effects at the organism level. It is
clearly understood that MMW penetration into biologi-
Sazonov et al. [1995] compared alterations of
cal tissues is rather shallow, and any primary response
spontaneous afferent firing in the bladder nerve in frogs
must occur in skin or subcutaneous structures, or at the
when the bladder was exposed to infrared radiation
eye surface. This primary response would then mediate
and to MMW (42.19 { 0.15 GHz, 10 mW/cm2). The
all subsequent reactions by means of neural and/or
infrared intensity was adjusted to produce the same
humoral pathways. The nature of the primary response
heating as MMW. In control experiments, the firing
and consequent events has been a subject of intense
rate was stable for at least 1 – 1.5 h, but MMW in-
speculation [Golant, 1989; Mikhno and Novikov, 1992;
creased it instantly from 30.9 to 32 spikes/s (P õ .05)
Rodshtadt, 1993], but there is little experimental proof.
and to 48.3 spikes/s (P õ .01) by the end of a 20-min
As a matter of fact, the link between cellular and organ-
exposure. Immediately after cessation of irradiation,
ismal effects is missing and remains the least under-
the rate fell to 35.8 spikes/s, which was still signifi-
stood area in the MMW field. However, several studies
cantly higher (P õ .05) than before the treatment. Infra-
have suggested that peripheral receptors and afferent
red irradiation did not cause statistically significant
nerve signaling could be involved in the whole organ-
changes. This difference was interpreted as a proof of
ism’s response to a local MMW exposure.
a specific (nonthermal) MMW effect, which might in
Akoev et al. [1992] studied the response of elec-
principle take place in skin receptors as well.
troreceptor Lorencini capsules in anesthetized rays.
In contrast, infrared light and MMW at equivalent
Spontaneous firing in the afferent nerve fiber from the
intensities produced similar effects on the firing rate
capsule could be either enhanced or inhibited by MMW
of crayfish stretch receptor [Khramov et al., 1991].
irradiation (33 – 55 GHz, CW). The most sensitive
Changes were proportional to the average incident
receptors increased their firing rate at intensities of
power, regardless of modulation or radiation fre-
1 – 4 mW/cm2, which produced less than 0.1 ЊC temper-
quency, and were regarded as merely thermal.
ature rise. Intensities of 10 mW/cm2 and higher could
The possibility of modifying the peripheral recep-
evoke a delayed inhibition of firing, so the response
tor function by low-intensity MMW has been demon-
became biphasic. The authors emphasized that what
strated directly by Enin and coauthors [1992]. An elec-
they observed was not merely a bioeffect of MMW,
trodynamic mechanostimulator was used to apply
but was indeed a specific response of the receptor.
mechanical stimuli (50-ms duration, 1 to 2 mm ampli-
Chernyakov and coauthors [1989] were able to
tude) to individual skin mechanoreceptors on the sole
induce heart rate changes in anesthetized frogs by
of the hind limb of anesthetized rats. Responses to the
MMW irradiation of remote skin areas. The latency of
stimuli were recorded from afferent fibers in the iso-
the changes was about 1 min. Complete denervation
lated and cut peripheral end of the tibial nerve. The
of the heart did not prevent the reaction, but decreased
sole was exposed to 55, 61, or 73 GHz radiation at
Bioeffects of Millimeter Waves Radiation Millimeter Pakhomov et al.
0.75, 2.90, or 7.81 mW/cm2, respectively. Exposure
after laying) and pupas at the stage of imago tissue
lasted for 35 min and caused no changes in the skin
formation were exposed in a waveguide at 46.35, 46.42,
temperature (0.01 ЊC accuracy). MMW did not excite
or 46.50 GHz, for 4–4.5 h at 0.1 mW/cm2, followed by
mechanoreceptors, but markedly altered the threshold
incubation at 25 ЊC. Irradiation at 46.35 GHz, but not at
and latency of their response to mechanic stimuli. In
46.42 or 46.50 GHz, caused marked effects. Exposure of
some receptors, the threshold gradually increased, up
pupas increased incidence of morphologic abnormalities
to 180% of the initial value. In others, the threshold
2-4.5 times (P õ .05), but did not influence imago sur-
initially decreased by 8 – 12%, recovered within
vival. Exposure of embryos decreased survival by about
10 min, and increased to 160% by the 25th min of
30% (P õ .05) and enhanced morphologic abnormalities,
irradiation. After that, the receptors became completely
but this effect was rather variable. Supposedly, MMW
inactive and no longer responded to mechanical stim-
disturbed DNA-protein interactions that determine the re-
uli. The receptor response latency under exposure
alization of the ontogenetic program.
could fall to 70% or rise to 120%; the changes could
High-Power MMW Effects
also be biphasic. The MMW-induced changes weremaximum at 73 GHz, intermediate at 55 GHz, and
Over the past several years, physiologic effects
minimum at 61 GHz, despite that the incident power
of high levels of MMW radiation have been intensively
at 61 GHz was 4-fold greater than at 55 GHz. The
studied by Frei et al. [1995], Frei and Ryan [1997],
authors supposed that sensations reported by patients
and Ryan et al. [1996, 1997]. In ketamine anesthetized
under MMW therapy (vibration, warmth, numbness,
rats, exposure to 35 GHz, 75 mW/cm2 radiation
etc.) may result from functional disturbances and
(12 – 13 W/kg whole body SAR) increased the subcuta-
neous temperature by 0.25 ЊC/min and the colonic tem-
The ability of humans to detect weak MMW has
perature by 0.08 ЊC/min. Concurrently with the hyper-
also been repeatedly established under double-blind
thermia, mean arterial blood pressure first increased
conditions [Lebedeva, 1993, 1995; Kotrovskaia, 1994].
slightly and then fell until the point of death. Hypoten-
An examinee was situated in an isolated room and had
sion was accompanied by vasodilation in the mesen-
no contact with the experimenter. The outer surface of
teric vascular bed, similar to what occurs in heat stroke
the hand was exposed 20 times, for 1 min each. Expo-
induced by environmental heating. However, the onset
sures were separated by 1 min intervals and random-
of vasodilation and hypotension occurred at much
ized with sham exposures. The start and end of each
lower colonic temperatures (õ 37.5 ЊC vs. ú 41.5 ЊC).
irradiation and placebo were accompanied by sound
The lethal effect became irreversible when the mean
clicks. The examinee had to push a button when he
arterial pressure fell to 75 mm Hg, even if the exposure
felt the field. Neither examinee nor researcher knew
was discontinued. Most intriguing, pathologic exami-
the sequence of exposures and sham exposures; correct
nation of the skin of lethally exposed animals revealed
and incorrect reactions were recorded automatically.
no significant thermal damage or full-thickness burn,
Field perception was characterized by the reaction re-
and cardiovascular responses did not mimic those ob-
liability (the percent of MMW exposures detected) and
served in traditional burn models. Searching for physi-
the false alarms level (the percentage of sham expo-
ologic mechanisms mediating the hypotensive re-
sures erroneously detected). An examinee was regarded
sponse, the authors established that nitric oxide, plate-
as capable of detecting the field if the reaction reliabil-
let-activating factor, and histamine did not contribute
ity consistently and statistically significantly exceeded
to it. Exposure of rats at 94 GHz at a similar SAR
the false alarm level. With different frequencies (37.7,
produced a comparable pattern of heating and cardio-
42.25, 53.57 GHz), intensities (from 5 to 15 mW/cm2)
and bandwidths, the radiation was detected by 30 to
Experimental MMW Therapy: Animal Studies
80% of examinees. Interestingly, 37.7 GHz radiationat 15 mW/cm2 was detected by far fewer people than
Except those cited above, virtually all animal
42.25 GHz at 5 mW/cm2. The reaction latency was
studies on MMW effects have been related to various
usually between 40 and 50 s. It was speculated that
issues of MMW therapy, such as stress relief, wound
MMW perception could involve some types of mecha-
healing, tissue regeneration, and protection from ioniz-
ing radiations. Paradoxically, these animal studies arestill less numerous and comprehensive than reports on
Teratogenic effects of MMW
MMW therapy in humans. Many applications of the
The only study of MMW teratogenic effects was
MMW therapy seem to have never been adequately
performed in Drosophila flies by Belyaev et al. [1990].
tested in animal experiments. For example, we counted
Embryos of the blastula and gastrula stages (2.5 – 3 h
38 publications (including meeting abstracts) on vari-
Bioeffects of Millimeter Waves
ous clinical aspects of the MMW therapy for peptic
significantly greater than in the control animals: 7.9%
ulcers, but could find just one animal study on this
vs. 3.2% in the aseptic groups, and 6.3% vs. 2.7%
subject. It seems that in some cases animal studies did
in the septic groups (P õ .05). Exposures stimulated
not precede the clinical use of MMW (as one would
phagocytic activity of neutrophils and decreased the
expect), but were carried out to create experimental
blood level of circulating immune complexes. Thus,
justification for already reported clinical data.
MMW irradiation enhanced both septic and asepticwound healing and stimulated immune function. Tissue repair and regeneration. Among possible ther-
Detlavs et al. [1993, 1994, 1995, 1996] have ex-
apeutic applications of MMW, the more plausible and
tensively studied MMW effects on the composition of
understandable are treatments of surface lesions
granulation fibrous tissue (GFT) during early stages of
(wounds, burns, ulcers), which are directly reachable
wound healing. Their experiments were performed in
by the radiation. Indeed, this application has gained
rats with incised full-thickness dermal wounds. The
sound experimental support from several independent
injured area was exposed for 30 min daily for 5 days
works. Other studies have demonstrated that repair of
at 10 mW/cm2 (53.53 or 42.19 GHz CW, or 42.19 GHz
deep tissues (bone and nerve) could also be stimulated
with 200 MHz frequency modulation. Control ani-
by MMW, suggesting that such effects are mediated
mals underwent the same manipulations, but were
by activation of the organism’s own recovery mecha-
sham exposed. GFT samples from the wound were
taken for analysis on the 7th day. CW irradiation sig-
Zemskov et al. [1988] studied MMW effects on
nificantly decreased the GFT contents of glycoproteins
healing of skin wounds in rabbits. The animals were
(hexosamines, hexoses, and sialic acids), indicating a
randomly assigned to four groups; wounds in groups
suppression of the inflammatory process. In contrast,
1 and 2 were kept aseptic, and those in groups 3 and
modulated MMW enhanced the inflammation and in-
4 were infected with a pathogenic Staphylococcus. The
creased the production of glycoproteins. CW exposure
wound surface in groups 1 and 3 was treated with 37
decreased the GFT content of hydroxyproline, which
or 46 GHz CW MMW at 1 mW/cm2 for 30 min, twice
is a marker for total collagen, to 79 – 85% of the control
a day for 5 days. A horn irradiator was placed 2–5 mm
(P õ .01), whereas the modulated regimen increased
over the wound surface. Rabbits in groups 2 and 4
it to 126-133% (P õ .001). CW radiation at 53.53 GHz
served as untreated control animals. MMW decreased
usually was more effective than at 42.19 GHz. Both
swelling of wound edges, hyperemia, and infiltration,
the anti- and proinflammatory effects of MMW could
and rapidly reduced the wound area in the first 24 h;
be useful in clinical practice. CW exposure can be
it also stimulated phagocytosis and reduced bacterial
recommended for early stages of the wound healing
contamination. Complete healing of aseptic wounds in
when control of the inflammatory reaction is desirable.
the exposed group took 2.9 days less than in the control
Modulated radiation can be used to promote ultimate
group. Infected wounds cleaned up and filled with
recovery in slow-healing wounds or in cases of healing
granulation tissue on days 14 – 16 in the exposed group
deceleration in the late stages of tissue repair.
and only on days 21 – 23 in the respective control ani-
Ragimov et al. [1991] used MMW to stimulate
the repair of an experimentally produced bone defects
A similar protocol was used in a double-blind
in rabbits. A hole 6 mm in diameter was drilled in the
replicative study by Korpan et al. [1994]. Rabbits with
lower jaw bone, and the wound was sutured. The first
4 1 6 cm cutaneous wounds were randomly divided
exposure for 30 or 60 min was performed the next day,
into four groups of 18 animals each. The wounds of
and six more exposures were done over the next
two groups were rendered septic by inoculating them
2 weeks. The shaven nape was exposed from a horn
with 109 Staphylococcus cells. The wound was exposed
(2-cm2 aperture) placed 3 – 4 mm from the skin
for 30 min a day (37 GHz CW, 1 mW/cm2), for 5 days
(5.6-mm wavelength, 25 mW output power). Control
in one aseptic group and for 7 days in a septic one.
animals were handled similarly. Five animals from
The horn aperture was 10 cm from the wound surface.
each group were killed every week for morphologic
The other two groups were sham-irradiated and served
and roentgenographic analysis of bone repair. One
as aseptic and septic control groups. In irradiated ani-
week after the operation, the extent of reparative os-
mals, wound edge swelling and hyperemia subsided
teogenesis was the same in all the groups. Later on,
faster, and granulation tissue filled the wound earlier.
the regeneration was faster in exposed animals, particu-
On day 7, for example, the surface area of septic
larly in the group with 60-min exposures. By the end
wounds decreased by 19% in the control group, and by
of the observation period (28 days), the appearance of
44% in the irradiated group. The mean daily decrease
the traumatic defect in the control group was nearly
in wound surface area of the irradiated animals was
the same as it was in exposed animals on day 21. Pakhomov et al.
Hence, irradiation shortened the bone repair time by
delivered at 40-s intervals. Two regimens were
tested: 8-mm wavelength at 4 – 5 MW output power,
Kolosova and coauthors [1996a] established that
yielding 20 kV/cm E-field level at the skin surface,
MMW treatment could promote regeneration of a dam-
and 5 mm, 8 – 10 MW, 30 kV/cm, respectively. The
aged peripheral nerve. The sciatic nerve in 40 rats was
first of these regimens retarded tumor growth 1.5
transected in the thigh region and sutured. Skin over
times and increased the life span by 17 – 25 days after
the injury area was irradiated every third day for
the inoculations with 10 and 25 (1 103) cells the
10 min with 4-mW/cm2, 54-GHz radiation for 7 or
other regimen was less effective. The antitumor ef-
20 days; control rats were sham irradiated. Exposures
fect was presumably mediated by stimulation of im-
did not change the skin temperature (0.1 ЊC accuracy).
mune system, namely the so-called skin-associated
Upon the completion of the treatment course, the nerve
lymphoid tissue. Preliminary studies with exposure
was isolated, and the extent of regeneration was as-
before tumor inoculation showed that MMW re-
sessed electrophysiologically. After the 7-day course,
tarded the tumor growth nearly twofold.
the regeneration distance was 4.8 mm vs. 3.0 mm in
Because of concern about possible adverse effects
the control animals (P ú .05). After the 20-day course,
of MMW use in cancer patients, Brill’ and Panina
the effect became statistically significant: the regenera-
[1994] studied the transplantability and growth of a
tion distance was 18.4 { 0.4 mm versus 14.0 {
benign tumor (mammary fibroadenoma) in rats. Two
1.4 mm (P õ .01). The nerve conduction velocity also
tumor pieces were implanted to the right and left sides
significantly increased, whereas the amplitude and du-
through a cut in the middle of the abdomen. In 20 of
ration of the action potential were not affected.
49 operated animals, tissues in the cut were exposed
In a continuation study [Kolosova et al., 1996b],
to MMW (42.0 – 43.3 GHz band) for 15 min before the
the same irradiations were performed for 2 weeks after
implantation, the other animals served as control. In
the injury, and the nerve was isolated for examination
3 weeks, 39 of 58 tumors (67.3%) resolved in the
in 5 months. Indices of regeneration were the com-
control group, but only 11 of 40 (27.5%) resolved in
pound action potential amplitude and conduction ve-
the exposed animals (P õ .001). The percentages of
locity at different distances (5 to 19 mm) distal from
stable and growing unresolved tumors in both the
the suture. Both parameters were higher in the exposed
groups were the same. Hence, a single MMW exposure
animals. For example, 19 mm from the suture, the
of the implantation area increased tumor transplantabil-
velocity was 20.4 { 0.9 m/s vs. 15.5 { 0.9 m/s in
ity, although did not affect its proliferation.
control animals (P õ .05), and the amplitude was 313{ 34 mV versus 156 { 15 mV (P õ .001). Hence,
Stress alleviation and prevention effects. Temur’iants
exposures not only stimulated the growth of nerve fi-
and Chuyan [1992] demonstrated that MMW can alle-
bers, but facilitated their functional maturation as well.
viate immobilization-induced stress in rats. The authorsestablished that this MMW effect differed in specimens
Tumor growth and development. Experiments by
with different characteristic levels of exploratory activ-
Smirnov et al. [1991] were designed to evaluate the
ity, as evaluated by an open-field testing. In further
possible use of MMW for the treatment of cancer.
studies, the open-field testing was always done before
VMR tumor cells with a high metastasizing activity
stressing and MMW exposures, to divide the popula-
were inoculated into the tibial muscle of A/SNL line
mice at 5 1 105 cells/animal. Exposure for 5 days, 1 h
One of these studies [Temur’iants et al., 1993]
daily (12.5 mW/cm2, 7.09- to 7.12-mm wavelength,
was performed on 350 animals divided by low (LA),
50 Hz modulation), increased the average life span by
medium (MA), and high (HA) activity. Each activity
17% compared with sham control cells. The number
level was subdivided into five groups; group 1 was
of visible metastases decreased by more than 50% in
cage control, and groups 2 – 5 were housed for 9 days
lungs, liver, kidney, and adrenal glands, but not in
in individual boxes restricting their motion. Animals
lymph nodes. The authors noted variability of the
in groups 3 – 5 received daily 30-min MMW exposures
MMW effect, and in one series exposure even intensi-
of the occipital area, left hip, or right hip, respectively
(5.6-mm wavelength, 10 mW/cm2). Stress severity was
Chernov et al. [1989] attempted to suppress ma-
quantified by indices of the ‘‘nonspecific resistivity’’ of
lignant growth by extremely high peak power nanosec-
the organism, which included the lipids and peroxidase
ond MMW pulses. Rats were exposed immediately
contents in neutrophils, and succinate and alpha-2-
after inoculation with 10, 25, or 50 (1 103) Walker tumor
glycerophosphate dehydrogenases activities in lym-
cells and received two more exposures during the
phocytes. A typical stress reaction developed in unex-
next 2 days. Each exposure consisted of 43 pulses
posed MA rats: by days 6 – 9, the contents of lipids and
Bioeffects of Millimeter Waves
peroxidase decreased by 21 – 24%, and the activity of
effect if the exposure duration is 60 min. The decreased
dehydrogenases fell by 36 – 46%. Occipital or right hip
efficacy of a more prolonged MMW irradiation has
MMW irradiation prevented the stress reaction in MA
been observed in some other clinical and experimental
rats, whereas the left hip exposure was not effective.
studies as well, but this unusual time dependence has
The immobilization stress was the most pronounced in
not yet been discussed or explained.
unexposed HA animals; MMW exposures of the lefthip or occipital area prevented stress, whereas expo-
Combined MMW and ionizing radiation exposure.
sures of the right hip had little effect. In LA animals,
Gubkina et al. [1996] researched whether low-intensity
the stress reaction was relatively weak, and all the types
MMW can alleviate the effect of X-rays in rats. The
abdominal area was shaved and exposed to MMW in a
The next study used 640 albino rats, all with a
frequency-sweep regimen (38 to 53 GHz) at 7 mW/cm2
medium level of locomotor activity [Temur’iants et al.,
for 23 days, 30 min/day. Control animals not treated by
1994]. The same indices as above were compared in
MMW underwent all the same manipulations, including
four groups: cage control, hypokinesia without expo-
shaving. Exposures to 150 keV X-rays were performed
sures, exposures without hypokinesia, and both. The
daily during the last 8 days of the MMW course up to a
occipital area was exposed for 30 min/day, 9 days at
total dose of 24 roentgen. Blood serum and brain tissue
either 5.6- or 7.1-mm wavelength. Exposures without
samples were collected the next day after the end of
hypokinesia strongly activated succinate dehydroge-
exposures. MMW alone did not alter the serum glucose
nase (up to twofold, P õ .05). Irradiation at 5.6 mm
level (6.24 { 0.79 mM versus 6.53 { 0.80 mM in con-
(but not at 7.1 mm) increased the activities of acid and
trol animals); X-ray exposure increased it to 10.37 {
alkaline phosphatases and glycerophosphate dehydro-
0.75 mM (P õ .05), but combining X-rays with MMW
genase by 20 – 30%. Both wavelengths prevented or
prevented this rise (6.81 { 0.37 mM). MMW decreased
reversed stress-induced changes, 5.6 mm was more
the content of the soluble form of the acidic glial fibrillar
effective. Further experiments with 5.6-mm radiation
protein (s-AGFP) 1.5–2 times (P õ .05) in all analyzed
established that exposures for 15 min/day were less
structures of the brain (cerebellum, midbrain, and medulla
effective than for 30 min/day, and, paradoxically, in-
oblongata) and did not change the content of its fibrillar
creasing the exposure duration to 60 min/day elimi-
form (f-AGFP). X-rays decreased the levels of both forms
of the protein two to three times. After combined treat-
A similar exposure technique was independently
ment with MMW and X-rays, both s- and f-AGFP levels
used by Arzumanov et al. [1994]. The occipital area
did not differ from control animals and were significantly
was exposed at 5.6 mm simultaneously with immobili-
(P õ .05 and P õ .01) higher than after X-rays only.
zation of the rat’s head for 60 min/day for 10 days.
The authors concluded that MMW alleviated the effect
This stressing suppressed feeding and sexual behavior.
of X-rays at both cellular and organism levels.
It also increased the motor activity in a swimming test
Two other studies are of interest, although they
to the same degree in exposed and unexposed groups.
are only brief reports that do not contain essential ex-
The authors hypothesized that the immobilization
perimental details. Kuzmanova and Ivanov [1995]
stress was too severe and might mask MMW effects,
studied changes in the surface electrical charge of
so in the next series rats were immobilized and exposed
erythrocytes after MMW and g-ray exposures in rats. The
for only 30 min/day for 9 days. The stress effect was
shin of the right hind limb was exposed to 5.6-mm
assessed by the electric shock threshold, free-access
radiation for 10 days, 20 min/day at 1.1 mW/cm2,
water consumption, and Vogel’s choice test (consump-
followed with a 6 Gy whole-body dose of 137Co g-rays.
tion of water when each attempt to drink is accompa-
The surface charge of erythrocytes was assessed from
nied by an electric shock). Immobilization without ex-
their electrophoretic mobility (EPM) 3, 7, 14, 21, and
posure decreased threefold the number of attempts to
30 days after the exposures. The MMW treatment alone
drink in Vogel’s test; but, when immobilization was
had practically no effect, whereas g-rays alone de-
combined with MMW exposures, this index remained
creased EPM for the whole period of observation.
the same as in cage control animals. The shock thresh-
When g-irradiation was preceded by MMW, the EPM
old and free-access water consumption were not
remained the same as in control animals. The authors
concluded that MMW stabilized the membrane struc-
It is interesting to note some parallelism in the
ture and increased its resistivity to g-radiation.
above two studies. Using the same exposure proce-
Tsutsaeva et al. [1995] examined MMW-induced
dures, but different protocols and end points, both re-
survival changes in mice after a lethal dose of X-rays.
search groups established that there is an anti-stress
Irradiation with pulse-modulated MMW at 1 mW/cm2
effect of a 30-min irradiation, but there is no such
continued for 80 or 24 h before X-ray exposure or was
Pakhomov et al.
simultaneous with the X-ray exposure. All tested X-
Diseases reported to be successfully treated with
ray doses (7, 7.5, and 8 Gy) were 100% lethal with an
MMW belong to rather diversified groups. The most
average life span of 6 – 8 days; the first fatalities oc-
common applications of MMW are for gastric and duo-
curred on days 4 – 6. MMW treatment for 80 h before
denal ulcers (about 25% of studies); cardiovascular dis-
7 Gy of X-rays delayed the first deaths until day 14;
eases, including angina pectoris, hypertension, isch-
50% of the population died within 30 days, and 100%
emic heart disease, infarction (about 25%); respiratory
of the animals died by day 96. The MMW treatment
sicknesses, including tuberculosis, sarcoidosis, bron-
for 24 h appeared even more effective: first deaths
chitis, asthma (about 15%); and skin diseases, includ-
occurred on day 8, 50% of the animals died within 30
ing wounds, trophic ulcers, burns, atopic dermatitis
days, but no more fatalities were observed through day
(about 10%). These percentages are approximate, be-
96. Microwave irradiation simultaneously with the X-
cause we could not cover all clinical studies published
rays (7 Gy) increased the survival and life span of mice
and because many authors reported treatment of several
approximately fivefold. The protective effect of 24-h
diseases in one paper (so the sum would be over 100%).
MMW pretreatment decreased with increasing X-ray
Isolated studies claimed successful MMW treatment
dose to 7.5 Gy and became insubstantial at 8 Gy.
for asthenia, neuralgia, diabetes mellitus, osteochon-drosis, acute viral hepatitis, glomerulonephritis, alco-
MMW Therapy: Clinical Studies
holism, etc. MMW were also used for alleviation oftoxic effects of chemotherapy in cancer patients and in
The first clinical trials of MMW therapy began
preventive medicine and health resort therapy.
in 1977, and today the method has been officially ap-
In most cases, physicians use specialized MMW
proved by the Russian Ministry of Health and is used
generators, which are produced commercially by the
widely. As mentioned in the Introduction section, by
medical equipment industry. These generators operate
1995 over 3 million people have been treated at more
at average radiation intensities of 10 mW/cm2 or less in
than a thousand specialized centers as well as at regular
CW or frequency-modulated regimens at certain fixed
hospitals [Lebedeva and Betskii, 1995].
frequencies or within a wide frequency band. Three
General issues of the MMW therapy. MMW therapy
models have been reported used more often than all
involves repetitive local exposures of certain body
others together: ‘‘Yav’-1-7,1’’ (7.1-mm wavelength,
areas with low-intensity MMW. The area(s) to be ex-
42.19 GHz) (36%), ‘‘Yav’-1-5,6’’ (5.6 mm, 53.53 GHz)
posed, the radiation wavelength, and daily duration of
(31%), and ‘‘Electronica-KVCh’’ (4.9 mm, 59 – 63
procedures are determined by the physician based on
GHz band) (10%). Different generators were often used
the disease and the condition of the particular patient.
within a single study to compare their therapeutic effi-
The radiation intensity is usually regarded as a less
cacy; and more often than not, the efficacy was differ-
important variable. For most diseases, the daily expo-
ent, depending on the disease and patients’ condition.
sure varies from 15 to 60 min, and the therapy lasts
Some authors used in vitro tests to determine which
wavelength is more suitable for a particular patient
Publications on the clinical use of MMW number
before the onset of the therapy [Novikova et al., 1995].
in the hundreds. Many of them have claimed that
However, we have been unable to identify references
MMW monotherapy is more effective (sometimes, far
to the original studies that had shown why the frequen-
more effective) than conventional methods, such as
cies of 42.19, 53.53, and 59 – 63 GHz (and not others)
drug therapy, for a variety of diseases and disorders.
In some cases, MMW has helped the patients who had
In about 30% of clinical studies, the radiation
already tried all other known therapies without success
is applied to standard acupuncture points or so-called
and were considered incurable. At the same time,
biologically active points. This procedure is often com-
MMW seldom caused any adverse effects or allergies.
bined with finding the individual ‘‘resonance’’ fre-
MMW in combination with drug therapy facilitated
quency based on MMW-evoked ‘‘sensations’’ of the
favorable effects and/or reduced adverse side effects
patient (a method called ‘‘microwave resonance ther-
of drugs. Some authors reported that MMW might be
apy’’). In our opinion, this procedure should be re-
highly effective or not effective at all, contingent on
garded as a variety of acupuncture techniques along
the patient’s condition, individual sensitivity to MMW,
with electropuncture, acupressure, etc. Assuming the
and parameters of irradiation. A few authors reported
therapeutic efficacy of these techniques, it is no sur-
that MMW therapy was always less effective than con-
prise that MMW can be effective as well: irradiation
ventional techniques, and we found only one clinical
at about 10 mW/cm2 can also stimulate acupuncture
study saying that MMW therapy was not effective at
points by subtle heating or thermal ‘‘micromassage.’’
all [Serebriakova and Dovganiuk, 1989].
Clinical effects of the ‘‘MMW-puncture’’ are nonspe-
Bioeffects of Millimeter Waves
cific, meaning that they are similar to those of tradi-
erapy in 317 patients with duodenal and gastric ulcers.
tional puncture-based techniques. These effects are de-
The ulcer diameter ranged from 0.3 to 3.5 cm, and
termined by the selection of acupuncture points, inten-
the disease duration was from several months to more
sity and duration of their stimulation, rather than by
than 10 years. The epigastric area was exposed at
using MMW or other means for the stimulation. There-
10 mW/cm2, 5.6-mm wavelength for 30 min daily,
fore, studies using the MMW-puncture seem to be of
excluding weekends, until complete ulcer cicatrization.
greater interest for the acupuncture practice than for
A comparable control group of 50 patients received
the bioelectromagnetic science; such studies will be
conventional drug therapy. The ulcers cicatrized in
left beyond the scope of the present review.
95.3% of MMW-treated patients, with mean healing
Other areas of MMW exposure include sternum
duration of 19.8 { 0.45 days. The respective control
and xiphoid process, skin projection of the diseased
group values were substantially worse, namely 78%
organ, large joints, and the surface of wounds and ul-
and 33.6 { 1.12 days. The ulcer relapse rate was sig-
cers. Once again, we could not identify the studies
nificantly lower after the MMW therapy.
that originally provided the rationale and experimental
Megdiatov et al. [1995] evaluated the efficacy of
proof for the useful nature of MMW exposure of these
MMW therapy (42.2 GHz, 10 mW/cm2) in 52 patients
particular body areas. Except for the surface lesions,
with neuralgia. The radiation was applied to areas
the radiation is unable to penetrate to diseased organs.
where branches of the affected trigeminal nerve ap-
This fact is understood and discussed by many physi-
proach the skin (10 exposures or sham exposures,
cians, but no proven explanation of the MMW therapy
15 min each, concurrently with medicinal therapy).
Evident clinical improvement (decrease of the inci-
Many clinical studies do not conform to conven-
dence and severity of pain attacks) was achieved in 19
tional quality criteria (double-blind protocol, placebo
of 27 patients treated with MMW, and only in 4 of 25
treatment, adequate statistics, etc.). However, still oth-
patients receiving placebo exposures.
ers do conform and a lot of matching results have been
Liusov et al. [1995] studied MMW therapy ef-
provided by independent groups of investigators. Some
fects in 100 patients with unstable angina pectoris (this
clinical data on the MMW efficacy are quite impres-
is an intermediate condition between stable angina pec-
sive, and a few examples are given below (see a spe-
toris and infarction, and is characterized by a high risk
cialized review by Rojavin and Ziskin [1998] for addi-
of myocardial necrosis). The patients were divided into
four groups. Group 1 was treated by MMW only (10exposures of the right shoulder joint for 30 min/day,
Examples of MMW therapy. Korpan and Saradeth
7.1 mm); these patients ceased taking any vasodilators
[1995] performed a double-blind controlled trial of
and antianginal medicines. In group 2, the same MMW
MMW therapy for postoperative septic wounds. The
therapy was combined with drugs (beta-adrenergic an-
study group consisted of 141 patients, 31 – 83 yr old,
tagonists, calcium blockers, organic nitrates, etc.).
with purulent wounds after an abdominal surgery. The
Group 3 received the same drug therapy and placebo
wounds were infected mostly with S. aureus and Bacte-
exposures, and group 4 received the drug therapy only. roides fragilis. MMW therapy with 1 mW/cm2, 37 GHz
The therapy in groups 1 and 2 substantially decreased
CW radiation was used in 71 patients. Wound surface
the rate and severity of angina attacks, making it possi-
and adjacent soft tissue were exposed for 30 min/day
ble to reduce the amount of nitroglycerin taken. It also
for 7 days. The remaining 70 patients received placebo
decreased blood levels of malonic dialdehyde and die-
therapy from a similar but defective MMW generator
nic conjugates, normalized T-helper and T-suppresser
(neither patients nor physicians knew it was defective).
ratios, reduced the diameter of venules, and increased
Radical surgical cleaning of the wounds was performed
the diameter of arterioles. No significant improvement
regularly in both groups. The MMW-treated patients
of the lipid peroxidation system, immune status, or
showed 1.8 times more rapid wound clearance (5.6 {
microcirculation was achieved in groups 3 and 4.
0.6 vs. 10.2 { 0.5 days in control subjects), 1.7 times
Karlov and coauthors [1991] used MMW in a
earlier onset of wound granulation (4.9 { 0.2 vs. 8.7
combined therapy for cerebral circulatory disorders.
{ 0.4 days), and 1.8 times earlier onset of epitheliza-
The 79 patients in the study were mostly 50-80 yr old
tion (7.0 { 0.4 vs. 12.8 { 0.6 days). The average daily
and suffered from hypertensive disease and/or athero-
decrease of wound surface area in the treated patients
sclerosis; 61 patients were hospitalized for acute isch-
was twice that of the control subjects (7.1% vs. 3.2%).
emic cerebral infarction, 13 for a transient disorder of
The authors concluded that low intensity MMW seems
the cerebral circulation, and 5 for circulatory encepha-
to be an effective postoperative wound treatment.
lopathy. Patients were divided into two comparable
Poslavsky et al. [1989] used MMW as a monoth-
groups. Both groups received the same drug therapy
Pakhomov et al.
(hypotensive, anticoagulant, cardiotonic, and other
culatory encephalopathy, and cerebral insult conse-
remedies), whereas the first one was also treated with
quences. Irradiation of the sinocarotid zone at various
MMW (10 days, 30 min/day, 4.9-mm wavelength).
frequencies between 58 and 62 GHz, 0.3 – 1 mW/cm2,
Patients of the second group were sham-exposed under
was performed for 20 min/day or less, for 4 to 10
a double-blind protocol. A favorable therapeutic effect
days. MMW therapy facilitated recovery in 56 – 77%
was reported in 70% of the patients in group 1 and in
of patients with different pathologies. However, it also
40% in group 2. MMW procedures helped decrease
caused adverse side effects, including elevation of the
blood pressure, normalize the blood glucose level, and
blood pressure (nine cases), induction of a diencephalic
crisis or paroxysm during irradiation (seven cases), an-
The efficacy of the MMW therapy is often illus-
gina attacks (three cases), fever (five cases), and en-
trated by individual clinical cases. Naumcheva [1994]
hancement of menstrual bleeding (six cases). In hyper-
described the history of a 54-yr-old male patient, who
tension patients, MMW usually decreased blood pres-
had two myocardial infarctions within a 2-yr interval.
sure by 10 – 15 mm Hg, but occasionally increased it
He experienced severe attacks of angina both on exer-
by 20-30 mm Hg. The author concluded that MMW
tion and at rest and took up to 80 nitroglycerin tablets
can be successfully used in cerebrovascular therapy,
a day (0.4 mg). Repeated courses of in- and outpatient
but possible complications must be taken into account.
treatment with beta-adrenoblockers, nitrates, plasma-
Afanas’eva and Golovacheva [1997] used MMW
pheresis, etc. had little effect. Finally, he was hospital-
therapy in 124 patients with stage II essential hyperten-
ized in a grave condition with a third infarction. Con-
sion (5.6- or 7.1-mm wavelength, CW, 10 mW/cm2, 10
ventional methods were ineffective, so MMW therapy
procedures for 30 min each). Unfavorable autonomous
was ordered on day 10 after admission (7.1-mm wave-
nervous system reactions (whole-body shivering,
length, for 30 min/day to the left border of sternum).
sweating, heart pains along with skin paling or redden-
Cardialgia decreased after two exposures and nighttime
ing) were observed in 18 patients (15.5%). In two
pain attacks ceased after seven procedures. The nitro-
cases, these reactions developed into hypertensive cri-
glycerin intake was decreased to 1 – 2 tablets/day after
ses, which had to be arrested by drug injections. In 33
12 exposures. After the MMW course, the patient did
patients (26.6%), MMW-induced fluctuations of the
not have angina attacks for 3 – 4 days, was able to walk
arterial blood pressure and enhanced headaches. A tem-
up to 5 km a day, and was discharged in a satisfactory
porary improvement after four to five exposures was
condition. Another man, age 62, was admitted to hospi-
followed by an increase in both systolic (by 25 {
tal with a severe macrofocal infarction, collapse, extra-
7.0 mm Hg) and diastolic (by 10.0 { 2.0 mm Hg)
systolia, and acute insufficiency and aneurysm of the
blood pressure, which required medicinal correction.
left ventricle. Three days of intensive treatment still
General adverse reactions after the entire MMW course
left the patient in this critical condition. Even the first
(six patients; 4.8%) included sleeplessness or sleep
MMW irradiation of sternum (5.6-mm wavelength,
with distressful dreams, weakness, emotional instabil-
three 10-min exposures with 5-min intervals) had a
ity, and irritability. These manifestations were not pro-
striking effect: it arrested angina attacks and normal-
found and disappeared without further treatment. The
ized sleep, and indices of hemodynamics stabilized
authors emphasized that these adverse reactions were
within 5 days of the MMW therapy. The patient was
not encountered in patients who received placebo expo-
discharged in a satisfactory condition and later under-
went two additional MMW courses as a preventive
Gun’ko and Kozshina [1993] tried MMW therapy
in 528 patients with various diseases (ulcerative dis-ease, ischemic heart disease, essential hypertension,
Side effects of MMW therapy. As a rule, MMW ther-
bronchitis, pneumonia, and others). Exposures at 5.6-
apy is well tolerated by patients, and this is regardedas one of its advantages over a drug therapy. Although
or 7.1-mm wavelength lasted from 15 to 60 min/day,
most investigators reported no negative reactions to
from 5 to 18 days. Three patients being treated for
MMW, others observed them in up to 26% of patients
rheumatic polyarthritis, psoriasis, and duodenal ulcer
[Golovacheva, 1995]. The possibility of induction of
(without any concurrent drug therapy) developed urti-
adverse health effects by a local, low-intensity MMW
caria (hives) on the fifth to seventh day of exposures.
irradiation is of potential significance for setting health
An itchy rash appeared first in the abdominal and tho-
and safety standards and requires special attention.
racic areas, and soon spread everywhere. Nevertheless,
Kuz’menko [1989] summarized experience with
the treatment of the main disease in all these cases was
MMW use in 200 patients with cerebrovascular dis-
successful. The rash disappeared 2-10 days after the
eases, such as cerebral circulation insufficiency, discir-
completion of the MMW therapy but reappeared during
Bioeffects of Millimeter Waves
the repeated MMW courses. The authors called for
replicated in the West. Replication is much needed
more studies of MMW effects on the immune system.
indeed, but it can hardly be anticipated without ade-quate attempts. To our knowledge, only three labora-tories throughout the U.S. (less than 10 scientists total)
DISCUSSION
are currently doing any research on MMW bioeffects,
In this review, we have found that recent research
which is by no means sufficient to match the amount
in the MMW area covers a variety of subjects. Pro-
and variety of the FSU research. Besides, many cited
found MMW effects were established at all biological
studies are very recent (1995 – 1997), so replication has
levels, from cell-free systems through cells, organs,
and tissues, to animal and human organisms. Although
With all the diversity of the MMW research and
trying to avoid a general discussion of thermal versus
differences in studied subjects and end points, some
nonthermal mechanisms in this review, we nonetheless
particulars seem to be common for various situations
must note that many of the reported effects were princi-
and MMW effects. Considering these particulars may
pally different from those caused by heating, and their
dose and frequency dependencies often suggested non-
(1) Individuals or groups in a population, which
thermal mechanisms. Regardless of the primary mecha-
would usually be regarded as uniform, may react to
nism, the possibility of significant bioeffects of a short-
MMW in rather different or even opposite ways. For
term MMW irradiation at intensities at or below current
example, Temur’iants et al. [1993, 1994] divided the
safety standards deserves consideration and further
vivarium population of rats by their open-field activity
before performing exposures. Not only the animal’s
The major question about FSU publications in the
reactions to MMW, but also their reactions to immobi-
MMW area is their reliability. A number of studies
lization stress, were very different in animals with low,
cited here were performed at the highest scientific
medium, and high activity levels. Pooling all the data
level. Other studies, perhaps the majority of those cited,
together, as well as neglecting the intrinsic differences
were flawed, but may still bear valuable information
in the population, would have inevitably masked
and should not be discarded without proper analysis.
For example, free-field dosimetry in the MMW band
(2) There seem to exist unknown and uncon-
is a serious technical problem. To our knowledge, no
trolled factors that determine the MMW sensitivity of
commercially available probes are rated for near-field
a specimen or a population. Irradiation could increase
measurements in the MMW band even in the U.S.
antibiotic resistivity in one experiment and decrease it
Therefore, it is not surprising that many investigators,
in the next one [Bulgakova et al., 1996]. It increased
particularly clinicians, have had to rely on manufac-
the beating rate in one isolated heart and decreased it
turer-specified field intensities, such as 10 mW/cm2 for
in the other [Chernyakov et al., 1989]. MMW therapy
‘‘Yav’-1’’ therapeutic generator. One may doubt that
usually decreased blood pressure, but eventually in-
the field actually was 5, 10, or 15 mW/cm2, but under
creased it greatly [Kuz’menko, 1989]. As long as these
no circumstances could it exceed a spatial average of,
changes exceeded the ‘‘noise’’ level and were not pro-
say, 50 mW/cm2, which is beyond the generator’s capa-
duced by a sham exposure, they can be regarded as
bilities. Thus, whereas the precise exposure parameters
MMW effects. Again, pooling all data together, regard-
may not be known, a range of possible exposure inten-
less of the direction of changes, could easily mask an
sities may be estimated. With an understanding of this
fact, the experimental data may still be important and
(3) Even robust MMW effects may be well repro-
ducible for a limited time and then disappear. The ef-
Another widespread shortcoming of clinical stud-
fects of complete suppression or 200 – 400% enhance-
ies occurs when MMW therapy is compared with drug
ment of chloride transmembrane current in alga cells
therapy, without using a sham-exposed control group.
were far beyond any spontaneous variations and could
MMW therapy was often reported to be more effective
hardly be confused with any artifact [Kataev et al.,
than drugs. This result could be a placebo effect; but
1993]. However, both effects weakened and disap-
if so, one would have to conclude that placebo was
peared by the end of winter without any apparent rea-
more effective than modern drug therapy. This possi-
son. MMW effects on isolated frog nerve also disap-
bility could certainly be true for certain patients and
peared in spring [Burachas and Mascoliunas, 1989],
certain disorders, but does not seem feasible for large
suggesting that MMW sensitivity may be somehow
populations and a wide scale of diseases.
related to the base level of metabolism.
A further source of skepticism about findings
4. MMW effects could often be revealed only in
made by FSU scientists is that they have not been
subjects that are experiencing some deviation from the
Pakhomov et al.
‘‘normal’’ state. MMW caused little or no reactions in
Air Force Armstrong Laboratory under U.S. Army con-
intact animals, but significantly alleviated effects of im-
tract DAMD17-94-C-4069 awarded to McKesson Bi-
mobilization, ionizing radiation, etc. Many clinical studies
oServices. The views expressed in this article are those
claim that MMW therapy is effective only when one or
of the authors and should not be construed as reflecting
another kind of pathology is present, whereas in a healthy
the official policy or position of the Department of the
organism MMW will not produce any reactions. How-
Army, Department of the Air Force, Department of
ever, this thesis has not been adequately proven.
Defense, or the United States Government.
5. Increased sensitivity and even hypersensitivity of
individual specimens to MMW may be real. Dependingon the exposure characteristics, especially wavelength, a
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A Randomized Comparison of Indwelling Pleural Catheter and Doxycycline Pleurodesis in the Management of Malignant Pleural Effusions Joe B. Putnam, Jr., BACKGROUND. The purpose of this study was to compare the effectiveness and Richard W. Light, safety of a chronic indwelling pleural catheter with doxycycline pleurodesis via R. Michael Rodriguez, tube thoracostomy in the treatment of
Chapter 22 Solutions 22.1. (a) Diagram below. (b) The null hypothesis is “all groups have the same mean rest period,” and the alternative is “at least one group has a different mean rest period.” The P -value shows significant evidence against H 0, and the graph leads us to conclude that caffeine has the effect of reducing the length of the rest period. Note: Students mig