• AC EM fields promote the repair of injured vascular networks (Herbst et al., 1988).

• EM devices have been patented for treating atherosclerotic lesions (i.e., small blood clots that build up on the walls of arteries and cause cardiovascular disease) and to control tissue growth (Gordon, 1986; Liboff et al., 1992b).

Osteoarthritis

In a recent clinical trial using a double-blind, randomized protocol with placebo control, osteoarthritis (primarily of the knee) treated noninvasively by pulsed 30-Hz, 60-G PEMFs showed the treatment group improved substantially more than the placebo group (Trock et al., 1993). It is believed that applied magnetic fields act to suppress inflammatory responses at the cell membrane level (O'Connor et al., 1990).

Electroacupuncture

Electrical stimulation via acupuncture needles is often used as an enhancement or replacement for manual needling. Clinical benefits have been demonstrated for the use of electrical stimulation (electrostimulation) in combination with acupuncture as well as for electrostimulation applied directly to acupuncture points.

As an enhancement of acupuncture, a smallscale study showed electrostimulation with acupuncture to be beneficial in the treatment of post-operative pain (Christensen and Noreng, 1989). Other controlled studies have shown good success in using electrostimulation with acupuncture in the treatment of chemotherapy-induced sickness in cancer patients (Dundee and Ghaly, 1989). In addition, electrical stimulation with acupuncture was recently shown to be beneficial in the treatment of renal colic (Lee et al., 1992).

As a replacement for acupuncture, electrostimulation applied in a controlled study to acupuncture points by a TENS unit was effective in inducing uterine contractions in postterm pregnant women (Dunn and Rogers, 1989). Further, research with rats has shown. that electrostimulation at such points can enhance peripheral motor nerve regeneration (McDevitt et al., 1987) and sensory nerve sprouting (Pomeranz et al., 1984).

Regeneration

Animal research in this area indicates that the body's endogenous EM fields are involved in growth processes and that modifications of these fields can lead to modest regeneration of severed limbs (Becker, 1987; Becker and Spadero, 1972; Smith, 1967). Russian research and clinical applications, along with studies now under way in the United States, indicate that low-intensity microwaves apparently stimulate bone marrow stem cell division and may be useful in enhancing the effects of chemotherapy by maintaining the formation and development, or hematopoiesis, of various types of blood cells (Devyatkov et al., 1991).

The following studies are also relevant to the use of BEM for regeneration:

• PEMF applications to promote peripheral nerve regeneration (Orgel et al., 1992; Sisken, 1992).

• The "diapulse" method of using pulsed, highfrequency EM fields for human wrist nerve regeneration (Wilson et al., 1974).

• DC applications to promote rat spinal cord regeneration (Fehlings et al., 1992; Hurlbert and Tator, 1992).

• Swedish work showing that BEM promotes rat sciatic nerve regeneration (Kanje and Rusovan, 1992; Rusovan and Kanje, 1991, 1992; Rusovan et al., 1992).

Immune System

During the past two decades, the effects of EM exposure on the immune system and its components have been extensively studied. While early studies indicated that long-term exposure to EM fields might negatively affect the immune system, there is promising new research showing that applied EM fields may be able to beneficially modulate immune responses. For example, studies with human lymphocytes show that exogenous EM or magnetic fields can produce changes in calcium transport (Walleczek, 1992) and cause mediation of the mitogenic response (i.e., the stimulation of the division of cellular nuclei; certain types of immune cells begin to divide and reproduce rapidly in response to certain stimuli, or mitogens). This finding has led to research investigating the possible augmentation by applied EM fields of a type of immune cell population called natural killer cells, which are

important in helping the body fight against cancer and viruses (Cadossi et al., 1988a, 1988b; Cossarizza et al., 1989a, 1989b, 1989c).

Potential Neuroendocrine Modulations

Low-level PEMFs have typically been shown to suppress levels of melatonin, which is secreted by the pineal gland and is believed to regulate the body's inner clock (Lerchl et al., 1990; Wilson et al., 1990b). Melatonin, as a hormone, is oncostatic (i.e., it stops cancer growth). Thus, if melatonin can be suppressed by certain magnetic fields, it also may be possible to employ magnetic fields with different characteristics to stimulate melatonin secretion for the treatment of cancer. Other applications may include use of EM fields to affect melatonin secretion to normalize circadian rhythms in people with jet lag and sleep cycle disturbances.

Table 2 provides an overview of selected citations to the refereed literature for these applications.

Future Research Opportunities

Although to date there is an extensive base of literature on the use of BEM for medical applications, the overall research strategy into this phenomenon has been quite fragmented. Because of BEM's potential for the treatment of a wide range of conditions, an integrated research program is needed that includes both basic and clinical research in BEM. These two approaches should be pursued vigorously and simultaneously along parallel tracks.

Basic research is needed to refine or develop new BEM technologies with the aim of establishing the fundamental knowledge about the body's endogenous EM fields and how they interact with clinically applied EM fields. A basic understanding of the BEM of the human body might provide insight into the scientific bioenergetic or bioinformational principles by which other areas of alternative medicine, such as homeopathy, acupuncture, and energetic therapies, may function. Furthermore, fundamental knowledge of BEM principles in the human body, in conjunction with psychophysiological states, might help facilitate understanding of mindbody regulation.

Clinical research, including preclinical assessments, is also essential, with the aim of bringing

the most promising BEM treatments and diagnostics from limited use into widespread use as quickly as possible. Although a number of BEM devices show promise as new diagnostics or therapeutics, they must be tested on humans to show exactly when they are effective and when they are not. Moreover, measures of clinical effectiveness and safety are required for FDA approval of BEM medical devices. Ultimately, knowledge about the safety of new BEM medical devices can be ascertained only from the appropriate clinical trials.

Basic

The current status of basic research in BEM may be summarized as follows:

• Nonionizing, nonthermal exogenous EM fields exert measurable bioeffects in living organisms. In general, the organism's response to applied EM fields is highly frequency specific and the dose-response curve is nonlinear (i.e., application of an additional amount of the EM field does not elicit a response of equal magnitude; the response eventually diminishes no matter how additional EM stimuli are applied). Extremely weak EM fields may, at the proper frequency and site of application, produce large effects that are either clinically beneficial or harmful.

• The cell membrane has been proposed as the primary site of transduction of EM field bioeffects. Relevant mechanisms may include changes in cell-membrane binding and transport processes, displacement or deformation of polarized molecules, modifications in the conformation of biological water (i.e., water that comprises organisms), and others.

• The physical mechanisms by which EM fields may act on biomolecules are far too complex to discuss here. However, the following references propose such physical mechanisms: Grundler et al., in press; Liboff, 1985, 1991; and Liboff et al., 1991.

Endogenous nonthermal EM fields ranging from DC to the visible spectral region may be intimately involved in regulating physiological and biochemical processes.

Consequently, the following pressing needs should be addressed in developing a basic BEM research program:

Table 2. Selected Literature Citations on Biomedical Effects of Nonthermal EM Fields (cont.)

Note: Reports listed in table 2 are selected from refereed medical and scientific journals, multiauthor monographs, conference proceedings, and patents. See References for identification of sources. This is a representative selection from a large body of relevant sources and is not meant to be exhaustive or definitive.