[C’è un uomo di spalle, in piedi. Indossa l’impermeabile e il cappello. Ha appena spento la luce della sua stanza d’ufficio. Con la mano destra reg- ge una borsa marrone di pelle, voluminosa; la sinistra è appoggiata alla maniglia interna della porta che sta per aprire. (Uscito, la richiuderà dietro di sé, si avvierà verso l’ascensore, saluterà il portiere nell’atrio con un «buon
Qj91010008From the Richard J. Fox Center for Biomedical Physics, Temple University School of Medicine,Philadelphia, USA The biological effects of millimetre waves (MWs) at tion resides in Soviet/Russian/Ukrainian reports on power levels <20 mW/cm2 were first discovered in the late 1960s, and within 10 years were studied in However, their analysis allows us to reveal some various countries including the former USSR,1–4 general features of MW therapy. Upon comparing Canada,5,6 France7 and Germany.8,9 These early the clinical information with the existing experi- studies used a wide variety of objects ranging from mental results, we can better understand the possible biomolecules to bacteria to tissues of higher organ- mechanisms involved, as well as the most potentially isms. Poor reproducibility of some of the experi- beneficial applications of MW therapy.
mental results and the lack of acceptable theoreticalmodels resulted in a significant delay to researchactivity in this area in the USA.10–12 In the meantime, based on the biological experi- ments, medical applications of MWs began in theformer Soviet Union in the 1970s,13,14 and since the MWs belong to a relatively narrow range of electro- mid–1980s, have been in widespread usage. Use of magnetic waves with wavelengths from 1 to 10 mm MWs for medical purposes is known as ‘Millimetre (corresponding to frequencies from 300 to 30 GHz, Wave Therapy’ (MW therapy), ‘Extremely High with 1 GHz=109 oscillations per second). MW gen- Frequency (EHF) therapy’, or, less frequently, erators and related equipment were produced primar- ‘Microwave Resonance Therapy’. With numerous ily for military purposes (short-range radar), which, medical MW generators now employed in hospitals to a large extent, explains the secrecy and predomin- and clinics in the former USSR and some other ance of incomplete publications on this topic in the European states (some estimates range as high as 50 000 units15), thousands of patients undergo The penetration depth of MWs into biological treatment with MWs every year. Some authors16,17 tissues is very small. Unlike centimetre and decimetre claim that there are several hundred thousand waves, MWs are absorbed in water and water- patients who have been treated with MWs. The containing media (including biological structures) reported success rate of MW therapy for various within the first 0.3–0.5 mm from the surface, pathologies is astonishingly high. However, this treat- depending on the frequency used.18–20 With energy ment modality is almost unknown to Western med- insufficient to break chemical bonds directly,21,22 ical scientists and practitioners. There is only one and a low average incident power density of <20 publication on this subject in Western peer-reviewed mW/cm2, MWs usually produce an average heating of an irradiated surface on the order of several tenths We present an overview of the available informa- of a degree C, which is usually imperceptible.
tion regarding MW therapy. The majority of informa- Obviously the range of reported biological and Address correspondence to Dr M. Rojavin, Center for Biomedical Physics, Temple University School of Medicine, 3400 N.
Broad St, Philadelphia, PA 19140, USA medical effects of MWs cannot be explained by such Physicians using MW therapy, irrespective of the a small bulk heating of structures. H. Fro¨hlich21,23–25 disease being treated, have observed some general suggested that such effects might occur through a features which form three main groups. They are: (i) resonance-type interaction, since some of the biomo- lecules and structural elements of the cells have their action and enhancement of tissue regeneration pro- own theoretically calculated resonant frequency cesses; and (iii) immune stimulation.
within the range of 1010–1011 Hz. Several experi-ments showing narrow resonant frequency depend- ence of biological effects of MWs seem to supportthis hypothesis.3,6–9,26,27 These are the most common effects of MW therapy However, other physical mechanisms may also be which are cited by the majority of physicians and responsible for the biological effects of MWs. It has patients. Usually, after the first 2–3 sessions of MW been shown, both theoretically28 and experiment- therapy, 73–100% of patients report alleviation of, ally,29,30 that not only the absolute value, but the rate or even total relief from, the pain accompanying the of heating is of critical importance for biological effects.
disease, whether peptic ulcer,34,36,62,63 heart dis- The initial rate of heating due to MW exposure is ease64,65 or a pruritic skin condition.48,49 This is usually very high, reaching 0.1–0.5 °C/s,30–32 and is followed by normalization of sleep and improvement sufficient to produce some biological effects, such as of general condition. Sleepiness sometimes develops an increase in neuronal firing rates.
during the MW therapy sessions.65 Efficacy of MW Another important characteristic of MWs is their therapy in treatment of males with psychogenic heterogeneous distribution on the surface of exposed sexual dysfunction66 can probably also be attributed objects. As shown by infrared thermography,33 so-called ‘localized hot spots’ with a temperature Pain relief is considered among the most general elevation several degrees Celsius higher than the purposes of MW therapy application: in one of the average can be formed on the surface of the skin.
largest cardiology centres in Russia, a clinical studyis underway in which the decreased level of bloodendorphins in patients with acute cardiac disordersis regarded as an indication for performing MW During the past 20 years, MW therapy has been Some recent experiments confirmed that low- used for a broad spectrum of diseases and conditions, power MWs are capable of interacting with neurons some of which are listed in Table 1. The list of affecting the electrical characteristics of neuronal pathological conditions treated with MW therapy functioning27,30 and the production of some neuro- includes: some gastrointestinal diseases (peptic ulcer, peptides.39 In vitro, MW directly affected such func- gastroduodenitis);34−39 diabetes;41 coronary artery tions of neurons as firing rate, amplitude and form disease and some other blood circulation dis- of the signal in marine skates,68 frogs,27,69 and orders;42–45 cerebral palsy;46 chronic non-specific snails.30 In vivo exposure of mice to MWs increased pulmonary diseases;47 skin diseases such as psoriasis by 40–50% the duration of anaesthesia caused by and atopic dermatitis;16,48,49 enhancement of bone several non-opioid anesthetics.70 The additional and wound healing.50–54 MW therapy has also been anaesthetic effect of MW was completely blocked used to treat cancer patients, as a means of increasing by pre-treatment with the opioid antagonist naloxone, their non-specific immunity and alleviating the toxic suggesting that MW therapy causes a release of side effects of chemo- and radiotherapy.55–57 There opiate substances in the exposed organism. It is too have been some promising results in the use of MW early at this stage to make definite statements that therapy for treating opioid, alcohol and nicotine opioids are being released in the body during MW therapy based on this one experiment, but some of In all of the above cases, MW therapy seems to the clinical data given below make such a possibility enhance regulatory effects, restoring a patient’s homoeostasis.17,39 This means that, depending on the A clinical study of 70 opioid drug abusers58 condition of a patient, MW therapy can cause such revealed that MW therapy alone can significantly changes as an increase or decrease of blood pres- improve the conditions of patients suffering from sure,45 stimulation of inhibited (or suppression of withdrawal symptoms. After the first session of MW excessive) immune activity,16,39,60,61 etc. For more therapy, symptoms of abstinence were relieved for data on efficacy of MW therapy in various diseases 2 h in 33.8% patients, up to 6 h in 50.7%, up to 12 h in 15.8%. Full relief usually developed after 3–12 Instead of sorting information according to disease, sessions (days) of MW therapy. Drug abusers reported we will analyse it by the types of effect generated.
the sensory feelings comparable with those from Efficacy of MWT in treating various diseases CD4+/CD8+ T-cells rationormalization, SOD activityincreased, serumcomplement activitydecreased * MWT was used together with an appropriate conventional drug therapy; ** MWT was used as a monotherapy.
drugs. About 60% of patients fell asleep during enhances the rate of the recovery process by 1.5–2 the MW therapy sessions. After the first session, the times by decreasing the duration of oedema and concentration of met-enkephalin in peripheral blood exudative-inflammatory phases of wound healing. It increased from 41±8 to 252±22 pg/ml, adaptogenic has also been reported that MWs, when applied hormone prolactin from 7.0±0.3 to 10.2±0.3 ng/ml.
directly to an infected wound surface, can cause a Other researchers also seem to be optimistic about sharp decrease in microbial contamination of the the therapeutic potential of MW therapy in treatment wound and favourable changes in the sensitivity of of opioid drug abuse, alcoholism, and tobacco smok- micro-organisms to some antibiotics.51,52,71,72 The ing.16,59 Experimentally-proven release of opioid sub- former can be a result of (i) the direct action of MWs stances in patients due to application of MW therapy on micro-organisms (in vitro inhibitory effects of would definitely substantiate such an optimism, as MWs on various bacteria have been reported by well as provide a basis for the wide use of MW several investigators4,6,8,9) and/or (ii) enhancement of therapy for any pathological condition where pain the host’s immune system. A decrease of R-plasmid- mediated resistance of E. coli to tetracycline hasbeen observed in vitro,51,73 and is potentially a veryimportant feature of MW. It would be of special value when applying MW therapy for treatment of infected surface wounds (trauma, burn patients, etc.).
Early experiments with wounded rabbits, mice and In clinics, MW therapy speeds up the recovery of other laboratory animals14,50–52,71,72 showed that the patients suffering from various kinds of infected or exposure of a wound surface to MW significantly clean wounds and fractured bones. The diseases where these characteristics of MW therapy are used formed granulation tissue. This granulation tissue range from gastric/duodenal ulcers to surface wounds contained fibroblasts, macrophages, mast cells and (including such conditions as stasis ulcers of diabetic lymphocytes. Plasma cells with an augmented secre- patients and infected burns) to complicated bone tion of immunoglobulins prevailed. Samples obtained fractures, even with osteomyelitis.53,56,74 after 10 procedures of MW therapy showed complete The only known double-blind clinical study epithelization of the former defect, frequently without of MW therapy in septic wound treatment was conducted by N. Korpan and colleagues at the The ability of MW to cause healing of skin without Department of General Surgery, Kiev State Medical scarification was also demonstrated by dermatologists University.75 This trial was a logical extension of who treated skin wounds and lesions.49,76,77 Based Korpan’s previous experiments on rabbits, in which on this, several beauty clinics in Moscow and Kiev continuous MW with a frequency of 37 GHz and started using MW therapy in cosmetology.
incident power density of 1 mW/cm2 applied directlyto the wound area significantly accelerated healingof the surface wounds.52,71 Two groups of patients with post-operative wounds (after surgery on bileducts, gallbladder, pancreas, appendix, and after Laboratory investigations have confirmed that MW herniotomy) were included in this study: group A therapy produces non-specific enhancement of the (71 patients) received standard wound treatment plus MW therapy; group B (70 patients) received, in increased phagocytic activity of macrophages,32,78 addition to standard treatment, a placebo MW expo- enhanced proliferation and normalization of the ratio sure from an ineffective generator. MW therapy was of CD4+/CD8+ T-lymphocytes,35,38,60,79 increased applied for 30 min daily for 7 consecutive days with amount of B-lymphocytes and normalized production the applicator of the generator placed 5–10 mm from the surface of the skin (wound area). Wound healing Human peripheral blood macrophages appear to was significantly accelerated in group A: 5.6±0.6 be very sensitive to MW therapy. For example, in a days vs. 10.2±0.5 days for the placebo group. The clinical study with active pulmonary tuberculosis time of initial epithelization, granulation, daily size patients,78 MW therapy was used in combination of wound surface area and duration of in-hospital with antibiotics. After 3 months of treatment, cavities stay were significantly reduced ( p<0.05), by 1.8–2 in lungs resolved in 59% of patients from the MW times lower for the patients treated with MW therapy.
therapy-treated group vs. 30% among the patients The authors concluded that MW therapy was an receiving antibiotics only. Numbers of macrophages effective method of post-operative treatment of puru- in peripheral blood and their phagocytic activity lent wounds after abdominal surgery. The above (determined by the nitroblue tetrazolium [NBT] study could be viewed as the first published attempt reduction test) were much higher in patients treated to organize a clinical trial of MW therapy according with MW therapy. In fact, the physicians used to Western standards, and its results are encouraging.
the NBT test as an indicator for the most effective In addition to treating the wound infections, MW frequency by exposing the blood samples in vitro therapy is reported to be an effective method of to MW of various frequencies, and then choosing preventing post-surgical infections in cancer patients.
the frequency producing the highest increase in According to Kabisov,56 application of MW therapy oxidative burst of macrophages. These data correlate in 50 nose, ear and throat cancer patients decreased with our findings that MW therapy can significantly the rate of infectious side-effects after surgery from increase the phagocytic activity of peritoneal macro- phages against Candida albicans in mice treated with Interestingly, it has been observed that in most cyclophosphamide.32 Here MW therapy caused cases when peptic ulcer is treated with MW therapy, enhanced antimicrobial immunity resulting in faster unlike any other known method, the ulcerous defect clearance of the affected organ/tissue from pathogens, is healed without formation of scar tissue. This as in several other experimental and clinical unique feature was first reported by the endoscopists who diagnosed peptic ulcer patients,37,76 and con- firmed by histological studies and electron micro- T-cells was observed in blood of patients with scopy. Biopsies from duodenal mucosa of 10 patients cardiac,83 diabetic,17,84 oncological16,57 and other with duodenal ulcers treated with five sessions of MW therapy showed proliferation of poorly differ- entiated duodenal epithelial cells; normalization of improved.32,48 Enhanced immune reaction mediated the endothelial cell structure of microvessels (capil- primarily through T-cells was found in mice exposed laries); and filling in the ulcer defect with a newly- to MW.85 The above combination of features, if confirmed, would make MW therapy a very powerful to MW at the power level 10 mW/cm2 for a period of 58 days. As a result of this direct exposure, theeyes of rats became 33% less transparent to visiblelight—the animals had developed cataracts. Such experimental conditions are however very different Several clinical studies with hundreds of patients from those used to treat patients: duration of exposure each45,86–88 have reported only a few side-effects to MW was at least several thousand times higher, of MW therapy, and these were established without and no medical protocol includes direct exposure of using a placebo control. Gunko and Kozshina86 eyes. Cataract formation was not found in other found that 3/528 patients (0.6%) with various internal studies in which more clinically-oriented protocols diseases treated with MW therapy developed urticaria were used. Furthermore, the very first publication on after 5–7 exposures. The pruritic rash in the abdom- medical use of MW came from an ophthalmological inal and thoracic area disappeared after the end of clinic.14 In this study, traumatic corneal wounds in the MW therapy course, and reappeared during the the eyes of rabbits were healed by direct irradiation following repeated courses. Nevertheless, treatment with MW. According to Cherkasov et al.,14 who of the patients with MW therapy was completed conducted these experiments, monitoring the animals for up to 1 year post exposure did not reveal any developed only in the patients who during treatment ophthalmologic abnormalities, including cataract had the radiator device in direct contact with skin development. Another experiment was performed in the area of the sternum. It is likely that urticaria recently by the team of H. Kues at John’s Hopkins was a result of mechanical irritation of skin or a University.90 They exposed the eyes of rabbits to MW localized allergic reaction, rather than of exposure with a frequency of 60 GHz at an incident power to MW per se. This could have been easily checked density of 10 mW/cm2 for 8 h. No changes were by a sham exposure of sensitive patients, although observed by macroscopic tests or by post-exposure the authors seem not to have done this.
In another study,87 6/326 peptic/duodenal ulcer It may be useful to mention here a clinical report patients (1.8%) receiving MW therapy, developed on the effects of MW therapy on the vision of headaches and/or an increased blood pressure. The patients with diabetes mellitus, which frequently doctors switched these patients to a conventional causes retinopathy.84 Exposure of the thymus and drug therapy. According to Golovacheva,88 who right shoulder areas of 20 patients (five with chronic treated 415 patients with cardiovascular diseases, recurrent uveitis and 15 with diabetic retinopathy in 5–26% of patients with hypertensive disease, heart the pre-proliferative stage) improved the immune rhythm disorders, and stable/unstable angina exposed status of patients; their condition improved by 5–10 to MW were ‘hypersensitive’ (the author’s term) days faster than when conventional therapy was to MW therapy, which resulted in a >5% decrease used. Electro-oculograms and electroretinograms of the initial blood pressure after the first 10 min of improved significantly, as well as the vision of treatment. Nevertheless, using a special schedule of treatment (decreased duration of MW therapy Based on the above reports, it is reasonable to procedures), the author successfully treated all her conclude that MW therapy, within the limits of frequency and power customarily used for medical A transient increase of blood pressure by purposes, is safe. However, it would be prudent to 20–30 mmHg during MW therapy sessions in a small avoid unnecessary direct exposure to the eyes.
portion of patients suffering from hypertension wasalso noticed by V. Kuzmenko,45 although a decreaseof this parameter by 15–20 mmHg occurred much more frequently. Other reported side-effects of MWtherapy in this paper included temperature increases Essentially, MW therapy consists of exposure of in subfebrile (body temperature 37–38 °C) patients, certain areas of the skin to low intensity MW (for chest pain, and enhanced menstrual bleeding in summary of MW therapy regimes see Table 2). Any women with abnormal menstrual cycles. Since no one of several sites of application appears to be double-blind or simple sham exposure was used in effective. Good results have been reported after the works cited, it is impossible to evaluate the role irradiating various locations over the sternal area;64,78 of such factors as mechanical irritation, psychological large joints such as the shoulder or hip;83,91 some influence of the operator, placebo effects, etc.
areas of the head such as the occipital area44 or The only known experimentally-observed potential pineal gland projection area in the middle of the risk of MW therapy is based on one published animal forehead;56,57 biologically active zones and acupunc- study,89 in which rats were constantly exposed ture points.35,48,54 In any event, with the exception of local treatment of skin diseases or open surface matched with the generator waveguide, positioned wounds,48,49,75 the affected organ/tissue is usually over an irradiation site. The spacing between the remote from the site of application of MW.
waveguide and the patient’s skin does not exceed The choice of frequency of MW is based on two alternative principles. According to the first one,backed by N. Devyatkov, M. Golant, and O.
Betskii,92 three ‘therapeutic’ wavelengths of 4.9, 5.6and 7.1 mm (respective frequencies of 61.22, 53.57 Initially, existing industrial millimetre wave gener- and 42.25 GHz) were established as those that ators (Soviet-made G4–141, G4–142, R2–68, R2–69) supposedly produce healing effects without harming were used for medical purposes.36,45,58,96 These the patient, and were approved by the Russian devices are capable of producing either a tuneable Ministry of Health. The second principle was intro- fixed-band output (G4 series) or sweeping a signal duced by S. Sitko et al.93,94 This approach is based within a set range of frequencies (R2 series).
on tuning the frequency output of the MW generator, Later, generators designed specifically for medical usually within 53–67 GHz range, according to the purposes appeared. They produced either a fixed sensory response of a patient. A tuneable MW frequency signal or a broad-band low-power noise generator or a device which produced a wide-band in the millimetre range. Medical generators such as noise signal with an extremely low power output the Elektronika KVCh36,40 and Yav62,64,77,97 were was used. The site of exposure to MW preferred by equipped with the generating heads emitting signals these researchers is an acupuncture point or points.
at one of the ‘therapeutic’ frequencies. Broad-band Sensory feelings that some patients report in generators such as the Porog36,43 are characterized response to MW therapy are described as warmth, by a very low power, and, theoretically, the patient pressure, tranquillity, comfort, tingling, relaxation, is supposed to react only to certain resonance light sleepiness.58,65,75 The perception of low- power MW by humans seems to be supported by During MW therapy, the average power density the results of a double-blind study in which objective incident to the skin of the patient is below 20 during exposure of volunteers; skin mechanorecep- These features of medical MW generators are tors and/or nociceptors are suggested as the primary characteristic of newer devices as well, and the sensors,95 although the mechanism(s) are still to be major trends in the modern and prospective models are miniaturization and a higher level of computer A typical therapeutic session lasts for 15 to 30 min control of wavelength, duration of exposure, and (sometimes up to 1 h), one exposure session per day, continuous or modulated signal output. With the with a course comprised of 10 to 15 sessions demand for medical generators still high, there are depending on the nature and stage of a disease. In now more than 100 models of medical MW gener- the course of treatment, the patient is positioned in ators on the market in the former USSR and some the sitting or recumbent position. The exposure European countries. The smallest models are the size system, a metal horn or a dielectric radiator antenna of a 25-cent coin, and some of the Russian firms, irradiation on growth of Saccharomyces cerevisiae. IEEE which previously were pre-eminent in military elec- tronics, are now involved in the development and 11. Blackman CF, Benane SG, Weil CM, Ali JS. Effects of nonionizing radiation on single-cell biologic systems. AnnNYAcad Sci 1975; 247:352–66.
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PROTOCOLOS ALTERNATIVOS PARA SINCRONIZAR LA OVULACIÓN CON DISPOSITIVOSINTRAVAGINALES EMEFUR® (Merial Argentina) NUEVOS Y DE SEGUNDO USOVenturini M¹, Daffner A², Rincón G³, Vervel D³1 - Unión Agrícola de Avellaneda Coop. Ltda. Actividad Privada2 - Merial Argentina SA. 3 - Universidad Nacional de Bogotá (Colombia)Se llevó a cabo un experimento, en el norte de la Pcia de Sta Fe, durante