1 H. U. MAY Facts and hypotheses concerning the causal or symptomatic therapeutic use of currents in oncology - direct and indirect effects upon cells tissues and the whole organism. The possibilities to optimize the efficacy of currents by variation or fixation of their parameters in dependence on the intended therapeutic purpose. 2 Introduction concerning the history of therapeutic use of currents for the treatment of tumor patients 3 Already in the middle of the 18th century the two German physicists HAUSEN WINKLER tried with their electrical machine based on friction to treat tumors. After the spreading of the inventions of GALVANI (1737 - 1798) and VOLTA (1745 - 1827) since the 19th century electricity has been used more frequently to treat tumor patients. Not only symptomatic treatments for pain relief but even mainly causal treatments consisting in trials to destroy the tumors were usual. 4 In standard dictionaries and encyclopedias from the second part of the 19th century and the first decades of the 20th century you can find very much more general information and special description of the electrolytic destruction of tumors by direct currents under the catchword electrotherapy than in the second part of the 20th century and today. 5 Until today the galvanic current as the primarily preferred current in the causal treatment of tumor patients is used in various clinics and hospitals for instance in Austria according the recommendations of PEKAR given in his 3 books about the percutaneous galvanotherapy in cases of tumors published since 1988 basing on experiences since 1977. Also in Sweden NORDENSTRÖM used direct currents (DC) for the treatment of tumors basing on his theory of biologically closed electric circuits (1983). The DC method requires needles to be placed inside the tumor. It is an invasive method. I know that in Germany Denmark Italy and China in special hospitals this invasive DC method is in use however in Germany without public advertising. 6 Just before the 1st world war VERAGUTH SEYDERHELM (1913 and 1914 Zürich and Straßburg) found the tendency of various direct and alternating currents applied as whole body treatments in a 4 cell bath to reduce the number of white blood cells in leukemia patients. The histories of RIFEs work in the United States and independently from him of LAKHOVSKYs work in France concerning cancer treatment using alternating electrical fields of various frequencies are well described in the RIFE Report written by Barry LYNES and published 1987 and in LAKHOVSKYs Secret of life published the first time 1929. 7 Tone frequency currents a not very precise term introduced by KOEPPEN 1935 in his paper Tone frequency currents in medicine has been changed 1944 by the German physiologist GILDEMEISTER in Leipzig into the term middle frequency currents (MF) defined by the frequency range between 1 kHz and ca. 100 kHz. GILDEMEISTER and his pupil SCHWARZ furthermore WYSS in Zürich investigated the very interesting and special advantageous physiological properties of these MF currents however more from the standpoint of physiology as a theoretical field of medicine than with a practical therapeutic view. Consequently they did not take into account any thoughts concerning the effects of MF upon tumors. 8 Without any knowledge about the publications concerning MF currents published mainly in journals of physiology the electronic engineer Doctor NEMEC from Austria in the late 40s up to 1952 used MF currents between 4000 and 4100 Hz for his invention of interferential current realized by the company NEMECTRON as the Nemectrodyn machine. 9 Dr. Hanna FRESENIUS a female general practitioner in Steinau in Hessen (Germany) was one of the first medical doctors who experienced the wide range of indications of the new equipment including pain relief in cancer patients. Additionally she observed in the majority of the patients not only pain relief but additionally a general increase of their condition of their quality of life in some of the patients even an inhibition of tumor growth or a shrinking of the tumor. 10 After several years of successful treatments of cancer patients with these interferential currents other medical doctors competitors which were not familiar with the new treatment suggested a damning of the new electrotherapeutic method in cancer patients by the regionally responsible professional instance. Dr. Hanna FRESENIUS was not agree. She moved with her practice to Bavaria and pursued successfully to treat cancer patients but more secretly. 11 Convinced by the beneficial effects of interferential currents in cancer patients Dr.Hanna FRESENIUS initiated animal experiments together with the University of Freiburg. She fed two groups of rats with the carcinogeneous butter yellow (dimethylaminoazobenzol). One group was treated nearly everyday with interferential current. Only the animals of the other group developed liver tumors. In this time I was as a neurologist physiologist and pharmacologist with long experiences in biomedical engineering and biocybernetics in the University of Karlsruhe a member of the medical-scientific research and development department of Nemectron in Karlsruhe responsible for all theoretical and practical medical questions. 12 (No Transcript) 13 With monetary technical and scientific support by Nemectron and with prepared rats from Prof. Ferdinand SCHMIDT (Institute for Preventive Oncology of the University Heidelberg-Mannheim) Hanna FRESENIUS started new series in rats suffering from chemically induced subcutaneous tumors. When the tumors were detected early enough and the diameter of the tumor was not larger than 8 to 10 mm the treatments with interferential current (carrier frequencies around 4000 Hz) leaded to a shrinking and finally to a disappearance of the tumors 14 Larger tumors did not disappear. They sustained to grow partially up to the size of apples and the tumors seemed to cause intensive itch sensations. The rats injured the skin in the region of the subcutaneous tumor and finally the tumor itself. The initially solid tumor had changed to a cyst filled with a fluid. The cyst opened by the teeth of the rat collapsed was infected and the rat died within hours or few days. These kinds of animal experiments could not be continued because of a new law concerning the use of animals for scientific research. 15 Therefore with financial support by the German Ministry for Research and Technology in the laboratories of Nemectron and 4 institutes of the medical faculties of various universities and scientific centers (Freiburg Aachen German Cancer Research Center Heidelberg German Nuclear Research Center Karlsruhe) investigations concerning the influences of middle frequency currents were carried out with normal and various tumor cells. In 2 doctor dissertations (M. NOSZVAI-NAGY Karlsruhe 1993/94 W. PETROW Aachen 1988) in lectures and papers on a symposium in Karlsruhe 1990 and a German Cancer Congress in Hamburg 1994 the results were presented. 16
The most important results were
Some kinds of tumor cells in vitro can be killed during the application of middle frequency currents (with frequencies in the lower MF range mainly 4000 Hz) they suddenly disappear by destruction of their cell membrane. Abnormal large cells appear to be more sensitive. However not all types of the tumor cells had the same sensitivity.
MF currents can facilitate the growth of normal fibroblasts in dependence on the strength of the electric field.
MF currents can influence the adenylcyclase resulting in changes of the intracellular cAMP formation that means MF currents can have hormone-like effects. This corresponds with the results of other authors.
MF currents can cause an increase of the number and the size of mitochondria.
Alternating electric fields within the MF range facilitate and consequently accelerate the diffusion along the lines of the electric fields in the two opposite directions. This result was predictable due to physical electrochemical and statistical considerations.
18 The cell culture research program supported by the German government unfortunately could not be continued because of monetary restrictions. Additional psychological problems between the supervisory board and the leading management of Nemectron caused repetitive changes within the top management team. Finally the owner of Nemectron the margrave of Baden had to sale his company. After few years the ownership changed again. 19 My own experiences with interferential current (MF between 4000 and 4100 Hz) as a neurologist not an oncologist in tumor patients were different. Some examples Tumor Result Astrocy toma No success Glioblastoma No success Chordoma Stop of the growth of the tumor for many years but not destruction Patient was found dead in his bed in the morning after a long evening of a festival during his vacation in Spain. 20 Tumor Result Melanoma with metastases in the central nervous system earlier and larger in the spinal cord resulting in paraplegia Slowing of growth later and smaller in the medulla oblongata causing dizziness and circulatory disturbances Not treatable In general Significant pain relief reduction of the analgesic drugs enhancement of the quality of life 6 months prolongation of the survival time life at home with his family instead of an immediate death under high dosages of narcotics at the intensive care station of the Dermatological department of the University of Köln 21 Tumor Result The same patient suffered since All the lipomas disappeared within his early childhood from multiple few weeks after the begin of the benignant tumors of the fatty daily electrical treatments. tissue lipomas disseminated to the whole body rump and limbs. 22 1981 THIESS DIETRICH in Heilbronn and 1994 KUKLINSKI in Rostock also reported conspicuous beneficial however finally not healing effects in tumor patients treated with interferential currents. In KUKLINSKIs study a group of 37 patients received interferential current (IFC) treatment twice per day. Modulation frequency was scanned between 0.5 and 150 Hz. Results Partial remissions were observed in patients with superficial cutaneous metastases or ulcerative mammary carcinomas (n3). Tumor progression was lowered in 2 patients with pancreatic carcinomas. Responses of tumors of the pulmonary and bowel tracts were generally poor. In many cases a considerable reduction of inconveniencies associated with the disease was noted (e.g. reduction of pain rapid improvement of physical condition etc.) Conclusion In order to improve the response of malignant tumors particularly of deep-lying tumors hitherto existing parameters and strategies of IFC-treatment seem to require revision. 23 Taking into account the fact that in cell culture experiments and in patients the desired effects of MF currents seemed to be dependent on the type of the tumor the question arose Is the sensitivity of the special type of tumor cells dependent on the frequency of the MF current 24 This was the origin of my idea to use the modulation of the frequency in a mathematically continual way over a wide range in accordance with the technical and legitimate possibilities avoiding arbitrary irregular and to large steps and to minimize the differences between the theoretically optimum frequency and the really generated frequency. 25 Additionallythe electrical neurophysiologic and psychophysical possibilities concerning the intensities of the applied frequency-dependent currents should be optimized. The distance to local and systemic tolerance limits should be as large as possible to maximize the therapeutic width. 26 Since 2000 my idea of simultaneous modulation of frequency and amplitude (SimulFAM) adaptable tothe individual and local frequency-dependent threshold of sensation is realized and available until now in Europe and Asia as HiToP High Tone Power Therapy (MAY 2002 and 2004). 27 The manufacturer is the company gbo Gerätebau Odenwald in Rimbach manufacturing and distributing too still traditional low-frequency and interferential electrotherapy units of Siemens. The frequency is modulated in quarter tone steps between 4096 and 32768 Hz. With 73 frequencies (tones in the high tone and low ultrasound ranges) 3 octaves are covered. The maximum distance to a theoretically optimum frequency or to a frequency in an harmonic relation to this optimum frequency is 1/8 tone step. 28 Facts and hypothesesconcerning the causal or symptomatic therapeutic use of currents in oncology direct and indirect effects upon cells tissues and the whole organism 29 Causal therapeutic use Facts Some facts as results of experimental studies are already itemized in the introduction under number 1 5. 30 Hypotheses regarding inhibitory effects of un-modulated amplitude-modulated and simultaneously frequency- and amplitude-modulated middle frequency currents upon tumor growth Direct effects of currents upon transformed cells Changes and renormalizations of pathological processes in tumor cells caused by stimulatory and multi-facilitatory (electro-biochemical non-stimulatory) effects induced by electrically triggered molecular conformation changes within the cell membrane that means a kind of simulation of hormone effects resulting in the (normalization of) formation of intracellular second messengers for example cyclic AMP 31 induced by capacitively coupled effectsthrough the cell membrane into the intracellular space (cytosol)through the outer mitochondrial membrane into the intermembrane space andthrough the inner mitochondrial membrane into the mitochondrial matrixfor instance multi-facilitatory effects upon the metabolism facilitation of diffusion processes facilitation of enzymatically mediated processes of the intracellular metabolism 32 facilitation of enzymatically mediated processes of the intracellular metabolism basing onthe increase of the kinetic energy of molecules involved in metabolic processes lowering the differences to the required activation energythe increase of the probability of the events of the important accidental meetings between enzyme and substratethe increase of the probability of the events of the important accidental meetings between enzyme and substrate in the correct position (according to DAFFORN KOSHLANDA. DAFFORN D. E. KOSHLAND jr. Biochem. Biophys. Res. Commun. 52 780 (1973) ) 33 direct influences upon the transport mechanisms of protons and electrons within the inner membrane of the mitochondria preference of the aerobic metabolic pathways instead of the anaerobic glycolysis 34 induced by direct influence upon theintercellular communication (cleaning effect concerning ion channels including gap junctions) resulting in partial or total recovery of the disturbed electrical and chemical communication between tumor cells mutually and between tumor cells and the cells in the adjacent tissue (one step to a redifferentiation) partial or total recovery of the disturbed metabolic cooperation between tumor cells mutually and between tumor cells and the cells in the adjacent tissue (a second step to a redifferentiation) partial or total recovery of the disturbed functional coordination between tumor cells mutually and between tumor cells and the cells in the adjacent tissue (a third step to a redifferentiation) 35 partial or total recovery of the disturbed probably electrically mediated control of the target of the normal topographic-anatomical and histological structure of the referred body region (last step and desired main goal of redifferentiation) 36 Over-stress of the pathologically changed metabolism of the tumor cell caused by frequently generated depolarization and the required repolarisation (stimulatory effect possible with supra-threshold intensities only) 37 Indirect effects Primary effects Activation of cells of the immune system by means of sustained depolarization (non-stimulatory effect) of the involved cells of the immune system causing an increase of cell division rates of normal cells which are able to increase their mitotic activity if such increase is required by means of cyclic AMP formation (non-stimulatory multi-facilitatory and stimulatory effect) within the involved cells of the immune system by facilitation of intercellular communication (non-stimulatory multi-facilitatory effect) 38 by an increase of generation of natural killer cells (NKC)observed by KUKLINSKI as a result of stimulatory effects probably possible with non-stimulating currents too. 39 Enhancement of the efficacy of the activity of the cells of the immune system in the neighborhood of the tumor by means of the equilibration effect upon concentration differences normalizing the pH values.Due to the preference of the anaerobic metabolism in tumor cells with an increase of lactic acid production the pH is lowered in the extracellular space within the tumor and in its neighborhood the lowered pH is impairing the function of the cells of the immune system. 40 Partial or total recovery of the disturbed communication between the asocial cells of the tumor takes place by means of the electrochemical shaking effect. Stimulation of the sympathetic nervous system (by stimulatory effects) orelease of transmitters (mainly nor-epinephrine) from the varicosities of the sympathetic nerve endings oreduction of inflammatory tissue changes in the neighborhood of the tumor o activation of receptors within the cell membranes involved in the tumor growth inhibiting processes 41 Secondary effects The activation of cells of the immune system could result in the following secondary effects Increase of phagocytosisIncrease of the release of mediators acting as inhibitors of tumor growth or even as tumor cell destroying agents (for instance tumor necrosis factor) 42
Symptomatic therapeutic use
The symptomatic therapeutic use concerns mainly
1. pain relief
prevention of venous thromboses
4. reduction of the required dosage of pain relieving and other drugs with reduction of their side effects
5. inhibition of cachexia by b-mimetic effects
6. general enhancement of the quality of life
43 The possibilities to optimize the efficacy of currents by variation or fixation of their parameters in dependence on the intended therapeutic purpose Pain reliefFive pain relieving effects are available 1. Distribution and thinning of mediators of pain and inflammation 2. Real nerve block by reversible sustained partial depolarization plateau effect 3. Pseudo block associated with tea transient excitatory activity 4. Counter-irritation (GAMMON STARR 1941) and b -endorphin release 5. In cases of painful swellings indirect causal pain relief by edema reduction 44 The following parameters should be preferred1. High intensities during blocks with higher fixed frequencies (max. 32768 Hz) or SimulFAM along the threshold curve SimulFAMi2. Maximum tolerable intensity with higher fixed frequencies (max. 32768 Hz)3. High intensity with higher fixed frequencies (max. 32768 Hz)4. SimulFAMX with crossing of the threshold curve frequency of modulation 100 Hz5. SimulFAMX with crossing of the threshold curve frequency of modulation 10 Hz 45 2. Edema reduction (in general) and prevention of venous thrombosesa. caused by stimulation of sympathetic fibersb. (in lower legs an feet) caused by activation of the muscle pumpc. caused by reversible sustained partial depolarization of the smooth muscles of the lymphatic vessels and the blood vessels plateau effectThe following parameters should be preferreda. SimulFAMX with crossing of the threshold curve frequency of modulation 10 Hzb. SimulFAMX with crossing of the threshold curve frequency of modulation 0.3 Hzc. High intensity with higher fixed frequencies (max. 32768Hz) 46 3. - 5.The therapeutically desired effects mentioned above concerning reduction of drugs and their side effects inhibition of cachexia andgeneral enhancement of the quality of life are present in all cases of parameter selection. They do not require special parameters. 47 Selected Literature dARSONVAL A. 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Oktober 1997 über eine von März bis September 1997 durchgeführte erfolgreiche Hochton-Behandlung einer Patientin mit Gallensteinen und häufigen Koliken. Clinical report dated from October 21st 1997 concerning a successful high tone therapy treatment of a female patient with gall-stones and frequent bilious colics over a period of seven months (March September 1997) HÖNES R. D. Der Einfluß von Interferenzstrom auf das Wachstumsverhalten von Zellkulturen. Inauguraldiss ertation. Freiburg i. Br. 1983 58 HUMPERT P. M. G. RUDOFSKY M. MORCOS A. BIERHAUS P. P. NAWROTH Hochtontherapie zu Behandlung schmerzhafter Neuropathie bei Typ 2 Diabetikern verbessert die mikrovaskuläre Endothelzellfunktion High tone therapy for the treatment of painful neuropathy in type 2 diabetic patients improves the microvascular endothelial function. Poster and Abstract. 41. Jahrestagung der Deutschen Diabetes-Gesellschaft Leipzig 24. 27. 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Deutscher Krebskongreß Hamburg 7.-11. März 1994 21th National Cancer Congress of the German Cancer Society Supplement to Journal of Cancer Research and Clinical Oncology Vol. 120 05.09.05 (1994) LAKHOVSKY Georges The secret of life. London 152 Landor road Stockwell S.W.9. 1951 64 LYNES B. The cancer cure that worked! Fifty years of suppression. The RIFE report. Queensville Ontario Canada Marcus Books 1st printing March 1987 6th pr. October 1997 MAY H. U. Simultaneous modulation of frequency and amplitude of middle frequency currents between high tone and low ultrasound range applied physiology for differentiated electrotherapy concerning the distinction and specific proportional mixture of stimulatory and non-stimulatory (metabolic and/or blocking) effects. In Abstracts of the Joint Meeting of The Physiological Society Scandinavian Physiological Society and Deutsche Physiologische Gesellschaft (81st Annual Meeting) 15-19 March 2002 Tübingen Germany Europ. J. Physiol. 443 Suppl. 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High Tone Power Therapy Scientific development to optimise the physical physiological and therapeutic effects of middle frequency currents Paper presented at the 6th Annual International Congress of Egyptian Society of Back Pain Cairo Egypt 19 20 April 2006 MAY H. U. A. HANSJÜRGENS Elektrische Differentialtherapie1 Electric Differential Therapy1 3 Posters (56 cm x 43 cm - in four languages) prepared for the Medical center of the Olympic Village during the Olympic Games in Seoul 1988 1) Electric Differential Therapy (in general) 2) Pain Management with EDiT 3) Treatment of edema usin EDiT Karlsruhe Nemectron 1988 67 MAY H. U. F. NIPPEL G. KONIECZNY Schmerzbehandlung als Voraussetzung für die Rehabilitation und die therapeutischen Möglichkeiten der Interferenzstromtherapie. Erfolgsraten und Anwendungsquoten bei verschiedenen mit Schmerzen verbundenen Krankheitsbildern - eine statistische Analyse. Zeitschrift für Physikalische Medizin 11 63 - 67 1982 MAY H. U. F. J. NIPPEL A. 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