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.

Introduction

concerning the history of therapeutic use of currents

for the treatment of tumor patients

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.

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.

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.

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 RIFE’s work in the United States and independently from him of LAKHOVSKY’s 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 LAKHOVSKY’s “Secret of life”, published the first time 1929.

“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.

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.

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.

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.

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.

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:

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.

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.

The most important results were:

1. 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.

2. MF currents can facilitate the growth of normal fibroblasts in dependence on the strength of the electric field.

3. 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.

4. MF currents can cause an increase of the number and the size of mitochondria.

5. 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.

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.

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

Astrocytoma No success

Glioblastoma No success

Chordoma Stop of the growth of the tumor for many years, but not destructionPatient was found dead in his bed in the morning after a long evening of a festival during his vacation in Spain.

Tumor Result

Melanoma with metastasesin the central nervous system, earlier and larger in the spinal cord resulting in paraplegia, Slowing of growthlater and smaller in the medulla oblongata causing dizziness

and circulatory disturbances Not treatableIn 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

Tumor Result

The same patient suffered since All the lipomas disappeared withinhis early childhood from multiple few weeks after the begin of the benignant tumors of the fatty daily electrical treatments.tissue, lipomas, disseminated tothe whole body, rump and limbs.

1981 THIESS & DIETRICH in Heilbronn and1994 KUKLINSKI in Rostock also reported conspicuous beneficial however finally not healing effects in tumor patients treated with interferential currents.

In KUKLINSKI’s 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 (n=3). 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.

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?

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.

Additionally,the 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.

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).

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.

Facts and hypothesesconcerning

the causal or symptomatic therapeutic use of currents in oncology –

direct and indirect effects upon cells, tissues and the whole organism

Causal therapeutic use

Facts:

Some facts as results of experimental studies are already itemized in the

introduction under number 1 – 5.

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) effectsinduced 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

induced by capacitively coupled effects

through the cell membrane into the intracellular space (cytosol),

through the outer mitochondrial membrane into the intermembrane space and

through the inner mitochondrial membrane into the mitochondrial matrix,

for instancemulti-facilitatory effects upon the metabolism:

facilitation of diffusion processesfacilitation of enzymatically mediated processes of the intracellular metabolism

facilitation of enzymatically mediated processes of the intracellular metabolism, basing on

the increase of the kinetic energy of molecules involved in metabolic processes, lowering the differences to the required activation energy,

the increase of the probability of the events of the important accidental meetings between enzyme and substrate,

the increase of the probability of the events of the important accidental meetings between enzyme and substrate in the correct position (according to DAFFORN & KOSHLAND:A. DAFFORN & D. E. KOSHLAND jr., Biochem. Biophys. Res. Commun. 52, 780, (1973) )

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

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)

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)

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)

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)

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.

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 it’s neighborhood; the lowered pH is impairing the function of the cells of the immune system.

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)

release of transmitters (mainly nor-epinephrine)

from the varicosities of the sympathetic nerve endings

reduction of inflammatory tissue changes

in the neighborhood of the tumor

activation of receptors within the cell membranes involved in

the tumor growth inhibiting processes

Secondary effects:

The activation of cells of the immune system could result in the following secondary effects:

Increase of phagocytosis

Increase of the release of mediators acting as inhibitors of tumor growth or even as tumor cell destroying agents (for instance tumor necrosis factor)

Symptomatic therapeutic use

The symptomatic therapeutic use concerns mainly

1. pain relief

2. edema reduction 3. 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 -mimetic effects

6. general enhancement of the quality of life

The possibilities to optimize the efficacy of currents by variation or fixation of their parameters in dependence

on the intended therapeutic purpose

Pain relief

Five 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 -endorphin release

5. In cases of painful swellings indirect causal pain relief by edema reduction

The following parameters should be preferred:

1. High intensities during blocks with higher fixed frequencies (max. 32768 Hz) or SimulFAM along the threshold curve, SimulFAMi

2. 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 Hz

5. SimulFAMX with crossing of the threshold curve, frequency of modulation: 10 Hz

2. Edema reduction (in general) and prevention of venous thromboses

a. caused by stimulation of sympathetic fibers

b. (in lower legs an feet) caused by activation of the “muscle pump”

c. caused by reversible sustained partial depolarization of the smooth muscles of the lymphatic vessels and the blood vessels, “plateau effect”

The following parameters should be preferred:

a. SimulFAMX with crossing of the threshold curve, frequency of modulation 10 Hz

b. SimulFAMX with crossing of the threshold curve, frequency of modulation 0.3 Hz

c. High intensity with higher fixed frequencies (max. 32768Hz)

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.

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MAY, H. U.:High Tone Frequency Power Therapy with HiToP® in general and particularly in cases of painful conditions of the musculo-skeletal system in special consideration of low back pain,including a part of the results of a clinical study carried out and evaluated by E. RHADES & B. SCHNEIDERPaper presented at the4th Annual International Congress of Egyptian Society of Back Pain, Cairo, Egypt, 16 - 17 April 2004

MAY, H. U.:High Tone Power TherapyScientific development to optimise the physical, physiological and therapeutic effects of middle frequency currentsPaper presented at the6th Annual International Congress of Egyptian Society of Back Pain, Cairo, Egypt, 19 – 20 April 2006

MAY, H. U., & A. HANSJÜRGENS:Elektrische Differentialtherapie1 Electric Differential Therapy13 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 EDiT3) Treatment of edema usin EDiT Karlsruhe, Nemectron 1988

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

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NEMEC, H.: Reizstromtherapie mit Interferenzströmen.Der Deutsche Badebetrieb 51, 320 – 323 (1960)

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NIKOLOVA-TROEVA, L.: Lecenije s interferenten tok. (Behandlung mit Interferenzstrom) Sofia: Medizina i Fiskultura 1971

NIKOLOVA-TROEVA, L.: Treatment with interferential current. Edingurgh, London, Melbourne, New York: Churchill Livingstone 1987

NIKOLOVA, L., & M. DAVIDOV: Fermentaktivitäten in traumatisierten Nerven und ihre Beeinflussung durch Interferenzströme (Experimentelle Untersuchungen). Voprosy Kurortol., Fisiotherap. i lecebn. Fisic. Kultury 43, 54 – 57 (1978)

NORDENSTRÖM, B. W. E. :Biologically closed electrical circuits:Clinical experimental and theoretical evidence for an additional circulatory system.Stockholm, Sweden: Nordic Medical Publications 1983

NOSZVAI-NAGY, M.: Wirkung mittelfrequenter Ströme auf Zellen in Suspension. Diplomarbeit, Universität Karlsruhe, Fakultät für Bio- und Geowissenschaften, März 1988

NOSZVAI-NAGY, M.: Wirkung des Mittelfrequenzstromes auf nicht-erregbare Zellen. Dissertation. Universität und Kernforschungszentrum Karlsruhe, 1993/94

PATTERSON, M.:Hooked? NET: The new approach to drug cure.London: Faber & Faber 1986

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PEKAR, R.:Die perkutane Bio-Elektrotherapie bei Tumoren.Eine Dokumentation zu Grundlage und Praxis der perkutanen Galvanotherapie Wien, München, Bern: Wilhelm Maudrich 1996

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PETROW, W., & H. W. KREYSEL:Adjuvant therapy of malignant melanoma by interferen tial currents21. Deutscher Krebskongreß, Hamburg, 7.-11. März 199421th National Cancer Congress of the German Cancer SocietySupplement to Journal of Cancer Research and Clinical Oncology Vol. 120, 05.09.04 (1994)

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SAVERY, F., A. A. ORTIZ & H. U. MAY:Clinical application and effects of EDiT® and Endosan® treatment on diabetic neuropathy and gangrene of toeAdvances in Therapy 7, 283 – 288 (1990)

SAVERY, F., A. A. ORTIZ, O. HAIKAL, K. FATHIE, G. S. CHOUDHURY, H. U. MAY & R. SORGNARD:Electric differential treatment (EDiT®) and Endosan® treatment for ischemic diseases.Advances in Therapy 8, 11 – 21 (1991)

SAVERY, F., F. SILVER, R. EDWARD, A. FANN, R. MANN, C. ROGERS, H. U. MAY & R. SORGNARD:Assessment of electric differential treatment (EDiT®) and Endosan® treatment for ovarian cysts and concomitant symptomsAdvances in Therapy 8, 243 – 249 (1991)

SCHWARZ, F.: (Physiolog. Inst. Universität Leipzig)Über die Reizung sensibler Nerven des Menschen durch mittelfrequente Wechselströme. Pflügers Arch. 247, 405 – 440 (1944)

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VERAGUTH, O., & R. SEYDERHELM: Über raschwirkende Beeinflussung abnormer Leukozytenbilder durch ein neues Verfahren.I. und II. Mitteilung.Münch. Med. Wochenschr., 2211 – 2214 (1913) und 301 – 304 (1914)

WILK, M., W. W. FIBIGER & B. FRANZUK:Zastowanie terapii energotonowej w rehabilitacji pacjentów po uszkodzeniach tkanek miekkich stawu kolanowego.The application of high-tone power therapy in rehabilitation of patients with soft-tissue damage to the knee joint.Fizjoterapia Polska (Polish Journal of Physiotherapy) 2, 118 – 121 (2002)