CA2285267A1 - Rf therapeutic cancer apparatus and method - Google Patents
Rf therapeutic cancer apparatus and method Download PDFInfo
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- CA2285267A1 CA2285267A1 CA002285267A CA2285267A CA2285267A1 CA 2285267 A1 CA2285267 A1 CA 2285267A1 CA 002285267 A CA002285267 A CA 002285267A CA 2285267 A CA2285267 A CA 2285267A CA 2285267 A1 CA2285267 A1 CA 2285267A1
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Abstract
An apparatus and method for treating cancer and other illnesses in humans and animals are described. The treatment involves the low-power, pulsed application of radio frequency (190) tuned with precision of at least one half part per million. Alternative embodiments are described for apparatus that generates the required RF signals and applies such signals therapeutically.
Laboratory data is reported, showing the successful use of the disclosed apparatus and methods to suppress and eliminate cancerous tumors in mice.
Laboratory data is reported, showing the successful use of the disclosed apparatus and methods to suppress and eliminate cancerous tumors in mice.
Description
WO 98129156 PCT/US97123845 w THERAPEUTIC APPARATUS AND METHOD
FIELD OF INVENTION
This invention generally relates to apparatus and methods for treating cancer and other illness in humans and animals, and more particularly to a therapeutic apparatus and method based upon the administration of precisely regulated, low power, pulsed electromagnetic radiation (EMR).
BACKGROUND OF THE INVENTION
There is a considerable body of early literature regarding treatment of various illnesses with radio frequencies (RF) in the 43 MHz range. In U.S. Patent No. ?,545,087, Iv.
J. Hart disclosed an appa-ratus for treating a subject with a sequence of radio frequencies in the 43 MHz. range, applied in a stepwise fashion. These frequencies were each modulated sinusoidally at 60 Hz., and further pulsed by a second slow sinusoidal oscillator operating at 90 cycles per minute (1.5 Hz.). 'rhe RF frequencies em-ployed by Hart were specified to tlmee decimal places.
The instruments available to Hart and the other researchers of his day were based on tube am-plifiers, which resulted in oscillators with considerable drift that could not be precisely tuned. Hart's means for applying the RF energy to a subject most often consisted of a metal plate acting as an an-75 tenna. As a result of such oscillator drift and imprecision, and the W
efficiency of the available output devices, Hart and his contemporaries were not able to conduct scientific tests with precisely controlled frequencies, or to discover optimal treatment modalities.
lvtodern electronic technologies make it relatively simple to construct more precise and stable instruments than Hart had at his disposal. As a consequence, it has bococne possibly to study systemati-'_'t~ tally tho potential therapeutic value of EMR. The present inventors have undertaken such studies over the course of many years, and as a result have perfected apparatus and methods which have proved effective in treating cancerous tumors W laboratory mice. 1'he inventors believe that the same methods can be effectively adapted for human treatment.
The present inventors have constructed apparatus designed to overcome the limitations of 25 Hart's approach. They have further sought to establish the utility of their invention through a program of animal testing, and have in turn used the results of such testing to refine the apparatus and the methods for effectively using such apparatus. The resulting apparatus and methods, and the experi-mental results of applying such apparatus and methods to treat cancerous tumors in mice, will be de-scribed below.
WO 98/29156 PCTlUS97/23845 -SUMMARY OF THE INVENTION
It is generally the object of the present invention to utilize electromagnetic radiation to provide effective treatments for cancer and other illnesses.
It is a further object of this invention to achieve reliable and reproducible therapeutic results from EMR treatment methods by achieving precise control over the treatment frequency.
It is also an object of the present invention to provide an efficient means of transmitting EMR
from the generating means to the subject.
It is another object of the present invention to provide an EMR treatment that may be applied at very low power levels that can cause no harm.
These and other objects are achieved in accordance with the present invention through the use of an apparatus involving an oscillator that outputs, at a power of less than one mw, an RF frequency W
the 43 MHz range, regulated and stabilized to the fifth or sixth decimal place, which is in turn modu-lated with a 60 I lz. 50% duty cycle square wave, which is in turn gated, again on a 50% duty cycle, at a rate of 1.167 Hz. (70 pulses per minute).
The RF frequency is chosen for a particular subject based on the believed effectiveness of the frequency in treating the illness in question, as summarized herein.
The modulated RF signal output by the apparatus of the present invention is applied to a flat loop of wire approximately 60 cm. long, grounded at one end and wound in five flat, concentric spiral-rectangular turns spaced about 3.175 mm. apart, the loop (herein referred to as a "treatment loop") be-ing mounted on an insulating layer adhesively bonded to a metal plate.
In using this apparatus, the metal plate is placed, loop down, on the subject's body near the area to~be treated. RF power is applied to the loop at one precise treatment RF frequency for at least one hour at a time. During treatment, the treatment loop is shielded from direct light and moving air cur-rents.
'There arc: alternative embodiments of the invention that differ somewhat in their circuit and construction details. The first, referred to as the "Battery SCPO," is a battery-powered "Single Crystal Pulsed Oscillator" in a metal housing with an internal quartz crystal, and an integral, externally mounted treatment loop. Each Battery SCPO is limited to a single frequency. A
variation is shown (the "Mouse SCPO") in which an SCPO is powered by an external DC power module rather than batteries.
An alternate embodiment, referred to as the "Generator Embodiment", derives its treatment signal from the modulated output of a Hewlett-Packard Model 8662A frequency generator, and supplies the signal to the treatment loop over a short coaxial cable. The frequency and power of the Generator Em-bodiment is easily adjusted with controls on the front panel of the 8662A
frequency generator. Another alternative embodiment, also based on the HP 8662A Frequency Generator, modulates the RF signal entirely externally to the HP 8662A, and employs a specific type of coaxial cable to carry the signal from the modulator to the treatment loop. These alternative embodiments differ somewhat in their circuitry and construction details, as will be more fully described below.
In any of the alternative embodiments, treatment is non-restrictive and utilizes a low power be-lieved to be completely safe for humans.
Other features and advantages of the present invention will become apparent from the follow-ing more detailed description, taken in conjunction with the accompanying drawings, which illustrate, by way of example, the principles of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
FIGS. 1A and IB show top and bottom external views of the Battery SCPO.
FIG. 2 is a block diagram of the major functional units of the Battery SCPO.
FIG. 3 is a schematic diagram of the Battery SCPO.
FIG. 4A shows the modulation waveform of the Battery SCPO. FIGS 4B through 4F
show spec-trum analyses of the output of the Battery SCPO.
FIG. 5 is an external view of the components of the Generator Embodiment.
FIG. 6 is a schematic dlagl'alll Of the modulator circuit for the Generator Embodiment.
FIGs. 7A and 7B show, respectively, the modulation waveform and a portion of the output waveform of the Generator F~.lnbodiment.
FIGS. 8A and 8B show front alld back views of the treatment loop used in connection with the Generator Embodiment.
FIGS. 9A1 - 9J4 shove the treatment housings and treatment loops used for treating mice in the experiments described herein.
FIGs. 10 through 29 show, for each treated and control mouse involved in the inventors' ex-perimental studies, A, the locations of the tumors (if any) that developed, B, plots (on a logarithmic scale) of the respective vohmlca of tl~c various tumors as a function of time, and C, plots of the mouse's weight and hematocrit measurements as a function of time.
FIG. 30 A and B shows bar graphs of the life spans of the treated and control mice, respectively.
FIG. 31 A and B shows bar graphs of the life spans of the treated and control mice, respectively, after tumors were detected.
FIG. 32 A and B shows bar graphs of the number of tumors in the treated and control mice, re-:~U specHvely.
FIELD OF INVENTION
This invention generally relates to apparatus and methods for treating cancer and other illness in humans and animals, and more particularly to a therapeutic apparatus and method based upon the administration of precisely regulated, low power, pulsed electromagnetic radiation (EMR).
BACKGROUND OF THE INVENTION
There is a considerable body of early literature regarding treatment of various illnesses with radio frequencies (RF) in the 43 MHz range. In U.S. Patent No. ?,545,087, Iv.
J. Hart disclosed an appa-ratus for treating a subject with a sequence of radio frequencies in the 43 MHz. range, applied in a stepwise fashion. These frequencies were each modulated sinusoidally at 60 Hz., and further pulsed by a second slow sinusoidal oscillator operating at 90 cycles per minute (1.5 Hz.). 'rhe RF frequencies em-ployed by Hart were specified to tlmee decimal places.
The instruments available to Hart and the other researchers of his day were based on tube am-plifiers, which resulted in oscillators with considerable drift that could not be precisely tuned. Hart's means for applying the RF energy to a subject most often consisted of a metal plate acting as an an-75 tenna. As a result of such oscillator drift and imprecision, and the W
efficiency of the available output devices, Hart and his contemporaries were not able to conduct scientific tests with precisely controlled frequencies, or to discover optimal treatment modalities.
lvtodern electronic technologies make it relatively simple to construct more precise and stable instruments than Hart had at his disposal. As a consequence, it has bococne possibly to study systemati-'_'t~ tally tho potential therapeutic value of EMR. The present inventors have undertaken such studies over the course of many years, and as a result have perfected apparatus and methods which have proved effective in treating cancerous tumors W laboratory mice. 1'he inventors believe that the same methods can be effectively adapted for human treatment.
The present inventors have constructed apparatus designed to overcome the limitations of 25 Hart's approach. They have further sought to establish the utility of their invention through a program of animal testing, and have in turn used the results of such testing to refine the apparatus and the methods for effectively using such apparatus. The resulting apparatus and methods, and the experi-mental results of applying such apparatus and methods to treat cancerous tumors in mice, will be de-scribed below.
WO 98/29156 PCTlUS97/23845 -SUMMARY OF THE INVENTION
It is generally the object of the present invention to utilize electromagnetic radiation to provide effective treatments for cancer and other illnesses.
It is a further object of this invention to achieve reliable and reproducible therapeutic results from EMR treatment methods by achieving precise control over the treatment frequency.
It is also an object of the present invention to provide an efficient means of transmitting EMR
from the generating means to the subject.
It is another object of the present invention to provide an EMR treatment that may be applied at very low power levels that can cause no harm.
These and other objects are achieved in accordance with the present invention through the use of an apparatus involving an oscillator that outputs, at a power of less than one mw, an RF frequency W
the 43 MHz range, regulated and stabilized to the fifth or sixth decimal place, which is in turn modu-lated with a 60 I lz. 50% duty cycle square wave, which is in turn gated, again on a 50% duty cycle, at a rate of 1.167 Hz. (70 pulses per minute).
The RF frequency is chosen for a particular subject based on the believed effectiveness of the frequency in treating the illness in question, as summarized herein.
The modulated RF signal output by the apparatus of the present invention is applied to a flat loop of wire approximately 60 cm. long, grounded at one end and wound in five flat, concentric spiral-rectangular turns spaced about 3.175 mm. apart, the loop (herein referred to as a "treatment loop") be-ing mounted on an insulating layer adhesively bonded to a metal plate.
In using this apparatus, the metal plate is placed, loop down, on the subject's body near the area to~be treated. RF power is applied to the loop at one precise treatment RF frequency for at least one hour at a time. During treatment, the treatment loop is shielded from direct light and moving air cur-rents.
'There arc: alternative embodiments of the invention that differ somewhat in their circuit and construction details. The first, referred to as the "Battery SCPO," is a battery-powered "Single Crystal Pulsed Oscillator" in a metal housing with an internal quartz crystal, and an integral, externally mounted treatment loop. Each Battery SCPO is limited to a single frequency. A
variation is shown (the "Mouse SCPO") in which an SCPO is powered by an external DC power module rather than batteries.
An alternate embodiment, referred to as the "Generator Embodiment", derives its treatment signal from the modulated output of a Hewlett-Packard Model 8662A frequency generator, and supplies the signal to the treatment loop over a short coaxial cable. The frequency and power of the Generator Em-bodiment is easily adjusted with controls on the front panel of the 8662A
frequency generator. Another alternative embodiment, also based on the HP 8662A Frequency Generator, modulates the RF signal entirely externally to the HP 8662A, and employs a specific type of coaxial cable to carry the signal from the modulator to the treatment loop. These alternative embodiments differ somewhat in their circuitry and construction details, as will be more fully described below.
In any of the alternative embodiments, treatment is non-restrictive and utilizes a low power be-lieved to be completely safe for humans.
Other features and advantages of the present invention will become apparent from the follow-ing more detailed description, taken in conjunction with the accompanying drawings, which illustrate, by way of example, the principles of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
FIGS. 1A and IB show top and bottom external views of the Battery SCPO.
FIG. 2 is a block diagram of the major functional units of the Battery SCPO.
FIG. 3 is a schematic diagram of the Battery SCPO.
FIG. 4A shows the modulation waveform of the Battery SCPO. FIGS 4B through 4F
show spec-trum analyses of the output of the Battery SCPO.
FIG. 5 is an external view of the components of the Generator Embodiment.
FIG. 6 is a schematic dlagl'alll Of the modulator circuit for the Generator Embodiment.
FIGs. 7A and 7B show, respectively, the modulation waveform and a portion of the output waveform of the Generator F~.lnbodiment.
FIGS. 8A and 8B show front alld back views of the treatment loop used in connection with the Generator Embodiment.
FIGS. 9A1 - 9J4 shove the treatment housings and treatment loops used for treating mice in the experiments described herein.
FIGs. 10 through 29 show, for each treated and control mouse involved in the inventors' ex-perimental studies, A, the locations of the tumors (if any) that developed, B, plots (on a logarithmic scale) of the respective vohmlca of tl~c various tumors as a function of time, and C, plots of the mouse's weight and hematocrit measurements as a function of time.
FIG. 30 A and B shows bar graphs of the life spans of the treated and control mice, respectively.
FIG. 31 A and B shows bar graphs of the life spans of the treated and control mice, respectively, after tumors were detected.
FIG. 32 A and B shows bar graphs of the number of tumors in the treated and control mice, re-:~U specHvely.
SUBSTfME SHEET iRULE 261 WO 98129156 PCTItTS97/23845 FIG. 33 A and B shows bar graphs of the outcome with respect to the tumors found in the treated and control mice, respectively.
FIG. 34 A and B shows bar graphs of the weight changes observed in the treated and control mice, respectively.
FIG. 35 A and B shows bar graphs of the maximum size of tumors observed in the treated and control mice, respectively.
FIG. 36 is a schematic diagram for an external modulator that attaches to the radio frequency output of an HP 8662A Frequency Generator and FIG. 36A is a top view of the exterior of the device.
FIG. 37 shows, for a mouse treated with a Generator Embodiment pulsed externally by the modulator shown in FIG. 36, A, the location of the tumor that developed, B, plots (on a logarithmic scale) of tumor volume as a function of time, and C, plots of the mouse's weight and hematocrit meas-urements as a function of time.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
1. DESIGN CONSIDERATIONS
According to experiments conducted by the present inventors, treatment with EMR is most ef-fective under the following conditions:
a) The treatment frequency is selected with a precision extending to the fifth or sixth decimal point, or at least one half part per million.
h) The frequency is extremely stable over the course of the treatment.
c) The precise frequency chosen is held at that frequency and applied without variation for at (east one hour.
d) RF p«wer applied to the subject is held to less than one milliwatt (mW).
e) The EMR is applied through a coiled loop of wire, which, for treatments in the 43 MNz.
Range, is approximately 60 Clll. long.
The frequencies listed in Table 1 are believed to be effective for treating the indicated maladies:
Table 1: Treatment Frequencies Frequency Malady 43,322,480 Sarcoma (generalized) 43,322,492 Sarcoma (intestines) SU6S'TU'UTE SHEEN" {RUI.~ 2~
WO 98!29156 PCT/US97123845 Frequency Malady 43,322,485 Sarcoma (breast) 43,346,000 Tuberculosis (general) 43,346,090 'Tuberculosis (intestines) 43,346,000 Tuberculosis (breast) 43,346,050 Common cold 43,353,800 Carcinoma (general) 43,353,800 Carcinoma (intestines) 43,353,850 Carcinoma (breast) 43,353,800 Malignancy 43,296,00() Strep 43,351,830 Treats several diseases 43,351,850 Treats several diseases 43,352,855 Treats several diseases 43,357,870 'Treats several diseases 43,352,000 Pneumonia 43,245,000 Staph The foregoing; list includes all of the frequencies studied by the present inventors and found to be effective. The inventors believe that different frequencies, even close to the above-stated frequencies are not effective. The~~ have found that the effectiveness of the treatment depends critically on the pre-cise frequency chosen, to the precision indicated herein. They have also found that steady treatment frequencies are more effective than swept or varied frequencies.
'this invention is not intended to be limited to the frequencies stated in the above table. The in-ventors believe that there may be other frequencies in the 43 MHz. range that the present inventors have not as yet studied, that may also be effective. Similarly, the present inventors believe that there may be effective treatment frequencies in completely different ranges, for example, at much higher fre-quencies. The most important factor, in the view of the present inventors, is a precisely chosen fre-quency steadily applied for at least an hour at a time.
FIG. 34 A and B shows bar graphs of the weight changes observed in the treated and control mice, respectively.
FIG. 35 A and B shows bar graphs of the maximum size of tumors observed in the treated and control mice, respectively.
FIG. 36 is a schematic diagram for an external modulator that attaches to the radio frequency output of an HP 8662A Frequency Generator and FIG. 36A is a top view of the exterior of the device.
FIG. 37 shows, for a mouse treated with a Generator Embodiment pulsed externally by the modulator shown in FIG. 36, A, the location of the tumor that developed, B, plots (on a logarithmic scale) of tumor volume as a function of time, and C, plots of the mouse's weight and hematocrit meas-urements as a function of time.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
1. DESIGN CONSIDERATIONS
According to experiments conducted by the present inventors, treatment with EMR is most ef-fective under the following conditions:
a) The treatment frequency is selected with a precision extending to the fifth or sixth decimal point, or at least one half part per million.
h) The frequency is extremely stable over the course of the treatment.
c) The precise frequency chosen is held at that frequency and applied without variation for at (east one hour.
d) RF p«wer applied to the subject is held to less than one milliwatt (mW).
e) The EMR is applied through a coiled loop of wire, which, for treatments in the 43 MNz.
Range, is approximately 60 Clll. long.
The frequencies listed in Table 1 are believed to be effective for treating the indicated maladies:
Table 1: Treatment Frequencies Frequency Malady 43,322,480 Sarcoma (generalized) 43,322,492 Sarcoma (intestines) SU6S'TU'UTE SHEEN" {RUI.~ 2~
WO 98!29156 PCT/US97123845 Frequency Malady 43,322,485 Sarcoma (breast) 43,346,000 Tuberculosis (general) 43,346,090 'Tuberculosis (intestines) 43,346,000 Tuberculosis (breast) 43,346,050 Common cold 43,353,800 Carcinoma (general) 43,353,800 Carcinoma (intestines) 43,353,850 Carcinoma (breast) 43,353,800 Malignancy 43,296,00() Strep 43,351,830 Treats several diseases 43,351,850 Treats several diseases 43,352,855 Treats several diseases 43,357,870 'Treats several diseases 43,352,000 Pneumonia 43,245,000 Staph The foregoing; list includes all of the frequencies studied by the present inventors and found to be effective. The inventors believe that different frequencies, even close to the above-stated frequencies are not effective. The~~ have found that the effectiveness of the treatment depends critically on the pre-cise frequency chosen, to the precision indicated herein. They have also found that steady treatment frequencies are more effective than swept or varied frequencies.
'this invention is not intended to be limited to the frequencies stated in the above table. The in-ventors believe that there may be other frequencies in the 43 MHz. range that the present inventors have not as yet studied, that may also be effective. Similarly, the present inventors believe that there may be effective treatment frequencies in completely different ranges, for example, at much higher fre-quencies. The most important factor, in the view of the present inventors, is a precisely chosen fre-quency steadily applied for at least an hour at a time.
2. CONSTRUCTION OF ALTERNATIVE TREATMENT DEVICES
For twenty years we have been working to obtain the correct frequencies with which to treat the mice and also the best possible instrument (method) with which to deliver the treatment to the mouse. Some of our experiments included using two plates (a hot and ground) rather than the treat-s ment loop. All things considered, we feel the embodiments employing treatment loop electrodes have performed the best in our experiments on the mice.
Detailed descriptions of the alternate embodiments of the invention are set forth here to dem-onstrate that the principles taught in this invention are readily reducible to practice. It should be under-stood that these embodiments represent but a few of the possible configurations of the present inven-tion, and that, utilizing the principles of the present invention as disclosed herein, analogous apparatus and methods may be readily devised for controlled therapeutic application of RF energy.
A. Batterc~ SCPO
Top and bottom external views of the battery-operated embodiment of the treatment device are shown in FIGS. lA and 1B. The device 100 is built in a small, self-contained rectangular metal package 75 measuring about 7.37 cm. long, 5.46 cm. wide, and 1.78 cm. in thickness.
Housing 110 is preferably metal. It provides mechanical protection for the apparatus and serves as a electromagnetic shield. Housing 110 is soldered shut. In battery holder 114 (Caltronics BI-I-124) ac-cessible from outside the package (and which may be recessed or attached to the exterior of housing 110), the housing accommodates four standard 1.5 volt "AA" alkaline batteries 115 of approximately 1.5 volts each, which provide the electrical power for the unit.
'fhe underside of the device, shown in FIG. 1B, accommodates a surface mounted coil of wire 120 referred to as the "treatment loop." One end of treatment loop 220 enters the bottom housing sur-face through a wire feed hole 140 in the bottom of housing 110. The other cnd of treatment loop is grounded at solder point I50 to the outside of housing 110. The treatment loop itself consists of five concentric, spiraled, rectangular turns of 20 AWG solid copper wire embedded in a 2 mm. (0.080 inch) thick sheet of high impact styrene 111 adhesively fastened to the bottom surface of housing 110.
(Alternatively, the treatment loop may be constructed on a printed circuit board.) 1'he windings are spaced 3.175 mm, apart and the overall dimensions of the loop are 2.858 x 5.258 cm.
The treatment loop 120 has a broad radiating pattern off the coil. It is not a "focused" radiation but a spreading radiation. More signal is available from the front then off the back of treatment loop 120 (the back is shielded by a ground plane). Tests were run using a loop without the back shield but dle results were not as good as with a back shield. The signal is strongest in the center since that is where the "hot" lead connects to treatment loop 120 .
The circuitry that drives treatment loop 120 is contained on a printed circuit board 190 (shown in the cutaway 180 in FIG. 1B) within housing 110. The schematic for this circuit is shown in FIG. 3. The circuit comprises two timer circuits 210 and 240, which provide approximately a 60 Hz. approximately 50% duty cycle square wave, and an approximately 70 pulse per minute (1.167 Hz.) approximate 50%
duty cycle square wave, respectively. These two square waves are combined in AND gate 260 in order to produce an approximately 60 Hz. square wave pulsed at approximately 1.167 I-Iz., each of the 60 Hz.
Square wave and the 1.167 Hz. pulse having an approximate 50% duty cycle. The waveform output by AND gate 260 is shown in Fig. 4A.
The output of AND gate 260 is then directed through filter 270, and then to quartz crystal XI
280. Although many frequencies could be chosen from, the Battery SCPOs built to date have used a crystal cut for a third harmonic frequency of 43.352830 ~ 20 Hz., 43.351850 ~
20 1 lz., 43.351855 t 20 Hz.
and 43.351870 ~ 20 Hz. (corresponding to base frequencies in the 14.450 MHz range). These frequencies have been found most effective for treating a broad range of maladies. The output of crystal 280 is di-reefed to treatment loop 120.
Viewed in further detail, the schematic diagram in FIG. 3 shows the power for the circuit de-rived from the four cell battery 301. 'This power supply feeds positive rail 302 and ground rail 303.
I5 The approximately 60 Hz. timing circuit 210 is based on a low power TLC 555 timer U2 311, set up as an astable mulHvibrator by connecting pins 2 (Trigger) and 6 ('Threshold) together. Pin 1 is con-nected to ground 303. Pins 4 and 8 are connected to the positive supply rail 302. 1'in 5 is connected to the midpoint of a voltage divider comprised of IK resistor R9 317 (this, and all other fixed resistors re-ferred to herein being 5%,'/a Watt, unless otherwise specified) from the positive supply and 2.2 K re-sistor RS 325 to ground 302. Pin 6 is in addition connected to 1N974, 75 PIV, switching; diode D2 319 forward biased from pin; to 0.22 uF (50 volt) electrolytic capacitor C3 327 to ground 303; to 47K resistor R5 321 to the wiper of 20K, 15 turn, 3/4 watt adjustable resistor R7 323, one end of which is open and the other end of which is connected to pin 7. Pin 7 in addition is connected to 33K resistor R4 313 to thc~
wiper of 20K, 15 turn, 3/4 watt adjustable resistor R6 315, one end of which is open and the other end of which is connected to the positive supply rail 302. PW 3 is the output.
The square wave frequency and duty cycle produced by 555 'l~imer U2 215 are adjusted by 20K, 15 turn, ~'ra watt adjustable resistors R6 315 and R7 323 in accordance with the following formulas:
tl (output high) = 0.693 x (R4 + R5 + R6 + R7) x C3 t2 (output low) = 0.693 x (R5 + R7) x C3 T (total period) = t1 + t2 f (frequency) = 1/T
D (duty cycle) _ (R5 + R7)/( (R4 + R6) + 2 x (R5 + R7) ) (Units: R - Ohms; C - Farads; t, T - Seconds, f - Hz.}
For twenty years we have been working to obtain the correct frequencies with which to treat the mice and also the best possible instrument (method) with which to deliver the treatment to the mouse. Some of our experiments included using two plates (a hot and ground) rather than the treat-s ment loop. All things considered, we feel the embodiments employing treatment loop electrodes have performed the best in our experiments on the mice.
Detailed descriptions of the alternate embodiments of the invention are set forth here to dem-onstrate that the principles taught in this invention are readily reducible to practice. It should be under-stood that these embodiments represent but a few of the possible configurations of the present inven-tion, and that, utilizing the principles of the present invention as disclosed herein, analogous apparatus and methods may be readily devised for controlled therapeutic application of RF energy.
A. Batterc~ SCPO
Top and bottom external views of the battery-operated embodiment of the treatment device are shown in FIGS. lA and 1B. The device 100 is built in a small, self-contained rectangular metal package 75 measuring about 7.37 cm. long, 5.46 cm. wide, and 1.78 cm. in thickness.
Housing 110 is preferably metal. It provides mechanical protection for the apparatus and serves as a electromagnetic shield. Housing 110 is soldered shut. In battery holder 114 (Caltronics BI-I-124) ac-cessible from outside the package (and which may be recessed or attached to the exterior of housing 110), the housing accommodates four standard 1.5 volt "AA" alkaline batteries 115 of approximately 1.5 volts each, which provide the electrical power for the unit.
'fhe underside of the device, shown in FIG. 1B, accommodates a surface mounted coil of wire 120 referred to as the "treatment loop." One end of treatment loop 220 enters the bottom housing sur-face through a wire feed hole 140 in the bottom of housing 110. The other cnd of treatment loop is grounded at solder point I50 to the outside of housing 110. The treatment loop itself consists of five concentric, spiraled, rectangular turns of 20 AWG solid copper wire embedded in a 2 mm. (0.080 inch) thick sheet of high impact styrene 111 adhesively fastened to the bottom surface of housing 110.
(Alternatively, the treatment loop may be constructed on a printed circuit board.) 1'he windings are spaced 3.175 mm, apart and the overall dimensions of the loop are 2.858 x 5.258 cm.
The treatment loop 120 has a broad radiating pattern off the coil. It is not a "focused" radiation but a spreading radiation. More signal is available from the front then off the back of treatment loop 120 (the back is shielded by a ground plane). Tests were run using a loop without the back shield but dle results were not as good as with a back shield. The signal is strongest in the center since that is where the "hot" lead connects to treatment loop 120 .
The circuitry that drives treatment loop 120 is contained on a printed circuit board 190 (shown in the cutaway 180 in FIG. 1B) within housing 110. The schematic for this circuit is shown in FIG. 3. The circuit comprises two timer circuits 210 and 240, which provide approximately a 60 Hz. approximately 50% duty cycle square wave, and an approximately 70 pulse per minute (1.167 Hz.) approximate 50%
duty cycle square wave, respectively. These two square waves are combined in AND gate 260 in order to produce an approximately 60 Hz. square wave pulsed at approximately 1.167 I-Iz., each of the 60 Hz.
Square wave and the 1.167 Hz. pulse having an approximate 50% duty cycle. The waveform output by AND gate 260 is shown in Fig. 4A.
The output of AND gate 260 is then directed through filter 270, and then to quartz crystal XI
280. Although many frequencies could be chosen from, the Battery SCPOs built to date have used a crystal cut for a third harmonic frequency of 43.352830 ~ 20 Hz., 43.351850 ~
20 1 lz., 43.351855 t 20 Hz.
and 43.351870 ~ 20 Hz. (corresponding to base frequencies in the 14.450 MHz range). These frequencies have been found most effective for treating a broad range of maladies. The output of crystal 280 is di-reefed to treatment loop 120.
Viewed in further detail, the schematic diagram in FIG. 3 shows the power for the circuit de-rived from the four cell battery 301. 'This power supply feeds positive rail 302 and ground rail 303.
I5 The approximately 60 Hz. timing circuit 210 is based on a low power TLC 555 timer U2 311, set up as an astable mulHvibrator by connecting pins 2 (Trigger) and 6 ('Threshold) together. Pin 1 is con-nected to ground 303. Pins 4 and 8 are connected to the positive supply rail 302. 1'in 5 is connected to the midpoint of a voltage divider comprised of IK resistor R9 317 (this, and all other fixed resistors re-ferred to herein being 5%,'/a Watt, unless otherwise specified) from the positive supply and 2.2 K re-sistor RS 325 to ground 302. Pin 6 is in addition connected to 1N974, 75 PIV, switching; diode D2 319 forward biased from pin; to 0.22 uF (50 volt) electrolytic capacitor C3 327 to ground 303; to 47K resistor R5 321 to the wiper of 20K, 15 turn, 3/4 watt adjustable resistor R7 323, one end of which is open and the other end of which is connected to pin 7. Pin 7 in addition is connected to 33K resistor R4 313 to thc~
wiper of 20K, 15 turn, 3/4 watt adjustable resistor R6 315, one end of which is open and the other end of which is connected to the positive supply rail 302. PW 3 is the output.
The square wave frequency and duty cycle produced by 555 'l~imer U2 215 are adjusted by 20K, 15 turn, ~'ra watt adjustable resistors R6 315 and R7 323 in accordance with the following formulas:
tl (output high) = 0.693 x (R4 + R5 + R6 + R7) x C3 t2 (output low) = 0.693 x (R5 + R7) x C3 T (total period) = t1 + t2 f (frequency) = 1/T
D (duty cycle) _ (R5 + R7)/( (R4 + R6) + 2 x (R5 + R7) ) (Units: R - Ohms; C - Farads; t, T - Seconds, f - Hz.}
The exact frequency and duty cycle of this square wave varies with the battery voltage and pre-cise component values The 60Hz. and 50% duty cycle figures required for successful operation of the preferred embodiment are believed to be plus or minus 10%, based on the condition of the batteries, exact component characteristics and environmental factors such as ambient and operating temperature.
The 1.167 Hz (70 pulse per minute) timing circuit 240 is similar to that of circuit 210. The ap-proximately 1.167 Hz. timer circuit 240 is based on a low power TLC 555 timer U3 341, set up as an as-table multivibrator by connecting pins 2 (Trigger) and 6 (Threshold) together.
Pin 1 is connected to ground 303. Pins 4 and 8 are connected to the positive supply rail 302. Pin 5 is connected to the mid-point of a voltage divider comprised of 1K resistor R24 347 from the positive supply and 2.2 K resistor TO R15 355 to ground 303. Pin 6 is in addition connected to 1N914, 75 PIV, switching diode D3 349 forward biased from pin 7; to 10.0 uF (16 volt) electrolytic capacitor C4 357 to ground 303; to 47K resistor Rll 351 to the wiper of 20K, 15 turn, 3/4 watt adjustable resistor R13 353, one end of which is open and the other end of which is connected to pin 7. Pin 7 in addition is connected to 33K resistor RIO 343 to the wiper of 20K, 15 turn, 3ra watt adjustable resistor R12 345, one end of which is open and the other end of 75 which is connected to the positive supply rail 302. Pin 3 is the output.
The output voltage of both TLC 555 timer circuits 210 and 240 is approximately 4 volts, which varies with battery supply voltage.
The approximately 7.667 Hz. signal is combined with the approximately 60 Hz.
signal in AND
gate 260 which consists of 330 Ohm input resistors R2 367 and R3 367, and MPS2907 PNP transistors Q1 20 280 and Q2 290. FIG. 4A shows the waveform output from AND gate 260.
From the output of the AND gate 260 is a 2.15K resistor R1 369 in series with 2 ma red light emitting diode (LED) Dl 117 (Radio Shack 276-044 or equivalent) forward biased to ground 303. The LED is visible on the outside of housing 110, and is in the circuit merely to provide a visual indicator that the Battery SCPO is operating.
25 T'he remainder of the circuit consists of 8.2 mII inductor L2 371 (Miller 8230-18), 5.5-18 pF
trimmer capacitor C2 372 (Sprague-Goodman Gl' A22000 or equivalent), duartz crystal X1 280 and treatment loop L7 T20 to ground 303.
Crystal X1 280 is cut so as to have a base frequency in the 14.4 MI-Iz. Range, and a third har-monic at one of the following frequencies: 43.351830 ~ 20 Hz., 43.351850 ~ 20 Hz., 43.351855 ~ 20 Hz 30 and 43.351830 ~ 20 I-Iz. Quartz crystal 280 is obtained from International Crystal Manufactures, P.O.
Box 26330, Oklahoma City, OK 73126, and selected with great care. Other sources for crystals that have been used include CTS Corporation, Knights Division, 400 East Reimann Ave., Sandwich IL 60548 (which is no longer in business) and NEL Frequency Controls, Inc. 357 Beloit Street, Burlington WI
Crystals are ordered approximately 25 - 50 at a time for each frequency, and are then individu-35 ally tested on a Saunders Crystal Test System so as to allow selection of crystals with the desired fre-quency characteristics. For one representative crystal, driven with a reference frequency near the ex-pected series resonance frequency, with a drive level of 2060 uWatts into 44 Ohms, with a 10 pF ca-pacitative load, the results of this testing were as shown in Table 2.
Table 2: Exemplary Crystal Measurements Parameter Description Value Fr(Hz.) Series resonant 43,351,870 frequency Hz.
Co(pF) Shunt capacity 4.0 pF
Rr(Ohms) Motional Resistance18.2 Ohms Q(k) Quality factor 161.0 K
C1(fF) Motional capacity 1.3 femtoParads L(mH) Motional Inductance10.7 mH
Fl(Hz.) Loaded resonant 43,353,820 frequency Hr.
Ts(ppm/pF) Trim sensitivity 3.2 ppm/ph PWR(uWatt) Power level 2740.0 uWatts No oven is used in this device. Instead, the unit is turned on for 10 minutes before use, and used in a room at an ambient temperature of approximately 72 degrees Fahrenheit.
The output portion of the Battery SCPO involves a series LC circuit, a series crystal, and the treatment loop, which is another W ductor. The large Motional Inductance of the crystal, and its very small Motional Capacitance, dominate the output circuit. This is driven by the square wave train com-ing out of AND gate 260. The modulation waveform output from AND gate 260, measured at the col-lector of transistor Q2 365, as shown in FIG. 4A, has a rise time of 18 nS and fall time approximately 120 nS. '1'o a reasonable approximation, each 60 Hz. cycle in the modulation wavefortn represents a 4 volt step input with the aforementioned rise and fall times, into a series LC
circuit with low series resistance.
'the high frequency components of the steep rise and fall of this square wave stimulates a ringing of the crystal at its characterisric base frequency and harmonics.
The actual output of the Battery SCI'O at the point of input to 'Treatment Loop 120 can be ob-served on an oscilloscope, and visibly contains RF frequencies. This was observed using an SCI'O con-structed with a 43.351870 Hz. Crystal. When the signal from the SCPO was input into a spectrum ana-lyzer, a -75 dB peak is observed at the 14.448461 MHz. base crystal frequency, and a -85 dB peak is seen at the 43.351870 MHz. third harmonic frequency of the crystal. An additional, weaker RF signal is ob-served at 43.420000 MHz. These various spectrum analyzer scans are shown in FIGS. 4B through 4F.
The 1.167 Hz (70 pulse per minute) timing circuit 240 is similar to that of circuit 210. The ap-proximately 1.167 Hz. timer circuit 240 is based on a low power TLC 555 timer U3 341, set up as an as-table multivibrator by connecting pins 2 (Trigger) and 6 (Threshold) together.
Pin 1 is connected to ground 303. Pins 4 and 8 are connected to the positive supply rail 302. Pin 5 is connected to the mid-point of a voltage divider comprised of 1K resistor R24 347 from the positive supply and 2.2 K resistor TO R15 355 to ground 303. Pin 6 is in addition connected to 1N914, 75 PIV, switching diode D3 349 forward biased from pin 7; to 10.0 uF (16 volt) electrolytic capacitor C4 357 to ground 303; to 47K resistor Rll 351 to the wiper of 20K, 15 turn, 3/4 watt adjustable resistor R13 353, one end of which is open and the other end of which is connected to pin 7. Pin 7 in addition is connected to 33K resistor RIO 343 to the wiper of 20K, 15 turn, 3ra watt adjustable resistor R12 345, one end of which is open and the other end of 75 which is connected to the positive supply rail 302. Pin 3 is the output.
The output voltage of both TLC 555 timer circuits 210 and 240 is approximately 4 volts, which varies with battery supply voltage.
The approximately 7.667 Hz. signal is combined with the approximately 60 Hz.
signal in AND
gate 260 which consists of 330 Ohm input resistors R2 367 and R3 367, and MPS2907 PNP transistors Q1 20 280 and Q2 290. FIG. 4A shows the waveform output from AND gate 260.
From the output of the AND gate 260 is a 2.15K resistor R1 369 in series with 2 ma red light emitting diode (LED) Dl 117 (Radio Shack 276-044 or equivalent) forward biased to ground 303. The LED is visible on the outside of housing 110, and is in the circuit merely to provide a visual indicator that the Battery SCPO is operating.
25 T'he remainder of the circuit consists of 8.2 mII inductor L2 371 (Miller 8230-18), 5.5-18 pF
trimmer capacitor C2 372 (Sprague-Goodman Gl' A22000 or equivalent), duartz crystal X1 280 and treatment loop L7 T20 to ground 303.
Crystal X1 280 is cut so as to have a base frequency in the 14.4 MI-Iz. Range, and a third har-monic at one of the following frequencies: 43.351830 ~ 20 Hz., 43.351850 ~ 20 Hz., 43.351855 ~ 20 Hz 30 and 43.351830 ~ 20 I-Iz. Quartz crystal 280 is obtained from International Crystal Manufactures, P.O.
Box 26330, Oklahoma City, OK 73126, and selected with great care. Other sources for crystals that have been used include CTS Corporation, Knights Division, 400 East Reimann Ave., Sandwich IL 60548 (which is no longer in business) and NEL Frequency Controls, Inc. 357 Beloit Street, Burlington WI
Crystals are ordered approximately 25 - 50 at a time for each frequency, and are then individu-35 ally tested on a Saunders Crystal Test System so as to allow selection of crystals with the desired fre-quency characteristics. For one representative crystal, driven with a reference frequency near the ex-pected series resonance frequency, with a drive level of 2060 uWatts into 44 Ohms, with a 10 pF ca-pacitative load, the results of this testing were as shown in Table 2.
Table 2: Exemplary Crystal Measurements Parameter Description Value Fr(Hz.) Series resonant 43,351,870 frequency Hz.
Co(pF) Shunt capacity 4.0 pF
Rr(Ohms) Motional Resistance18.2 Ohms Q(k) Quality factor 161.0 K
C1(fF) Motional capacity 1.3 femtoParads L(mH) Motional Inductance10.7 mH
Fl(Hz.) Loaded resonant 43,353,820 frequency Hr.
Ts(ppm/pF) Trim sensitivity 3.2 ppm/ph PWR(uWatt) Power level 2740.0 uWatts No oven is used in this device. Instead, the unit is turned on for 10 minutes before use, and used in a room at an ambient temperature of approximately 72 degrees Fahrenheit.
The output portion of the Battery SCPO involves a series LC circuit, a series crystal, and the treatment loop, which is another W ductor. The large Motional Inductance of the crystal, and its very small Motional Capacitance, dominate the output circuit. This is driven by the square wave train com-ing out of AND gate 260. The modulation waveform output from AND gate 260, measured at the col-lector of transistor Q2 365, as shown in FIG. 4A, has a rise time of 18 nS and fall time approximately 120 nS. '1'o a reasonable approximation, each 60 Hz. cycle in the modulation wavefortn represents a 4 volt step input with the aforementioned rise and fall times, into a series LC
circuit with low series resistance.
'the high frequency components of the steep rise and fall of this square wave stimulates a ringing of the crystal at its characterisric base frequency and harmonics.
The actual output of the Battery SCI'O at the point of input to 'Treatment Loop 120 can be ob-served on an oscilloscope, and visibly contains RF frequencies. This was observed using an SCI'O con-structed with a 43.351870 Hz. Crystal. When the signal from the SCPO was input into a spectrum ana-lyzer, a -75 dB peak is observed at the 14.448461 MHz. base crystal frequency, and a -85 dB peak is seen at the 43.351870 MHz. third harmonic frequency of the crystal. An additional, weaker RF signal is ob-served at 43.420000 MHz. These various spectrum analyzer scans are shown in FIGS. 4B through 4F.
In sum, rather than using a conventional crystal oscillator circuit, the battery SCPO uses a crystal series driven by audio range square wave input pulses, in order to generate low power, yet pre-cisely tuned, pulsed RF energy.
The treatment device is used by applying it, treatment loop down, to the subject's body in the area desired to be treated. The unit is left in place for approximately one hour at a time.
As indicated above, battery SCPOs have been built with crystals tuned to 43.351830 ~ 20 Hz., 43.351850 ~ 20 Hz., 43.351855 ~ 20 Hz and 43.351870 ~ 20 Hz. These frequencies were chosen because they are each believed to be useful for treating a plurality of illnesses, and because a multipurpose de-vice is advantageous by reason of the inconvenience of changing crystals.
However, there is no reason why this embodiment, would not be effective at any of the frequencies identified above as being thera-peutically useful, as well as, with an appropriately tuned output element, if necessary, at any frequency found in the future to be therapeutically useful.
A parts list for the Battery SCPO is set forth in Table 3.
Table 3: Parts List for Battery SCPO
Ref. Descri lion Source No.
71(1 SCPO Housin Fabricated -See text 114 Battery Holder Caltronics BH-124 715 "AA" Battery 4ea Wall reens 1.5V AA Ultra Alkaline ur a utv.
117 Dl Indicator Li ht - 2 Radio Shack 276-044 or mA LED Diode a uiv.
120 Treatment Loo Fabricated - See text 127 Backin ~ for treatment Hi h Im act S rent 0.080"
loo thick 2K0 Quartz Crystal ICM, CT'S, or NEL - See text 31 U2 - TLC 555 Timer Radio Shack 276-1723 or 1 a uiv.
373 R4 33K +/- 5%. 7 /4 Watt Radio Shack 271-1341 or Carbon Resistor ec uiv.
315 R6 20K 15 Turn 3/4 Watt Radio Shack 271-34(1 or Ad'. Resistor a uiv.
317 891.(1 K +/- 5/ 1/4 Watt Radio Shack 271-1321 or Carbon Resistor a uiv.
319 U2 IN914 Switchin Diode Radio Shack 276-1122 or 75 PIV a uiv.
321 R5 47K +/- 5%. 1/4 Watt Raclio Shack 271-1342 or Carbon Resistor c uiv.
323 R7 20K 75 T'um 3/4 Watt Radio Shack 277-340 or Ad . Resistor a uiv.
325 R8 2.2K +/- 5iL 1 /4 Wait Radio Shack 271-1325 or Carbon Resistor a utv.
327 C3 0.2?uf Electrolytic Radio Shack 272-1070 or Ca acitor, 50Volis a uiv.
341 U3 - TLC 555 Timer Radio Shack 276-7723 or ec uiv.
393 R10 33K +/- 5r~ 7 /4 Watt Radin Shack 271-1341 or Carbon Resistor ec uiv.
395 R12 20K 15'I'um 3/4 Watt Radio Shack 271-340 or Ad . Resistor cc un~.
347 R14 7 K +/- 5"r., 1 /4 Radio Shack 271-1321 c>r Watt Carbon Resistor ec my 34~> D3 1N914 Switchin Uiode Radio Shack 276-1722 or 75 P1V a mv.
:151 Rll 47K +/- 5% 7 /4 Watt Radio Shack 271-1342 or Carbon Resistor er uiv.
353 R73 20K 75'furn 3/4 Watt Radio Shack 271-34(1 or Ad . Resistor a ucv.
35~ R75 2.2K +/- 5%. 1/4 Watt Radio Shack 271-1325 or Carbon Resistor a uiv.
357 C4 lOuf Electrol tic Ca Radio Shack 272-1436 or acitor, 76Volts a uiv.
367 R2 33(1 Ohm +/- 5%. 1/4 Radio Shack 271-1315 or Watt Carbon Resistor a uiv.
363 QI MPS2907 PNP Transistor Radio Shack 276-2023 or a uiv.
365 Q2 MPS2907 PNP Transistor Radio Shack 276-2023 or a uiv.
367 R3 330 Ohm +/- 5 % 1 /4 Radio Shack 271-7315 or Watt Carbon Resistor a uiv.
369 Rl 2.2K +/- 5 % 7 /4 Watt Radio Shack 271-1325 or Carbon Resistor ec uiv.
371 L2 8.2 uH Inductor Miller 8230-18 372 C2 5.5 - 18 F Trimmer Ca S ra ue-Goodman GYA22000 acitor or ec uiv.
B. Generator Embodiment The alternate embodiment of the treatment device is shown in FIG. 5. It employs a model 8662A
frequency generator 500 manufactured by the Hewlett-Packard Company. Frequency generator 500 has a modulation input 520, to which is connected modulator unit 540, which provides an approximate 60 Hz square wave with an approximate 50% duty cycle, which is in turn gated with an approximately 1.T67 (70 pulse per minute) square wave, also with an approximately 50% duty cycle.
The circuitry of modulator unit 540, which is more fully described below, is similar to that of the Battery SCPO, up to the point of AND gate.
As shown in FIG. 6, power is provided by a plug-in DC power module 550, Radio Shack Cat.
No. 273-1455C or equivalent, which is rated at J volts D.C. at 0.3 amperes.
The positive lead from the module is switched through power switch SW1 542, and then directed to a 7805 5 volt voltage regulator Ul 605. The negative lead of the supply is attached to the unit's ground rail 603. Both the input and output of voltage regulator U1 605 is bypassed to ground by a 0.01 uF, 500 volt disc ceramic capacitor, Cl 606 and C2 607. The output, a regulated 5 volts, is applied to positive supply rail 602.
The circuitry associated with the TLC 555 timers 611 and 641 1S S110WI1 Ill FIG. 6, and is identical with the corresponding circuitry described above in the context of the Battery SCPO. The reference nu-merals "6I1" through "657" in FIG. 6 correspond to the identical elements "311" through "357" in FIG.
The AND gate of the modulator for the Generator Embodiment is configured identically here as in the Battery SCPO. R2, R3, Ql and Q2 (661, 663, 665, and 667) have the same values as in the SCPO
circuit (361, 363, 365 and 367).
The LED indicator circuit Rl 669 and Dl 541 differs from its counterpart in the Battery SCPO in that R1 669 is 330 Ohms rather than 2.15K. The resistor difference is for the:
purpose of obtaining the proper LED brightness in each circuit.
Adjustable resistor R77 677 provides a voltage divider between positive rail 602 and ground 603. The wiper of R17 677 provides a positively offset "ground" for purposes of output to the HP
8662A. The reason for this is that the I-IP 8662A expects an DC signal for purpos<a of modulation, so this adjustment is provided to offset the output around "zero volts" as referenced to the chassis of the I-IP 8662A.
The output of AND gate at the emitter of Q2 665 is connected to 8.2 uH
inductor L2 671 (Miller 8230-18). The resultant signal is bypassed to ground by a relatively large electrolytic capacitor, 2.5 uF, rated at 35 volts C5 673, and then passed to the center lead of output BNC
connector 521.
The approximate modulation waveform produced by modulator unit 540 iS shown in FIG. 7A.
The rounding of the rise and fall of the waveform is the result of capacitor C5 673. The modulated WO 98/29156 PCTlUS97123845 waveform of one of the 60 Hz. cycles output by the HP 8662A is shown in FIG.
7B (the RF component in this figure is not drawn to scale). The output power of the frequency generator is less than 1 mw.
The output of frequency generator 500 is directed through a second BNC
connector 531 con-nected to the panel of that instrument, and through a 50 Ohm, double-shielded coaxial cable 567 (RG
174 cable, Mouser #515-156-12 or equivalent). The coaxial cable is directed to a treatment loop 565 mounted on 2.0 mm. (0.080 inch) thick styrene sheet 566 which is laminated on stainless steel plate 560.
The plate has dimensions of approximately 10.2 cm. by 6.35 cm. The treatment loop 565 is a 20 AWG
solid copper wire approximately 60 cm. long, wound in a flat rectangular spiral comprising five turns, with a turn-to-turn spacing of approximately 3,275 mm. and overall dimensions of 2.858 x 5.258 cm.
The center of the loop is soldered to the center lead of coaxial cable 567.
Shield 863 of coaxial cable 567 is soldered to the back of plate 560 at solder point 861. The outer end of treatment loop 565 is grounded by being soldered at solder point 570 to the loop side of plate 560. (Use A
and B figures to show both sides of the plate.
The signal from the frequency generator based embodiment of the treatment device is sh~onger electromagneHcally than that output by battery operated device 100. It is also characterized by having only a single pure RF component at the desired frequency in the 43 Ml-1T
range. The treatment loop of generator embodiment is applied to the subject in the same manner as in the case of the battery pow-ered embodiment.
A parts list for the Generator Embodiment is set forth in Table 4.
Table 4: Parts List for Generator Embodiment Ref. Descri lion Source No.
5(10 Hewlett-Packard 8662A FrecHewlett-Packard Com an ucnc Generator 541 Dl Indicator Li ht - 2mA Radio Shack 276-044 or LED Diode ec uiv.
542 SWl Power Switch Radio Shack 275-67 2 or a uiv.
550 9V DC I'lu ~-In Power Su Radio Shack 273-14550 1 Module or ec uw.
560 Treatment Loo holder Fabricated - See text 565 'l reatment Loo Habricated -See text 567 Coaxial Cable, 50 ohm, RG774 cable Mouser #515-7156-12 Shielded 605 U 1 7805 5 Volt Volta ~e Radio Shack 276-177() Re ulator IC or a uiv.
60c, 0.01 ul' Disc Ceramic Ca Radio Shack 272-131 or acitor, 5()0 Volt cc uiv.
60;' 0.( ur Disc Ceramic Ca Radio Shack 272-13i or acitor, 500 Volt a urv.
611 U2 - TLC 555 Timer Radio Shack 276-7723 or c uiv.
61:1 R4 33K +/- 5.~ I /4 Watt Radio Shack 271-1341 or Carbon Resistor ec uiv.
615 R6 2(1K 15 Turn 3/4 Watt Radio Sltack 277-340 or Ad'. Resistor a uiv.
617 R9 7 .0 K +/- 5 % 1 /4 Radio Shack 271-1321 or Watt Carbon Resistor ec uiv.
61 D21 N914 Switchin Diode Radio Shack 276-1122 or ~t 75 PIV ec uiv.
621 R5 47K +/- 5% 1 /4 Watt Radio Shack 271-1342 or Carbon Resistor ec uiv.
623 R7 20K 15 Tum 3/4 Watt Radio Shack 271-340 or Ad'. Resistor a uiv.
625 R8 2.2K +/- 5% 1/4 Watt Radio Shack 271-1325 or Carbon Resistor ec uiv.
627 C3 0.22uf Electrol tic Radio Shack 272-1070 or Ca acitor, 50 Volts ec uiv.
641 U3 - TLC 555 Timer Radio Shack 276-1723 or a uiv.
643 R 10 33K +/- 5 % 1 /4 WattRadio Shack 271-1341 or Carbon Resistor a uiv.
645 IZ 12 20K 15 Tum 3/4 Watt Radio Shack 277-340 or Ad'. Resistor a uiv.
647 R 141K +/- 5/ 1 /4 Watt Radio Shack 271-1321 or Carbon Resistor a uiv.
649 D31N914 Switchin Diode Radio Shack 276-1122 or 75 PIV a uiv.
651 RI1 47K +/- 5~ 1/4 Watt Radio Shack 271-1342 or Carbon Resistor a uiv.
653 R73 20K 15 Turn 3/4 Watt Radio Shack 271-340 or Adj. Resistor equiv.
Ref. Descri lion Source No.
655 R15 2.2K +/- 5 % 1/4 Watt Radio Shack 271-232 Carbon Resistor 5 or e2uiv.
657 C4 lOuf Electrol tic Ca _ acitor, l6Volts Radio Shack 272-1436 or a uiv.
661 Pv2 330 Ohm + - 53'0 1 Radio Shack 271-1315 or /4 Watt Carbon Resistor a uiv.
663 Qi MPS2907 PNP Transistor Radio Shack 276-2023 or a uiv.
665 02 MPS2907 PNP Transistor Radio Shack 276-2023 or a uiv.
667 R3 330 Ohm +/- 5% 7 /4 Radio Shack 271-1315 or Watt Carbon Resistor a uiv.
669 Rl 330 Ohm +/- 5 ~0 1 /4 Radio Shack 271-1315 or Watt Carbon Resistor a uiv.
671 L2 8.2 uH Inductor Miller 8230-18 673 C5 1.47 uF Electrol tic Radio Shack 272-1433 &
Ca acitor, 35 Volts 1434 677 R 17 5K Aci'. 15 Turn 3/4 Radio Shack 271-340 or Watt Ad'. Resistor a uiv.
C. Alteniative "Mouse SCPO" for Mouse Studies For purposes of the mouse studies described below, an alternative embodiment of the treat-ment device was developed, hereinafter referred to as the "Test Embodiment".
The Mouse SCPO con-s sisted of an apparatus similar to the battery SCPO described above, but without a battery compartment, and powered by an external AC power adapter. The power adapter used was the same Radio Shack adapter 550 used with the modulator for the Generator Embodiment. The power supply circuit in the Mouse SCPO was identical to that used in the modulator for the Generator Embodiment, comprising the 7805 regulator U1 605, and the two 0.01 uF bypass capacitors C7 606 and C2 607. In all other re-spects, the Mouse SCPO was as shown in FIGs.1, 2 and 3, using the components listed in Table 4.
The feature lacked by the Mouse SCPO is the lack of restraint resulting from not being tethered by a wire. However, in the case of treating mice, this feature is irrelevant, since the mice must be immo-bilized for treatment in any event. On the other hand, the Test Embodiment had the advantage that it had no batteries to run low and to be checked and replaced.
7 S D. Extcr~eally Pulsed Generator Embodiment A further alternative embodiment of the treatment apparatus was developed, herein referred to as the "Externally Pulsed Generator." The Externally Pulsed Modulator embodiment is identical to the apparatus shown in FIG. 5, except that (1) the modulator does not attach to the Modulator Input of the 111' 8662A, but rather attaches directly via a BNC cotulector to the Rl~ ouput of the I11' 8662!1, (2) the ?0 modulator externally modulates the RF signal and does not utilize the internal modulation circuitly~
provided by the HI' 8662A; and (3) the cable used to connect the modulator to the 'l'reatment Loop is a specific type of coaxial cable, i.e., a I-Iewlett-1'ackard 10501 A, 50 Ohtn coaxial cable approximately 1.1 meters long.
The modulator in the Externally Pulsed Generator embodiment contains a series solid state RF
25 switch and associated connectors, which is pulsed by a pulsing circuit identical to that shown in FIG. 6, except that potentiometer R17 677 and capacitor C5 671 have been removed and the ground is taken from the main power supply ground rail 1303 (corresponding to rail 603 in F1G.
6). (Since there is no need to interface with the modulator input of the 8662A, there is no need for the floating ground used in the output circuit of FIG. 6.) The schematic diagram in FIG. 36 shows the entire circuit of this external modulator. In Fig.
36A, which shows the exterior of the device, shielded box 3601 is attached to the end of modulator housing 3600. Male BNC connector 3610 attaches directly to the RF output of the 8662A. Female BNC
connector 3620 attaches to the 10501 coax which in turn leads to the Treatment Loop. (Since this unit is a self-contained external modulator, it is necessary to turn off the modulation internal to the HP 8662A
using the switch for that purpose on the control panel of the HP 8662A.}
In the RF switching circuit, the output of inductor L2 3671 is a 60 I-iz/1.667 Hz. waveform 3640 (also as shown in FIG. 7A}. This waveform shifts the bias on D4 3651 and D5 3652 so as to switch the RF
applied to input 3653 in accordance with the pulses from L2 3671. In addition, inductor L2 3671 serves in this circuit as an RP choke keeping excessive RF from going back into the pulsing circuitry.
Table 4A: Additional fart for Externally Pulsed Generator Embodiment Ref. Descri lion Source No.
500 C511.01 yf ca acitor Radio Shack 272-131 or a uiv.
547 C6 0.111 yt ca ~acitor Radio Shack 272-131 or c mv.
542 R17 3:10 Ohm + /- ~';" Radio Shack 275-1375 or ':, lNatt Carbon Resistor a uiv.
542 R18 33o Ohm +/- 5'iL via Radio Shack 275-1:115 Watt Carbon Resistor or a uiv.
550 U41N~)14 Switchm; Lhode Radio Shack 273-1122 ore 75 T'IV uiv.
5f~(1 Metal T3ox Anv suitable su lier 565 Male BNC connector Anv suitable su lier 567 Female BNC conmctor Anv suitable supplier 3. EXPERIMENTAL PROCEDURE AND RESULTS
A controlled set of experiments were conducted during 1995 and 1996, to June 25, 1996, to test the utility of the present invention with respect to the suppression and elimination of cancerous tumors, cysts, lesions, and neoplasia. The crperiments were performed upon mice, by the topical application of electromagnetic (LMR) radiation at specific frequencies and intensities on a regular schedule, using the apparatus of the present invention as adapted for applying EMR to mice. tNe also present some addi-tional measurements taken in 1997 with respect to one mouse that was treated using the Externally Pulsed Generator ~rllt7(7(~111lCIlt.
"Suppression anti elitnination" IneallS that tumors, etc. that do develop are smaller in size, oc-cur relatively infrequently and are likely to disappear over time, as opposed to unheated tumors that are larger al size, occur more frequently and are unlikely to disappear before the death of the subject.
Use of TAX Mice as Experimental Subjects The Jackson Laboratory at liar Harbor, Maine, 04609 supplies mice for scientific research. These special mice are "JAX Mice," of a special inbred breed identified as C3H HeOu . These mice are highly abnormal, in that they are inherently very susceptible to adenocarcinoma of the mammary gland, due to the contributing factors of inherited genes, excessive hormonal stimulation, and the mouse mammary SU9STIME SHEET °~RULE 2S1 WO 98/29!56 PCT/US97I23845 tumor virus, which is passed to the young through the mother's milk. The adenocarcinomas develop spontaneously in these mice, and the breed is characterized by a high incidence of mammary tumors by eight months of age. Our project has used "JAX Mice" type C3H HeOu throughout all of its research for treatment of mouse tumors, including all of the treated and control mice referred to herein.
The JAX C3H HeOu mice were selected in order to provide a sensitive animal model for test ing anticancer treatments. The effectiveness of various treatments for such tumors is measured by de termining improvements in lifespan or other physical characteristics, such as gross appearance, health status, and other related data, of groups that have received the treatment, as against untreated controls.
This maruzer of testing using JAX mice is accepted as a valid animal model for determining the pro spective utility of cancer treatments in humans.
In a memorandum dated March 18,1997, The Jackson Laboratory notified users of C3I-I/HeOuJ
that it had observed an alteration over time of the development and incidence of tumors in this strain.
Our experunents were primarily conducted in a much earlier time frame than that concerned in this memorandum, and we do not believe any of our experimental results were affected thereby.
I5 Summary of Experimental Procedures and Results "Control" and "treated" selections of JAX mice (70 mice per group) were observed over the du-ration of their lives. Control mice were not exposed to the treatment procedure at all. The treated mice were exposed to EMR at the skin layer.
The treatment given was exposure to electromagnetic radiation applied to the skW of the mouse, with the radiation held at a given frequency throughout dte tr~catment.
The duration of treat-ment was usually one-half to one hour, and during the treatment, the treatinT;
electrode Has shielded from undue light and moving air currents.
The data from our experiments, discussed in detail below, show that:
I. 'Treated mice live much longer than controls.
2. The life spans of treated mice compare favorably H-ith life spans of normal (i.e., non-JAX) mice.
3. 'Treated mice have good health throughout their life.
4. Prior treatment has prevented abdominal tumor development.
5. When an abdominal tumor has been treated directly on the electrode it is caused to dis-appear.
6. By contrast:
a) Tumors on control mice grow rapidly until death of the mouse, b) And as tumors grow, a control mouse gains weight, its hematocrit decreases and its health fails rapidly until death.
Treatment of the particular mice herein discussed was by exposure of the JAX
mice to radiation from an electrode which was energized by a low power source that was preset to provide frequencies of 43.351830 MHz, 43.351850 MHz and 43.351870 MHz. In some cases, an HP-8662A
Signal Generator preset to these frequencies was used, equipped with a modulator (in all but the 1997 data, an internally coupled modulator), to provide approximately 1.667 and 60 Hz., approximately 50°/ duty cycle square wave pulse trains as previously described. In other cases, the same pulsed treatment frequencies were obtained with the "Mouse SCPO" embodiment described above, which contained its own modulator circuit, driving an internal quartz crystal.
The frequencies selected, as listed in the preceding paragraph, were based on prior experiments conducted over a period of many years, during which a large number of mice were treated under varying conditions and with various treatments. The three frequencies specified in the preceding para-graph are believed by the inventors to be among the most effective frequencies for treating a range of maladies. When using the Mouse SCPO embodiment, the treatment frequency used 69% of the time (659 hours out of a total of 950) was 43351870 Hz. When using the I-1P 8662A
signal generator for treat-ment, many (35) different frequencies were used.
Treatment Procedures One of the treated mice (OUJ-479) received treatments before a tumor appeared and lived and died tumor free.
7'reaiment of the remaining mice started as soon as a tumor reached 0.07" in length, width, and height, corresponding to an ellipsoid having a volume of 0.0295 cubic cm.
(0.00018 cubic inches). The treatments for all these ten mice were every day except Sunday. Thc: treatment frequencies are limited to a few specific frequencies within a narrow range, and the intensities are normally set to 0 dBm into a 5() ohm load.
I7ue to variations among individual mice (as in other species, including humans), a treatment configuration that is effective for one subject doesn't always work for another. Frequencies of 43.351850 Mi-iz and 43.351870 MHz were used for standard treatment on almost all of the mice. These frequencies have demonstrated good result's. Treating mice with 43.351850 MHz from a signal generator and/or pulsed crystal, appears to clear up their secondary infections, and treating with 43.351870 MHz seems to restore their general health. All of the treated mice appeared to be very lively and have a very healthy skin and hair appearance. Of the mice listed below, all hematocrit values have stayed in the healthy range of 38% to 46%, and their weight basically stayed the same since they began treatment.
Hematocrits for both the treated and the control mice were measured in accordance with the following procedure. The hematocrit was taken once a week. The mouse was placed under a heat lamp for a few minutes to cause the veins in the tail to dilate, thus making it easier to extract the blood for the sample. The amount of blood taken was about one-half of the standard 75 mm long capillary tube. The capillary tubes containing the blood are spun in a Micro-Hematocrit Centrifuge, at its "number three' marking. The capillary tubes are removed and placed in the Micro-hematocrit Tube Reader, which gives the percent of red blood cells found in the sample.
We have observed that tumors that have reached 0.07" in length, 0.07" in width, 0.07" in height are definitely a malignant growth, and benign or cystic lesions can be ruled out. Neoplasia measured under the agreed size are questionable. Almost all of the neoplasia encountered measured 0.07", 0.07", 0.07" and above.
The treatments employed a variety of treatment electrodes and housings, as shown in FIG. 9.
The preferred housing was the "E" housing shown in FIG. 9A, and the preferred electrodes were the "I"
electrode associated with the Mouse SCPO, FIG. 9J, and the "F" electrode used with the Hewlett-Packard signal generator, Fig. 9B.
Tumors treated directly on the treatment electrode slowly regressed until they were gone. Tu-mors that Here not on, or only partially on, the electrode showed a decrease in growth rate, but the tu-mor would steadily grow and not regress back The electrode was re-designed so that any tumor could be treated. The tumor must be directly on the electrode to receive the maximum treatment needed for complete regression of growth. Mice with lesions on their abdomen had direct contact with the elec-trode, and all completely regressed back to zero. We've had similar success with some mice with lesions on the neck, left leg, right neck, right side, etc.
SW ce mammary tumors occur spontaneously in these mice, some mice were also treated before any tumors appeared in the hope of preventing the inevitable fate of the cancerous C3H strain, which have an almost 100°ro occurrence rate. At present one of the mice lived out its life span tumor free and died of old age.
Treated Mice The following describes our experimental results with respect to each individual treated mouse.
For each mouse, there is a corresponding drawing showing where on the mouse tumors appeared, and in which the tumors are identified by a "tumor number" T-X, as well as a drawing reference numeral; a graph showing tumor volume in cubic inches vs. time in days; a graph showing mouse weight in grams and hematocrit readings vs. time in days; and an Appendix setting forth all experimental measure-menu taken with respect to the mouse.
F.ach tumor growth graph (FIGS. 10B, T1B, etc.) shows the size of each tumor, in cubic inches, on the mouse in question as a logarithmic function of days after the appearance of the subject's first tu-mor. Tumor volume, in cubic inches, was calculated based on the assumption that the tumor was ap-proximately an ellipsoid, and had a volume equal to 1/2 length x 1/2 width x height x 2.094.
Each weight and hematocrit graph (FIGS. 10C, 11C, etc.) shows, in two separate plots, (a) the weight of the mouse, in grams, and (b) the subject's hematocrit values (percentage of red blood cells) as a linear function of days after the appearance of the subject's first tumor.
The detailed data collected with respect to each treated mouse is shown in tabular form in Ap-pendices A-1, A-2, etc. attached hereto, and the data collected with respect to each control mouse is shown in tabular form in Appendices, B-1, B-2, etc. attached hereto. The data with respect to one mouse tested in 199 is shown in tabular form in Appendix C.
Example 1 - Treated Mouse OUJ-456 Table 5: Treatment Summary for OUJ-456 Date of Birth: 09/08/94 Date Died: 08/04/95 Lived: 310 days Treated: 91 days Tumor measurements 05/05/95 started:
Tumor measurements 9I days taken for:
This mouse lived 219 days before any tumor appeared. Notice (in PIG. 1013) that T-2 1002, which was hard to reach with our electrodes, gre~n~, but at a slower rate than a typical control mouse. As will be seen from this and the other examples hereW , treated mice live three times I<»iger than controls after a tumor appears.
WO 98/29156 PCTlUS97/23845 Example 2 - Treated Mouse OUJ-470 Table 6: Treatment Summary for OUJ-470 Date of Birth: 03/03/94 ate Died: 07/30/95 Lived: 515 days Treated: 257 days Tumor measurements 11/16/94 started:
Tumor measurements 257 days taken for:
This mouse lived 258 days before any tumor appeared. Notice (in FIG. 11 B) that 'I'-1 1101 ap-peared and went away at two different times. T-2 1102 appeared for a short period. T-3 1103 appeared when this mouse was 496 days old. This is one of the longest-lived mice in our experiments.
Example 3 - Treated Mouse OUJ-471 Table 7: Treatment Summary for OUJ-471 Date of Birth: 03/03/94 Date Died: 07/20/95 Lived: 504 days Treated: 799 days Tumor measurements 01/02/94 started:
'tumor measurements799 days taken for:
'This mouse lived 305 days before any tumor appeared. Notice that 'I'-1 1201 and T-2 1202 ap-peared for a short period. Notice (in FIG. 12C) the steady weight at 30 grams and constant high hema-tocrit percentage readings. This was also one of our longest-lived mice.
Example 4 - Treated Mouse OUJ-473 Table 8: Treatment Summary for OUJ-473 Date of Birth: 03/03/94 Date Died: 07/28/95 Lived: 514 days Treated: 211 days Tumor measurements 12/29/94 started:
Tumor measurements 211 days taken for:
As an experiment, we treated this mouse before any tumors appeared. This mouse never de-veloped any tumors (FIG. 13B). She lived 303 days before we started treatments. Notice (in FIG. 13C) die steady weight at 28 grams. This was also one of our longest-lived mice.
Example 5 - Treated Mouse OUJ-475 Table 9: Treatment Summary for OUJ-475 Date of Birth: 03/03/94 Date Died: 07/28/95 Lived: 514 days Treated: 256 days 'Tumor measurements11/14/94 started:
Tumor measurements 256 days taken for:
This mouse lived 258 days before any tumor appeared. Notice (FIG. 14B) that T-1 1401 and T-2 1402 appeared for a short period. Notice (FIG. 13C) the steady weight at 30 grams and quite-constant high hematocrit percentage readings. This was also one of our longest-lived mice.
Example 6 - Treated Mouse OUJ-496 Table 10: Treatment Summary for OUJ-496 Date of Birth: 12/21/94 Date Died: 01/05/96 Lived: 380 days Treated: 213 days Tumor measurements 09/15/95 started:
Tumor measurements 113 days taken for:
This mouse lived 267 days before any tumor appeared. Notice (FIG. 15B) that T-1 1501and 'f-5 2505 appeared and left. Notice (FIG. 15C) dte steady weight at 30 grams and high hematocrit percent-s age readings. Even with all these tumors, this mouse stayed healthy until the end and lived a long time.
Example 7 - Treated Mouse OUj-506 Table 11: Treatment Summary for OUJ-506 Date of Birth: 01/05/95 Still living: 06/25/96 Lived: 537 days Treated (and/or 250 days took data):
Tumor measurements 70/19/95 started:
Tumor measurements 250 days taken for:
This mouse lived 287 days before any tumor appeared. Notice (F1G. 16B) that T-1 1601 , T-2 1602, and T-3 1603 appeared for a short period. After 170 days, T-21602 reappeared. Notice (FIG. 16C) 70 d1e constant high hematocrit percentage readW gs. 'This was our longest-lived mouse, and it had a long healthy life.
Example 8 - Treated Mouse OUj-516 Table 12: Treatment Summary for OUJ-516 Date of Birth: 02/02/95 Date Died: 03/ 26/ 96 Lived: 418 days Treated: 240 days Tumor measurements 07/31/95 started:
Tumor measurements 240 days taken for:
This mouse had a record number of tumors, many of which Here not on the abdomen (PIG.
17A). After treatment all tumors disappeared except T5 1705, T71707, T8 1708, and T9 1709 (PIG. 17B).
In spite of the large number of tumors, she lived 418 days.
Example 9 - Treated Mouse OUJ-526 Table 13: Treatment Summary for OUJ-526 Date of Birth: 02/02/95 Date Died: 04/12/96 Lived: 435 days Treated: 168 days Tumor measurements 20/28/95 started:
Tumor measurements 168 days taken for:
This mouse had three tumors which disappeared and never returned (1'IG. 18B).
She lived 267 days before any tumor appeared. T41804 and T5 1805 grew together as one tumor.
Hematocrit percent 7 0 (FIG. 18C) stayed quite high throughout her life.
Example 10 - Treated Mouse OUJ-650 Table 14: Treatment Summary for OUJ-650 Date of Birth: 04/04/95 Still living: 06/ 25/ 96 Lived: 448 days Treated: 195 days Tumor measurements 12/13/95 started:
Tumor measurements 195 days taken for:
This mouse had three tumors, all of which disappeared and never re-appeared (FIG. 19B). Her hematocrit percent and remained high and her weight stayed constant throughout the measurement period (FIG.19C).
Control Mice The controls listed below all had spontaneous occurrences of multiple tumors that arose in various areas of the mammary gland region, and also had a very short survival time once the tumors appeared, usually around a two-month period.
None of the control mice in this study received EMR treatments or any other type of interven-tion methods. Daily weight and tumor measurements and observations were noted, as well as hema-tocrits to indicate the mouse's present health status at the time. These non-treated mice appeared to be in excellent health and appearance when the tumor remained small and didn't metastasize, but as the malignancy progressed and spread to other tissues, the effects on the mouse were readily seen.
The tumor measurements showed a rapid increase in tumor size that continuously rose almost every day, accompanied with a steady gain in weight, especially, H~ith the arrival of neH~ neoplasms.
The hemah~ocrit steadily lowers with the increase in tumor measurements. Other side-effects were also observed in the controls, such as, the coat began to show a rougher appe>aran ce, the back bone pro-truded out, they appeared to be malnourished, and the normal curiosity and physical activity seen in healthy mice were absent. The neoplasms' appearance also changed once the tumor reached a certain size, usually around 1.5 cm. in diameter and up. They usually would start to appear red and puffy, which would deepen in color showing areas of purple and black sores, which eventually ulcerated with severe bleeding. Some of the mice also appeared to get secondary W fections once the tumor ulcerated, accompanied by the draining of clear fluid and WBC present in the wound. When the tumor reached a diameter of 1.8 cm., and the hematocrit value was 25 % or lower, the mouse usually died within a cou-ple of days.
As will be illustrated by the experimental data that follows, the characteristics of all control mice observed in the lab included the following: a rapid growth rate of tumors shown in the increasing size measurements and weight gain; metastasis; and continual decrease W
hematocrit with the increas-ing tumor measurements. All the above symptoms affect the mouse's gross appearance, tumor appear-ance and shortened survival span once the tumors appear. This is reflected in the data that follows in the controls' rate of growth, and their decrease in hematocrit and length of survival period.
Example 11 - Control Mouse A-486 Table 15: Summary for A~86 Date of Birth: 04/04/95 Date died: 06/25/96 Lived: 448 days 'Treated: Not treated Tumor measurements 08/09/95 started:
Tumor measurements 97 days taken for:
This mouse had one tumor which grew very rapidly to a large size (FIG. 20B).
She had another tumor which appeared for 8 days. Her weight started to increase near the end, and the low hematocrit readings indicated a poor general health (FIG. 20C).
Example 12 - Control Mouse A-488 Table 16: Summary for A-488 Date of Birth: 11/28/94 Date died: 11/13/95 Lived: 350 days Treated: Not treated Tumor measurements 07/20/95 started:
Tumor measurements 116 days taken for:
This mouse had one tumor (T'1 2101) which didn't change much for forty days then grew rap-idly (FIG. 21B). T-2 2102 came in and left after 32 days. T-3 2103 stayed constant in size for about 90 days, then grew rapidly.
Example 13 - Control Mouse A-490 Table 17: Summary for A-490 Date of Birth: 12/19/94 Date died: 11/29/95 Lived: 345 days 'Treated: Not treated Tumor measurements 10/11/95 started:
'Tumor measurements50 days taken for:
This mouse had four rapidly growing tumors and lived only fifty days after the first tumor ap-peared (FIG. 22B). After 20 days her weight increased and hematocrit reading steadily dropped (FIG.
22C).
Example 14 - ControI Mouse A-492 Table 18: Summary for A-492 Date of Birth: 12/19/94 Date died: 12/29/95 Lived: 375 days Treated: Not treated Tumor measurements 09/15/95 started:
Tumor measurements 105 days taken for:
At 375 days, this is the longest lived control mouse. (Nine of our ten treated mice lived longer.) She had two tumors that left (FIG. 23B). But, after thirty days, T3 2303 and T4 2304 appeared and started to grow very rapidly. Her hematocrits dropped rapidly after 70 days of measurements (FIG.
23C).
Example IS - Control Mouse A-500 Table 19: Summary for A-500 Date of Birth: 01/04/95 Date died: 10/ 11 /95 Lived: 280 days Treated: Not treated Tumor measurements 09/15/95 started:
Tumor measurements 26 days taken for:
This mouse did not live very long and was observed only twenty-six days then she died. Tu-moss grew rapidly (FIG. 24B) and hematocrits were quite low (FIG. 24C).
Example 16 - Control Mouse A-538 Table 2Q: Summary for A-538 Date of Birth: 03/24/95 Date died: Ol / 15/96 Lived: 297 days Treated: Not treated Tumor measurements 10/19/95 started:
Tumor measurements 88 days taken for:
This mouse had three large tumors (FIG. 25B) and rapid weight increase and very low hema-tocrit percent readings (FIG. 25C). This mouse also did not live very long and was quite unhealthy.
Example 17 - Control Mouse A-540 Table 21: Summary for A-540 Date of Birth: 03/25/95 Date died: 01/02/96 Lived: 283 days Treated: Not treated Tumor measurements 7 7 / 15/95 started:
Tumor measurements 48 days taken for:
This mouse had one tumor that grew to a large size and grew fast (PIG. 26B).
Low hematocrits caused this mouse to die in a short period (PIG. 26C).
WO 98/29156 PCTlUS97/23845 -Example 18 - Control Mouse A-542 Table 22: Summary for A-542 Date of Birth: 03/25/95 Date died: 01/18/96 Lived: 299 days Treated: Not treated Tumor measurements11/27/95 started:
Tumor measurements52 days taken for:
This mouse had two tumors that grew to a large size and grew fast (I~IG. 27B).
Weight contin-ued to increase as the tumors grew (FIG. 27C). A tumor size of 0.1 to 0.5 cubic inches on a mouse tlzis small is duite a burden for the mouse. They do not survive for long; with tumors that size.
Example 19 - Control Mouse A-592 Table 23: Summary for A-592 Date of Birth: 06/27/95 Date died: 02/14/96 Lived: 232 days 'Treated: Not treated 'Tumor measurements02/19/96 started:
Tumor measurements26 days taken for:
'This mouse had one tumor that grew to a one cubic inch in size and grew fast (FIG. 28B). Rapid decline in hematocrits caused this mouse to die iii a short period (FIG. 28C).
Notice the rapid increase in weight: the mouse nearly doubled in weight in twenty days. This was a very short-lived mouse.
Example 20 - ControI Mouse A-594 Table 24: Summary for A-594 Date of Birth: 06/27/95 Date died: 02/15/96 Lived: 233 days Treated: Not treated Tumor measurements 01/12/96 started:
Tumor measurements 34 days taken for:
This mouse also had one tumor that grew to a large size and grew fast (FIG.
29B). Rapidly de-clining hematocrits caused this mouse to die in a short period (FIG. 29C).
This is one of the shortest-lived control mice of the group.
Experimental Conclusions Our principal conclusion, based on the experiments described above, is that the cancer-prone JAS mice benefited considerably from the therapeutic apparatus and method of the present invention.
The subsidiary experimental conclusions that support this assertion are as follows:
1. Total Days of Life: Treated Mice Live 50'%. Loner The bar-graphs in PIG. 30 show that the treated mice lived approximately 50%
longer on aver-age than the controls. L,ach Gar indicates: Days of Waiting 3001, Days of Treatment (or Measurement) 3002, 3003, and Total Days Of Life 3004.
Tlu~ data underlying FIG. 30 (as well as I:IGs. 31 and 32, discussed below) is presented below in tabular form.
Table 25: Days of Life, Measurement, and Number of Tumors SUBJECTNON MEASUREDQTY TOTAL
MEASUREDDAYS OF LFE
DAYS TUMORS
l OUJ-506287 250 5 481 ~
SUBJECTNON MEASUREDQTY TOTAL
MEASUREDDAYS OF LIFE
DAYS TUMORS
Totals:2594 1976 37 4,458 Totals:2405 641 27 3,046 2. Starting Treatment After First Tumor Appears: Treated Mice Live More than 300"/..
Lo- nger FIG. 31 shows that after the first tumor appeared, the treated mice lived longer than the control mice. The bars u1 these graphs represent Days of Treatment for treated mice or Days of Measurement for control mice. The data underlying FIG. 31 is set forth in Table 25 above.
3. The Treated Mice Had Morc Tumors (b~37"/o But Thcy Lived Longer FIG. 32 shows the number of tumors that developed in each mouse. It must be noted that even though there were 37io more tumors in the treated mice, they lived longer than the controls. The data underlying FIG. 32 is set forth in Table 25 above.
70 4. Tumors that Appeared were Five Times More Likely to Disappear in the Treated Mice than in the Controls.
FIG. 33 shows the total number of tumors in each mouse, and those tumors that disappeared or were cured and the remaining tumors at the death of each mouse. (Note: OUJ-506 and OUJ-650 were still living as of June 25,1996, when this data was compiled.) 25 The data underlying FIG. 33 is set forth in Table 26 below.
Table 26: Tumors That Disappeared SUBJECTMEASUREDREMAININGCUREDITOTAL NON
DAYS TUMORS GONE LIFE MEAS-TUMORS URED
DAYS
Totals:1976 13 24 4,570 2594 Totals:641 23 4 3,046 2405 5. The Weight of the Treated Mice Remained Stable Whereas the (:ontrol Mice Markedly Gamed We.~ht FIG. 34 shows that the treated mice maintain their weight on average, while the control mice gain considerable weight due to tumor growth. (Note: The weight change shown is the last 10 day weight average minus the first 10 day weight average of each mouse.) The data underlying FIG. 34 is set forth in Table 27 below.
Table 27: Comparative Weight Changes Treated Weight ControlWeight Mouse Change Mouse Change OUJ-456 5.85 A-592 20.31 OUJ-526 2.37 A-538 15.42 OUJ-470 1.31 A-490 14.32 OUJ-471 -0.15 A-542 g,g7 OUJ-473 -1.36 A-486 6.54 OUJ-475 -2.22 A-540 6.15 OUJ-506 -0.66 A-492 3.gg OUJ-650 -0.75 A-500 0.02 OUJ-516 0.07 A-488 -1.73 OUJ-496 -4.92 A-594 -4.92 Totals: 0.14 70.06 6. The Control Mice Had More Large Tumors FIG. 35 shows the maximum sizes of each tumor on the twenty different mice.
Some of these tumors disappeared. The vertical scale is tumor size in cubic inches. There were 37 treated and 27 control tumors hut this grnph shows the 27larQest treated tumors and all 27 control tumors.
The data underlying FIG. 35 is set forth in Tables 28A and B below.
Table 28A: Comparison of Maximum Tumor Size (in cubic inches) TreatedTumor Tumor Tumor Tumor Tumor Tumor Tumor Tumor Tumor Subject1 2 3 4 5 6 7 8 9 OUJ-4560.000014130.27320000 OUJ-4700.000179600.000014130.00954900 OUJ-4710.000261800.00009161 OUJ-4750.000014130.00036650 OUJ-4960.001178000.037990000.006332000.010990000.000153900.00029680 OUJ-5060.000014130.018660000.000014130.000179600.01682000 OUJ-5160.000014130.000179600.000065440.006533000.081790000.000483700.036240000.0556 00000.17990000 OUJ-5260.000014130.000829200.000065440.065790000.00533600 OUJ-6500.002419000.000065440.00006544 Total0.004108000.331400000.016090000.083490000.104100000.000780500.036240000.05 5600000.17990000 Average0.000456500.036820000.002682000.020870000.026030000.000390300.036240000.
055600000.17990000 Table 28B : Comparison of Maximum Tumor Size (in cubic inches) ControlTumor Tumor Tumor Tumor subject1 2 3 4 A-486 0.439200000.00001413 A-488 0.417900000.006193000.007622000.01493000 A-490 0.208000000.470800000.049130000.02954000 A-492 0.000523500.000065440.106900000.16280000 A-500 0.064780000.042520000.20560000 A-538 0.563500000.323100000.03216000 A-540 0.39520000 A-542 0.368200000,13700000 A-592 0.819200000.004192000.01504000 A-594 0.19090000 Total 3.467000000.983800000.416400000.20730000 Average0.346700000.123000000.069400000.06910000 Test of Externally Pulsed Generator FIG. 37 shows the results of treating mouse OUJ-738 in 1997 with the Externally Pulsed Gen erator embodiment. Treatment was with the HP 8662A frequency generator externally modulated with the modulator shown in Fig. 36, coupled to a treatment loop as shown in FIGS.
8A and 8B deployed in the "E" housing shown in FIG. 9A. The corresponding experimental data is shown in Appendix C.
FIG. 37A shows that a single tumor TI 3701 developed on this mouse W the left arm position.
This position is difficult to treat because it is out of the way and as a consequence it is difficult to posi-tion the treatment electrode close to the tumor. Nevertheless, the results with this mouse were ex-tremely good for the period of testing. As shown in FIG. 37B, the tumor stayed small for the entire pe-riod, and as shown in FIG. 37C, the weight was stable and the hematocrits remaitled high. The data ex-tends up to a few days prior to the filing of this application, and at the end of this period the mouse was alive and healthy.
In addition, data were compiled in 2997 with respect to tumors that disappeared after treat-ment with the generator embodiment. This data, which otherwise appears in the Figures hereto, is as follows:
Table 29: Disappearance of Tumors on Mice Treated with HP 8662A Frequency Generator Embodiment Treated Mouse Tumor Tumor Tumor Tumor Tumor Tumor # 1 2 3 4 5 6 OUJ-650 Yes Yes Yes OUJ-526 Yes Yes Yes OUJ-516 Yes Yes Yes Yes Yes OUJ-506 Yes Yes Yes Yes OUJ-496 Yes Yes OUJ-471 Yes Yes OUJ-470 Yes Yes OUJ-456 Yes It is apparent from the foregoing that a new treatment has been developed which has shown great effectiveness in treating cancer and other illnesses in laboratory mice and is believed to be a promising treatment for humans. While only presently preferred embodiments have been described in detail, it will be apparent to those skilled in the art that certain changes and modifications can be made without departing from the scope of the invention, as defined in the followin f; claims.
TREATED MOUSE DATA
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r..oeoooooooowwwwwm'8m°m$.°°~~aoge°°' APPEND/CES B~ - B~ 0 CONTROL MOUSE DATA
Index (I':~ges numbered on back) Apperrdir Sabjecl Prrges f32 A 488 98-I()(1 f33 A 490 101-10?
l34 A 492 l03-10~
135 A 500 ! 06 ~ Surbeck, et al , Therapeutic Apparatus and Method a~
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The treatment device is used by applying it, treatment loop down, to the subject's body in the area desired to be treated. The unit is left in place for approximately one hour at a time.
As indicated above, battery SCPOs have been built with crystals tuned to 43.351830 ~ 20 Hz., 43.351850 ~ 20 Hz., 43.351855 ~ 20 Hz and 43.351870 ~ 20 Hz. These frequencies were chosen because they are each believed to be useful for treating a plurality of illnesses, and because a multipurpose de-vice is advantageous by reason of the inconvenience of changing crystals.
However, there is no reason why this embodiment, would not be effective at any of the frequencies identified above as being thera-peutically useful, as well as, with an appropriately tuned output element, if necessary, at any frequency found in the future to be therapeutically useful.
A parts list for the Battery SCPO is set forth in Table 3.
Table 3: Parts List for Battery SCPO
Ref. Descri lion Source No.
71(1 SCPO Housin Fabricated -See text 114 Battery Holder Caltronics BH-124 715 "AA" Battery 4ea Wall reens 1.5V AA Ultra Alkaline ur a utv.
117 Dl Indicator Li ht - 2 Radio Shack 276-044 or mA LED Diode a uiv.
120 Treatment Loo Fabricated - See text 127 Backin ~ for treatment Hi h Im act S rent 0.080"
loo thick 2K0 Quartz Crystal ICM, CT'S, or NEL - See text 31 U2 - TLC 555 Timer Radio Shack 276-1723 or 1 a uiv.
373 R4 33K +/- 5%. 7 /4 Watt Radio Shack 271-1341 or Carbon Resistor ec uiv.
315 R6 20K 15 Turn 3/4 Watt Radio Shack 271-34(1 or Ad'. Resistor a uiv.
317 891.(1 K +/- 5/ 1/4 Watt Radio Shack 271-1321 or Carbon Resistor a uiv.
319 U2 IN914 Switchin Diode Radio Shack 276-1122 or 75 PIV a uiv.
321 R5 47K +/- 5%. 1/4 Watt Raclio Shack 271-1342 or Carbon Resistor c uiv.
323 R7 20K 75 T'um 3/4 Watt Radio Shack 277-340 or Ad . Resistor a uiv.
325 R8 2.2K +/- 5iL 1 /4 Wait Radio Shack 271-1325 or Carbon Resistor a utv.
327 C3 0.2?uf Electrolytic Radio Shack 272-1070 or Ca acitor, 50Volis a uiv.
341 U3 - TLC 555 Timer Radio Shack 276-7723 or ec uiv.
393 R10 33K +/- 5r~ 7 /4 Watt Radin Shack 271-1341 or Carbon Resistor ec uiv.
395 R12 20K 15'I'um 3/4 Watt Radio Shack 271-340 or Ad . Resistor cc un~.
347 R14 7 K +/- 5"r., 1 /4 Radio Shack 271-1321 c>r Watt Carbon Resistor ec my 34~> D3 1N914 Switchin Uiode Radio Shack 276-1722 or 75 P1V a mv.
:151 Rll 47K +/- 5% 7 /4 Watt Radio Shack 271-1342 or Carbon Resistor er uiv.
353 R73 20K 75'furn 3/4 Watt Radio Shack 271-34(1 or Ad . Resistor a ucv.
35~ R75 2.2K +/- 5%. 1/4 Watt Radio Shack 271-1325 or Carbon Resistor a uiv.
357 C4 lOuf Electrol tic Ca Radio Shack 272-1436 or acitor, 76Volts a uiv.
367 R2 33(1 Ohm +/- 5%. 1/4 Radio Shack 271-1315 or Watt Carbon Resistor a uiv.
363 QI MPS2907 PNP Transistor Radio Shack 276-2023 or a uiv.
365 Q2 MPS2907 PNP Transistor Radio Shack 276-2023 or a uiv.
367 R3 330 Ohm +/- 5 % 1 /4 Radio Shack 271-7315 or Watt Carbon Resistor a uiv.
369 Rl 2.2K +/- 5 % 7 /4 Watt Radio Shack 271-1325 or Carbon Resistor ec uiv.
371 L2 8.2 uH Inductor Miller 8230-18 372 C2 5.5 - 18 F Trimmer Ca S ra ue-Goodman GYA22000 acitor or ec uiv.
B. Generator Embodiment The alternate embodiment of the treatment device is shown in FIG. 5. It employs a model 8662A
frequency generator 500 manufactured by the Hewlett-Packard Company. Frequency generator 500 has a modulation input 520, to which is connected modulator unit 540, which provides an approximate 60 Hz square wave with an approximate 50% duty cycle, which is in turn gated with an approximately 1.T67 (70 pulse per minute) square wave, also with an approximately 50% duty cycle.
The circuitry of modulator unit 540, which is more fully described below, is similar to that of the Battery SCPO, up to the point of AND gate.
As shown in FIG. 6, power is provided by a plug-in DC power module 550, Radio Shack Cat.
No. 273-1455C or equivalent, which is rated at J volts D.C. at 0.3 amperes.
The positive lead from the module is switched through power switch SW1 542, and then directed to a 7805 5 volt voltage regulator Ul 605. The negative lead of the supply is attached to the unit's ground rail 603. Both the input and output of voltage regulator U1 605 is bypassed to ground by a 0.01 uF, 500 volt disc ceramic capacitor, Cl 606 and C2 607. The output, a regulated 5 volts, is applied to positive supply rail 602.
The circuitry associated with the TLC 555 timers 611 and 641 1S S110WI1 Ill FIG. 6, and is identical with the corresponding circuitry described above in the context of the Battery SCPO. The reference nu-merals "6I1" through "657" in FIG. 6 correspond to the identical elements "311" through "357" in FIG.
The AND gate of the modulator for the Generator Embodiment is configured identically here as in the Battery SCPO. R2, R3, Ql and Q2 (661, 663, 665, and 667) have the same values as in the SCPO
circuit (361, 363, 365 and 367).
The LED indicator circuit Rl 669 and Dl 541 differs from its counterpart in the Battery SCPO in that R1 669 is 330 Ohms rather than 2.15K. The resistor difference is for the:
purpose of obtaining the proper LED brightness in each circuit.
Adjustable resistor R77 677 provides a voltage divider between positive rail 602 and ground 603. The wiper of R17 677 provides a positively offset "ground" for purposes of output to the HP
8662A. The reason for this is that the I-IP 8662A expects an DC signal for purpos<a of modulation, so this adjustment is provided to offset the output around "zero volts" as referenced to the chassis of the I-IP 8662A.
The output of AND gate at the emitter of Q2 665 is connected to 8.2 uH
inductor L2 671 (Miller 8230-18). The resultant signal is bypassed to ground by a relatively large electrolytic capacitor, 2.5 uF, rated at 35 volts C5 673, and then passed to the center lead of output BNC
connector 521.
The approximate modulation waveform produced by modulator unit 540 iS shown in FIG. 7A.
The rounding of the rise and fall of the waveform is the result of capacitor C5 673. The modulated WO 98/29156 PCTlUS97123845 waveform of one of the 60 Hz. cycles output by the HP 8662A is shown in FIG.
7B (the RF component in this figure is not drawn to scale). The output power of the frequency generator is less than 1 mw.
The output of frequency generator 500 is directed through a second BNC
connector 531 con-nected to the panel of that instrument, and through a 50 Ohm, double-shielded coaxial cable 567 (RG
174 cable, Mouser #515-156-12 or equivalent). The coaxial cable is directed to a treatment loop 565 mounted on 2.0 mm. (0.080 inch) thick styrene sheet 566 which is laminated on stainless steel plate 560.
The plate has dimensions of approximately 10.2 cm. by 6.35 cm. The treatment loop 565 is a 20 AWG
solid copper wire approximately 60 cm. long, wound in a flat rectangular spiral comprising five turns, with a turn-to-turn spacing of approximately 3,275 mm. and overall dimensions of 2.858 x 5.258 cm.
The center of the loop is soldered to the center lead of coaxial cable 567.
Shield 863 of coaxial cable 567 is soldered to the back of plate 560 at solder point 861. The outer end of treatment loop 565 is grounded by being soldered at solder point 570 to the loop side of plate 560. (Use A
and B figures to show both sides of the plate.
The signal from the frequency generator based embodiment of the treatment device is sh~onger electromagneHcally than that output by battery operated device 100. It is also characterized by having only a single pure RF component at the desired frequency in the 43 Ml-1T
range. The treatment loop of generator embodiment is applied to the subject in the same manner as in the case of the battery pow-ered embodiment.
A parts list for the Generator Embodiment is set forth in Table 4.
Table 4: Parts List for Generator Embodiment Ref. Descri lion Source No.
5(10 Hewlett-Packard 8662A FrecHewlett-Packard Com an ucnc Generator 541 Dl Indicator Li ht - 2mA Radio Shack 276-044 or LED Diode ec uiv.
542 SWl Power Switch Radio Shack 275-67 2 or a uiv.
550 9V DC I'lu ~-In Power Su Radio Shack 273-14550 1 Module or ec uw.
560 Treatment Loo holder Fabricated - See text 565 'l reatment Loo Habricated -See text 567 Coaxial Cable, 50 ohm, RG774 cable Mouser #515-7156-12 Shielded 605 U 1 7805 5 Volt Volta ~e Radio Shack 276-177() Re ulator IC or a uiv.
60c, 0.01 ul' Disc Ceramic Ca Radio Shack 272-131 or acitor, 5()0 Volt cc uiv.
60;' 0.( ur Disc Ceramic Ca Radio Shack 272-13i or acitor, 500 Volt a urv.
611 U2 - TLC 555 Timer Radio Shack 276-7723 or c uiv.
61:1 R4 33K +/- 5.~ I /4 Watt Radio Shack 271-1341 or Carbon Resistor ec uiv.
615 R6 2(1K 15 Turn 3/4 Watt Radio Sltack 277-340 or Ad'. Resistor a uiv.
617 R9 7 .0 K +/- 5 % 1 /4 Radio Shack 271-1321 or Watt Carbon Resistor ec uiv.
61 D21 N914 Switchin Diode Radio Shack 276-1122 or ~t 75 PIV ec uiv.
621 R5 47K +/- 5% 1 /4 Watt Radio Shack 271-1342 or Carbon Resistor ec uiv.
623 R7 20K 15 Tum 3/4 Watt Radio Shack 271-340 or Ad'. Resistor a uiv.
625 R8 2.2K +/- 5% 1/4 Watt Radio Shack 271-1325 or Carbon Resistor ec uiv.
627 C3 0.22uf Electrol tic Radio Shack 272-1070 or Ca acitor, 50 Volts ec uiv.
641 U3 - TLC 555 Timer Radio Shack 276-1723 or a uiv.
643 R 10 33K +/- 5 % 1 /4 WattRadio Shack 271-1341 or Carbon Resistor a uiv.
645 IZ 12 20K 15 Tum 3/4 Watt Radio Shack 277-340 or Ad'. Resistor a uiv.
647 R 141K +/- 5/ 1 /4 Watt Radio Shack 271-1321 or Carbon Resistor a uiv.
649 D31N914 Switchin Diode Radio Shack 276-1122 or 75 PIV a uiv.
651 RI1 47K +/- 5~ 1/4 Watt Radio Shack 271-1342 or Carbon Resistor a uiv.
653 R73 20K 15 Turn 3/4 Watt Radio Shack 271-340 or Adj. Resistor equiv.
Ref. Descri lion Source No.
655 R15 2.2K +/- 5 % 1/4 Watt Radio Shack 271-232 Carbon Resistor 5 or e2uiv.
657 C4 lOuf Electrol tic Ca _ acitor, l6Volts Radio Shack 272-1436 or a uiv.
661 Pv2 330 Ohm + - 53'0 1 Radio Shack 271-1315 or /4 Watt Carbon Resistor a uiv.
663 Qi MPS2907 PNP Transistor Radio Shack 276-2023 or a uiv.
665 02 MPS2907 PNP Transistor Radio Shack 276-2023 or a uiv.
667 R3 330 Ohm +/- 5% 7 /4 Radio Shack 271-1315 or Watt Carbon Resistor a uiv.
669 Rl 330 Ohm +/- 5 ~0 1 /4 Radio Shack 271-1315 or Watt Carbon Resistor a uiv.
671 L2 8.2 uH Inductor Miller 8230-18 673 C5 1.47 uF Electrol tic Radio Shack 272-1433 &
Ca acitor, 35 Volts 1434 677 R 17 5K Aci'. 15 Turn 3/4 Radio Shack 271-340 or Watt Ad'. Resistor a uiv.
C. Alteniative "Mouse SCPO" for Mouse Studies For purposes of the mouse studies described below, an alternative embodiment of the treat-ment device was developed, hereinafter referred to as the "Test Embodiment".
The Mouse SCPO con-s sisted of an apparatus similar to the battery SCPO described above, but without a battery compartment, and powered by an external AC power adapter. The power adapter used was the same Radio Shack adapter 550 used with the modulator for the Generator Embodiment. The power supply circuit in the Mouse SCPO was identical to that used in the modulator for the Generator Embodiment, comprising the 7805 regulator U1 605, and the two 0.01 uF bypass capacitors C7 606 and C2 607. In all other re-spects, the Mouse SCPO was as shown in FIGs.1, 2 and 3, using the components listed in Table 4.
The feature lacked by the Mouse SCPO is the lack of restraint resulting from not being tethered by a wire. However, in the case of treating mice, this feature is irrelevant, since the mice must be immo-bilized for treatment in any event. On the other hand, the Test Embodiment had the advantage that it had no batteries to run low and to be checked and replaced.
7 S D. Extcr~eally Pulsed Generator Embodiment A further alternative embodiment of the treatment apparatus was developed, herein referred to as the "Externally Pulsed Generator." The Externally Pulsed Modulator embodiment is identical to the apparatus shown in FIG. 5, except that (1) the modulator does not attach to the Modulator Input of the 111' 8662A, but rather attaches directly via a BNC cotulector to the Rl~ ouput of the I11' 8662!1, (2) the ?0 modulator externally modulates the RF signal and does not utilize the internal modulation circuitly~
provided by the HI' 8662A; and (3) the cable used to connect the modulator to the 'l'reatment Loop is a specific type of coaxial cable, i.e., a I-Iewlett-1'ackard 10501 A, 50 Ohtn coaxial cable approximately 1.1 meters long.
The modulator in the Externally Pulsed Generator embodiment contains a series solid state RF
25 switch and associated connectors, which is pulsed by a pulsing circuit identical to that shown in FIG. 6, except that potentiometer R17 677 and capacitor C5 671 have been removed and the ground is taken from the main power supply ground rail 1303 (corresponding to rail 603 in F1G.
6). (Since there is no need to interface with the modulator input of the 8662A, there is no need for the floating ground used in the output circuit of FIG. 6.) The schematic diagram in FIG. 36 shows the entire circuit of this external modulator. In Fig.
36A, which shows the exterior of the device, shielded box 3601 is attached to the end of modulator housing 3600. Male BNC connector 3610 attaches directly to the RF output of the 8662A. Female BNC
connector 3620 attaches to the 10501 coax which in turn leads to the Treatment Loop. (Since this unit is a self-contained external modulator, it is necessary to turn off the modulation internal to the HP 8662A
using the switch for that purpose on the control panel of the HP 8662A.}
In the RF switching circuit, the output of inductor L2 3671 is a 60 I-iz/1.667 Hz. waveform 3640 (also as shown in FIG. 7A}. This waveform shifts the bias on D4 3651 and D5 3652 so as to switch the RF
applied to input 3653 in accordance with the pulses from L2 3671. In addition, inductor L2 3671 serves in this circuit as an RP choke keeping excessive RF from going back into the pulsing circuitry.
Table 4A: Additional fart for Externally Pulsed Generator Embodiment Ref. Descri lion Source No.
500 C511.01 yf ca acitor Radio Shack 272-131 or a uiv.
547 C6 0.111 yt ca ~acitor Radio Shack 272-131 or c mv.
542 R17 3:10 Ohm + /- ~';" Radio Shack 275-1375 or ':, lNatt Carbon Resistor a uiv.
542 R18 33o Ohm +/- 5'iL via Radio Shack 275-1:115 Watt Carbon Resistor or a uiv.
550 U41N~)14 Switchm; Lhode Radio Shack 273-1122 ore 75 T'IV uiv.
5f~(1 Metal T3ox Anv suitable su lier 565 Male BNC connector Anv suitable su lier 567 Female BNC conmctor Anv suitable supplier 3. EXPERIMENTAL PROCEDURE AND RESULTS
A controlled set of experiments were conducted during 1995 and 1996, to June 25, 1996, to test the utility of the present invention with respect to the suppression and elimination of cancerous tumors, cysts, lesions, and neoplasia. The crperiments were performed upon mice, by the topical application of electromagnetic (LMR) radiation at specific frequencies and intensities on a regular schedule, using the apparatus of the present invention as adapted for applying EMR to mice. tNe also present some addi-tional measurements taken in 1997 with respect to one mouse that was treated using the Externally Pulsed Generator ~rllt7(7(~111lCIlt.
"Suppression anti elitnination" IneallS that tumors, etc. that do develop are smaller in size, oc-cur relatively infrequently and are likely to disappear over time, as opposed to unheated tumors that are larger al size, occur more frequently and are unlikely to disappear before the death of the subject.
Use of TAX Mice as Experimental Subjects The Jackson Laboratory at liar Harbor, Maine, 04609 supplies mice for scientific research. These special mice are "JAX Mice," of a special inbred breed identified as C3H HeOu . These mice are highly abnormal, in that they are inherently very susceptible to adenocarcinoma of the mammary gland, due to the contributing factors of inherited genes, excessive hormonal stimulation, and the mouse mammary SU9STIME SHEET °~RULE 2S1 WO 98/29!56 PCT/US97I23845 tumor virus, which is passed to the young through the mother's milk. The adenocarcinomas develop spontaneously in these mice, and the breed is characterized by a high incidence of mammary tumors by eight months of age. Our project has used "JAX Mice" type C3H HeOu throughout all of its research for treatment of mouse tumors, including all of the treated and control mice referred to herein.
The JAX C3H HeOu mice were selected in order to provide a sensitive animal model for test ing anticancer treatments. The effectiveness of various treatments for such tumors is measured by de termining improvements in lifespan or other physical characteristics, such as gross appearance, health status, and other related data, of groups that have received the treatment, as against untreated controls.
This maruzer of testing using JAX mice is accepted as a valid animal model for determining the pro spective utility of cancer treatments in humans.
In a memorandum dated March 18,1997, The Jackson Laboratory notified users of C3I-I/HeOuJ
that it had observed an alteration over time of the development and incidence of tumors in this strain.
Our experunents were primarily conducted in a much earlier time frame than that concerned in this memorandum, and we do not believe any of our experimental results were affected thereby.
I5 Summary of Experimental Procedures and Results "Control" and "treated" selections of JAX mice (70 mice per group) were observed over the du-ration of their lives. Control mice were not exposed to the treatment procedure at all. The treated mice were exposed to EMR at the skin layer.
The treatment given was exposure to electromagnetic radiation applied to the skW of the mouse, with the radiation held at a given frequency throughout dte tr~catment.
The duration of treat-ment was usually one-half to one hour, and during the treatment, the treatinT;
electrode Has shielded from undue light and moving air currents.
The data from our experiments, discussed in detail below, show that:
I. 'Treated mice live much longer than controls.
2. The life spans of treated mice compare favorably H-ith life spans of normal (i.e., non-JAX) mice.
3. 'Treated mice have good health throughout their life.
4. Prior treatment has prevented abdominal tumor development.
5. When an abdominal tumor has been treated directly on the electrode it is caused to dis-appear.
6. By contrast:
a) Tumors on control mice grow rapidly until death of the mouse, b) And as tumors grow, a control mouse gains weight, its hematocrit decreases and its health fails rapidly until death.
Treatment of the particular mice herein discussed was by exposure of the JAX
mice to radiation from an electrode which was energized by a low power source that was preset to provide frequencies of 43.351830 MHz, 43.351850 MHz and 43.351870 MHz. In some cases, an HP-8662A
Signal Generator preset to these frequencies was used, equipped with a modulator (in all but the 1997 data, an internally coupled modulator), to provide approximately 1.667 and 60 Hz., approximately 50°/ duty cycle square wave pulse trains as previously described. In other cases, the same pulsed treatment frequencies were obtained with the "Mouse SCPO" embodiment described above, which contained its own modulator circuit, driving an internal quartz crystal.
The frequencies selected, as listed in the preceding paragraph, were based on prior experiments conducted over a period of many years, during which a large number of mice were treated under varying conditions and with various treatments. The three frequencies specified in the preceding para-graph are believed by the inventors to be among the most effective frequencies for treating a range of maladies. When using the Mouse SCPO embodiment, the treatment frequency used 69% of the time (659 hours out of a total of 950) was 43351870 Hz. When using the I-1P 8662A
signal generator for treat-ment, many (35) different frequencies were used.
Treatment Procedures One of the treated mice (OUJ-479) received treatments before a tumor appeared and lived and died tumor free.
7'reaiment of the remaining mice started as soon as a tumor reached 0.07" in length, width, and height, corresponding to an ellipsoid having a volume of 0.0295 cubic cm.
(0.00018 cubic inches). The treatments for all these ten mice were every day except Sunday. Thc: treatment frequencies are limited to a few specific frequencies within a narrow range, and the intensities are normally set to 0 dBm into a 5() ohm load.
I7ue to variations among individual mice (as in other species, including humans), a treatment configuration that is effective for one subject doesn't always work for another. Frequencies of 43.351850 Mi-iz and 43.351870 MHz were used for standard treatment on almost all of the mice. These frequencies have demonstrated good result's. Treating mice with 43.351850 MHz from a signal generator and/or pulsed crystal, appears to clear up their secondary infections, and treating with 43.351870 MHz seems to restore their general health. All of the treated mice appeared to be very lively and have a very healthy skin and hair appearance. Of the mice listed below, all hematocrit values have stayed in the healthy range of 38% to 46%, and their weight basically stayed the same since they began treatment.
Hematocrits for both the treated and the control mice were measured in accordance with the following procedure. The hematocrit was taken once a week. The mouse was placed under a heat lamp for a few minutes to cause the veins in the tail to dilate, thus making it easier to extract the blood for the sample. The amount of blood taken was about one-half of the standard 75 mm long capillary tube. The capillary tubes containing the blood are spun in a Micro-Hematocrit Centrifuge, at its "number three' marking. The capillary tubes are removed and placed in the Micro-hematocrit Tube Reader, which gives the percent of red blood cells found in the sample.
We have observed that tumors that have reached 0.07" in length, 0.07" in width, 0.07" in height are definitely a malignant growth, and benign or cystic lesions can be ruled out. Neoplasia measured under the agreed size are questionable. Almost all of the neoplasia encountered measured 0.07", 0.07", 0.07" and above.
The treatments employed a variety of treatment electrodes and housings, as shown in FIG. 9.
The preferred housing was the "E" housing shown in FIG. 9A, and the preferred electrodes were the "I"
electrode associated with the Mouse SCPO, FIG. 9J, and the "F" electrode used with the Hewlett-Packard signal generator, Fig. 9B.
Tumors treated directly on the treatment electrode slowly regressed until they were gone. Tu-mors that Here not on, or only partially on, the electrode showed a decrease in growth rate, but the tu-mor would steadily grow and not regress back The electrode was re-designed so that any tumor could be treated. The tumor must be directly on the electrode to receive the maximum treatment needed for complete regression of growth. Mice with lesions on their abdomen had direct contact with the elec-trode, and all completely regressed back to zero. We've had similar success with some mice with lesions on the neck, left leg, right neck, right side, etc.
SW ce mammary tumors occur spontaneously in these mice, some mice were also treated before any tumors appeared in the hope of preventing the inevitable fate of the cancerous C3H strain, which have an almost 100°ro occurrence rate. At present one of the mice lived out its life span tumor free and died of old age.
Treated Mice The following describes our experimental results with respect to each individual treated mouse.
For each mouse, there is a corresponding drawing showing where on the mouse tumors appeared, and in which the tumors are identified by a "tumor number" T-X, as well as a drawing reference numeral; a graph showing tumor volume in cubic inches vs. time in days; a graph showing mouse weight in grams and hematocrit readings vs. time in days; and an Appendix setting forth all experimental measure-menu taken with respect to the mouse.
F.ach tumor growth graph (FIGS. 10B, T1B, etc.) shows the size of each tumor, in cubic inches, on the mouse in question as a logarithmic function of days after the appearance of the subject's first tu-mor. Tumor volume, in cubic inches, was calculated based on the assumption that the tumor was ap-proximately an ellipsoid, and had a volume equal to 1/2 length x 1/2 width x height x 2.094.
Each weight and hematocrit graph (FIGS. 10C, 11C, etc.) shows, in two separate plots, (a) the weight of the mouse, in grams, and (b) the subject's hematocrit values (percentage of red blood cells) as a linear function of days after the appearance of the subject's first tumor.
The detailed data collected with respect to each treated mouse is shown in tabular form in Ap-pendices A-1, A-2, etc. attached hereto, and the data collected with respect to each control mouse is shown in tabular form in Appendices, B-1, B-2, etc. attached hereto. The data with respect to one mouse tested in 199 is shown in tabular form in Appendix C.
Example 1 - Treated Mouse OUJ-456 Table 5: Treatment Summary for OUJ-456 Date of Birth: 09/08/94 Date Died: 08/04/95 Lived: 310 days Treated: 91 days Tumor measurements 05/05/95 started:
Tumor measurements 9I days taken for:
This mouse lived 219 days before any tumor appeared. Notice (in PIG. 1013) that T-2 1002, which was hard to reach with our electrodes, gre~n~, but at a slower rate than a typical control mouse. As will be seen from this and the other examples hereW , treated mice live three times I<»iger than controls after a tumor appears.
WO 98/29156 PCTlUS97/23845 Example 2 - Treated Mouse OUJ-470 Table 6: Treatment Summary for OUJ-470 Date of Birth: 03/03/94 ate Died: 07/30/95 Lived: 515 days Treated: 257 days Tumor measurements 11/16/94 started:
Tumor measurements 257 days taken for:
This mouse lived 258 days before any tumor appeared. Notice (in FIG. 11 B) that 'I'-1 1101 ap-peared and went away at two different times. T-2 1102 appeared for a short period. T-3 1103 appeared when this mouse was 496 days old. This is one of the longest-lived mice in our experiments.
Example 3 - Treated Mouse OUJ-471 Table 7: Treatment Summary for OUJ-471 Date of Birth: 03/03/94 Date Died: 07/20/95 Lived: 504 days Treated: 799 days Tumor measurements 01/02/94 started:
'tumor measurements799 days taken for:
'This mouse lived 305 days before any tumor appeared. Notice that 'I'-1 1201 and T-2 1202 ap-peared for a short period. Notice (in FIG. 12C) the steady weight at 30 grams and constant high hema-tocrit percentage readings. This was also one of our longest-lived mice.
Example 4 - Treated Mouse OUJ-473 Table 8: Treatment Summary for OUJ-473 Date of Birth: 03/03/94 Date Died: 07/28/95 Lived: 514 days Treated: 211 days Tumor measurements 12/29/94 started:
Tumor measurements 211 days taken for:
As an experiment, we treated this mouse before any tumors appeared. This mouse never de-veloped any tumors (FIG. 13B). She lived 303 days before we started treatments. Notice (in FIG. 13C) die steady weight at 28 grams. This was also one of our longest-lived mice.
Example 5 - Treated Mouse OUJ-475 Table 9: Treatment Summary for OUJ-475 Date of Birth: 03/03/94 Date Died: 07/28/95 Lived: 514 days Treated: 256 days 'Tumor measurements11/14/94 started:
Tumor measurements 256 days taken for:
This mouse lived 258 days before any tumor appeared. Notice (FIG. 14B) that T-1 1401 and T-2 1402 appeared for a short period. Notice (FIG. 13C) the steady weight at 30 grams and quite-constant high hematocrit percentage readings. This was also one of our longest-lived mice.
Example 6 - Treated Mouse OUJ-496 Table 10: Treatment Summary for OUJ-496 Date of Birth: 12/21/94 Date Died: 01/05/96 Lived: 380 days Treated: 213 days Tumor measurements 09/15/95 started:
Tumor measurements 113 days taken for:
This mouse lived 267 days before any tumor appeared. Notice (FIG. 15B) that T-1 1501and 'f-5 2505 appeared and left. Notice (FIG. 15C) dte steady weight at 30 grams and high hematocrit percent-s age readings. Even with all these tumors, this mouse stayed healthy until the end and lived a long time.
Example 7 - Treated Mouse OUj-506 Table 11: Treatment Summary for OUJ-506 Date of Birth: 01/05/95 Still living: 06/25/96 Lived: 537 days Treated (and/or 250 days took data):
Tumor measurements 70/19/95 started:
Tumor measurements 250 days taken for:
This mouse lived 287 days before any tumor appeared. Notice (F1G. 16B) that T-1 1601 , T-2 1602, and T-3 1603 appeared for a short period. After 170 days, T-21602 reappeared. Notice (FIG. 16C) 70 d1e constant high hematocrit percentage readW gs. 'This was our longest-lived mouse, and it had a long healthy life.
Example 8 - Treated Mouse OUj-516 Table 12: Treatment Summary for OUJ-516 Date of Birth: 02/02/95 Date Died: 03/ 26/ 96 Lived: 418 days Treated: 240 days Tumor measurements 07/31/95 started:
Tumor measurements 240 days taken for:
This mouse had a record number of tumors, many of which Here not on the abdomen (PIG.
17A). After treatment all tumors disappeared except T5 1705, T71707, T8 1708, and T9 1709 (PIG. 17B).
In spite of the large number of tumors, she lived 418 days.
Example 9 - Treated Mouse OUJ-526 Table 13: Treatment Summary for OUJ-526 Date of Birth: 02/02/95 Date Died: 04/12/96 Lived: 435 days Treated: 168 days Tumor measurements 20/28/95 started:
Tumor measurements 168 days taken for:
This mouse had three tumors which disappeared and never returned (1'IG. 18B).
She lived 267 days before any tumor appeared. T41804 and T5 1805 grew together as one tumor.
Hematocrit percent 7 0 (FIG. 18C) stayed quite high throughout her life.
Example 10 - Treated Mouse OUJ-650 Table 14: Treatment Summary for OUJ-650 Date of Birth: 04/04/95 Still living: 06/ 25/ 96 Lived: 448 days Treated: 195 days Tumor measurements 12/13/95 started:
Tumor measurements 195 days taken for:
This mouse had three tumors, all of which disappeared and never re-appeared (FIG. 19B). Her hematocrit percent and remained high and her weight stayed constant throughout the measurement period (FIG.19C).
Control Mice The controls listed below all had spontaneous occurrences of multiple tumors that arose in various areas of the mammary gland region, and also had a very short survival time once the tumors appeared, usually around a two-month period.
None of the control mice in this study received EMR treatments or any other type of interven-tion methods. Daily weight and tumor measurements and observations were noted, as well as hema-tocrits to indicate the mouse's present health status at the time. These non-treated mice appeared to be in excellent health and appearance when the tumor remained small and didn't metastasize, but as the malignancy progressed and spread to other tissues, the effects on the mouse were readily seen.
The tumor measurements showed a rapid increase in tumor size that continuously rose almost every day, accompanied with a steady gain in weight, especially, H~ith the arrival of neH~ neoplasms.
The hemah~ocrit steadily lowers with the increase in tumor measurements. Other side-effects were also observed in the controls, such as, the coat began to show a rougher appe>aran ce, the back bone pro-truded out, they appeared to be malnourished, and the normal curiosity and physical activity seen in healthy mice were absent. The neoplasms' appearance also changed once the tumor reached a certain size, usually around 1.5 cm. in diameter and up. They usually would start to appear red and puffy, which would deepen in color showing areas of purple and black sores, which eventually ulcerated with severe bleeding. Some of the mice also appeared to get secondary W fections once the tumor ulcerated, accompanied by the draining of clear fluid and WBC present in the wound. When the tumor reached a diameter of 1.8 cm., and the hematocrit value was 25 % or lower, the mouse usually died within a cou-ple of days.
As will be illustrated by the experimental data that follows, the characteristics of all control mice observed in the lab included the following: a rapid growth rate of tumors shown in the increasing size measurements and weight gain; metastasis; and continual decrease W
hematocrit with the increas-ing tumor measurements. All the above symptoms affect the mouse's gross appearance, tumor appear-ance and shortened survival span once the tumors appear. This is reflected in the data that follows in the controls' rate of growth, and their decrease in hematocrit and length of survival period.
Example 11 - Control Mouse A-486 Table 15: Summary for A~86 Date of Birth: 04/04/95 Date died: 06/25/96 Lived: 448 days 'Treated: Not treated Tumor measurements 08/09/95 started:
Tumor measurements 97 days taken for:
This mouse had one tumor which grew very rapidly to a large size (FIG. 20B).
She had another tumor which appeared for 8 days. Her weight started to increase near the end, and the low hematocrit readings indicated a poor general health (FIG. 20C).
Example 12 - Control Mouse A-488 Table 16: Summary for A-488 Date of Birth: 11/28/94 Date died: 11/13/95 Lived: 350 days Treated: Not treated Tumor measurements 07/20/95 started:
Tumor measurements 116 days taken for:
This mouse had one tumor (T'1 2101) which didn't change much for forty days then grew rap-idly (FIG. 21B). T-2 2102 came in and left after 32 days. T-3 2103 stayed constant in size for about 90 days, then grew rapidly.
Example 13 - Control Mouse A-490 Table 17: Summary for A-490 Date of Birth: 12/19/94 Date died: 11/29/95 Lived: 345 days 'Treated: Not treated Tumor measurements 10/11/95 started:
'Tumor measurements50 days taken for:
This mouse had four rapidly growing tumors and lived only fifty days after the first tumor ap-peared (FIG. 22B). After 20 days her weight increased and hematocrit reading steadily dropped (FIG.
22C).
Example 14 - ControI Mouse A-492 Table 18: Summary for A-492 Date of Birth: 12/19/94 Date died: 12/29/95 Lived: 375 days Treated: Not treated Tumor measurements 09/15/95 started:
Tumor measurements 105 days taken for:
At 375 days, this is the longest lived control mouse. (Nine of our ten treated mice lived longer.) She had two tumors that left (FIG. 23B). But, after thirty days, T3 2303 and T4 2304 appeared and started to grow very rapidly. Her hematocrits dropped rapidly after 70 days of measurements (FIG.
23C).
Example IS - Control Mouse A-500 Table 19: Summary for A-500 Date of Birth: 01/04/95 Date died: 10/ 11 /95 Lived: 280 days Treated: Not treated Tumor measurements 09/15/95 started:
Tumor measurements 26 days taken for:
This mouse did not live very long and was observed only twenty-six days then she died. Tu-moss grew rapidly (FIG. 24B) and hematocrits were quite low (FIG. 24C).
Example 16 - Control Mouse A-538 Table 2Q: Summary for A-538 Date of Birth: 03/24/95 Date died: Ol / 15/96 Lived: 297 days Treated: Not treated Tumor measurements 10/19/95 started:
Tumor measurements 88 days taken for:
This mouse had three large tumors (FIG. 25B) and rapid weight increase and very low hema-tocrit percent readings (FIG. 25C). This mouse also did not live very long and was quite unhealthy.
Example 17 - Control Mouse A-540 Table 21: Summary for A-540 Date of Birth: 03/25/95 Date died: 01/02/96 Lived: 283 days Treated: Not treated Tumor measurements 7 7 / 15/95 started:
Tumor measurements 48 days taken for:
This mouse had one tumor that grew to a large size and grew fast (PIG. 26B).
Low hematocrits caused this mouse to die in a short period (PIG. 26C).
WO 98/29156 PCTlUS97/23845 -Example 18 - Control Mouse A-542 Table 22: Summary for A-542 Date of Birth: 03/25/95 Date died: 01/18/96 Lived: 299 days Treated: Not treated Tumor measurements11/27/95 started:
Tumor measurements52 days taken for:
This mouse had two tumors that grew to a large size and grew fast (I~IG. 27B).
Weight contin-ued to increase as the tumors grew (FIG. 27C). A tumor size of 0.1 to 0.5 cubic inches on a mouse tlzis small is duite a burden for the mouse. They do not survive for long; with tumors that size.
Example 19 - Control Mouse A-592 Table 23: Summary for A-592 Date of Birth: 06/27/95 Date died: 02/14/96 Lived: 232 days 'Treated: Not treated 'Tumor measurements02/19/96 started:
Tumor measurements26 days taken for:
'This mouse had one tumor that grew to a one cubic inch in size and grew fast (FIG. 28B). Rapid decline in hematocrits caused this mouse to die iii a short period (FIG. 28C).
Notice the rapid increase in weight: the mouse nearly doubled in weight in twenty days. This was a very short-lived mouse.
Example 20 - ControI Mouse A-594 Table 24: Summary for A-594 Date of Birth: 06/27/95 Date died: 02/15/96 Lived: 233 days Treated: Not treated Tumor measurements 01/12/96 started:
Tumor measurements 34 days taken for:
This mouse also had one tumor that grew to a large size and grew fast (FIG.
29B). Rapidly de-clining hematocrits caused this mouse to die in a short period (FIG. 29C).
This is one of the shortest-lived control mice of the group.
Experimental Conclusions Our principal conclusion, based on the experiments described above, is that the cancer-prone JAS mice benefited considerably from the therapeutic apparatus and method of the present invention.
The subsidiary experimental conclusions that support this assertion are as follows:
1. Total Days of Life: Treated Mice Live 50'%. Loner The bar-graphs in PIG. 30 show that the treated mice lived approximately 50%
longer on aver-age than the controls. L,ach Gar indicates: Days of Waiting 3001, Days of Treatment (or Measurement) 3002, 3003, and Total Days Of Life 3004.
Tlu~ data underlying FIG. 30 (as well as I:IGs. 31 and 32, discussed below) is presented below in tabular form.
Table 25: Days of Life, Measurement, and Number of Tumors SUBJECTNON MEASUREDQTY TOTAL
MEASUREDDAYS OF LFE
DAYS TUMORS
l OUJ-506287 250 5 481 ~
SUBJECTNON MEASUREDQTY TOTAL
MEASUREDDAYS OF LIFE
DAYS TUMORS
Totals:2594 1976 37 4,458 Totals:2405 641 27 3,046 2. Starting Treatment After First Tumor Appears: Treated Mice Live More than 300"/..
Lo- nger FIG. 31 shows that after the first tumor appeared, the treated mice lived longer than the control mice. The bars u1 these graphs represent Days of Treatment for treated mice or Days of Measurement for control mice. The data underlying FIG. 31 is set forth in Table 25 above.
3. The Treated Mice Had Morc Tumors (b~37"/o But Thcy Lived Longer FIG. 32 shows the number of tumors that developed in each mouse. It must be noted that even though there were 37io more tumors in the treated mice, they lived longer than the controls. The data underlying FIG. 32 is set forth in Table 25 above.
70 4. Tumors that Appeared were Five Times More Likely to Disappear in the Treated Mice than in the Controls.
FIG. 33 shows the total number of tumors in each mouse, and those tumors that disappeared or were cured and the remaining tumors at the death of each mouse. (Note: OUJ-506 and OUJ-650 were still living as of June 25,1996, when this data was compiled.) 25 The data underlying FIG. 33 is set forth in Table 26 below.
Table 26: Tumors That Disappeared SUBJECTMEASUREDREMAININGCUREDITOTAL NON
DAYS TUMORS GONE LIFE MEAS-TUMORS URED
DAYS
Totals:1976 13 24 4,570 2594 Totals:641 23 4 3,046 2405 5. The Weight of the Treated Mice Remained Stable Whereas the (:ontrol Mice Markedly Gamed We.~ht FIG. 34 shows that the treated mice maintain their weight on average, while the control mice gain considerable weight due to tumor growth. (Note: The weight change shown is the last 10 day weight average minus the first 10 day weight average of each mouse.) The data underlying FIG. 34 is set forth in Table 27 below.
Table 27: Comparative Weight Changes Treated Weight ControlWeight Mouse Change Mouse Change OUJ-456 5.85 A-592 20.31 OUJ-526 2.37 A-538 15.42 OUJ-470 1.31 A-490 14.32 OUJ-471 -0.15 A-542 g,g7 OUJ-473 -1.36 A-486 6.54 OUJ-475 -2.22 A-540 6.15 OUJ-506 -0.66 A-492 3.gg OUJ-650 -0.75 A-500 0.02 OUJ-516 0.07 A-488 -1.73 OUJ-496 -4.92 A-594 -4.92 Totals: 0.14 70.06 6. The Control Mice Had More Large Tumors FIG. 35 shows the maximum sizes of each tumor on the twenty different mice.
Some of these tumors disappeared. The vertical scale is tumor size in cubic inches. There were 37 treated and 27 control tumors hut this grnph shows the 27larQest treated tumors and all 27 control tumors.
The data underlying FIG. 35 is set forth in Tables 28A and B below.
Table 28A: Comparison of Maximum Tumor Size (in cubic inches) TreatedTumor Tumor Tumor Tumor Tumor Tumor Tumor Tumor Tumor Subject1 2 3 4 5 6 7 8 9 OUJ-4560.000014130.27320000 OUJ-4700.000179600.000014130.00954900 OUJ-4710.000261800.00009161 OUJ-4750.000014130.00036650 OUJ-4960.001178000.037990000.006332000.010990000.000153900.00029680 OUJ-5060.000014130.018660000.000014130.000179600.01682000 OUJ-5160.000014130.000179600.000065440.006533000.081790000.000483700.036240000.0556 00000.17990000 OUJ-5260.000014130.000829200.000065440.065790000.00533600 OUJ-6500.002419000.000065440.00006544 Total0.004108000.331400000.016090000.083490000.104100000.000780500.036240000.05 5600000.17990000 Average0.000456500.036820000.002682000.020870000.026030000.000390300.036240000.
055600000.17990000 Table 28B : Comparison of Maximum Tumor Size (in cubic inches) ControlTumor Tumor Tumor Tumor subject1 2 3 4 A-486 0.439200000.00001413 A-488 0.417900000.006193000.007622000.01493000 A-490 0.208000000.470800000.049130000.02954000 A-492 0.000523500.000065440.106900000.16280000 A-500 0.064780000.042520000.20560000 A-538 0.563500000.323100000.03216000 A-540 0.39520000 A-542 0.368200000,13700000 A-592 0.819200000.004192000.01504000 A-594 0.19090000 Total 3.467000000.983800000.416400000.20730000 Average0.346700000.123000000.069400000.06910000 Test of Externally Pulsed Generator FIG. 37 shows the results of treating mouse OUJ-738 in 1997 with the Externally Pulsed Gen erator embodiment. Treatment was with the HP 8662A frequency generator externally modulated with the modulator shown in Fig. 36, coupled to a treatment loop as shown in FIGS.
8A and 8B deployed in the "E" housing shown in FIG. 9A. The corresponding experimental data is shown in Appendix C.
FIG. 37A shows that a single tumor TI 3701 developed on this mouse W the left arm position.
This position is difficult to treat because it is out of the way and as a consequence it is difficult to posi-tion the treatment electrode close to the tumor. Nevertheless, the results with this mouse were ex-tremely good for the period of testing. As shown in FIG. 37B, the tumor stayed small for the entire pe-riod, and as shown in FIG. 37C, the weight was stable and the hematocrits remaitled high. The data ex-tends up to a few days prior to the filing of this application, and at the end of this period the mouse was alive and healthy.
In addition, data were compiled in 2997 with respect to tumors that disappeared after treat-ment with the generator embodiment. This data, which otherwise appears in the Figures hereto, is as follows:
Table 29: Disappearance of Tumors on Mice Treated with HP 8662A Frequency Generator Embodiment Treated Mouse Tumor Tumor Tumor Tumor Tumor Tumor # 1 2 3 4 5 6 OUJ-650 Yes Yes Yes OUJ-526 Yes Yes Yes OUJ-516 Yes Yes Yes Yes Yes OUJ-506 Yes Yes Yes Yes OUJ-496 Yes Yes OUJ-471 Yes Yes OUJ-470 Yes Yes OUJ-456 Yes It is apparent from the foregoing that a new treatment has been developed which has shown great effectiveness in treating cancer and other illnesses in laboratory mice and is believed to be a promising treatment for humans. While only presently preferred embodiments have been described in detail, it will be apparent to those skilled in the art that certain changes and modifications can be made without departing from the scope of the invention, as defined in the followin f; claims.
TREATED MOUSE DATA
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r..oeoooooooowwwwwm'8m°m$.°°~~aoge°°' APPEND/CES B~ - B~ 0 CONTROL MOUSE DATA
Index (I':~ges numbered on back) Apperrdir Sabjecl Prrges f32 A 488 98-I()(1 f33 A 490 101-10?
l34 A 492 l03-10~
135 A 500 ! 06 ~ Surbeck, et al , Therapeutic Apparatus and Method a~
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11 22-Jan0 0290D.160.00874.00000 3B
12 23-Jan0.39D0.3000.230.01409.DOD00 39 17 24-Jan0 0 0.240.01922.00000 39 74 25-Jan0,4800 0.260.02254.00000 39.32 26.Jan0.5000.3800.290.02960.00000 39 16 27Jan0.52004200.280.03376.00000 3860 17 2B-Jan0.53001400.290.03540.00000 30.30 16 29-Jan0 0 0.290D3824 .00000 37 19 JO-Jan0.5600.4900.290.04166.DOD00 3B
31-JanD 0 0.34005566 .OOODO 38 21 SFeb D 0.5700.34006493 00000 39 22 2FeD 0 0 0.360.07702.OOODO 39 23 3-Feb0 0 0 OB67B DOD00 39 24 4Feb D D 0 .09344.00000 35 5-Feb0 0 0 t 0422.00000 40 26 6Feb O.B600 0 .7067D00000 39 790300 5;f 27 7.Feb0.9200.9400.340.1539300000 3B
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l0.feb1.05D10500.280.16760DOD00 3500 3t t 1 1.0700280.16625D0000 33 t.FeD060 50 32 72.Feb1070 7.0800.280.16939.00000 31.95 33 13-Feb1.1107 0.31079094 .00000 30 34 14-Feb1 1 0.27017258 .00000 33 lS.Feb1.1701 0.270.18D26.00000 34 36 l6.FebDIe tI2/i6N6 pVALUEI.00000 Prepared by Bob DeVries 4!11!97 Page 1 WO 98!29!56 PCT/US97/23845 APPEND.~X C
TREATED MOUSE DATA (EXTETZNAL
MODULATOR EMBODl: MINT) Index (fates numbered on back) Appeudir Srebject Pubes C 1 OtJJ-738 1 1 G
Surbeck, el al , Therapeutic Apparatus and Method n n n n n n n n n a n n n a n n n n n n n n n a n n n a x x x x Z z Z 2 Z x x x x x x x x x x x x x x x x x x j ca .,b .R w .a w .t~ .a as as .a as .a .a w ra w oa x~ oz .a oa as .a .zy en .b a 0 3 3 3 3 3 3 3 ~ 3 ~ ~ 3 ~ 3 3 ~ ~ ~ 3 ~ 3 ~ ~ ~ 3 3 ~
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31-JanD 0 0.34005566 .OOODO 38 21 SFeb D 0.5700.34006493 00000 39 22 2FeD 0 0 0.360.07702.OOODO 39 23 3-Feb0 0 0 OB67B DOD00 39 24 4Feb D D 0 .09344.00000 35 5-Feb0 0 0 t 0422.00000 40 26 6Feb O.B600 0 .7067D00000 39 790300 5;f 27 7.Feb0.9200.9400.340.1539300000 3B
28 B~FCb1.0201.0100.290.15640.OOUOU 37 29 9-Feb1.0301.0300.290iBlOfi.00000 364D
l0.feb1.05D10500.280.16760DOD00 3500 3t t 1 1.0700280.16625D0000 33 t.FeD060 50 32 72.Feb1070 7.0800.280.16939.00000 31.95 33 13-Feb1.1107 0.31079094 .00000 30 34 14-Feb1 1 0.27017258 .00000 33 lS.Feb1.1701 0.270.18D26.00000 34 36 l6.FebDIe tI2/i6N6 pVALUEI.00000 Prepared by Bob DeVries 4!11!97 Page 1 WO 98!29!56 PCT/US97/23845 APPEND.~X C
TREATED MOUSE DATA (EXTETZNAL
MODULATOR EMBODl: MINT) Index (fates numbered on back) Appeudir Srebject Pubes C 1 OtJJ-738 1 1 G
Surbeck, el al , Therapeutic Apparatus and Method n n n n n n n n n a n n n a n n n n n n n n n a n n n a x x x x Z z Z 2 Z x x x x x x x x x x x x x x x x x x j ca .,b .R w .a w .t~ .a as as .a as .a .a w ra w oa x~ oz .a oa as .a .zy en .b a 0 3 3 3 3 3 3 3 ~ 3 ~ ~ 3 ~ 3 3 ~ ~ ~ 3 ~ 3 ~ ~ ~ 3 3 ~
VI tn N V7 N VI UI 41 N UI f~ N V7 V7 N VI fn N V! In VI N (n (n !n In !n m M
n ~ ~ .- ~ ~ .- .- ~ ~ ~ .- ~ .- ~ ~ ~ .- '- .- ~ ~ .- ~ .-- .- ~ ~ ~ .- ~ .- ._ ~ .. ~ .- ~ ~ '- .- ~ ~ '- ~ ~ ~ ~ .- .- .-m m m m m m m m m m m m m m m m m m m m m m m m m m m w a a a a a a v a v a a a a a a a a a a a v a a a a a a ~ 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 H N d O O O O O O U O O O O O O O O O v, ~ O O O O O O O O O
y'7 "~ N O D O O Z O O D O O O Z O O O o O O Z O O O O O O Z O O o O O Z
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tG ~n m D m m m m m m m m m m m m m m m m m m m m m m an m m m m n h a C m v M v ~ a Q Q v v = a f-= V1 M O N r!1 ID N m ~ '- ef O m u'1 10 .- (v M M M ~ 01 V1 M ~ m ~ n7 .- O m O Q1 m O O N u'1 M m ~ Q1 m N t!1 N 10 m lD m N lO O l0 N lD ~ M tD m ~ m Q1 y~ ~ I~ lD l0 10 tD ID V1 v VI Q 'Y Lt) V1 V7 M M N N M M M N .- ' ~ ~ ~ ,.~ p M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M M
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Claims (19)
1. Therapeutic apparatus, comprising means for generating an approximately 60 Hz., 50% duty cycle square wave signal pulsed at a second 50% duty cycle at approximately 1.167 Hz., a quartz crystal with a resonant frequency in the radio frequency range, serially driven by said signal, a wire loop, the input of which is serially driven by the output of said quartz crystal, and the other end of which is grounded with respect to said square wave generating means.
2. The apparatus of claim 1, wherein the frequency of the crystal is selected from the group of frequencies consisting of: 43,322,480 Hz., 43,322,492 Hz., 43,322,485 Hz., 43,346,000 Hz., 43,346,090 Hz., 43,346,000 Hz., 43,346,050 Hz., 43,353,800 Hz., 43,353,800 Hz., 43,353,850 Hz., 43,353,800 Hz., 43,296,000 Hz., 43,351,830 Hz., 43,351,850 Hz., 43,351,855 Hz., 43,351,870 Hz., 43,352,000 Hz., and 43,245,000 Hz., all ~ 20 Hz.
3. The apparatus of claim 1, wherein the means for generating said approximately 60 Hz., 50% duty cycle square wave signal pulsed at a second 50% duty cycle at approximately 1.167 Hz., comprises means for generating a first square wave of approximately 60 Hz., at a duy cycle of approximately 50%, means for generating a second square wave of approximately 1.167 Hz., at a duty cycle of approximately 50%, and means for ANDing said first square wave and said second square wave.
4. The apparatus of claim 3, wherein between said ANDing means and said crystal there is inserted a series LC filtering means comprising an inductor and a variable capacitor.
5. The apparatus of claim 4, wherein said wire loop is made from approximately five turns spaced approximately 3.175 mm. apart of a wire approximately 60 cm. long.
6. The apparatus of claim 5, wherein said wire loop is mounted on the housing of the apparatus.
7. The apparatus of claim 6, wherein the power supply for the apparatus comprises a battery housed within the apparatus so as to render the apparatus self-contained.
8. The apparatus of claim 6, wherein the power supply for the apparatus comprises an external, power line driven transformer.
9. Therapeutic apparatus, comprising, a stable frequency generator means having a modulation input, a range of radio frequency out-puts, the ability to provide output at a steady power of 1 mw or less, and the ability to provide radio frequency output tunable to at least one half a part per million, a modulator, connected to said modulation input, providing an approximately 60 Hz., 50%
duty cycle square wave signal pulsed at a second 50% duty cycle at approximately 1.167 Hz., and a wire loop, one end of which is connected to the output of said frequency generator means, and the other end of which is grounded with respect to said frequency generator means.
duty cycle square wave signal pulsed at a second 50% duty cycle at approximately 1.167 Hz., and a wire loop, one end of which is connected to the output of said frequency generator means, and the other end of which is grounded with respect to said frequency generator means.
10. The apparatus of claim 9, wherein said radio frequency output is selected from the group of frequencies consisting of: 43,322,480 Hz., 43,322,492 Hz., 43,322,485 Hz., 43,346,000 Hz., 43,346,090 Hz., 43,346,00D Hz., 43,346,050 Hz., 43,353,800 Hz., 43,353,800 Hz., 43,353,85D Hz., 43,353,800 Hz., 43,296,000 Hz., 43,351,830 Hz., 43,351,850 Hz., 43,351,855 Hz., 43,351,870 Hz., 43,352,000 Hz., and 43,245,000 Hz., all ~ 20 Hz.
11. The apparatus of claim 9, wherein said modulator comprises means for generating a first square wave of approximately 60 Hz. at a duty cycle of approximately 50%, means for generating a second square wave of approximately 1.167 Hz. at a duty cycle of approximately 50%, and means for ANDing said first square wave and said second square wave.
12. Therapeutic apparatus, comprising, a stable frequency generator means having a range of radio frequency outputs, the ability to provide output at a steady power of 1 mw or less, and the ability to provide radio frequency output tunable to at least one half a part per million, a modulator, connected in series to the radio frequency output of said modulation input, providing an approximately 60 Hz., 50% duty cycle square wave signal pulsed at a second 50%
duty cycle at approximately 1.167 Hz., and a wire loop, one end of which is connected to the output of said frequency generator means, and the other end of which is grounded with respect to said frequency generator means.
duty cycle at approximately 1.167 Hz., and a wire loop, one end of which is connected to the output of said frequency generator means, and the other end of which is grounded with respect to said frequency generator means.
13. The apparatus of claim 12, wherein said radio frequency output is selected from the group of frequencies consisting of: 43,322,480 Hz., 43,322,492 Hz., 43,322,485 Hz., 43,346,000 Hz., 43,346,090 Hz., 43,346,000 Hz., 43,346,050 Hz., 43,353,800 Hz., 43,353,800 Hz., 43,353,850 Hz., 43,353,800 Hz., 43,296,000 Hz., 43,351,830 Hz., 43,351,850 Hz., 43,351,855 Hz., 43,351,870 Hz., 43,352,000 Hz., and 43,245,000 Hz., all~20Hz.
14. The apparatus of claim 12, wherein said modulator comprises means for generating a first square wave of approximately 60 Hz. at a duty cycle of approximately 50%, means for generating a second square wave of approximately 1.167 Hz. at a duty cycle of approximately 50%, means for ANDing said first square wave and said second square wave, and means responsive to said ANDed first and second square wave for switching a series radio frequency signal.
15. The apparatus of claim 12 wherein, said wire loop is connected to the output of said frequency generator means by a Hewlett-Packard 10501A or equivalent shielded coaxial cable.
16. A method for treating cancer and other illnesses in a human or animal subject, comprising, generating a radio frequency signal tuned to a treatment frequency that has been specified to a precision of at least one half of a part per million;
modulating said radio frequency with an approximately 60 Hz. square wave with an approximately 50% duty cycle which has been gated by an approximately 1.167 Hz. square wave with an approximately 50% duty cycle applying said modulated radio frequency signal at a power of 1 mw or less to one end of a wire loop and grounding the other end of said loop, placing said wire loop to which said modulated radio frequency signal has been applied on the surface of the subject's body for a period of at least one hour.
modulating said radio frequency with an approximately 60 Hz. square wave with an approximately 50% duty cycle which has been gated by an approximately 1.167 Hz. square wave with an approximately 50% duty cycle applying said modulated radio frequency signal at a power of 1 mw or less to one end of a wire loop and grounding the other end of said loop, placing said wire loop to which said modulated radio frequency signal has been applied on the surface of the subject's body for a period of at least one hour.
17. The method of claim 16, wherein said radio frequency is selected from the group of frequencies consisting of: 43,322,480 Hz., 43,322,492 Hz., 43,322,485 Hz., 43,346,000 Hz., 43,346,090 Hz., 43,346,000 Hz,., 43,346,050 Hz., 43,353,800 Hz., 43,353,800 Hz., 43,353,850 Hz., 43,353,800 Hz., 43,296,000 Hz., 43,357,830 Hz., 43,351,850 Hz., 43,351,855 Hz., 43,351,870 Hz., 43,352,000 Hz., and 43,245,000 Hz., all ~ 20 Hz.
18. The method of claim 16, wherein said wire loop is made from approximately five hwns spaced approximately 3.175 cm. apart of a wire approximately 60 cm. long
19. A low power, precisely tuned, stable RF generator comprising, means for generating a sequence of audio frequency square waves, and a quartz crystal tuned to an RF frequency, connected in series to said square wave generating means.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US3456196P | 1996-12-30 | 1996-12-30 | |
| US4376497P | 1997-04-11 | 1997-04-11 | |
| US60/034,561 | 1997-04-11 | ||
| US60/043,764 | 1997-04-11 | ||
| PCT/US1997/023845 WO1998029156A2 (en) | 1996-12-30 | 1997-12-29 | Rf therapeutic cancer apparatus and method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2285267A1 true CA2285267A1 (en) | 1998-07-09 |
Family
ID=26711118
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002285267A Abandoned CA2285267A1 (en) | 1996-12-30 | 1997-12-29 | Rf therapeutic cancer apparatus and method |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP1011807A4 (en) |
| JP (1) | JP2001517975A (en) |
| CA (1) | CA2285267A1 (en) |
| WO (1) | WO1998029156A2 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AT411427B (en) * | 2002-02-20 | 2004-01-26 | Efp Elektronik Gmbh | DEVICE FOR EXCITING PULSING MAGNETIC FIELDS FOR MEDICAL PURPOSES |
| US20060047328A1 (en) * | 2004-08-31 | 2006-03-02 | Patrick Murphy | Multi-frequency electrical field generator and use thereof |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2545087A (en) | 1948-01-30 | 1951-03-13 | Electronic Medical Foundation | Electrical therapeutic device |
| US3609566A (en) * | 1969-03-05 | 1971-09-28 | Georgy Vasilievich Roschin | Device for transformation of voltage coordinates in simulation of transients in complex power systems |
| US3800802A (en) * | 1972-01-07 | 1974-04-02 | Int Medical Electronics Ltd | Short-wave therapy apparatus |
| US5099756A (en) * | 1989-06-01 | 1992-03-31 | Harry H. Leveen | Radio frequency thermotherapy |
-
1997
- 1997-12-29 WO PCT/US1997/023845 patent/WO1998029156A2/en not_active Application Discontinuation
- 1997-12-29 CA CA002285267A patent/CA2285267A1/en not_active Abandoned
- 1997-12-29 EP EP97954226A patent/EP1011807A4/en not_active Withdrawn
- 1997-12-29 JP JP53019498A patent/JP2001517975A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| EP1011807A2 (en) | 2000-06-28 |
| WO1998029156A2 (en) | 1998-07-09 |
| WO1998029156A3 (en) | 1998-09-11 |
| JP2001517975A (en) | 2001-10-09 |
| EP1011807A4 (en) | 2001-07-11 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued | ||
| FZDE | Discontinued |
Effective date: 20021230 |