text:
|Publication number
|Publication type
|Application number
|Publication date
|May 31, 2011
|Filing date
|Oct 25, 2005
|Priority date
|Jul 25, 2001
|Fee status
|Also published as
|Publication number
|Allan Foreman, Wolfgang Daum
|Original Assignee
|Allan Foreman, Wolfgang Daum
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (109), Non-Patent Citations (96), Referenced by (11), Classifications (10), Legal Events (7)
|External Links: USPTO, USPTO Assignment, Espacenet
This is a Continuation-in-Part Application claiming the benefit of and priority to Non-Provisional patent application Ser. No. 10/176,950 filed on Jun. 18, 2002, and Provisional Patent Application No. 60/307,785, filed on Jul. 25, 2001, both of which are incorporated herein by reference.
The present invention relates generally to thermotherapy devices, more specifically, devices for use with magnetic material compositions, and thermotherapeutic methods related thereto.
Despite considerable research effort and some success, cancer is still the second leading cause of death in the United States, claiming more than 500,000 lives each year according to American Cancer Society estimates. Traditional treatments are either invasive or expose the patient to considerable toxicity with often only modest success. Early detection, a result of better diagnostic practices and technology has improved the prognosis for many patients. Nevertheless, some cancers defy currently available treatment options, despite these improvements. Of the many forms of cancer that still pose a medical challenge, prostate, breast, lung, and liver claim the vast majority of lives each year.
Conventional treatments for many cancers, both in late and early stages, typically include surgery followed by radiation and/or chemotherapy both of which carry with them damaging side effects and considerable patient discomfort. Neither is completely effective against recurrence. For these reasons, it was desirable to provide improved and alternative techniques for treating cancer, particularly less invasive techniques that result in minimum or no collateral damage, and effective locally within target sites of the diseased organs. It was also desirable to provide techniques capable of being performed in a single or multiple treatment session(s), with minimal toxicity to the patient, and which could be targeted to the diseased tissues without requiring significant operator skill and input.
One such alternative technique is immunotherapy, which is a rapidly expanding type of therapy used for treating a variety of human diseases, including cancer. The FDA has approved a number of antibody-based cancer therapeutics. The emergence of antibody therapies is made possible by important advances in antibody technologies. The ability to engineer antibodies, fragments, and peptides with altered properties such as antigen binding affinity, molecular architecture, specificity, and valence has enhanced their use in therapies. The advantages of antibody engineering have overcome the limitations of mouse monoclonal antibodies. Cancer immunotherapeutics have made use of advances in the chimerization and humanization of mouse antibodies to reduce immunogenic responses in humans. High affinity human antibodies have also been obtained from transgenic mice that contain many human immunoglobulin genes. In addition, phage display technology, ribosome display, and DNA shuffling have allowed for the discovery of antibody fragments and peptides that have the desirable properties of high affinity and low immunogenicity for use as targeting ligands. All of these advances have made it possible to design an immunotherapy that has a desired antigen binding affinity, specificity, and minimal immune response.
The field of cancer immunotherapy makes use of markers that are expressed or over-expressed on cancer cells in comparison to normal cells. The identification of such markers is ongoing and the choice of a ligand/marker combination is critical to the success of any immunotherapy. Immunotherapy has fallen into several classes: (1) antibodies themselves that target growth receptors, disrupt cytokine pathways, or induce complement or antibody-dependent cytotoxicity; (2) direct arming of an antibody with a toxin, a radionucleotide, or a cytokine; (3) indirect arming of an antibody by attachment to immunoliposomes used to deliver a toxin or by attachment to an immunological cell effector (bispecific antibodies). Although armed antibodies have shown more potent tumor activity in clinical trials, there have been unacceptably high levels of toxicity. The disadvantage of therapies that rely on delivery of immunotoxins or radionucleotides (direct and indirect arming) has been that these agents are active at all times. There have been problems with damage to non-tumor cells and toxicity issues along with delivery challenges. Many immunotherapies have faced challenges with shed markers and delivery to the intended target. Cancer cells commonly shed antigen targets into the blood stream. Many antibody-based therapies are diluted by interaction with shed antigens. In addition, immune complexes can be formed between the immunotherapeutic and the shed antigen, which can lead to dose-limiting toxicities.
Generation of heat in a range of about 40� C. to about 46� C. (classical hyperthermia) can cause irreversible damage to diseased cells, whereas normal cells are not similarly affected. Diseased tissue may be treated by elevating the temperature of the individual cells contained within to a lethal level (cellular thermotherapy) using a suitable magnetic material confined to the vicinity of the cell and induction heating the material using an alternating magnetic field (AMF).
Hyperthermia may hold promise as a treatment for cancer because it induces instantaneous necrosis (typically called thermo-ablation) and/or a heat-shock response in cells (classical hyperthermia), leading to cell death via a series of biochemical changes within the cell. State-of-the-art systems that employ radio-frequency (RF) hyperthermia, such as annular phased array systems (APAS), attempt to tune E-field energy for regional heating of deep-seated tumors. Such techniques are limited by the heterogeneities of tissue electrical conductivities and that of highly perfused tissues, leading to the unsolved problems of 'hot spot' phenomena in unintended tissues with concomitant under-dosage in the desired areas. These factors make selective heating of specific regions with such E-field dominant systems very difficult.
Another strategy that utilizes RF hyperthermia requires surgical implantation of microwave- or RF-antennae or self-regulating thermal seeds. In addition to its invasiveness, this approach provides only limited (if any) treatment options for metastases because it requires knowledge of the precise location of the tumor, and is thus incapable of targeting undetected individual cancer cells or cell clusters not immediately adjacent to the primary tumor site. Clinical outcomes of these techniques are limited by problems with deposition of physical power to the desired tumor tissues.
Hyperthermia for cancer treatment using colloidal single domain magnetic suspensions (i.e., magnetic fluids) exposed to RF fields has been recognized for several decades. However, a major problem with magnetic fluid hyperthermia has been the inability to selectively deliver a lethal dose of particles to the tumor cells.
In view of the above, there is a need for a device for a safe and effective hyperthermia based device that involves the selective delivery of magnetic fields to diseased tissue. It is also desirable to have methods for treating diseased tissue, that incorporate selective delivery of magnetic fields to the diseased tissue in a safe and effective manner, with minimal invasion, and short treatment periods.
It is, therefore, an object of the present invention to provide a device capable of delivering an alternating magnetic field of known and controllable amplitude to a specific area of the body.
It is another object of the present invention to provide a device that can treat diseased tissue in a safe and effective manner.
It is another object of the present invention to provide a method that utilizes the devices of the present invention in conjunction with compositions of nanoscale magnetic materials and target-specific ligands to treat diseased tissue via hyperthermia.
It is a further object of the present invention to provide methods for the treatment of diseased tissue in a safe and effective manner, with minimal invasion, and short treatment periods.
The present invention pertains to devices for treating diseased tissue, such as cancer, by interacting with magnetic particles targeted to diseased cells in a patient. Such a device comprises a magnetic generator having a magnetic circuit defining at least part of a magnetic circuit, two poles of the magnetic circuit defining a gap therebetween, a magnetic field passing between two poles, the gap being of sufficient size to receive a portion of the patient containing the disease cells or targeted entities; and a power supply coupled to provide energy to the magnetic generator so that the magnetic field passing between the two poles alternates at a frequency of about 1 kHz or more.
The present invention also pertains to methods for the treatment of diseased tissue with the devices of the present invention. One such method comprises the administration to the patient of a magnetic material composition that comprises at least one magnetic particle attached to a ligand specific to a diseased-cell, and application of an alternating magnetic field to a region of the patient containing the diseased cells so as to inductively heat the magnetic material composition and kill the diseased cells.
The therapeutic device and methods of the present invention provide means for the treatment of diseased tissue in a safe and effective manner, with minimal invasion, and short treatment periods.
The above summary of the present invention is not intended to describe each illustrated embodiment or every implementation of the present invention. The figures and the detailed description which follow more particularly exemplify these embodiments.
The invention may be more completely understood in consideration of the following detailed description of various embodiments of the invention in connection with the accompanying drawings, in which:
While the invention is amenable to various modifications and alternative forms, specifics thereof have been shown by way of example in the drawings and will be described in detail. It should be understood, however, that the intention is not to limit the invention to the particular embodiments described. On the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the invention as defined by the appended claims.
The present invention pertains to devices for treating diseased tissue, and methods for treating diseased tissue utilizing such devices and magnetic material compositions. The devices and methods of the present invention may be used for the treatment of a variety of indications, including cancer. The methods of therapy using the disclosed device comprise the administration of a therapeutic composition comprising magnetic particles to a patient, and the application, via said device, of an alternating magnetic field to an area of the patient containing the magnetic particle composition to heat the bioprobes sufficiently to kill targeted cells. The present invention, or aspects thereof, may be amenable to use in conjunction with other methods or apparatus.
1. Definitions
The term "bioprobe", as used herein, refers to refers to the composition comprising at least a magnetic particle, a biocompatible coating material, and a target-specific ligand.
The term "core", as used herein, refers to the certain sections of a magnetic circuit that comprise a magnetic material; the purpose of the core is to lower magnetic reluctance.
The term "device", as used herein, refers to a combination of components that comprise the apparatus of the present invention. However, one or more component may be functional as a stand-alone device outside of the purposes of the present invention.
The terms "diseased tissue" or "diseased cell", as used herein, refer to tissue or cells associated with any type of a cancer, diseases of the immune system, pathogen-borne diseases, hormone-related diseases, and undesirable matter, such as toxins, reaction-by-products associated with organ transplants, and other abnormal cell or tissue growth.
The term "hyperthermia", as used herein, refers to an effected increase in physiologic temperature of the diseased tissue such that eventual death of the diseased tissue results. This may comprise, but is not limited to classical hyperthermia, ablation, other necrotic tissue death, or initiation of apoptotic cell death.
The term "ligand", as used herein, refers to a compound which targets biological markers. Examples of ligands include proteins, peptides, antibodies, antibody fragments, saccharides, carbohydrates, glycans, cytokines, chemokines, nucleotides, lectins, lipids, receptors, steroids, neurotransmitters, Cluster Designation/Differentiation (CD) markers, imprinted polymers, and the like.
The term "magnetic circuit", as used herein, refers to a specific route leading from one magnetic pole to the opposite pole in which materials have been placed to reduce magnetic reluctance and to provide a preferred path for the magnetic flux.
It is to be understood that the singular forms of "a", "an", and "the", as used herein and in the appended claims, include plural reference unless the context clearly dictates otherwise.
2. The Targeted Delivery Device
The targeted delivery device of the present invention, an embodiment of which is illustrated in
In one embodiment of the present invention, the disclosed device is utilized for the treatment of a patient with cancer, as illustrated in
It will be appreciated that other types of cancers, such as lung, prostate and the like, and other types of indications, such as diseases of the immune system, pathogen-borne diseases, non-cancerous diseased cells or tissue, and undesirable matter, such as toxins, reaction-by-products associated with organ transplants, hormone-related diseases, may be treated using the device of the present invention. Further, the poles 104 may be formed from pieces the gap of which is adjustable, so as to permit other parts of the body of patient 105 to be treated. It is advantageous to set the gap between the poles 104 to be sufficiently large to permit the part of the body containing the cancer to enter the gap, but not be so large as to reduce the magnetic field strength.
In one embodiment, an alternate means of producing AMF is utilized, as illustrated in
In another embodiment, which is a variation of the device illustrated in
In another embodiment of the present invention, another apparatus is used for producing an AMF, as illustrated in
Measuring alternating magnetic fields directly is extremely difficult. Because the AMF is proportional to the current in the coil 322, characteristics of the AMF may be defined in terms of the coil current, which can readily be measured with available test equipment. For example, the coil current may be viewed and measured with a calibrated Rogowski coil and any oscilloscope of suitable bandwidth. The fundamental waveform may be observed as the direct measure of the magnitude and direction of the coil current. Many different types of fundamental waveforms may be used for the AMF. For example,
Most practical generators produce an approximation of these waveforms with some amount of distortion. In most applications, this waveform may be nearly symmetrical around zero, as illustrated in
The amplitude of the waveform may also be modulated.
The AMF produced by the generator may also be pulsed. Pulse width is traditionally defined as the time between the −3 dBc points of the output of a square law crystal detector. Because this measurement technique is cumbersome in this application, we use an alternate definition of pulse width. For the purpose of this invention, pulse width may be defined as the time interval between the 50% amplitude point of the pulse envelope leading edge and the 50% amplitude point of the pulse envelope trailing edge. The pulse width may also be modulated.
The pulse repetition frequency (PRF) is defined as the number of times per second that the amplitude modulation envelope is repeated. The PRF is typically in the range between 0.0017 Hz and 1000 MHz. The PRF may also be modulated. The duty cycle may be defined as the product of the pulse width and the PRF, and thus is dimensionless. In order to be defined as pulsed, the duty of the generator 318 must be less than unity (or 100%).
The AMF may be constrained to prevent heating healthy tissue to lethal temperatures (typically ≧43� C.). This may be accomplished in a variety of ways.
These four characteristics may be adjusted to maximize heating rate of the bioprobes and, simultaneously, to minimize the heating rate of the healthy tissue located within the treatment volume. These conditions may vary depending upon tissue types to be treated, thus the operator may determine efficacious operation levels. In one embodiment, one or more of these characteristics are adjusted during treatment based upon one or more continuously monitored physical characteristics of tissue in the treatment volume by the probe 354, such as temperature or impedance. This information is then supplied as input to the generator 318, via the monitor 352, the data bus 324, the controller 356, and the data bus 358 to control output. The generator output may be adjusted so that the peak AMF strength is in the range between about 10 Oersteds (Oe) and about 10,000 (Oe). Preferably, the peak AMF strength is in the range between about 20 Oe and about 3000 Oe, and more preferably, between about 100 Oe and about 2000 Oe.
In another embodiment of the present invention, the differential heating of the bioprobes, as compared to that of the healthy tissue, is maximized. The bioprobes 210 heat in response to each cycle of the AMF. Assuming the fundamental frequency, the PRF, and the pulse width remain constant, the heat output of the bioprobe 210 continues to increase as peak amplitude of the AMF increases until the magnetic material of the bioprobe reaches saturation. Beyond this point, additional increases in AMF amplitude yield almost no additional heating. However, at AMF amplitudes below saturation, it can be said that bioprobe heating is a function of AMF amplitude. Unlike bioprobes, healthy tissue heating is a result of eddy current flow and a function of the rate of change of the AMF. In particular, the eddy current and resultant tissue heating are described by the following expressions:
Ieddy∝dB/dT (1)
Tissue Heating∝Ieddy 2 (2)
From the relationships (1) and (2), it is evident that reducing the rate of change of the AMF yields a significant reduction in tissue heating. In one embodiment of the present invention, this relationship is exploited by using a symmetrical triangular wave as the fundamental waveform, as shown in
The heating of both the tissue and the bioprobes increase with increased AMF amplitude. At low AMF amplitudes, small increases yield significant increases in magnetic heating. As the bioprobes approach saturation however, their relationship with the AMF amplitude becomes one of diminishing return. This relationship is unique to the particular magnetic material, as are the values that constitute "low" or "saturating" AMF amplitudes. Bioprobe heating is at first related to the AMF amplitude by an exponent >1, which gradually diminishes to an exponent <1 as saturation is approached.
It is desirable to apply the AMF to the treatment area 103 of the patient 105. Generating high peak amplitude AMF over a large area requires a very large AMF generator and exposes large amounts of healthy tissue to unnecessary eddy current heating. Without some means of directing the field to where it is useful, disease in the chest or trunk could only be practically treated by placing the patient within a large solenoid coil. This would expose most of the major organs to eddy current heating, which must then be monitored and the AMF adjusted so as not to overheat any part of a variety of tissue types. Each of these tissue types has a different rate of eddy current heating. The peak AMF strength would need to be reduced to protect those tissue types that experience the most extreme eddy current heating. If the varieties of exposed tissue are minimized, it is likely that the AMF strength can be increased, and thereby reducing the treatment time and increasing the efficacy. One method for confining the high peak amplitude AMF to treatment area 103 involves defining the lowest reluctance path of magnetic flux with high permeability magnetic material. This path is referred to as a magnetic circuit (102 in
The material used for fabricating the magnetic circuit 302 may be appropriate to the peak amplitude and frequency of the AMF. The material may be, but is not limited to, iron, powdered iron, assorted magnetic alloys in solid or laminated configurations, magnetic fluids and paste, magnetic material suspended in a polymer matrix, such as Fluxtrol� (available from Fluxtrol Inc. Auburn Hills Mich.), and ferrites. The pole faces 104 and 304 may be shaped and sized to further concentrate the flux produced in the treatment area. The pole faces 304 may be detachable. Different pole pieces having different sizes and shapes may be used as pole faces 304 so that the treatment area and volume may be adjusted. When passing from one material to another, the lines of magnetic flux 312 travel in a direction normal to the plane of the interface plane. Thus, the pole face 304 may be shaped to influence the flux path through gap 333. As the gap 333 between pole faces 304 increases relative to the pole diameters, this technique becomes less useful. The pole faces 304 may be detachable and may be chosen to extend the magnetic circuit 302 as much as possible, to minimize the gap 333 while leaving sufficient space to receive that portion of the patient being treated.
An embodiment of the invention for use in treating diseases that are located closer to the surface of a patient's body is illustrated in
A support arm 621 (shown only in
A cross sectional view of a treatment head 601 that may be used in the system described in
Alternative configurations of the treatment head 601 may also be useful in the present invention, an example of which is illustrated in
In one embodiment of the present invention, the coils (322 in
In one embodiment of the present invention, the surface area of the coils is increased to enhance conductivity due to skin effect as well as to aid in the removal of heat.
In one embodiment, helper coils are utilized to confine or alter the distribution of magnetic flux. These helper coils may be wired in series or in parallel with the main coils, and their phase is adjusted to best enhance the therapy. They can be positioned to maximize magnetic flux in the treatment area or positioned to divert magnetic flux from a specific area. The helper coils may also be powered by a separate power supply as long as they are phase locked to the main coils.
In one embodiment, the magnetic circuit is omitted and an air return path used. Multi-turn coils of decreasing diameter, oriented such that the smallest diameter turns are closest to the patient, are used to increase the peak AMF amplitude in the gap. Alternatively, single-turn conical shaped coils may be used, with their narrow end closest to the patient, to accomplish the same. Either of these coil types may also be used in a configuration comprising a magnetic circuit or a partial magnetic circuit.
In one embodiment of the present invention, multiple magnetic circuits 701 may be used in parallel, as illustrated in
It is preferable that the AMF is used efficiently to heat bioprobes.
In one embodiment of the present invention, numerical simulations are used to plan the treatment procedure. The method of planning the treatment procedure involves simulation of the magnetic flux in a patient's body, utilizing the pole geometry and electrical parameters of the coils. From an anatomical conductivity tissue model, the specific absorption rate for magnetic energy and eddy current heating are simulated. The optimal treatment parameters are then determined by iteratively adjusting the electromagnetic parameters (e.g., frequency, coil current, pulse shape, pulse repetition envelope, pulse repetition frequency, duration, duty cycle, and magnet position) in the magnetic flux simulation to yield an optimal treatment plan. In this manner, the energy necessary for heating the particles in the diseased tissue is maximized while the eddy current heating of the healthy tissue is minimized.
In one embodiment of the present invention, thermoplastic masking is used to fix the location of a patient's body relative to the AMF, and to aid in targeting the desired treatment area, as used in the same manner as in imaging applications and in some radio, laser and ultrasonic therapies and procedures.
Having generally described the invention, a more complete understanding thereof may be obtained by reference to the following examples that are provided for purposes of illustration only and do not limit the invention.
In general, a fundamental frequency of several MHz is effective for inductive heating. At such frequencies, however, tissue heating may be problematic. Because eddy current heating of the tissue is approximately proportional to the square of the frequency and hysteretic heating of the particles is approximately proportional to frequency to the first power, lower frequency tends to favor hysteretic heating. More precisely, reducing the frequency yields a greater reduction in tissue heating than in bioprobe heating for a specific AMF amplitude.
Eddy current heating of tissue is also proportional to the square of the AMF amplitude. Hysteretic heating of the bioprobes has a more complex relationship with AMF amplitude. A typical relationship between AMF amplitude and hysteretic heat output is described in
The bioprobes used in this example included 50-nm, Fe3O4 particles surrounded by a dextran shell, to which the monoclonal antibody (mAB) for Her-2 was covalently linked. The particles were suspended in cellular growth media including Modified Eagle's Medium (MEM) containing 10% fetal calf serum, insulin (10 μg/ml), fungizone, glutamine, penicillin, streptomycin, sodium pyruvate and non-essential amino acids, which was then added to cultures of MCF-7 cells. The MCF-7 cells represent an estrogen receptor-positive human breast carcinoma, and were grown on tissue culture inserts with a 10 mm diameter possessing porous frits with pore sizes of 0.02 or 0.2 μm.
The alternating magnetic field source was an industrial 3.5 kW variable duty radio-frequency generator with a frequency of 740 kHz and time-averaged field amplitude of 500 Oe (peak field amplitude, 1300 Oe). The generator produced pulses with a length of 4.174 ms, at a pulse repetition rate of 121 Hz, to give a duty cycle of 50.6%. The generator provided power to a 14-mm (inner diameter), 5-turn copper solenoid coil into which sample containers were inserted. The average temperature of the media in all samples monitored in situ using silicon dioxide temperature probes resistant to electromagnetic (EM) fields (obtained from FISO Technologies Inc., Ste-Foy, Quebec, Canada).
A series of water bath tests was conducted to determine the hyperthermia tolerance of the cell cultures. The purpose of these tests was to obtain "positive control" data on the effects of hyperthermia on the cancer cell cultures and to aid in the interpretation of experiments using the bioprobe system. Exposing cellular culture media to an alternating magnetic field, without the presence of the bioprobes, may cause some tissue heating. Such magnetic induction heating is determined by the frequency and field strength of the magnetic field. Thus, to avoid overheating the media with the applied magnetic field, water bath tests were conducted to provide threshold limits of magnetic induction heating of the media containing cells not receiving the treatment. Table 1 lists results of cell death fraction as a function of exposed temperature and exposure time. The MCF-7 cell line is shown to be unaffected by heat exposure to 42� C. for 30 minutes. Thus, for all in vitro experiments, the magnetic field strengths were fixed at levels where the average temperature of the cellular growth media (containing no cells or magnetic fluid) remained at or below 42� C.
Result of water bath tests with MCF-7 cells
Temperature (� C.)
Time Of Exposure (Min.)
% Dead Cells
*Represents a control cell culture sample not placed into water bath.
Cells intended for treatment were combined with bioprobes containing the Her-2 antibody and incubated for 8 minutes at 20� C., followed by three rinses with growth media, to remove unattached bioprobes. The cell cultures were analyzed before and 6 hours after the 20-minute treatments with the alternating magnetic field (AMF). The fraction of dead cells for the targeted sample (T1) and control samples (C1-C3) are presented in Table 2. In the targeted sample, 91%�5% (n=7) of the MCF-7 cells were killed. Of the cells killed, about 70% cells were be lysed by the treatment, as measured by spectrophotometric analysis of cytoplasmic lactate dehydrogenase (LDH), an enzyme produced by living cells. The remaining approximately 20% underwent apoptosis, as measured using a commercial fluorescent apoptosis-staining assay. The kill rates for the targeted cells are significantly higher than baseline death and apoptotic rates of 4%�1% in all controls (Table 2). Control groups include: 1) cells receiving no exposure to either the AMF or bioprobes (Sample C1); 2) cells exposed to the bioprobes alone (Sample C2); and 3) cells exposed to the AMF alone (Sample C3). Similar baseline deaths of all controls confirm that neither the AMF alone, nor only the presence of the bioprobes, is toxic to the cells. Higher than normal cell death occurs only when the AMF is applied after the bioprobes have attached to a cell.
In vitro results with MCF-7 cells
% dead cells (n = 7)
4 � 1
5 � 1
4 � 1
91 � 5
In a treatment cycle, the bioprobes 110 may be exposed to and become attached to metastatic cells in the treatment area. Pole pieces 304 may be chosen to provide treatment in a selected treatment area, for example, approximately 6 inches in diameter. The patient 105 is typically placed on the treatment bed 106, and the bed controller 108 is typically adjusted to place the targeted tissue at the region of maximum field strength between the poles 304. The pulse width, duty cycle, and peak amplitude of the AMF and the treatment time may be adjusted. Several temperature probes, for example, four temperature probes, may be inserted into the treatment volume. One probe may be located centrally and the other three may be inserted into tissues, within the treatment area that are heated by the AMF. As the tissue heats under the applied AMF, the temperature probes 354 send data to the probe monitor 352. The monitor sends the temperature data via the feedback loop 324 to the RF generator controller 356. Monitoring may be continuous, for example at a data rate of 10 samples per second, and the duty of the RF generator 318 may be adjusted once per second based on individual, 10 sample averages from each probe. If none of the probes 354 sense a temperature greater than the preset limit, the RF generator 318 may be permitted to operate at the original settings. If one or more of the probes 354 senses a temperature over the preset threshold, the controller 356 may send a command to reduce at least one of the duty cycle, the PRF, the magnitude of the magnetic field. This process continues until the treatment is completed.
Bioprobes with comprising ligands specific to inflammatory breast cancer are injected into a patient with legions on the chest. After an appropriate circulation time, the patient is exposed to an AMF to inductively heat and kill the cancer cells. The patient is positioned on a non-conductive treatment table 623 and the treatment head 601 is positioned to target the diseased area, as illustrated in
While the above description of the invention has been presented in terms of a human patient, it will be appreciated that the invention may also be applicable to treating cancers in other mammals.
As noted above, the present invention is applicable to devices for use with magnetic material compositions, and thermotherapeutic methods related thereto. The present invention should not be considered limited to the particular examples described above, but rather should be understood to cover all aspects of the invention as fairly set out in the attached claims. Various modifications, equivalent processes, as well as numerous structures to which the present invention may be applicable will be readily apparent to those of skill in the art to which the present invention is directed upon review of the present specification. The claims are intended to cover such modifications and devices.
|Cited Patent
|Filing date
|Publication date
|Jan 22, 1976
|Aug 15, 1978
|Robert Thomas Gordon
|Cancer treatment method
|May 12, 1978
|Dec 1, 1981
|Gordon Robert T
|Cancer treatment
|Apr 5, 1978
|Jan 26, 1982
|C.G.R. Mev
|Apparatus for localized heating of a living tissue, using electromagnetic waves of ultra high frequency, for medical applications
|May 19, 1980
|Apr 6, 1982
|Corning Glass Works
|Radio frequency induced hyperthermia for tumor therapy
|Jan 9, 1981
|Jul 5, 1983
|Rand Robert W
|Induction heating apparatus for use in causing necrosis of neoplasm
|Apr 5, 1982
|Jun 5, 1984
|Canadian Patents And Development Limited
|Magnetic iron-dextran microspheres
|Dec 30, 1981
|Jun 12, 1984
|Czerlinski George H
|Coated magnetizable microparticles, reversible suspensions thereof, and processes relating thereto
|Apr 13, 1983
|Oct 8, 1985
|Rand Robert W
|Induction heating method for use in causing necrosis of neoplasm
|May 24, 1983
|Feb 11, 1986
|Gordon Robert T
|Cancer treatment by intracellular hyperthermia
|Nov 21, 1983
|Mar 11, 1986
|Corning Glass Works
|Radio frequency-induced hyperthermia for tumor therapy
|Aug 19, 1983
|May 27, 1986
|Gordon Robert T
|Use of ferromagnetic, paramagnetic and diamagnetic particles in the treatment of infectious diseases
|Jul 3, 1984
|Sep 9, 1986
|Gordon Robert T
|Atherosclerosis treatment method
|Dec 14, 1984
|Nov 18, 1986
|Gordon Robert T
|Cancer treatment method
|Sep 23, 1983
|May 5, 1987
|Robert T. Gordon
|Use of magnetic susceptibility probes in the treatment of cancer
|Jul 2, 1985
|Jul 7, 1987
|501 Regents of the University of California
|Macrocyclic bifunctional chelating agents
|Jul 2, 1985
|Nov 24, 1987
|Target Therapeutics
|Hyperthermic treatment of tumors
|May 7, 1985
|Apr 5, 1988
|Gordon Robert T
|Ferromagnetic, diamagnetic or paramagnetic particles useful in the diagnosis and treatment of disease
|Jan 11, 1985
|Jun 28, 1988
|Cetus Corporation
|Monoclonal anti-human breast cancer antibodies
|Nov 4, 1985
|Jul 19, 1988
|Gordon Robert T
|Method for the treatment of arthritis and inflammatory joint diseases
|Jul 3, 1984
|Aug 30, 1988
|Gordon Robert T
|Method for affecting intracellular and extracellular electric and magnetic dipoles
|Jul 18, 1986
|Mar 21, 1989
|Gordon Robert T
|Process for the treatment of neurological or neuromuscular diseases and development
|May 27, 1986
|Dec 26, 1989
|Gordon Robert T
|Method for the connection of biological structures
|Sep 27, 1988
|May 8, 1990
|Gordon Robert T
|Process for applying a localized magnetic or electric field
|Sep 27, 1988
|Aug 21, 1990
|Gordon Robert T
|Process for affecting molecules in tissue
|Sep 23, 1988
|Dec 25, 1990
|Olympus Optical Co., Ltd.
|Body depth heating hyperthermal apparatus
|Sep 17, 1986
|Jan 8, 1991
|Rand Robert W
|Inductive heating process for use in causing necrosis of neoplasms at selective frequencies
|Feb 22, 1990
|Mar 5, 1991
|Gordon Robert T
|Method for following the distribution of particles in neurological or neuromuscular tissue and cells
|Mar 29, 1988
|Aug 27, 1991
|Gordon Robert T
|Ferromagnetic, diamagnetic or paramagnetic particles useful in the diagnosis and treatment of disease
|Apr 2, 1990
|Nov 26, 1991
|Gudov Vasily F
|Method and apparatus for treating malignant tumors by local hyperpyrexia
|Jul 20, 1988
|Feb 11, 1992
|Gordon Robert T
|Method for affecting intracellular and extracellular electric and magnetic dipoles
|Jun 1, 1989
|Mar 31, 1992
|Harry H. Leveen
|Radio frequency thermotherapy
|Aug 6, 1990
|Jul 7, 1992
|Thermal Developments, Inc.
|Heat intensifier and localizer for radiofrequency thermotherapy
|May 6, 1988
|Dec 8, 1992
|Cetus Oncology Corporation
|Monoclonal anti-human breast cancer antibodies
|Mar 26, 1991
|Apr 20, 1993
|Gudov Vasily F
|Method and apparatus for treating malignant tumors by local hyperpyrexia
|Oct 10, 1991
|Apr 5, 1994
|Metcal, Inc.
|Thermal induction heater
|Jul 20, 1993
|May 2, 1995
|Research Corporation Technologies, Inc.
|Magnetic microparticles
|Dec 9, 1993
|Jul 4, 1995
|Pegasus Medical Technologies, Inc.
|Cobalt palladium seeds for thermal treatment of tumors
|May 5, 1993
|Aug 15, 1995
|Molecular Bioquest, Inc.
|Electromagnetic wave absorbing, surface modified magnetic particles for use in medical applications, and their method of production
|Apr 22, 1994
|Nov 21, 1995
|Tanaka Kikinzoku Kogyo K.K.
|Process of thermal treatment in tissue
|Oct 25, 1994
|Apr 9, 1996
|Dana-Farber Cancer Institute, Inc.
|Antibodies specific for the DF3 carcinoma associated antigen
|Jul 20, 1994
|Aug 20, 1996
|Bioquest, Incorporated
|Preparation and use of novel injectable RES avoiding inorganic particles for medical application
|Feb 14, 1994
|Mar 18, 1997
|Gordon, Deceased; David
|Diagnosis and treatment of HIV viral infection using magnetic metal transferrin particles
|Sep 20, 1994
|Apr 15, 1997
|Urologix, Inc.
|Method for treating benign prostatic hyperplasia with thermal therapy
|Jun 7, 1995
|Apr 22, 1997
|Gordon, Deceased; David
|Diagnosis and treatment of viral effects using magnetic metal transferrin particles
|Aug 11, 1994
|May 13, 1997
|Cetus Oncology Corporation
|Monoclonal anti-human breast cancer antibodies
|Jul 24, 1995
|Aug 19, 1997
|J. D. Technologies, Inc.
|Method for treating tumors
|Aug 5, 1994
|Oct 14, 1997
|Genentech, Inc.
|Monoclonal antibodies directed to the HER2 receptor
|Jun 6, 1995
|Dec 2, 1997
|Epigen, Inc.
|Antibodies to human carcinoma antigen
|Nov 30, 1994
|Jan 6, 1998
|The Trustees Of The University Of Pennsylvania
|Methods of treating cancerous cells with anti-receptor antibodies
|May 23, 1995
|Feb 24, 1998
|Genentech, Inc.
|Monoclonal antibodies directed to the HER2 receptor
|May 23, 1995
|Jun 30, 1998
|Genentech, Inc.
|Monoclonal antibodies directed to the HER2 receptor
|Apr 11, 1995
|Jan 12, 1999
|Genentech, Inc.
|Antibodies specific for heregulin 2-α
|Nov 17, 1995
|Apr 6, 1999
|Centro De Inmunologia Molecular
|Humanized and chimeric monoclonal antibodies that recognize epidermal growth factor receptor (EGF-R); diagnostic and therapeutic use
|Mar 17, 1994
|Jun 29, 1999
|Silica Gel Ges. M.B.H.
|Superparamagnetic particles, process for producing the same and their use
|Jul 11, 1996
|Jul 13, 1999
|Medarex, Inc.
|Therapeutic multispecific compounds comprised of anti-Fcα receptor antibodies
|Jun 8, 1992
|Aug 10, 1999
|Binax Nh, Inc.
|Preparation of sub 100 A magnetic particles and magnetic molecular switches
|Dec 17, 1996
|Sep 28, 1999
|The Regents Of The University Of California
|Method for preparing radionuclide-labeled chelating agent-ligand complexes
|Mar 25, 1997
|Oct 19, 1999
|Genentech, Inc.
|ErbB3 antibodies
|Jul 12, 1996
|Dec 28, 1999
|Glycotech Corp.
|Methods for treatment of EGF receptor associated cancers
|Apr 14, 1995
|Jan 18, 2000
|Genentech, Inc.
|HER2 extracellular domain
|May 28, 1998
|Mar 14, 2000
|Medical University Of South Carolina
|Multi-marker RT-PCR panel for detecting metastatic breast cancer
|Jun 7, 1995
|Apr 25, 2000
|Chiron Corporation
|Antigen-binding sites of antibody molecules specific for cancer antigens
|Nov 16, 1998
|Jun 13, 2000
|Ablation Technologies, Inc.
|Combination radioactive and temperature self-regulating thermal seed implant for treating tumors
|Oct 29, 1998
|Nov 21, 2000
|Paragon Medical Limited
|Targeted hysteresis hyperthermia as a method for treating tissue
|Jul 9, 1998
|Dec 26, 2000
|Board Of Regents, The University Of Texas System
|Radiation and nanoparticles for enhancement of drug delivery in solid tumors
|Mar 17, 1998
|Dec 26, 2000
|Genetech, Inc.
|Monoclonal antibodies directed to the HER2 receptor
|May 9, 1997
|Dec 26, 2000
|Sirtex Medical Limited
|Targeted hysteresis hyperthermia as a method for treating diseased tissue
|Jun 21, 1996
|Feb 20, 2001
|Amcell Corporation
|Efficient enrichment and detection of disseminated tumor cells
|Dec 11, 1997
|Jun 5, 2001
|Dana-Farber Cancer Institute
|Methods and pharmaceutical compositions for inhibiting tumor cell growth
|Jun 10, 1999
|Jun 26, 2001
|Genentech, Inc.
|Method for making monoclonal antibodies and cross-reactive antibodies obtainable by the method
|Aug 23, 1999
|Aug 28, 2001
|Glycotech Corp.
|Pharmaceutical compositions for treatment of EGF receptor associated cancers
|Mar 4, 1999
|Oct 16, 2001
|Medarex, Inc.
|Therapeutic multispecific compounds comprised of anti-FCA receptor antibodies
|Sep 27, 1996
|Feb 5, 2002
|The Austin Research Institute
|Mimicking peptides in cancer therapy
|Jan 14, 2000
|Feb 19, 2002
|First Circle Medical, Inc.
|Treatment of hepatitis C using hyperthermia
|Jun 25, 1999
|May 14, 2002
|Genentech, Inc.
|Monoclonal antibodies directed to the HER2 receptor
|Sep 30, 1998
|May 14, 2002
|American Foundation For Biological Research, Inc.
|Immunotherapy of cancer through expression of truncated tumor or tumor-associated antigen
|Sep 16, 1999
|May 21, 2002
|Pro Duct Health, Inc.
|Methods and systems for treating breast tissue
|Mar 29, 2000
|Oct 22, 2002
|The Regents Of The University Of California
|Diagnosis and treatment of cancers using in vivo magnetic domains
|Nov 22, 2000
|Feb 4, 2003
|The Research Foundation Of State University Of New York
|Magnetic nanoparticles for selective therapy
|Jun 19, 1998
|Apr 1, 2003
|Institut F�r Neue Materialien Gem. Gmbh
|Nanoscale particles having an iron oxide-containing core enveloped by at least two shells
|May 12, 2000
|May 20, 2003
|Sirtex Medical Limited
|Targeted hysteresis hyperthermia as a method for treating diseased tissue
|Jan 18, 2001
|Jun 10, 2003
|Mfh Hyperthermiesysteme Gmbh
|Magnetic field applicator for heating magnetic substances in biological tissue
|Mar 3, 2000
|Jul 29, 2003
|Sirtex Medical Limited
|Heating of magnetic material by hysteresis effects
|Nov 20, 2000
|Oct 28, 2003
|Herbert Pilgrimm
|Super-paramagnetic particles with increased R1 relaxivity, process for producing said particles and use thereof
|Aug 9, 2000
|Dec 30, 2003
|Magforce Applications Gmbh
|Medical preparation for treating arthrosis, arthritis and other rheumatic joint diseases
|Jan 18, 2001
|Aug 2, 2001
|Peter Feucht
|Magnetic field applicator for heating magnetic substances in biological tissue
|Jan 18, 2001
|Aug 9, 2001
|Peter Feucht
|Magnetic field applicator for heating magnetic substances in biological tissue
|Dec 5, 2001
|May 2, 2002
|Immunomedics, Inc.
|Method and kit for imaging and treating organs and tissues
|Feb 22, 2002
|Sep 12, 2002
|Peter Feucht
|Magnetic coil apparatus for heating magnetic substances in biological tissue
|Jun 18, 2002
|Feb 6, 2003
|Triton Biosystems, Inc.
|Thermotherapy via targeted delivery of nanoscale magnetic particles
|Jun 6, 2002
|May 15, 2003
|Lee Josephson
|Magneitc-nanoparticle conjugates and methods of use
|Mar 17, 2003
|Sep 25, 2003
|Institut Fur Neue Materialien Gem. Gmbh
|Nanoscale particles having an iron oxide-containing core enveloped by at least two shells
|May 10, 2005
|Nov 10, 2005
|Yousef Haik
|Magnetic particle composition for therapeutic hyperthermia
|Nov 1, 2005
|Jun 29, 2006
|Robert Ivkov
|Magnetic nanoscale particle compositions, and therapeutic methods related thereto
|Dec 16, 2005
|Jul 6, 2006
|Lanza Gregory M
|Integrin targeted imaging agents
|Jun 30, 1982
|Jan 21, 1986
|Method for treating benign and malignant tumors utilizing radio frequency, electromagnetic radiation
|Nov 19, 2001
|Jun 18, 2003
|Chemagen Biopolymer Technologi
|Vorrichtung und Verfahren zum Behandeln von Magnetpartikeln
|May 13, 1981
|Nov 25, 1981
|Corning Glass Works
|Ceramic suitable for inducing localised heating in the presence of a radio frequency magnetic field, and use thereof
|Title not available
|Nov 9, 1993
|Aug 22, 2001
|Ludwig Institute For Cancer Research
|Monoclonal antibody which specifically binds to tumor vascular endothelium and uses thereof
|Oct 27, 1998
|May 6, 1999
|Paragon Medical Limited
|Improved targeted hysteresis hyperthermia as a method for treating tissue
|Title not available
|Title not available
|Title not available
|Nov 9, 1993
|May 26, 1994
|Ludwig Institute For Cancer Research
|Monoclonal antibody which specifically binds to tumor vascular endothelium and uses thereof
|May 9, 1997
|Nov 20, 1997
|Paragon Medical Limited
|Targeted hysteresis hyperthermia as a method for treating diseased tissue
|Oct 8, 1998
|Apr 22, 1999
|The Research Foundation Of State University Of New York
|Controlled size polymeric microspheres with superparamagnetic cores
|Mar 3, 2000
|Sep 8, 2000
|Paragon Medical Limited
|Heating of magnetic material by hysteresis effects
|Dec 3, 2002
|Jun 12, 2003
|Nanospectra Biosciences, Inc.
|Treatment of angiogenesis disorders using targeted nanoparticles
|Aguilar et al., The transmembrane heregulin precursor is functionally active, 2001, J. Biol. Chem. 276: 44099-44107 (Abstract).
|Babino et al., Tn antigen is a pre-cancerous biomarker in breast tissue and serum in n-nitrosomethylurea-induced rat carcinogenesis, 2000, Int. J. Cancer 86: 753-759 (Abstract).
|Bacri et al., Use of magnetic nanoparticles for thermolysis of cells in a ferrofluid, 1997, Scientific and Clinical Applications of Magnetic Carriers, Hafeli et al., eds., pp. 597-606, Plenum Press, New York, USA.
|Barker et al., The MAGE proteins: emerging roles in cell cycle progression, apoptosis, and neurogenic disease, 2002, J. Neurosci. Res. 67: 705-712 (Abstract).
|Barratt-Boyles, Making the most of mucin: a novel target for tumor immunotherapy, 1996, Cancer Immunol. Immunother. 43(3): 142-151.
|Bartlett et al., On the use of ferromagnetic microparticles in microwave and radio frequency hyperthermia, 1988, J. of the Inst. of Electronic and Radio Engineers 58: 197-201.
|Borelli et al.., Hysteresis heating for the treatment of tumours, 1984, Phys Med Biol. 29 No. 5: 487-494, England.
|Brusentsov et al., Evaluation of ferromagnetic fluids and suspensions for the site-specific radiofrequency-induced hyperthermia of MX11 sarcoma cells in vitro, 2001, J. Magnetism and Magnetic Materials, 225: 113-117.
|Carter, Improving the efficacy of antibody-based cancer therapies, 2001, Nature Reviews 1: 118-129.
|Chan et al., Synthesis and evaluation of colloidal magnetic iron oxides for the site-specific radiofrequency-induced hyperthermia of cancer, 1993, J. Magnetism and Magnetic Materials, 122: 374-378, Holland.
|Chan et al.., Physical chemistry and in vivo tissue heating properties of colloidal magnetic iron oxides with increased power adsorption rates in Scientific and Clinical Applications of Magnetic Carriers, Hafeli et al. eds., 1997, pp. 607-618, Plenum Press, New York, USA.
|Coles et al., Pulsed monoclonal antibody treatment and autoimmune thyroid disease in multiple sclerosis, 1999, Lancet 354: 1691-1695 (Abstract).
|Csuka et al., Prognostic factors of breast cancer, 2000, Magy. Onkol 44: 53-60 (Abstract).
|Davidson et al., Ovarian carcinoma and serous effusions. Changing views regarding tumor progression and review of current literature, 2001, Anal. Cell Pathol. 23: 107-128 (Abstract).
|Defazio et al., Expression of c-erbB receptors, heregulin and estrogen receptor in human breast cell lines, 2000, Int. J. Cancer 87: 487-498 (Abstract).
|DeNardo et al., "Development of tumor targeting bioprobes (I I I In-Chimeric L6 monoclonal antibody nanoparticles) for alternating magnetic field cancer therapy", 2005, Clinical Cancer Research 11(19 Suppl):7087s-7092s.
|Denardo et al., Development of Tumor Targeting Bioprones (111In-Chimeric L6 Monoclonal Antibody Nanoparticles) for Alternating Magnetic Field Cancer Therapy, 2005, Clin. Can. Res. 11(19Suppl.):7087s-7092s.
|Diaz et al., Expression of epithelial mucins Muc1, Muc2, and Muc3 in ductal carcinoma in situ of the breast, 2001, Breast J. 7(1): 40-45 (Abstract).
|Esteva et al., Expression of erbB/HER receptors, heregulin and P38 in primary breast cancer using quantitative immunohistochemistry, 2002, Pathol. Oncol. Res. 7: 171-177 (Abstract).
|Garcia-Pachon et al., Diagnostic value of C-reactive protein in exudative pleural effusions, 2002, Eur. J. Intern. Med. 13: 246-249 (Abstract).
|George et al., Functional inhibition of Ras by S-trans, trans-farnesyl thiosalicylic acid attenuates atherosclerosis in apolipoprotein E knockout mice, 2002, Circulation 105: 2416-2422 (Abstract).
|Gilchrist et al., Selective inductive heating of lymph nodes, 1957, Annals of Surgery 146: 596-606.
|Gion et al., CA27.29: a valuable marker for breast cancer management. A confirmatory multicentric study on 603 cases, 2001, Eur. J. Cancer 37: 355-363 (Abstract).
|Goldin et al.., The effects of diapulse on the healing of wounds: a double-blind randomized controlled trial in man, 1981, Brit. J. of Plastic Surgery 34: 267-270.
|Gordon et al., Intracellular hyperthermia: a biophysical approach to cancer treatment via intracellular temperature and biophysical alterations, 1979, Medical Hypothesis 5: 83-102.
|Gourevitch et al., Polymorphic epithelial mucin (MUC-1)-containing circulating immune complexes in carcinoma patients, 1995, Br. J. Cancer 72: 934-938 (Abstract).
|Graef, Materials for low Curie temperature induction hearing of tumors (Hyperthermia), 1991, Ph.D. Dissertation, University of Arizona (Abstract).
|Gruttner et al., Synthesis and Antibody Conjugation of Magnetic Nanoparticles with Improved Specific Power Absorption Rates for Alternating Magnetic Field Cancer Therapy, 2007, J. Magnetism and Magnetic Materials 311:181-186 (Dec. 13, 2006-available online).
|Hadden, The immunology and immunotherapy of breast cancer: an update, 1999, Int. J. Immunopharacol., 21(2): 79-101 (Abstract).
|Hadden, The immunology and immunotherapy of breast cancer: an update, 1999, Int. J. Immunopharmacol. 21: 79-101 (Abstract).
|Hergt et al., Physical limits of hyperthermia using magnetite fine particles, 1998, IEEE Trans. On Mag., 34: 3745-3754.
|Hiergeist et al., Application of magnetic ferrofluids for hyperthermia, 1999, J. Magnetism and Magnetic Materials 201: 420-422.
|Hynynen et al., State of the art in medicine: Hyperthermia in cancer treatment, 1990, Investigative Radiology, 2: 824-834.
|Ibrahimi et al., Role of CD36 in membrane transport of long-chain fatty acids, 2002, Curr. Opin. Clin. Nutr. Metab. Care 5: 139-145 (Abstract).
|International Search Report for PCT/US02/23650, Apr. 22, 2003.
|Isaacs et al., Humanized anti-CD4 monoclonal antibody therapy of autoimmune and inflammatory disease, 1997, Clin. Exp. Immunol, 110: 158-166 (Abstract).
|Isaacs et al., Humanized monoclonal antibody therapy for rheumatoid arthritis, 1992, Lancet 240:748-752 (Abstract).
|Ivkov et al., "Application of high amplitude alternating magnetic fields for heat induction of nanoparticles localized in cancer", 2005, Clinical Cancer Research 11(19 Suppl):7093s-7103s.
|Ivkov et al., Application of High Amplitude Alternating Magnetic Fields for Heat Induction of Nanoparticles Localized in Cancer, 2005, Clin. Can. Res. 11(19Suppl):7093s-7103s.
|Jiang et al., Vaccination with a mixed vaccine of autogenous and allogenic breast cancer cells and tumor associated antigens CA15-3, CEA and CA125-results in immune and clinical responses in breast cancer patients, 2000, Cancer Biother. Radiopharm. 15: 495-505 (Abstract).
|Jones et al., Evaluation of ferromagnetic materials for low-frequency hysteresis heating of tumors, 1992, Physics in Medicine and Biology 37: 293-299.
|Jones et al., Experimental examination of a targeted hyperthermia system using inductively heated ferromagnetic microspheres in rabbit kidney, 2001, Physics in Medicine and Biology 46: 385-398.
|Jordan et al., Inductive heating of ferromagnetic particles and magnetic fluids: physical evaluation of their potential for hyperthermia, 1993, Int. J. Hyperthermia 9: 51-68.
|Jordan et al., Magnetic Fluid Hyperthermia (MFH) in Scientific and Clinical Applications of Magnetic Carriers, Hafeli et al., ed, 1997, 569-595 USA.
|Jordan et al., Magnetic fluid hyperthermia (MFH): Cancer treatment with AC magnetic field induced excitation of biocompatible superparamagnetic nanoparticles, 1999, J. Magnetism and Magnetic Materials, 201: 413-419.
|Jordan et al.., Cellular uptake of magnetic fluid particles and their effects on human adenocarcinoma cells exposed to AC magnetic fields in vitro, 1996, Int. J. Hyperthermia 12: 705-722.
|Kobayashi et al., Targeting hyperthermia for renal cell carcinoma using human MN antigen-specific magnetoliposomes, 2001, Japanese J. of Cancer Res. 92: No. 10 (Abstract).
|Krishnamurthy et al., Molecular and biologic markers of premalignant lesions of human breast, 2002, Adv. Mat. Pathol. 9: 185-197 (Abstract).
|Lakhani et al., The pathology of familial breast cancer: predictive value of immunohistochemical markers estrogen receptor, progesterone receptor, HER-2, and p53 in patients with mutations in BRCA1 and BRCA2, 2002, J. Clin. Oncol. 20: 2310-2318 (Abstract).
|Lapetti et al., Controlling tumor-derived and vascular endothelial cell growth: role of the 4Ff2 cell surface antigen, 2001, Am. J. Pathol. 159: 165-178 (Abstract).
|Luderer et al., Glass-ceramic-mediated, magnetic-field-induced localized hyperthermia: Response of a murine mammary carcinoma, 1983, Radiation Research 94: 190-198.
|Luftner et al., Nuclear matrix proteins as biomarkers for breast cancer, 2002, Expert Rev. Mol. Diag. 2: 23-3 (Abstract).
|Ma et al., Molecular cloning and expression analysis of feline melanoma antigen (MAGE) obtained from a lymphoma cell line, 2001, Vet. Immunol. Immunopathol. 83: 241-252 (Abstract).
|McDevitt et al., Tumor Therapy with targeted atomic nanogenerators, 2001, Science, 294: 1537-1550.
|McTernan et al., Increased resistin gene and protein expression in human abdominal adipose tissue, 2002, J. Clin. Endocrinol. Metab. 87: 2407 (Abstract).
|Menard et al., Role of Her2 gene overexpression in breast carcinoma, 2000, J. Cell Physiol. 182(2): 150-162 (Abstract).
|Mitsumori et al., Development of intra-arterial hyperthermia using a dextran-magnetite complex, 1994, Int. J. Hyperthermia 10: 785-793.
|Mitsumori et al., Targeted hyperthermia using dextran magnetite complex: A new treatment modality for liver tumors, 1996, Hepato-Gastroenterology, 43: 1431-1437.
|Miyawaki et al., Inhibition of gastric inhibitory polypeptide signaling prevents obesity, 2002, Nat. Med. 8: 738-742 (Abstract).
|Molina et al., Tastuzumab (herceptin), a humanized anti-Her2 receptor monoclonal antibody, inhibits basal and activated Her2 ectodomain cleavage in breast cancer cells, 2001, Cancer Res. 61: 4744-4749 (Abstract).
|Molina et al., Trastuzumab (herceptin), a humanized anti-Her2 receptor monoclonal antibody, inhibits basal and activated Her2 ectodomain cleavage in breast cancer cells, 2001, Cancer Research Jun. 15, 61(12) 4744-4749 (Abstract).
|Moritani et al., Availability of CD10 immunohistochemistry as a marker of breast myoepithelial cells on paraffin sections, 2002, Mod. Pathol. 15: 397-405 (Abstract).
|Moroz et al., Targeting liver tumors with hyperthermia: Ferromagnetic embolization in a rabbit liver tumor model, 2001, J. of Surgical Oncology 78: 22-29.
|Moseley et al., HMFGI antigen: a new marker for carcinomatous meningitis, 1989, Int. J. Cancer 44: 440-444 (Abstract).
|O'Hanlon et al., An immunohistochemical study of p21 and p53 expression in primary node-positive breast carcinoma, 2002, Eur. J. Surg. Oncol. 28: 103-107 (Abstract).
|Opezzo et al., Production and functional characterization of two mouse/human chimeric antibodies with specificity for the tumor associated Tn antigen, 2000, Hibridoma 19: 229-239 (Abstract).
|Palmu et al., Expression of C-KIT and HER-2 tyrosine kinase receptors in poor-prognosis breast cancer, 2002, Anticancer Res. 22: 411-414 (Abstract).
|Parker et al., E-cadherin as a prognostic indicator in primary breast cancer, Br. J. Cancer 85: 1958-1963 (Abstract).
|Paulus et al., Corrosion analysis of NiCu and PdCo thermal seed alloys used as interstitial hyperthermia implants, 1997, vol. 18: 1609-1614 (Abstract).
|Peasley, Destruction of human immunodeficiency-infected cells by ferrofluid particles manipulated by an external magnetic field: mechanical disruption and selective introduction of cytotoxic or antiretroviral substances into target cells, 1996, Medical Hypotheses, 46: 5-12, No. 1 England (Abstract).
|Peterson et al.., Effect of multiple, repeated doses of radioimmunotherapy on target antigen expression (breast MUC-1 mucin in breast carcinomas, 1997, Cancer Res. 57(6): 1103-1108 (Abstract).
|Petrarca et al., Isolation of MUCI-primed B lymphocytes from tumour-draining lymph nodes by immonomagnetic beads, 1999, Cancer Immunology Immunotherapy 47 No. 5: 272-277 (Abstract).
|Ramakrishna et al., Generation and phenotypic characterization of new human ovarian cancer cell lines with the identification of antigens potentially recognizable by HLA-restricted cytotoxic T cells, 1997, Int. J. Cancer 73: 143-150 (Abstract).
|Reiter et al., Recombinant immunotoxins in targeted cancer cell therapy, 2001, Adv. Can. Res. pp. 93-124.
|Richman et al., Systemic radiotherapy in metastatic breast cancer using 90Y-linked monoclonal MUC-1 antibodies, 2001, Crit Rev Oncol Hematol 38: 25-35, Ireland (Abstract).
|Segal et al., Introduction: bispecific antibodies, 2001, J. Immunol. Methods, 248: 1-6.
|Shinkai et al., Antibody-conjugated magnetoliposomes for targeting cancer cells and their application in hyperthermia, 1994, Biotechnol. Appl. Biochem. 21: 125-137.
|Shinkai et al., Intracellular hyperthermia for cancer using magnetite cationic liposomes: In vitro study, Jpn, 1996, J. Cancer Research 87: 1179-1183.
|Shinkai et al., Targeting hyperthermia for renal cell carcinoma using human mn antigen-specific magnetoliposomes, 2001, Jpn. J. Cancer Res. 92: 1138-1145 (Abstract).
|Snijdewint et al., Cellular and humoral immune responses to MUC1 mucin tandem-repeat peptides in ovarian cancer patients and controls, 1999, Cancer Immunol. Immunother. 48: 47-55 (Abstract).
|Spizzo et al., Prognostic significance of Ep-CAM and Her-2/neu Overexpression in invasive breast cancer, 2002, Int. J. Cancer 98: 883-888 (Abstract).
|Stockhammer et al., Vascular endothelial growth factor in CSF: a biological marker for carcinomatous meningitis, 2000, Neurology: 54: 1670-1676 (Abstract).
|Suo et al., EGFR family expression in breast carcinomas. C-erbB-2 and c-erbB-4 receptors have different effects on survival, 2002, J. Pathol. 196: 17-25 (Abstract).
|Suzuki et al., Preparation and characteristics of magnetite-labelled antibody with the use of poly(ethylene glycol) derivatives, 1995, Biotechnol. Appl. Biochem. 21: 335-345.
|Suzuki et al.., Studies on liposomal ferromagnetic particles and a technique of high frequency inductive heating, Jpn, 1990, J. Soc. Cancer Ther., 25: 2649-2658.
|Takegami et al., New ferromagnetic bone cement for local hyperthermia, 1998, J. Biomedical Materials Research 43: 210-214 (Abstract).
|Taylor et al., Shed membrane fragment-associated markers for endometrial and ovarian cancers, 2002, Gynecol. Oncol. 84: 443-448 (Abstract).
|Torchilin et al., Magnetic sephadex as a carrier for enzyme immobilization and drug targeting, 1985, J of Biomedical Materials Res. 19: 461-466, No. 4 United States (Abstract).
|Tucker et al., Defining the heating characteristics of ferromagnetic implants using calorimetry, 2000, J. of Biomedical Materials Research 53: 791-798 (Abstract).
|Van Poznak et al., Assessment of Molecular Markers of Clinical Sensitivity to Single-Agent Taxane Therapy for Metastatic Breast Cancer, May 1, 2002, J. Clin. Oncol., 20(9):2319-2326.
|Winthrop et al., Development of a hyperimmune anti-MUC-1 single chain antibody fragment phage display library for targeting breast cancer, 1999, Clin Can Research Oct; 5(10 suppl.): 3088-3094.
|Wong et al., Human scFv antibody fragments specific for the epithelial tumor marker MUC-1, selected by phage display on living cells, 2001, Cancel Immunol. Immunother. 50::93-101 (Abstract).
|Wong et al., Human scFv antibody fragments specific for the epithelial tumour marker MUC-1, selected by phage display on living cells, 2001, Cancer Immunol. Immunother, Apr.; 50(2): 93-101 (Abstract).
|Wu et al., Activated matrix metalloproteinase-2-a potential marker of prognosis for epithelial ovarian cancer, 2002, Gynecol. Oncol. 84: 126-134 (Abstract).
|Xu et al., Altered tumor necrosis factor-alpha (TNF-alpha) processing in adipocytes and increased expression of transmembrane TNF-alpha in obesity, 2002, Diabetes 51: 1876-1883 (Abstract).
|Young et al., A pulsed power supply system for producing high intensity magnetic and electric fields for medical applications, IEEE Conference Record-Abstracts, PPPS-2001 Pulsed Power Plasma Science 2001, 28th IEEE International Conference on Plasma Science and 13th IEEE International Pulsed Power Conference (Cat. No. 0ICH37255) 2001, pp. 322, USA (Abstract).
|Citing Patent
|Filing date
|Publication date
|Jan 24, 2011
|Jun 24, 2014
|Actium BioSystems, LLC
|System for defining energy field characteristics to illuminate nano-particles used to treat invasive agents
|Jan 24, 2011
|Mar 3, 2015
|Endomagnetics Limited
|System for correlating energy field characteristics with target particle characteristics in the application of an energy field to a living organism for imaging and treatment of invasive agents
|Sep 7, 2011
|Apr 14, 2015
|Choon Kee Lee
|Thermal apparatus
|Jul 13, 2015
|Jun 20, 2017
|Endomagnetics Limited
|Apparatus for the generation of an energy field for the treatment of cancer in body cavities and parts that are cavity-like
|Aug 21, 2012
|Jun 27, 2017
|Endomagnetics Limited
|Treatment of cancer in body cavities and parts that are cavity-like
|Apr 19, 2002
|Oct 24, 2002
|Kensuke Yoshizawa
|Vacant channel searching method
|Mar 11, 2010
|Sep 15, 2011
|Empire Technology Development, Llc
|Eddy current induced hyperthermia using conductive particles
|Aug 21, 2012
|Aug 27, 2014
|Apparatus for the generation of an energy field for the treatment of cancer in body cavities and parts that are cavity-like
|Aug 21, 2012
|Nov 25, 2015
|Apparatus for the generation of an energy field for the treatment of cancer in body cavities and parts that are cavity-like
|Aug 21, 2012
|Mar 7, 2013
|Actium BioSystems, LLC
|Apparatus for the generation of an energy field for the treatment of cancer in body cavities and parts that are cavity-like
|Sep 5, 2014
|Mar 12, 2015
|Google Inc.
|Nanoparticle phoresis
|U.S. Classification
|International Classification
|Cooperative Classification
|European Classification
|Feb 14, 2006
Owner name: TRITON BIOSYSTEMS, INC., MASSACHUSETTS
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:FOREMAN, ALLAN;DAUM, WOLFGANG;REEL/FRAME:017166/0202;SIGNING DATES FROM 20051031 TO 20051114
Owner name: TRITON BIOSYSTEMS, INC., MASSACHUSETTS
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:FOREMAN, ALLAN;DAUM, WOLFGANG;SIGNING DATES FROM 20051031 TO 20051114;REEL/FRAME:017166/0202
|Aug 28, 2008
Owner name: NANOTX, INC., CALIFORNIA
Free format text: MERGER;ASSIGNORS:TRITON BIOSYSTEMS, INC.;ONCOLOGIC, INC.;REEL/FRAME:021450/0525
Effective date: 20080327
Owner name: NANOTX, INC.,CALIFORNIA
Free format text: MERGER;ASSIGNORS:TRITON BIOSYSTEMS, INC.;ONCOLOGIC, INC.;REEL/FRAME:021450/0525
Effective date: 20080327
|Aug 29, 2008
Owner name: ADURO BIOTECH, CALIFORNIA
Free format text: FICTITIOUS BUSINESS NAME STATEMENT;ASSIGNOR:NANOTX CORP.;REEL/FRAME:021450/0900
Effective date: 20080422
Owner name: ADURO BIOTECH,CALIFORNIA
Free format text: FICTITIOUS BUSINESS NAME STATEMENT;ASSIGNOR:NANOTX CORP.;REEL/FRAME:021450/0900
Effective date: 20080422
|Jun 11, 2012
Owner name: ASPEN MEDISYS, LLC, MASSACHUSETTS
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:ADURO BIOTECH;REEL/FRAME:028353/0473
Effective date: 20120605
|Jan 9, 2015
|Maintenance fee reminder mailed
|May 31, 2015
|Lapse for failure to pay maintenance fees
|Jul 21, 2015
|Expired due to failure to pay maintenance fee
Effective date: 20150531


text:
|Start new thread in this topic | Flip this thread | Refresh the display
MIrena Coil and weight gain!!!!!! Anyone else have it?(277 Posts)
I have had the mirena coil for just over a year now and have put on massive amounts of weight!! I have put on around 1 1/2 stone!!!!!! I go to the gym at least 3 times a week but try to go 4. i do a hard work out for an hour and am actually quite fit for a fatty!! But what is really annoying is the fact that despite all this I never seem to lose weight. Infact it is the oppposite the pounds just seem to creep on. It is really getting me down now. Has anyone else had the same problems with the mirena coil? I am going to get an appointment with the doctors hopefully next week but just wanted to hear from anyone else who may of had the same problems!
I had my mirena coil fitted about 8-10 weeks ago. I thought it would be the ideal solution for contraception and help with quite heavy periods. All seemed to be going quite well and on my six week check up I did say at the clinic that I had put on 7 pounds quite quickly - was the coil to blame? I was told it was because alot of people relax more about their bodies and their periods are lighter that they seem to perhaps eat more?? (and toblerone was BOGOF at Tesco?), but I don't think this is the case shock . I am the heaviest I have ever been and am not happy if the coil is having this affect on my body. The plus side is the lighter non-existant periods but if your body isn't expelling much is it just harbouring it all and putting it in your bigger size jeans?? I will have to seriously consider having it taken out and going back on the pill - what other choice is there???
This is my first post here. It is so good to read other peoples' experiences. I have struggled with my weight all my life. I discovered weight watchers though and it really worked for me - I lost 4 stone and kept it off. This was before my coil was fitted. After a fourth baby, I decided that I didn't want any more kids and the doctor recommended the coil as a good contraceptive solution.
I noticed the weight problems from very early on - within the first two months - I really struggled to stay the same weight and if I wasn't walking every day and eating healthily, I gained weight.
This along with lethargy, moodiness, depression, ibs, weak bladder conrol, insomnia, restless legs and big sore boobs does not make for a happy camper!
My doctor said that there were rarely any side effects with the mirena so I never would have put all these symptoms together. Now that I have done my research, I can see that it is most certainly my coil that has left me in a physical and emotional mess.
I had it removed 3 days ago and have now taken my period and it has never felt so good - like a release. Yes the bleeding is a nuisance, but I really feel that its right for me. Girls who have had success with this are very lucky, those of us who haven't been so lucky, would need to think again. I have a few friends who have a mirena fitted and bewtween us all we didn't really add up all the symptoms we were having. We were putting down to our age - only in our mid-thirties mind you-they are all making Gp appointments for a chat.
Good luck to you all, you deserve to feel better and be in control of your body.
I totally relate to this - I had a Mirena for 18 months during which I gained weight for the first time in my life and became very spotty. I also had hideous breast tenderness and mastitis!!
Had it removed and skin cleared up and weight fell off, boobs returned to normal - am convinced that for some, hormone in Merina is not a good thing.
Hi blowsy, how soon after removal did your boobs go down and the weight start to drop? Did your GP have anything to say about the side effects you experienced, and how they went away when had it removed?
I just don't know why they are so keen for us all to have them fitted. They should point out that these side effects are a possibility and that we should look out for them.
I am just glad that I have discovered why I feel the way I do now, and not in 5 or 10 years' time. I want to be 'fab at 40' not 'fat at 40'!!!!
Will check in again soon.x
I'm so glad I have found this thread, i thought I was going mad or just being weird.
I had my 2nd child 14 weeks ago and had the mirena fitted about 5-6 weeks ago and at my check up said all was well but this last week I cannot get full. I am constantly hungry despite eating reasonable portions of healthy food. Prior to mirena I was also doing quite well with losing baby weight now it has come to a dead stop and if anything I am doing moreexercise etc in my days than before. I have always been slightly overweight but determined after this baby to get to my correct weight but with this hunger I can't see it being possible as I am bloody miserable and obsessed by food all the time. I don't really have other choices though due to family history I can't have the pill and my hubby and I am are very fertile, both babies on first time trying, so don't wanna take chances. Has anyone experienced this hunger and how did you cope with it?
Hi happyjot
My hunger pangs started at about 6 or 7 weeks too. I gave my mirena 2 1/2 years, thinking it would all settle down. I thought it was just me being greedy as far as the appetite was concerned, but having found this thread, i know i was not going crazy. It affected my whole life - my husband and 4 kids would vouch for that! I also felt like the more I exercised the more I weighed. I have successfully lost weight and maintained it in the past, between children, but I could just not do it with that thing inside me. I am almost 3 weeks since removal and I feel much,much better.
The appetite has reduced already - I now eat my meals and enjoy them and then forget about it until I am hungry again. I gained around 14 lbs while I had it in, and it would have been more if I hadn't been walking everyday and eating healthily as much as I possibly could.
As for contraception, my hubby has agreed to go for the snip!! Sorry I can't advise you on your situation. maybe talk to your doctor about the copper coil with no hormone in it?
Ive had the mirena coil fitted since july 07, i bled for 6 weeks when it was fitted,then my heavy periods seemed to settle down,to almost none or a one day event.BUT........... 24 days ago i started bleeding really heavy,far worse than before i had the coil fitted,going through 7 pairs of jeans in 5 days at one point,i feel totally drained,its still really heavy after 24 days.
And as for the weigh gain,ive put 2 stone on in 13 months,which i just cant seem to shift,my stomach seems to be swollen.
I want it taken out asap,but as im constantly bleeding,so i cant go to my gp,until ive stopped
Has anyone else experience this kind of problem with the mirena? Im wondering if it has become dislodged! Hope someone can help me out,as i feel as thought im going to bleed to death.
I had mirena fitted 3 years ago and I am still 8st the same weight I was before.
I have no periods at all. I do occasionally get acute ovulation pain on alternative sides.
Still get a bit emotional once a month for a day or so, sore boobs etc. but generally everything ok.
Much better than heavy periods and PMT.
Its me again! no one really answered my question,so im trying again,as im getting desperate!
Ive now had a period for 29 days,and losing such huge clots, gone through so many clothes,and bed sheets.
I have a mirena coil fitted,and my periods had almost stopped, but this has just drained me completely, as well as gaining 2 stones in weight in 13 months.
Ive also got a pain in my lower right side of my stomach, and feel pretty lousy.
god if only i had found this site earlier!!!!
I had the mirena fitted 4 and half years ago. I have suffered with what was thought to be major depession then that changed to extreme pms for which the g.p prescribed yet more anti depressants. I have virtually wrecked my marriage cos of my mood swings and whatever he does is just not good enough (angry) my poor kids especially the eldest says you've got the look and goes upstairs. I have had extreme bouts of anger where I have physically ripped doors off. I can't bloody remember hardly anything and am always so confused (hmm) and have suffered bad headaches/migraines. i have even been so low that i tried to top me self. with the weight i have always had a bit of a problem but since the coil was put in I am like a bloody beached whale even though i dont sit down to eleven at night normally always on the bloody go! Non of this was my personality I had always been known as being lively and bubbly and great fun to be around (not now)
I was givien this miracle coil to stop the heavy bleeding that i suffered for 3 weeks out of 4.what a price to pay to not bleed lucky me NOT. I am going straight to get the coil taken out and hopefully get back to my former self. Wouldn't mind but I didn't think anything about the coil till ablout 3 days ago and thought hold on you've been like this since it was fitted could this be whats wrong with me then hallujah i found that i am not the only one thanks girls thought i was completely mad.
hi tobleedornottobleed
Please keep me posted as to how you get on, I tried to get mine out last week,but now its disapeared, got to go for a scan now,to try and find the bloody thing, im really fed up of it,i just want it out asap
I've just come across this site and am amazed that so many women are experiencing the same negative symptoms that I have been. I wanted to share my symptoms with you in case you find solace in them like I did reading about others (when I thought I was going mad).
I had the mirena fitted in July 07 following a laparoscopy for endometriosis. I had happily been using the depo injection for 4 years before hand with no symptoms at all.
My endo specialist advised this was the best form of treatment for endo and also the best option for preserving fertility for later in life.
Almost immediately I had excruciatingly painful breasts (which lasted for 9 months) so that high impact exercise was ruled out during that time. My breasts also grew and I'm now a full cup bigger than I was and I'm now almost going into the next cup size (a 2 cup increase).
I have also steadily gained weight despite going to weight watchers religiously and following the program (no cheating!) as well as intensive exercise. I have now put on 6 kgs (1 stone) which is very depressing.
As a result of this constant weight gain I have seen a dietician who has been monitoring my daily food intake, as well as my weight watchers leader, and both feel my food intake is extremely healthy and shouldn't be resulting in this constant gain. I have even been tested for food intolerances to see if this was causing the weight gain, but all tests have come back negative.
I have also been able to feel the coil almost daily, often getting cramping and pain down one leg. It sometimes feels like it catches on something which sends a wave of nausea through me.
As a teenager I suffered terribly from bad acne but went on roacutan to clear it up. Since going on the mirena my acne has slowly but surely returned.
The only benefit for me has been the complete stopping of periods, which have been traditionally heavy and painful, and I can now have sex pain free (but this is probably more due to the laparoscopy than the mirena).
I think the mirena could work wonders for people who are suited to it but it clearly has some very negative side effects for others.
I have become increasingly depressed over my constant weight gain and acne return and I whilst I'm not unhappy that my breasts are now bigger, the pain I experience with them outweighs the positives.
I have a doctors appointment next week and I will be having it removed as I think being happier and weighing less is far more important than period free and fat! I will post an update once it has been removed - fingers crossed it will be about weight loss and improved happiness!
Hi Coomsey,
Glad to hear I am not the only women going nuts after having the mirena fitted, I only had mine in on 31st May this year and thank god it is coming out on Monday, I am counting down the hours.
I had it fitted purely for contraception and nothing else, periods were fine etc. Since having it fitted dreadful stomach cramps, have had a cist appear on my right ovary which I am told can be a side effect... great did not know about that one along with weight gain, sporadic periods and the most awful mood swings my Husband cannot wait for me to get rid of this. I was before a very happy go lucky person who has now become moody, miserable and suddenly developed a sweet tooth which I have never had.
I think this is good for some women out there, but I have more bad than good reports about and am not keen at all. Roll on Monday morning when I be skipping out the Doctors with a huge sigh of relief. Would be interested in your update after removal, I just hope my system settles down and more importantly the weight starts to shift.
I too have gained over 1 stone since my Mirena was put in last autumn, I seem to be constantly hungry! On the plus side I have virtually no periods and my boobs have grown about a size!
I'm giving Slimming World a go first, but if that's not successful, it's coming out!
Hi, I have had the mirena coil removed in July and a Nova T coil put in its place. Although my first period was hell, the mood swings and headaches have all but disappeared which is great. The downside is that the weight has not come off as yet but the good news is that at least the weight is not getting worse. Any idea how long it was for others to see weight loss??
Firstly, thanks to everyone who has taken the time to write something! I have been so relieved to read it all, without it I think I would feel alot worse. My experience with the mirena has been the same as most. Weight gain. I have never ever had a problem with my weight despite 2 kids and after 18months of the coil I have gained 1 1/2 stone. The worst of it is, alot of the weight is on my stomach which is unusual for me, if I have ever gained a pound ere and there it has always been bum and thighs. My stomach looks bloated. Nothing has changed in my diet or lifestyle in fact I would say I eat way more sensibly now. I have had the coil removed for 3 months now and nothing has changed, I have cut out ANY treats and have been to gym which I never used to do and not a pound have I shifted. Very depressing. Did anyone else suffer with itching? I felt instant relief when it was taken out.... like a fire had been put out? Can anyone tell of having lost the weight and how long and the measures
I have had only 1 migraine in 40 years, then I had the Mirena put in in May and had 3 and constant dull headaches. Doctor hasn't mentioned that it could be Mirena, she just says I have to get on with dealing with the migraine. One was so bad I couldn't talk ( migraine with aura) and hardly see and ended up in hospital. Perhaps it could be the Mirena, I just thought it was my age at 41!!
What does anyone think???? HELP!!
Message withdrawn
This is really interesting. I've had my Mirena for 3 1/2 years, and from a contraception and no periods point of view it's great.
My mum has always said she thought it hadn't helped my weight, and I dismissed the idea, but having looked at the list of side effects and seen some other stuff that I have been experiencing (cysts, acne, depression) am seriously considering having it removed.
Time to send hubby for the snip methinks!
Hi Everyone
I wish I had came across this website sooner. I have had my mirena coil in for a year and a half. I have put on 3 stone and feel like a zombie as I am so tired. I am getting it taken out in 2 weeks time and I cant wait. I am so embarrassed about my weight gain that I dont like going out. I cant get into the clothes I love and I feel like a 90 year old. My appetite has increased so much and I am ravenous for sugary stuff. I just feel like a "thing" and not a person ( Has anyone had similar experiences? Has anyone got the mirena out and been transformed back to their former self?
oh, bloody hell...I'm having one put in in a few weeks.
Might have a copper instead...
Hi, got a smear done, mirena taken out and T Safe copper coil put in today. I hope the weight shifts soon!! not to mention the fluid retention!! fingers crossed!
I have also had the Mirena coil for about 3 years. My weight has steadily increased by about half a stone. My legs feel massive at times from fluid retention, I do now suffer from headaches, and I am on a topical anitbiotic lotion for my skin as I was getting Acne breakouts around the jaw line. I didn't have any of these things before. Maybe mildly but very occasionally. I mean we all feel bloated at times, get headaches and have a few spots but not like this. I put the weight gain down to feeling content and possibly my age as I am now in my early thirties. When I first had it put in my moods were awful, my legs blew up and I had a some ruptured cycts on my ovaries where I had to have a little trip to A & E. I am still having periods but they are lighter than before. You have to way up the symptoms you get from this compared to other contraception and pregnancy.Anyway all in all I am fed up with this and it has to be replaced next year anyway. My husband has made an appointment to have his vasectomy over Christmas so as soon as we have the all clear it def. coming out.....I can't wait.
Hi Beautie
I have fluid retention as well my face and hands swell up and my skin is sore with the tightness. I got rashes of spots on the back of my neck and round my hairline. I am hoping I can recover from the nightmare of the mirena quickly now that my copper coil is in. I had the copper one before and didnt experience any side effects such as this. Good luck and shake your husbands hand for me for being so supportive to you!
I have had the Mirena for just over a year - have no periods at all but initially gained about 1.5 stone!! Have managed to lose 10lbs and keeping it off, but feel generally slower and more sluggish. Want to tackle the rest of the weight gain - but really don't eat that much! Damn coil - but it does the job it's designed for I suppose...
|Start new thread in this topic | Flip this thread | Refresh the display
Join the discussion
Registering is free, easy, and means you can join in the discussion, get discounts, win prizes and lots more.Register now
Already registered with Mumsnet? Log in to leave your comment or alternatively, sign in with Facebook or Google.
Please login first.

subset: commoncrawl


text:
Condition: Brand new Original, 12 months warranty.
Tech Specs:
Device Type : Network adapter
Networking: Connectivity TechnologyWireless
Data Link Protocol :Bluetooth 2.0 EDR
Data Transfer Rate:3 Mbps
Frequency Band: 2.4 GHz
Max Range Open Space: 33 ft
Antenna; Antenna
Internal integrated : Expansion / Connectivity
Interfaces 1 x USB
Connections: 1 x USB - 4 pin USB Type A Software / System Requirements
OS Required: Microsoft Windows 2000, Microsoft Windows XP
Part Number:
Dell P/N : MU833 430-2366 RJ421 CW725 0CW725
Fit Laptops:
Dell Latitude D400, D410, D420, D430, D505, D510, D520, D530, D531, D610, D620, D630/D630c, D631, D800, D810, D820, D830, X1, X300
Dell Inspiron 300M, 510M, 630M, 640M/E1405, 1410, 1420, 1520, 1521, 1525, 1720, 1721, 6000, 6400/E1505, 8500, 8600, 9100, 9200, 9300, 9400/E1705
Dell Precision M20, M60, M70, M90, M4300
Dell XPS M140, M1330, M170, M1210, M1710, M1730, M2010
DELL Vostro 1310, 1400/1420, 1500, 1700, DELL 500
Wireless range of up to 30 ft
Offers 128-bit encryption security
Enhanced Data Rate (EDR) capability allows for data transfer rates of up to 3 Mbps
Compatible with Dell Inspiron 1525/ 1526 Laptops
Enjoy cable-free computing between Bluetooth-enabled keyboards, mice, mobile phones, headsets, printers and more, with the Wireless 355 Bluetooth® Card from Dell. This card provides enhancements in technology, speed, and compatibility. This Bluetooth Card for the Windows Vista® operating system is based on the Bluetooth 2.0 standard with EDR (Enhanced Data Rate) technology. EDR technology boosts bandwidth while reducing power consumption and maintaining backward compatibility with older Bluetooth devices. It offers data transfer rates of up to 3 Mbps so you can transfer files with ease. This product has been tested and validated on Dell systems and is compatible with Dell Inspiron 1525/ 1526 Laptops. It is supported by Dell Technical Support when used with a Dell system.
1x Dell Wireless 355 Bluetooth V 2.0+EDR Module Card


text:
DSM Computer introduced their Infinity 96M1594-ATXQ67 19-inch industrial computer. The Infinity 96M1594-ATXQ67 supports the second generation Intel Core processor with four or two cores. It features an industrial ATX motherboard, Intel Q67 chipset, four DIMM slots (up to 32 GB), twelve external and two internal USB 2.0 ports, dual GigaBit LAN, two PS/2, two COM, audio, DVI-I and display port.
The DSM Infinity 96M1594-ATXQ67 has seven slots: a PCI Express x8 (one lane), a PCI Express 2.0 x16, a PCI Express 2.0 x16 (four lanes) and four PCI-slots. The industrial computer features four 5.25-inch drive bays and a 3.5-inch bay. A SATA removable frame is also available (upon request). All drives and controls are protected behind a lockable metal door.
DSM Infinity 96M1594-ATXQ67 Features
- Intel Core i3-2120 3.3 GHz / 3 MB cache / 2 cores
- Intel Core i7-2600 3.4 GHz / 8 MB cache / 4 cores (optional)
- Intel Core i5-2400 3.1 GHz / 6 MB cache / 4 cores (optional)
- Intel Pentium G850 2.9 GHz / 3 MB cache / 2 cores (optional)
- Socket H (1155), DMI (Direct Media Interface) with at least 5 GT/s (GigaTransfers per second)
- Intel Q67 chipset
- Four DIMM sockets, DDR3 1333 SDRAM, maximum memory 32 GB (max. 3 GB for 32 bit OS)
- Intel HD Graphics (partially integrated in processor), DirectX 10.1
- Dual Intel GigaBit LAN, 10/100/1000 Base-T/TX support, full duplex, 2 x RJ45 port, one LAN with AMT 7.0, Intel vPro
- Intel HD audio, 5.1 CH
- Supports four SATA II 300 drives, two SATA III 600 drives, RAID 0, 1, 0+1, 5
- Two PS/2, DVI-I, DisplayPort 1.1, two COM
- Audio (line-In, line-Out, mic), on request LPT
- 14 x USB 2.0, 12 x external, 1 x internal, 1 x internal for USB Stick
- Seven slots: a PCI Express x8 (one lane), a PCI Express 2.0 x16, a PCI Express 2.0 x16 (four lanes) and four PCI-slots
- Four 5.25-inch drive bays and a 3.5-inch bay
More info: DSM Computer


text:
Manabadi AP EAMCET Medical Results 2016 Rank Card download: The AP Eamcet 2016 results for the medical and agriculture stream are going to be released today at 11 AM by Andhra Pradesh Chief Minister Sri Nara Chandra Babu Naidu. This enlargement is announced by Human Resource minister Ganta Srinivasa Rao on May 20, 2016. Hence the students those who had taken written the Eamcet medical and Agriculture exam 2016 are eagerly looking for their AP EAMCET results 2016 as well as rank cards also. Manabadi AP EAMCET Medical results 2016 are hereby informed to check their results from the official website or from the direct link provided below.
Eenadu Pratibha AP EAMCET Results 2016 for medical
But from then the students those who wrote written the exam are eagerly waiting for the results declaration. A total of 98,750 students were appeared for AP EAMCET 2016 written the exam. The results of the AP Engineering examinations were declared previously, but the results of medical examinations and agriculture were held for some time because of supreme courts mandating NEET decision for all states. But SC had passed an ordinance now that postponing NEET for the next year. Here we have given AP EAMCET Medicine results 2016 by Eenadu, sakshi, Manabadi, schools9.
Manabadi AP EAMCET Medicine Results 2016 Toppers list
Jawaharlal Nehru Technological University, Kakinada (JNTU Kakinada) is a public university located in Kakinada, East Godavari district, north of the Indian state of Andhra Pradesh. It is one of the main of India teaching universities focusing on engineering. The results is going to be released today at 11 AM by the Andhra Pradesh Chief Minister Sri Nara Chandra Babu Naidu garu. Now, Medical and Agriculture Students who had taken the written examination are eagerly looking for their own AP EAMCET Results 2015 medical. Here below we have mentioned top 10 toppers list of AP EAMCET Medicine examination. So candidates can download their AP EAMCET Medical results 2016 and also download AP EAMCET Rank card 2015 Medical.
హేమలత- 1- 156( కర్నూలు)
సాత్విక్రెడ్డి-2- 155(రంగారెడ్డి)
యజ్ఞప్రియ -3 -153( హైదరాబాద్)
చిట్లూరి నేహ-4- 152(కృష్ణా)
సాహితీ సావిత్రి-6- 152(హైదరాబాద్)
పి.శైలజ-7- 150(విశాఖపట్నం)
బి.గ్రీష్మా మీనన్-8-150(వరంగల్)
డి.శివకుమార్-9-150( నల్గొండ)
కె.సాయి ప్రదీప్రెడ్డి-10-150(ప్రకాశం)
How to Check AP EAMCET Medical & Agriculture Results 2016 Rank Card?
- Candidates should visit the official website or the direct link provided below.
- The homepage will be displayed.
- Click on AP EAMCET Results 2016.
- Enter all the required details in the provided fields.
- Click on submit button.
- The results will appear on the screen.
- Check the results.
- Download/ Take a printout for further reference.
Download AP EAMCET Medicine Rank Card 2016


text:
GOMES GAMING | Executives
Vast Experiences. Refined Expertise.
The GGI team is well aware that casinos under management transition will be subject to attack from every direction imaginable. During these difficult periods, owners can either prepare for this onslaught or become victims of it. GGI is the best possible solution to help creditors/owners get through the initial several years of transition, a period of time during which they are most vulnerable.
Of course in order to successfully accomplish this, more is needed than a management company that can just protect against these kinds of expected predations. A company that can also insure that revenues and profits will be maximized is also necessary in order to insure that when creditors/owners are ready to sell casino assets, they will get the maximum returns possible.
GGI has both the proven ability and experience to protect casino assets during this most vulnerable period, and also have a proven record of operating casinos from the smallest Las Vegas "grind joints" to the largest and most opulent casino at a level that has always far exceeded the performance levels of the other casinos in the marketplace. GGI is the only management company in the gaming industry that can offer proven performance in casino marketing, high-end table and slot player development, security, surveillance, casino controls, casino operations, information technology, food and beverage and hotel operations.
Jonathan A. Arnesen
Chief Administrative Officer
Jean Price
Vice President of Administration
Sherry Amos
Vice President of Marketing
George Wackenheim, PHR
Vice President Human Resources
Alisa Elkis
Vice President of Casino Marketing
Donald Hoover
Interactive Gaming Consultant
Anthony Celona
Vice President of Slot Operations
Nicholas Moles
Vice President and General Counsel
Watch the Obama Commercial
A Good Sign For Resorts
Gomes Gaming - EBITDA Growth
Latest News...
The Top 40 Under 40 - Aaron Gomes
3/2012 Atlantic City Weekly
Read more...
Co-Owner of Resorts casino brings glitz (and controversy) back to AC
9/25/2011 The Star-Ledger
Read more...
VIPs Who Will Change Atlantic City - Aaron Gomes
1/2012 | Casino Connection
Read More...
Bad Beat - Will Table-Game Discounting Be The Downfall Of The Casino Industry?
9/2011 | Global Gaming Business
Read More...
Dennis Gomes interviewed by Global Gaming Business
11/5/2010 | Global Gaming Business
Read More...
New Resorts Atlantic City owner will rebrand casino in style of Boardwalk Empire
10/22/2010 | NJ.com
Read More...
Gomes Gaming CEO, Dennis Gomes, announces Resorts Hotel and Casino Official Property Theme
10/7/2010 | Gomes Gaming
Read More...
Pair could enable new era for Atlantic City
10/5/2010 | Gaming History
Read More...
Dennis Gomes relishes challenge of running Resorts
9/10/2010 | Philadelphia Daily News
Read More...
Resorts purchase marks return of Morris Bailey to his hometown, Atlantic City
9/4/2010 | Press of Atlantic City
Read More...
Gomes, N.Y. real estate mogul reveal details of $35M. Resorts casino purchase in Atlantic City
9/2/2010 | Press of Atlantic City
Read More...
INSIDE GAMING: Optimistic spirit down on the Boardwalk
8/29/2010 | Las Vegas Review Journal
Read More...
Investors hope Resorts sale inspires more just like it
8/29/2010 | Press of Atlantic City
Read More...
Go-Go Gomes
8/27/2010 | GGB News
Read More...
Hope for Atlantic City as Gomes Buys Iconic Casino
8/26/2010 | CompatiblePoker.com
Read More...
Casino Mogul Dennis Gomes Buys Resorts Atlantic City
8/26/2010 | SportsInteraction.com
Read More...
Casino Executive to Buy Aging Resorts Atlantic City
8/26/2010 | CakePoker.com
Read More...
Gomes Gaming agrees to buy Atlantic City's Resorts Casino Hotel
8/24/2010 | Philly.com
Read More...
AC HOPE - Gomes may jump-start ailing city
8/24/2010 | GamingToday.com
Read More...
Resorts casino in Atlantic City sold to Gomes Gaming
8/24/2010 | Press of Atlantic City
Read More...
Resorts casino is just the latest challenge for "visionary" Dennis Gomes
8/23/2010 | Press of Atlantic City
Read More...
Dennis C. Gomes, Prominent Casino Industry Leader and Visionary, Returns to Atlantic City, NJ with Purchase of Resorts Casino Hotel
8/23/2010 | Gomes Gaming, Inc. Press Release
Read More...
Former Tropicana executive Dennis Gomes expresses interest in buying Resorts Atlantic City
8/7/2010 | Press of Atlantic City
Read More...
© 2017 Gomes Gaming, Inc. | 1133 Boardwalk | Atlantic City, NJ 08401


text:
Forgot your password? Enter the email address you signed up with and we will send you a link to create a new password.
Your password reset has been submitted to the address provided.
Standard character mark
Nutritional and dietary supplements derived from corn plants and corn plant parts, such as corn leaves, corn grass or corn silk
Business in Alpine, UT


text:
Power of Attorney
There are many times through the cargo shipping and import process that efficient transit is not possible due to waiting for officially approved documentation to be made available. Clients who experience such delays can avoid them by choosing our Power of Attorney (POA) services which allow us to take on the legal administration of your shipping, customs clearance and import duty payment activities. This simply allows us to complete import paperwork much more quickly and has no impact on your other interests outside the import/shipping process specified in the POA document.
Beja has plenty of experience in this process and access to specialist attorneys who have worked with us for years. We can complete legal administration related to your imports and customs clearance that will comply with the law in every detail and ensure you are protected at all times.
If you need to have your imports cleared quickly through customs, call us now Toll Free at 866-791-2649 and we will ensure you enjoy optimum freight transportation performance with expert import services backed up by Power of Attorney and experienced customs brokerage.


text:
The converter regulator spring controls converter charge and feeds the lubrication circuit. When the spring becomes weak or broken, converter pressure is reduced. This causes delayed engagements, reduced torque output and increased operating temperatures.
The lube regulator spring affects converter pressure as well as lubrication pressure within the cooler and unit. When this spring breaks or becomes fatigued, converter temperature and gear train temperatures increase.
If either spring is excessively strong, both converter and cooler pressure increases. This can result in converter flex and cooler circuit cross leakage.
These springs should be replaced as a pair, due to the pressure effects on each valve.
These springs work in '03-earlier units only. These units can be identified by counting the solenoids: The earlier units have 6 solenoids. Do not use in '04-later (7-solenoid) units.
Contact a Sonnax Parts Distributor.


text: 934 WWUS81 KALY 200410 SPSALY Special Weather Statement National Weather Service Albany NY 1110 PM EST Sun Nov 19 2017 MAZ001-025-NYZ038>040-047>054-058>061-082-200615- Northern Berkshire-Southern Berkshire-Southern Herkimer- Southern Fulton-Montgomery-Schoharie-Western Schenectady- Eastern Schenectady-Southern Saratoga-Western Albany- Eastern Albany-Western Rensselaer-Eastern Rensselaer- Western Greene-Eastern Greene-Western Columbia-Eastern Columbia- Northern Fulton- Including the cities of Dalton, Hancock, Pittsfield, Florida, North Adams, Sandisfield, Great Barrington, South Egremont, Ilion, Herkimer, Little Falls, Mohawk, Frankfort, Dolgeville, Gloversville, Johnstown, Amsterdam, Cobleskill, Breakabeen, Gilboa, Livingstonville, Middleburgh, North Blenheim, Jefferson, Mariaville, Delanson, Duanesburg, Schenectady, Rotterdam, Burnt Hills, Ballston Spa, Mechanicville, Clifton Park, Waterford, Westerlo, Altamont, Berne, Knox, Preston Hollow, Albany, Troy, Berlin, Eagle Bridge, Hoosick Falls, Stephentown, Hunter, Tannersville, Windham, Prattsville, Catskill, Coxsackie, Athens, Cairo, Jefferson Heights, Hudson, New Lebanon, and Caroga Lake 1110 PM EST Sun Nov 19 2017 ...Snow showers may result in quick accumulation tonight... At 11 pm, a band of moderate snow was located roughly along and just south of I-90, moving east at roughly 45 mph. This band is be capable of a quick dusting of snow, especially on secondary and untreated roadways. Travelers should use caution for slippery roads and rapid reductions in visibility. $$