1. Field of the Invention
The present invention relates to devices, systems, and processes useful for compressing a uterine artery, and more particularly to devices and systems capable of easily locating, compressing, and/or monitoring or characterizing the blood flow through a uterine artery.
2. Brief Description of the Related Art
It has been proposed that occlusion of the uterine arteries of a human female patient can kill myomata, i.e., fibroids, because of the relative frailty of the fibroids to anoxia or hypoxia, and the relatively high resistance of uterine tissues to anoxia or hypoxia. See Burbank, Fred, M.D., et al, Uterine Artery Occlusion by Embolization or Surgery for the Treatment of Fibroids: A Unifying Hypothesis-Transient Uterine Ischemia, The Journal of the American Association of Gynecologic Laparoscopists, November 2000, Vol. 7, No. 4 Supplement, pp. S3-S49. U.S. Pat. No. 6,254,601, to Fred Burbank et al, entitled “Methods for Occlusion of the Uterine Arteries”, describes numerous devices and methods useful for occluding a uterine artery by penetrating the tissue of the patient to access the uterine artery. The devices and methods described in Burbank '601 have been useful in occluding a uterine artery, however there have been some difficulties encountered with their use.
Specifically, the aligned orientations of the imaging device, e.g., Doppler ultrasound device, and the element which passes through the tissue of the patient to occlude the uterine artery can be, for some patients and for some procedures, difficult to maintain. Additionally, the devices and methods described in the '601 patent do not necessarily take advantage of the structure and symmetry of the female human anatomy to facilitate occlusion of a uterine artery. The devices and methods of the '601 patent also are not well adapted for performing blood flow studies of a uterine artery.
Current devices available for uterine artery identification and characterization include two-dimensional Doppler color flow ultrasound systems with vaginal, abdominal, or intracavity probes. Typical machines are manufactured and distributed by General Electric Medical Systems, Toshiba, and Acuson, among other sources.
These machines require an ultrasound technologist to utilize the vaginal probe and position the probe sensor array within the vagina, near the cervix, while looking at the ultrasound machine's display screen, position the probe, and then select an appropriate setting to evaluate blood flow. Currently available devices thus require a high degree of skill to identify and then position the Doppler gate approximately to obtain an optimum signal for characterizing the blood flow. During this time, the probe must be held in as steady a position as possible to eliminate erroneous readings and signals. As will be readily appreciated by those of skill in the art, prior devices are therefore difficult to use successfully.
Current ultrasound machines can provide readings of peak blood velocity, pulsatility and resistive index, once a good Doppler wave form has been recorded. As discussed above, the trouble is in identification of the artery and, once identified, maintaining a good position for obtaining the desired data is difficult. No device which is currently commercially available can be used to simultaneously identify and occlude a uterine artery. Physicians, including gynecologists, have ligated the uterine artery surgically by using metal vascular clips or suture material, access having been achieved by surgical dissection. These surgical procedures have been performed by open abdominal surgery and laparoscopically, and require a great deal of surgical skill to access, identify, dissect, and ligate the uterine artery. This high skill requirement has limited the use of surgical ligation of the uterine arteries as a clinical alternative for treatment of uterine fibroids and other uterine disorders.
Ultrasound devices have been proposed for measuring blood flow in a blood vessel. See, e.g., U.S. Pat. Nos. 5,411,028, 5,453,575, 5,535,747, and 5,967,987.
Pessaries have been used for many years to treat numerous conditions, such as uterine prolapse, vaginal vault prolapse, urinary incontinence, cystocele, rectocele, enterocele, and some preoperative preparation. Pessaries have been available in numerous configurations, but are generally torus-shaped, somewhat elastic devices.
In an article published in 1964, Bateman reported that uterine artery vessel ligation or division, achieved via intra-abdominal surgery similar to hysterectomy, was effective in treating menorrhagia both with and without myomectomy. Bateman, W., M.D., “Treatment of intractable menorrhagia by bilateral uterine vessel interruption”, 89 Am. J. Obstet. Gynecol. 825-827 (Harcourt Health Sciences, Jul. 15, 1964). While Bateman reported some success, this procedure involves opening the abdominal cavity, with the known attendant risks and disadvantages.
There therefore remains a need in the art to develop apparatus and methods which further assist a medical practitioner in accessing, occluding, and/or measuring the blood flow characteristics in a uterine artery.
According to a first aspect of the invention, a device useful for compressing a uterine artery of a patient comprises a handle having a proximal end and a distal end, and a compressing portion mounted to the handle distal end, the compressing portion having a distal end face and a side surface.
According to another aspect of the present invention, a device useful for compressing a uterine artery of a patient comprises a handle having a proximal end and a distal end, and a cylindrical compressing portion mounted to the handle distal end, the compressing portion including a distal end having a distal end face, and including a hollow interior space sized to receive a cervix of a female human patient therein when the compressing portion is located around the cervix and the distal end face is positioned against the vaginal fornix of a female human patient.
According to yet another aspect of the present invention, a device useful for compressing a uterine artery of a patient comprises a compressing portion having a distal end face, a proximal end, and a side surface, a force transmission block on the compressing portion, and a grasping device attached to the force transmission block, the grasping device extending adjacent to the compressing portion.
According to yet another aspect of the present invention, a method of occluding a uterine artery of a female human patient, the patient having a uterus, a cervix with a cervical os, and a vaginal wall with a vaginal fornix, comprises pushing a compressing member upwardly toward the uterine artery until the compressing member reaches the vaginal fornix, pushing the compressing member upwardly to distend the vaginal wall at the vaginal fornix adjacent to the uterine artery, and pushing the uterine artery with the compressing member upwardly to compress the uterine artery against the uterus.
Still other objects, features, and attendant advantages of the present invention will become apparent to those skilled in the art from a reading of the following detailed description of embodiments constructed in accordance therewith, taken in conjunction with the accompanying drawings.
The invention of the present application will now be described in more detail with reference to preferred embodiments of the apparatus and method, given only by way of example, and with reference to the accompanying drawings, in which:
Referring to the drawing figures, like reference numerals designate identical or corresponding elements throughout the several figures.
The inventors herein have discovered that the uterine arteries of female humans typically are about 3 cm or less from the vaginal wall at the vaginal fornix where the uterine artery meets the uterus, although the uterine arteries for a single patient sometimes are spaced at slightly different distances (see distances X1 and X2 in
Devices and methods of the present invention can simplify the process of identifying a uterine artery and permits simultaneous interrogation and gathering of blood flow data for the artery. The device can be held in place and either selectively or automatically identifies the artery location and characteristics of the left and/or right side uterine artery without the need to reposition the Doppler array. Errors generated from positioning and repositioning the device in situ, and differences in the amount of pressure applied to the uterine artery for identification and interrogation, can successfully be lowered or eliminated. Devices according to the present invention permit simultaneous identification and occlusion of a uterine artery in a non-invasive manner, and lowers the level of skill needed to identify and occlude the artery because the devices and methods do not require surgical intervention to perform the occlusion.
Once the compressor 100 has been advanced into the fornix as described above, further pushing of the compressor 100 upwardly toward the uterine artery causes the uterine artery (and adjacent tissues) to be pinched between the distal end 106 of the portion 104 and the uterus itself. As discussed above, the uterus is a firm, muscular organ and therefore acts as a backstop or anvil against which the uterine artery can be compressed. Thus, pushing on the compressor 100 compresses the uterine artery, at least partially, and optionally completely, stopping the blood flow through the artery. As described in the '815 application, cessation of blood flow through the uterine artery can have beneficial effects for the patient.
The direction in which the compression force is applied against the vaginal fornix VF, and therefore against the uterine artery (UA1, UA2), includes at least an axial component FA (see
By way of example and not of limitation, a compressor useful for bilaterally compressing the uterine arteries of a female human patient has a hollow interior space which is generally cylindrical with a inner radius between about 1 cm and about 2 cm, preferably about 1.5 cm, an outer radius between about 1.5 cm and about 2.5 cm, preferably about 2 cm, i.e., the wall thickness of the distal end of the compressor is about 0.5 cm or less, and the distal compressing portion is about 1.0 cm or less long longitudinally. These dimensions, and in particular the inner dimension of the distal compressing portion, have been found to be similar in size to the exterior of the cervix of adult female human patients.
Turning back to the exemplary embodiment illustrated in
The distal compressor portion 204 includes right 206 and left 208 distal ends which engage the vaginal wall VW at the vaginal fornix VF on opposite lateral sides of the cervix when the compressor is pushed up the outside of the cervix. Optionally, the distal compressor portion 204 includes one, and preferably two, cutout portions 210, 212 between the distal ends 206, 208. The cutout portions 210, 212 can be optionally provided in the compressor 200 to accommodate the urethra and bladder neck on the anterior side of the cervix, and the rectum on the posterior side of the cervix. That is, the cutouts 210, 212 are sized, both in their circumferential length and their longitudinal depth, so that when the compressor 200 is used to compress the left and right uterine arteries of a female human patient, the urethra, bladder neck, and rectum are not compressed as much, or are not compressed at all, which can limit or eliminate complications with these structures. Further optionally, one of the cutouts 210 can be formed as a longitudinally extending slot 210′ which extends completely along the length of the compressor portion 204, which permits the compressor 200 to be more easily used with other devices, described in greater detail below.
The use of the compressor 200 is similar to the uses of compressors 100 and 150, described above, except that the bilateral structures of the compressor 200 permit both the left and the right uterine arteries UA1, UA2 to be compressed at the same time upon upward pushing of the compressor, and using the body of the uterus as an anvil against which to compress the arteries.
Turning back to
The crystals 302i are preferably positioned at the distal face 304 of the compressor so that any data derived from the signals received by the Doppler crystals can be more easily correlated to the distance of the uterine artery from the distal end 304. The crystals 302i can be integrated into the compressor 300, e.g., molded into the compressor itself, or alternatively can be removably mounted in the compressor. By way of example and not of limitation, the Doppler crystals 302i can each be in a Doppler probe 306i which is received in a correspondingly configured holder 308i formed in distal portions of the compressor. While many commercially available Doppler probes are suitable in the present invention, a Vascular Technology, Inc. (Lowell, Mass.) 8 MHz Doppler probe, or a Koven 8 MHz Doppler probe (Koven, St. Louis, Mo.), can be used as a Doppler probe 306i.
Those of skill in the art will recognize that the frequency of the Doppler crystal will change the viewing angle of the crystal. One aspect of the present invention is the use of Doppler crystals 302i which permit Doppler data to be gathered at distances up to about 3 cm, so that when the compressor on which the Doppler crystals are mounted is pushed against the vaginal wall at the vaginal fornix VF, the Doppler crystals 302i will received signals back from the uterine artery of interest. Thus, while many different Doppler crystals are suitable in the present invention, those which operate at about 8 MHz have been found to be particularly suitable.
The signals from the Doppler crystals 302i or probes 306i are transmitted to a suitable signal processor which displays data derived from the signals. According to yet further aspects of the present invention, the data from each of the Doppler crystals 302i is either manually or automatically examined to ascertain if the waveform received by the crystal is representative of the blood flow through a uterine artery UA1. Because the Doppler crystals 302i are selected to have relatively narrow angles of view, the process of examining the signals received by each crystal will reveal which crystal is pointed most directly at the uterine artery. As illustrated in
Turning now to the drawing figures, the compressor 400 includes a distal compressing portion 402, which can take the form of any of the other compressing portions described herein (e.g., 100, 150, 200, 250, 300), a tenaculum-like grasping device 404, and a force transmission block 406. A constant force generating member 410 is mounted between the proximal end 416 of the compressing portion 402 and the distal end 420 of the block 406. An example of a constant force generating member 410 is a constant force helical spring. The compressing portion 402 includes a distal compressing face 414, and the block includes a proximal end 418.
The compressing portion 402 illustrated in
A holding element 412 is provided on the block 406 for holding the grasping device 404 securely to the block and against relative longitudinal movement between the two structures. The holding element 412 can either removably or permanently hold the grasping device to the block 406. By way of example and not of limitation, a removable holding element 412 can include a hinged snap which traps a portion of the grasping device between two jaws, while a permanent holding element 412 can include the grasping device being molded into the block.
The grasping element includes a longitudinally extending first element 422, a second angled element 424, and a hinge or pivot 428 connecting the first and second elements together. The second element 424 includes an inwardly directed grasping portion 426, which can have a claw-like shape to grasp tissue between the grasping portion and the first element 422. A ratcheting lock 434 releasably holds together proximal portions of the first element 422 and the second element 424, as are well known to those of skill in the art. The proximal ends of the first element 422 and the second element 424 can include finger rings 432, 430, respectively.
The grasping device 404 is positioned with the first element 422 in the cervical canal and the second element 424 outside of the cervix C. The grasping device is then manipulated to push the grasping portion 426 medially into the cervix C to grasp the tissue of the cervix, while the ratcheting lock 434 holds the first and second elements 422, 424 in their relative angular orientation. For those embodiments of the present invention in which the holding element 412 releasably holds the proximal portions of the grasping device 404, the compressing portion 402 is slipped over the grasping device 404 and pushed up against the vaginal wall at the vaginal fornix, compressing the uterine arteries UA1, UA2. The holding element 412 is then secured to the grasping device 404 to hold the compressing portion 402 in place, while the constant force element 410 exerts a constant force on the compressing portion, and therefore on the uterine arteries UA1, UA2.
For those embodiments of the present invention in which the holding element 412 permanently holds the proximal portions of the grasping device 404, the compressing portion 402 is pushed over the outer surface of the cervix C at the time that the first element 422 is pushed into the cervical canal.
With the grasping device 404 holding the cervix C and the block 406 secured to the grasping device, the constant force element 410 pushes with a constant force on the compressing portion 402 in at least a distal, longitudinal direction.
Yet a further aspect of the present invention, as described above, is the addition of a medially directed force. According to yet another embodiment of the present invention, the compressing portion 402 is formed as a frustocone, and the block 406 is formed to have a larger transverse size at it's distal end 420 that the transverse size of the proximal end 416 of the compressing portion. In this manner, the constant force element 410 also takes the shape of a frustocone, and the force generated by the element 410 includes both longitudinal and medial components.
Yet another aspect of the present invention is that, as discussed above, the compressing portion 402 can be shaped more like compressing portion 154, that is, is not tubular as illustrated in
Yet further optionally, the cervix C can be pulled by the grasping device 404, and more particularly by the claw 426, prior to securing the compressing portion 402 to the grasping device.
Yet further aspects of the present invention exclude the constant force generating element 410, and the compressing portion and the force transmission block are directly connected together. While eliminating the functions provided by the constant force generating member 410, the resulting compressor is simpler in construction, and easier and less costly to manufacture. This aspect is the present invention is suggested by phantom line 450.
In the embodiment illustrated in
As further option, a releasable lock (not illustrated) may be included which releasably locks together the handles 512, 514, so that the dilator 510 can be released by the practitioner while maintaining the positions of the arms 518, 520 relative to one another.
Turning now to
Further optionally, the pivot points 608 can be formed integrally with the arms, either as a living hinge, or the arms themselves, e.g., arms 600 and 602, are formed as a single bow or malecot 612, 614 (see
Another aspect of the present invention relates to further processes of treatment of a patient, e.g., using a compressor. Once it has been established that the blood flow through the uterine artery or arteries has stopped for a therapeutically effective period of time, the practitioner can release the compressing member from compressing the uterine artery, and remove the compressing member from the patient. In the context of compressor 400, for example, the practitioner releases the ratchet lock and retracts the compressor 400 from along the cervix of the patient. This removal step can also be performed for any of the devices, and in combination with any of the methods, described herein. As used herein, the term therapeutically effective time and its equivalents are used as in U.S. patent application Ser. No. 09/556,934, filed Apr. 21, 2000, by Burbank et al., now U.S. Pat. No. 6,550,482, and U.S. patent application Ser. No. 09/908,815, filed Jul. 20, 2001, by Burbank et al.,now U.S. Pat No 7,223,279, the entireties of both of which are incorporated herein by reference.
According to a particularly preferred embodiment of the present invention, the hollow interior space of the cylindrical compressing portion has an inner diameter between about 2 cm and about 4 cm, and more preferably about 3 cm, because this size matches well the outer diameter or size of the cervix of many females. As will be well appreciated by those of ordinary skill in the art, the size of the hollow interior space can be larger or smaller according to the present invention, to fit a larger or smaller cervix.
Another aspect of the present invention includes that one or more of the surface(s) of the compressor, including each of the compressors described herein, which bears against the outer surface of the cervix can be formed as a generally flat surface instead of a concave surface.
The present invention also relates to devices, systems, and processes which can be useful in treating dysfunctional uterine bleeding (DUB). As the skilled artisan readily appreciates, DUB can be a very frustrating and troublesome condition because the actual cause of the bleeding is, by definition, unknown. Stated somewhat differently, DUB is a diagnosis of exclusion; if a woman has menorrhagia and no organic abnormality can be identified, she is given the diagnosis of DUB. Women with DUB are debilitated just as are women with fibroids and menorrhagia: they can be socially restricted during times of high menstrual blood loss and are anemic. Other aspects of the present invention relate to treating a patient who is diagnosed with DUB by compressing one or both uterine arteries, either serially or simultaneously, so that the uterine blood supply is greatly diminished or completely cut off. Without the blood supplied by the uterine arteries, the uterus stops bleeding, which can permit the medical practitioner to better diagnose the patient's condition. Without being limited to a particular theory, it is also posited herein that at least some cases of DUB can be treated effectively by uterine artery compression as described herein, that is, that DUB will not reoccur upon reestablishment of the blood supply to the uterus through the uterine arteries. To put it somewhat colloquially, the apparatus and methods of the present invention can be used to ‘reset’ the uterus by going through a period of induced anoxia or hypoxia. The Bateman article, mentioned briefly above, lends support to this hypothesis.
The present invention also includes as an aspect the treatment of bleeding associated with Caesarian section. Caesarian delivery results in at least two sources of post partum bleeding: blood loss at the Caesarian incision site; and blood loss at the placental separation site. Generally, natural mechanisms control blood loss at the placental separation site, while blood loss at the Caesarian incision site is typically achieved by suturing the two margins of the incision firmly together. The pressure of the sutures slows blood flow at the incision site and clot then forms; however, until sufficient suturing has been accomplished, blood loss occurs. Because suturing the Caesarian incision site is performed under urgent circumstances, to minimize blood loss, suturing quality of the incision is performed as if the uterus were composed of one layer of tissue, instead of three. Consequently, the outcome of this prior method is suboptimal at the endometrial, myometrial, and serosal levels. Thus another aspect of the present invention is the use of devices and/or the performance of methods in accordance with the present invention instead of, or in conjunction with, these prior suturing methods to treat Caesarian delivery bleeding. More specifically, devices and/or methods of the present invention re used and/or implemented to slow or stop blood flow to the uterus through the uterine arteries immediately after a baby is delivered. Subsequently, Caesarian incision repair can be performed in a manner that optimizes surgical closure, without worry about blood loss control at the time of closure.
The present invention also includes as an aspect the treatment of bleeding associated with Post Partum Hemorrhage (PPH). PPH is defined in the medical literature as the estimated loss of more than 500 ml of blood following delivery of a baby. It can occur for a wide variety of reasons and occurs following at least 5% of deliveries. Most often it occurs because the uterus fails to contract following placental separation (uterine atony). Without adequate post partum uterine contractions, blood does not slow enough in the uretoplacental arteries to clot. Without clot formation in the uretoplacental arteries, bleeding from the uretoplacental arteries persists.
Many treatments exist for hemorrhage secondary to uterine atony, including massage of the uterus through the abdominal wall, administration of drugs that encourage myometrial contraction (e.g., oxytocin, methylergonovine, and prostaglandins), uterine cavity packing with, e.g., cloth materials, balloon tamponade of the uterine cavity, bilateral surgical ligation of the uterine artery, ovarian arteries, or internal iliac artery, bilateral uterine artery embolization, suturing through the uterus (e.g., B-Lynch Brace technique), and hysterectomy. Many of the existing treatments are ineffective; others are overly complex, invasive, and slow to initiate.
According to aspects of the present invention, when it is recognized that bleeding has not stopped normally as it should after delivery, devices and/or methods in accordance with the present invention can be employed as described herein to slow or stop PPH.
The present invention extends at least to include devices and methods including combinations of all of the features and steps described above. By way of example and not of limitation, the Doppler probe array(s) described herein can be incorporated into any of the exemplary devices described herein, arranged at the distal end(s) of the device(s) as will be readily apparent to one of skill in the art. In a similar manner, methods of the present invention can include, but are not limited to, any one or combinations of the steps described above. Furthermore, any of the above described devices and methods which are described as useful for occluding a single uterine artery can be incorporated into bilateral devices and methods, that is, two of the unilateral devices can be joined into a single, bilateral device, with each of the two unilateral devices positioned in the bilateral device to access and/or locate a single uterine artery, and the steps of a method for accessing and/or locating a single uterine artery can be performed bilaterally, either serially or simultaneously.
While the invention has been described in detail with reference to preferred embodiments thereof, it will be apparent to one skilled in the art that various changes can be made, and equivalents employed, without departing from the scope of the invention. Each of the aforementioned documents is incorporated by reference herein in its entirety.
This application is related and claims priority under 35 U.S.C. § 119 to U.S. provisional patent application Ser. No. 60/279,477, filed Mar. 28, 2001, the entire contents of which are incorporated by reference herein. This application is also related to an application filed on Mar. 28, 2002, entitled “Multi-axial uterine artery identification, characterization, and occlusion pivoting devices and methods”, by Fred Burbank, Grieg E. Altieri, and Michael L. Jones, assigned U.S. application Ser. No. 10/107,810, now U.S. Pat. No. 6,905,506, the entire contents of which are incorporated by reference herein.
Number | Name | Date | Kind |
---|---|---|---|
105901 | unkn | Aug 1870 | A |
319954 | unkn | Jun 1885 | A |
1715089 | Jones | May 1929 | A |
1789524 | Hall | Jan 1931 | A |
1806441 | Bauer et al. | May 1931 | A |
2400251 | Nagel | May 1946 | A |
2522293 | Noble | Sep 1950 | A |
2723666 | Greenberg | Nov 1955 | A |
3063455 | Markley | Nov 1962 | A |
3411505 | Nobis | Nov 1968 | A |
3777740 | Hokanson | Dec 1973 | A |
3779248 | Karman | Dec 1973 | A |
4073533 | De brey et al. | Feb 1978 | A |
4120302 | Ziegler | Oct 1978 | A |
4192313 | Ogami | Mar 1980 | A |
4206750 | Kaivola | Jun 1980 | A |
4226240 | Walker, Jr. | Oct 1980 | A |
4292960 | Paglione | Oct 1981 | A |
4428374 | Auburn | Jan 1984 | A |
4428379 | Robbins et al. | Jan 1984 | A |
4475544 | Reis | Oct 1984 | A |
4509528 | Sahota | Apr 1985 | A |
4589419 | Laughlin et al. | May 1986 | A |
4650466 | Luther | Mar 1987 | A |
4757823 | Hofmeister et al. | Jul 1988 | A |
4768288 | Culbertson | Sep 1988 | A |
4771788 | Millar | Sep 1988 | A |
4945896 | Gade | Aug 1990 | A |
4994069 | Ritchart et al. | Feb 1991 | A |
5037430 | Hasson | Aug 1991 | A |
5081997 | Bosley, Jr. et al. | Jan 1992 | A |
5108408 | Lally | Apr 1992 | A |
5201314 | Bosley et al. | Apr 1993 | A |
5226911 | Chee et al. | Jul 1993 | A |
5275166 | Vaitekunas et al. | Jan 1994 | A |
5289831 | Bosley | Mar 1994 | A |
5336231 | Adair | Aug 1994 | A |
5383922 | Zipes et al. | Jan 1995 | A |
5427108 | Bollinger | Jun 1995 | A |
5447351 | Klunder | Sep 1995 | A |
5447515 | Robicsek | Sep 1995 | A |
5456693 | Conston et al. | Oct 1995 | A |
5458596 | Lax et al. | Oct 1995 | A |
5488958 | Topel et al. | Feb 1996 | A |
5507744 | Tay et al. | Apr 1996 | A |
5520698 | Koh | May 1996 | A |
5542944 | Bhatta | Aug 1996 | A |
5549624 | Mirigian et al. | Aug 1996 | A |
5549824 | Trumpf et al. | Aug 1996 | A |
5556396 | Cohen et al. | Sep 1996 | A |
5588960 | Edwards et al. | Dec 1996 | A |
5591173 | Schifano | Jan 1997 | A |
5598841 | Taniji et al. | Feb 1997 | A |
5601323 | Kaiser | Feb 1997 | A |
5614204 | Cochrum | Mar 1997 | A |
5662676 | Koninckx | Sep 1997 | A |
5662680 | Desai | Sep 1997 | A |
5672153 | Lax et al. | Sep 1997 | A |
5674243 | Hale | Oct 1997 | A |
5691314 | Hodgen | Nov 1997 | A |
5697942 | Palti | Dec 1997 | A |
5713371 | Sherman et al. | Feb 1998 | A |
5713896 | Nardelia | Feb 1998 | A |
5713942 | Stern et al. | Feb 1998 | A |
5715832 | Koblish et al. | Feb 1998 | A |
5716389 | Walinsky et al. | Feb 1998 | A |
5720743 | Bischof et al. | Feb 1998 | A |
5759154 | Hoyns | Jun 1998 | A |
5766135 | Terwilliger | Jun 1998 | A |
5776129 | Mersch | Jul 1998 | A |
5792059 | Furia et al. | Aug 1998 | A |
5797397 | Rosenberg | Aug 1998 | A |
5800378 | Edwards et al. | Sep 1998 | A |
5817022 | Vesely | Oct 1998 | A |
5836906 | Edwards | Nov 1998 | A |
5840033 | Takeuchi | Nov 1998 | A |
5895386 | Odell et al. | Apr 1999 | A |
5899861 | Friemel et al. | May 1999 | A |
5910484 | Haupert, Jr. | Jun 1999 | A |
5911691 | Mochizuki et al. | Jun 1999 | A |
5916173 | Kirsner | Jun 1999 | A |
5921933 | Sarkis et al. | Jul 1999 | A |
5922008 | Gimpelson | Jul 1999 | A |
5941889 | Cermak | Aug 1999 | A |
5979453 | Savage et al. | Nov 1999 | A |
6013088 | Karavidas | Jan 2000 | A |
6015541 | Greff et al. | Jan 2000 | A |
6019724 | Gronningsaeter et al. | Feb 2000 | A |
6032673 | Savage et al. | Mar 2000 | A |
6033398 | Farley et al. | Mar 2000 | A |
6034477 | Peeters et al. | Mar 2000 | A |
6035238 | Ingle et al. | Mar 2000 | A |
6045508 | Hossack et al. | Apr 2000 | A |
6066139 | Ryan et al. | May 2000 | A |
6077257 | Edwards et al. | Jun 2000 | A |
6080118 | Blythe | Jun 2000 | A |
6106473 | Violante et al. | Aug 2000 | A |
6152874 | Looney et al. | Nov 2000 | A |
6169914 | Hovland et al. | Jan 2001 | B1 |
6175751 | Maizes | Jan 2001 | B1 |
6210330 | Tepper | Apr 2001 | B1 |
6231515 | Moore et al. | May 2001 | B1 |
6254601 | Burbank et al. | Jul 2001 | B1 |
6261234 | Lin | Jul 2001 | B1 |
6280441 | Ryan | Aug 2001 | B1 |
6293954 | Fogarty et al. | Sep 2001 | B1 |
6299621 | Fogarty et al. | Oct 2001 | B1 |
6494517 | Durant | Dec 2002 | B1 |
6602251 | Burbank et al. | Aug 2003 | B2 |
6610074 | Santilli | Aug 2003 | B2 |
6764488 | Burbank et al. | Jul 2004 | B1 |
6905506 | Burbank et al. | Jun 2005 | B2 |
7141057 | Burbank et al. | Nov 2006 | B2 |
7172603 | Burbank et al. | Feb 2007 | B2 |
7207996 | Burbank et al. | Apr 2007 | B2 |
7223279 | Burbank et al. | May 2007 | B2 |
7229465 | Burbank et al. | Jun 2007 | B2 |
7329265 | Burbank et al. | Feb 2008 | B2 |
7354444 | Burbank et al. | Apr 2008 | B2 |
7404821 | Burbank et al. | Jul 2008 | B2 |
20020111537 | Taylor et al. | Aug 2002 | A1 |
20020165579 | Burbank et al. | Nov 2002 | A1 |
20020183771 | Burbank et al. | Dec 2002 | A1 |
20020188306 | Burbank et al. | Dec 2002 | A1 |
20030018270 | Makin et al. | Jan 2003 | A1 |
20030120306 | Burbank et al. | Jun 2003 | A1 |
20040097962 | Burbank et al. | May 2004 | A1 |
20040153097 | Burbank et al. | Aug 2004 | A1 |
20050113634 | Burbank et al. | May 2005 | A1 |
20050113852 | Burbank et al. | May 2005 | A1 |
Number | Date | Country |
---|---|---|
195 28 440 | Feb 1997 | DE |
0 472 368 | Feb 1992 | EP |
0 598 579 | May 1994 | EP |
0 890 342 | Jan 1999 | EP |
1 072 282 | Jan 2001 | EP |
1 220 773 | May 1960 | FR |
2 302 025 | Jan 1997 | GB |
2 311 468 | Jan 1997 | GB |
63-46105 | Mar 1988 | JP |
1159821 | Nov 1989 | JP |
7-008493 | Jan 1995 | JP |
WO 9502370 | Jan 1995 | WO |
WO 9502371 | Jan 1995 | WO |
WO 9819713 | May 1998 | WO |
WO 9838486 | Sep 1998 | WO |
WO 9911179 | Mar 1999 | WO |
WO 0033724 | Jun 2000 | WO |
WO 0168720 | Sep 2001 | WO |
WO 0180713 | Nov 2001 | WO |
WO 0200192 | Jan 2002 | WO |
WO 0278521 | Oct 2002 | WO |
WO 02078522 | Oct 2002 | WO |
WO 2004045420 | Jun 2004 | WO |
WO 2004045426 | Jun 2004 | WO |
WO 2004071275 | Aug 2004 | WO |
Number | Date | Country | |
---|---|---|---|
20020165579 A1 | Nov 2002 | US |
Number | Date | Country | |
---|---|---|---|
60279477 | Mar 2001 | US |