WO2001036046A1 - Dual-chambered pacemaker and defibrillator - Google Patents
Dual-chambered pacemaker and defibrillator Download PDFInfo
- Publication number
- WO2001036046A1 WO2001036046A1 PCT/US2000/031567 US0031567W WO0136046A1 WO 2001036046 A1 WO2001036046 A1 WO 2001036046A1 US 0031567 W US0031567 W US 0031567W WO 0136046 A1 WO0136046 A1 WO 0136046A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- atrial
- ventricular
- rate
- patient
- pacing
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
- A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
- A61N1/362—Heart stimulators
- A61N1/365—Heart stimulators controlled by a physiological parameter, e.g. heart potential
- A61N1/36514—Heart stimulators controlled by a physiological parameter, e.g. heart potential controlled by a physiological quantity other than heart potential, e.g. blood pressure
- A61N1/36542—Heart stimulators controlled by a physiological parameter, e.g. heart potential controlled by a physiological quantity other than heart potential, e.g. blood pressure controlled by body motion, e.g. acceleration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
- A61N1/38—Applying electric currents by contact electrodes alternating or intermittent currents for producing shock effects
- A61N1/39—Heart defibrillators
- A61N1/3925—Monitoring; Protecting
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
- A61N1/38—Applying electric currents by contact electrodes alternating or intermittent currents for producing shock effects
- A61N1/39—Heart defibrillators
- A61N1/3956—Implantable devices for applying electric shocks to the heart, e.g. for cardioversion
- A61N1/3962—Implantable devices for applying electric shocks to the heart, e.g. for cardioversion in combination with another heart therapy
- A61N1/39622—Pacing therapy
Definitions
- the present invention relates generally to implantable medical mterventional devices
- defibrillator for ventricular defibriUation, with pacing and sensing of the atrium and related
- Implantable defibrillators perform a variety of functions designed to treat ventricular arrhythmias, including sensing of ventricular signals, detection of ventricular
- arrhythmias consisting of bradycardia, tachycardia, and fibrillation, and delivery of
- implanted devices have Holter function capabilities, and study of the recorded time period
- the ventricle is driven at a high rate. If the ECG criteria for the atrioventricular (AV) node, the ventricle is driven at a high rate. If the ECG criteria for
- implantable defibrillator devices are unable to provide the solution because their focus is on
- dysrhythmia or absence thereof — allows the device to more properly respond with a
- the device can better distinguish which heart chamber is attributable to the arrhythmia, so as to
- defibrillators is the prominence of atrial arrhythmias which occur in implant patients because
- the current devices perform
- Another aim of the present invention is to provide an implantable
- defibrillator that performs pacing of the atrium as well as the ventricle, so as to enable better
- pacing function with enhanced criteria for classification of arrhythmias.
- an implantable defibrillator configured to provide an implantable defibrillator
- the device has the capability to pace the atrium to assure a
- SA sinoatrial
- paced i.e., stimulated
- pacing assures that AV synchrony will be maintained, i.e., ventricular depolarizations are
- defibrillator by which the overall cardiac performance of these patients is improved to an
- the defibrillator device is provided with a capability to
- the implanted device can provide a more precise diagnosis of the nature of the atrial rhythm, i.e., the atrial signal, independently of the ventricular signal. By doing so, and applying appropriate algorithms which compare the atrial and ventricular status, the implanted device can provide a more precise diagnosis of the nature of the atrial rhythm, i.e., the atrial signal, independently of the ventricular signal. By doing so, and applying appropriate algorithms which compare the atrial and ventricular status, the implanted device can provide a more precise diagnosis of the nature of the atrial rhythm, i.e., the atrial signal, independently of the ventricular signal. By doing so, and applying appropriate algorithms which compare the atrial and ventricular status, the implanted device can provide a more precise diagnosis of the nature of the atrial rhythm, i.e., the atrial signal, independently of the ventricular signal. By doing so, and applying appropriate algorithms which compare the atrial and ventricular status, the implanted device can provide a more precise diagnosis of the nature of the atrial rhythm, i.e.
- rhythm disorder For example, if ongoing ventricular tachycardia is detected by
- the implanted device the presence of normal sinus rhythm at the atrial sense signal input
- the device senses ventricular tachycardia while the atrial sense signal reveals atrial flutter or
- the origin of the rhythm disorder is determined to be in the atrium with a
- the implantable device of the invention effectively combines the advantages of DDD
- DDD defibriUation of the ventricle.
- ICHD Inter-
- the device is adapted to provide dual chamber pacing, dual chamber sensing, and both triggered
- the invention employs an accelerometer as a sensor of activity of the patient.
- the DDD pacemaker with which the defibrillator is combined becomes a
- Atrial monitoring detection and treatment which are effective to terminate an
- Atrial flutter is broken by rapid atrial stimulation and atrial fibrillation is terminated
- finding has to a certain class (e.g., the extent of truth or falsity of the finding).
- Another feature of the invention is that the number of leads to be implanted for use
- Two transvenous leads having a size of about 6-1/2 French may be employed,
- pacing/sensing cathodal tip and sensing/pacing/shocking anodal ring for conventional bipolar pacing and sensing, and low polarization electrodes for shocking to allow intrinsic
- pacing capability to improve detection, diagnosis, and treatment of arrhythmias, including
- the device electrically stimulates fat pads associated with the S A node and AV
- origin of a tachyarrhythmia is determined from an observation of which fat pad, when
- the tachyarrhythmia is stimulated, the tachyarrhythmia is deemed to be supraventricular in origin, or a sinus
- tachycardia Although the '980 patent describes an implantable pacemaker/cardioverter/ defibrillator including possible DDD pacing, neither the type of pacing nor the identification
- FIG. 1 is a cutaway view of the patient's heart showing placement of signal generator
- FIG. 2 is a functional block diagram of the signal generator of FIG. 1 illustrating
- FIG. 3 is a simplified partial block diagram of the signal generator of FIG. 1;
- FIG. 4 is a simplified functional flow diagram of the operation of the implanted
- defibrillator using evaluation logic for analysis and diagnosis.
- a medical mterventional device such as implantable defibrillator
- the 13 includes a signal generator 14.
- the generator is implanted in a surgically-formed pocket
- Signal generator 14 is conventional except as will otherwise be described herein, incorporating electronic
- a metal case (can) 15 compatible with the tissue and fluids of the body (i.e.,
- the device is microprocessor-based with substantial memory, logic and
- VF ventricular tachycardia
- VT ventricular bradycardia
- Composite electrical lead 18 which includes separate leads 22 and 27 with distally
- Electrodes is coupled at the proximal end to signal generator 14 through an electrical
- case 15 is also employed as an electrode
- the signal generator and lead(s) of the present invention are
- SVC superior vena cava
- distal tip electrode 32 to a separate conductor
- electrode 32 is positioned in the right atrium against either the lateral or anterior atrial wall
- electrode 35 is positioned in the right ventricle at the apex thereof. Active or
- 35 preferably has a standard 4 to 8 millimeter (mm) configuration, and is provided with soft
- defibriUation and cardioversion as well as those used for sensing and for pacing, are
- electrode 38 implanted subcutaneously is used. This serves to enhance the effectiveness of
- lead 38 is electrically connected directly to the high voltage output circuitry in signal
- generator 14 via connector block 20, and runs subcutaneously for connection to an epicardial
- the conductor for electrode 36 of lead 38 may be any conductor for electrode 36 of lead 38.
- the lead 38 is run parallel to the
- pericardial sac It may even be threaded through the thoracic cage, the pericardial space
- the distal end 36 of lead 38 is preferably placed close to the left atrium of the patient's heart to provide an increase in electric field strength and support the strong vector of the electric field according to the heart chamber to be defibrillated. Selection of the chamber
- Atrial coil electrode 21 is used for bipolar sensing as well as a counter-electrode for
- electrode 21 is preferably
- ventricular electrode 26 of lead 27 is positioned for use
- defibriUation electrode as well as for bipolar sensing in the ventricle.
- electrode 26 also cooperates with the metal case 15 and/or subcutaneous or pericardial electrode 36, whichever of these latter electrodes is used in the defibrillator implementation.
- the coil structure for electrode 26 provides it with an effective surface for defibriUation
- the electrode maybe composed of fine metallic filaments or fibers
- the tip electrodes of leads 22 and 27 are used for sensing and pacing of the
- the defibrillator 13 uses a transvenous electrode for ventricular defibriUation and stimulation
- Atrial bipolar lead for sensing and atrial defibriUation, so that atrial defibriUation is
- transvenous lead 22 may have electrode 21 positioned at a mid-point of that chamber, and
- Electrode 42 can be applied between electrode 42 and atrial defibriUation electrode 21 upon detection of
- electrode 42 would replace signal generator case 15
- electrode 42 is desirably positioned in the
- distal coronary sinus for defibriUation of the atria in conjunction with electrode 21, and can
- ventricle also serve for defibriUation of the ventricle as well as for sensing and stimulation of especially the left ventricle for improved hemodynamics.
- electrode 36 between electrode 36 and electrode 21 for atrial fibrillation, or between electrode 42 and
- electrode 21 for atrial fibrillation or between electrode 36 and electrode 26 for ventricular
- Atrial electrode 21 can be used additionally as either anode or cathode.
- the case 15 can serve as the anode for delivery of the shock as well, and can provide ground
- the implantable defibrillator is provided
- an accelerometer 40 as an activity sensor
- associated may include a micro-miniaturized silicon structure incorporating an electro ⁇
- the sensor detects movement or acceleration of the patient in the course of
- accelerometer is preferably mechanically isolated from the wall of the case to avoid a false
- the accelerometer sensor signal is used to
- controlled variation of the atrial rate serves as a detenent against atrial dysrhythmias.
- accelerometer 40 also functions to provide information to confirm or reject a diagnosis
- the cardiac activity sensor(s) or analysis of a dysrhythmia detected by the cardiac activity sensor(s). For example, the cardiac activity sensor(s).
- accelerometer may indicate that a tachycardia is physiologic rather than pathologic, or vice
- accelerometer may aid in demonstrating that a perceived ventricular dysrhythmia is in fact
- An evaluation of the accelerometer signal will determine whether a given atrial rate
- a conditional ventricular tracking limit is established so that the
- FIG.2 is a functional block diagram of signal generator 14. Cardiac activity (internal)
- ECG ECG signals detected by tip electrodes 32 and 35 of atrial and ventricular transvenous leads
- the signal information generated by the accelerometer indicates physical movement
- the non-ECG sense channel provides additional evidence for enhancing the
- Each evaluation logic circuit uses its input signal to develop a general finding or
- Atrial evaluation logic 55 may examine the processed
- ventricular evaluation may indicate that the atrial rate is normal (or fast, or slow).
- ventricular evaluation may indicate that the atrial rate is normal (or fast, or slow).
- logic 56 may make a determination from its criteria that the ventricular rate is fast.
- activity evaluation logic 58 may determine that the patient has commenced walking, from
- ECG criteria may be applied to diagnose atrial tachycardia, including, for example,
- ECG criteria may be applied to discriminate stable atrial rhythms, which may be sinus
- rhythm be sinus anhythmia, sinus arcest, ectopic atrial beats, atrial flutter and atrial fibrillation.
- process is a type of bi-level logic in which the degree of membership in a statement is
- Fuzzy logic may be implemented in
- fuzzy logic comparator 60 looks at the inputs derived
- the implanted defibrillator establishes an
- the atrial rate is more than 300 beats per minute (bpm) and the cycle
- ventricular rate is between 120 bpm and
- Atrial flutter is diagnosed by the detection algorithm. Further confirmation of this diagnosis
- defibrillator applies a burst or other form of rapid atrial stimulation as a therapeutic option
- flutter is to apply a low energy atrial shock starting with about 0.3 joule, and to increase the
- a further example is a situation in which the ventricular rate fulfills the criteria of
- the defibrillator is directed to immediately commence charging
- one rule maybe: LF (ventricular rate is FAST .AND. atrial rate is NORMAL. AND.
- Another fuzzy logic rule may be: IF (atrial rate is FAST .AND. ventricular rate is FAST .AND. patient MOTIONLESS) THEN (DEFIBRILLATION of atrium).
- relatively low energy shocks e.g., 5 joules or less
- Atrium from an atrial defibrillator or cardioverter.
- a conventional automatic implantable defibrillator in which a high energy (e.g.,
- shock maybe delivered to the patient's heart despite the case
- rhythm disorder It may indeed exacerbate the problem by creating an environment
- the therapy designated by the output signal of the fuzzy logic comparator 60 is the therapy designated by the output signal of the fuzzy logic comparator 60.
- DDD-R defibriUation pacing
- antitachycardia pacing 63 antitachycardia pacing 63
- atrial defibriUation (or cardioversion) 64 or
- the fuzzy logic comparator recognizes this state of affairs from the output signal information supplied by the
- an appropriate rule may be: IF (atrial rate is
- the specified maintenance may be to continue
- FIG. 3 is a simplified block diagram of a portion of the signal generator 14 of the
- implantable defibrillator illustrating component blocks used in treating pacing problems
- bradycardia and tachycardia as well as in treating both atrial and ventricular fibrillation.
- Circuit details are minimized or omitted for the sake of convenience and clarity, such as
- the subsystem includes a microprocessor 70 with associated
- memory 71 which may, for example, be volatile SRAM, for storing cardiac rhythm data from
- DDD-R pacemaker 80 is also responsive to the ECG sense signal inputs, and has
- variable rate control which is activated by module 81 in response to the physical activity
- evaluation logic circuits 55 and 56 perform independent checks
- fuzzy logic can more easily diagnose an atrial or ventricular rhythm disorder
- a decision for example, of whether to shock the atrium to return the heart in atrial fibrillation or atrial flutter to sinus rhythm, or to pace the ventricle to break a ventricular
- an implantable device offers advantages over the prior art. By stimulating the atrium at a
- stimulation is applied in conjunction with antianhythmic medications or beta-blockers.
- implanted device capable of sensing and responding to the status of the atrium, independent
- Atrial stimulation is normally ca ied out to assure a constant or
- the objective is to
- Sensing and pacing are also performed in the DDD mode in both the atrium and ventricle.
- implanted medical mterventional device includes device-implemented steps illustrated in the
- Cardiac activity of the ventricle is sensed at 100 to detect whether
- rhythm disorders are present at 101. Concurcently, atrial activity is sensed at 103 to detect atrial activity. Concurcently, atrial activity is sensed at 103 to detect
- rhythm disorders in that chamber at 105 When a dysrhythmia is detected in the atrium or
- a diagnosis is performed to identify the heart chamber in which it originated.
- an appropriate therapy is then selected and delivered to the heart chamber identified as the
- the ECG signal of the respective chamber is analyzed with respect to at
- ventricular chambers is compared with previous ECG data for the respective chambers, to
- the implanted device continues
- an appropriate therapy is selected at 108 from among a plurality
- the atrium is paced continuously at the preselected minimum rate, except when the
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Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP00980456A EP1233814A4 (en) | 1999-11-18 | 2000-11-17 | Dual-chambered pacemaker and defibrillator |
CA002397852A CA2397852A1 (en) | 1999-11-18 | 2000-11-17 | Dual-chambered pacemaker and defibrillator |
AU17714/01A AU1771401A (en) | 1999-11-18 | 2000-11-17 | Dual-chambered pacemaker and defibrillator |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/442,550 US6327499B1 (en) | 1997-08-01 | 1999-11-18 | Cardiac stimulator and defibrillator |
US09/442,550 | 1999-11-18 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2001036046A1 true WO2001036046A1 (en) | 2001-05-25 |
WO2001036046A8 WO2001036046A8 (en) | 2001-06-21 |
Family
ID=23757228
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2000/031567 WO2001036046A1 (en) | 1999-11-18 | 2000-11-17 | Dual-chambered pacemaker and defibrillator |
Country Status (5)
Country | Link |
---|---|
US (1) | US6327499B1 (en) |
EP (1) | EP1233814A4 (en) |
AU (1) | AU1771401A (en) |
CA (1) | CA2397852A1 (en) |
WO (1) | WO2001036046A1 (en) |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008116067A2 (en) * | 2007-03-20 | 2008-09-25 | Medtronic, Inc. | Methods and apparatus for patient notification of physiologic events and device function |
US8131043B2 (en) | 2005-09-16 | 2012-03-06 | The Ohio State University | Method and apparatus for detecting interventricular dyssynchrony |
EP1803486A3 (en) * | 2003-05-29 | 2012-05-09 | Cameron Health, Inc. | Method for discriminating between ventricular and supraventricular arrhythmias |
US8280136B2 (en) | 2005-09-16 | 2012-10-02 | The Ohio State University | Method and apparatus for detecting intraventricular dyssynchrony |
CN109982738A (en) * | 2016-11-21 | 2019-07-05 | 心脏起搏器股份公司 | Delivery device and wall attach sensing |
FR3102936A1 (en) * | 2019-11-13 | 2021-05-14 | Pierre LE FRANC | Cardiac pacemaker, subcutaneous cardiac defibrillator, and methods of cardiac stimulation and defibrillation |
Families Citing this family (23)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6519490B1 (en) | 1999-12-20 | 2003-02-11 | Joseph Wiesel | Method of and apparatus for detecting arrhythmia and fibrillation |
US6490486B1 (en) * | 2000-04-27 | 2002-12-03 | Pacesetter, Inc. | Implantable cardiac stimulation device and method that monitors displacement of an implanted lead |
US7386344B2 (en) | 2004-08-11 | 2008-06-10 | Cardiac Pacemakers, Inc. | Pacer with combined defibrillator tailored for bradycardia patients |
US6751502B2 (en) | 2001-03-14 | 2004-06-15 | Cardiac Pacemakers, Inc. | Cardiac rhythm management system with defibrillation threshold prediction |
US6987999B1 (en) | 2002-05-02 | 2006-01-17 | Pacesetter, Inc. | Implantable defibrillator with alternating counter electrode |
US7085520B2 (en) * | 2003-03-25 | 2006-08-01 | Seiko Epson Corporation | Developing device, image forming apparatus, and image forming system |
US8002553B2 (en) | 2003-08-18 | 2011-08-23 | Cardiac Pacemakers, Inc. | Sleep quality data collection and evaluation |
US7887493B2 (en) | 2003-09-18 | 2011-02-15 | Cardiac Pacemakers, Inc. | Implantable device employing movement sensing for detecting sleep-related disorders |
EP1670547B1 (en) | 2003-08-18 | 2008-11-12 | Cardiac Pacemakers, Inc. | Patient monitoring system |
US7996072B2 (en) | 2004-12-21 | 2011-08-09 | Cardiac Pacemakers, Inc. | Positionally adaptable implantable cardiac device |
US7680532B2 (en) * | 2005-02-25 | 2010-03-16 | Joseph Wiesel | Detecting atrial fibrillation, method of and apparatus for |
US20070118180A1 (en) | 2005-11-18 | 2007-05-24 | Quan Ni | Cardiac resynchronization therapy for improved hemodynamics based on disordered breathing detection |
EP2525870B1 (en) | 2010-01-19 | 2019-03-13 | Heartware, Inc. | Physiologically responsive vad |
US9681819B2 (en) | 2013-08-30 | 2017-06-20 | Joseph Wiesel | Method and apparatus for detecting atrial fibrillation |
US11147499B2 (en) | 2013-08-30 | 2021-10-19 | Joseph Wiesel | Method and apparatus for detecting atrial fibrillation |
CN106456984B (en) | 2014-02-24 | 2019-07-09 | 元素科学公司 | External defibrillator |
US10245362B2 (en) | 2015-02-24 | 2019-04-02 | Heartware, Inc. | Blood pump for treatment of bradycardia |
AU2016312681B2 (en) | 2015-08-26 | 2021-01-21 | Element Science, Inc. | Wearable devices |
CN108025121B (en) | 2015-09-25 | 2021-03-12 | 心脏器械股份有限公司 | Blood pump for ischemia detection and treatment |
EP3528702A1 (en) * | 2016-10-18 | 2019-08-28 | Cardiac Pacemakers, Inc. | System for arrhythmia detection |
US10542939B2 (en) * | 2016-11-14 | 2020-01-28 | Medtronic Monitoring, Inc. | System and methods of processing accelerometer signals |
WO2020077113A1 (en) | 2018-10-10 | 2020-04-16 | Element Science, Inc. | Wearable medical device with disposable and reusable components |
EP3914345A1 (en) * | 2019-01-23 | 2021-12-01 | Impulse Dynamics NV | Discrimination of supraventricular tachycardias in combined ccm-icd device |
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-
2000
- 2000-11-17 CA CA002397852A patent/CA2397852A1/en not_active Abandoned
- 2000-11-17 AU AU17714/01A patent/AU1771401A/en not_active Abandoned
- 2000-11-17 EP EP00980456A patent/EP1233814A4/en not_active Withdrawn
- 2000-11-17 WO PCT/US2000/031567 patent/WO2001036046A1/en active Application Filing
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US9155485B2 (en) | 2003-05-29 | 2015-10-13 | Cameron Health, Inc. | Method for discriminating between ventricular and supraventricular arrhythmias |
US10183171B2 (en) | 2003-05-29 | 2019-01-22 | Cameron Health, Inc. | Method for discriminating between ventricular and supraventricular arrhythmias |
US11020602B2 (en) | 2003-05-29 | 2021-06-01 | Cameron Health, Inc. | Method for discriminating between ventricular and supraventricular arrhythmias |
EP1803486A3 (en) * | 2003-05-29 | 2012-05-09 | Cameron Health, Inc. | Method for discriminating between ventricular and supraventricular arrhythmias |
US9555259B2 (en) | 2003-05-29 | 2017-01-31 | Cameron Health Inc. | Method for discriminating between ventricular and supraventricular arrhythmias |
US8942802B2 (en) | 2003-05-29 | 2015-01-27 | Cameron Health, Inc. | Method for discriminating between ventricular and supraventricular arrhythmias |
US9968796B2 (en) | 2003-05-29 | 2018-05-15 | Cameron Health, Inc. | Method for discriminating between ventricular and supraventricular arrhythmias |
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WO2008116067A3 (en) * | 2007-03-20 | 2008-12-04 | Medtronic Inc | Methods and apparatus for patient notification of physiologic events and device function |
CN109982738A (en) * | 2016-11-21 | 2019-07-05 | 心脏起搏器股份公司 | Delivery device and wall attach sensing |
FR3102936A1 (en) * | 2019-11-13 | 2021-05-14 | Pierre LE FRANC | Cardiac pacemaker, subcutaneous cardiac defibrillator, and methods of cardiac stimulation and defibrillation |
WO2021094692A1 (en) | 2019-11-13 | 2021-05-20 | Le Franc Pierre | Subcutaneous cardiac defibrillator and cardiac pacemaker |
Also Published As
Publication number | Publication date |
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CA2397852A1 (en) | 2001-05-25 |
EP1233814A4 (en) | 2009-05-27 |
WO2001036046A8 (en) | 2001-06-21 |
US6327499B1 (en) | 2001-12-04 |
EP1233814A1 (en) | 2002-08-28 |
AU1771401A (en) | 2001-05-30 |
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