text:
|Numéro de publication
|Type de publication
|Numéro de demande
|Date de publication
|6 juil. 2010
|Date de dépôt
|28 aoűt 2006
|Date de priorité
|28 aoűt 2006
|État de paiement des frais
|Numéro de publication
|Stuart O. Schecter
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|Pacesetter, Inc.
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|BiBTeX, EndNote, RefMan
|Citations de brevets (32), Citations hors brevets (1), Référencé par (14), Classifications (8), Événements juridiques (3)
|Liens externes: USPTO, Cession USPTO, Espacenet
The invention generally relates to implantable cardiac stimulation systems for use in stimulating the heart and, in particular, to techniques for delivering inotropic stimulation, i.e. stimulation intended to affect the contractility of the heart.
A variety of medical conditions affect the ability of heart muscle to properly contract in response to electrical stimulus—either intrinsic stimulus generated by the sinus node and conduction system of the heart or therapeutic pacing pulses delivered by a pacemaker or other implantable cardiac stimulation device. In particular, various cardiomyopathies of differing etiologies can affect myocardial contractility, and the temporal relationships of motion/contractility of various regions (dysynchrony). These effects can be secondary to a combination of primary disturbances in electrical conduction and pathologic myocardial tissue.
Cardiomyopathy, i.e. "heart muscle disease", pertains to the deterioration of the function of the myocardium. Cardiomyopathy often results in heart failure as the pumping efficiency of the heart is diminished. Patients with cardiomyopathy are often at risk for arrhythmia and/or sudden cardiac death (typically due to ventricular fibrillation). Some cardiomyopathies are deemed extrinsic, whereas others are intrinsic.
Extrinsic cardiomyopathies are those in which the primary pathology is outside the myocardium itself and include such cardiomyopathies as ischemic cardiomyopathy, hypertensive cardiomyopathy, valvular cardiomyopathy, inflammatory cardiomyopathy and cardiomyopathy secondary to systemic diseases. Of these, the most common is ischemic cardiomyopathy, which pertains to weakness in the myocardium due, e.g., to coronary artery disease. Patients with ischemic cardiomyopathy often have a history of acute myocardial infarction (i.e. heart attack), although chronic ischemia can cause sufficient damage to the myocardium to cause a clinically significant cardiomyopathy even in the absence of myocardial infarction. Typically, the area of the heart affected by a myocardial infarction becomes necrotic and is replaced by scar tissue (fibrosis). Fibrotic tissue is "akinetic", i.e. it no longer functions as muscle and hence does not contribute to the heart's pumping function. In many cases, the affected side of the heart (i.e. the left side or the right side) will go into failure. Heart failure that is sufficiently severe is referred to as congestive heart failure (CHF), which is a frequent cause of mortality in elderly patients. Intrinsic cardiomyopathy, in contrast, pertains to a weakness in the myocardium that is not due to an identifiable external cause.
Intrinsic cardiomyopathy can arise due to certain infections (including Hepatitis C, Coxsackie viruses), and various genetic and idiopathic (i.e., unknown) causes as well as from alcohol and drug use. Exemplary types of intrinsic cardiomyopathies include dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy and restrictive cardiomyopathy.
In general, with diseased myocardium, there is a combination of denervation or impairment of the normal physiologic conduction system, myocardial stunning, hibernation and cell death. (Myocardial stunning is the phenomenon in which brief, reversible episodes of ischemia leave a prolonged depression of cardiac function that recovers only slowly over several hours or days.) Myocardial stunning, hibernation and cell death lead to hypocontractility, i.e. reduced contractility. Reduced contractility often results in a loss of cardiac output and also a lack of synchronous depolarization, i.e. a lack of coordination between the left and right chambers, atrial and ventricular chambers or within the left ventricular chamber itself (intra-ventricular dysynchrony). These impairments are often segmental, i.e. regional rather than global, especially in patients with ischemic heart disease.
As can be appreciated, the impairment in myocardial contractility arising from cardiomyopathy or other causes can significantly impair the functioning of the heart, leading to debilitated lifestyle and, in all too many cases, death. Accordingly, it would be highly desirable to remedy or mitigate any loss of contractility and reduce dysynchronous electro-mechanical activation. Various pharmacological treatments are available but these tend to affect the entire myocardium and do not target particular parts of the heart that may be impaired, i.e. the treatments do not specifically address segmental impairments. Many patients with impaired myocardial contractility have pacemakers, implantable cardioverter-defibrillators (ICDs) or other medical devices implanted therein that permit electrical stimulation to be selectively delivered to particular portions or chambers of the heart. Accordingly, techniques have been developed that seek to improve myocardial contractility using such devices by delivering non-pharmacologic inotropic therapy (NPIT) and improving synchronous electro-mechanical activation with Cardiac Resynchronization Therapy (CRT). CRT is the sum and substance of currently implanted biventricular pacing systems. NPIT is not yet widely available and still is under investigational study. However, a wealth of literature exists, which demonstrate the benefits of CRT for improving heart failure symptoms and even reducing mortality (see, e.g., the "Cardiac Resynchronization in Heart Failure" study, i.e. the "CARE-HF" study, Cleland et al. on behalf of The CARE-HF study Steering Committee and Investigators, "The CARE-HF study (CArdiac REsynchronisation in Heart Failure study): Rationale, Design and End-points, Eur Heart J, 2001; 3: 481-489). CRT is also discussed in, for example, U.S. Pat. No. 6,643,546 to Mathis, et al., entitled "Multi-Electrode Apparatus and Method for Treatment of Congestive Heart Failure"; U.S. Pat. No. 6,628,988 to Kramer, et al., entitled "Apparatus and Method for Reversal of Myocardial Remodeling with Electrical Stimulation"; and U.S. Pat. No. 6,512,952 to Stahmann, et al., entitled "Method and Apparatus for Maintaining Synchronized Pacing".
Techniques for delivering non-excitory inotropic stimulation to the heart in an effort to improve contractility are just emerging. See, for example, U.S. Pat. No. 6,233,484 to Ben-Haim et al. entitled "Apparatus and Method for Controlling the Contractility of Muscles" and related patents and patent applications of Impulse Dynamics N.V. The techniques described therein generally involve delivering relatively high voltage electrical stimulation pulses during a refractory period (during which the myocardium is not capable of contracting in response to electrical stimulation). The stimulation pulses are apparently intended to enhance calcium flux so as to improve contractility such that subsequent contractions are more hemodynamically effective.
Although refractory period-based inotropic techniques appear to be promising, it is believed that effective inotropic treatment can also be obtained by selectively delivering electrical stimulation outside of the refractory period, and it is to this end that certain aspects of the present invention are directed. In particular, it is desirable to provide techniques for applying subthreshold inotropic stimulation (i.e. stimulation below a threshold sufficient to trigger depolarization of the myocardium) outside the refractory period for the purposes of improving myocardial contractility. Among other potential advantages, subthreshold stimulation generally uses less power than the comparatively high voltage refractory period-based inotropic stimulation and hence does not significantly deplete battery power. Other aspects of the invention pertain to techniques for delivering suprathreshold inotropic stimulation (i.e. electrical stimulation above the threshold necessary to trigger depolarization) outside refractory periods and at the appropriate times to reduce dysynchronous activation patterns. Still other aspects of the invention are applicable to providing improvements to refractory period-based inotropic stimulation. Thus, the technologies described offer a combined approach to regionally improve contractility and reduce electromechanical dysynchrony in territories that have pathologic contractility and conductivity and allow normal tissue to function unaffected. These device based therapies are implemented when and where needed based, e.g., on repeated measurements of impedance based metrics that reflect contractile and conductive cardiac properties.
In accordance with a first general embodiment, techniques are provided for delivering inotropic electrical stimulation or other forms of electrical stimulation to the heart of a patient using an implantable cardiac stimulation device that takes into account dynamic impedance waveforms. The dynamic impedance waveforms represent electrical impedance as a function of time (i.e. Z(t)). During systole, the impedance along a direction of contraction of myocardial tissue increases due to an increase in myocardial thickness during contraction and due to a reduction in blood volume and perhaps due to other factors. The dynamic impedance waveform of healthy myocardial tissue differs from the corresponding waveforms of diseased or ischemic tissues, i.e. tissues with impaired contractility. Typically, the dynamic impedance waveform of diseased tissues exhibits a less significant change in impedance during systole than that of healthy tissue.
In one example, information pertaining to dynamic impedance waveforms within the heart of the patient (i.e. Zpatient(t)) is measured or otherwise obtained by the implanted device. Information pertaining to dynamic impedance waveforms within the healthy or eucontractile hearts (i.e. Zeucontractile(t)) is input. Zeucontractile(t) can be obtained, e.g., from data collected from patients implanted with devices who have had reverse remodeling and no longer suffer from cardiomyopathy. Alternatively or additionally, data can be derived from devices implanted in patients with primary electrical disturbances (e.g. long QT syndrome, Brugada syndrome) with structurally normal hearts. In any case, electrical stimulation is then delivered to the heart of the patient by the device based on a comparison of Zpatient(t) and Zeucontractile(t). Preferably, the electrical stimulation is delivered so as to reduce or minimize a difference between Zpatient(t) and Zeucontractile(t). It is believed that stimulation that tends to reduce the difference between Zpatient(t) and Zeucontractile(t) likewise tends to improve contractility within the myocardial tissue being stimulated, i.e. the stimulation is inotropic. In one particular example, Zpatient(t) is compared against Zeucontractile(t) to determine parameters that minimize an average difference between Zpatient(t) and Zeucontractile(t) throughout systole. In another example, an integral of Zeucontractile(t) (i.e. ∫Zpatient(t)dt) is compared against an integral of Zeucontractile(t) (i.e. ∫Zeucontractile(t)dt) to determine parameters that minimize a measure of incongruence of the integrals during systole. Preferably, these procedures are applied along each of a plurality of stimulation vectors, i.e. dynamic impedance is measured between each of a set of pairs of pacing/sensing electrodes, so as to address segmental contractility deficits. Note that the parameters set forth herein are merely exemplary and are by no means restricted to integration techniques applied to the dynamic impedance waveform. Other indices derived from impedance data may instead be implemented including, but not limited to, measurements of first and second order derivatives of the impedance waveform during different time periods of the cardiac cycle. Importantly, the parameters do not necessarily need to be based on Zeucontractile(t) but can be based on monitoring changes in any impedance based metric while the pacing modalities described herein are active.
In one particular implementation, parameters defining the characteristics of electrical stimulation, such as voltage, current, polarity, timing, stimulation frequency and the particular electrodes used to deliver the stimulation (i.e. the stimulation vector) are automatically adjusted or varied by the implanted device. Resulting dynamic impedance waveforms Zpatient(t) occurring within the patient are measured and compared against a template representative of the dynamic impedance waveforms of healthy hearts Zeucontractile(t) so as to determine a set of parameters associated with any or all stimulation vectors that minimizes the average difference between Zpatient(t) and Zeucontractile(t) or that minimizes a difference between integrals of Zpatient(t) and Zeucontractile(t). That is, the parameters are adaptively adjusted to minimize differences between the dynamic impedance waveforms of the patient and those of healthy persons. (Additionally, or alternatively, parameters can be determined that optimize other impedance measurements such as positive and negative dZ/dt, dZ′/dt). Thereafter, further delivery of stimulation is performed using the adaptively adjusted set of parameters so as to remodel the myocardium. This procedure may be periodically repeated to further adjust the parameters to take into account progression or regression of cardiomyopathies, new episodes of ischemia, myocardial stunning, etc.
Various impedance based indices may be derived from quantitative analysis of the dynamic impedance waveform and used alone or in combination for such comparisons. These indices provide the system with a physiologically relevant parameter that reflects the cardiac pathologic state. Quantitative analysis of the dynamic impedance waveform derived from various electrode combinations is suitable for such a technique as this data is representative of the contractile state and timing of contraction.
Note that, depending upon the needs of the particular patient and the programming of the device, the inotropic stimulation thus delivered may be subthreshold, suprathreshold or a combination of the two. Furthermore, the inotropic stimulation may be selectively delivered during a refractory period or during non-refractory periods, again depending upon the patient, regional properties of any given innervated region and the programming of the device. Insofar as inotropic stimulation delivered during refractory periods is concerned, the invention provides a technique for automatically adjusting the parameters defining such non-excitory stimulation so as to potentially improve its inotropic effect where and when needed. Insofar as inotropic stimulation delivered outside refractory periods is concerned, such stimulation may include both subthreshold and suprathreshold components, delivered during systole and/or diastole. In particular, depending upon the needs of the patient, suprathreshold stimulation may be selectively delivered during systole along particular stimulation vectors while timed to trigger local depolarization that fuses with intrinsic and more global myocardial depolarization. That is, the suprathreshold inotropic stimulation triggers an evoked response that fuses with an ongoing intrinsic depolarization arising due to natural pacing signals generated by the sinus node and intact portions of the conduction system. This procedure is referred to herein as "multidimensional forced fusion" (MDF). Multidimensional refers to both spatial and temporal components of electromechanical activation, i.e. MDF refers to the delivery of one or more suprathreshold pulse(s) triggering localized depolarizations that fuse with intrinsic depolarization in a synchronous fashion as to optimize both spatial and temporal aspects of myocardial electro-mechanical activation. This synchronous, inotropic pacing modality thereby seeks to minimize anisotropic properties in contractility and electro-mechanical dysynchrony, leading to multidimensional forced fusion. Thus, this technology serves to reduce anisotropic contractile properties and dysynchronous electromechanical activation. MDF represents one particularly promising technique for modifying a patient's dynamic impedance waveform to more closely match the dynamic impedance waveform of healthy hearts thereby restoring normal contractility and mechanical synchrony as is described in more detail below.
In accordance with a second general embodiment of the invention, techniques are provided for delivering a series of subthreshold stimulation pulses to the heart of a patient along with at least one suprathreshold pulse so as to achieve an inotropic effect, appropriately timed relative to depolarization of normally functioning myocardium. In one example, a series of subthreshold stimulation pulses are delivered prior to systole. At least one suprathreshold stimulation pulse is then delivered to the heart to trigger systole and then a series of additional subthreshold pulses are delivered following the suprathreshold pulse. In other examples, subthreshold pulses are only delivered just prior to the suprathreshold pulse or only just following the suprathreshold pulse. It is believed that, in at least some patients, the subthreshold pulses delivered before and/or after the suprathreshold pulse tend to improve myocardial contractility during systole. Preferably, the initial set of subthreshold pulses delivered prior to systole includes high frequency pulses having incrementally increasing pulse magnitudes. The pulse magnitudes increase until a depolarization threshold is eventually exceeded, thus providing at least one suprathreshold pulse that triggers depolarization. The subsequent set of subthreshold pulses delivered following the suprathreshold pulse are high frequency pulses having incrementally decreasing pulse magnitudes (i.e. decrementing magnitudes). The pulse magnitudes decrease throughout systole and during at least a portion of a subsequent period of diastole. Such incremental and/or decremental high frequency pacing algorithms may be modified as appropriate. By way of example, an initial decremental reduction in pulse magnitude followed by an incremental increase in pulses magnitudes may be beneficial in specific clinical scenarios.
In one particular example, the aforementioned dynamic impedance waveform techniques are employed to adjust the parameters defining the subthreshold pulses so as to improve their inotropic effect. Further, the suprathreshold pulse delivered along with the subthreshold pulses may be timed and directed so as to achieve MDF with an intrinsic depolarization, in accordance with techniques already summarized.
System and method implementations of these and other exemplary techniques are described herein.
The above and further features, advantages and benefits of the present invention will be apparent upon consideration of the present description taken in conjunction with the accompanying drawings, in which:
The following description includes the best mode presently contemplated for practicing the invention. This description is not to be taken in a limiting sense but is made merely to describe general principles of the invention. The scope of the invention should be ascertained with reference to the issued claims. In the description of the invention that follows, like numerals or reference designators will be used to refer to like parts or elements throughout.
Inotropic Stimulation Controlled Using Dynamic Impedance Waveforms
Referring first to
The term "eucontractile" is a nonstandard term used herein to generally convey that the dynamic impedance waveforms generated are from the chambers of hearts with normal contractility and synchronous electromechanical activation. By way of example, such eucontractile impedance waveforms can be derived from structurally normal hearts and/or hearts that have had reverse remodeling after recovering from cardiomyopathy. In order to compile such template impedance waveforms for comparative purposes, this data is acquired from patients implanted with devices that are no longer pathologic or are structurally normal with primary electrical disturbances and not myopathic (e.g. Brugada syndrome, long QT syndrome). The techniques of the invention seek to render the dynamic impedance waveform from a patient's heart as eucontractile as possible.
In one example, dynamic impedance waveforms from a population of healthy patients are obtained in advance using the techniques of U.S. Pat. No. 7,010,347. These waveforms are averaged or otherwise combined into a waveform template (referred to herein as a "eucontractile waveform template"), which is stored in the memory of the pacer/ICD following device implant. In this regard, note that many patients with pacer/ICDs do not have ischemic heart disease or cardiomyopathy and hence represent a population of patients from which eucontractile data can be readily obtained for use in creating the eucontractile waveform template.
As already summarized, the impedance along a direction of contraction of myocardial tissue increases during systole due to an increase in myocardial thickness that occurs during contraction and due to a reduction in blood volume and perhaps due to other factors. The dynamic impedance waveform of healthy (i.e. eucontractile) myocardial tissue Zeucontractile(t) differs from the corresponding impedance waveforms of diseased or ischemic tissues, i.e. tissues with impaired contractility. Typically, the dynamic impedance waveform of diseased tissues exhibits a less significant change in impedance during systole than that of healthy tissue. This is illustrated by the upper graph of
Returning to
At step 202, the pacer/ICD inputs from memory an initial, default set of inotropic stimulation pulse parameters including voltage, current, polarity, timing and the particular stimulation vector(s) to be used. The default inotropic pulse parameters typically differ significantly from the default parameters used for conventional pacing pulses. For example, the inotropic parameters may specify subthreshold pulse voltages timed for delivery just before or after suprathreshold pacing pulses. As another example, the inotropic parameters may specify "suprathreshold" pulse voltages timed for delivery during refractory periods. As will be explained further below, the inotropic pulse parameters may also specify the parameters of an entire sequence or train of subthreshold pulses. In one particular example, the default inotropic parameters are parameters found to be effective in other patients having similar medical conditions to the patient to receive the therapy as determined, e.g., based on otherwise routine experimentation involving populations of like patients. Typically, the default inotropic parameters are programmed or loaded into the pacer/ICD following device implant along with other default operational parameters of the device, such as default pacing parameters.
At step 204, the pacer/ICD delivers inotropic stimulation using the currently loaded set of inotropic pulse parameters. Hence, if the parameters specify that a set of subthreshold inotropic pulses are to be delivered during systole using a particular set of stimulation vectors, then such stimulation is generated by the pacer/ICD and delivered to the heart of the patient by the appropriate set of electrodes implanted within the heart at that time. The inotropic stimulation is typically in addition to otherwise conventional pacing pulses that might be delivered. At step 206, the pacer/ICD measures the dynamic impedance waveform of patient Zpatient(t) along the various stimulation vectors specified at step 200. Again, techniques described in U.S. Pat. No. 7,010,347 may be used. At step 208, the pacer/ICD then compares Zpatient(t) against Zeucontractile(t) for each stimulation vector and adjusts the inotropic pulse parameters associated with any or all stimulation vectors in an attempt to reduce an average difference between Zpatient(t) and Zeucontractile(t) along the various stimulation vectors. A variety of otherwise conventional mathematic techniques may be used quantify the amount of difference between or among the various dynamic impedance waveforms along the various stimulation vectors. (Techniques exploiting integrals are discussed below in connection with
In this manner, an iterative and adaptive procedure is provided for optimizing inotropic stimulation parameters. In particular, the pacer/ICD is preferably programmed to select different stimulation vectors for delivery of the inotropic stimulation during initial iterations of the procedure so as to identify the particular stimulation vectors that have the greatest affect on contractility. Typically, these will be the vectors that are aligned with the direction of contraction of the hypocontractile myocardial tissues. By selecting particular stimulation vectors or combinations of stimulation vectors, multidimensional inotropic therapy is thereby achieved. Once the optimal stimulation vector(s) has been identified, the other parameters defining the inotropic stimulation pulse are then iteratively and adaptively adjusted to refine the efficacy of the pulses. Typically, the range of adjustment of the various parameters is constrained in advance. For example, to provide subthreshold inotropic pacing outside of refractory periods, the pulse voltage and current magnitudes are constrained to remain at subthreshold levels. As another example, to provide nonexcitory inotropic pacing within refractory periods, the pulse voltage and current magnitudes may exceed threshold levels, but the timing of those pulses is constrained to ensure the pulses are delivered within refractory periods.
In one example, this iterative procedure is performed continuously or at least very frequently to substantially continuously update the inotropic pulse parameters. Alternatively, the procedure may instead be performed only until further adjustments do not achieve significant gains in myocardial contractility or until some fixed number of iterations is compete. If so, the procedure is preferably reactivated periodically to adjust the inotropic parameters in response to changes within the patient, such as progression or regression of cardiomyopathy or the onset of additional episodes of cardiac ischemia. Indeed, detection of an episode of cardiac ischemia may be used to trigger activation of the procedure so as to promptly address any localized changes in contractility arising due to the ischemia. Techniques for detecting cardiac ischemia using a pacer/ICD are described in, e.g., U.S. patent application Ser. No. 10/603,429, entitled "System and Method for Detecting Cardiac Ischemia Using an Implantable Medical Device", of Wang et al.; U.S. patent application Ser. No. 10/603,398, entitled "System and Method for Detecting Cardiac Ischemia Based on T-Waves using an Implantable Medical Device", of Min et al.; and in U.S. patent application Ser. No. 11/394,724, of Ke et al. entitled "System and Method for Detecting Cardiac Ischemia in Real-Time using a Pattern Classifier Implemented within an Implantable Medical Device". Procedures for detecting progression or regression of cardiomyopathies may also be used to trigger the iterative procedure. See, for example, U.S. Pat. No. 6,922,587 of Weinberg, entitled "System and Method for Tracking Progression of Left Ventricular Dysfunction Using Implantable Cardiac Stimulation Device". See, also, U.S. patent application Ser. No. 11/397,066 of Koh, entitled "QT-Based System and Method for Detecting and Distinguishing Dilated Cardiomyopathy and Heart Failure Using an Implantable Medical Device".
These integral values or cardiac performance indices can be acquired over specific time frames. By way of example, the limits for integration can be between time of aortic valve opening and aortic valve closure, so as to derive an index of systolic cardiac performance. Likewise, a diastolic cardiac performance index can be derived during the time frame between aortic valve closure and end-diastole. Any number of indices may be derived and compared using impedance data and those discussed in this invention are by way of example. Other such indices are described in U.S. Pat. No. 7,010,347. In some implementations, it may be appropriate to use line integrals.
At step 308, the pacer/ICD then compares ∫Zpatient(t)dt against ∫Zeucontractile (t)dt for each stimulation vector and makes adjustments to the inotropic pulse parameters associated with any or all stimulation vectors in an attempt to reduce arithmetic differences between ∫Zpatient(t)dt and ∫Zeucontractile(t)dt along the various stimulation vectors, such as an area difference between the integrals (e.g. minimal integral difference). A variety of otherwise conventional mathematic techniques may be used to quantify the difference between or among the various dynamic impedance waveforms along the various stimulation vectors. Processing then returns to step 304 where additional inotropic stimulation is delivered using the adjusted set of parameters. Steps 304-308 proceed in a loop to repeatedly and iteratively adjust the inotropic parameters in an effort to improve patient contractility by reducing the degree of incongruence between ∫Zpatient(t)dt and ∫Zeucontractile(t)dt along the various stimulation vectors. Thus, again, an iterative and adaptive procedure is provided for optimizing inotropic stimulation parameters. As with the technique of
Additionally, or alternatively, derivatives of the dynamic impedance waveform may be exploited to determine optimal inotropic parameters. Exemplary derivatives are illustrated in
The aforementioned techniques may be advantageously employed to determine a set of inotropic parameters sufficient to achieve forced fusion between intrinsic depolarization and evoked responses triggered by inotropic pulses. Forced fusion is illustrated in
Note also that the techniques of either
Multiple Pre- and Post-Systolic Subthreshold Inotropic Pulses
Turning now to
At step 506 of
In one example, the frequency of the inotropic stimulation pulses is in the range of 16 to 256 Hz and pulse widths are in the range of 0.5-20 ms. (E.g., a 10 ms pulse delivered at 50 Hz.) The total number of inotropic stimulation pulses delivered prior to depolarization should be adequate to achieve inotropy without excessive costs to the system (e.g. battery depletion). By way of example, the total number of inotropic stimulation pulses delivered before and/or following depolarization is in the range of 1 to 100 pulses. The magnitude of the weakest of the inotropic stimulation pulses, expressed as a percentage of a depolarization threshold voltage for the patient, may be in the range of 12.5 to 87.5%. The first set of incrementally increasing subthreshold pulses are preferably delivered just prior to the suprathreshold pulse. Likewise, the second set of incrementally decreasing (i.e. decrementing) subthreshold pulses are preferably delivered just following to the suprathreshold pulse. In one example, all of the first set of subthreshold pulses are delivered within a time period extending 100 milliseconds prior to the suprathreshold pulse. All of the second set of subthreshold pulses are delivered within a time period extending 100 milliseconds following the suprathreshold pulse. Note also, that in some examples, it may be appropriate to only deliver subthreshold pulses prior to the suprathreshold pulse. In other examples, it may be appropriate to only deliver subthreshold pulses following to the suprathreshold pulse. Hence, the example wherein subthreshold pulses are delivered both prior to and after the suprathreshold represents just one implementation and various characteristics and durations of such pulse trains may be optimal in different clinical scenarios. In some implementations, the pre- and post-pulses are inotropic pulses whereas the pulse that triggers depolarization is a more typical 0.1-2 ms duration pulse. The duration of the pulse train is not necessarily inclusive of (or not necessarily exclusive of) the absolute and relative refractory periods. Pulse widths can be decremented and/or incremented along with changes in the amplitude or magnitude of the stimuli.
The techniques described above with reference to
Note that this is somewhat contrary to the principle that myocardial depolarization is "all or none". Indeed for any region of myocardium (e.g. individual myofibrils) once depolarization occurs, contraction ensues and neighboring myofibrils depolarize secondary to being a conductive tissue (via gap junctions that electrically connect neighboring myofibrils.) However, it is believed by the inventor that not all regions necessarily depolarize simultaneously, as specific areas may have high pacing thresholds and/or are electrically isolated secondary to scar tissue. Although late depolarized regions may indeed contract (assuming the tissue is not electrically isolated or dead), the myofibrils may contract so late during the cardiac cycle (i.e. dysynchronous contraction) as to be a detriment and not contribute to global systole. MDF is, at least in part, intended to rectify this pathologic state by augmenting contraction in myocardium that is depolarized and ensuring depolarization of myocardium that has high pacing thresholds and/or is electrically isolated enough to either not be depolarized or be depolarized so late that there is no contribution to global systole. The use of different stimulation vectors allows the gradual recruitment to proceed from different directions to encourage forced fusion. The pulse trains are preferably applied during each heart beat to remodel the myocardium over time, but may be applied at periodic intervals or on an "as needed" basis. Note that, regardless of whether "all or none" depolarization does indeed occur, the techniques of the invention are believed to have advantageous effects.
Although described primarily with reference to ventricular stimulation examples, atrial inotropic stimulation may alternatively or additionally be employed. The various techniques may be exploited using any appropriate implantable cardiac stimulation device. For the sake of completeness, an exemplary pacer/ICD will now be described.
Exemplary Pacemaker/ICD
To sense left atrial and ventricular cardiac signals and to provide left chamber pacing therapy, pacer/ICD 610 is coupled to a "coronary sinus" lead 624 designed for placement in the "coronary sinus region" via the coronary sinus os for positioning a distal electrode adjacent to the left ventricle and/or additional electrode(s) adjacent to the left atrium. As used herein, the phrase "coronary sinus region" refers to the vasculature of the left ventricle, including any portion of the coronary sinus, great cardiac vein, left marginal vein, left posterior ventricular vein, middle cardiac vein, and/or small cardiac vein or any other cardiac vein accessible by the coronary sinus. Accordingly, an exemplary coronary sinus lead 624 is designed to receive atrial and ventricular cardiac signals and to deliver left ventricular pacing therapy using at least a left ventricular tip electrode 626, left atrial pacing therapy using at least a left atrial ring electrode 627, and shocking therapy using at least a left atrial coil electrode 628. (To the extent that atrial pacing is relevant to the invention, the examples herein pertain to right atrial pacing/sensing but left atrial pacing/sensing may also be used.) With this configuration, biventricular pacing can be performed. Although only three leads are shown in
A simplified block diagram of internal components of pacer/ICD 610 is shown in
At the core of pacer/ICD 610 is a programmable microcontroller 660, which controls the various modes of stimulation therapy. As is well known in the art, the microcontroller 660 (also referred to herein as a control unit) typically includes a microprocessor, or equivalent control circuitry, designed specifically for controlling the delivery of stimulation therapy and may further include RAM or ROM memory, logic and timing circuitry, state machine circuitry, and I/O circuitry. Typically, the microcontroller 660 includes the ability to process or monitor input signals (data) as controlled by a program code (i.e. software) stored in a designated block of memory. Software running within the microcontroller 60 includes various components for controlling the functions described above in connection with
In particular, the microcontroller includes a dynamic impedance-based inotropic stimulation controller 701 operative to control delivery of inotropic therapy based on dynamic impedance waveforms in accordance with the techniques of
The details of the design of the microcontroller 660 are not critical to the invention. Rather, any suitable microcontroller 660 may be used that carries out the functions described herein. The use of microprocessor-based control circuits for performing timing and data analysis functions are well known in the art.
As shown in
The microcontroller 660 further includes timing control circuitry (not separately shown) used to control the timing of such stimulation pulses (e.g., pacing rate, atrio-ventricular (AV) delay, atrial interconduction (A-A) delay, or ventricular interconduction (V-V) delay, etc.) as well as to keep track of the timing of refractory periods, blanking intervals, noise detection windows, evoked response windows, alert intervals, marker channel timing, etc., which is well known in the art. Switch 674 includes a plurality of switches for connecting the desired electrodes to the appropriate I/O circuits, thereby providing complete electrode programmability. Accordingly, the switch 674, in response to a control signal 680 from the microcontroller 660, determines the polarity of the stimulation pulses (e.g., unipolar, bipolar, combipolar, etc.) by selectively closing the appropriate combination of switches (not shown) as is known in the art.
Atrial sensing circuits 682 and ventricular sensing circuits 684 may also be selectively coupled to the right atrial lead 620, coronary sinus lead 624, and the right ventricular lead 630, through the switch 674 for detecting the presence of cardiac activity in each of the four chambers of the heart. Accordingly, the atrial (ATR. SENSE) and ventricular (VTR. SENSE) sensing circuits, 682 and 684, may include dedicated sense amplifiers, multiplexed amplifiers or shared amplifiers. The switch 674 determines the "sensing polarity" of the cardiac signal by selectively closing the appropriate switches, as is also known in the art. In this way, the clinician may program the sensing polarity independent of the stimulation polarity. Each sensing circuit, 682 and 684, preferably employs one or more low power, precision amplifiers with programmable gain and/or automatic gain control and/or automatic sensitivity control, bandpass filtering, and a threshold detection circuit, as known in the art, to selectively sense the cardiac signal of interest. The automatic gain/sensitivity control enables pacer/ICD 610 to deal effectively with the difficult problem of sensing the low amplitude signal characteristics of atrial or ventricular fibrillation. The outputs of the atrial and ventricular sensing circuits, 682 and 684, are connected to the microcontroller 660 which, in turn, are able to trigger or inhibit the atrial and ventricular pulse generators, 670 and 672, respectively, in a demand fashion in response to the absence or presence of cardiac activity in the appropriate chambers of the heart.
For arrhythmia detection, pacer/ICD 610 utilizes the atrial and ventricular sensing circuits, 682 and 684, to sense cardiac signals to determine whether a rhythm is physiologic or pathologic. As used herein "sensing" is reserved for the noting of an electrical signal, and "detection" is the processing of these sensed signals and noting the presence of an arrhythmia. The timing intervals between sensed events (e.g., P-waves, R-waves, and depolarization signals associated with fibrillation which are sometimes referred to as "F-waves" or "Fib-waves") are then classified by the microcontroller 660 by comparing them to a predefined rate zone limit (i.e., bradycardia, normal, atrial tachycardia, atrial fibrillation, low rate VT, high rate VT, and fibrillation rate zones) and various other characteristics (e.g., sudden onset, stability, physiologic sensors, and morphology, etc.) in order to determine the type of remedial therapy that is needed (e.g., bradycardia pacing, antitachycardia pacing, cardioversion shocks or defibrillation shocks).
Cardiac signals are also applied to the inputs of an analog-to-digital (A/D) data acquisition system 690. The data acquisition system 690 is configured to acquire intracardiac electrogram signals, convert the raw analog data into a digital signal, and store the digital signals for later processing and/or telemetric transmission to an external programmer device 702. The data acquisition system 690 is coupled to the right atrial lead 620, the coronary sinus lead 624, and the right ventricular lead 630 through the switch 674 to sample cardiac signals across any pair of desired electrodes. The microcontroller 660 is further coupled to a memory 694 by a suitable data/address bus 696, wherein the programmable operating parameters used by the microcontroller 660 are stored and modified, as required, in order to customize the operation of pacer/ICD 610 to suit the needs of a particular patient. Such operating parameters define, for example, pacing pulse amplitude or magnitude, pulse duration, electrode polarity, rate, sensitivity, automatic features, arrhythmia detection criteria, and the amplitude, waveshape and vector of each shocking pulse to be delivered to the patient's heart within each respective tier of therapy. Other pacing parameters include base rate, rest rate and circadian base rate. Still other parameters are the aforementioned inotropic pulse parameters.
Advantageously, the operating parameters of the implantable pacer/ICD 610 may be non-invasively programmed into the memory 694 through a telemetry circuit 700 in telemetric communication with the external device 702, such as a programmer, transtelephonic transceiver or a diagnostic system analyzer. The telemetry circuit 700 is activated by the microcontroller by a control signal 706. The telemetry circuit 700 advantageously allows intracardiac electrograms and status information relating to the operation of pacer/ICD 610 (as contained in the microcontroller 660 or memory 694) to be sent to the external device 702 through an established communication link 704. Pacer/ICD 610 further includes an accelerometer or other physiologic sensor 708, commonly referred to as a "rate-responsive" sensor because it is typically used to adjust pacing stimulation rate according to the exercise state of the patient. However, the physiological sensor 708 may, depending upon its capabilities, further be used to detect changes in cardiac output, changes in the physiological condition of the heart, or diurnal changes in activity (e.g., detecting sleep and wake states) and to detect arousal from sleep. Accordingly, the microcontroller 660 responds by adjusting the various pacing parameters (such as rate, AV Delay, V-V Delay, etc.) at which the atrial and ventricular pulse generators, 670 and 672, generate stimulation pulses. While shown as being included within pacer/ICD 610, it is to be understood that the sensor 708 may also be external to pacer/ICD 610, yet still be implanted within or carried by the patient. A common type of rate responsive sensor is an activity sensor incorporating an accelerometer or a piezoelectric crystal, which is mounted within the housing 640 of pacer/ICD 610. Other types of physiologic sensors are also known, for example, sensors that sense the oxygen content of blood, respiration rate and/or minute ventilation, pH of blood, ventricular gradient, etc.
The pacer/ICD additionally includes a battery 710, which provides operating power to all of the circuits shown in
As further shown in
In the case where pacer/ICD 610 is intended to operate as an implantable cardioverter/defibrillator (ICD) device, it detects the occurrence of an arrhythmia, and automatically applies an appropriate electrical shock therapy to the heart aimed at terminating the detected arrhythmia. To this end, the microcontroller 660 further controls a shocking circuit 716 by way of a control signal 718. The shocking circuit 716 generates shocking pulses of low (up to 0.5 joules), moderate (0.5-10 joules) or high energy (11 to 40 joules), as controlled by the microcontroller 660. Such shocking pulses are applied to the heart of the patient through at least two shocking electrodes, and as shown in this embodiment, selected from the left atrial coil electrode 628, the RV coil electrode 636, and/or the SVC coil electrode 638. The housing 640 may act as an active electrode in combination with the RV electrode 636, or as part of a split electrical vector using the SVC coil electrode 638 or the left atrial coil electrode 628 (i.e., using the RV electrode as a common electrode). Cardioversion shocks are generally considered to be of low to moderate energy level (so as to minimize pain felt by the patient), and/or synchronized with an R-wave and/or pertaining to the treatment of tachycardia. Defibrillation shocks are generally of moderate to high energy level (i.e., corresponding to thresholds in the range of 5-40 joules), delivered asynchronously (since R-waves may be too disorganized), and pertaining exclusively to the treatment of fibrillation. Accordingly, the microcontroller 660 is capable of controlling the synchronous or asynchronous delivery of the shocking pulses.
What have been described are various systems and methods for use with a pacer/ICD. However, principles of the invention may be exploiting using other implantable systems or in accordance with other techniques. Thus, while the invention has been described with reference to particular exemplary embodiments, modifications can be made thereto without departing from the spirit and scope of the invention. Note also that the term "including" as used herein is intended to be inclusive, i.e. "including but not limited to."
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|Classification aux États-Unis
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|Classification internationale
|Classification coopérative
|Classification européenne
|28 aoűt 2006
Owner name: PACESETTER, INC., CALIFORNIA
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:SCHECTER, STUART O.;REEL/FRAME:018181/0825
Effective date: 20060822
|3 févr. 2014
|Fee payment
Year of fee payment: 4
|3 févr. 2014
|Surcharge for late payment


text:
August 15, 2007
Virtually any U.S. reform proposal promising "universal coverage" will reduce health care spending. Why? Because Congress has a long and sordid history of support for health-care price controls, says Merrill Matthews, director of the Council for Affordable Health Insurance and a resident scholar with the Institute for Policy Innovation.
- Medicare reimbursements to hospitals have been price-controlled since 1983 and to physicians since 1992.
- If Medicare represented 1 percent or 2 percent of the health care market -- as the U.S. Department of Veteran's Affairs (VA) does with respect to prescription drugs -- price controls would create distortions, but they would likely be manageable.
- However, Medicare is the dominant insurer in the country; its price controls become the benchmark.
Whenever the government controls prices, it arbitrarily determines who it will pay, how much, and for what, explains Matthews. Vendors that provide goods and services generally begin to work the system in order to maximize their gain -- or more accurately when referring to doctors in Medicare, minimize their losses. When Medicare distorts a price -- and virtually all government-set prices are distorted -- the reverberations are felt throughout the health-care system.
Consider the case of physician reimbursements:
- Every year, doctors face a cut in Medicare reimbursements, even though their costs for providing care continue to rise.
- The American Medical Association's lobbying effort has managed to keep current reimbursements about the same as they were in 2001, in part by backing the Medicare Modernization Act in 2003; that's six years without an increase.
- And unless Congress acts, doctors face a 10 percent cut in reimbursements in 2008, and a 40 percent cut by 2016.
Because politicians want to keep health-care spending as low as possible, they have very little incentive to raise those reimbursement rates, says Matthews.
Source: Merrill Matthews, "Cost Control for Dummies," Wall Street Journal, August 15, 2007.
For text:
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subset: commoncrawl


text:
Southern Sweden » Havet Marstrand
The magnetic attraction of Marstrand is really completely understandable. Where else can one find such a location? With such a wealth of bathing, beautiful houses, an impressive fortress, cafes and restaurants, regattas and entertainment, it's easy to understand why people flock here. Just as they have for centuries.
Malstrand, Masstrandir, Måsestrand. Marstrand has had many names throughout its long history. This is perhaps not so surprising since the town was founded as long ago as the 13th century by a Norwegian king, and has also been under Danish hegemony.
One thing is certain: Marstrand boasts an exciting and lively history, filled with a sprinkling of riches, depraved living and celebrities.
If you have ever been a guest at Havet Marstrand and enjoyed the beautiful surroundings, the inspiring environment and all the other tasteful experiences that Marstrand has to offer, you will find yourself longing to return. Whether you want a sunshine and swimming holiday, or to celebrate a special occasion, work with your colleagues or have a relaxing weekend – you are always welcome.
Havet Marstrand
During high season we only rent out the apartments on a weekly basis. High season is from week 27 up to week 33.


text:
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Judy Sanqunetti's Portfolio


text: Shelbyville is a city located adjacent to Springfield. Shelbyville and Springfield are treated in the series as twin cities, though with an intense rivalry between the two. The city of Shelbyville was founded by Shelbyville Manhattan in 1796, who held the belief that people should be allowed to marry their cousins, a practice disallowed by fellow explorer and founder of Springfield, Jebediah Springfield. As a result of this disagreement, the two founders and their party split into separate groups, and went their own ways; since that time, the populaces of Springfield and Shelbyville have held a strong rivalry.


text:
Hello everyone,
Chartered Accountancy is the widely opted course which provides various jobs in the private and the public sectors. It is one of the beneficial jobs which comprise work of accounting, business laws, taxation, auditing, corporate governance, project evaluation and corporate finance.
This biggest exam is conducted in the name of CPT Common Proficiency Test and Integrated Professional Competence Examination IPCC by the Institute of Chartered Accountants of India (ICAI). IPCC was held in November and CPT in December 2011. The sources said that 1.2 lakhs students had appeared for IPCC and 8 lakhs for CPT.
They have announced that the results will be declared in the month of January or February. But, still it is not announced. The students can check the official website for the latest updates and they can get their results by enrolling their roll-number alone. www.icai.org.
If you have any views and opinions about CA Results 2012, please share it here!


text:
That's just awesome
SL Rahat Loukoum
Je Reviens
There are more, but my mind has gone blank!
Angel. And some hugely indolic fake-y fake jasmine by Floris -- it took liquid Tide to get that one off my skin. Annick Goutal Sables, although I'll have to give that one another chance once the weather cools off some more. And I'm having a problem with Bond No. 9's Chinatown, which I got in a swap recently, but is sweet, sweet, sweet on my skin -- going to give that another chance, too.
also at http://olfactarama.blogspot.com
Musings and random thoughts about the genie in the bottle
"I don't know the key to success,
but the key to failure is trying to please everybody."
Bill Cosby
I think Chinatown is worth persisting with - very gingerly mind! I hated it on card, wasn't too struck with it the first couple of times on skin, but one day it just worked for some reason, and it was impressive as gourmands go. Maybe the dosage has to be spot on. So I would apply it sparingly and wait a fair while before sniffing! Possibly several hours...
And the blasted stuff sticks to my skin like glue.
"A woman who doesn't wear perfume has no future." Coco Chanel
I'm streamlining my collection http://community.basenotes.net/showt...29#post1219729
Thanks so much, Wordbird, for the heads up on Cabochard. It is one I have been toying with trying, for like Guerlain Vetiver, it came into the world in the same year as me. It got a slating in The Guide, and whilst that alone would not have stifled my curiosity, your exclamatory capitals have killed it stone dead .
Personal notes from "perfume reviews.txt"
-Neil Morris - Afire - smells like tandori spices. Supposed to be berries and caramel but if its caramel, it's in the same way as "Safran brulant" which was gourmand, but disgusting due to smelling more like cooking spices than dessert.
-Artisan Parfumeur - Piment Brûlant - Bell pepper, it makes me sick after a few minutes.
-CB I Hate Perfume - In the Summer Kitchen - smells like a summer kitchen garbage can with old banana peels in it, and spices. Don't like it at all.
CB I Hate Perfume - CB 93 - Disgusting! Smells like herbs and spices, some that stink. Says geranium, but I dunno what that is.
-Creed - Millesime Imperial (horrible, just horrible)
I'd like to add that at first, Coup de Fouet and Anarchiste, both from Caron, seemed like scrubbers... but I forced myself to wear them and ended up loving them. I find them kinky.
I have never had such an extreme aversion to a fragrance when I tried Jicky , it literally made me feel physically sick , now I dont know if that makes me a philistine in the world of fragrance , I so wanted to like it too
I love this thread! Misery loves company....
I got a horrid headache today shortly after spraying on Aqua Allegoria Rosa Magnifica, newly purchased unsniffed (silly me.) Tried scrubbing but it wouldn't come off entirely. Could something else have been giving me the headache and maybe that's why the scent hit me the wrong way?
I must be a glutton for punishment, but I'm giving it one more chance tomorrow.
If that produces the same result, the bottle will need to find a new home.
I do feel your pain here...
I had a new scrubber experience today, though it was only a tester squirt on the back of the hand - of DKNY Woman. I was going to characterise it as "malevolent grapefruit" but I am going to regrade it as "grapefruit serial killer" for the fact that it killed my divine sample of Chanel Beige (further round the hand) stone dead. A grapefruit version of Beige is not what the world needs, and a nail brush and strongly scented soap have failed to shift it.
Further up the arm is Clinique Happy and it too is struggling to raise a smile at this point.
There are somethings I'm not a fan of (iris, leather, birch tar) but don't quite get me to the point of scrubbing. The only thing that really does is it jasmine. I love jasmine in the garden in full bloom - it's just divine. But in perfume on my skin all I get is terribly fecal indole. My worst ever perfume experiences were with Luten's Sarassins, Patou's Joy and L'Artisan's The Pour un Ete. All lovely for 10 minutes and then sheer scrubbing hell. Uggg.
P.S. I love Aromatics Elixir and tuberose anything. No problems with those!
Last edited by rachelsf; 26th September 2008 at 10:04 PM.
Aquolina Blue Sugar. Deep-fried licorice. Could not scrub it off fast enough..
When I read the title right away I thought of both
Miss Dior & 24 Faubourg and quickly thereafter
of Caron Narcisse Noir. This is way too funny actually.
I thought for sure I will be scorned for not being able to appreciate
those two fine fragrances, but honestly, they could not smell
worse with my ungrateful chemistry! I know, I know my loss.
But as I read your list, I cannot help but realize that in fact
that's really what it comes down to, CHEMISTRY!
So I have to fully agree with you on the following:
And yet, there are so many out there who LOVE these scents,
and so many I loved them on. Just not on me!!! No way, no how!
And then, there are those scents that many of you dislike
like L Ete en Douce, Chinatown, Boudoir and
Rose Alexandrie but do I ever adore those scents!!!
And they work wonderfully with my chemistry.
I guess you can't wear them all
Autumn treasures: Magnetism, Midnight Orchid, Tea for Two,
Aimez-Moi, Chinatown, Dzongkha, Five O'Clock Au Gingembre,
Cittá di Kyoto, Jasmin de Nuit, Jasmin Full, Kelly Calèche, Venezia,
Douce Amère, Eau de Charlotte, Falling In Love, Chergui, Prada,
Rose Alexandrie, Hypnôse, Omnia, Flowerbomb, Poivre Piquant,
Cuir Beluga, 7:15am in Bali, Lolita Lempicka, Fumerie Turque,
Datura Noir, Songes, Gaultier², L'Ombre Fauve, Kors, My Couture,
Ligea "La Sirena", Red Aoud, Rose Absolu, Cèdre, Milk, No. 23
Bending backwards is like falling in love, come bend with me
The mind is like a drunken monkey, it constantly jumps here and there.
Swami Niranjan-ananda
"Our life is shaped by our mind; we become what we think."
That's interesting, AP! You may turn out to be the closest match to a "scrubber twin" for me! I am very keen to try Rose Alexandrie as it happens, but Boudoir is a nightmare on me and you know I have fallen out of love with L'Ete en Douce.
Do you also like the AP range? I am not so keen on the original - bit 50's retro talcum powder - but Maitresse is quite nice, also the Eau Emotionelle or whatever the lighter one is called. Strip is a bit mad as I recall - must be the geranium.
Wow, so many frags I enjoy are other's scrubbers !
Schiaparelli Schocking, Anais Anais, 24 Faubourg, Angel, Lou Lou, Estee Lauder Private Collection Tuberose Gardenia, Joop pour Homme ( on my boy, yum ! ), Opium, Flower Bomb, JPG Classique...*sigh*
Recent scrubbers for me, The new Chloe, and Agent Provocateur.
The only ones that I had to shower off were:
Creed Orange Spice (same as Kouros to me)
The funny thing is I have tried Kouros and TdH more than once but each time I have to shower it back off. I want to like them.
Jazz smelled like dog poop on me. Unfortunately I sampled it at the Shanghai airport and had to "enjoy" it for the 14 hour trip back home. It smelled fine on paper.
I keep checking back with this thread because the replies are so fascinating. Have any of your scrubbers morphed into scents you decide you can tolerate, or even like, after all? Or is it "once a scrubber, always a scrubber?" I ask because I initially had the same reaction to Tolu mentioned by at least a few of you, yet the other day after bravely (insanely?) trying it again, I did not detest it any more. I am not sure I like it yet, but I did not have the urge to scrub it off.
If you like Chinatown but it is a bit too much, try Fracas
But once you get locked into a serious perfume collection, the tendency is to push it as far as you can.
But once you get locked into a serious perfume collection, the tendency is to push it as far as you can.
If I hadn't experienced it myself I don't know if I would have believed it. I'm not sure what actually changes, if it is one's exposure to different smells, or what exactly happens or can happen. It would be interesting to understand the multiple dimensions of this phenomena.
Cabotine....I tried...it just kept getting stronger.
Velvet Gardenia ( CHEEEEEEEEEESE! And death. )
Secretions Magnifique ( Saliva and metal )
Yatagan ( BBQ'd meat and pine... oh joy )
Duro ( sweet candy frosting amber )
There are more, but those are the worst to date.
Though, to be fair to "scrubbers", two have since become well-liked fragrances - Rasa Extreme and Aoud Cuir D'Arabie
I'm glad this thread has been resurrected. I have new entries:
Bond No. 9 Madison Soiree: A fabulous new fusion appetizer of heavily veined blue cheese on a decaying gardenia petal. Three Michelin stars. Customers flock. Restaurant closes within a year, the victim of the customers' common sense.
Nuit de Cellophane: Oh, the sheer joy of hairspray lacquered over jellied osmanthus! It's stiff and crinkly. On this basis alone, a triumph. But who would want the bouquet contained within? If there were some sort of aerosol preservative that would keep flowers looking fresh indefinitely, this would be it. Great environmental damage would occur.
Any Angel flanker: Why are these so bad? Is the original bad and I just don't realize it? Why is there a pronounced note of wet hay in all of them?
Parfum de Therese: The ultimate in jolie laide. Trust me, this one is legendary. I'm not even that sure that I dislike it. "Womanly" and overripe melon, sweating in the heat--a feast for flies. More disturbing than ugly. Gives "mature" a bad name.
Last edited by Orion; 8th May 2009 at 05:50 AM.
This week, 'Chanel Cuir de Russie: Skin Scent' at http://thescentimentalist.blogspot.com/
Comme des Garcons PARFUMS Series 3 Incense: Avignon: OLD MOLDY DAMP CHURCH CURTAIN!
OMG I nearly ran from myself trying to get away from it. Tried to cover it, didn't work. Tried to scrub it, didn't work. Showered and changed clothes...could still faintly smell it! Doused the area with a stronger beast and prayed not to smell it ever again. Run, people! As far away from a bottle of this as you can! Interestingly enough I love most of your scrubbers. Love youth dew, bronze goddess, and I adore tuberose (carnal flower, anyone?) Hello, that's to die for! So maybe my nose leads me a tad askew compared to others...hilarious thread my friends, you guys crack me up!
These posts are hilarious! There is something about the combination of wit, indignation, yet respect for everyone who might love the offensive brews: one perfumista's scrubber is another one's paradise. Or something like that!
I am trying to remember....usually i can tough it out through a fragrance in the interest of "science", and I often hand in there b/c I change my mind. But there are a few i just can't wear:
Angel , Covet, Lovely Tocade
...come to mind as fragrances I simply couldn't have on my skin, even in the interest of testing and comparing.
Sweet + fruity+ vanilla is usually the recipe for a shower one me (Tocade, Angel); there is something about the musks in Lovely and COvet that nauseate me (esp. the musk chocolate combo in Covet)
Leesee, yes there are several in the From Scrub to Love category for me: FIrst time: blech. Tried again--bought the full bottle!
Eau des merveilles
Bal à versailles
Iris Ganache
Bois d'Armenie
Jean Louis Scherrer
Last edited by Nostalgie; 8th May 2009 at 02:37 PM.
"You...put on cologne to write?"(From Midnight in Paris)
Stop by for a chat: http://perfumedletters.wordpress.com/
My book reviews: http://www.nstperfume.com/author/Cheryl/


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Kristina Lucas-Hayden
Born in California, Lucas attended UCLA where she received her BA, MA and MFA in sculpture. Along with husband/artist Michael Hayden, Lucas co-owns Thinking Lightly, Inc. Her sculptures designed to merge with architecture can be found in both corporate and private collections. Lucas lives in Santa Rosa.
Working site specifically allows me a total freedom from any preconception with regard to materials. For each location, I select and utilize the material(s) that best suit my concept for that particular place. I believe sculpture must not only withstand the physical rigors of the environment, but also the elusive and constantly changing aesthetic demands of sophisticated viewers, day after day. My repertoire of media consists of all the traditional sculptural materials, including clay, metals, wood, plaster, and stone, as well as glass, plastics, fabrics, concrete, and holographically originated diffraction gratings, transparent films and flexible inks and dyes, resin, epoxy paints, mechanically created composites , light, and I love technology. Not that I know much, but I know that anything I can imagine can probably be done somehow and I enjoy the search for a link to that technology or technologist who may be able to help me realize my vision. I consider communication to be the most valuable part of the sculptural process.
Suspended sculptures allow one to be both inside and outside the work. The sculpture must either have its own structural integrity, or be supported by a superstructure [architecture or nature]. I see walls, ceilings and floors of interior spaces as potential frameworks for sculptures. Atriums, vaulted ceilings, and stairwells, which naturally draw the eye upward, in my mind are empty volumes of air waiting to be given definition and purpose by sculpture. In Marijke's Grove the trees hold the sculpture. I created "Cloud" after several different attempts at outdoor installation, the challenge always being to stand up against natural forces and still maintain a certain fragility. Like a poem engraved in marble, read in a whisper… Nature is my inspiration and the sculpture is my interpretation.
My sculptures are simple, dynamic, kinetic and unique. They occur to me spontaneously, but come into physical existence by lengthy and labor intensive processes which both exhaust and energize.
Beyond the initial encounter, I hope my works continue to offer revelation… that each sculpture will continuously present new aspects of itself for discovery by viewers who may see it only once, or those who pass it many times every day for years and years.
I didn't know Al Voigt. I know I would have been honored to have his support of my work. I like to think that "Cloud" would have surprised and intrigued him a little. I am so delighted to be included in this exhibition. Art is a universal language… a luxury… a necessity.
Kristina Lucas, Sculptor


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Prague Travel Blog› entry 2 of 8 › view all entries
Hello all once again. We are currently in the city of Prague we had just gotten here at about 8 am on Saturday June 24th. The trip here and using our Eurail passes for the first time was an experience we totally didnt have this one ticket we needed for a portion of our trip that wasnt covered on our Eurail pass so we got into it with the character on the train giving us a hard time and he finally decided for about 24 Euros a piece he wouldnt bother us anymore. What a pile!!! We had taken an overnight train from Amsterdam on Friday night because we couldnt stay in our hostel in Amsterdam anymore due to the fact that the government was shutting it down on Friday at noon. Yeah it was that nice. Anyway we have about a half an hour before we can check into our hostel here and I think we are planning on staying here two nights and going to Munich on Monday but nothing is set in stone yet so we will see. Until next time Have a great day


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Wednesday, March 17, 2010
My First E-Book Coming Soon!
The image above is a sneak peek at my very first e-book, "Learn About Liberty." I will be making it available here at The Humble Libertarian as early as tomorrow, or by the end of the week at the latest.
People are more interested now than ever before in the philosophy of libertarianism, so I thought it was amiss not to have a general overview of some kind available from THL. I am presently hard at work putting the finishing touches on it and I could really use all your help in promoting Learn About Liberty once it's released.
If this goes over well, I'll be releasing a second e-book sometime this Spring- one that I'm very, very excited about. In the meantime, I am still working on a much more in-depth project, a book entitled Bush 2.0 that I hope to start promoting to major publishers by the Summer.
The pen is mightier than the sword. A revolution in government will only occur as the result of a revolution in the minds and hearts of its people, which must be driven by the effective communication of ideas. It is this ideological revolution that I am hard at work to affect with my writing. The Cato Institute quotes Mr. Adams, who says it all too well:
The American Revolution is all too often confused with the War for Independence. As John Adams noted in a letter of 1815 to Thomas Jefferson, "What do we mean by the Revolution? The war? That was no part of the Revolution; it was only an effect and consequence of it. The Revolution was in the minds of the people, and this was effected, from 1760 to 1775, in the course of fifteen years before a drop of blood was drawn at Lexington. The records of thirteen legislatures, the pamphlets, newspapers in all the colonies, ought to be consulted during that period to ascertain the steps by which the public opinion was enlightened and informed concerning the authority of Parliament over the colonies."
Thank you so much for supporting The Humble Libertarian's mission to enlighten and inform the American people about the proper nature and role of government in a civil society.
5 comments:
So, you're saying that 15 years after you convince people, we have blood to look forward to....ReplyDelete
I most sincerely hope not. Of all libertarians, I have been the most conspicuously opposed to the use of violence to accomplish our ends. (See http://bit.ly/bBQyxn, http://bit.ly/dv2MzG, & http://bit.ly/axYj4G.)ReplyDelete
And if there is blood to be shed, I hope it's the blood of we patriots, not that of our enemies, that the world would see and judge between us and know that we are for peace while the nations rage. While I think George Washington's actions were just and justified, I prefer Gandhi's tactics to Washington's.
Though in the end I very seriously doubt we'll even need to suffer as Gandhi and many of his followers did to affect revolutionary change in America. We're very lucky. The tools and institutions of peaceful revolution are already in place for us.
We simply need to enlighten hearts and minds with a powerful, but hardly original Idea. That is exactly that I mean to do.
While I disagree with your belief in not taking a proactive role in our national defense I applaud you and congratulate you on your first e-book published.ReplyDelete
BTW- How did you go about publishing an e-book? I have something more sociologically oriented than politically related that I want to publish but its only 9 pages long?
Good stuff. I'll post a link to it on my blog (RTR) when it's ready..ReplyDelete
Teresa, thanks so much! As for this one- I'm actually just going to make it available for free (donations welcome though!) right here on the website. I'm going to charge for the next one I'm working on however, and I'll probably use e-junkie.com to make that work. As I understand, it's like $10/month, so if you sell one book a month at $10 you'll break even. You could also just charge people with PayPal and then e-mail them the Word or PDF file of the book manually if you want to keep your upfront costs down. If you have more questions, Teresa, don't hesitate to e-mail me. I'd love to help in any way I can.ReplyDelete
Ryan, thanks so much! I'm pumped.
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There a number of different ways to flavor milk kefir: blending it with fruit, blending it with spices, and using it as a base for other foods, like salad dressings or chilled soup, which is common in Eastern European cuisine.... Read More
Fancy, Flavored Oatmeal Made 4 Ways {Better Than a Coffee Shop}by Ann Timm
Written by Stephanie, Creator and Editor of Keeper of the Home Eating oatmeal has suddenly become trendy. I'm not sure when or how it happened, but lately I've seen more and more coffee shops (even McDonald's, for goodness sake!) offering... Read More
How to Make Fabulous Soup From Scratch Without a Recipeby Ann Timm
Image by Magic Madzik Learning to cook without recipes can be not only a huge time-saver in the kitchen, but a money-saver as well. Soup is an incredibly versatile food. It can be hearty and chunky, or light and refreshing,... Read More
Explore the Keeper of the Home CollectionHomemade/DIY Real Food Healthy Living For Women Keeping the Home Family Life Do It Yourself Natural Remedies Recipes
Have a Question? Ask Ann!


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Disney Infinity 3.0: Star Wars Rise Against the Empire Play Set Review
Obi-Wan has taught you well.
When people think 'Star Wars', they don't think about Episodes I through III. They think of the original trilogy -- A New Hope, The Empire Strikes Back, Return of the Jedi. Because as much fun as Anakin, Obi-Wan, Ezra, Sabine and the other launch day characters are, I've raised my kids to know who the real stars of this franchise are.
They know that Han hot first. They know that you always let a Wookie win, especially Chewbacca. They know that Luke is a Jedi, like his father before him. They know Princess Leia can doesn't betray the Rebel Alliance in the face of evil. And they know Darth Vader is the best villain ever. With all of this knowledge, all they wanted from Disney Infinity 3.0 was a way to play as these characters and experience their story, then go on to make their own.
Alas, we have the Star Wars Rise Against the Empire play set, which comes with an adventure that spans the events of Episodes IV through VI (differently, though), and comes with Luke Skywalker and Princess Leia (Han Solo, Chewbacca and Darth Vader are sold separately). From Tatooine and Hoth, to Endor and the Death Star, the Rise Against the Empire play Set takes you on a journey through your favorite movies with the characters you love the most. But does it do them justice while fitting in with Disney Infinity?


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After his big primary victory in Louisiana on Saturday, Rick Santorum isn't listening to the people in his party who say it's time to start coalescing around Mitt Romney. Santorum says there would be nothing better for the Republican Party than a long nomination battle and a short general election.
Speaking with reporters over coffee on Capitol Hill Monday morning, Santorum said Republicans would be better off with a relatively brief general election campaign because it would negate the financial advantage he expects President Obama to have over the Republican nominee.
A short campaign is the "best thing that could happen," he said. "If we only have a two-month campaign, their money advantage . . . won't make as much difference. There's only so much money you can spend in two months. . . . If we have a nominee next week, all of the money advantages they have now are going to be trained on destroying whoever the nominee is."
The former Pennsylvania senator sounded ready to do whatever he could to make sure the nomination contest runs as long as possible. With about half the states having voted, he pointed to the fact that Romney has fewer than half of the 1,144 delegates needed to win the nomination. "Our feeling is we have just as good a chance of getting there as he does. It's going to be hard for anybody to get there."
He also argued that his deficit in the delegate race is less than some organizations have tallied. "Our math is actually based on reality of what's going on in the states as opposed to this fuzzy idea that it's going to be apportioned based upon what the votes are in the states."
Santorum's campaign advisers made a similar argument last week and on Monday the candidate promised that they would follow that with a detailed, written estimate of where they see the delegate battle with Romney.
Santorum acknowledged that he faces a difficult month in April and sounded pessimistic about being able to win next Tuesday's primary in Wisconsin, which shapes up as the next showdown with Romney.
Santorum said he believes he will win Pennsylvania's primary on April 24, but acknowledged that some of the other states that vote that day—among them New York, Rhode Island and Connecticut—will be far more difficult.
"Obviously Connecticut and Rhode Island are not necessarily in my sweet spot," he said.
Santorum said he is looking forward to the month of May, when states like Texas, Arkansas, Kentucky, North Carolina, West Virginia, Oregon and Nebraska hold contests. "If you look at the May calendar, that's a very, very nice calendar for us," he said. "I think we can go out there and . . . come close to winning everything in May."
As if to emphasize the disagreement with Romney over health care, Santorum spent Monday in Washington and even held a campaign event outside the Supreme Court as the justices were concluding the first of three days of oral arguments on the constitutionality of the national health-care overhaul. Romney was in California on a trip mostly devoted to fundraising.
Santorum's campaign has used the days surrounding the high court's oral arguments to step up its attacks on Romney, with daily e-mails highlighting the Massachusetts law and what campaign officials say was Romney's advocacy for using his state as a model for national health care reform.
Santorum has said repeatedly that Romney would be an extremely poor choice as nominee because he would forfeit one of the biggest issues Republicans should have to run against Obama in the general election.
"It is the mega issue," he said. "It is the biggest issue and it's one as you've seen President Obama won't talk about. He's not running around defending this thing. It is his huge Achilles' heel and I argue we're putting up the one guy who can't make the case."
Santorum made a similar comment over the weekend, calling Romney "the worst Republican in the country to put up against Barack Obama." Later he blew up at New York Times reporter Jeff Zeleny, who asked him to clarify the comment.
"Stop lying!" he said. "I said he was the worst Republican to run on the issue of Obamacare. And that's what I was talking about!" He uttered an expletive to show his displeasure at what he said were distortions by the media about his positions.
Santorum's campaign sent out a fundraising appeal early Monday morning based on that exchange. A campaign official said the e-mail had generated a big response.
Santorum said Monday that Romney has been hurt badly in the primaries because of the Massachusetts law. "I think that's one of the reasons the jury's still very much out," he said.
He added that, were it not for the former governor's huge financial advantages, the nomination contest would be far closer than it is today. He said Romney has benefited from spending the last four years courting the Republican establishment for money and support.
"He's worked the establishment. I haven't," the former Pennsylvania senator said. "I don't call these guys up on the Hill. I don't call governors. . . . If you look at the fact that we've now won 11 states, it's pretty remarkable given the resources we've had."


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Separate names with a comma.
Discussion in 'PS3 - Hacking & Homebrew' started by Subzero100, Feb 18, 2013.
how does one go about getting this done, and is it easier or better than a modded 360?
if you are on 3.55 or below it is a softmod and extremely easy to mod it. if you are above 3.55 then you have to own a ps3 that came with 3.55 or lower whenever you purchased it and downgrade it with a chip. so let's say you bought one from walmart that came with 3.55 on it originally and you upgraded to 4.3 or w/e. you would be able to downgrade it. if it came with something like 4.0 as the stock firmware then no you cannot do anything really right now.
so the 360 is a best bet then?


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Macau - MGM Grand Opening Party @ 12.18.2007
Macau Travel Blog› entry 1 of 4 › view all entries
Remembered that I first stepped on the territory of Macau - it was 10 sth. years ago. Hone Kong is located so close to Macua which only a one hour distance by Ferry. When I was young, we travel at least once a year to Macau during Lunar New Year. Can't remember too much and just remained few pieces of memory thou.
When I grow up, sometimes will travel with frds over the weekends. Of course not for gambeling, but just for fun and it is the only possible way to get out from Hong Kong with our affordability. Same as most of the other gals in the world, "Dieting" is always at the top priority on my hobby list. In fact, it is a life-long business, never stop till I died. (haha.......) Thus, when all my frds were enjoying the foods, I was the one and only sitting at the corner sliently and just having my cup of tea or coffee all the times.
This time, I went there for FREE. (I was invited to the MGM Grand Macau Grand Opening) I stayed there for 4 days. Eat a lot, Drink a lot, Play a lot. To recall the advertising headline of MGM's : "Players Wanted". It seems the upcoming hippest chilling place in town. Like their European stlyle decorations, Like the delicious foods offered in every restaurants, Like the Spa Treament offered at Six Sense Spa, Like the black coffee and homemade cakes offered at MGM Patisserie, Like the Shark Fin in soup with Fresh Hawaiian Papaya (which managed by Chef Chow Chung) at Imperial Court, Like the art pieces displayed in the Grand Hall, Like the Glass art pieces made by Dale Chihuly decorated along the sides at lobby. There are too many....not allow to mention all indeed.
Wat a pity that I forgot the DC charger. I promise I will visit again soon and lots of photos coming soon. At the meantime, please enjoy the pics we took in the party.


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Amy (Boolajoojoo) TTC#1
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June 24th, 2013, 10:36 AM
Super Mommy
Join Date: Jan 2013
Location: USA
Posts: 723
My digging on the internet says it's most likely from ovulation. The spotting finally stopped, but it went on for about 3 days. The sites I read on said things like "it could mean you're extra fertile" or that separation of the uterine lining happens because of hormones during ovulation, and a few other random things. The thing is, this never used to happen and it's very troubling... and I got to thinking of all of these different unlikely things that maybe could be related or not related... and I think the most significant change is that a few months ago I stopped drinking tea because I went to donate blood and they said that my iron was low and asked if I was a tea drinker. I said yes, and they said the tannins in tea can block iron absorption. But aside from that, tea has a lot of good qualities, and different teas can have an effect inflammaton, menstruation, cycle regularity, and alleviate cramping which I think might all be part of the issue... so I figured, I will just allow myself to have tea again. I'm not donating blood anymore because of TTC, so I don't think I'm truly at risk of becoming anemic. Other than that... 4 DPO... we'll see what happened. I am itching to test! I hate the 2WW.
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Debrecen University has a deserved reputation for offering high quality education and receives universal praise for the quality of its facilities. Situated in Hungary's second city, the university offers internationally respected programmes in Medicine and Dentistry. Medical Doorway are proud to be the official representative of this large and historic university which has been educating students since the 1500s.
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The highly successful Medical and Dental programmes enable you to complete your training and - for UK/EU nationals - be eligible to apply for GMC registration or GDC registration. You can even prepare for the USMLE at the university if you wish to consider career opportunities in the United States or Canada. Study Medicine or Dentistry at Debrecen University with Medical Doorway.
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The new brainchild of Riton and DJ Mehdi had internet life breathed into it today. The duo will be touring Europe and the US in May/June playing strictly house music. Last year seemed more like the year for super-duos, but the way things looking 2010 may bring the thunder. Their first EP is set to drop this May on Ed Banger.
Carte Blanche – In The Mix (320 kbps)


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Lapeer Grain Company has been serving the community's needs for nearly 100 years. We carry a complete line of Purina products as well as other nationally recognized brands. We have the ability to
custom mix feed and can take care of most of your animal's needs.
Learn more about us. Browse through the gallery showcasing some of the many brands and products we carry. We look forward to serving you!
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Lowongan Kerja Legal Officer PT. Bahana Pembinaan Usaha Indonesia (Persero)
- Bachelor degree in law
- Have Min. 2 year of working experience as Legal Officer
- Have experience in capital market industry
- Good command in English both oral and written
- Good understanding of any aspect of Indonesia law.
- Able to work as team.
- Fluent in English, both oral and written.
- Having good communication and interpersonal skills.
- Proactive and high initiative.
- Able to work under pressure and tight deadline.
- Computer literate (especially Microsoft office).
If you are interested to join our company, please send us your CV or resume to firstname.lastname@example.com (please make sure the email do not exceed 1MB), Please write the desire position on the email subject. Only qualified candidate will be processed. For further information please visit : www.bahana.co.id