CHRONOSPHERE » cryopreservation http://chronopause.com A revolution in time. Fri, 03 Aug 2012 22:34:48 +0000 en-US hourly 1 http://wordpress.org/?v=3.5.1 Myth and Memory in Cryonics http://chronopause.com/index.php/2012/05/12/myth-and-memory-in-cryonics/ http://chronopause.com/index.php/2012/05/12/myth-and-memory-in-cryonics/#comments Sat, 12 May 2012 19:45:41 +0000 chronopause http://chronopause.com/?p=2122 Continue reading ]]> By Mike Darwin

Steven B. Harris, M.D.

In September of 1988, Steve Harris, M.D., published an essay entitled The Day the Earth Stood Still: Cryonics and the Resurrection of the Mythic Hero. It was one of his best in a formidable roster of insightful articles that he wrote dealing with the likely cultural requirements and cognitive limitations that inform humanity’s acceptance, or lack thereof, of cryonics.  I strongly recommend cryonicists read it. Steve’s articles had a great deal of influence on my thinking,  and both Steve and I were, in turn,  influenced by  the philosopher-mythologist-historian Joseph Campbell. I don’t know how Steve was introduced to him, but I first heard of Campbell as a result of the PBS series THE POWER OF MYTH WILL BILL MOYERS, (downloadable here)  which aired in the late 1980s.

I remember breaking out in goose bumps (I have them now) many times during Campbell’s program and, subsequently, when reading his books. His book of the same title as the series is an excellent introduction to his work. I had the same reaction when reading  Steve Harris’ brilliantly insightful articles dealing with issues critical to human perception of, and reaction to cryonics when I read them for the first time in manuscript form, before they were published in Cryonics And I had it again when I read them in “in print” as the final, published product. These works bear reading and rereading and reading again.

The Dead Ant Heap & Our Mechanical Society: http://www.alcor.org/Library/html/DeadAntHeap.html

The Return of the Krell Machine: http://www.grg.org/charter/Krell2.htm

Will Cryonics Work?: http://www.alcor.org/Library/html/probability.html

The Society for the Recovery of Persons Apparently Dead: http://www.alcor.org/Library/html/PersonsApparentlyDead.htm

Many are Cold But Few Are Frozen: http://www.cryocare.org/index.cgi?subdir=&url=humanist.html

Frankenstein and the Fear of Science (Lecture), VHS tape: http://www.worldcat.org/title/frankenstein-and-the-fear-of-science/oclc/043933281

There are very powerful ideas and insights in these essays which should be a source of influence and inspiration to many more cryonicists, than to those relatively few who have read them, to date.

One of my central points about the reason for the continued “failure” of cryonics, and for its very slow growth, both absolutely and relatively,  is the near total lack of any kind of memory of what has gone before, let alone a sorting out of what part of that history is vitally important to be remembered. It’s as if most cryonicists live only in the present, looking forward to a future exclusively of their own imagining, with just a dim halo of memory extending, perhaps 5 years back, at most.

A few days ago, I had my nth practical example of that. I was contacted by some people interested in establishing cryonics Elsewhere. One of the interesting (and depressing) things they had been told by “cryonics people in the US,” was that it was a “good idea to establish companion for profit and non-profit organizations” to carry out the various functions of the cryonics undertaking with minimal liability.

Really?

Maybe that is the best system, but if it is, there is no evidence I know of to support it, and substantial empirical evidence to refute it.

This is an edited version of my response t0 that recommendation:

“I can only tell you what I have observed here over and over again. Maybe you can figure a way around it, or maybe you won’t have the same problems in the first place, owing to cultural differences. I just don’t know.

You will notice that all of the cryonics organizations in the US consist of fully integrated providers. Suspended Animation is the (recent) exception. What’s remarkable about this situation is that it is the polar opposite of what all of us intended when we started cryonics operations here (myself included). There were always paired for profit and not for profit companies, and for just the reasons you’ve stated. CSNY & Cryo-Span, CSC & Cryonic Interment, BACS & Trans Time, IABS & Soma, Cryovita, Manrise & Alcor… And yet there are only single entities around today. Why?

I do not know about your local law, but in the US, it is forbidden for non-profit organizations (NPOs) and for-profit corporations (FPCs) to have interlocking directorates. In fact, it is generally prohibited for corporations related to, or doing business with each other to have interlocking directorates, unless one is mostly or wholly owned by the other, regardless of their status as FPCs, or NPOs. The reasons for this are many and are deeply rooted in corporate law, but mostly can they be reduced to “conflict of interest” issues. In the early days of cryonics, this ban on interlocking directorates was flagrantly disregarded. The inevitable result was that the FPCs completely dominated the NPOs. In fact, FPCs used the NPOs as a convenient shill for doing all the things that were unprofitable, risky, or otherwise not desirable, such as being stuck with the open-ended custody of the patient!

While the initial reason for this was the use of the Uniform Anatomical Gift Act (UAGA) to accept the patients, the eventual reason for it became (obviously), proprietary interest. People in the FPCs got paid for their work (usually in shares in the FPC) and people in the NPO didn’t – couldn’t, in fact. Valuable work, work that would earn shares, got done by the FPCs, and everything else got shuffled off onto the NPOs. You can actually  see this happening at the time, if you take a look at the issues of “Life Extension”/”Long Life Magazine” on the CryoEuro Wiki, because people didn’t talk about BACS, they talked about Trans Time… And where the reward, or the potential for reward exists is also typically where all the time, attention and money will flow.

Eventually, as visibility increased, the state began to menace, and the directorates were fully separated. That’s when all hell broke loose! The people running the NPOs had to be disinterested directors, and they did not stand to make money (or shares), or gain in any way from giving advantage to the FPCs. Contracts, fee increases, and all the other “taken for granteds” between the FPCs and NPOs were now up for debate and consideration. And since they were now two truly separate organizations, jealousy, resentment, and plain old proprietary interest and territoriality took over.

I pretty much thought the FPCs would win, primarily because they did have that huge advantage of proprietary interest on their side. But what I hadn’t figured on was the patients! The NPOs had control of the patients; and it was with the patients that the real loyalties ultimately rested. TT and BACS pretty much destroyed each other. In the case of Alcor, Alcor prevailed, and in the case of CI, well, there was never an issue in the first place, since CI was always an integrated operation. And yet, why this happened remains a mystery to many, even to those who have put some effort into finding out what happened.

In a large, diverse and robust marketplace, commercial service providers servicing NPOs could possibly work. SA may be the first of these, but only time will tell.

However, while cryonics is small and not subject to normal market forces, the two organizations model has not been proven workable. It becomes particularly vicious when there is only one service provider and one NPO, but totally different directors (as the law here requires), because then it becomes like a long-married couple who hate each other, but because of children, fiances and other reasons, cannot divorce. Far from creating the checks and balances it was anticipated to, this set-up created a state of gridlock and animosity. Ultimately, it degenerated to people on both sides screaming that the other was trying to screw them. And since they couldn’t stop dealing with each other and go to the “competition,” it just ground on until there was little or nothing left. That is, in fact, in significant measure, how Alcor was reborn.

Finally, you will encounter this problem: the FPC will be absolutely essential to the NPO, because the FPC will hold all the assets for delivering the up-front (immediately legally riskiest) part of cryopreservation (CP). They will own the equipment, employ the people, own the vehicles…. So the NPO eventually finds itself not just held hostage to FPC , but at risk if the FPC screws up.

I’ll give you a highly personal example. I was a major shareholder in Cryovita, the service provider to Alcor, but Jerry Leaf held most of the shares. Alcor relied on Cryovita completely for rescue and perfusion and there were no alternative service providers available – none. Alcor didn’t own so much as a cannula, or a set of scrub clothes. Cryovita was a shares corporation and the shares were distributed in a complex and potentially problematic way. It seemed possible that if Jerry were to suddenly experience medico-legal death, that the continued smooth functioning of Cryovita could be at risk of being disrupted. That became one of several causes of a major split between Jerry and I, because I realized, as President of Alcor (which I was, at that time), that if Jerry dropped “dead,” Alcor’s ability to deliver CP could be at risk of disruption. Alcor didn’t have cash lying around to go buy all the required equipment in a hurry! It had taken Jerry and me many years to patiently accumulate it, and to do so at well below market rates.

But it was worse than that, because over the years, Cryovita had generated patents, made exclusive agreements, and otherwise done all kinds of normal business things that corporations do. The problem was, all that “stuff” was also needed and used by Alcor! So, I began acquiring those same capabilities for Alcor, which was, of course, a costly duplication of capital equipment and it caused a feeling of resentment in Jerry/Cryovita.

So, what actually happened when Jerry did have a heart attack and was CPed? Well, exactly what I thought might happen, but in a way I never could have imagined. Cryovita did split from Alcor (kindly selling Alcor some of the most critical assets Alcor needed to stay in business), but the people who took Cryovita away were Kathy Leaf (Jerry’s widow), Saul Kent, Paul Wakfer, Brenda Peters and myself – the very people who had been the most ardent advocates of Alcor for so hard and long.

What happened to Cryovita? Well, it morphed in various ways, but today it is known as 21st Century Medicine!

Naturally, this version of events will be strongly biased by my point of view, so I would suggest you ask others and check it out for yourself. Look at the back issues of “Life Extension” and “Long Life” magazine on the CryoEuro Wiki to get a feel for the “Trans Times” of the 1970s and ’80s. Jim Yount, John Day and especially Frank Rothacker of ACS, may also be able to provide you with valuable perspective.”

My guess is that almost all of the newcomers to cryonics over the past decade, or so, have not read any of Steve Harris’ essays. And they clearly know little of the actual history of cryonics, let alone have any distillation (regardless of the direction of its bias) of what is important in that history to remember and act upon.

If you Google “history of cryonics” this what comes up on the first page (and subsequent pages offer no greater resources). Ben Best’s article is actually the most popular (longitudinally). It’s a fine, bare-bones factual narrative. But it is bloodless and lesson-less; it provides no instruction for others striving to create cryonics without recreating our errors. [I want to be very clear here that this is not a criticism of Ben's article: it was not written to be a tutorial on the lessons to be learned from the history of cryonics.]

What makes history both “teachable” and “leanable” is the humanity of it. We are, as Campbell so eloquently said, “story creatures”; we learn through guided narrative informed by the power of the mythic. BACS, TT, CSNY, Cryo-Span, Alcor, Manrise, CI, these entities were created by individual people for very personal reasons, as well as for the visible and easily understood public ones. Most contemporary cryonicists seem to recoil from any consideration of the “messy” and “untidy” aspects of the personal motivations and dynamics that drove (and drive) organizations, in and out of cryonics. And yet, that’s where a lot of the most important reasons and answers are to be found that will lead on to successes, or doom us to repeated failures.

 

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Dr. Crippen on Mr. Darwin* http://chronopause.com/index.php/2012/05/05/dr-crippen-on-mr-darwin/ http://chronopause.com/index.php/2012/05/05/dr-crippen-on-mr-darwin/#comments Sat, 05 May 2012 07:44:49 +0000 chronopause http://chronopause.com/?p=1964 Continue reading ]]> By introduction, I am Dave Crippen, MD, Professor of Critical Care Medicine and Neurological Surgery at the UPMC Medical Center in Pittsburgh. Some of you may know me. I’m the moderator for 18 years duration of CCM-L, the International Critical Care Internet Group (~1000 members).  If you ask almost anyone in the in critical care medicine global village, they probably know me, or know of me.

 

I have followed the saga of Mike Darwin beginning back in the day of Usenet where Mike maintained a cryonics list. I came upon this list while “surfing the ‘net” and found his editorials interesting. I wrote him an idle question and he wrote back, initiating a sixteen-year roller coaster friendship.

Now in 2012, I hope to make some observations from one who knows him intimately (not too intimately).

18 or so years ago, none of us could have predicted where the miracle of the Internet would take us.  Would any of you have believed ago that many global health care providers would have embraced a hard-core cryonicist as an authoritative voice in medicine?  By “embraced”, I mean they all hang on his every word.  Back in about 2000 they all took up a collection to purchase him a new computer to keep him on-line. Small denomination money came in from all over the world.

Because of that miracle, Mike has most assuredly entered the arena of “legitimate” medicine more than any of you can imagine.  Certainly more than anyone in the self-limiting field of cryonics.  His writings enjoy wide readership among working physicians and health care providers. He has contributed to several articles in a world-class clinical journal “Critical Care” with a journal “impact rating” (lots of clinicians read it) near the top three Critical Care journals in the world.

But it wasn’t an easy task.  As most of you know, Mike is a very unusual person on almost every level. I’ve known him for a very long time and I’ve seen the patterns emerge and descend in his life and I think I know him better than most, if for no other reason than he doesn’t keep friends long.  Like many of the rest of us, Mike has very potent talents combined with demons that keep those talents from wide expression.

Mike’s passion is what most physicians consider the pseudoscience of Cryonics, and he lives for little else. It is his passion and his obsession. At some point years ago, he reached a point in his life where his demons fully expressed themselves and he burned many bridges to those doing administrative and research Cryonics. To this day, those factions exclude him from those activities.

So for a few years around the turn of the century, he didn’t have lot to do with his time. Mike decided that he liked conversing with the members of CCM-L because it allowed him to pontificate about science and other things in life, and all always enjoyed his missives. As time progressed, he got more involved in Cryonics again, and slowly withdrew from CCM-L.

As a practical matter, his baseline default is to be culturally and socially isolated and he seems to be at home there. He works hard to maintain that isolation. He has an extensive history of effectively burning bridges over issues that could probably be resolved with even rudimentary diplomacy; an alien concept to him.

Over the years I have tried to understand why former friends and colleagues so relentlessly exclude him.  Conversations with some of them wondering why his strengths cannot be mined as his (perceived) shortcomings managed. The universal answer is that his (perceived) shortcomings have the capability of being so malignant that they are either afraid of him or any potential benefit isn’t worth the effort.

But Mike is an authentic Genius in Aspic (my term).  He chose to pursue a course of science that: 1. Limited his colleagues to a relatively small culturally isolated group, and 2.  Almost completely excludes him from many of the goals in life he would like to have in a perfect world. He is a genius trapped in Aspic and the “Richest Man in Bogota” ( H.G Wells).  His formidable talents are trapped.  Had he chosen to pursue righteous scientific disciplines, he would be mentioned in the same breath as Feynman.

My role in all this was to try to keep him visible to (for want of a better term) “traditional” science by keeping doors open for him as a writer in the literature of and speaker at meetings attended by scientists of the real world that righteously excludes Cryonics. To some degree, I have been successful in that endeavor, but it hasn’t been easy. Mike’s boundless energy, enthusiasm and confidence is pretty much limited to Cryonics, for which he writes extensive blogs and argues endlessly with critics thereof. His interest in mainstream science has dwindled, and that includes the mainstream scientists of CCM-L, for which he hasn’t much time or energy or interest in being a part of.

I’ve seen this coming for a while which is Why I chose to compile a history of his contributions to CCM-L for posterity. His response was that this volume was a waste of time and of no value to anyone, which is completely in character. I find it curious that this volume is the only book ever written about him that is complimentary.  He rejected all this and quickly evolved attempts to divert or stop altogether any involvement in these projects.

OK, he can be hard to get along with and he can be abrasive and irritating and emotional. We deal with these types with surgeons all the time, but if their benefit exceeds their detriment, we simply manage them more effectively.  Darwin is an authentic genius with a passionate and encyclopedic knowledge of medicine and science. There isn’t enough gold in Ft. Knox to buy that. It’s a gift from God.

I will tell you that I continue to use my influence to get him further inducted into the global medical community because I sincerely believe he is a valuable resource. He’s honest to a fault, beyond intelligent, has impeccable scientific integrity, works hard and has uncanny ability to communicate complex concepts to an eclectic audience. For those reasons, he has the potential to get the ear of clinical medicine.  He has great potential as a writer for medical subjects, and speaker at international meeting. Mike sitting in a 2 X 4 shack in Arizona spending his days grooming the surrounding desert is a waste when his knowledge base and communication abilities have such potential benefit to science.

There is a window of opportunity here to re-think former misadventures in terms of the current needs of science and medicine. The world evolves and we all need to evolve with it, or we’ll become extinct. Mike needs to evolve to something other than lethal or self-limiting iterations.  Who knows, he may be the ticket infiltrating the legitimacy of Cryonics in the global medical community. Weirder things have happened. We, in clinical medicine, learned long ago that the mission transcends personal problems. We learn to manage them better to facilitate a greater good.

*If you are British, yes, he is related to that Crippen, and no, I’m not related to that Darwin.

 

 

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Much Less Than Half a Chance Part 4 http://chronopause.com/index.php/2012/04/04/much-less-than-half-a-chance-part-4/ http://chronopause.com/index.php/2012/04/04/much-less-than-half-a-chance-part-4/#comments Thu, 05 Apr 2012 03:00:22 +0000 chronopause http://chronopause.com/?p=1630 Continue reading ]]>  

Screening for the Risk of Deanimation

The term “screening” is used in medicine to describe routine examinations or diagnostic procedures of a defined group of individuals to identify diseases or risk factors for same at an early stage. Screening is usually categorized as a  “preventive medical examination” or a  “checkup,” and its aim is to increase the life expectancy of those examined  by reducing the incidence or severity of life threatening disease and enhancing the quality of life. The most accurate examination methods possible should be used to identify as many diseases as possible still in their non-symptomatic phase, so that early treatment or change in life style can be initiated.

It is critically important to understand that the purpose of a “deanimation screening scan” (DSS) is not primarily to interfere with the course of disease or to extend the duration of life during this life cycle. Rather, it is to predict or to warn of impending  deanimation with increased accuracy and precision. Any contemporary medical or health benefits are thus incidental. Indeed, it is precisely when DSSing is used to determine or influence current medical interventions that it becomes dangerous. Knowing when you are likely to deanimate with greater precision, for sole purpose of improving your cryopreservation, carries little if any risk of iatrogenesis beyond that which would be present if you found out you were dying at a later time, or didn’t find out and suddenly collapsed in cardiac arrest from a heart attack, or suffered a massive stroke. It is only when the course of treatment is altered by obtaining the data, or looking at it (see “The Black Box of the Baseline,” below) that DSSing becomes either a practical or an ethical conundrum.

The first problem we confront in a screening test for deanimation risk is that we are moving in completely uncharted waters. We have no benchmarks or baselines on which to structure our screening program, save for a modest number of pilot programs that have been undertaken to evaluate full body scanning as a primary tool for the detection of cancer and atherosclerosis in the general population, or in selected subpopulations. For now, these will have to serve as the basis for our protocols, as well as the important cautionary lessons learned from other screening programs.

For reasons of safety, (see Radiation & Risk, below) Magnetic Resonance Imaging (MRI) is preferred over Computerized Tomography (CT), because no ionizing radiation is employed in making the image. MRI has some important limitations at this time, most notably only a few centers have devices that image the coronary vessels with sufficient precision  to allow risk  assessment for coronary artery disease (CAD).  Similarly, screening for Alzheimer’s Disease (AD),(beta amyloid deposits) also requires CT-PET scanning and the associated exposure to ionizing radiation.  So, for the present, CT is the only way to screen for CAD and AD. For this reason, and for those who for economic reasons may need to use CT imaging, it is worthwhile to briefly discuss the much hyped “risks” of radiation from whole body CT scans and this is done in some detail below.

Figure 25: Typical finding in an elderly woman who under prophylactic full body MRI scanning during a clinical trial in Germany to determine if full body scanning would reduce morbidity and mortality from cardiovascular disease and cancer. (Gohde, et al.)

A specimen imaging protocol is presented as Appendix 1 and is taken from the study by Gohde, et al., “Prevention without radiation – a strategy for comprehensive early detection using magnetic resonance imaging,” which was itself a pilot study in the use of MRI as a screening tool for cancer and cardiovascular disease.

The Mechanics

Currently, there is only one way to get a  DSS and that is to do it yourself.  There are several reasons, which will be discussed directly, why that is not a good idea, or certainly not the ideal way  to pursue DSSing. There are a number of reasons for this, starting with the potential for harm. Primum non nocere is the first dictum in medicine: first do no harm. Information is the most powerful force in the universe and information concerning you own health and welfare is especially important. It is also information that you cannot be objective about. It just isn’t possible. It is for this reason that no good physician treats himself or his immediate family in life or death matters as the sole or usually even the primary caregiver. In fact, speaking from experience as a person knowledgeable in medicine, I have found that wise counsel and advice I can (and do) easily give to others  is strangely absent from my own ears when I am the patient.

This lack of objectivity is more than a nuisance, it can be truly dangerous; and here I will have recourse to an actual example. The first four people to undergo DSSing have done so over the past 11 months. These were all individuals who were over 60 and who had not had consistent (or recent) “physicals.” All were counseled about the dangers of VOMIT and about the negative psychological impact of potentially finding out “something was wrong.” All four individuals had significant anomalies on their scans – two of which were life threatening and these were (or are) being medically managed.

In the other two cases, the scans revealed anomalies that might merit further medical evaluation in testing, and in both cases, the decision was wisely made not to pursue those tests. Why? That’s a complicated question, and I’ll answer it by explaining the circumstances of one of these people:

Mr. Ling is an 82 year old man who is in excellent health. He is physically active, mentally sharp and still working part time in his profession of many years.  He underwent a DSS five months ago. The findings were, overall, very good. His coronary calcium score was roughly a third lower than expected for his age, he had no signs of neoplasms, or of peripheral or central atherosclerosis, and the only abnormal cardiovascular finding was evidence of mitral valve regurgitation, which was deemed not serious and not likely to progress rapidly. However, a number of nodules were found in his right lung, along with some enlarged lymph nodes. The radiologist who reviewed the scan suggested a possible biopsy, with or without “bronchoalveolar lavage” (BAL).

While Mr. Ling is in good health, he is an 82 year old man and BAL requires sedation with propofol or a similar drug, and carries with it the risk of significant complications.  As to a CT-guided needle biopsy of the lung masses or the lymph nodes, this is this discussion that took place between Mr. Ling and the radiologist who interpreted his scan: “OK, let’s consider what this could be? I’m not sick – never felt better, so it’s not TB or something infectious? And if it’s cancer, well, what kind of treatment options would I have at my age for lung cancer with lymph node involvement?”

Those were great questions, and as it turned out, the radiologist was only playing it safe – he doesn’t want to get sued if Mr. Ling finds out he has cancer and a lawyer says to  a jury, “The doctor who imaged him said, ‘You’re in you 80s, I see this kind of thing all the time. Don’t worry about it.”  The radiologist ended by noting, “Since you are planning on following up in a year with another scan, we’ll see if anything has changed then.” And Mr. Ling is fortunate to have sufficient financial means that if he wants to pop in for a scan two months later, he can do that, too.

The problem is, most people aren’t in Mr. Ling’s position, and many will be unable to reason their way past the information that they have “masses” or “lumps” in their lungs and “enlarged lymph nodes in their chests!” That kind of worry cannot only be expensive, it can be damaging to one’s health, and corrosive to one’s quality of life. The information from DSSing should be given in the proper context, in the proper way, by the proper people, with the proper knowledge.  Absent that, it can do real harm. And if the scan does reveal a grave or untreatable medical condition, then there is all the more reason for the person to have the necessary resources at hand to help him cope and plan.

Ideally, this program would be part of a comprehensive Member Survival Program (MSP) administered by the cryonics organization (CO) and there would be a staff person whose job it would be to maintain communications with members, encourage compliance with MSP protocols (including the preferred imaging protocol) and collect and manage the resulting data stream.

Under such a scheme, upon intake (approval of cryopreservation arrangements) all members would have (at their option) completed a comprehensive health history and demographic information questionnaire, most of which would be completed as part of their membership application. The data from this questionnaire, as well as any electronic medical records the member may choose to provide, would be entered into the CO’s comprehensive member data base. The availability of this data would then allow for downstream refinement of the “one size fits all” scan protocol being proposed here, by allowing for individual risk assessment for CVD and cancer. This would flag members at elevated risk of early onset of these diseases to consider commencing scanning surveillance at an earlier age.

The Schrödinger Scan: the Black Box of The Baseline

Unless otherwise indicated, the first (baseline) scan would be done at age 45 for men and age 50 for women. In order to completely avoid any deleterious negative psychological effects, as well any potentially harmful effects from VOMIT (as discussed above), the baseline scan remains blinded and unexamined for 1 year after it is made. This done by providing written instructions to the radiologist reviewing the scan to seal the report unless there are unequivocal findings of life threatening pathology.

At the end of the year long blind period, the scan is examined and any anomalies noted. If the member chooses, a repeat scan can be done to resolve any questions or concerns raised by the baseline imaging. For example, if what appears to be a suspicious mass or nodule was found, a rescan a year later will very likely disclose if it is a neoplasm e.g., it will have grown or spread). It may seem counter intuitive to not look at data which you have paid for, experienced inconvenience to get, and which “might” save your life, but that is the necessary price that must be paid for this intervention to be used safely.

The baseline scan must be regarded as the first part of something that will not “happen,” or be completed for another year – like a bulb that has been planted to bloom in the spring, or a bond that will not mature for another 12  months. The scan itself is only a part of the process: the necessary information to safely interpret it does not appear until the required interval of time has elapsed. After all, before this protocol was proposed, no one ever got scanned and they felt just fine about it (until they dropped over in cardiac arrest).  For those of a quantum bent, consider it an extended version of Schrödinger’s famous experiment, except instead of the cat in the box, it’s a CAT scan in the box.

Scan Intervals & Exceptions

If the baseline is “negative,” showing no evidence of evolving pathological processes that merit intervention or further monitoring, then it is being proposed that the next scan take place 5 years later. Similarly, with each subsequent negative “healthy” scan, the next scan would be 5 years hence until age 81, at which point scans would be done every 2 years until cryopreservation ensues.

Figure 26: Proposed algorithm for Deanimation Screening Scan intervals and actions.

These scan intervals are arbitrary and will no doubt need to be refined over time as experience is gained. Intuitively, it seems that there should be a relationship between scan intervals and increasing age, and it is possible to configure scan intervals based on things like increasing risk of SCA or terminal illness with age. However, until some real world experience is gained, a conservative approach which minimizes costs and maximizes the opportunity for benefit, seems best. There are lots of programmers, mathematicians and similarly qualified people in cryonics and if any are interested in working with me, I am interested in generating scan interval algorithms based on the rising risk of disease and death with age (if you are interested, contact me at m2darwin@aol.com)

Going it Alone?

If a decision is made to proceed with DSSing on an individual basis, there are a number of important things to keep in mind and to do:

* Do consider carefully the possible impact this decision will have on you and on your family. In fact, give some thought to discussing this with your spouse or significant other before moving ahead.

* Do select a good imaging center with competent and caring staff who can give you good counsel about the procedure and the results. Imaging centers that offer full body scans are often used to counseling patients: make sure the one you select is a good one. Talk with the staff about your concerns before you commit to being imaged.

* Do explain to the radiologist who will interpret your images that you are having a baseline scan done and you only want to know if there is unequivocal pathology present that requires immediate or urgent medical intervention. If you can’t get that assurance from him, ask for your results only in writing on the same disk on which your scan is written.

* Don’t look at your scan or the written report that accompanies it. If you have a reliable and willing CO, send a copy to them and ask them to send you the results a year from when they receive the media with the images and the report on it. Duplicate CDs are typically made and given upon request at no charge, or for a small fee at the time you are imaged, or when you come for your results. Bring your own media to save money!

* Do provide a copy of the disk with the scan on it to your medical surrogate and to anyone who is on you ICE (in case of emergency) contact list on your mobile phone. The reason for doing so is that, should you experience SCA during the blinded waiting period, the scan may still save you from autopsy if it documents the presence of CAD, or some other pathology that could have caused your sudden and unexpected deanimation.

* Don’t  rely on the DSS to keep you out of trouble, or to reassure that everything is OK, should you develop serious health concerns. Just because a scan shows no indication of pathology does not necessarily mean that there is none. If you have signs or symptoms that would have prompted medical attention absent scanning, act on them in the same way after scanning. Let your physician decide if the scan is significant in the context of any illness or concerns.

* Don’t forget that the scan intervals are 5 years and that is more than enough time for serious disease to develop. Indeed, the 5 year window is a long one, especially where cancer is concerned. A DSS is not a health promotion or a disease prevention program. It’s primary purpose is to let you know you are terminally ill, not to assist you in avoiding that eventuality.

* Do know that if you have atherosclerosis, “vasculopathy” and you want to monitor progression of the disease, your scan intervals will have to be much shorter than 5 years – probably 6 months to 1 year, depending upon the severity, your response to medical intervention, and so on.

Economies of Scale?

Medical imaging is a highly competitive, non-monolithic industry consisting of many operators, large and small, both independent and institutionally affiliated. Such market environments inevitably encourage the drive to survive, and thus typically offer the discriminating consumer the opportunity for real bargains. I made a number of calls to imaging centers around the US and discussed the possibility of group discounts and “scan plans” wherein members of an organization or group, even just a group of like minded individuals, could get deep discounts on scans. The majority of centers I spoke with were receptive to this idea, and several discussed specific numbers which were anywhere from 20% to 60% lower than their standard walk-in fee.

Thus, it should be possible for groups of cryonicists in a given geographical area to make arrangements with a local imaging center for scans. The same was also true when I inquired about group or institutional discounts for carotid and abdominal ultrasound screenings, with the difference being that in some cases, prices went from ~ $350 per screen to ~ $60 per screen, providing the group could be scheduled for the same time and place.

The Pre-Cryopreservation Baseline CT Scan

Figure 27: A hypothetical pre- and post-cryopreservation  CT cerebral angiogram. The post-perfusion image would be obtained by administering radiocontrast agent(s) into the perfusate immediately, or shortly before discontinuing cryoprotective perfusion, prior to deep cooling to storage temperature.

If it is at all possible, a final vital CT scan of the head (at least) should be done as close to the time of cryopreservation as possible. This scan should be done with contrast and with no concerns about clinical radiation dose limitations, since the member will be terminal. The objective of this scan is to document, in as much detail (highest resolution) possible, the morphology of the brain and its vasculature. The imaging technique used should be one that optimizes resolution of the cerebral angiogram. The reason for making these images is that they should allow for many important determinations about the quality of initial stabilization and cryoprotective perfusion and cryoprotectant distribution in the brain to be made, at leisure, during the period the patient is in storage.

If contrast agent(s) is injected into the perfusion circuit shortly, or immediately prior to the discontinuation of perfusion, it should be possible to obtain a post-vitrification angiogram, which in turn should allow for evaluation of cerebrovascular patency, as well as assist in determining the anatomical landmarks within the cryopreserved tissue. It should also be possible to add other kinds of tracers to the perfusate, which might allow for quantification of regional distribution of cryoprotectants, or of other molecular species of interest not only within the brain vasculature, but within the brain parenchyma, as well. Again, the presence of a baseline pre-cryopreservation scan will likely be of great importance in allowing accurate interpretation of post-cryopreservation images.

This scan must be a CT, as opposed to an MRI, since MRI scans are unobtainable in deep hypothermia, or in the solid state.

Radiation & Risk

When the mass media talk about the “risks” from radiation associated with CT scanning, the first question that should spring to mind is, “Risks to who?” Sensitivity to ionizing radiation varies based on the cell age and mitotic cycle, and what this means in practical terms is that the younger you are, the greater the risk radiation presents to you.  Children thus have a much higher relative risk when compared to adults due to their rapid cell division and cell differentiation rate.

Figure 28: The risk of developing cancer as a result of radiation exposure is strongly age dependent and decays dramatically as people age. By the time an individual is in his 60s, 70s or 80s, the risk of neoplastic disease from medical imaging becomes negligible. Adapted from ICRP Publication 60 (1990).
 

Table 1: Nominal Risk for Cancer Effects *
Exposed population Excess relative risk of cancer
(per Sv)
entire population 5.5% – 6.0%
adult only 4.1% – 4.8%
*relative risk values based on ICRP publications 103 (2007) and 60 (1990)

 

Table 2: Relative Radiation Level Scale
Relative Radiation Level

Effective dose range

None 0
Minimal Less than 0.1 mSv
Low 0.1 – 1.0 mSv
Medium 1.0 – 10 mSv
High 10 – 100 mSv
* Adapted from American College of Radiology Appropriateness Criteria, Radiation Dose Assessment Introduction 2008

These data also demonstrate that you cannot simply use the average relative risk shown in Table 1 to estimate the increased incidence of cancer due to radiation exposure. In order to do this analysis correctly, you need take into consideration the age of all individuals in the irradiated group. For instance, a man of 80 has a life expectancy of about 8 years, versus 33 years for a man of 45. Thus the risk to individuals over the age of 70 is, for all practical purposes, essentially nil. Table 2 illustrates what the  American College of Radiology considers minimal to high radiation doses in “absolute” terms.

 

Table 3: Average Effective Dose in CT
Exam Relative Radiation Level Range of values (mSv)
Head 0.9 – 4
Chest (standard) 4 – 18
Chest (high resolution,
e.g., pulmonary embolism)
13 – 40
Abdomen 3.5 – 25
Pelvis 3.3 – 10
Coronary Angiogram 5 – 32
Virtual Colonoscopy 4 – 13
Calcium Scoring 1 – 12

This is why there is an increase in the relative risk values for the “entire population”  if children are included in that evaluation. However, even a quick glance at Figure 28 (above), where the estimated lifetime risk that radiation will result in cancer (carcinogenesis) is presented relative to the person’s age, shows that children have a 10% – 15% lifetime risk from radiation exposure, while individuals over the age of 60 have minimal to no risk (due to the latency period for cancer and the person’s life expectancy).  The accepted latency period is, by the way ~ 10 years.

Table 1 shows the relative risk of developing cancer per sievert (Sv) unit of radiation exposure. Tables 3 and 4 provide some comparison benchmarks of radiation exposure both in relative terms (low, medium, high) and in terms of common, specific medical imaging procedures used in regional CT.

So, let’s put this information in the context of a cryonicist wishing to reduce his risk of unexpected deanimation. The protocol being proposed here assumes a baseline scan at age 45 for males (50 for females) which, if free of any indication of ongoing morbid processes, is to  be repeated in 5 years, at age 51. If than scan is negative, subsequent scans would be performed at intervals of 5 years (if negative) until age 81, at which time the scan interval would decrease to 2 years. If we assume a lifetime cancer risk of approximately 1 in 1000 and a total of 7 scans  until age 81, at which point any further risk from radiation exposure becomes irrelevant, we might expect to see an increase in the lifetime risk of cancer from approximate 33% to 34%.  Even if the number of scans were more than doubled to 20; one per two years during the interval between age 50 and age 80, the lifetime risk of cancer would increase at most to ~ 35%.[1] This of course, assumes that all DSSs are CT, as opposed to MRI.

Table 4: Some Exposure Risks for Comparison

Activity/Exposure mSv/year
Smoking 30 cigarettes a day 60–80
New York-Tokyo flights for airline crew 9 .0
Average radiation dose for Americans 6.0
Dose from cosmic radiation at sea level: 0.24

 

These risk calculations are based on the linear no-threshold (LNT) model of radiation risk.  This model assumes that the carcinogenicity of radiation is proportional to dose, even down to the lowest levels.  No one really knows how carcinogenic low-dose radiation is, because the carcinogenicity of low doses is so small that it’s practically impossible to measure. The official position of the Health Physics Society is that quantitative estimates of risk for doses below 50 mSv per year (100 mSv lifetime) cannot be made.[2]

___________________________________________________

As useful aside, if you are interested in the progress being made in medical imaging, I would highly recommend the blog Magnetic Resonance Imaging: To See and Be Amazed: http://limpeter-mriblog.blogspot.com/ The site contains many beautiful images and is a treasure trove of information on both the mainstream progress, and the esoterica of MRI

_________________________________________________

End of Part 4



[1] This also does not take into consideration the possible brief use of radioprotective nutrients taken prior to the scan.

[2] My thanks to Dr. Brian Wowk, Ph.D. from whom I stole this paragraph.
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 Appendix 1

Appendix I: Specimen Protocol for Whole Body MRI Examination to Predict Early Deanimation

Table A-1: Protocol for a whole-body MRI examination for atherosclerosis and colonic polyps. The total examination time (“in-room time ”) is approx. 60 min. SE: spin-echo sequence; TSE: turbo spin echo sequence; CA: contrast agent; FLAIR: fluid-attenuated inversion recovery sequence; HASTE: half-Fourier single-shot turbo spin-echo sequence; true FISP: true fast imaging with steady-state precession

A protocol for a comprehensive examination, not only of the vascular system, is presented as follows (Table A-1). Due to the systemic nature of atherosclerosis, a specific screening protocol has to demonstrate high accuracy in the detection of vascular changes over several regions of the body. This includes the cerebrovascular system with its extracerebral and intracerebral arteries, as well as the parenchyma supplied by these vessels. It is really rather difficult to predict cerebrovascular disease; only 26–50% of patients with a peripheral vascular occlusive disease (PVOD) have a cerebral component [79, 80]; many patients with a vascular disease are however only diagnosed once they have become symptomatic [1].

The screening protocol for atherosclerosis also includes the vascular examination of the aorta, supraaortal branches, visceral vessels, and the periphery. The possibility of imaging all these vessels in a single, brief examination has significantly changed the diagnostic procedure in centers having his facility. Finally, the heart should be examined. Even though the examination may often “only” be able to look for wall motion disorders and previous cardiac infarcts for reasons of time pressure or the lack of suitable sequences, even this provides important information, since the rate of unknown cardiac infarcts/unidentified CHD is not inconsiderable [2].

The whole-body MR angiography was performed with the aid of a system-compatible “roller-mounted table platform” (back then the newer systems with integrated whole body image acquisition were not yet available) [3]. This platform allows acquisition of 5–6 three-dimensional angiography data sets following a single administration of contrast agent using the “bolus chase” technique. Besides the possibility of now covering a field of view in excess of 180 cm without repositioning the volunteer, an advantage of this system is the use of surface coils, which, thanks to their higher signal-to-noise ratio, deliver significantly improved image quality compared to the body coil integrated into the scanner.

Heart imaging involves an axial T2-weighted “dark-blood” sequence to produce a morphological overview; this is however extended in the craniocaudal direction to include the entire lung. Images of this type are very sensitive for the detection of focal lung nodules [4].

Functional imaging with fast gradient-echo sequences (T2/T1 contrasts are most informative), as well as late enhancement sequences using inversion recovery sequences to optimize the contrast of infarctions versus healthy myocardium, are acquired in several short and long axis sections. Here, late enhancement imaging uses the intravenous contrast agent previously applied for MR angiography, and repeated administration of contrast agent is not required.

In the last part of the whole-body MRI, attention is then turned to malignomas, and MR colonography is performed. Colon carcinoma, as the second most frequent malignant cause of death after bronchial carcinoma, is the special focus of attention. A three dimensional T1-weighted gradient-echo sequence is acquired following spasmolysis and rectal enema [5].

Appendix References

1. McDaniel MD, Cronenwett JL. Basic data related to the natural history of intermittent claudication. Ann Vasc Surg 1989; 3: 273–7.

2.  Lundblad D, Eliasson M. Silent myocardial infarction in women with impaired glucose tolerance: The Northern Sweden MONICA study. Cardiovasc Diabetol 2003; 2(1): 9.

3. Goyen M, Quick HH, Debatin JF, et al. Whole body 3D MR angiography using a rolling table platform: initial clinical experience. Radiology 2002; 224: 270–7.

4. Vogt FM, Herborn CU, Hunold P, Lauenstein TC, Schroder T, Debatin JF, Barkhausen J. HASTE MRI versus chest radiography in the detection of pulmonary nodules: comparison with MDCT. AJR Am J Roentgenol 2004; 183(1): 71–8.

5. Ajaj W, Pelster G, Treichel U, Vogt FM, Debatin JF, Ruehm SG, Lauenstein TC. Dark lumen magnetic resonance colonography: comparison with conventional colonoscopy for the detection of colorectal pathology. Gut 2003; 52(12): 1738–43.

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Much Less Than Half a Chance Part 3 http://chronopause.com/index.php/2012/04/04/much-less-than-half-a-chance-part-3-2/ http://chronopause.com/index.php/2012/04/04/much-less-than-half-a-chance-part-3-2/#comments Wed, 04 Apr 2012 09:42:05 +0000 chronopause http://chronopause.com/?p=1589 Continue reading ]]> How to avoid autopsy and long ‘down-time’

(ischemia) ~85% of the time!

By Mike Darwin

Removing a Central Objection to Cryonics

In case you missed it, what I just said in that slim paragraph at the end of the preceding part of this article has profound implication because it has the potential to remove what is unarguably one of  the largest and the most rational objections that there are to cryonics. That objection is that roughly two-thirds of those who have made cryonics arrangements will not be cryopreserved under good conditions, and that half of all those signed up will be cryopreserved under very adverse conditions, such as autopsy or long (greater than 12 hours) post cardiac arrest delay. The recent advances in non-invasive medical imaging I’m about to discuss here offer the opportunity to we cryonicists to make many, if not most such losses all but unnecessary.

Figure 17: False color CT 3-D reconstruction of a patient’s intracranial arterial vascular tree. The orange-red, cheery shaped anomaly behind the right eye is a large aneurysm. The brain and other intracranial soft tissues have been digitally subtracted to facilitate a complete and unobstructed view of the patient’s arterial vasculature.

The image that you see in Figure 17 is now a perfectly pedestrian medical image that can be obtained from a garden variety CT scanner available at most diagnostic imaging centers in mid-sized cities anywhere in the world. This particular image has the brain, the soft tissue and everything digitally subtracted from it but the patient’s arterial tree and skull. The cherry shaped protrusion on the right is an aneurysm which, if were to rupture, could cost the patient his life or leave him profoundly disabled.

Figure 18: Many brain aneurysms can be treated non-surgically by passing a very thin platinum wire within the aneurysm where the wire coils up to form a yarn-like ball inside the weakened, ballooned-out area of the vessel wall. A clot subsequently forms around the coil and the vessel eventually closes off the opening to what was once the aneurysm.

Fortunately, there is a procedure  called “coiling” (Figure 18) which allows most such aneurysms to be successfully treated. Sadly, very people with brain aneurysms know that they have one until it ruptures – by which time it is almost always too late treat it effectively.

Scan Your Troubles Away?

The question logically arises, “Why not look inside everyone’s head if we have the technology to do so? Wouldn’t that allow us to identify not only the people who have aneurysms they don’t know about, but also everyone who has a tumor, or a narrowed coronary or carotid artery, or a gallstone, or anything else wrong with them that they don’t know about? In fact, why not scan their whole bodies and see if anything is amiss? Wouldn’t that allow us to nip most slowly progressing degenerative diseases in the bud?”

The answer to that question is a qualified “Yes and no.” The first and most important qualification to consider is the very substantial difference between them and us. They are going to die and, hopefully, we are not. Once you are content to die, it doesn’t really make a great difference exactly how it happens and it certainly doesn’t make any difference what happens to you afterwards. They will pay exactly nothing to avoid laying around dead for x-hours, or to avoid being autopsied. We, on the other hand, will pay something. That is a huge divide, because, as it turns out, the first and greatest barrier to such universal screening using CT and/or MRI is its adverse cost to benefit ratio.

Figure 19:  The rapid advance of computing and the high demand for ever more sophisticated medical images has driven the cost of 3-D CT and MRI scanning down to ~ $200 for a head scan $800 for a whole body scan.  http://www.superiorbodyscan.com/?gclid=CP_d5Neyiq8CFWwGRQodsHQX-w

While there are many CT and MRI machines, they are kept adequately busy, or perhaps just a little less busy than some of their owners would like, imaging sick and the worried well or hypochondriacal people. If the entire population, or even some modest fraction of it were to suddenly present for imaging, the system would crash. CT and MRI machines are very expensive and while the cost of scans has dropped dramatically, they are still not free. On the macro-level, governments, insurance companies and economists are constantly struggling to determine which therapeutic and diagnostic interventions offer the best return for the money invested in them.

The Problems of Bite Back and VOMIT

Surprisingly, information obtained from diagnostic tests can sometimes not only fail to yield any benefit, in which the case the money spent on the test is wasted, they can also cause harm. A recent example of this, much in the news, is the Prostate Specific Antigen (PSA) test used as a screening tool for prostate cancer (Figure 20). (http://www.pbs.org/newshour/rundown/2011/10/psa-testing-controversy-reignites-over-screening-debate.html) The problem with the PSA test as a screening tool is that to be effective in that capacity it requires a fairly long baseline, a good deal of contextual information (the patient’s race, family history, medications, and so on) and it requires good clinical judgment as well as a ‘patient’ patient.

Figure 20: It was anticipated that the PSA test, used as a screening tool for prostate cancer, would significantly reduce both the morbidity and mortality from the disease. It has so far failed to do so.

A single high PSA reading, or even several, may mean nothing. Most often it is the trend, rather than the absolute number; this is particularly true for black men.  In short, it’s a test that takes a lot of time and thought to interpret and use well and as such is probably not well suited to mass screening where a “yes” or “no” answer is sought before proceeding to costly, invasive and possibly injurious further evaluation.  Yet another problem is that even when prostate cancer is found and treated, it turns out that very few lives are saved because most of those cancers are slow growing and in men who will die of something else before the cancer kills them. Thus, the cost to benefit ratio of the PSA is being questioned, not the least of which because it causes many men to suffer and even die from treatments from which they did not benefit!

This is very much where medicine is today with respect to the “medical imaging singularity.” While it is possible to “look inside” just about everybody, the cost to benefit ratio for the health care system and for the “man on the street” would not justify it. In fact, it would be a medical catastrophe.

To understand why this is so it is necessary to understand three things. The first and most important of these is something called VOMIT, which is a very serious form of bite back associated with our new found ability to see inside patients with increasing exactitude. VOMIT stands for Victim of Medical Imaging Technology and refers to patients who suffer unnecessary interventions for abnormalities observed by imaging or other investigational technology, but which were not found during surgery or subsequent invasive diagnostic interventions. (Hayward, 2003) Here, I will go further and extend the definition of VOMIT to include any diagnostic finding which result in a diagnostic or therapeutic intervention which is not cost effective or causes harm to the patient. That is a very important caveat and tall order to fill, as we shall soon see.

The second is the relatively straightforward one of the ratio of the dollar benefit of resources expended to dollar benefit returned in years of productive life saved as a result of the intervention. Even in cases where early diagnosis saves lives, such as in breast cancer screening, the economic returns are equivocal. It is also often the case that “early” diagnosis with existing imaging technology is still not early enough to cure the disease. As a result, the patient suffers a longer, more miserable course of treatment and the healthcare system is subjected to greater expense with no return.

The third is the problem of information overload and it is somewhat related to VOMIT. The truism that a picture is worth a thousand words is probably a vast understatement. A single 3-D medical image contains a vast wealth of information – information which has heretofore been unavailable to both the clinician and his patient.  This might seem like a good thing, and in the long run it will be, but for now, and for a long while to come the details of the landscapes being revealed will, to a great extent, be terra incognito.

The Danger of TMI

When advances in microelectronics allowed for 24-hour ECG monitoring in the 1970s,  it became possible for clinicians for the first time to see the beat by beat electrical activity of their patients’ hearts for up to a day at a time, or longer. Prior to that, they were limited by the enormous quantities of paper tracings that would be required and the need to confine the patient to the clinic or laboratory. Now, with the advent of the compact and mobile “Holter monitor,” it was possible to capture the patient’s ECG data continuously under ambulatory, real-world conditions (Figure 21). Physicians were awash in a veritable sea-tide of data!

Figure 21: The Model 445 Mini-Holter Recorder which was released in 1976 allowed clinicians for the first time to “see” their patients’ ECGs under real-world conditions and for prolonged periods of time.

The problem was , they assumed, quite understandably, that they knew what it all meant. After all, doctors had been looking at patients’ ECGs for decades in their offices, in hospitals, at bedsides in homes and in physiology laboratories. They knew how to read  an ECG! So, when they discovered that some of their patients had periodic bouts or “runs” of very worrisome arrhythmias, they did the prudent and rational thing – they treated them for these arrhythmias with medications. Unfortunately, the result was the opposite of that expected; a significant increase in morbidity and mortality in these patients, because it turns out that in a subpopulation of healthy people, those arrhythmias were benign and not indicative of any health problem.  Thus, misinterpretation of the “same” information they were confident in dealing with in small chunks, presented in bulk and in a different context, was one of the unforeseen and arguably unforeseeable bite back consequences of Holter monitoring technology. (Harrison, 1978)

The Last Heart Attack?

If you assemble and then read over the Alcor case summaries of the last 40 years it is impossible not to be shocked by the seemingly high incidence of sudden and unexpected cardiac arrests. Because my data set is incomplete for Alcor, I can’t be definitive, but the number seems to be somewhat higher than for the same subpopulation of people from the general population (white, middle class, etc). Until, that is, you consider that most cryonicists are male. So, as you read accounts of cryonicists in their 40s and 50s arresting while scuba diving, while taking a nap or watching television, in part what you are seeing is selection bias at work. The point is, no one ever died of “sudden heart disease” a “sudden aneurysm” or, for that matter “a sudden cancer.” These are degenerative disease that takes years to decades to develop. While still difficult to detect in their nascent stages, their terminal lesions are usually very visible many months and sometimes for even for many years before they end lives.

Figure 22: Coronary artery calcium scoring using computed tomography and carotid intima media thickness and plaque using B-mode ultrasonography offer the prospect of detecting almost all coronary artery disease before it reaches the stage where it can cause a heart attack or sudden cardiac arrest.

 

 

There has been a great deal of media attention lately to an initiative called SHAPE; The Society for Heart Attack Prevention and Eradication,  which aims to all but eliminate heart attacks by combining CT of the heart to obtain a “myocardial calcium score” (a powerful risk predictor of heart attack)(Figure 22) and carotid intima media thickness and plaque using B-mode ultrasonography as part of a three step program to eliminate heart disease. The next two steps in SHAPE’s plan are a “polypill” combination of blood pressure and anti-atherosclerosis drugs and finally, perhaps, a vaccine. A similar “Last Heart Attack in America” initiative focused on coronary scanning along with dietary interventions to reverse atherosclerosis has been the focus of a feature length documentary on CNN in which former US President Bill Clinton is prominently  featured as a spokesman and advocate. The common ground of these two initiatives is that almost no one dies of a heart attack without there being  glaring evidence present in their hearts years before the infarct occurs. It is only necessary to look for it!

There can be no question that as imaging technology evolves, and as medical acumen catches up with what is available, that such imaging will become a routine part of any checkup  for patients whose age and risk profile merit it (and eventually, if they live long enough, that means most patients). As it stands right now, if you are a middle aged man or woman with a significant risk profile for heart disease, and you have a heart attack, it’s my personal opinion you have ample grounds to sue your physician for negligence.  Right now, that’s just my opinion, so it doesn’t count for anything, but the point is that sooner or later this, or a better coronary imaging modality is going to become the standard of care and heart attacks will become a rare event – a thing of the past – a relic from a time when doctors couldn’t see inside of you.

Ultrasound Investigations

There are cheaper, simpler and completely risk free ways (in terms of radiation) to  find out whether you have atherosclerosis or not.  The most predictive of these for money is the carotid ultrasound (CUS) test.

Figure 23: The carotid ultrasound scan is  a simple, non-invasive diagnostic investigation that employs sound waves to create an image of the two large blood vessels in the neck that supply most of the blood to the brain. If there is a buildup of plaque or a thickening of the limning of these two arteries the person is at increased risk of stroke and there is a high probability that there is also systemic atherosclerosis present. If there is evidence of severe narrowing of one or both of the vessels, then it becomes urgent that medication and possibly surgery be used to correct the condition in order to avoid the likelihood of a crippling or lethal stroke.

This simple, non-invasive test takes just a few minutes and uses ultrasound waves to image the carotid arteries and the blood flowing through them (Figure 23). If there is thickening of the arterial wall, or plaque present, then it is a virtual certainty that the person has systemic atherosclerosis and warrants a more extensive workup. This test is often also “packaged”  with a quick “look-see” at the abdominal aorta also using ultrasound, to rule out the possibility of an abdominal aortic aneurysm – something that is more common in smokers once they reach middle age, and beyond.

If you shop around diligently, the cost a CUS can be as little as your transportation costs to the health fare or community center where it is being offered, often as a “loss leader” by health care providers or medical imaging companies seeking more remunerative business opportunities (if they find something amiss during the CUS).  The cost of such an evaluation can range from as little as $60, to as much as $380.

A CUS is ideal for people on a budget and for those under age 45 with no history of heart disease, cancer or other pathology or risk factors that might put them at increased risk of sudden cardiac arrest.

Why Full Body Scans?

Figure 24: The full body CT or MRI scan is often offered as “add-on” to the complete or the “executive’s” physical. Many imaging centers offer these scans without the need of the patient’s person physician prescribing the scan using their in-house radiologists to write the order for the test. http://www.prevenium.com/contact.asp

 Put simply, there is no substitute for seeing, or to put a new twist on an old adage: a picture is worth a thousand medical tests. While the origins of all of the degenerative diseases that kill us are at the molecular level, mostly we die as a consequence of the macro-level changes they inflict on our bodies, even if the coup de gras is rooted in the action of things like adhesion molecules and inflammatory pathways; as is the case with most heart attacks. It is the large, easily “seen” bulges of aneurysms, masses of plaque or tumor that kill, and these almost always take years to develop. What this means practically is that, with a few exceptions, aside from suicide, homicide and accident, virtually no one has to die – or to deanimate without plenty of advance warming. The implications for cryonics are as obvious as they are profound.

End of Part 3

 

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Much Less Than Half a Chance? Part 2 http://chronopause.com/index.php/2012/04/03/much-less-than-half-a-chance-part-2/ http://chronopause.com/index.php/2012/04/03/much-less-than-half-a-chance-part-2/#comments Tue, 03 Apr 2012 16:59:05 +0000 chronopause http://chronopause.com/?p=1587 Continue reading ]]> How to avoid autopsy and long ‘down-time’

(ischemia) better than ~85% of the time!

By Mike Darwin

Ischemia: The Problem of “Long Down Time”

 Almost every cryonicist I’ve ever spoken with envisions his cryopreservation will occur under ideal circumstances. He will be diagnosed with  some vague and ill defined terminal illness, bravely decide to end futile treatment and then enter hospice with a team of skilled and caring cryonics personnel at his bedside. He will nap, read, watch TV, and then, near the end, nod off surrounded by loved ones as the cryonics personnel hover nearby. This may not be the most attractive picture in any absolute sense, but it is certainly as reassuring a one as it is possible to find in contemporary cryonics. And while many, or even most cryonicists may find this scenario credible, much of the rest world doesn’t.

 Figure 10:  Approximate U.S. distribution of predictable deaths by cause based on 2004 data. Note that ~57% of all deaths occur sufficiently suddenly, or under circumstances such as accidents, which preclude standby or other cryonics stabilization measures. Chart derived from data: [National Vital Statistics Report, Volume 53, Number 5 (October 2004)]. This data may be compared to the data in Figure 10 to see how closely the US national incidence of sudden and unpredictable death map that of Alcor’s experience (Figure 11).

One likely reason for the scarcity of biomedical people involved in cryonics is that their actual, day-to-day experience is at sharp odds with the scenario I’ve just laid out above.  In countless hours of both focused and casual conversations with such individuals, what emerges is a sense of incredulity about the reversibility of the damage these professional and technical people witness as a part of their duties caring for the very old, and the critically ill dying; not to mention that large fraction of people who die suddenly and without warning, end up as DOAs in the emergency department or coroner’s cases. Regardless of whether their opinions prove the valid ones, we are clearly failing to communicate to them and to the community at large, an experience of cryonics which is not so biomedically adverse.

To do that, it is first necessary to move beyond  anyone’s scenarios or suppositions and evaluate the reality of what is actually happening to the patients we cryopreserve. That turns out to be a hard thing to determine with any degree of precision, because none of the cryonics organizations maintain any kind of statistical database on their members’ cryopreservations. How many cryopatients have dementia? How many were autopsied? What is the mean ischemic time from cardiac arrest to the start of cardiopulmonary support (CPS)? How many patients have ischemic times of 2-5 minutes, 5-10 minutes, 15-30 minutes, 12 hours, 14 hours, 5 days? What is the mean age at cryopreservation? [Absence of data on this last question I find particularly amusing in a group of people supposedly preoccupied with longevity and "life extension": how long are they living, on average?]  There is currently no way to tell.

There is not even any way to determine the age, gender, or any of dozens of other potentially critically important demographic details that are, or could be vital in assuring quality cryopreservations, reducing ischemic times, or reducing known iatrogenenic events. A concern of mine for onto three decades now is that we have no way to spot adverse epidemiological events that might be associated with our unique dietary supplement or other lifestyle practices. Perhaps most incredibly, there are no written criteria, however arbitrary, to assign any degree of quality, or lack thereof, to the cryopreservation a given patient has received (let alone that a given Cryonics Organization (CO) provides, on average). This had lead to what has become known as “the last one is always the best one” to date rating system, wherein each case that is not either an existential or an iatrogenic disaster, is pronounced by the staff who carried it out as, “the best case we’ve done so far!”

We cryonicists may be in some kind of willful, data free fog about what our situation is, however, it’s a safe bet to assume that most of the rest of the world, based on their own professional and personal experiences, are not so ignorant. The first step towards a solution is to understand the scope and severity of the problem by getting reliable numbers. While that is not easy to do, the Alcor Life Extension Foundation does maintain a crude, if incomplete accounting of all the patients they have placed into cryopreservation: http://www.alcor.org/cases.html. A cursory analysis of this yields the following breakdown. Even basic data such as cause and mode of death are missing from ~20 of the cases listed there – these have necessarily been excluded from the analysis below.

Figure 11: A major hurdle to evaluating quality in cryonics operations is the lack of any outcomes (e.g., reanimation followed by evaluation) or of any surrogate markers or scoring systems to serve as evaluation tools to determine not only the quality of cryopreservation care being given, but also the objective neurocognitive status of the patients when they enter cryopreservation. For the purposes of this analysis very crude criteria were used to assess the quality of the patient as a finished product at the end of cryopreservation. These were normothermic ischemic time between cardiac arrest and the start of CPS, catastrophic peri-arrest brain injury such as an intracranial bleed followed by prolonged cerebral no-flow before pronouncement of medico-legal death, very long warm ischemic times (> or = to 12 hours) and autopsy.

Using the criterion of “minimal ischemia” (≤15 minutes)[1], 48% of Alcor’s patients are cryopreserved under these conditions (Figure 10).  Thirty-nine percent of their patients suffer long ischemic periods of 6-12 hours or more (mostly as a result of SCA and UDA); and 13% suffer very long periods of ischemia (> or = to 24 hours) which are not currently preventable, or which conclude in autopsy prior to cryopreservation.  Put more cogently, you have less than a 50% chance of being cryopreserved (with Alcor) under conditions of minimal ischemia. While this number is discouraging, it is spectacular when compared to the Cryonics Institute, where it is somewhere in the low single digits.

 

Figure 12: The graph above is the same as in Figure 11, with the difference being that the losses have been expanded to include those that would be expected if the population wide incidence of end-stage, GDS-7 dementias were imposed on all the groups. The result is that percentage of patients who might reasonably be expected to have both minimal ischemia and no pre-cryopreservation GDS-7 dementias drops to just 26%.

But once again, these numbers are misleading if the criterion is cryopreservation under minimal ischemia conditions, because they do not take into account the number of patients who enter cryopreservation with dementia, or severe brain injury due to stroke, other neurovascular disease, or massive head trauma. If only dementia, at the current incidence for the general population is factored into the analysis, then the picture becomes considerably more bleak, as can be seen in Figure 10, with only 26% of  Alcor cryonics patients being preserved with relatively intact brains under reasonably good conditions.[2]

Impact of the BDDs on the Likely Survival of Personhood

 

Figure 13: The effect of advanced Alzheimer’s Disease on the macroscopic appearance of the brain is evident when coronally sectioned brains from an AD (R) patient and a healthy person in their mid-20s (L) are compared side by side.

Deaths from AD are typically deaths from end-stage AD, which usually implies severe global destruction of both cerebral hemispheres (Figures 13 & 14) on both a macro and microscopic level. Death due to AD is a prolonged process (~8 years from diagnosis to death), and the neurological deterioration that occurs as the disease progresses is often scored using the global deterioration scale (GDS) of primary degenerative dementias, which ranges from 1 (least) to 7 (worst) in severity. GDS scores in excess of 5 are associated with major loss of macro- and micro-scale brain structure and will be assumed here to represent serious compromises to, or the destruction of personhood.

Figure 14: The histological appearance of the brain in AD is shown in panels b and c above. In many areas of the brain there is virtually complete loss of the neuropil; the synaptic weave that interconnects neurons which can be seen in its normal state in c, the panel at the far left. The majority of the neurons and many of their supporting glial cells have died and been scavenged by macrophages and histiocyytes.  There are abundant deposits of proteinaceous plaque containing the  neurotoxin protein beta amyloid neurofibrillary tangles which are the remnants of neuronal long processes such as axons and dendrites. The extent and uniformity of the changes seen above varies from patient to patient during the course of the disease, but becomes increasingly uniform throughout both hemispheres of the cortex the longer the patient survives with a GDS score of 7 (end stage dementia).

A Deanimation Warning Device?

Figure 15: The medical imager as a deanimation prediction device?

 In his 1939 science fiction story Life-Line,” Robert Heinlein envisions a device that can predict, with considerable precision, when a person is going to die. While none of us cryonicists wants to die, most of us could certainly profit from knowing when we are going to deanimate. Better still would be also finding out how to postpone our cold dip in liquid nitrogen for a while, if it was possible to do so.

Many cryonicists will be familiar with this graph of Ray Kurzweil’s showing the impending arrival of the singularity (Figure 16).

Figure 16: Ray Kurzweil’s graph showing the exponential increase in neuro-image reconstruction which has occurred largely as a function of the exponential growth in computing capacity since 1970.

Well, if you are a cryonicist, I’m here to tell you that insofar as non/minimally-invasive medical imaging is concerned, the singularity is here.

From the earliest days of medicine physicians have desired one thing almost above all others and that is to possess the power to peer into their patients bodies and observe the goings on there. Since the discovery of x-rays by Wilhelm Conrad Röntgen in 1895 (Crane, 1964) there has been steady progress towards the satisfaction of that desire. The development of contrast media, endoscopy, computerized axial tomography (CAT or CT) scanning and magnetic resonance imaging (MRI) scanning have allowed increasingly exact and impressive images of the interior of the living body to be made.

However, a number of serious limitations have, and to a great extent still do prevent the full realization of the physician’s idealized desire to see inside his patients at will. Those barriers are field, dimensionality and point of view, as well as resolution, color, contrast and the dollar cost of the imaging.

In the case of CT and MRI those barriers have been breached to such a degree that it is now possible for cryonicists to be able to determine with a very high degree of accuracy and precision both of what and when they are going to experience medico-legal death. A corollary of this is that in many cases it will be possible for them to avoid what would have otherwise been an unavoidable very long period of ischemia and quite likely a medico-legal autopsy  as well.

End of Part 2



[1] This criterion is being very generous because it assumes that all interventions that begin within ~15 min of cardiac arrest are effective at preventing further ischemic injury. This is not the case for most cryonics patients where external cardiopulmonary support is not effective at restoring adequate perfusion and gas exchange, core cooling may be delayed by several hours, and cold ischemic times may be in the range of 12 to 24 hours.

[2] Again, using the very generous criteria of assuming that all CPS is effective CPS and that no iatrogenic events compromised the quality of the cryopreservations.

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Much Less Than Half a Chance? Part 1 http://chronopause.com/index.php/2012/04/02/much-less-than-half-a-chance-part-1/ http://chronopause.com/index.php/2012/04/02/much-less-than-half-a-chance-part-1/#comments Tue, 03 Apr 2012 05:31:57 +0000 chronopause http://chronopause.com/?p=1575 Continue reading ]]>

How to avoid autopsy and long ‘down-time’

(ischemia) better than ~85% of the time!

By Mike Darwin

It’s easy to concentrate on the biggest and most obvious reason that cryonics hasn’t attracted wider acceptance, principally the fact that it doesn’t work “yet” and it will be a long time before we know if does. But there’s a clue to another capital reason for its slow adoption which is to be found in the failure of cryonics to attract much enthusiasm or activism within its own ranks. Why is this?

I believe a central reason for this failure is that cryonics, even as it is currently configured and accepted by those who embrace it, performs dismally. Everyone seriously involved with cryonics is painfully aware, either consciously or subconsciously, that cryonics is at least a two tier lottery. Sure, everyone knows that we’re taking a “chance” on being recovered in the future by being cryopreserved in the first place. But to even get to that round of the lottery, you have to get cryopreserved, and it would seem material whether or not you are cryopreserved well.

For some, perhaps cryonics is a ritual exercise. As long as there are remains, a freezer, someone to take the money and hang picture on the wall, then you have a chance; and all chances are created equal. Their position seems to be same as that of the millions of lottery ticket holders before the winning number is announced: we all have the same chance at the prize. If that’s your attitude, you can stop reading this right now, there’s nothing more here to interest you – not even in terms of idle entertainment value, because this discussion, from here on out is deadly serious, and brass tacks practical.

 Figure 1: The autopsy rate has declined by half in the United State between 1972 and 2007, although it has shown a slight increase since these data were collected. Source: http://www.cdc.gov/nchs/data/databriefs/db67.pdf

As Figure 1 shows, the autopsy rate, which can serve as the ultimate, population wide indicator of a very bad cryopreservation,  constituted 8.5% of all deaths in 2007. That percentage has risen slightly since then and is now at ~ 9%. The situation isn’t quite as grim as it might first appear if you break down the reasons for autopsy and note that 55.4% of autopsies were conducted as a result of deaths due to “external causes,” which means suicide, accident or homicide. If you think you are in a “lower risk” category for these, you may  be right, in which your case your risk may be fractionally smaller. And of course, not all of these autopsies were state mandated: some were requested by the next of kin, or even the decedents themselves. Still, 9% seems a reasonable, overall unavoidable loss number currently confronting cryonicists given the culture we inhabit.

Figure 2: Since the first man was cryopreserved in 1967, the demographics of autopsy have shifted increasingly from the aged to those in younger population cohorts. Source: http://www.cdc.gov/nchs/data/databriefs/db67.pdf

If the age distribution of autopsies in the US is examined, the picture gets even more uplifting if you are, or you expect to live in into old age (which is, incidentally, medically defined as 65 years of age, or older). In this age group, the incidence of autopsy has declined dramatically from 37% of all postmortems since 1972,  near the time cryonics began, to only 17% as of 2007.

However autopsy is only one of a number of factors that can and do interfere with  cryonicists achieving “good,” or even “acceptable,”  (forget  ideal), cryopreservations. The other three factors which loom large are sudden cardiac arrest (SCA), unexpected death (UD, which is different than SCA) and brain destroying diseases ( BDDs, or dementias). While Alzheimer’s Disease is the most common of the BDDs, there are others such as Pick’s, Lewy Body, Parkinson’s and the vascular dementias, which together account for 20-30% of all age-associated BDDs.

Brain Destroying Diseases (Dementias)

Autopsy is only one of a number of factors that can and do interfere with  cryonicists achieving “good,” or even “acceptable,”  (forget  ideal), cryopreservations. The other three factors which loom large are sudden cardiac arrest (SCA), unexpected death (UD, which is different than SCA) and brain destroying diseases (BDDs).

 Figure 3: Incidence of dementias as a percentage of all cause mortality in males, females and the United States population as a whole. Prepared from data in the National Vital Statistics Report Volume 59, Number 10 December 7, 2011Deaths: Final Data for 2008: 2008http://www.cdc.gov/nchs/data/nvsr/nvsr59/nvsr59_10.pdf

 Currently, the BDDs in aggregate (including catastrophic stroke) account for ~3.2% of all deaths in the US (Figure 3). However, insofar as cryonicists are concerned, this number is likely to be misleadingly low, because most cryonicists enter cryopreservation at or after age 65, the point at which the incidence of BDDs begin to climb exponentially. (Evans DA, 1990) This number is expected to, and in fact is exploding as a consequence of both the demographic shift due to an aging population in the West and increasingly longer life spans (Figure 4).

 Figure 4: The large increase in Alzheimer’s Disease as a cause of death in the United States is largely a function of the increasing average age of the population and the survival of many additional individuals into advanced old age. Source: http://www.alz.org/downloads/Facts_Figures_2012.pdf

 

 Figure 5: A breakdown of dementias by type shows that Alzheimer’s Disease accounts for 47% of the total as the sole cause of the dementia and is a major contributing factor in another 28% making it by far the most common pathological mechanism in play as the cause of dementia in the elderly.  [S. Seshadri, S, Wolf, PA, Beiser, A,  Au, RU, McNulty, K, White,R, et al. Lifetime risk of dementia and Alzheimer's disease: The impact of mortality on risk estimates in the Framingham Study. Neurology, 49:1498-1504,1997.]

 Figure 6: Incidence of Alzheimer’s Disease by age cohort in the US population as of 1988.[ Evans D, et. al. Prevalence of Alzheimer' s Disease in a community population of older persons. JAMA, 262:18;2551-6, 1989.]

In the 74-84 age cohort, 19% of that population has AD (exclusive of other dementias) and in those individuals over the age of 85, the diagnosed incidence is 47%. These numbers are almost certainly low, because many of the elderly are who are institutionalized for falls, or other issues not ostensibly related to primary brain disease, go on to develop brain disease in an institutional setting and ultimately have listed as their causes of death, pneumonia, urosespsis, sepsis  secondary to decubitus ulcers, or other causes that escape epidemiological surveillance for AD. Currently, AD is responsible for 2.8% of deaths in white males men aged 65  or older and 4.7% of white males who are 85 years of age, or older. These numbers are expected to triple by the year 2050.

 Figure 7: The incidence of Alzheimer’s Disease rises roughly exponentially with age such that over 1,100 people out of 100,000 aged 86 or older have the disease.

When cryonics was launched in the mid-1960s the problem of BDDs as a threat to the workability of cryonics was not even considered.  In 1967, the year the first man was cryopreserved, the average life expectancy in the US was ~70 years and the problem of dementias was a fraction of what it currently is.  Additionally, comparatively little was known about the pathophysiology of the BDDs at that time, and there was little or no awareness within the cryonics community of their potential to degrade or altogether destroy personal identity, perhaps even years in advance of the pronouncement of medico-legal death. The problem of BDDs and of age-associated destruction of the brain is arguably the foremost biomedical obstacle confronting cryonics in the long term, and it is for this reason that I will return to this topic again later in this article in the context of discussing its early detection, with a brief discussion of treatment, and ultimately, definitive interventions to halt and reverse it.

Figure 8: The Siemens Biograph mCT PET is a positron emission tomography/computed tomography (PET•CT) scanner that enables precise measurement of metabolic processes and data quantification, including the assessment of neurological disease and malignant tissues (resolution and molecular characterization of neoplasms as small 3 mm in diameter). The device can provide quantitative measurements of brain beta amyloid protein burden.

For now, I will note that because AD is by far the most common of the BDDs and because it has a unique pathophysiological feature, a remarkable advance in early diagnosis via noninvasive  computerized tomography (CT) and positron emission tomography (PET) imaging has recently become clinical available. Beta amyloid is the protein found in the plaques characteristic of AD, and there has been intensive research over the past decade to identify radiolabeled tracer compounds that will safely cross the blood brain barrier (BBB) and bind to both beta amyloid and tau proteins. (Barrio 2008), (Black, 2004)  In February of this year, the US FDA approved the Siemens Biograph mCT, a positron emission tomography-computed tomography (PET-CT) scanner capable of not only detecting, but of quantifying  amyloid in the brain. The Biograph mCT has been very well received, and within the space of a few months the machines have appeared in most major cities in the US. The Biograph mCT in conjunction with the recently developed FDDNP, (2-(1-6-[(2-[F-18] fluoroethyl)(methyl)amino]-2-naphthylethylidene) malonitrile) tracer allows for calculation of total brain amyloid burden (Wang, 2004) and visualization of discrete amyloid containing lesions as small as ~ 3 mm in diameter (tracers for tau protein, the other primary pathological protein in AD are currently in the pipeline for FDA approval).

 Figure 9: Top: PET scan of beta amyloid deposits in the brain of a patient with early moderate Alzheimer’s disease appear in red in the image above. The beta amyloid deposits are concentrated, as expected, in the frontal and prefrontal cortices as well as in the hippocampus. Bottom: Beta amyloid distribution in the brain of a patient with early moderate AD (L) versus normal control (R). One important consequence of this imaging is the growing realization of the global range of AD’s impact on the brain. As recently as a decade ago it was believed that the destruction of brain tissues was confined largely to the hippocampus and the prefrontal cortex, especially early in the disease. It is now understood that the histological destruction of AD is widespread and that during the end-stage of the disease few if any areas can be expected to be spared.

Very early detection of AD may turn out to be critical to achieving effective treatment, or even slowing progression of the disease, since significant beta amyloid and tau deposition seem to promote ongoing inflammation and interfere with putative therapeutic drugs. A good example of this is the recent fate (Vellas, 2010) of the investigational drug  tarenflurbil ((R)-flurbiprofen ) which inhibits gamma-secretase, the enzyme that produces beta amyloid AB-42, the species of beta-amyloid that forms fibrillary plaques. (Black, 2008) Unfortunately, the drug does nothing to remove existing existing AB42 deposits, which presumably continue to exert their neuron killing and pro-inflammatory actions.

(R)-flurbiprofen is highly effective in animal models of very early AD and the drug showed significant promise in Phase I & II clinical trials. However, development of (R)-flurbiprofen was dropped when it became apparent in Phase III trials that the drug would likely only be effective in a clinical setting if it its administration was begun before clinical signs of AD developed; in other words, when beta amyloid levels were very low and would be detectable only by testing cerebrospinal fluid or, now with sensitive CT molecular imaging techniques involving the screening of subpopulations of healthy individuals at risk.

This kind of effort and application of technology and pharmacotherapy may not profitable for pharmaceutical companies, but that does not mean that it would be be worthwhile for us cryonicists. (R)-flurbiprofen  is a close chemical relative of the OTC NSAID ibuprofen and it is a metabolite of the prescription NSAID flubiprofen.  (R)-flurbiprofen  is an enantiomer of flurbiprofen (~ 5%  of (L) flubiprofen is metabolized into (R) flubiprofen by the liver after ingestion) which is completely inactive as  a COX inhibitor, and is thereby free of the anti-COX side effects associated with NSAIDS.  Despite it’s lack of both COX-I and COX-II activity, the drug does have strong anti-inflammatory activity by acting through inhibition of NF-κB and AP-1 activation pathways, and this may provide added benefit in controlling the inflammatory processes associated with AD. (Tegeder, 2001)  As an interesting aside,  (R)-Flurbiprofen has also been shown to suppress prostate tumor cells by inducing p75NTR protein expression. (Quann, 2007)

(R)-Flurbiprofen is an example of a drug with considerable therapeutic potential that will almost certainly not see clinical application due to the high cost associated with regulatory burden and the logistical hurdle of needing to start therapy years before symptoms of AD manifest themselves. (R)-Flurbiprofen might also conceivably be useful as combination therapy with  the already FDA approved skin cancer drug bexarotene (Targretin), an antineoplastic, which has been shown to reverse beta amyloid deposition in a rodent model of AD as well as to improve cognitive function. Targretin rapidly cleared beta amyloid from the brains of animals in a variety of models of AD (<2 months) and while it is not a cytotoxic chemotherapeutic agent, the drug has sufficient adverse effects that it would be problematic to administer over a period of years or decades. A combination of short term therapy with Targretin to remove beta amyloid, followed by long term administration of (R)-Flurbiprofen is a possible treatment strategy that would seem attractive to explore. The ability to dynamically monitor beta amyloid levels in the brains of patients undergoing such novel therapeutic regimens, especially outside the confines of the medical-industrial establishment, is yet another advantage of this evolving singularity in medical imaging.

End of Part 1

 

 

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Inheritance and Disinheritance Are Not For Us http://chronopause.com/index.php/2012/03/08/inheritance-and-disinheritance-arent-for-us/ http://chronopause.com/index.php/2012/03/08/inheritance-and-disinheritance-arent-for-us/#comments Thu, 08 Mar 2012 08:16:48 +0000 chronopause http://chronopause.com/?p=1422 Continue reading ]]> by Mike Darwin

Michael B. Federowicz and Ella A. Rorhman circa 1954

Yesterday, I learned my parents, both of them, had died a little over 4 months ago. The call came from a staffer at the Alcor Life Extension Foundation. Alcor had been contacted by the attorney handing probate for my parents’ estate. My parents had died within a day of each other. My mother passed on 1 November, my father on 2 November of 2011.

It was not unexpected news. My mother had developed Alzheimer’s disease some years ago and had been frankly demented for the past several years – unable to recognize me or hold meaningful conversations for the past two years. About 8 months ago, my father, 90 years old, informed me, during one of our increasingly infrequent and unpleasant phone calls, that he was not going to call me when my mother died. My response was to inform him that I had no plans for further phone calls to him. It was the end of what had been a sharply deteriorating relationship since my mother’s illness eliminated her role as a buffer between us – a role I had not even understood existed, let alone previously appreciated was necessary.

I had no bad blood with my few other remaining relatives in Indiana, but they apparently chose not to notify me, either. To be fair, I found it difficult to communicate with them  and I’m sure the same was true for them. Neither of our phones or mailboxes were often, dare I say ever, burdened with communications.

Mike Darwin and his parents, April, 1955

My parents lived long, happy and productive lives. They gave me a great childhood, free of cares and worries, and afforded me every opportunity for education, knowledge and personal growth. My youth was a time of warmth and loving security. My parents worked hard, earned and enjoyed financial security, and enjoyed a long and happy retirement; free from worry or want. Their “golden years” were spent in remarkably good health. My father, despite being a 3-pack a day smoker since age 13, was lucky to escape with only an aortic replacement, a carotid endarterectomy and a coronary angioplasty, all of which he made rapid and astonishingly complete recoveries from. Aside from a few months of morbidity associated with these illnesses, his retirement years were active and free from any significant cognitive impairment. My mother also remained active and cognitively functional into her late 80s. Both my parents enjoyed active social lives diminished only by the relentless and ever accelerating loss of dear friends, most of whom they had the good (or mis-) fortune to outlive, depending upon your point of view. By the time they reached their mid-80s, they had outlived almost all of their cohorts. This took an especially heavy toll on my mother, who defined herself to a far greater extent than did my father, through her social relationships and through her shared memories with her girlhood friends.

One of the many backyard social gatherings with friends and neighbors my parents held. My mothers is the lady in the big sunglasses. Photo is circa mid-to early 1970s.

My Mother and my good grade school friend, Hubert Holman, preparing a package containing a red eared slider turtle for launch into the upper atmosphere, circa 1968.

How many parents would let their 13 year old kid freeze a veritable zoo of animals, or send turtles careening off into the stratosphere? And how many loving parents (and they were loving parents) would their 14 year old son go off to spend summers with a mad body freezer on Long Island, and, a scant 3 years later, run off to “freeze dead bodies” in the same place – and take a week of his senior year in high school to do so in the bargain?

Me at the Cryonics Society of New York in the summer of 1972.

 

 

 

 

Me freezing “dead” people in 1973 at age 17.

 

 

 

 

 

 

My parents gave me a great childhood. They offered me every opportunity for education and personal growth any boy could want and as only child they and I had the economic opportunity for both toys in an abundance that many children in larger families don’t enjoy. I’d like to think that both they and I took full advantage of that opportunity.

Clockwise: Christmas, 1956, Halloweenwith my dad, 1957, a von Braun rocket set with “grandma” looking on circa 1962, playing with rabbit in the early 1960s, summer in New York city in 1962. 

In looking over the hundreds of photos that now constitute almost all that is left of my parents’ past, I am struck by the evidence therein, or rather lack of evidence, of my integration into their lives after the onset of puberty. This reflects the deep sense of alienation that I felt, as well the visible absence reflected in the photographic record. Not only was I was sexually alienated from the lives they were leading by the biological accident of being homosexual – I was morally and intellectually alienated, as well. For it was at this time that I realized that religion was a farce, that death was both a great evil and personally unacceptable, and that the social and moral constructs on which the civilization I was embedded in were based were, at best, a pastiche of make believe and brutal pragmatism held together with spit and sealing wax.

Thus, intellectually, I had very little attachment to my parents. And as time went on, that meant that increasingly I had less and less emotional attachment, as well. Being home with them for visits was awkward under the best of circumstances, and had been for many years. Gratitude isn’t the same thing as genuine intimacy. My mother’s love and longing for me – the me she remembered – was tragic and pitiful – in large measure because it could not be returned – that person had long ago ceased to exist – and there was no possibility of the easy, spontaneous interaction that been there as a child. In its place was a forced simulacrum that had to be called up mechanically.

And then, she ceased to exist – which was both terrible and terrifying.

When I spoke with the probate attorney’s secretary, I was also not surprised to find that my father had replaced me as the executor and the beneficiary of the estate. My parents loathed cryonics. That is why, in no small measure, I have such high praise for them as parents for in allowing me the autonomy they did, and especially at such a young age to pursue it (cryonics). My mother, in particular, was continually nervous that I was going to “freeze her” and in fact, during her last days “semi-compos mente” whist hospitalized and gravely ill, she grasped my hand and earnestly pleaded with me, “not freeze me – or my brain!” What goes around comes around, and I had far too much love and respect for the autonomy they had shown me, so many years before, and at such a high emotional cost to themselves, to betray them in that way. They should have had no worries – and they should have known that that was the case.

My mother clearly loved me very much and she showed that in countless ways, small and large over the years, right up until she became demented. However, from the time I left Indianapolis in 1981, my parents never came to visit me in California, nor did they call me more than once or twice. When the Alcor facility opened in Riverside, I pleaded with them to come to the Grand Opening. They declined. They came to Las Vegas several times to vacation and they visited friends and family elsewhere on the West Coast – but never me. I never asked them to accept or to believe in cryonics, let alone my homosexuality. But I did ask them to accept a moment of what I considered genuine triumph in my life – the building of Alcor into a respectable place and organization that was not a seedy back-room garage operation. All they had to do was to show up – they could even have come afterwards, and just walked through the place. That rejection was incredibly wounding and, unlike my sexuality, it was not necessary and it was not rooted in religion or morality. Later, with the success of 21st Century Medicine I had another triumph, the successful recovery of dogs with no neurological deficit after 15+ minutes of complete cardiac arrest at 37°C. Again, I asked that they come. Again, they refused. That time, cryonics was not at issue. For me, that was, I think (in hindsight) the final divide between me and them, between ‘us’ and ‘them.’ It was then that I realized that symmetry. Just as I had, many years before as a boy becoming man, felt alienated from and unable to participate in their lives and in their world, so too had they been alienated from and unable to participate in mine. At last, the circle was complete. As I remarked to a dear friend later: “I’m not sure about us cryonicists and the rest of the world. Are they ants that gave birth to giants, or are we giants that gave birth to ants?” His, answer was as true as it was wise: “Both.”

Over the subsequent years, and especially after the full maturation of my bipolar disorder and my breakdown in early 2003, my father became increasingly venomous about cryonics and about me, losing no chance to denigrate or deride either of us – pointing out that I was an abject failure, an impoverished “nut case” that his tax dollars were supporting; and that if my mother had anything to say about it, his money would probably keep supporting me after he was dead – and most likely even after I was dead. I suppose there is truth in what he said. But it was very wounding.

However, the ultimate truth, which I remain convinced of, is that he was wrong about cryonics. Certainly, he was wrong about his money supporting me, either after his death, or mine.That was a simple matter his own actions quite simply, and quite righteously saw to.

The day after I got the news about my parents death, Dr. Brian Wowk kindly offered his condolences and in so doing he used the term “disinherited.” That shocked me, because I in no way feel (or felt) disinherited. This so because I never considered my parents’ money mine. I told them this often, and for many, many years when they were alive. Starting from when I was a teenager, actually.  I didn’t earn that money – they did. I told them to spend it on themselves. And as they lived into old age in good health, I cautioned them to save for “spend down” and for the quality nursing home and assisted living care they would very likely need. As it was, they both had and were able to pay for very good nursing home and assisted living care until the day they died. I never wanted nor expected their money. So, I suffered no hurt at all about being “disinherited.” If my father wanted the money to go elsewhere, then I’m happy he was able to see, or at least know, it would do so.

One of the things my parents had no way of knowing I would learn  as a teenager banging around the Cryonics Society of New York (CSNY),was the utter contempt I would learn for inheritance – for the very concept of it – and for its fundamental incompatibility with a cryonicist/immortalist existence. My days as a kid at CSNY made me sick to the core at the avarice of children for the unearned money of their dead parents. Seeing that contemptible greed in action sickened me on inheritances at an early age; and nothing in my subsequent experience – right on through to fantastic grab for the wealth of Dick Jones, did anything to improve my opinion of it. I still wince every time I think of, or look at a picture of Clara Dostal – and that is often, since one of she and I hangs on the wall next to where I am sitting now, as I write this. Inheritance is based on the FACT of and the INEVITABILITY of death. And that fact is anathema to us. It is also based on the concept of the unearned at the expense of the lives of the others. And that concept ought to be anathema to everyone.

No, the only things that distresses me about the way my parents passing was handled were that I wasn’t told about their deaths until four month later, and about the obituary my father prepared for submission to the local paper. I would be dishonest if I said I was not relieved about being freed from the socially expected obligations, (and the attendant  financial and psychological/emotional ones), of attending the funeral/burial. I said my goodbyes to my mom several years ago, when she was still barely oriented enough to understand. Burials and funeral Masses are rituals for them, not us. They are things for us only when we fail. When they are things of conscious choice made by others, they are unnecessary horrors, and we are under no obligation to participate.

As long as I live, I will not forget my parents, nor will I ever cease to be grateful to them. But they chose, quite consciously, to die. I respected their right to that decision and to their autonomy in making it. But it is a terrible and forever isolating thing to do. It is a thing that starts isolating and alienating years before death actually occurs, because once you accept death and decide to die, you must, inevitably, begin surrendering the struggle to stay involved with life and living, and thus to stay current and a part of the world of today.

This was something that both of them did increasingly, quite independent of their involuntary, age-associated deteriorating cognitive reserves. And that is one huge difference I’m increasingly noticing with experience between cryonicists and non-cryonicists. Even those cryonicists who are sorely neurocognitively challenged struggle mightily to stay involved with, and in love with life and the technologies that drive it. Men like Curtis Henderson and Bob Krueger come to mind. I am humbled and in awe of the nobility of their struggles, and of their courage in confronting the debilities of old age.

I would never call my parents cowards, but there is something terrible, small and lacking in their resignation to death and in their lack of vision. They are in a graveyard now, side by side. It is for that, and for their very conscious choice to be there, that I grieve for them.

No doubt much of the pain I am now feeling is socially programmed. Some of it is genuine sorrow at the loss of what was and what can never be again – brought to the forefront of consciousness by the reality of their deaths. Some of it is, no doubt, the realization of the loathing that my father had for me – a loathing so great that he chose not to even acknowledge me as his son in the obituary he prepared for the mortuary to submit to the local paper.

Ella and Michael Federowicz

Ella A. Federowicz

Michael B. Federowicz

Ella A. Federowicz, 90, Indianapolis, passed away Tuesday November 1, 2011 and her husband Michael B. Federowicz, 90, Indianapolis, passed away Wednesday November 2, 2011. Ella was born in Indianapolis on August 6, 1921 to William and Carrie Forway Rohrman. She retired in 1981 as the supervisor of data entry from Dow Chemical after working there for 25 years. Michael was born in Brooklyn, New York on January 1, 1921 to Benjamin and Constance Jakuc Federowicz. He retired from the Indianapolis Police Department with the rank of Sergeant in 1985 after 31 years of service. Michael also served in the U.S. Army for over 10 years during WWII and the Korean War. He was a member of the Knights of Columbus Council 3660, Fraternal Order of Police Lodge 86, IPD Retired Officers and the Ernie Pyle Post VFW. Ella was preceded in death by her brothers, Virgil and Irvin Rohrman and Michael was preceded by his sister, Anna Kraska. They are survived by a sister-in-law, Janis Rohrman and several nieces and nephews.

A Mass of Christian Burial will be celebrated for Ella and Michael on Tuesday November 8, 2011 at 11 a.m. at St. Barnabas Catholic Church where they were members. Visitation will be Tuesday from 10 a.m. until 11 a.m. at the church. Burial will be in Calvary Cemetery. Online condolences may be shared at: orileyfuneralhome.com

Published in the The Indianapolis Star on November 4, 2011

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