Installment 19 - 10+1 Questions with Dr. Anthony G. Payne, Ph.D

[Technocracy]

Ask The Ph.D.

This month's column is being hosted by Dr. Anthony G. Payne. As always a hearty thank you to all of the experts that answer our questions.



1) Is it crucial that umbilical cord stem cells be "gender matched" to the recipient?

A. If by “crucial” you mean absolutely essential to realize clinical benefits, I’d say no. I have, however, seen evidence that suggests that cord blood stem cells are likely cleared by the human immune system within days or weeks of being infused. Part of the reason for this clearance is immunoreactivity – the immune system recognizes the stem cells as being foreign and dispatches them. Mind you, immunoreactivity is relatively low with respect to cord blood stem cells so the process is somewhat phlegmatic and inefficient. One way to decrease having the body adversely react to infused umbilical cord stem cells is to use cells that were extracted from cord blood that is blood type, Rh and gender matched to the recipient. This is the approach advocated and used by Nepsis Institute-Mexico.


2) Has Nepsis done any treatments for PAH? If so, can you give a range of improvements for patients? Does treatment tend to fade away requiring a booster? I have read testimonials on other sites, but I also have read your article, "For Those Considering Doing Stem Cell Therapy Abroad" where you warn that "testimonials are the weakest kind of evidence." Would you introduce either an endothelial or mesenchymal stem cell line for the treatment and what type of manipulation would be used?

A. Nepsis has not been involved in the treatment of PAH. However drop down to question #9 which concerns “alternatives” for pulmonary hypertension.


3) I am considering treatment for MS. A local doctor gave me some verbal warnings on the danger of the lumbar puncture and also about tumor risk from adult stem cells. Can you address these issues please?

A. There are risks associated with a lumbar puncture (intrathecal) procedure, which are summarized in this article http://emedicine.medscape.com/article/1189617-overview by Roy Sucholeiki, MD, Medical Director, Comprehensive Seizure and Epilepsy Program, The Neurosciences Institute at Central DuPage Hospital:
·Post–spinal tap headache
·Nerve root trauma (eg, previous surgery in the area, scar tissue)
·CNS infection (eg, immunocompromised patients)
·Cranial, cervical, and lumbar subdural (more common) hematomas (eg, patients on anticoagulation therapy)
·Also possible but very rare are discitis, system/portal venous gas (following a traumatic tap), clinical deterioration in the presence of dural arteriovenous fistula, symptomatic pneumocephalus in a patient with normal pressure hydrocephalus, cranial nerve palsies (4th and 6th)
Blue Cross Blue Shield of California delves into the complications and risks on its website https://www.blueshieldca.com/hw/arti...uestid=2796732 :
“Some people (10% to 25%) develop a headache after having a lumbar puncture. Of those who do get headaches, only about half report that they are severe. These headaches last 24 to 48 hours and go away on their own. Pain medicine does not help control the headache, but lying flat in bed for several hours after the procedure may help the headache.You may feel tired and have a mild backache the day after the procedure. Some people have trouble sleeping for 1 to 2 days.

RisksA lumbar puncture is generally a safe procedure. In some cases, a leak of cerebrospinal fluid (CSF) may develop after a lumbar puncture. Symptoms of this problem are a headache that does not go away after 1 to 2 days. A CSF leak can be treated with a blood "patch," in which the person's own blood is injected into the area where the leak is occurring in order to seal the leak.
About 1 in 1,000 people who have a lumbar puncture have a minor nerve injury. This heals on its own with time. There is also a small chance of infection of the CSF (meningitis), bleeding inside the spinal canal, or damage to the cartilage between the vertebrae. Your doctor will talk with you about these risks.
People who have bleeding problems and those who are taking blood-thinning medicine (such as warfarin or heparin) have a higher chance of bleeding after the procedure. A lumbar puncture may not be done unless it is needed for a life-threatening illness.
A lumbar puncture may cause serious problems for people who have high pressure in the brain caused by a tumor, a pocket of infection in the brain (abscess), or major bleeding inside the brain. Your doctor will check your nervous system, spinal cord and brain before doing a lumbar puncture. In some cases, a computed tomography (CT) scan or magnetic resonance imaging (MRI) scan may be done before the lumbar puncture to know that it is safe to do the puncture.”

As you can plainly see, the risks are pretty low. I might add that of scores of lumbar punctures I have followed done by Nepsis associate Dr. Fernando Ramirez and his medical team in Mexico – both before his affiliation with Nepsis (2203-2007) and after (2008-present) – the worst adverse side effect I have seen to-date is minor headaches.

As for the question of tumor formation: If you look at all the adult stem cell treatments that have been done worldwide in the past decade or so – umbilical cord, bone marrow, fetal cell – you will find very few cases in which cancers arose that are clearly linked to the treatment. The risk of this occurring seems extremely remote.


4) If you are familiar with ICM of Costa Rica and X-cel of Germany, is there a major difference in how the two therapies are administered and do you think one is better than the other? X-cel gives one treatment in one week. ICM gives several treatments over a 2-4 week period. There is a major cost difference. This treatment would be for MS. What is the cost for treatment for MS at Nepsis and what does your treatment consist of?

A. I am acquainted with both firms and their treatment offerings, but cannot really say which approach (if either) is best in terms of clinical benefits as neither (to my knowledge) has published or posted data or information that would make such a determination possible.

The Nepsis approach involves taking a small sample of bone marrow, isolating specific precursor and stem cells, then priming them to zero in on target tissues and become cells specific to the disease being treated. I am simplifying some very complex and sophisticated science – including technology and laboratory methods that are proprietary and USPTO patent pending (And by virtue of this cannot be divulged). Suffice it to say this body of highly innovative work was done by a team of US scientists lead by one of the leading lights in stem cell research (So acknowledged by leading authorities in the field such as Dr. Hans Keirstead at UCI).
Since the Nepsis program is just 3 months old it is, of course, too soon for any appreciable patient response statistics to have been accrued with respect to MS or any other disease. But be this as it may, there are some “hints” that what was seen in lab animal experiments stateside is now proving true of patients treated in Mexico. Some of these are summarized on http://www.nepsisinstitute.com/testimonials.php

The cost? Currently $8500.00 (This includes medical care, the surgical team’s fees, required drugs and hormones, and lab processing. Transport to and from Mexico is extra and runs $250.00) The price is actually quite low all-things-considered, and was so set by those involved in the program in order to keep this novel therapy within the reach of the working middle class.
The entire procedure presently takes one day in an outpatient setting. A more extensive ultra-high tech version will debut later this summer that will require patients to spend at least 4 days in southern California – and make two trips into and out of Mexico (Tijuana).


5) Is Nepsis treating Cerebral Palsy? If so, please describe the treatment that would be administered.

A. At this time Nepsis is not treating cerebral palsy in children. Once additional high tech equipment is installed in the lab in Mexico (July or August), treatment of CP with enhanced cord blood stem cells as well as select autologous bone marrow stem cells will become available.


6) I have read with great dismay the agony that movie actress Farrah Fawcett is going through. Would stem cell treatment in any way help in a situation so grave? I believe she suffers from anal cancer that has spread to her liver.

A. I tend to doubt it. Many cancers arise because of stem cells that have lost normal controls on proliferation, and it is highly unlikely that infused allogenic or autologous normal stem cells would in any way bring about tumor stasis or die-off. This said, using Nepsis’ technology one could genetically engineer stem cells from a patient’s own bone marrow such that they will churn out anti-tumor compounds, and then target these cells to zero in on the tumors. In theory they should engraft, proliferate and go to work dispatching the cancer in question.
In addition, I have developed a new approach to effecting oncolysis (tumor die off) that involves use of reprogrammed microorganisms; exploiting them (so to speak) to eradicate cancer cells without effecting normal cells. It is mostly white board stuff at this point-in-time, but I am told by the molecular biologists and genetics engineers I work with that the idea is both sound, innovative and likely to pan out. Time and animal experimentation will tell.



7) Can you provide an itinerary of what a patient would go through that is interested in having treatment at Nepsis? Please start at the initial application process and walk me through the rest.

A.It would take me a great deal of space to lay all this out – six (6) pages of text actually. Rather than fill up so much space on this forum, I would ask that you and anyone else who is interested in receiving an outline of the application-through-treatment process e-mail me a request for this to info@nepsisinstitute.com


8) When a clinic says they do anti-aging treatments using stem cells, what does this really mean and is it something a person would need to do every so often?

A. Generally speaking, a stem cell anti-aging treatment typically refers to an infusion of umbilical cord, fetal or other stem cells (sometimes along with cord serum and/or growth factors, hormones, etc.) that is suppose to either slow aging or actually turn the clock back in terms of the vitality and function of an aged organ(s) or tissue(s). Is there any hard scientific evidence that these treatments actually have a genuine anti-aging effect? In-a-word, there is precious little to none. This said, I have examined medical reports submitted by a handful of people who underwent such treatments which indicate at least some of them experienced improved skin and muscle tone, increased physical energy, plus varying degrees of functional improvement in various organs. Some had biomarkers related to aging decline, though I do not recall this as being statistically significant. As best I could ascertain, these improvements faded over time, though this varied from person-to-person (No doubt a reflection of genetic individuality and variability and such).

As I am not an expert in the field of geriatrics or anti-aging medicine, I cannot declare that there is emphatically not some anti-aging stem cell treatment or cocktail that might slow or reverse aging to a degree. This would require me to prove a negative which is impossible. However, I can state that I am aware of no definitive scientific proof that any such treatment indisputably turns back the clock. This lack of evidence coupled with the fact the history books (not to mention court records) are filled with all kinds of anti-aging scams pulled off by charlatans, con artists and delusional “true believers” argues for maintaining a skeptical stance when it comes to anyone who claims they can undo the ravages of Father Time – whatever his or her method.

There is, by the way, at least one promising way in which to restore tissues to a more youthful level – namely taking pristine DNA from a person and essentially inserting it in a specific stem cell that has had its nucleus removed (This cell is then carefully expanded yielding hundreds of millions of identical copies and is then infused into the patient). Mind you, the DNA used is unaffected by age or free radical damage or such; something which does exist in each of us. Bench scientists I work with have carried out experiments using a version of the approach I’ve outlined above on aged animals. The end result was clear evidence of fairly significant body-wide anti-aging or as I call it “youthification.” This approach is very experimental and will likely remain a lab novelty for at least 3 to 5 more years.


9) I have primary pulmonary hypertension, understand Dr. Zannos Grekos has successfully helped this, but cannot afford the $56K he charges. Are there any “economical” options?

A. First off, for the sake of readers who may not be acquainted with primary pulmonary hypertension (PH): This insidious terminal condition basically arises from constricted blood vessels in the lung. Over time the affected vessels become stiffer and thicker (fibrotic in technical parlance), giving rise to even greater pressure within the lungs. The load on the heart typically leads to enlargement and thickening of the right ventricle which makes it less efficient in pumping blood through the lungs which results in heart failure.
Though the exact cause of PH is unknown, there is at least one line of research that indicates that a deficiency of antioxidants sets the stage for onset: http://www.sciencedaily.com/releases/2008/09/080923164718.htm

As for treatment, medical standard of care is essentially aimed at reducing pressure in the lungs and dealing with the negative cardiovascular impact of the disease process, i.e., drugs are prescribed to reduce the workload on the heart, diuretics and other pharmaceuticals to reduce blood pressure, etc.
This brings us to the promise of stem cell therapy for PH. In-a-word most stem cell approaches to PH involve creating new blood vessels to take over for diseased (fibrotic) ones. Before we get into the mechanics of this let me introduce some terms:

The first is vasculogenesis, which involves making new blood vessels via differentiating (transforming) endothelial cells on blood vessel walls.

The second is angiogensis, which refers to sprouting new blood vessels from existing ones.

In PH, angiogenesis has less impact on draining off blood and reducing blood pressure (BP) because the blood vessels are fibrotic and thus stiff and unable to work efficiently.

This leaves vasculogenesis which makes sense from a physiological point-of-view; that is to say, putting in new plumbing to drain off blood and reduce pressure trumps trying to add on pipe to existing but clogged up, damaged pipes (Angiogenesis).

So how does one go about stimulating vasculogenesis in pulmonary blood vessels? Before we get into this it is important to get acquainted with the three types of cells that play various roles in blood vessel formation, repair and maintenance:

(1) Endothelial Colony Forming Cells (ECFC): These are genuine endothelial stem cells according to stem cell experts as they have a vast potential to engraft in a damaged blood vessel and help bring about the creation of new ones. They are, however, quite rare with only about 1000 circulating at any given time in our bodies.

(2) Endothelial progenitor cells: These are bone marrow derived cells that bear the cell-surface markers CD34 and CD133. Current thinking is that these cells zero in on damaged or diseased blood vessels, make some temporary repairs and send out signals that summon ECFCs which then set up shop and facilitate long term regeneration. They also can be transformed into endothelial cells which contribute to new blood vessel formation, but generally must be taken into the lab to reliably pull this transformation off and also to expand their numbers to levels needed to be therapeutically effective.

(3) Circulating Angiogenic Cells (CAC). These cells are derived from monocytes, which are bone marrow mononuclear cells. Owed to their limited capacity to expand (multiply) plus their role in vascular health, these cells are favored for combined cell-gene therapy approaches to PH (They won’t multiple in the body ceaselessly and thus create a situation of “too much of a good thing”). For example, researchers have inserted genes that transform these cells into little factories that churn out specific growth factors such as Vascular Endothelial Growth Factor (VEGF), vasoactive peptides such adrenomedullin (AM), and compounds that dilate blood vessels such as Nitric Oxide (NO).
Armed with the foregoing it follows that taking CACs and inserting genes that stimulate vasculogenesis would tend to ameliorate PH. Many researchers are pursuing this in animal models. In addition, this sort of approach appears to be utilized by at least one private stem cell operation -- that of cardiologist Zannos Grekos, MD and his associates at Regenocyte http://www.regenocyte.com (Though I do not know if he and his scientific team is utilizing CACS or some other cell to pull off effecting vasculogenesis in the lungs). And it works -- at least this is what Dr. Grekos et al reported in a November 2008 news release http://regenocyte.com/pdf/market_watch.pdf

Coming full circle: The issue for the individual who e-mailed me the question that launched this foray into PH -- is cost. The price tag ($56K) levied by Dr. Grekos et al is not something (s)he can handle which brought her/him to my cyber-doorstep seeking any viable alternative approach to ameliorating his/her condition. As I am a theorist and not a physician, I now step into the realm of possibilities whose actual clinical safety and utility must be weighed by an MD or DO knowledgeable in such matters.

In no particular order:

(1) Hyperbaric oxygen therapy: A recent animal study indicates that Hyperbaric oxygen stimulates vasculogenic stem cell growth and differentiation in vivo. In this study, 2.8 ATA was used for 90 minutes at a time. This kind of pressure can only be attained in a hard-shell chamber and not a flexi-chamber (The best soft “home use” chambers can achieve is 1.3 ATA). This website features a list of HBOT treatment centers state-by-state (But is not exhaustive): http://www.netnet.net/mums/hbolistAK-FL.htm (Nota bene: I have no connection to this website or any of the clinics listed)

(2) Despite the controversy surrounding endothelial precursor cells – some saying they contribute to ameliorating PH initially but in large numbers could lead to complications--while others assert that augmenting EPCs is a prudent measure—increasing them might be worth trying (This, again with the input of a physician knowledgeable in such matters). There are a number of ways to liberate or otherwise increase the number of circulating EPCs:

(a) Sildenafil. Treatment with the phosphodiesterase inhibitor sildenafil (Viagra®) has been shown to result in a dose-dependent rise in EPC numbers, resulting in levels consistently above those found using most other therapies.

(b) Granulocyte colony-stimulating factor

(c) Erythropoetin. In a paper titled “Role of erythropoietin for angiogenesis and vasculogenesis: from embryonic development through adulthood.” The authors found the erythropoietin influenced specific cells from mice, e.g., embryoid EB and isolated endothelial cells from EB (EBEC) plus human adult endothelial progenitor cells, so as to promote vasculogensis.

(d) Berberine. In a study carried out in China, researchers found that a plant based alkaloid called berberine increased plasma Nitric Oxide (NO) levels and by so doing enhanced endothelial progenitor cell mobilization and activity. Berberine is found in plants such as Berberis, goldenseal (Hydrastis canadensis), and Coptis chinensis, usually in the roots, rhizomes, stems, and bark. Commercial preparations include PhytoPharmica’s “Berberine Complex” (Note that I have no financial or other interest in this firm or this product).

(e) High dose L-Arginine. Arginine is used in the body to create Nitric Oxide. There are a handful of studies that indicate that L-Arginine can ameliorate PH, among them L-arginine promotes angiogenesis in the chronically hypoxic lung: a novel mechanism ameliorating pulmonary hypertension.

The questions naturally arises: Are there any “low cost” stem cell approaches that might stand a good chance of ameliorating PH?

Some might advocate extracting and infusing a patient’s own bone marrow, as this would be one way to turn loose a variety of cells that might benefit PH. The problem with this approach is that cells might also be liberated that could exacerbate PH. A cell selective and expansion approach is probably more prudent (Which involves manipulating the cell mix in a properly equipped lab run by suitably qualified scientists and technicians. This kind of manipulation constitutes creation of a new drug according to FDA regulations and thus requires formal consent in the form of an IND here in the USA)

Then there is cord blood: Cord blood contains Endothelial Colony Forming Cells (ECFC) in very small numbers. Before this could be effective the ECFCs would have be extracted and expanded in the lab (This would require an IND in the USA). Of course, the problem with umbilical cord ECFCs is the fact the recipient’s immune system may clear them after a few days time (Before they can do much good). Indeed, some scientists have found that this sort of immune disposal does occur when cord stem cells are infused into human recipients. Can this natural immune mechanism be obviated or its activity reduced? I believe using cells extracted from blood that are type, Rh and sex matched to the recipient will likely help reduce immunoreactivity and immune clearance of these cells. At present I know of no lab that performs this for use in a clinical setting anywhere abroad (Albeit the Nepsis Institute lab in Mexico is gearing up to do this very thing. The cost for this should be very reasonable).

In addition, as a theorist I have come up with a unique spin on how to employ a particular adult stem cell that will by its very nature (with minor tweaking) will ably encourage vasculogenesis. I have entrusted my brainchild to the bench researchers that work for and with Nepsis Institute. Once developed and tested out, the cost to patients for treatment using these modified adult stem cells should be quite reasonable. To coin an old phrase, stay tuned!

And finally, I hope that the questioner and his primary care physician will find something of merit in what I have shared above that will accord him/her relief and a better quality of life.


10). My wife had stem cell treatment for ALS and is tube fed. Can you recommend anything that would help her as far as diet goes ? She can eat things that have a pudding consistency and that's about it. She is tube fed once a day and I try to get her to eat things like ice cream, pudding, applesauce, etc., but her appetite isn't so great.

A. The diet I advocate as a theorist with respect to ALS is the ketogenic diet and a variant known as the Medium Chain Triglyceride Diet (MCT). This particular diet is reflected in a regimen of my own devising that appears to have slowed progression of ALS in four individuals who have been adhering to it since 2005; a regimen that I captured in a professional paper that was recently published in the peer reviewed journal “Medical Hypotheses” (Elsevier): “Experimental regimen targeting the ependyma slows disease progression in four patients with amyotrophic lateral sclerosis” Med Hypotheses. 2009 May;72(5):548-50. Epub 2009 Feb 5.

Additional support for the ketogenic diet for ALS can be found in these on-line sources:

http://www.biomedcentral.com/content...-2202-7-29.pdf - A ketogenic diet as a potential novel therapeutic intervention in amyotrophic lateral sclerosis.

http://www.alsforums.com/definitions...enic-diet.html - Ketogenic diet - ALS forum

And this from the entry under “Ketogenic Diet” http://en.wikipedia.org/wiki/Ketogenic_diet which points out that medium chain triglycerides are especially good way to get one’s body to churn out ketones:

“Most dietary fat contains long-chain triglycerides (LCT), but a form of coconut oil can be manufactured that contains only medium-chain triglycerides (MCT), which are much more ketogenic.[1] A variant of the diet known as the MCT ketogenic diet=2 0uses MCT oil to provide between 30 and 60% of the calories. Carbohydrates and protein can be increased a little, which allows for greater freedom in planning meals.[2]“

So, what makes the ketones people generate while on the Ketogenic diet so special? This excerpt from the Wikipedia entry under “ketones” http://en.wikipedia.org/wiki/Ketone tells the tale:

“At the NIH, Dr. Richard Veech refers to ketones as "magic" in their ability to increase metabolic efficiency, while decreasing production of free radicals, the damaging byproducts of normal metabolism. His work has shown that ketone bodies may treat neurological diseases such as Alzheimer's and Parkinson's disease,[5] and the heart and brain operate 25% more efficiently using ketones as a source of energy.[6] Research has also shown ketones play a role in reducing epileptic seizures with the so-called high-fat, near-zero carbohydrate Ketogenic Diet. [1] “With respect to individuals who are unable to chew and swallow foods, there are ways to “go ketogenic ” by judicious use of liquid commercial or powder products such as:

http://www.shs-nutrition.com/products/liquigen - Liquigen
https://www.trueprotein.com/Product_...?cid=24&pid=86 – MCT powder
Extra virgin coconut oil can also be used in pureed or semi-liquid foods: http://www.iherb.com/Jarrow-Formulas...08-g/7227?at=0 http://www.iherb.com/Now-Foods-Virgi...1-ml/7090?at=0
Amazon.com carries a variety of ketogenic diet cookbooks that contain a wealth of recipes, many of which can likely be pureed into a pudding-like form for tube feeding: http://www.amazon.com/s/ref=nb_ss_b?...+diet+cookbook – Ketogenic diet cookbooks
NOTE: I have no commercial or other interest in any of the products or books cited above.


11) What does Nepsis offer in the way of treatment for COPD and why would treatment at Nepsis be something I should consider?

A: The cornerstone of the Nepsis-Ramirez stem cell program in Mexico is the use of novel, patent pending technologies and lab methods that make it possible to take stem cells and prime them to become whatever cell type is needed to provide support, repair or restoration to diseased or injured tissues and organs. In addition, this body of science makes it possible to target the cells, which is to say program a group of cells to zero in on specific a tissue or organ.

In the case of COPD, bone marrow derived pluripotent cells AKA marrow-isolated adult multilineage inducible (MIAMI) cells plus other bone marrow stem and precursor cells are extracted from a very small sample (~1 tsp) of bone marrow and then primed and targeted to seek out diseased lung tissue, engraft and proliferate.


Why are bone marrow stem cells such a good choice for COPD?
(1) A number of published studies indicate that various bone marrow derived stem cells hold promise for ameliorating COPD (Emphysema):
Bone marrow-derived cells contribute to=2 0lung regeneration after elastase-induced pulmonary emphysema.
Bone marrow-derived mesenchymal stem cells in repair of the injured lung.
Repopulation of human pulmonary epithelium by bone marrow cells: a potential means to promote repair.
Bone marrow-derived mesenchymal stem cells in repair of the injured lung.
(2) Marrow-isolated adult multilineage inducible (MIAMI) cells are pluripotent as opposed to multipotent. This means they can be more readily differentiated (transformed) into the 220 different cell types in the human body than multipotent adult stem stems such as most umbilical cord stem cells as well as other bone marrow stem cell types. In terms of the technology and lab methodology unique to Nepsis, the transformation of MIAMI cells into cells that will benefit diseased lungs is relatively quick and straightforward.
(3) Utilization of highly sophisticated, patent pending technology and lab methods aside, there is the matter of cost: The Nepsis-Ramirez program strives to keep the cost of the therapy within the reach of the working (US) middle class. In most instances, the tally including all medical care, cost of adjunctive drugs, hormones, etc., and all laboratory processing runs between $6000.00-$8500.00 USD (If cells are delivered by catheter infusion into an organ – say the lungs – the cost goes up to $15K). Patients must pay their own airfare, lodging and meals, of course. Many foreign private stem cell clinics offering far less sophisticated, less effective adult stem cell therapies charge much, much more than the Nepsis-Ramirez stem cell program.

__________________________________________________ __________

Anthony G. Payne, Ph.D. literally wrote the book on Umbilical Cord Stem Cell Therapy, which is to say he co-authored one of the first lay level books on the subject ever in the English-speaking world (Basic Health Publications). He is currently resident biological theoretician, senior science writer, and Interim Director of Clinical Research at the Weller Health Institute & Laboratory (California) and also patient educator-liaison for Nepsis Institute (Mexico). Readers can get a feel for his passion to help the sick and dying by reading “Embracing the Disenfranchised” and for his adult stem cell therapy-related activism by visiting one of the advocacy organizations he is a member of: American Stem Cell Therapy Association. Payne can be readily reached by e-mail at attachi-mailbox@yahoo.com (“Attachi” is a Choctaw word for healer. Dr. Payne is a BIA certified American Indian and member of the Choctaw Nation).



** This post updated at Dr. Payne's request**