Makes my brain explode — but now it can be repaired

It’s almost impossible to discuss this article without leaping out of the chair and waving my arms around, squealing with the sheer thrill of its deep and wide implications for treatment and understanding:

Precisely Engineering 3-D Brain Tissues

Using a 3-D printer, transparencies, and binder clips, these wunderkinder can create neural tissues that mimic the cellular proportions and relationships of real, living brains.

On this basis, here are some possibilities discussed in the article:

  • Watch how brain tissue responds under different circumstances, leading to new understanding of brain growth, disease progression and structure-dependent brain abnormalities.
  • Repair damaged brain tissue. With historic rates of traumatic brain injury in the most productive age group, this alone is world-changing.
  • With samples from patients, custom brain cultures can be grown, and drugs tested against them, targeting drug treatment that works on the first trial. This saves people who need CNS-affecting drugs countless weeks and months — even years — of untold misery, as different drugs get pushed through their systems in an effort to find one that works.

Harvard Med and MIT at their collective finest.

The great challenge, of course, is getting this OUT of the lab and INTO the populations that need it. I hope it’s not kyboshed by those whose profits depend on the current ineffective, inefficient, expensive, and unspeakably brutal systems of CNS treatment.

Let good medicine prevail.

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Closed-heart aortic valve replacement, good surgery and good science

Here is an article from a San Antonio, Texas paper about replacing the aortic valve in the heart without cracking the chest, but instead using a minimally-invasive catheter technique:

http://www.kens5.com/news/New-heart-valve-replacement-doesnt-involved-open-heart-surgery-146475805.html

This is absolutely thrilling news. Open-heart surgery is one of the most inherently worrisome and fraught forms of surgery, with an unbelievably painful post-op recovery phase. Simply cracking the chest is a big deal, and anything they do after that might be tricky but it’s not nearly as shocking to the body.

Taking the chest-cracking out of heart surgery is the single biggest change we can make to safer, saner, faster-healing, less complicated heart surgeries. We WANT people to survive the experience intact, we really do!

Aortic valve issues are, as I recall from my ICU/Telemetry nursing, one of the more common heart issues; although it’s not often life-threatening, it is often life-limiting, because without that “aortic kick” that the heart gets from a good, solid snapping-closed of the aortic valve during a heartbeat, the pumping action just isn’t as good, and that has knock-on effects that can pile up over time.

Weak aortic valves can contribute to everything related to an impaired heartbeat, including blood pressure, vessel competence (think of congestive heart failure and tissue swelling/edema), and most obviously to cardiac hypertrophy, where an underpowered heart grows extra muscle to try to push blood around. What that really does is create more demand for blood from the heart itself, and push more blood back out the incompetent aorta!

Now that surgery can correct aortic valve issues without open-heart surgery, watch the medical news over the next 2-3 years: you’re going to see a lot more studies directly relating aortic valve problems to other conditions, like those mentioned above. Why now? Because, once a problem can be solved, physicians are much more willing to look at the problem directly.

Just like the rest of us. :)

It’s important to note that, for people with CRPS who have to avoid surgery as much as is compatible with life, and for those with dysautonomia for other reasons, this surgery is a game-changer. No longer do we have to choose between increasingly incompetent valves and a lifelong upsurge in agony, disruption, and dysregulation. Now, we can have a surgery that goes near two major nerve bundles but, if properly done, touches neither; solves the problem and gives us our hearts back; and lets us get on with making the best of our lives.Talk about a win/win!

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SSRI can improve cognition after a stroke

This came out 2/2010, right in the middle of my being horribly overdosed on SSRI and SNRI medications:

http://www.sciencedaily.com/releases/2010/02/100201171523.htm

(This is where I give myself points for not being violently and irrationally opposed to the class of drugs that did me, personally, so much harm. It’s important not to throw the baby out with the bathwater.)

129 patients were divided into roughly 3 groups, one of which got 5-10 mg Lexapro daily, another got placebo, and the third were assigned to “a problem-solving therapy program developed for treating patients with depression.” (No idea what program that is and they weren’t specific about it.)

The Lexapro group had the best neurocognitive scores after 12 weeks, though the author doesn’t say by how much, or how they processed the data. These are both important issues in scientific studies, since some differences are significant and others are just curious, and how you arrived at those figures can have a considerable effect on how seriously your readers should take them.

“…reported changes in neuropsychological performance resulted in an improvement in related activities of daily living” — which makes perfect sense. When all is said and done, healing of any kind is about what more you can DO afterwards! Doctors, patients, and significant others tend to lose sight of that, getting lost in the compelling drama of symptomatology, misery, and pain. It’s not that that isn’t important, but being able to take care of yourself — or making it so your patient can do so — is absolutely primal.

This study used low doses, which I suspect is key to unimpaired cognitive function — not to mention avoiding the usual side effects of this class of drugs, as they did.

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Pain Manifesto

This came out of cold chronic CRPS type 1, a debilitating condition of intractable chronic pain, nervous system disruption, and multi-system dysregulation — destroying the body’s ability to manage heat/cold, blood sugar, immune defense, circulation, sensation, bone density, movement, vision, digestion, heart function, and ultimately survival.

“Standard” treatments don’t work well for me; moreover, they involve invasive procedures too brutal to tolerate and medications I’m either outright allergic to, or that impair me so profoundly I can no longer function. At all.

So I took myself off my meds, thought things over, and came to the following conclusions.

MY CHRONIC PAIN MANIFESTO

Yes, it hurts.
It’s going to anyway.

So should I hoard my days
And fast from life?
Comfort myself with poisons,
Blister-packed and FDA approved?

Some think it would be best all ’round.
I’d cure them if I could (heh!)
But I’m too tired for
Yet another pointless struggle.

The sunlight pours through trees like prosecco
And reminds me what it means to live:

Voices warm with love, the
Mouth-smack of good food,
The hug of hills and the
Rough snuggles of the sea.

Hoard my days? I’ll spend each one
Like it’s stuffed with jewels
Pouring through my hands like a miser’s dream.

Feast on this:
The cost of life is much the same.
The difference lies in how you spend it.

How is this relevant to medical science? For one thing, it shows just how badly off base it is in vivo. Like any manifesto, it makes an explicit declaration: fundamental attitudes must change.

Policy determines what will be profitable, and profit opportunities determine what science gets funded. There is no profit in fully-functioning people, but there’s plenty in people who are too sick to function but not sick enough to die … for awhile.

Policy could allow my insurance to cover the things that do work (massage, reiki, homeopathy, yoga), especially given the detailed and vivid documentation I’ve provided of just how well they work. Nobody will fund science studies on these in any volume, because it is so much more profitable to drug people into silence.

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Curing the incurable: type 1 diabetes in mice, with 78% success rate

Next Big Future: Gene therapy reverses type 1 diabetes in mice with 78% success rate

Intriguing approach: providing gene therapy to both protect and rebuild the Islets of Langerhans, which means blocking the T cells from the islet cells without compromising them otherwise.

For an early trial of a complex therapy, this is rather brilliant and very promising. Of course, humans are not mice, but type 1 diabetes is generally type 1 diabetes – or something very similar.

Next up: a cure for CRPS, Alzheimer’s, and AIDS. Hey, it could happen.

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Digestive problems early in life may increase risk for depression, study suggests

http://www.sciencedaily.com/releases/2011/05/110512171517.htm?utm_source=feedburner&utm_medium=email&utm_campaign=Feed%3A+sciencedaily%2Fmind_brain+%28ScienceDaily%3A+Mind+%26+Brain+News%29

This article states that gut disturbance in early infancy/lifelong gut disturbance (the language is kinda sloppy) can trigger lifelong depression and anxiety.

This doesn’t surprise me, but most of the rest of the article does.

The rat-botherers who did the study presume it’s all about the vagus nerve. Recently, a deliciously expensive procedure which stimulates the vagus has been found to alleviate some depression. It’s good to know that.

It’s good to keep a couple other things firmly in mind first, though:

- Serotonin is produced in the small intestine, as well as the brain. It helps to digest protein. It also plays a role in immune signaling. Think that could possibly be related, either to depression or to inflamed gut syndromes? H’mmm…

- My first thought: get right on top of infant digestive problems. That means getting serious about both prevention and cure.

Oddly, that idea wasn’t even mentioned, even though prevention is infinitely better than trying to manage a lifelong downer like IBS or depression — let alone both!

Prevention is simple in concept, but inexcusably difficult in our current system. With babies, it’s easy: get dead-serious about breastfeeding. Where that’s not possible, put aside formulas at the first sign of allergy. Don’t switch between cow and soy milk, two of the most allergenic infant proteins on the planet; milk more goats and camels. Go to a breastmilk-bank. Find your local midwives because they are much better with the idea that birth is only the beginning of a much longer life, and they should know how to figure this out. If they don’t, they can tell you who else to call.

And punctual treatment for troublesome insides — with the least invasive meds. Interfere with their little regulatory systems as little as possible, but take care of the problem. For indigestion, chamomile and calcium carbonate are much better than h2-inhibitors (Zantac, Prilosec and the like.) Chamomile also soothes the mind and settles the emotions, so the kid can relax.

Try elimination diets to screen for allergies. Sadly, wheat, eggs, cow dairy, soy, and corn are common allergens which affect the developing gut — and the developing skin and brain, because their little bodies never got the memo that all of these systems are supposed to be separate from each other.

Google those terms, discuss them with your midwife/pediatrician/nurse practitioner, and take care of the problem at its source.

You don’t want more depressed people in the world. There are better things to do with infants than let their guts screw up a good life, handing them into the craps-shooting care of multiple pharmaceuticals and invasive procedures.

When I get on the CPU, I’ll set up more links for my factual statements. This is it from the iPhone.

Bon appetit!

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Putting the "con" in mitochondria, the "funk" in dysfunction

Mitochondria (from the Greek, meaning “string grain” — yeah, it’s lame, but it sounds good in Greek) are independent little one-celled organisms that live inside your cells and make energy for them. If you ever studied the ATP cycle (also called the Krebbs cycle or the citric acid cycle, depending on where you went to school and how deeply they went into it), then you should know that this is where the ATP cycle takes place.

Without mitochondria, you have no way of converting food into energy.

When you were being conceived, half your cells’ genes came from your mother and half from your father. All of the other stuff that goes inside a cell came from your mother. This includes the mitochondria. (This is why mitochondrial DNA is used to track maternal inheritance: it always comes down the female line.) Your mother’s cell hosts conception, just as (normally) your mother’s body hosts gestation.

Mitochondria have a fairly smooth outer layer and a deeply-rumpled inner layer. Most of the action happens inside the rumpled layer. This is where the ribosomes, most of the fluids and loose protein, and the ATP-making particles hang out.

Cells, including mitochondria, need various proteins to do their work with. Large proteins get carefully handed from the outside world, through the outer layer of the mitochondrion (singular of “mitochondria” — sorry, it’s still Greek), then into the inner layer.

If the smooth outer layer is damaged, this makes this transfer process screw up, and the inner layer gets disrupted, ripping up the cell. Granules and nucleic acids all over the place. Bang goes that ATP production.

Those are some busted mitochondria.

This kind of damage happens in response to certain kinds of toxins (including certain medications for AIDS and all psychoactives — including antidepressants and pain medications, which seems especially mean!), occasionally from genetic disturbance, and occasionally as a consequence of illness — or nerve injury and its complications.

Mitochondrial dysfunction has been repeatedly and profoundly linked to neurogenerative diseases like Alzheimer’s and Parkinson’s; cell-metabolism problems like heart disease, insulin resistance and type II diabetes; and several diseases often mistaken for CRPS.

Not surprisingly, symptoms of mitochondrial dysfunction are the worst in tissues that use the most energy and have the largest number of mitochondria per cell: nerves, muscles, brain.

Recently, it has been strongly associated with CRPS. And the cherry on top: it plays a vital role in neuroplasticity, or the way your nerves and brain change — for better or worse.

Hell-o, “pain-brain.” We thought we knew ya!

Knowing why it’s so damnably exhausting to walk a mile, when it used to be fun — fun! — to run 3, is a bit of a relief. First question that leaps to my mind: How do I fix ‘em? How do I give them what they need to get better and protect themselves?  The answer seems simple: antioxidants are what’s needed to prevent and repair that damage (good explanation of that here) to the walls of the mitochondrial cell.  Mitochondria are both the biggest makers of reactive oxygen species and the biggest scavengers of them, so of course it makes sense that that’s exactly the kind of help they need when they can’t keep up.

Downing antioxidants by the bucketful is one way to get them in. Intriguing for three reasons:

  • Taking moderate amounts of the antioxidant Vitamin C after surgery hugely reduces your chances of getting CRPS. (Upper limb and lower limb surgeries were studied.)
  • There’s some indication that Vitamin K may help combat the progress of CRPS.
  • Taking antioxidants is pretty easy: delicious food, accessible pills, not bad.

Kind of depressing for one simple reason: it’s iffy whether, once you’ve got the disease process going, the antioxidants can get where they’re needed and save your poor beleaguered mitochondria. … Having said that, I notice that the writers of that article seem to be trying to sell something, and that makes me very suspicious of their conclusions.

Next, I’ll offer suggestions for patients, suggestions for clinicians, and then wind this up with a foray into the question of whether mitochondrial issues have a genetic component, like being X-linked — the way a cat’s fur color is! 

For people with CRPS — So what is a poor, confused CRPSer to do?

Two things that you hardly need reminding of:

  1. Trust your sense of your own body.
  2. Do what works for you.

Most antioxidants are not going to hurt you, without letting you know first (that is, make you nauseous or feel funny.) Take vitamin C in doses no larger than 500mg, since larger doses tend to trigger your gut to throw the C away. Go ahead and try stress-vitamins, co-enzyme Q-10, N-acetylcysteine, hair-skin-&-nails vitamins (these are really fat-soluble antioxidants) … try things, take what helps, and put aside the rest if they don’t do anything. Keep in mind that things change: what doesn’t work now might work later, and vice-versa.

Also, eat all the leafy greens you can get: seaweed snacks, Mom’s collard greens, kale krunchies, spinach salad, you name it. It’s amazing nerve food.

For antioxidant powerhouses, look for dark-red and dark-blue fruits: pomegranates, blueberries, red wine, chocolate (though some CRPS people have to avoid that for its nerve effects), mangosteen (my favorite fruit), cranberries, and so on.

Stay smart. Stay loose. Keep going.

For medical people — clinical takeaways:

Most treatment standards, particularly for CRPS, are based on science that’s over a decade old. They shouldn’t be changed blithely but they can certainly be improved. There is plenty of room for that.

The following points are intended as additions to the standards you follow for CRPS, as they are good guidelines for mitochondrial and neurologic support in a system compromised by CRPS.

  •  After any limb surgery, give Vitamin C 500 mg, QD or BID, for a couple weeks beforehand and 30-50 days after — or to metabolic tolerance, if that’s too much. Use a food-associated form for best uptake. This one intervention will reduce the risk of developing CRPS by 80%, according to the best current data.
  •  We assume your patients are taking an adequate multivitamin and are eating plenty of greens, dark fruits, and wholesome proteins. So make sure they are.  Direct them to food bank, food stamps or other food assistance as needed. Give recipes. (No kidding.)  2 benefits: better antioxidant uptake if taken with antioxidant-rich food, and increasing the patient’s own sense of agency/participation improves pain and affect.  (If you don’t believe in multivitamins, then get out of the supermarket/pharmacy and get some real ones.)
  •  Stress the antioxidant vitamins.  In acute CRPS, give water-soluble antioxidant vitamins in 1-3x the doses you’d give a healthy person.  Give fat-soluble antioxidants (A, D, E) up to 2x normal, testing levels as indicated.  Consider vitamin K inj.
  •  In cold/chronic CRPS, give water-soluble antioxidant vitamins in 3-5x the doses you’d give a healthy person (start at 2x and work up).  Give fat-soluble antioxidants (A, D, E) up to 2-4x normal, testing levels as indicated; consider weekly mega-dose D (as used in AIDS.)  Give vitamin K inj.  Check serum or urine levels as indicated, especially as we develop absorption disorders.
  •  Give “uber-antioxidants” like ubiquinone (co-Q 10), N-acetylcysteine, or glutathione. There are indications that these can provide substantial benefit — though again, not normally curative of chronic CRPS. They are impressive, especially for mitochondrial-dysfunction issues.

These ranges are empirical; if you can find the funding to do the science to develop more reliable ranges for this population, so much the better.

Adequate tissue oxygenation and perfusion can return substantial function and significantly reduce pharmacologic burden. Patients can demonstrate this, even where the data have not been published and peer reviewed. Therefore, use antioxidants rigorously and intelligently.

Image credit: http://www.vrp.com/antioxidants/-r-lipoic-acid-unique-mitochondrial-antioxidant-fights-premature-aging.  (Article’s not bad.)

Why all that anti-oxidation when the medical literature is not definitive?  2 reasons, which you ought to know for yourselves:

  1. Between the cortisol and systemic oxidative stresses, it can’t hurt and it will help something. You’ll see a distinct improvement in affect, activity, motivation and well-being when the dose is optimized, even if it can’t be expected to be curative.  Making your patient’s life more bearable is an essential part of your job.
  2. Let’s say this together, everyone: statistics mean nothing in the case of the individual.  Accepted, standardized medicine is what you start with, but, when your case is taking you out to the margins, you go to the margins, because that’s where your success is most likely to await.  

Keep in mind that doctors are not the only scientists interested in the human body.  Be prepared to look into other disciplines for leads when your own offers no good options.

Try Nursing, PT, Nutrition, Therapeutic Massage — you’ll realize that nobody knows more about soft tissue’s functional physiology in vivo than therapeutic massage science, and if nothing else, the exercise in intellectual flexibility might do you good.

The accepted style is very different, but the info they have is tremendous.

Forward-looking thoughts:

  • Consider infusing vitamin K into CRPS-damaged tissues. I would love to see studies on that.
  • Figure out how to deliver antioxidants in a targeted way. (Now! Please!) This would be a good way to save a lot of lives and end tons of misery.

… And for all curious people …

Let’s go back to mitochondria in reproduction. Kind of in an X-rated way, figuratively speaking.

We know that women have two X chromosomes. The Y chromosome is a stubby little object with hardly any data to use, unless you’re into color-blindness or hemophilia; this means women have quantities of extra data, which can have even more devastating effects (as in, Down syndrome.) So how to handle the extra genes?

Pick one. Simple as that.

Shortly after conception, when the cells are just dividing like mad and haven’t decided what to be yet, every single cell turns off one of its two X chromosomes; each of that cell’s daughter cells inactivates the same X chromosome. As the cells continue to multiply, then fill out, fold, bend around, and specialize, to become a whole, separate being, it means that X-linked traits appear in a mottled pattern throughout the body, as the two sets of daughter cells continue reproducing and passing on their particular X-activations.  Isn’t that curious?

As an especially decorative instance, cats’ hair color is an X-linked trait:

Cool, huh? Love her accent, too.

But this fact brings me to a serious question about mitochondrial disease. If mitochondria are sex-linked, is there a relationship between the X chromosome and mitochondrial expression? It seems improbable that there wouldn’t be, because mitochondria reside inside the cell, and the cell’s action is determined by the genes within it. The mitochondria had to have developed a special relationship with the X’s in the 23rd chromosomal pair, after all those millenia.

It’s generally accepted that mitochondrial diseases are due to toxification or to complex, multigenetic issues. Ok, fine. But what about mitochondrial vulnerabilities that don’t become pathologic until they are damaged in some other way? To what degree is toxification an issue related to X-activation? In other words, is mitochnodrial vulnerability related to vulnerabilities in the active X chromosome?

Is there a patchy characteristic to the early stages of mitochondrial destruction? — You know, the early stages of rare disorders, the time when it’s impossible to get a diagnosis because the doctors are all so busy chasing their own tails around your irrational symptoms and their own ignorance.

Is that initial “mottled” activity one reason why these diseases are so damn weird?

Link list:

Wikipedia’s entry on mitochondria is pretty good:
http://en.wikipedia.org/wiki/Mitochondria

On mitochondria and AIDS meds:
http://www.ncbi.nlm.nih.gov/pubmed/20818734
On mitochondria and pyschoactives:
http://www.ncbi.nlm.nih.gov/pubmed/18626887

Alzheimer’s Foundation:
http://www.alzfdn.org

Michael J. Fox’s Parkinson’s foundation:
http://www.michaeljfox.org/

United Mitochondrial Disease Foundation, listing diseases which are often mistaken for CRPS:
http://www.umdf.org/

Mitochondria and neuroplasticity:
http://www.ncbi.nlm.nih.gov/pubmed/20957078

A good rundown (so to speak) of antioxidants’ function:
http://www.ionizedwateronline.com/Antioxidants.html

Vitamin C around surgery.
Upper limb:
http://www.ncbi.nlm.nih.gov/pubmed/17606778
http://www.ncbi.nlm.nih.gov/pubmed/20224742
Lower limb:
http://www.ncbi.nlm.nih.gov/pubmed/19840748

Vitamin K and CRPS progression:
http://www.ncbi.nlm.nih.gov/pubmed/20378261

Getting antioxidants where they’re most needed. Ignore the shystering towards the end:
http://www.ncbi.nlm.nih.gov/pubmed/21422516

ALA and regeneration of Vitamin E:
http://www.vrp.com/antioxidants/-r-lipoic-acid-unique-mitochondrial-antioxidant-fights-premature-aging

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