NOTICE: Posting schedule is irregular. I hope to get back to a regular schedule as the day-job allows.

Wednesday, February 29, 2012

NEWS: Blogger Appreciation Day [Full link to blog for email clients.][FT:C44]

From my friend Sarah A. Hoyt: 
Today is blogger appreciation day. (Yes, it's made up. I know that. But as the poster said, traditions have to start somewhere.) We labor all year, year after year and Feb. 29 is when you tell us you love us. Of course money to buy a six pack of beer is the sincerest form of flattery and my button is up there somewhere. Myself, I'm going to hit the tip jars of Kris Rusch, and the Passive Voice who are my regular industry-reads. I'll probably hit the tip jar for Michael Totten later today and there are other bloggers which are none of your business but whom I will support. I would like to donate to Flinders Family Freer but I can't find a "donate" button. Feel free to go over and demand he put one up (my minions) since you bullied ME into putting one up. However, if you can't donate or don't want to, leave a message telling your favorite blogger how much you enjoy his/her work. It's a tradition that SHOULD get started, because it helps on this side of the trenches when the going gets tough and we wonder if we're just talking to ourselves. And once in four years is not too much trouble.
Well - I don't have a "tip jar" - so why don't y'all go find a favorite blogger that does - and put some cash in their pocket! - Speaker

Monday, February 27, 2012

The GUIDE: "Three M's" - Part 1 Multiple Sclerosis [Full link to blog for email clients.][FT:C44]

Image Copyright Alila Sao Mai, 2012
Used under license from
Today we start with the three M's of neuromuscular diseases with Multiple Sclerosis.  The name "sclerosis" means "scar" and one of the characteristics signs of MS in autopsy is the scar-like appearance of the long neurons in "multiple" locations throughout the body, spinal cord and brain.

Way back in the dim mists of this blog (just over a year ago), I described the basic mechanism of neurons, the building blocks of the brain and nervous system.  The blog is here ( if you need to refresh your memory on the subject.  One of the key features of neurons are their long axons which conduct an electrochemical signal over long distances - many meters in some cases.  One of the means of speeding up the transmission is to insulate most of the axon, leaving periodic gaps for the chemical channels required to propagate the action potential.

That insulation is illustrated on a neuron in the figure abovet.  The left neuron is normal and has intact myelin insulating its axon.  The right neuron has damaged myelin, which slows and even stops the signal, due to the fact that once an axon is wrapped with myelin, it doesn't have ion channels under the insulation.  Without ion channels covered the whole length of the (exposed) axon, an action potenial cannot keep occurring in sequence down the length of the axon.  Without an action potential, the neuron cannot transfer information from brain to muscle or from sensory organs to the brain.  Even inside the brain, axons that cover "long distances" (more than a few millimeters) are also insulated, thus MS can affect the normal function of information processing in the brain.

So - three questions come up: What is myelin?  How does the degeneration of MS occur?  How can it be treated?

Myelin is actually a special type of cell - called a "Schwann Cell" - that wraps itself around an axon many times.  The normal cell membrane is supplemented with thick lipid (fat or oil) deposit within the layers of cell 
surrounding the neuron, forming an electrical insulator - much the way non-conducting grease or transformer oil is used in high-voltage electrical installations.  The insulation serves two purposes - it prevents the "leakage" of electrical charge from axons, and the thick blanket of Schwann Cell surrounding the axon prevents any of the fluid surrounding the neuron from making contact with the membrane (and any ion channels located there).  The neuron adapts to the insulation by moving it's ion channels to the gaps between Schwann Cells.  These gaps have the name "Nodes of Ranvier" and are a key component of the signal speed increase caused by myelination.  With ion channels concentrated at the Nodes, the action potentials are actively generated only at the nodes, then passively conducted through the now very efficiently insulated spaces between the nodes.  The speed of action potential propagation is at least ten times faster in myelinated vs. unmyelinated axons, which is very important for sending signals to distant muscles.

MS is an "autoimmune" disease, meaning that the bodies own antibodies attack the Schwann Cells and cause the damage to the myelin that is characteristic of MS.  The location and extent of myelin damage controls the severity and type of symptom, which can range from dizziness, unusual sensations and muscle tremors at it's mildest, to muscle spasms, paralysis, blindness, at worst.  All of the causative factors are not clear, but MS affects more women than men, runs in families and also is also more frequent in certain parts of the world.

Symptoms of MS can occur in multiple parts of the muscle and nervous system - hence its designation as a neuromuscular disease.  Muscle symptoms include loss of balance, weakness, spasms, problems with coordination and/or tremor.  MS can cause vision problems including double vision, sudden eye movement and blindness; it can cause hearing loss, speech problems, dizziness, depression, memory loss, decreased attention, difficulty reasoning and making decisions. MS is also associated with many internal issues as well, constipation, trouble swallowing, incontinence, erectile dysfunction.  The most notable symptoms with the most difficult treatment are a burning/tingling/crawling sensation of the skin, painful spasms, facial pain and fatigue.  MS is diagnosed via tests of nerve and muscle conduction speed, an MRI, spinal tap to look for inflammation proteins in the cerebrospinal fluid, and physical examination for changes in vision, hearing, sense of touch, pain sensation, balance, muscle coordination, etc.  [As usual, the PubMed Health site on MS: is an excellent place to start for more information.]

Since MS is an autoimmune disease, one course of treatment is to suppress inflammation and immune function using chemotherapy, interferon or antibodies to immunoglobin E (IgE) - the primary immune system
protein responsible for autoimmune reactions.  However, these drugs will only slow the course of the disease, they cannot restore lost function.  Given that damaged neurons will not regrow, it is possible to supplement the normal neuron function by replacing or reinforcing the action of certain neurotransmitters - such as GABA-like medicines for muscle spasms, acetylcholine for urinary problems or antidepressants for the mental changes.

This will seem a bit strange for those who know my stand on medical marijuana, but cannabinoids have been shown to reduce spasms, reduce pain and alleviate mood changes.  I still maintain that these effects would be better served by a true medicinal cannabinoid with controlled formulation and dosing, but in the case of MS and cancer pain, smoked marijuana appears to be quite effective.

Patients with MS can live quite a long time (20+ years) with minimal symptoms, or may have periodic attacks with severe symptoms, but be symptom-free for months or even years in between.  Keeping in mind that I am writing about neurological and neuromuscular disorders at fictional plot devices, MS is the sort of disorder that a person can have and show no overt symptoms, while the disease continues to affect neurons until a tipping point is reached in which the patient experiences loss of both voluntary and involuntary muscle control and requires assistance caring for themselves.

I highly recommend that anyone desiring more information visit the PubMed Health site and start there.

We will continue with the "Three M's" next time, with Myasthenia Gravis, a disease that can have many overlapping symptoms with MS, but with a totally different causative source.

Sunday, February 26, 2012

Updated NEWS: Stellarcon 2012, March 2-4, High Point, NC. [Full link to blog for email clients.][FT:C44]

Finding Baen folks at Stellarcon, Mar. 2-4.

Bar Fly Central, Suite 215.

UPDATED, with panelist changes and moderators now indicated by "(M)".
Also note my science talk "I Remember When" on Saturday at 3 PM.

Friday 4 PM, Programming 3, "Con Health", Speaker to Lab Animals, Chris Ross

Friday 5 PM, Programming 1, "Hard Science Fiction", Paula Jordan, Gray Rinehart, Speaker to Lab
Animals (M), Michael A. Stackpole, Toni Weisskopf

Friday 5 PM, Programming 3, "The Pirate Panel", Danny Birt (M), James Fulbright, Laura Haywood-Cory

Friday, 6 PM, Main Programming, “Stellarcon Opening Ceremonies”, James Fulbright, Tera Fulbright, Albin Johnson,John Kovalic, Mark Poole, Patrick Rothfuss, Brad Sappington, Michael A. Stackpole, Chris Weed, Michael Z. Williamson

Friday, 7 PM, Programming 1, “Writing Action Scenes”, Chris Berman, Podcasting's Rich Sigfrit (M), Michael Z. Williamson

Friday, 8 PM, Programming 1, "Research for the Writer", Theresa Bane (M), Paula Jordan, Karen McCullough, Speaker to Lab Animals, Amy H. Sturgis

Friday, 8 PM, Programming 2, "Short Stories and Publication", Barbara Friend Ish (M), Stuart Jaffe, Andi
Newton, Gray Rinehart

Friday, 8 PM, Programming 3, "Shooting First: Moral Ambiguity and Star Wars", Davey Beauchamp (M),
James Fulbright, Jim Minz, Podcasting's Rich Sigfrit, Michael A. Stackpole

Friday, 9 PM, Programming 3, “Surviving the Zombie Apocalypse”, Brad Sappington, Speaker to Lab Animals (M), Chris Weed, Michael Z. Williamson

Friday, 9 PM, Workshops/Reading, "Filk Circle", Danny Birt, Gray Rinehart, Blibberering Humdingers


Saturday, 9 AM, Offsite, “Bar Fly Range Trip to Proshots Range in Winston-Salem” (Exit 118 off of US. 52 North, about 40 minutes from Stellarcon)

Saturday, 12 PM, Programming 1, "Character Building Workshop", Barbara Friend Ish, Steve Long (M), Gray Rinehart, Patrick Rothfuss

Saturday, 1 PM, Main Programming, “Interview with Michael Z. Williamson”, Speaker to Lab Animals (M), Toni Weisskopf(M), Michael Z. Williamson

Saturday, 2 PM, Programming 1, "The Role of the Publisher in Today’s Market", Barbara Friend Ish, John G. Hartness, J.L. Hilton (M), Misty Massey, Toni Weisskopf

Saturday, 3 PM, Programming 2, "SONAR 2012: Symposium On Nerdy Academic Research", Dr. Tedd Roberts, "I Remember When…"

Saturday 3 PM, Programming 3, "The Art of Revision", Marilynn Byerly, Tony Daniel, Laura Haywood-
Cory, Stuart Jaffe (M)

Saturday 4 PM, Main Programming, “Baen Travelling Roadshow”, Tony Daniel, Laura Haywood-Cory, Jim
Minz, Gray Rinehart, Toni Weisskopf, Michael Z. Williamson

Saturday, 6 PM, Programming 3, "I'd Rather Be _________", Danny Birt (M), Jim Minz, Janine K. Spendlove, Michael A. Stackpole, Allen Wold

Saturday, 9 PM, Programming 3, “Dystopian Literature: how political philosophy can influence depictions of dystopia”, Nicole Givens Kurtz, J.L. Hilton, Speaker to Lab Animals (M), Michael Z. Williamson

Saturday, 9 PM, Workshops/Reading, "Filk Circle", Danny Birt, Gray Rinehart, Blibberering Humdingers

Saturday, 10 PM, Programming 3, “Messiest Way to Kill a Zombie”, Dan Johnson, Stephen Mark Rainey, Brad Sappington, Chris Weed, Michael Z. Williamson (M)


Sunday 10 AM, Programming 3, “Strong Female Characters”, Diana Bastine, Chris Berman, Teresa Frohock (M), Michael Z. Williamson

Sunday 11:30 AM, Workshops/Reading, “Reading”, Michael Z. Williamson

Sunday 12 PM, Dealer Room, “Signing”, Michael Z. Williamson

Wednesday, February 22, 2012

The GUIDE: Neuromuscular Diseases [Full link to blog for email clients.][FT:C44]

I am running into some commitments on the Day Job that have derailed my ability to get the next series of blogs written, so instead of launching right into the blogs on the "Three-M's" of Multiple Sclerosis (MS), Myasthenia Gravis (MG) and Muscular Dystrophy (MD), I am writing this brief introduction to the topic.

Neuromuscular diseases are basically those disorders in which the majority of damage is to the nerves that carry signals from the brain/spinal cord to the muscles.  Essentially, the breakdown in communication can be in the brain (but we have covered those syndromes elsewhere), in the spinal cord, in the nerves as they leave the spinal cord, at the junction between nerve and muscle, or in the muscle itself.

Technically, the catch-all term "muscular dystrophy" refers to the latter category - those diseases or disorders in which theproblem is with the muscles themselves.  However, common use includes amyotrophic lateral sclerosis (ALS - Lou Gehrig's Disease, which we'll cover later), MS and MG - particularly when mentioned in a fundraising telethon.

Several significant differences exist with respect to the MD-category of diseases.  Again, MD is a catch-all term, but the implication is a disorder of the muscles.  MS is a disorder of the nerves, both in the brain & spinal cord and between spinal cord and muscle.  The "insulation" that allows nerves to conduct electrical activity very fast over long distances begins to break down in MS.  This results in muscle spasm and weakness, but also pain and distorted sensation.  MG is specifically a disease of the chemical neurotransmitter receptors at the junction between nerve and muscle.  The bodies own immune system attacks the proteins at the junction, preventing the neurotransmitter from being recognized by the muscle, weakening the signals from brain to muscle.  ALS is a disease in which the nerve axons themselves begin to die.  Each of these disease disconnects the brain from the muscles, and in some cases, the brain from the sensory receptors for touch and position of the body.  Muscle weakness, tremors, spasms and pain are the result.

We'll resume the next blog with a look at Multiple Sclerosis, causes, and treatments, followed by Myasthenia Gravis, Muscular Dystrophy, then ALS. 

Monday, February 20, 2012

COMMENT: The Big Lie [Full link to blog for email clients.][FT:C44]

For years, a prominent animal rights activist group - whom I shall NOT name, because I don't want to give them the search boost - has been telling Americans and the world that animal researchers are heartless sadists who enjoy torturing animals in the name of worthless science.


In the first place, scientists quite frequently have pets and care for animals in many ways.  Some of the research done on animals in the name of human medicine really does benefit animals.  For example, I had a dog that required two knee surgeries.  I have known people whose pets and even farm animals have had cataract operations, treatment for heart disease, diabetes, leukemia, lymphoma.

Second, bad health makes bad data.  Results obtained from mistreated or sick animals is worthless to scientific research.  The guiding principle of the experimental method is control of variables.  That is difficult with living tissues, more so with behaving animals.  Why would anyone think a scientist would complicate matters by working with sick, abused, distressed animals?  Under such circumstances, there would be totally different results with each trial, each animal. 

Third, the accusation of worthless repetitive science shows a fundamental lack of understanding of the scientific method.  Experiments must be repeated under controlled, identical conditions to ensure that the outcome is in fact due to the drug or treatment being tested.  Then experiments should be repeated under different conditions to ensure that the treatment will work each time.  You have certainly all seen this - a friend tells you about a great new drug, diet or exercise, it worked wonders for them.  You try it and it doesn't work, was it that you did it wrong?  Was your friend mistaken as to what actually produced the results?  Or did the diet just not work for *you*?

Frankly, animal rights activists betray a fundamental lack of education in science, and a profound selfishness. 

Selfishness?  Yes - the philosophy that "A rat, is a pig, is a dog, is a boy" does not mean that the speaker values animal life as much as human, but that they have *devalued* *other* human lives much less than their own.  Basically, *they* must be important, or else they would eagerly sacrifice their own lives for the cause.  No, they'd rather sacrifice *your* life by denying scientific and medical advances.  The animal rights organization does not believe in rights, but in control.

Animal rights activism is a Big Lie.  

Today my lab lost a valuable lab animal.  I have spent all day in a surgical and autopsy suite trying first to save it, then to figure out why this happened.  Preliminary findings suggest that it was an infection unrelated to our experimental procedures. This animal had been involved in many studies, and helped provide data that may one day be used to counter drug addiction, alleviate sleep deprivation or result in prosthetic devices for the brain.  I feel the loss much the same as when my family lost our dog to lymphoma a few years ago.  

But then, it was just an animal - and I'm just a cruel, heartless scientist.

The Big Lie.  Will you believe it?  Or reject it as just another means of manipulation and control. 


This event has altered my posting schedule.  The start of the blogs on dystrophies and neuromuscular diseases are postponed until Wednesday.

Wednesday, February 15, 2012

NEWS: We interrupt this blog to bring you... [Full link to blog for email clients.][FT:C44]

Happy Belated Valentine's Day.   I missed yesterday's blog because of planning to take my wife out for a nice Valentine's Day meal - until we encountered the crowds which accompany the date.  So, I quickly dashed to the store, picked up some goodies, and went home to try to recreate the meal I had intended - with pretty reasonable success.  I do a decent job of cooking and am not above experimenting without a cookbook.  I suppose that's not the right thing to say as an experimental scientists, but it's fun and an interesting exercise of memory.

Anyway, for today, in lieu of the regularly scheduled blog I am going to direct you to my rather lengthy essay over at Baen Books' website.  Each month starting on the 15th, they publish a free short story and a free non-fiction essay on the Baen site at  This month the essay is by yours truly, and is called "Putting the Science in Science Fiction" (  It is rather lengthy, so bookmark it and read at your leisure. 

This will serve as the main post for yesterday/tomorrow, and I'll be back on Friday with some commentary and news on Post-Traumatic Stress Disorder and Traumatic Brain Injury.  I'll resume the Guide blogs next week with the "M-is-for-Muscle" trio of Multiple Sclerosis, Myasthenia Gravis and Muscular Dystrophy.


Tuesday, February 14, 2012

COMMENT: Traumatic Brain Injury and Purple Heart [Full link to blog for email clients.][FT:C44]

A recent discussion on another board discussed the issue of Traumatic Brain Injury and Post-Traumatic Stress as battlefield injuries, and whether they could or should merit a Purple Heart  This blog contains most of my response - my OPINION - as well as what I hope is some useful information to explain what is really going on in cases of TBI and PTSD.

My understanding is that Purple Heart is awarded to a person who is wounded in a battle-field setting – and again, my understanding, the wound is received while actively performing their combat-related duties.  It would seem that one "purpose" of a PH is to acknowledge that the recipient may have lasting medical issues related to a wound received while defending our country.  A piece of tin can never compensate for life-long loss of a limb, an eye, part of a liver, etc.  but the recognition said injury occurred is of use to medical systems, the VA and other disability considerations. 

So – I pose the following rhetorical questions with regard to an attitude that TBI is not worthy of a PH – Would multiple broken bones be worthy of a PH?  If so, TBI is often accompanied by multiple skull fractures.

Are pneumothorax and/or cardiac tampanade (pressure on the heart caused by bleeding into the pericardial sac) worthy of a PH?  The *damage* of TBI occurs because of a buildup in pressure after the shock wave, resulting in damage and death of brain tissue due to compression of the blood vessels similar to stroke or heart attack.  Is loss of vision via loss of an eye, an ear or a jaw somehow more PH-worthy than loss of the ability to speak, hear or read because that section of the brain is irreversibly damaged?

TBI is not just a concussion.  Concussion is caused by a hard shock to the head that moves the brain within its fluid cushion so that it hits the inside of the skull.  The result is a temporary swelling that compresses blood vessels causing the a temporary impairment of brain function since it does not receive all of the blood flow that it needs (see my discussion of migraines here:  The swelling subsides in a day or so and no permanent damage occurs.  

TBI on the other hand is much more severe, and results from either a closed-head trauma (i.e. a hit, blow or fall) that cracks the skull, or an explosive shockwave directed at the head.  Note that I am still talking about closed-head injuries here, a penetration or laceration injury that opens the skull is still TBI, but the consequences of such an injury are rather more obvious than the closed-head type.  Critical differences between closed-head TBI and concussion are the severity and duration.  The shock to the skull is enough to cause multiple back and forth impacts between brain and inside of the skull, and an explosive shock wave can cause distortions as it passes through the brain causing shearing or tearing of the nerve axons, blood vessels, and other tissues.  The resultant bruising and/or hematoma again causes pressure and symptoms of a concussion, but the effects last much longer and may be permanent.  

Doctors can tell whether TBI has occurred by brain scans such as MRI and CT scan or by looking for protein, blood, or immune system cells  in the fluid from around the brain (the cerebrospinal fluid, CSF, obtained from a spinal tap, but on the battlefield, there is not much that can be done to tell the difference.  It is only by looking at the long-term consequences that the true picture of TBI occurs, such as long-term impairment of memory, personality changes, loss of vision, hearing - and in particular, sense of smell.  The latter is important, because it is very easy for movement of the brain within the skull to separate the nerve endings of the nose from the olfactory nerve, so loss of smell is a key indicator of TBI, although it is not always present, nor is it exclusive.  

So in many ways, TBI is long-term  damage to the brain, it make take days to weeks for the real symptoms to show up, and months, years (or never) to go away.  Unlike a traumatic amputation, the reality of TBI is much harder to see, but in my opinion, it is no less battlefield trauma than any of the other injuries that qualify for the Purple Heart.  Fortunately, the trend in not acknowledging TBI was reversed over the past several years and I have been told that TBI is now recognized by the U.S.Army with a Purple Heart.  
With respect to PTSD, I am sure there are malingerers among the ranks of those claiming PTSD.  However, there are many more *suffering* from PTSD and not reporting it than there are faking it.  I *don't* know if PTSD deserves a PH, because I think you'd essentially be giving one to every soldier.  Many of the problems with understanding the severity of PTSD come from not understanding what it actually *is.*

PTSD is a fear reaction.  There are soldiers - both active duty and retired - who have argued with me that what society calls PTSD, the combat soldier calls survival skill:  hypervigilence, light sleep, aggression.

NOTE:  They are wrong.

PTSD is not any of those things. PTSD is not aggression or attempts at combat.  The issue comes from misguided attempts to put a clinical label on adaptive or maladaptive behaviors so that they can be excused or dismissed.  This point is also why PTSD is over-diagnosed and can often be used to excuse malingering.  

PTSD is a physiological fear reaction that is essentially triggered by memory.  The heart beats faster, breathing is faster and shallower, adrenaline and other hormones triggered by stress are dumped into the blood.  A key difference is in the reactions of the autonomic nervous system which controls many of the unconscious reactions of the body.  However, the precise reactions are important - for example, pupil dilation (fear) vs. constriction (aggression), dry mouth (fear) vs. excess saliva (aggression - think "foaming at the mouth"), sweating (fear) vs. dry skin (aggression), muscle rigidity (fear) vs. a slight tremor or twitch indicating readiness to spring into action (aggression).   The PTSD reaction can be triggered by nightmares, a sudden touch, sound or even a smell.  The trigger is tightly tied to memory as I describe below, so I will need to drop into lecture mode a bit.  

However, again I emphasize that all of these triggers can result in aggression - which is adaptive for combat, and even though inappropriate in a civilian setting, it *is* a survival skill set - but it is not PTSD.  It is the fear reaction that is the hallmark of PTSD that is totally maladaptive and counter to survival (i.e. "freezing in the face of the enemy"). 

Memory is a key component of PTSD.  Scientists who study memory know that there are instances in which memory is abnormally strong.  Under normal conditions, items must be repeated in order to be remembered:  addresses, phone numbers, SSNs, etc.  Yet it is relatively easy to remember where you parked each day because you use all sorts of cues to help remember these single, nonrepeated, data points. 

There are two circumstances in which an event is powerful enough to be remembered in "one trial" without resort to cues and references:  one relies on simultaneous activation of powerful emotion – we see that as "flashbulb memory" and it is common in the question: "Do you remember what you were doing when... " You can fill in the blank with:  Kennedy was assassinated, Apollo 11 landed, OJ was found not guilty, Challenger exploded, 9/11 occurred, Columbia  exploded, etc.  The commonality is strong emotion.  We also see this is lab rats with fear and pain.  If you put a rat in a box with one half in bright light, but the other in the dark, they will avoid the light and preferentially stay in the dark.  But it you electrify the floor and deliver a rather mild shock when they run into the dark, they will avoid it.  One time is all it takes, and the memory lasts for a very long time until you specifically teach the rat that it won't get shocked even if you never shock them again!

I mentioned a second type of abnormal memory, and this is the one that has the most to teach us about PTSD and the emotion-laden memory mentioned above:  drug-assisted memory.  One of the key findings with respect to drug relapse is that stimulant drugs like cocaine, crack, meth stimulate the part of the brain that encodes reward vs. risk.  An important part of learning is the relative reward or "payoff" for the item to be remembered.  This forms the motivation which controls the strength and speed of forming long-term memory.  "Learn to pedal the bike otherwise you will fall and hurt yourself" is a high motivation.  Remember the phone number of the cute chick who blew you a kiss from across the bar is high motivation.  Remembering your sister-in-law's birthday is low motivation.  Stimulant drugs, and most especially cocaine "crank the dial to eleven" and artificially strengthen the memory or events and surroundings associated with the drug high.  It is *hard* to erase the memories thus formed, because the brain chemistry changes the structure of the brain in such a manner that the memories become "hard-coded" and not just like erasable bits in a computer.   

We now know that during combat, the neurochemical reaction to fear and stress does the same thing to memory.  It's actually why "flashbulb" memories occur, but the neurochemical factors are not as strong unless you perceive your life to actually be in danger.  A major component of PTSD is the inability to forget the memories stored during highly painful, emotional, stressful experience. 

The other thing we know about these abnormally strong memories is that every time you recall the scenes, they may be subject to subtle alterations.  I remember events that I think are associated with the JFK funeral, but are really from Eisenhower's funeral.  People who discuss 9/11 may associate people, places and conversations that  occurred later – but when they were discussing their original memories of 9/11.  Scientists call this "conflation" and it is because memory recall is not simply pulling a copy of a memory then discarding it, it is actually replaying the original memory, then rewriting it to reinforce it.  Additional events can easily be tacked on later, resulting is false memories conflating the flashbulb memory. 

What this means for PTSD, though, is that drug and PTSD memories are much less subject to conflation due to the "hard-coded" nature of the memory.  PTSD memories *can* be lessened with appropriate therapy, but it is *hard* and requires reliving the experience with appropriate counseling and therapeutic controls.  Virtual reality seems to be helping in this regard.

About a year ago, there were several reports of a blood test for PTSD.  The utility and accuracy of such tests are still very much in doubt.  One group was looking at the effects of stress hormones and their  metabolites ("allostatic load") that could be quantified to give a green "healthy" reading or a red "unhealthy" reading indicative of unresolved/maladapted stressors.  The inventors of the test - which dates back to research published in 2000 (B. McEwen, Allostasis and Allostatic Load, Neuropharmacology, 22:108-124, 2000) claim 85% correspondence between a "red" allostasis and PTSD.  The Israelis also have a test that reveals levels of a particular type of immune cells (gamma delta T-lymphocytes) that also appear to be characteristic of PTSD.  The problem with both of these tests is that many stressors also increase the stress hormones and immune response.  In addition, T-cell sensitivity in particular varies between males and females, although the same is true for the stress hormone cortisol to a lesser extent.  Prolonged illness, physical trauma and TBI can also result in positive indicators, but in the absence of those causes, a positive blood test could be a good indicator of unresolved stress or medical issues. 

The net result of PTSD is essentially a rewiring of the brain due to abnormality in memory.  Stress and fear reactions take the place of normal response (on or off the battlefield) and the memories are unusually persistent.  The blood test data suggest fundamental changes in the body's own natural mechanisms for dealing with stressors, and the sufferer is essentially no less damaged than the amputee who has to learn to use an artificial limb.  It may seem surprising to those of you who know my stand on medical marijuana, but there are some interesting medicinal uses for the cannabinoid-based drugs as treatment for PTSD – but note I said "cannabinoid-based"  I mean purified extracts, compounds and synthetics, not pseudo-medical pot-smoking.

As for the original question of Purple Heart awarded for PTSD, I think I come down on the side of those who say no.  At present we still don't have accurate tests, there is certainly abuse of the diagnosis, and we don't always have a definite link between the triggering event (which my understanding suggests should be honorable combat duty) and the disorder.  On the other hand, we shouldn't stigmatize those who really do need medical intervention to get their lives back in order.

More research is needed, but then you probably knew I would say that.

Sunday, February 12, 2012

NEWS: Behind the headlines [Full link to blog for email clients.][FT:C44]

Many times I am asked by friends - particularly writers - to comment on sensational headlines in Medicine and Biology.  Examples are recent columns on the "dangerous super flu" ( and the follow-up (,  marijuana treatment of autism (, peer review (  There are many more that I have answered in personal emails and other discussion forums.

Usually when I am asked one of these questions, I first read the headline article, then look for the reference to the actual scientific study.  I then read the study and try to find out what else has been done in the field.

Sometimes I go to Wikipedia.  GASP!  "NO," you say, "not that!"  Well, it's true.  Many research departments have encouraged graduate students to update Wiki articles with references to their professors' research.  You have to treat it with a bit of skepticism, because Wiki authors have biases that blind them to countervailing viewpoints, as well as the obvious (do they ever, just ask Stephanie Osborn!), and there is a tendency to disbelieve anything that the inner circle doesn't originate.  However, wiki articles that contain citations to primary material are a good source... of citations to primary material.  It's a starting point, but you should always do your own investigation.

Well, now there is a tool to help you do just that!

The U.S. National Institutes of Health provides a website called "PubMed Health: Behind the Headlines" (  Doctors, researchers and students around the world probably know PubMed as the gateway to the NIH's National Library of Medicine.  A massive database originally called "Medline" provides the ability to track down just about any biomedical article published (in English) since 1966.  In the last 10 years, PubMed has allowed anyone - not just librarians - to search Medline and many associated databases.  More recently, NIH/NLM started using PubMed to fulfill its public education mission, with articles and news of general interest.

Interestingly, "Behind the Headlines" is not a U.S., product, but comes from England's National Health Services.  Many of the most sensational medical-related headlines seem to appear in The Guardian, The Sun, The Daily Mirror, The Daily Mail, so it is somehow appropriate that "Behind the Headlines" comes from those very same shores.

What this site does, is take current medical headlines apart, showing what is told in the news article (and how it frequently differs from the sensationalist headlines), where the story came from, and what kind of an article it references (i.e. original research, news release or opinion).  When the original source is a research article, it takes time to explain the results, what they mean... what they don't mean, and what conclusions the authors drew from the research.

The founder of Behind the Headlines - Sir Muir Gray - very clearly states the rationale behind the site as "“Scientists hate disease and want to see it conquered.  But this can lead to them taking an overly optimistic view of their discoveries which is often reflected in newspaper headlines."  [Actually, I have found that most scientists really don't like talking to the press, and that most headlines are written by university PR departments.  The disconnection from the actual science is one reason why articles featuring synthetic drugs that could never be found in a cannabis sativa leaf get headlined "Medical Marijuana cures..."]

I've researched a couple of recent news stories - particularly one that seems to claim a looming "flesh eating bacteria" epidemic.  Behind the Headlines, we find that the actual science said that some of the types of drug-resistant bacteria found in hospitals seem to have traded virulence for resistance to drugs.  Thus the really powerful bugs "in the wild" (i.e. in public) can be easily treated with antibiotics, while the drug-resistant bugs in hospitals and nursing homes really don't spread easy between patients. That's a big difference from the headline.

So give it a try, next time you see a news article with a confusing or sensational claim, check out Behind the Headlines and learn the real science. 

Friday, February 10, 2012

The GUIDE: Treating Alzheimer's Disease [Full link to blog for email clients.][FT:C44]

The plain truth of the matter is that there is no cure for Alzheimer's Disease (AD).  If neurons in the brain could be grown and replaced like skin, muscle or liver cells,  then it might be possible to regrow the lost brain cells, but unfortunately, just replacing cells is not enough - our memory, everything we have learned, and even our very personality is a product of the connections between neurons that have built up over a lifetime.

Image Copyright Alila Sao Mai, 2012
Used under license from
What we can do is to support the functions of the undamaged neurons while the symptoms of AD are still mild.  In the previous blog is was mentioned that neurons using acetylcholine (ACh) seems to be preferentially affected by AD.  Whether the disease specifically targets these neurons or they simply happen to be prevalent in the first brain areas affect is immaterial.  What happens is that as acetylcholine neurons die, the amount of signal they can represent is decreased, somewhat like listening to a music player radio with dying batteries.  The brain is highly redundant, and most neural signals are carried by multiple neurons.  Thus if we could find a way to boost the signal of the remaining neurons, we might be able to delay the debilitating phase(s) of AD. 

In the diagram at right, I show a typical "synapse" between neurons.  At the top is the "presynaptic neuron" which is the one sending the signal.  At the bottom is a portion of the "post synaptic" neuron which receives the signal. Signals in the brain are represented as the distribution of electrical energy - similar, but not exactly like the digital "bits" of a computer.  However, in order to cross the gap between neurons, that electrical signal is converted to a chemical one.  The positive electrical potential that results from activity in the presynaptic neurons causes release of a stored chemical - the neurotransmitter.  The neurotransmitter diffuses into the space between neurons, and when it encounters the neurotransmitter receptors on the postynaptic neurons, it causes the protein to change shape, quite frequently opening a channel that allows positively charged molecules into the neuron.  Accumulating positive charge starts the entire process of electrical activation again in the new neuron and the process repeats with transfer of signal from neuron-to-neuron. 

The neurotransmitters are short lived - there are enzymes which break them apart, as well as means for the presynaptic cell to reabsorb the components.  The reason is that neuron-to-neuron signals should be short, otherwise the information will get lost in continuous signal.  But, if the signal is getting weaker due to AD, it makes sense to boost it by prolonging the action at the postsynaptic neuron.

There are a few classes of drugs that can perform that action - the most prevalent drugs - donepizil (Aricept), rivastigmine (Exelon) and galantamine (Razadyne) all work by stopping or slowing down the breakdown of ACh.  They are useful to "boost the signal" that naturally occurs by prolonging the activation of the postsynaptic neuron.  A second method would be to raise the background activity at ACh receptors by supplying a small amount of an ACh-like drug so that the ACh released by neurons would be more effective in activating the post-synaptic neurons.  While much work is ongoing in this field, no drugs of this type are currently in any but experimental use. A third method is to reduce some of the other, "competing"  activity in the brain, particularly in areas in which there are many ACh and glutamate neurons.  Mematine (Namenda) blocks one type of glutamate receptor, thus producing a "quieter environment" for the ACh neurons.  As a last resort, once AD patients start to show symptoms of personality disporders, aggressiveness, hallucination, etc., those symptoms can be treated with antipsychotic drugs.

It should be noted that all of these treatments are symptomatic ones, and they nothing can "cure" or reverse AD.  However, there is hope in that supporting memory, decision-making and other activities of the brain can slow the progress of the disease and postpone the onset of more symptoms.  There is an old saw about "use it or lose it" and it appears to be true - using the brain strengthens the synapses between neurons.  Strong synapses deteriorate slower, and while starting Aricept or other treatment after the onset of AD won't bring back lost function, it will help to maintain what remains.

By the way, vitamins and gingko biloba have no effect on the onset or progress of Alzheimer's disease, no matter what any source may say.  No effect means no effect.  Obviously a good diet is important, and omega-3 fatty acids and antioxidants are important to normal brain health, so certainly include them (within reason) in your daily intake.

Ideally, as stated above, we should find a way to replace the neurons, remove the amyloid plaques, or fix the neurofibillary tangles.  In fact, there are stem cell therapies designed to supply the glial cells that normally support the active neurons.  Replacement of neurons may have some benefit, but as stated above, they would need to be "taught" with all of the experience of a lifetime.

Perhaps what is really needed is a science fiction nanomachine that can selectively break up beta-amyloid and fix neurofibrillary tangles.  Then we could move on to more nanomachines that rebuild the lost synapses and restore memory from a previous template.

Hmmm.  Where have I heard that before?

Wednesday, February 8, 2012

The GUIDE: What is Alzheimer's Disease? [Full link to blog for email clients.][FT:C44]

This post gets directly at a question asked a couple of weeks ago, in terms of exactly what Alzheimer's Disease (AD) is in terms of a neural disease.  Knowing what the actual disease process is, coupled to a discussion of what brain areas and neuron types are affected, will help to explain many of the effects. 

To start out, I am going to bring back the illustration from last blog, and explain what is going on.
PubMed Health. A service of the National Library of Medicine, National Institutes of Health.
Illustration URL:
  In short, AD is a disease in which certain types of neuron die due to an accumulation of proteins that are normally broken down and metabolized.  Instead of being broken down, the proteins accumulate both within neurons and "plaques" of dead and dying cells.  These dense masses also exert pressure on other neurons and cause problems due to impaired blood and circulation and "lymph" flow (in brain, it's not really lymph, but a thinner, filtered electrolyte solution called "Cerebrospinal Fluid").

I will digress for but a moment - many if not most cells in the body are round or squarish shapes, but neurons have long branches called dendrites (from the Latin for tree) and even longer axons which connect neurons together in a manner similar to electrical wiring. Forming and maintaining this shape requires an internal structure, and that is provided by very fine filaments and tubes called, unsurprisingly,neurofilaments and neurotubules.  These structures form what is common called the "cytoskeleton" and are responsible not just for holding the cell's shape, but for providing a transportation pathway for movement of chemicals throughout the neurons. Under normal circumstances, the neurofilaments consists of polymer chains of a protein called "Tau."  In the AD brain and certain other neural disorders, Tau proteins do not assemble properly, and the neurofilaments become tangled and random.  These tangles can be seen when the brain tissue is examined under a microscope, and excess Tau can be detected both in the AD brain and in tissue where cell damage has occurred.  Thus it is not entirely clear whether the AD-affected neurons make too much Tau, or simply that excess Tau is available due to death of neurons and attempts to make more  and appropriate neurofilaments for the neurons.

The membranes of cells in the body consist mostly of lipid molecules with a few proteins floating in the lipid.  Think of how a soap bubble forms, trapping air inside of a thin film of detergent, with swirls of color and pattern in the soap.  Now think of the appearance of oil on water.  That same swirl of color indicates that a thin film of oil - lipid - is dispersed over the surface of the water.  Shake the mix, and you will see tiny bubles of oil, some with water trapped inside.

Cells are like that, a thin film of lipid, with water and proteins on the inside, salt water on the outside, and proteins plus complex oily molecules (triglycerides and cholesterol!) to stabilize the film of lipid into a membrane.  One of the stabilizing proteins that is particularly important to forming the synapses which connect neurons, is amyloid precursor protein (APP) is important, but when excess APP is produced, it can be broken down into fragments of "beta-amyloid" which are insoluble and difficult to metabolize.  Deposits of beta amyloid accumulate and essentially "choke" neurons.  As neurons die, the beta-amyloid remains and builds up, leaving "plaques" and dead neurons in the brain in place of healthy neurons.

AD is characterized by the presence of neurofibrillary tangles - indicating cells that are nonfunctional or dying - and plaques, indicating large ares where many neurons have died.  Neurons do not regrow, and the accumulations of Tau and beta-amyloid are dense, so the total brain volume shrinks.  Once this process occurs, the symptoms match the brain areas most affected - temporal lobe plaques are associated with memory problems, frontal lobe with decision-making and movement planning, parietal and occipital lobe with sensory inputs and hallucinations, the "basal nuclei" with movement disorders and all of the above.

Thus the many symptoms of AD can be explained by examining the progress of the disease - AD tangles and plaques typically show up in temporal lobe, then parietal/frontal lobes and finally thalamus and the deep nuclei - resulting in amnesia, then personality changes, difficulty making decisions, and gradual worsening of all of the above.

An additional consideration that had neuroscientists chasing in the wrong direction for a few years is that the initial stages of the disease appear to preferentially affect that neurons that use acetylcholine for neurotransmitter.  You may recall that there the most common chemicals associated with communication between neurons are (in order of prevalence)glutamate, gamma-amino-butyric acid, norepinephrine, and acetylcholine (ACh).  ACh does double duty by also being the neurotransmitter that is present in muscles and forms the junction between motor nerve (for control of muscles) and the muscle itself.  ACh is also very prevalent in the hippocampus, and is associated with memory storage and recall processes.  AD was origianlly thought to be a disease solely of ACh neurons, and thus could be treated much the same as Myasthenia Gravis - a disease of the ACh receptors in muscles.  Alas, AD affects all types of neurons, but the presence of many ACh neurons in the hippocampus associated with the early symptoms of the disease do make it a candidate for treatment drugs.

The next blog will discuss treatment and therapeutic options, and perhaps provide a bit of hope for the future in the treatment of AD.

Thanks for reading.

Monday, February 6, 2012

The GUIDE: "Whatizname's Disease" [Full link to blog for email clients.][FT:C44]

Alzheimer's Disease.

This is the big one.  I have actually put writing this segment off as long as I could due to the complexity of the subject. It will also probably take more than one post to do justice to the topic.  SO, you have been warned!

In a list of top 10 questions that many Neuroscientists are asked about the brain, one of the following questions: "What is Alzheimer's Disease?" "What causes it?" and "How can we treat it?" will usually be in the top three.

Right from the top I am going to admit that I need help with this one.  I know the effects, the symptoms and what happens, but there is so much more to the topic, that I need an expert resource for assistance.  Fortunately, the U.S. National Institutes of Health feel the same way, so the National Library of Medicine, via its "PubMed" database, has help for you and me on the subject.  So, I acknowledge considerable help from the Alzheimer's disease page of Pubmed Health (

I will start with my personal encounter with the disease.  In 1979, I was a recent college graduate lookign to go to medical school to study Neurology or Neurosurgery.  My grandmother was in her 70's and started showing signs of senile dementia.  Alois Alzheimer had identified the disease process in 1906, but it wasn't until the 60's that researchers linked the Alzheimer's brain cell abnormalities to cognitive decline and memory loss.  By 1979, the term "Alzheimer's Disease" was starting to be heard by the American public.  My aunts immediately latched onto AD as the explanation for my grandmother's problems, but I wasn't so sure.  AS understood in 1979, AD was presenile dementia, meaning it hit at a much earlier age than "normal" senility.  Many of the known cases of AD at that time were in patients of age 50-70.  I felt that claimed AD for my grandmother was stretching the definition, but I would certainly do some research to find out.

It turns out that I was right and wrong.  My grandmother had actually suffered a "psychotic break" we didn't realize it at the time, but she had undergone a severely stressful experience that caused her to withdraw from normal social interaction, while at the same time appearing to lose the inhibitions that normally keep a person from acting on impulse.  Still, over the years, as AD was better understood, and as we watched her deteriorate, it became apparent that she did indeed have a steady decline in mental abilities and memory, thus whether she had AD in 1979 was a moot point, she certainly had it in later years.  Instead of going to medical school for a clinical Neuro specialty, I obtained a doctorate in Neuro research - at a medical school, so I did take many of the same classes - and I specialized in memory, which brought me face to face with Alzheimer's Disease on many occasions.

So, to finish off today's blog, I'll discuss the two main types of AD and what they are.  For the next couple of blogs I'll talk about diagnosis, treatment, and the research being done on AD.
PubMed Health. A service of the National Library of Medicine, National Institutes of Health.
Illustration URL:

AD can only be accurately diagnosed by looking directly at the brain tissue and neurons.  That means that autopsy is really the only way to be certain, but brain scans such as CT and MRI may show damaged areas in advanced cases.  "Early Onset AD" is the "presenile" type that I was familiar with in 1979.  The symptoms typically appear before age 60, it runs in families, and the course of the disease is very fast.  Early onset AD often leads to death in a few years.  "Late Onset AD" typically shows up after age 60, and in many ways is not very different from classical "senility."  In fact, there are some who argue that all humans would get AD if they lived long enough.  This form of the disease may also run in families, but the genetic component is not very clear.

Many doctors and neuroscientists view AD as a multi-step process as in the figure above.  A third type of "pre-AD" called "Mild Cognitive Decline" frequently occurs as patients age and develop difficulty retrieving some memories or making certain decisions.  The onset of MCI is often in the 50's prior to the age when such memory difficulties are "normal" (i.e. late 70's and older).  The decline continues until a threshold is reached - at any age - and frank AD symptoms are seen, accompanied by a rapid loss of memory and cognitive ability.

Symptoms:  (again I am indebted to Pubmed Health)

Dementia usually first appears as forgetfulness, then changes in emotional behavior or personality, mild aphasia, changes in perception, then impairment of thinking and judgment.  The precursor stage - MCI - appears with the difficulty in doing more than one task at a time, inability to tune out distractions, difficulty solving problems, forgetting recent events or conversation, and constantly restarting or taking longer to complete difficult activities. AD itself is characterized as difficulty learning new tasks or performing old tasks that used to be easy, getting lost in familiar places, extreme aphasia and difficulty with language or understanding, mood changes and loss of interest, loss of social skills.  As AD gets worse, these symptoms impair the ability to take care of one's self, result in inappropriate actions, depression, irrationality, hallucination, and eventually loss of memory, inability to speak or understand speech, inability to recognize family members, loss of control of bodily functions.

Alzheimer's disease is a sad, heartbreaking condition for families, and it is not a matter to be taken lightly, hence my reluctance to cover the subject until now.

I'll be back over the next few blogs to discuss more of the brain science behind AD and to give some hope for future scientific developments in this field.

Until then, take care of your brain... please.