I AM A DOCTOR

I am not a Provider!  

pro·vi·der n

1.            somebody who provides the material means of support for somebody, especially a family

2.            an organization or company that provides access to a service or system, for example, a cellular phone, cable, or computer network

I am a Doctor! 

doc·tor n

1.            a title given to somebody who has been awarded a doctorate, the highest level of degree awarded by a university

2.            in the earlier history of the Roman Catholic Church, an eminent and influential theologian

3.            a teacher, or somebody very knowledgeable (archaic)

After many years of practicing medicine, I have come to realize that patients look upon doctors as belonging to their family of friends. They share their hopes and dreams. They talk about illness and the dread that comes with it. They speak about their families and what the children, grandchildren or their spouses, nieces and nephews have to say about inconsequential things. They talk about life.

From that, I decipher the heartache within, which has caused the calamity that has propelled the patient to arrive at my doorstep. I am a human like my patient. I have the same fears. I revel in in the joys similar to the ones they, the patients have. I rejoice in the same accolades that they do. I cry because of similar threads of loss and grief. But here is where the unpleasant thoughts must end in caring for the patient. With all the empathy endowed upon me through living a life, I must detach myself from the emotive expressions and with a critical eye towards facts and none towards the bubbling brook of emotions, cast my analysis in accordance with knowledge and experience. To help my patient!

The frown of thought, the wrinkle of concern, the detachment in the question must accomplish one and only one purpose; regaining the past splendor of a life in turmoil. So I listen and think and listen some more. And at the end, I have a plan.

Explaining the technical details to the patients are as important for their understanding as it is to mine. They must understand what I plan to do. I must understand what they expect of me in return for subjecting themselves to the rigors of my plan. This understanding is an education, which must not be cut short, abbreviated or rendered moot. It is crucial to both of us. It is crucial to the wellbeing of the patient and is equally crucial to the promise of my dedication to this noble profession of medicine.

Why then do the “experts” continue to use the jargon of “provider” when they talk about me? Why, am I to them, someone who provides only “material means of support?” I ask myself. Is that what I do? Am I a car salesman that provides a material means of support to a customer to ease their travels? Am I a plumber that provides a material means of support for a burst pipe? Both professions in light of need have an important place and need in society, but I believe in my heart, I give more than that. I give of myself, my experience, my knowledge, my humanity, my support, my confidence, my empathy, my emotions and a share of unquantifiable intellect gathered through years of practice and familiarity, that are all a part, which enrich me.

What then is the purpose of this changed definition? The lexicon seems to have permeated into the professors, experts, journalists, lay-people and even intellectuals who think for a living, in their daily conversation. I believe it is a means of diminishing the significance of a doctor! Reduce the perceived value of the doctor through this lexical obfuscation and then use that proposition to demonize, demonetize, and vilify at random. Ultimately, one must wonder, to what end? Is it because of money? Unfortunately, from my perspective, all trails lead to the pot of gold at the end of their rainbow! 

A noble profession does not and has never meant aloofness, superiority and arrogance. It is meant an unvarnished reality of alleviating human disease and restoring health.

This discussion is not about dipping in a pool of nostalgia, it is about reality. As a doctor, I must maintain my side of the bargain of caring for the sick and educating them in health and leave to others to call me what they want. 

But in my own infinite space, I am and will always be a Doctor!

"Three-quarters of the sicknesses of intelligent people come from their intelligence. They need at least a doctor who can understand this sickness." ~ Marcel Proust

NFkB ~ The Myopic Salesman

I came across this story in which several people got hurt. All of them belonged to disparate families and in different regions. The calamity wrought upon each community was immeasurable. Several squads of police cars and CSI units were dispatched to find out what happened in each locality. Yet the mystery continued.

Distraught from the pain and suffering, a young girl, while reading a newspaper realized that the events at the other places seemed to match in some respect the one that had ravaged her community. Taking the thread, she began to sow the fabric of the mystery and eventually found out the culprit; a quiet, myopic, unassuming but well dressed salesman who had keys to the hearts of willing and gullible individuals.

And it made me think of NFkB

You should right about now give a hooting laughter. What did he say?

Yup! I stand by it and here is how.

25 years ago, David Baltimore and Ranjan Sen discovered this DNA binding ubiquitous protein complex that has become the focus of our attention.

NFkB (or nuclear factor kappa-light-chain-promoter of B-cells), is a n interesting little fellow that resides in the cytoplasm of the cell. There it sits quietly as heterodimers, until provoked. Once provoked it phosphorylates and takes the shoots down into the nucleus. And that is where the climactic journey begins.

“NF-kappa-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis.

“All proteins of the NF-κB family share a Rel homology domain in their N-terminus. A subfamily of NF-κB proteins, including RelA, RelB, and c-Rel, have a transactivation domain in their C-termini. In contrast, the NF-κB1 and NF-κB2 proteins are synthesized as large precursors, undergoing processing to generate mature and active NF-κB subunits.

NF-κB is detected in most cell types, and specific NF-κB binding sites are identified in promoters and enhancers of increasing number of inducible genes. The transcription factor NF-κB consists of homo- or heterodimers of different subunits, members of a family of structurally related proteins – Rel / NF-κB proteins. Rel proteins contain a conserved N-terminal region, called the Rel Homology Domain (RHD), which contains the DNA-binding and dimerization domains and the nuclear localization signal of the Rel proteins.

NFkB exists in five forms within the cytoplasm and is bound exclusively to the Rel proteins, where they exist in quiet and peaceful harmony watching the daily chores of the cell go by. But, and here is the big but, if one of the invaders dares interfere with the cellular function and by that I mean, say a virus, bacterium, a foreign particle, lipopolysccharide, or even LDL float inside the cytoplasm through the cellular membrane that degrades the binding protein and releases the activated NFkB. Receptor activator of nuclear factor kappa B, which is a type of TNFR, is a central activator of NF-κB.

http://youtu.be/WgqAjYKjXAc

All hell breaks loose.

NF-κB can be activated by a number of stimuli, including exposure of cells to Lipopolysaccharides or inflammatory cytokines such as Tumor Necrosis Factor or Interleukin-1, growth factors, lymphokines, oxidants, free radicals, inhaled particles, viral infection or expression of certain viral or bacterial gene products. 

The first event of a loose NFkB (so to speak) is to acquire a phosphorous group which kicks it into motion (like an energy pill). Once the NFkB has been phosphorylated it rapidly activates it’s N and C-terminal groups for travel into the nucleus of the cell where it attaches itself to the DNA with its DNA binding site. It is like a hello with a shaking of the hands, transiently in some cases and in other cases the hand-shaking never ends, lke some relatives you want to avoid.

Let me get to those two phases:

Transient hand shaking occurs in most infectious and irritant causes. A virus attacks and the cell releases its NFkB to proceed down the hatch and bind to the DNA to promote the genes required for cellular response to create more immune cells against invader. Since NFkB is in the “Rapid Response Team” this is a “Fast and Furious” process.

In some cases the NFkB through its activation can bind selectively to the “inhibitor gene” that suppresses the cellular growth phenomenon also.

Why the disparity of action, you might ask?

The Growth Switch

Well, you see eons of evolution between the bugs and us humans has helped evolve different mechanisms of coexistence. Some, as in E Coli have tendency to suppress the NFkB in the Urinary tract so that the E Coli can continue to do its monkey-business. Equally the Epstein Barr Virus or EBV does the same suppression in order to cause infectious mononucleosis. These mechanisms are defined by the claiming of advantage for survival for the bug. We on the other hand without a remedy an antibiotic (in E Coli case) are at its mercy.

The Kill Switch

On the other hand, the EBV can play a two-faced-Janus type of a drama where it can instead of inhibiting, start promoting the cellular gene that causes proliferation and there in lies the tragedy of diseases like nasopharyngeal cancer and the real baddy, Burkitts Lymphoma caused by the EBV. You can see the deviousness of this salesmanship cant you? Come in to sell something and ransack the place instead.

Now let us look at the SWOT analysis of this tiny speck within the tiny speck.

NFkB                         Strengths:

1. It is Ubiquitous in nature and in all living cells.
2. It has a direct link to the DNA.
3. It can promote or regress a cellular response.
4. It helps against infections
5. It causes diseases including cancer with sustained activity on promoter genes.

          Weakness:

1. It is susceptible to intervention.

           Opportunities  

     1.   Through research, one can activate it to bind with the inhibitor gene as in cancer.

                                   Threats

     1.   Unintended Consequences within the cellular mechanism and framework

Any signal that presages the need for an immune or inflammatory response and both are closely related cousins, by the way, the NFkB has the answer. It gets activated (chatty) then transfers itself to the nucleus (runny) and binds to one of two signaling genes (friendly) on the grand double-helical loop of our existence called the DNA.

Our immunity is based on a cascade of events that occur. But for any of those events to be initiated, the culprit responsible is our very own, NFkB. It is needed for various functions including, monocyte adhesion, macrophage recruiting, platelet activation and smooth muscle contraction, all necessary components to save us from the dread of an allergen, virus, bacterium and even mold.

Several studies are in progress to quiet this little critter. After all unchecked, it can cause significant and unabated inflammation as in Ulcerative Colitis, Crohn’s Disease, Autoimmune disorders; like lupus, and of course the scourge of humanity, cancer itself. But in passing let me throw this soft toss at my cardiology friends. NFkB is intimately involved with the induced inflammation from the lipolysaccharides, and the VLDL, LDL that promote atherosclerosis. Understanding of course that something other, like a bacterium, eg. Chlamydia can provoke the initiating event in the coronary blood vessel that starts the heartache.

In other cancers it can stifle the immune network by not reacting to the wayward cancer cell and allow the disease to flourish. Or it can maintain the inflammatory response which by its own attributes can liberate other factors that can promote various receptors on cells surfaces to signal the nucleus to start proliferating and proceed to a malignancy.

Few of the many Pathways that dictate cellular Growth

There are many transcription factors housed within the cell and an activated NFkB can “touch” their “sensitivity” and activate them to release their signals into the nucleus for cellular growth too. Cancer itself is mainly a process with unchecked signaling of the promoter genes of cell proliferation. These promotional events within the cell can be checked if a strong enough barrier of suppressor genes are also cohabiting the nucleus and are active. That would be like sitting in a Ferrari and pressing both the accelerator and the brakes. Who wins, depends on, who blinks!

I hope you can see the blinding fury of a myopic salesman. Can"t you?

And of course we can devise an Anti NFkB antibody and check out its presence in cancers and other tissues for posterity.

Red colored cells indicate cancer with NFkB activation

The moral of this story is not to let the salesman in!

Keep the Inflammation Out!

Diet: Eat healthy; vegetables and fruits.

Exercise: in Moderation.

Stress: Limit ~ since it jogs the immune system too.

Wash hands frequently especially before eating ~ but do not get paranoid with Purells.

Remember: "Cleanliness is next to Godliness."

References:

Perkins ND (January 2007). "Integrating cell-signalling pathways with NF-κB and IKK function". Nat. Rev. Mol. Cell Biol. 8 (1): 49–62.

Ghosh S, May MJ, Kopp EB (1998). "NF-κB and Rel proteins: evolutionarily conserved mediators of immune responses". Annu. Rev. Immunol. 16: 225–60.

Gilmore TD (1999). "The Rel/NF-κB signal transduction pathway: introduction". Oncogene 18 (49): 6842–4

Chandel NS, Trzyna WC, McClintock DS, Schumacker PT (July 2000). "Role of oxidants in NF-kappa B activation and TNF-alpha gene transcription induced by hypoxia and endotoxin". J Immunol 165 (2): 1013–1021.

Gilmore TD (2006). "Introduction to NF-κB: players, pathways, perspectives". Oncogene 25 (51): 6680–4

Karin M, Ben-Neriah Y (2000). "Phosphorylation meets ubiquitination: the control of NF-κB activity". Annu. Rev. Immunol. 18: 621–63.

Hayden MS, West AP, Ghosh S (October 2006). "NF-κB and the immune response". Oncogene 25 (51): 6758–80

ALCHEMY and EPIDEMIOLOGY

"Alchemy is the art of manipulating life, and consciousness in matter, to help it evolve, or to solve problems of inner disharmonies" ~Jean Dubuis

  

The other, hot and humid, day as I sat wishing the sun would quickly drown itself in the Pacific Ocean and cool the air off a bit, A thought came to me…

Why do apples fall from the tree?

Indeed why do they?

It could be that they get so ripe and heavy and unsupportable that the Newton’s defined gravitational pull brings them down. Or the birds alight on the branches and shake them off. Or the breezes swoop in and shake the branches to dislodge their burden. Or the farmers harvest them. Or maybe the worms eat at them and their larvae pupate inside making them heavier. Or maybe there is a botanical mechanism that pinches off the nutrient supply to the stalk that holds a ripe fruit.

Now if one were to be present at any of these events and records them, he or she would consider that as a cause and effect. Simple. You see, record and determine! Whichever was the observed event becomes the cause. But there is more to it when you start seeing other possible mechanisms and then the simplicity is no longer there. It becomes a complex argument. Which of these is the likely cause or are there many other mechanisms that are the cause of the apple falling from the tree? For instance the breeze only shook off the ripe apples but not the green ones, The farmer harvested only the ripe apples too, the animal lunged for the ripe ones too and the birds that sit atop an apple tree branch is unable to dislodge some of the ripe ones, yet the green ones fell to the ground. The conundrum is quite unnerving. Isn’t it?

Heady, wily, thought-provoking but at its very essence, the argument is worth a look.

That phase transition of thought into reality without supporting information becomes the alchemist’s Philosopher’s Stone. It suddenly turns from white to yellow and instead of silver it yields gold by the conjurations of the alchemist. There is where we are in our processes at present. In the rush to decision, in a rush to claiming the fame, in the rush to reaping the rewards, in the rush to immortality, the alchemist uses, that sprinkle of magic dust and what was once steel is now the much lusted over, gold.

The projections of the physicians, physicists, chemist glitterati are being discounted in glorious fashion because they have all fallen victim to the alchemy trap. Some have conjured, cajoled, manipulated and forced a squared peg into a round hole through the art of this magic. Some have done so unknowingly while others deliberately. This art form hurts us all. Unfortunately the peer-review that peers at these out of the box events seem to be taken in by the alchemy too and they, the peers, sign their names on the dotted lines. No one really thinks, except maybe to determine how they, themselves would use this new scientific information or its methodology to advance their own field of inquiry.

Read not to contradict and confute; nor to believe and take for granted; nor to find talk and discourse; but to weigh and consider. ~ Francis Bacon

The burgeoning science of Epidemiology has taken a front seat in medicine and we hear of “this causes that.” The other day, one “study” determined that Vitamin D was good for health and the very next day another stated, it wasn’t. One study stated that the length of the index finger was a risk factor for prostate cancer (all on the basis of a subjective survey), while another professed that earlobe crease was a risk factor for heart disease (from the days of yore). The newspaper and the media love to publish nonsense because they have now become a part of the problem. They are illiterate in judging the benefits of a study and parrot anything that is considered a “Study.”  Any one with good writing skills can now do the devil’s work.

Deciding the fate of many through limited observation

Epidemiology has a place in science. It is at best a correlative discipline, at its worst a terrible stitched together rag of lies. A good epidemiology study is one that would be a prospective, one, which would then be confirmed by basic science. If the correlation is determined then the cause has to be proofed out before subjecting the populace to the nonsense that currently pervades.

How this current form of “science” hurts us is by enabling behaviors that serve a purpose other than for the benefit of the individual. It provokes a fear of things, a sense of loss, a sense of meaninglessness in life. When confrontation and retractions become a daily discourse, belief itself is violated. “Throw some mud and something will stick.,” is the current mantra. A society so narcissistically tuned with subjugated belief in the provocative untruth, is ripe for inaction, lethargy and annihilation. No belief to guide, leads to no morals to comply with. And no morals, leads to a state of subjugated indifference.

In the name of Good Science, let us all think and do better to serve each other. We should learn from the past to advance the future with real progress.

Histories make men wise; poets witty; the mathematics subtile; natural philosophy deep; moral grave; logic and rhetoric able to contend. ~ Francis Bacon

HACKED

 "One good thing about music, when it hits you, you feel no pain." ~ Bob Marley

Listening to music, the only thought that comes to mind is the raw emotions of peace and tranquility. Of course it depends on the kind of music that is playing. But hear me out on this one for a moment.

Why does music change our being as it enters through the portals of our brain? How does it assimilate and recruit the neuronal cell mass within our brains to collectively enter into this lowered key of existence? But syncing billions of neurons into a coordinated step as in a dance to evoke emotional and physical behavior is a mystery that many neuroscientists have been working to solve. Some say it is hard-wired and others say that the individual cells are programmed to the cadence of a certain key. While others express the mathematical formula based on the octave and its 3^rd, 5^th and 7^th sine wave. The key of "A" vibrates at 110Hz and any frequency other than a multiple would be disharmonious. From Beethoven's Moonlight Sonata to the Arpeggios of J.S. Bach in Prelude to C Major the sea of sounds recruit our sense of wonder and capture our imagination. This recruitment phenomenon is not limited to the neurons alone, since the limb muscle cells also get secondarily recruited by the evoked potential from the brain cells to do their bidding, the whole human element eventually in gear. It is a cascade effect, touching, invoking, evoking and expressing the base pattern of a willingness to belong. A religion, if you will, of emotions expressed in the coordinated motion; Life!

"If music be the food of love, play on." ~ William Shakespeare

Now imagine that an old vinyl record is playing the beautiful symphony and someone drags the needle across the vinyl record. Imagine the grating sound that suddenly shuts down the blissful harmony and drags you back to reality.

Ah yes, that is where we live today, in that grating, caustic world of dissonance.

We are constantly being challenged by the grating noise. The news feed of the 24/7 outlets that must express news and then by virtue of their value proposition, create news just to keep our interest and the constant barrage of bad news emanating from all sources that surround us.

“The boyfriend killer!” the girlfriend killer!” “the abductor!” and the “child molester!” All are sensational stories of illicit human behavior. All such sensational stories gather and collate our desires, wrap them up in a crinkled bag of emotions and throw them out in the garbage everyday for us to, in a warped sort of a way, to yearn for more!

This has become our music!

This, then has become our reality!

We have been hacked and we don’t know it. The societal persona has changed from the house with an open door welcoming neighbors to one jammed with four bolts for security. Today the society rests on the prime of a primal thought; what next?

The real question then is how can we get “un-jacked” from this matrix? How can we resist the illusion of this horrible reality and redefine it the way it used to be, or better yet a way that could be better then the yesterdays and the yesteryear?

It would take a simple act…

Recognition.

Once we recognize that, that is where we are, the next step is to figure out what can be done about it.

Hack back into our brain with that, which creates a positive emotion in life like music, laughter, family and love. Things that some consider “corny.”

Remembering that it takes a hacker to hack into your personal liberty and steal from you what is yours. Hack back into yourself and change the domain password. Create a firewall with passwords encrypted with simplicity and beauty that the corrupted minds will not be able to decipher.

And live your life in peace and tranquility.

I am going to leave you with this beautiful rendering from Daniel Sierra to ponder upon.

http://vimeo.com/65475425

OSCILLATE from Daniel Sierra on Vimeo.

Degrees of Freedom

“Why are Docs afraid of the technological innovations?” he asked. There was some degree of defiance in the verbiage.

    That set me thinking. Are we as physicians afraid of innovation? Are we afraid that the smart-phones now have apps that help individuals take self responsibility? My immediate answer was “No, of course not! No doctor worth his salt would be afraid. From time immemorial, doctors have embraced innovative tools to help against maladies. Why should we be afraid?”

But then, it got me thinking.

“Prediction is very difficult, especially if it is about the future.” ~ Niels Bohr

     Using a portion to describe the whole is a monumental task. It is based on many assumptions. The largest one of these assumptions is the belief that every portion is identical to the whole. But nature is not like that. Is it? Even worms exposed to similar circumstances have different genomic structural activity. So to buy into a concept that has its main pillar of support made of fudge is not too firm a foundation to bank on. Is it?

     We are progressively evolving into the linear algorithms of Boolean Logic. If this, then that mind set. We are taking a sampling of the population and deriving methodologies to render therapies. Is that an advance in medicine? After all it is as all men and women inspired by mastering public health seem to determine that what’s good for the public interest is good for the individual. And now we are relegating those human inspired tools to the linear logic of machines. Yes, yes, they claim to have the fuzzy logic and the Artificial Intelligence of a rat or a mouse, or a monkey. But do these machines have the antero-lateral prefrontal cortex? If they don't, can we invoke a verisimilitude of the same in their machine - structured software driven un-empathic hard drives? 

Can we?

     Yet the larger argument diffuses the one above easily. Even the statisticians who develop these wonderful equations to satisfy societal issues consider the possibility of outliers in the field. Due deference is accorded to these few percentages of men and women that don’t fit the mold of the many. And even looking at the classic Bell curve, one finds that 95% of the “majority” nicely fits between the two bookends of 2 standard deviations. And each deviation amounts to roughly 34% on either side of the mean. So the populace in between the first and second deviation is roughly 14% on wither side and they obviously would have variances in their makeup with some discord to the mean populace, now wouldn’t they?

(Here x is the individual data, u (mu) is the population mean and n is the total number, all this results in (sigma) the standard deviation).

      Now given this degree of error even sampling formulas have allowed for some degree of freedom in the form of (N-1) rather than (N). Which basically means that even the statisticians realize there is some error associated with the formula and they further acknowledge that the sampling error albeit small still remains even when allowing for the (N-1) in the equation.

So when someone says that we as doctors are afraid of the algorithms defined by guidelines and mandates that define the best form of therapy for a patient, aren’t they missing something? When One of One becomes One of Many, is the treatment rendered appropriate?

Let me ask a question…

     A patient aged 44 comes for a physical examination. The ensuing examination is normal. The patient asks for a PSA test, because he has heard that it detects prostate cancer and since he has never had it before, he wants to stay on top of the “game.” The results of the PSA fall in the normal range at 2.0ng/L. But then he states that some difficulty with ejaculation after sex but it has resolved. What would you tell him? “Everything is okay?” “Your PSA is normal?” “Come back in a year?”

If you did bat it off based on the guidelines and the algorithms on the computer, what would be the consequences to the patient when a year later he was discovered to have advanced prostate cancer? Was the population-based scenario treatment was none better then quackery?

     Is there then some room in the robotic devices, the computer hard drives loaded with 1 and 0s that give the doctors the degrees of freedom to practice the art of medicine on a One on One basis? Or is that passé? 

From, "e Pluribus Unum" we are morphing into "Ex Uno Plures!" 

Just some food for thought!