Wednesday, July 25, 2007

Medicine and optimism

To be or not to be
This NY Times article was sent to a skeptical internet discussion group. It provides interesting insight into some challenging philosphical considerations regarding phsyciatric medicine and is food for thought when thinking about medicine and science in general.

Medicine, Constantly Redefined and Redefining Lives
By ELISSA ELY, M.D.

"About 15 years ago, I had a shy patient who ate nothing but white foods and
who assaulted anyone who entered her air space on the hospital ward. She was
mute but not uncommunicative, and with a little effort it was possible to
learn her language.

Some of her problem was her psychosis. Most of it was her mother, who was her
legal guardian, appointed by a court to monitor her medications. But the
mother was also convinced that psychiatric medications were poison; the
patient would go home on weekend passes and return with all her pills in
bottles and without a shred of sanity.

This continued for months. Her mother brought a notebook listing side effects
to each visit. She said the medication caused seizures, diabetes and heart
disease, though the studies at the time showed none of these side effects
associated with the drug we were giving. We thought she was sadistic, intent
on standing between her daughter and independence. She thought we were evil
experimentalists. The patient herself dreaded controversy and wished,
wistfully, to please everyone.

Finally, we petitioned to remove the mother as guardian. It was controversial,
against nature, to question a family member's competency or guidance. When we
met before a judge, both sides were filled with strong emotion. But we were
also filled with strong data.

I remember looking at the mother across the courtroom while testifying about
the hazardous nature of her beliefs and their effects on the patient's mental
state and future. Her size had changed. When she visited the hospital,
something vibratory and angry about her made her seem to swell, so that
neither her daughter nor I could look her in the eye. From the secure height
of the witness box, though, she seemed to be shrinking - an ineffectual old
woman, laboring under false beliefs, growing smaller as these beliefs were
exposed one by one.

The judge listened without expression and took the case under consideration.
We had no doubt about the power of our presentation. Within a week he had
ruled in our favor. The new guardian did not oppose our antipsychotic drug,
and the patient flourished. It was like time-lapse photography: in what seemed
like only a day, she smiled, spoke, became lucid, joined a day program, began
overnights in a residential house and was discharged.

We were full of public satisfaction, and private righteousness. Some aspects
of psychiatry are clear-cut; they can be counted on. There might be no proof
of the existence of Freud's ego and id. But antipsychotic medications treat
psychosis - this can be proven - and the patient's life was going to be better
for taking them.

It was, too. For a while, she sent happy, mostly intelligible letters from her
residential house. The letters became holiday cards, and eventually, in the
fullness of her world, they stopped. Someone else told me, years later, that
she had developed diabetes and required insulin. The research by that time was
clear: there was no doubt whatsoever of an association between her
antipsychotic and diabetes and other metabolic problems. The studies had been
confirmed again and again.

Kierkegaard wrote that we understand backward but live forward. Politicians
say - using a tense so passive that it slinks out of the room before it can be
noticed - "Mistakes were made."

The facts we had then were incomplete, even if we didn't know it at the time.
We were right but we were wrong, innocent but at fault, acting in good faith
with bad results. The ground beneath professional feet should grow firmer over
time - one ought to feel more certain of what one knows. But the more I know,
the more I am afraid."

This story is interesting on a few levels:

It is reminiscent of other "state vs guardian" under age face offs like the Abraham Cherrix or Katie Wernecke cases where the legal system wrestled with the concept of informed choice and the meaning of responsible parental guidance among other things (such as what constitutes acceptable medical treatment?). Very broad grey areas of meaning an intent, especially in older children makes it very difficult to navigate on generic terms- what precedence should be used? The interests of the child from the courts or the parents point of view? Is it a case by case issue? The age old canard of medical "free choice" can be heard rumbling in the background; but does take a back seat to a bigger issue here. (Incidentally, with the increasing societal awareness of possible animal abuse/human abuse correlations, along with expanding knowledge of veterinary forensic science, the guardians leeway for "proper and acceptable care" of animals may become more limited or at least better defined- certainly could have obligatory implications for vets).

Interestingly, today I was reading the history of the Apollo One tragedy . Although on a different scale, it seems to resonate with Dr Elys' story. It manages to describe through tragedy a larger point of view reflecting a way of thinking, of achieving goals through critical analysis, expanded understanding, and knowledge. So maybe "mistake" may not be the best descriptor of Dr Elys story given a larger context- though the legal realm (i.e.; often an "answer the question- yes/no" scenario) might describe it this way. Scientific evidence can be exceptionally difficult to explain and interpret and inappropriate assumptions can be made even by "experts". On the other hand, if you take a more strict approach (i.e.; take away historical context, balanced intent, past knowledge levels) you could almost call Dr Elys' experience an example of gross neglect and abuse of power.


Though philosophy of science discussions often revolve around fascinating "what is true scientific observation and what does it mean?" teleological knots, the scientific grunt work goes on and some times manages to improve the human condition (i.e.; Norman Borlaug).

In this vein, phsycology is now probing huge unknown mental territories in new ways. Neuroscience and neuropshycology are shedding light on cognition, brain region dynamics, and neurological functional parameters unimagined a few short years ago and promising new treatments and therapeutic modalities may loom close.


Though Dr Elys' angst is understandable- most doctors (or anybody for that matter), are often tormented by "what ifs", "I thought", or "if only"s', she seems to take a rather pessimistic view of what can be known. Dr Ely mentions Kierkegaard and seems to (at least implicitly) concur with his "subjectivity is reality" form of existentialism by expressing doubt regarding the firmament of medicines knowledge base; a "the more you know, the less you know" restrictive perspective. Many would disagree and posit a "the more you know, the more you need to re-know, then the more you need to know" expansive perspective. Perhaps neuroscience will bring more empirical insight into some of these apparently metaphysical matters.


At any rate, if Dr Elys' goal is to remind us that medicine is a sometimes equivocal and uncertain affair- all well and good. But where Dr Ely seems to give way to fear when faced with doubt, change, and the unknown, others might be humbled, excited, and awed.

Monday, July 23, 2007

Glimpsing the Origin of life

A look at an interesting theory

Theories regarding the ancient elemental substances that gave rise to the origin of life as we know it remain clouded in the shrouded mystery of time. Even the infinite evolutionary permutations and adaptation of life itself have, as one effect of success, brushed away many of the “footprints” that lead back to this far off ancient epoch.


Even so, here and there, scattered throughout the interactive biochemical and physiological reactions of the myriads of structural and functional elements, there are hints and glimpses of just how present life may have once been like. In fact, some of these clues may provide the beginnings of a general theory, of not just evolutionary development, but of the foundation of possible mechanisms that allowed for life to become life.


Realizing that the quintessential core information source of present life; DNA and its associated complex protein creations are far too complex and co-dependent to have provided the first building blocks for life, scientists have delved deeper into the biochemical cauldron for simpler structures that may have opened the doors to life.


These structures or molecular compounds would need to fulfill a primal requirement in order to be considered a viable precursor. It would have to be able to self replicate itself- thread a line of information through time- in some sustainable fashion. The implications here are huge. This simple, yet possibly improbable event would open the gateway to the process of evolutionary dynamics if enough time could pass.


Obviously, one primary candidate which may fulfill this primal role is the RNA molecule. This compound has a variety of blended functions that are DNA and functional protein “like” realizing replicating reactions, information transfer roles, and protein synthesis functions that opens the doors to theories that posit RNA as that primal replicator.


Although an original replicator theory is a very attractive possibility, it does present challenges among which is how such a relatively large molecule could have formed before evolutionary processes began as well as managing to survive in a rich organic primordial soup without being smothered amongst a plethora of chemical reaction. Research continues down this theoretical path.


However, there are other theories that are looking deeper beyond the RNA molecule for a yet simpler and possibly more plausible mechanism. These theories probe the molecular soup of what might have been a primordial earth for chemical reactions with certain life-like properties. These are known as a small molecule or metabolic approach to life origins.


These small molecule theories posit that life can be defined not in a genetic context but by describing it as a thermodynamic phenomenon. Carl Sagan noted that life could be stated as “a localized region that increases in order (decreases in entropy) through cycles driven by an energy flow.”


These approaches may provide a theoretical underpinning to a multiple origins theory for life origins and may provide for a far less improbable scenario for its beginnings. The natural constraints required for these small molecule theories to work are less complex than those necessary for RNA first approaches.


According to Robert Shapiro there are five basic conditions that would allow for the possibility of small molecular life to “congeal” and open the way for more complex forms. These conditions include:



  1. A boundary is needed to separate life from nonlife. Living cells convert energy or radiation to heat. The released heat increases the entropy of the environment, compensating for the decrease in living systems. The boundary maintains this division of the world into pockets of life and the nonliving environment in which they must sustain themselves.

  2. An energy source is needed to drive the organization process. …the transformations [producing energy] that are involved are called redox reactions. They entail the transfer of electrons from an electron rich (or reduced) substance to an electron poor (or oxidized) one.

  3. A coupling mechanism must link the release of energy to the organization process that produces and sustains life. Everyday, in our own cells, each of us degrades ponds of ATP. The energy released by this reaction serves to drive the processes necessary for our biochemistry that would otherwise proceed too slowly or not at all. Linkage is achieved when the reactions share a common intermediate, and the process is sped up by the intervention of an enzyme. One assumption of the small molecule approach is that coupled reactions and primitive catalysts sufficient to get life started exist in nature.

  4. A chemical network must be formed to permit adaptation and evolution. Imagine, for example, that an energetically favorable redox reaction of a mineral drives the conversion of an organic chemical A, to another one, B, within a compartment. I call this key transformation a driver reaction, because it serves as the engine that mobilizes the organization process. If B simply reconverts back to A or escapes from the compartment, we would not have a path that leads to increased organization. In contrast, if a multi-step chemical pathway-say, B to C to D to A- reconverts B to A, then the steps in that circular process (or cycle) would be favored to continue operating because they replenish the supply of A, allowing the continued useful discharge of energy by the mineral reaction.

  5. The network must grow and reproduce.”


To date, little validating research has been done to confirm this attractive theory there are some tantalizing studies that support its plausibility. The focus may be to seek out an example of the previously mentioned “driver reaction” which may reveal the theorized connection between this chemistry and sustainability, eventually leading to evolutionary mechanisms.


In essence, origin of life research is still in its infancy, and it is likely many new ideas and concepts will present themselves in a fascinating quest to uncover life’s most basic beginnings.


Ref: Shapiro, Robert. A simpler origin for life.Scientific American 2007. Vol 296, No6

MMR and psuedoscience

Many of today’s fringe belief based groups like those promulgating Intelligent Design, HIV & germ theory denialism, or the anti-MMR vaccine crowd have long attempted to wrap themselves with a cloak of scientific legitimacy.


That these attempts have been repeatedly exposed for the false claims and misrepresentations that they are consistently falls on the deaf ears of many “believers”- a trait rather typical of the pseudoscientific mindset. It has long become apparent these groups have agendas that do not include honest and authentic scientific inquiry.


In this age of instant media coverage and increasingly competitive news markets it seems more and more difficult to find truly balanced, well researched, and thoughtful news pieces regarding important issues of the day. Sound bits, noise, and color flood media outlets as available news information seems to dumb down to basic instinctual reactions or short lived emotional fixes. Whether this is a problem of the media or their response to consumer demand can be argued, but that this phenomenon smothers clear thinking and paused reflection is increasingly difficult to argue against.


So it is that the recent MMR article debacle at the Observer (UK) comes immediately to mind. It is well worth the effort to chase the links and follow the sequence of events and Ben Goldacres (Bad Science) response to this classic example of media misrepresenting science. Goldacre puts it succinctly after a well done critique:


“I am pretty jaded and sceptical, but this front page story has completely stunned and astonished me. The misrepresentations and errors went way beyond simply misunderstanding the science, and after digging right to the bottom of it all, knowing what I know now, I have never resorted to hyperbole before, but I can honestly say: this episode has changed the way I read newspapers.”


This incident is a good example of the potential damage a well placed, yet very misguided newspaper headline and article can do. Though I am not familiar with the Observer or its qualities as a media outlet, this type of reporting certainly does not impress.


What ever the case may be, this whole event demonstrates the effort and care it takes to respond and counteract pseudoscience in general, and highlights the urgent need to address the educational shortfalls (i.e.; in science) of the populace that give opportunity for quackery to flower beyond reason.

Friday, July 20, 2007

A way of thinking

Thoughts on science and society


Much more than a strict methodological formula or inflexible algorithm, the process of scientific discovery uses a uniquely human form of cognitive reasoning. It is a form of inquiry that pools together often seemingly unrelated perspectives and reveals profound “truisms” beyond cultural and societal constraints regarding the natural world.


Though, unlike other human activities (i.e.; song, dance, and culture) it is probably much more difficult for scientific inquiry to take root and flower in a given society. Contrary to what many might assume, it is not a particularly “western” phenomenon. Several cultures and societies gave rise to the elements necessary allowing for a scientific form of inquiry.


These conditions, however can be fleeting and temporary as Susan Haak (Defending Science-within reason) notes “As Glasglow reminds us, Arab astronomy, mathematics, and chemistry were once unrivalled; but the rise, early in the second millennium, of Taqlid, the Islamic doctrine that there are no truths beyond those revealed in the Koran, scientists and scholars were banished. And so, rather than growing and flourishing, Arab science declined- leaving its footprints on our language, however, from “alkali” to “zenith”. The ancient Chinese…invented gunpowder and the compass, and were great navigators- until in the fifteenth century they decided that nothing beyond the celestial empire was worthy of discovery, and burnt their great ships just before Columbus set forth with his tiny flotilla to discover a New World.”


Indeed, these histories threaten to repeat themselves as todays' societies struggle with many fears- whether or not they are legitimate- regarding scientific inquiry and often recoil from disturbing realities and philosophical implications. For example, the cost of research might be exorbitant compared to other demands, technological advances (cloning, genomics, and fetal research) force a re-evaluation of deeply held beliefs, and the lack of science education can lead to a profound mistrust of this way of thinking.


Further, science does seem to have limits in answering critical questions with respect to a variety of human endeavors such as politics, literature, entertainment, law, and logic. Additionally, there are a multitude of scientific questions science can not answer or has even thought of asking. Haak states “…we humans have limited intellectual and other resources: limited intellectual integrity, respect for evidence; limited imaginative powers; limited capacity to reason; and limited sensory reach.”


On the other hand there is reason to be optimistic with what this form of inquiry can offer. It should be possible to follow a dream, ride the ebb and flow of emotion; that is, live a fully human life and pursue the realities of true inquiry. Haak notes “…one of the most remarkable things about the natural sciences has been the ways they have found to overcome human limitations: instruments of every kind, extending innate human powers of observation; the calculus, statistics, computers, extending innate human powers of reasoning; metaphors, analogies, linguistic innovations, extending innate human powers of imagination.”


Many so called metaphysical questions may never have answers, but there might be a place where some of these questions may eventually blend with those of the natural world. Again Haak notes “…there is no sharp line between cosmological and metaphysical questions; nor are there very clear criteria for identifying and individualizing questions. Thinking of how cosmologists first transmuted, and then at least partially answered, the metaphysicians’ question, ‘Why is there something rather than nothing?’ when they developed their account of the accretion of matter, we might speculate that, if physicists were to find the ultimate laws, the demand for an explanation of those laws might be eventually transmuted into a kindred, yet different and more answerable, question.”


This way of thinking; that a combination of probing inquiry and honest realism might be implemented in a way to help resolve, or at least honestly consider solutions to a variety of human issues and problems heretofore assumed to be non science related may open new vistas of meaningful discovery.


Ben Goldacre probes this idea in an interesting post relating that scientific inquiry may indeed prove useful for effectively evaluating different possible solutions to societal problems. He notes “There is no sense in which I am a hardliner on trials, and I’m totally down with the idea that there can be many different kinds of evidence, but one thing has always puzzled me: in these days of “evidence based thinking” in Whitehall, why don’t we do randomised controlled trials on social policy?”


In a similar vein Haak states that “The social sciences, of course insofar as they concern themselves with local and contingent social roles, rules, and institutions, have a much more markedly historical aspect than the natural sciences. And that the historical contingencies of human societies might eventually be derivable from completely universal laws of nature seems, to put it mildly, much farther-fetched than the idea that cosmological events such as the big bang might be. Even if there are laws governing the universal aspects of human nature variously expressed in this society or that, and even if such laws were known, there would remain not only a vast array of details to be discovered, not only the ramifications of self-fulfilling (or self-undermining) predictions, but also the permanently open possibility of new manifestations of those laws in new social arrangements. So, though thus far the social sciences seem to lag far behind the natural sciences, the scope for future spurts and breakthroughs seems enormous, and the future prospects limited only by the possibility of the extinction of human societies.”


This is indeed food for thought especially considering that old societal paradigms may not provide the stable structure needed to sustain humanities present expansion into previously unexplored philosophical, mental, and physical realms.


Ref:

Haak, Susan. Defending science- within reason. Prometheus books. New York. 2003

Thursday, July 19, 2007

Wednesday, July 18, 2007

CAM and higher education


A tragedy in the making?
During the course of clinical practice, veterinarians (and physicians) often encounter a variety of circumstances that affect the daily course of administrating care to a patient. They can either be a hindrance or a help towards the goal of attaining the most appropriate medical treatment for a given individual.

For example, refusing a blood transfusion or declining blood work can greatly impede ones ability to treat or diagnose whereas people jumping in line to donate an organ opens the doors to previously impossible therapies. Such is the way of clinical practice as the doctor blends his or her experience, current available science based knowledge, and the patients (or owners) perspectives in order to come up with a “do-able” strategy. These approaches vary depending upon the balance between these spheres of influence and often translate into unique therapeutic approaches. The ultimate goal is to find an effective balance that is heavily tempered with the hammer of scientific methodology.


In other words, even though an elected therapy may vary in some way depending upon a given situation, it needs to “pass muster” so to speak. It needs to demonstrate a level of effectiveness, plausibility, and repeatability that results from steady and rigorous inquiry from a serious- admittedly imperfect- community of humans involved in an intense endeavor; the search for reality based solutions.


This has been the responsibility society has given to the medical community, especially in the last century. Though the nature of healing may have a seemingly infinite set of variable influences and built in uncertainties, it has been wisely placed under the guiding light of methodologies that allows for consistent and tangible results.


Herein lays the growing concern when faced with a set of practices that walk away from these hard won lessons regarding healing. Though science is not a cult, religion, or some particular “post-modern” version of reality there are those who think that it is one or all of these things. Due either to misunderstandings, misrepresentations, and mostly, a lack of adequate science education many people falsely compare the hard won knowledge of modern medicine equally with archaic and implausible modalities such as homeopathy, the five elements, and most of chiropractic theory.


The alarms of reason and truth should be sounding all around the halls of higher education as these types of belief based and unreasonable systems gain a foothold within the realm of hard won legitimacy- without having any!


Dr RW discusses this very concern regarding the uncritical teaching of alternative therapies in US medical schools noting the alarming trend towards incorporating Complementary and Alternative Medicine (CAM) courses into their regular curricula. Are these courses being critically examined for plausibility and efficacy? The unfortunate answer is no! Sampson (University School of Medicine, California) cites in a 2001 study:


“Advocacy and non-critical assessment are the approaches currently taken by most U.S. medical schools in their courses covering what is commonly called "complementary and alternative medicine" (CAM). CAM therapies are anomalous practices for which claims of efficacy are either unproved or disproved. The author's research indicates that most medical schools do not present CAM material in a form that encourages critiques and analyses of these claims. He presents the reasons for the unwarranted acceptance of CAM. These include the CAM movement's attempt to alter standards of evaluating therapies. A survey of CAM curricula in U.S. medical schools in 1995-1997 showed that of 56 course offerings related to CAM, only four were oriented to criticism. The author's course at Stanford University School of Medicine approaches CAM with the skepticism and critical thinking appropriate for unproven therapies. The author concludes by calling on all medical schools to include in their curricula methods to analyze and assess critically the content validity of CAM claims.”


Another recent 2007 survey reviewing preclinical students at Georgetown University School of Medicine reflects a possible receptivity to CAM and illustrates that science based education and critical thinking skills may be lacking in earlier formal education:


Interest in and enthusiasm about CAM modalities was high in this sample; personal experience was much less prevalent. Students were in favor of CAM training in the curriculum to the extent that they could provide advice to patients; the largest proportions of the sample planned to endorse, refer patients for, or provide 8 of the 15 modalities surveyed in their future practice.”


This 2002 survey explored the apparent lack of familiarity in US medical schools of CAM and the disconcerting assumption that these modalities are effective therapies:

“A wide variety of topics are being taught in U.S. medical schools under the umbrella of CAM. For the most part, the instruction appears to be founded on the assumption that unconventional therapies are effective, but little scientific evidence is offered. This approach is questionable, especially since mainstream medicine owes much of its success to a foundation of established scientific principles.”

Another eye-opening reason to be concerned about the infiltration of uncritical thinking and associated CAM modalities into medical education is the example of the insidious growth of CAM in the nursing profession as described by Sandy Szwarc.


“…it is also important that the public understand what is happening and that we hear the voices of nurses who are concerned about the growing adoption into nursing practice of alternative modalities that have no scientifically valid theoretical underpinnings or proven medical efficacy.”


Together, these observations reflect important warning signs the medical community needs to take seriously if the foundation of a reality based/critical thinking education is to continue to hold its proper role as the gateway to effective modern medicine.

Tuesday, July 17, 2007

Those gut feelings….

The foundation of a primal self


There is a functional region deep within the core of the mammalian (and possibly most vertebrate) brains that may give rise one of the most basic forms of awareness that has been described as the primal self. This is an area where a variety of sensory inputs and reactionary responses are blended to create a deep, visceral sense of self.


In humans, peeling away the layered complexities of higher cognitive forms of consciousness eventually reveals a primordial self awareness a step above simply reactive neural responses. Based on the precursors of emotions these responses are integrated with sensory inputs to create “intent”, that is a proactive disposition. Jaak Pankepp (Affective Neuroscience) notes “The rudiments of consciousness were probably built upon neural systems that symbolize biological values- the basic motivational and emotional systems of the brain that inform organisms how they are faring in the game of survival.”


These neural networks are concentrated in the primitive midline brainstem regions, near the ventricles, and extend into critical areas of the limbic system. Where these networks converge could be thought of as the source from where core feelings of self arise. This is a core self more profound than a higher self- it is that gut awareness of body.


Among the more dense and ancient midbrain neural convergences, the periaqueductal gray region (PAG) is rich in visceral sensations that stimulate behavioral emotional responses. The PAG also has a multitude of connections to other brain regions that allows other brain/mind (i.e.; other levels of consciousness) to coordinate with emotional responses. Interestingly, when this area is damaged in animals, they lose their sense of conscious “presence” with the world around them.


The PAG is strategically located close to areas that integrate vision, touch, and hearing- a region known as the four twins (the four protuberances along the back of the brainstem identified as the superior and inferior colliculi) as well as other motor regions. The general effect is an integration of internal sensory and motor “mapping” of the body providing appropriate emotionally tagged responses to external stimuli.


It is this functional interaction that provides the dynamic basis for primordial gut awareness. Pankepp concludes “These closely integrated areas appear to neuro-symbolically represent the organism as a coherent living creature and may constitute a core SELF for each organism- a Simple Ego-type Life Force, which provides an archetypal homuncular form, a primal soul if you will- upon which innumerable brain complexities were built.”



Ref:

Carter, Rita. Exploring consciousness. Univ of CA press. California.2002.

Panksepp, Jaak. Affective neuroscience: the foundations of human and animal evolution. Oxford univ press. New York. 1998.

Monday, July 16, 2007

Feynman diagrams




Grasping the many strange and often counter intuitive phenomena that comprise “normal” quantum phenomena is a daunting task for many non-physicists. It takes time, persistence, and careful consideration to visualize these fascinating concepts-but when you do the rewards are worth the effort.


So it is that when an exceptional description or concise, easy to understand representation of quantum theory comes along it is immensely appreciated. Among the more difficult quantum level events to grasp are the various force/particle interactions, their relationship to virtual particles, and the unconventional use of space time that allows for the unfolding of a beautiful interplay of interactions.


If many quantum features such as granular matter, uncertainty, and the constant annihilation/creation of particles can be visualized, a much clearer understanding of larger physical concepts can be attained. Learning about the nature of how these subatomic particles interact and understanding that these are events of the very small can help one avoid the pitfalls of confusing these phenomena with more mundane esoteric beliefs (i.e.; quantum consciousness as alternative medicine describes it). The Feynman diagrams attain just this kind of connection to natural events.


As Kenneth Ford (The Quantum World) notes “Richard Feynman invented a method for diagramming events in the subatomic world that is a great aid to visualizing what is going on there. In particular, these ‘Feynman diagrams’ reveal what we think is ‘really’ happening when a force carrier gets exchanged between two other particles, accounting for an interaction between them.” He adds “A Feynman diagram is a miniature space time map.” They could be considered shorthand science.jrank.org/pages/2699/Feynman-Diagrams.html outlining the calculations depicting electromagnetic and weak interactions between particles.


In essence, these diagrams provide a visual glimpse into this strange world while combining a variety of ideas into one dynamic representation. Ford clarifies “In relativity theory, an ‘event’ is something that happens at a particular space time point- that is, at a point in space and at an instant of time….In the particle world, events seem to occur at exact space time points, not spread over space and not spread over time. Indeed, experiments indicate that everything that happens in the subatomic world happens ultimately because of little explosive events at space time points-events, moreover, in which nothing survives. What comes into this point is different from what leaves it.”


hyperphysics


The hyperphysics web site details the diagrams as follows “The time axis points upward and the space axis move to the right. Particles are represented by lines with arrows to denote the direction of their travel, with antiparticles having their arrows reversed. Virtual particles are represented by wavy or broken lines and have no arrows. All electromagnetic interactions can be described with combinations of primitive diagrams like this one.”



hyperphysics


These diagrams reveal two central and critical qualities that define quantum interactions. The first is the fact that where the lines meet describe an interaction in space time called a vertex. Ford notes “Here is the stunning generality that physicists now believe to be true. Every interaction in the world results ultimately from the emission and absorption of bosons (the force carriers) by leptons and quarks at space time points. Three-prong vertices's lie at the heart of every interaction.”


The second quality involves a fascinating reality. Ford elucidates “…the interaction event is a truly catastrophic event in which every particle is either annihilated or created…The electron flying upward to the left in the figure [above] cannot be said to be the same as the electron that entered from the lower left. They are identical, because they are both electrons, but saying that the one leaving is the same as the one that arrived has no meaning.”


Another rather amazing fact about this quantum world is how particles essentially move independent of time- anti-particles could be looked at as a particle moving backward through time. Again Ford explains “To think of this process proceeding forward in time, you could again imagine a horizontal ruler moved slowly upward [see first two illustrations below]...the arrows are labels…Their purpose is to tell whether the line is that of a particle or an anti-particle. So the line on the right with a downward-pointing arrow represents a positron moving forward in time- that is, upward in the diagram. But…the forward in time positron is equivalent to a backward in time electron…An electron comes along from the left, moving forward in time, emits photons…and then reverses its course through time. Strange but true. Wheeler and Feynman showed that the descriptions in terms of a forward in time and a backward in time electron are both ‘correct’ because they are mathematically equivalent and indistinguishable.”


The Feynman diagrams shed light on these peculiar subatomic interactions and help reduce some of the confusion in other areas of quantum phenomena .They provide the basis for an improved view of a profoundly mysterious realm. In addition, the foundational concepts that gave rise to these diagrams provide the basis for formulating a complementary- yet alternate description (Feynman’s sum over histories description of quantum phenomena) of particle/wavelength behavior that diminishes, to some degree, the confusion caused by the wavelength description of events at this level of reality.




Ref: Ford, Kenneth. The quantum world. Harvard univ press. Mass. 2004

Sunday, July 15, 2007

The southpaws’ dilemma

Left-handedness in a world of “right”

Even as recently as in my childhood, the left-hander or “southpaw” had an implicit negative social connotation; a “sub” status of sorts. Teachers, parents, and even religious advisers openly discouraged left-handedness, with varying degrees of success. The reasons for these suppressive pressures against left-handedness were never made clear.


Indeed, the quality of left-handedness has been associated with all types of negative human social behaviors. These include decreased mental capacity to associations with hygienic standards and demonic connections. There have even been suggestions of left-handedness being correlated with shortened life-spans and other behavioral anomalies (i.e.; dyslexia and psychosis).


Even today, with our expanded knowledge of brain functionality and much wider acceptance of the left-handed individual, there remains a palpable impression that the ghostly negative stigma still permeates, at some level, our general societal consciousness.


That the quality of left or right handedness is essentially a function of brain hemisphere interaction, genetic influence, varying and sometimes competing cognitive abilities (i.e.; language versus spatial skills) all interacting together under the sway of human cultural pressures opens the doors to a fascinating and nuanced understanding of left-right handed phenomena. Understanding these complex interactions may help those of us “afflicted” with left-handedness comprehend why this quality may have been so shunned- and perhaps decrease the ill will some might still hold against their teachers or parents.


Studies in comparative brain structure are beginning to reveal that the human brain, instead of evolving through some wholesale structural change via systems “add-ons” or massive re-wirings, is in fact the result of general systematic re-organizations, elaborations or reductions of existing structures, and proportional changes in existing connections.


Among the bubbling hominid evolutionary pressures, developing language and other human qualities played a large role in defining many general socio-cultural elements. Somewhere around 90% of humans depend on the left side of the brain for speech and the same number use the right hand for writing- also a generally left hemisphere function. Interestingly, the right hemisphere has predominant functions related to recognizing faces, understanding spatial relationships, and responding to emotional cues.


What is interesting here is that there is a population of individuals where the hemispheric influences are less clear- left handers and mixed-handers for instance. Theories abound, often connecting these observations to abnormalities, diseases, or handicaps. There are some observations supporting this concept to some extent. Early brain injuries do increase the probability of left-handedness; hence the observed increase with left handedness and mentally handicapped individuals. However, other explanations are needed in light of the fact that there are any numbers of normal and exceptionally gifted left-handers. Add to this the fact that left-handedness occurs naturally in about half of the populations of our closest primate relatives, and the need for broader theories becomes evident.


Marian Annett notes “Handedness in all species with hand and paw preferences, including humans, may result from chance differences between the two sides of the body that arise during early growth. In most humans an additional factor gives a slight advantage to the left hemisphere over the right one. This is sufficient to displace the chance distribution in a dextral direction.”


Known as the “right-shift principle”, Annett describes a Menedelian approach that may provide a better understanding of "handedness". This theory suggests a gene based concept as the foundation to this “dextral direction” where a combination of a dominant gene that increases selective bias for right-handedness and a recessive allele giving to no bias on either side exist work together to reflect the observed human "handedness" patterns.


Annett adds “The link between brain specialization and handedness could thus depend on a factor (the rs+ allele) that give the left hemisphere an advantage for speech and incidentally increases the chances of right-handedness. Those who do not carry the gene have equal chances of developing speech in either hemisphere , and perhaps both; they should be equally often left- and right-handed for skill, but cultural pressures to use the right hand would make more right- than left- handed.”


This obviously begs the question as to why then, if this gene favors speech, hasn’t it spread throughout the population relegating other options to the dust bin of extinction? The reason may have something to do with some variant of the evolutionary stable strategy theory. Though a bit of an extreme example, consider the increased resistance to malaria in heterozygous individuals and the invariably associated balance with those unfortunate homozygous who suffer from sickle cell anemia.


Annett explains “Perhaps the gene carries disadvantages as well as advantages, because it works by handicapping the right hemisphere. The estimates of genotype proportions suggest that there might be advantages for those with one copy, in comparison with those with no copies and those with two copies.” In other words, there seems to be disadvantages to both end of the “handedness” phenomena, and a blend of brain hemisphere function may be most efficacious, even if it appears right-handers predominate.


These findings add color and nuance to the complexity and function of the human brain, and at the same time, reveal how immersed we are within a sea of vast evolutionary influences everywhere we look.


Ref: Annett, Marian. The brain and left-handedness.Human evolution 9th ed.Cambridge university press, UK. 2005. pg122

Thursday, July 12, 2007

Animal supplement sales

Huge gains/scant evidence

A recent headline article in a veterinary news source trumpets the large gains in sales animal supplement manufacturers have been experiencing the last several years. The article states that “…animal supplements saw double digit increases- up to 35 percent and 40 percent. Several factors fueled the growth, consumer demand among them.” Quoting Robert Devlin, veterinary products marketing manager at Nutramax Laboratories, it adds “There’s a growing awareness and acceptance of complementary medicine. It’s becoming more mainstream.” If true, this is sad news indeed.


The article goes on to state “Today, science sells. Companies stress their ingredients’ purity, independent testing, and dedication to quality control.” In fact, as it goes through a description of several companies and their products, quality control is emphasized just as much if not more than references to claims of efficacy.


Though this seems like a small matter, it raises a red flag. Questions of quality control have long been a problem plaguing the nutritional supplement industries. The fact that it is mentioned so frequently here is a small indicator that it remains a problem manufacturers are still struggling with- at least in the eyes of consumers as companies like consumerlabs continue to reveal some big deficiencies in ingredient label claims. If this basic requirement isn’t being fulfilled by some in the industry, those that do strive for high standards in manufacturing are affected by association.


Another, more concerning problem though goes deeper and entails the use of science as a marketing tool. “Science sells” or at least the veneer of science, and it is sprinkled throughout the statements of many of the featured industry representatives. Companies such as Nutramx, Vetri-science Laboratories, GLC Direct, Petlabs 360, and Rx Vitamins for Pets are among those propping the importance of “quality control”. Nutramax and GLC add to the tenor of scientific legitimacy by mentioning a variety of limited studies that seem to support evidence of efficacy. Interestingly, though they tout a variety of specialty products designed for a variety of immune disorders, liver, cognitive, skin, and behavioral maladies most of these studies refer to the old familiar joint supplement products, glucosamine and condroitin.


Indeed, though the mention of these studies may seem impressive at first glance, they are far less so upon closer scrutiny. Vetri-science “announced results of a three year study on hounds at Washington State. The results of the study support that Glyco-flex 111 may reduce the severity of cartilage breakdown and synovitis and help normalize joint function in dogs with stifle joints affected by osteoarthritis.”


GLC Direct describes a study where “a private practitioner studies 10 competitive hunter/jumpers over eight years to determine the effect of oral supplementation on the frequency of therapeutic injections in joints. The frequency of…injections decreased from a mean of 1.7 injections a year prior to glucosamine/chondrotoin supplementation to 0.85 per year.”


Nutramax “has a 16 page booklet of abstract of clinical studies of the products [Cosequin] effectiveness on its website.” The company emphasizes that they follow manufacturing purity standards similar to those used by the pharmaceutical industry.


All good and well, but a closer look raises some questions. For example, the study Vetri-science refers to is not directly mentioned as part of the North American Veterinary Conference Proceedings, although there was a lecture by Dr John Innes titled “Evidence for nutraceuticals in osteoarthritis- cutting through the sales platter.” Though the transcript to this lecture is not immediately available, Dr. Innes et al, have published a review in the Critical Reviews in Food Science and Nutrition in 2005 titled “ Nutraceutical therapies for degenerative joint diseases: a critical review."


Here, the authors describe the current state of knowledge regarding nutraceuticals and highlight the need for further research “so that current therapy and future treatments may be better focused.” A related study done in 2007 evaluated the current state of evidence for nutraceutical supplementation and osteoarthritis and echoed the need for further study. There was work done at Washington State University regarding a dietary supplement and canine osteoarthritis, but there are no readily available published reports or abstracts as of yet. At any rate, that the product used in the study “may reduce… and help” hardly constitutes the evidence needed to promulgate it as heavily as it is for osteoarthritis.


The GLC Direct study is small, offering little detail as to the study parameters. There may be a variety of confounding factors affecting these results and at any rate is only more of an anecdotal mention in the article.


The broad abstract described by Nutramax provides more information and an accumulation of data. Even these studies, though, are not the convincing mass of positive evidence one would think. A numbers of these abstracts deal only with the safety of their product. One study evaluates possible interactions of several substances, including Cosequin, with thyroid hormone levels. A variety of studies do discuss possible positive conclusions related to product efficacy in canines and equines that need to be weighed and analyzed for quality and significance.


A search of the Pubmed, Cochrane, and Relemed data bases reveal limited animal related published efficacy studies and reviews. Those that exist offer a mixed bag of findings. Essentially, they are negative or indicate there is not enough information gathered as of to yet make a solid conclusion.


An interesting 2007 systematic study that utilized FDA evidenced based ranking system found that, as a group, a number of studies focusing on a variety of nutraceuticals and one non-steroidal anti-inflammatory fall under the type two level of evidence. The good news here is that this indicates a fairly high confidence level relating to test quality and objectives (i.e.; validity for discerning efficacy). However, the bad news is very large caveats exist due to the extremely low number of quality published studies to date.


In these situations, it is helpful to observe the results of larger studies and reviews, if they exist, in other animals. obviously, the human research perspective has a plethora of pooled information. In theses cases, the results are far clearer and reveal very little support for the efficacy of at least glucosamine and chondroitin.


It is also interesting to mention that the nutraceutical industry is just as able to twist the facts and spin the available research in the best light possible for their products as any other industry. For example according to the Nutramax website, the recent NIH funded GAIT study concludes:


National Institutes of Health GAIT Study Results


Clegg DO, Reda DJ, Harris CL, et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. New England Journal of Medicine 2006;354(8):795-808.

"In this double-blinded study sponsored by The National Institutes of Health (NIH) and led by various clinical investigators at 16 U.S. rheumatology centers, safety and efficacy were assessed on both glucosamine hydrochloride and chondroitin sulfate individually as well as in combination (all ingredients required to meet pharmaceutical standards). The chondroitin sulfate selected for use in this study is found in Cosequin.

Men and women over 40 years of age with knee pain persisting at least 6 months and with radiographic evidence of cartilage breakdown were each randomized to receive one of five agents: a placebo, celecoxib (a positive control), glucosamine hydrochloride, chondroitin sulfate, and the combination of glucosamine hydrochloride and chondroitin sulfate. The study concluded that the combination of glucosamine hydrochloride and chondroitin sulfate is effective in managing moderate to severe knee pain. Of note, response to either glucosamine or chondroitin sulfate alone was not significant. This study provided further support for Cosequin research documenting effects and benefits of using low molecular weight chondroitin sulfate and glucosamine hydrochloride in combination over using the individual agents alone."

The GAIT study actually states:


RESULTS: The mean age of the patients was 59 years, and 64 percent were women. Overall, glucosamine and chondroitin sulfate were not significantly better than placebo in reducing knee pain by 20 percent. As compared with the rate of response to placebo (60.1 percent), the rate of response to glucosamine was 3.9 percentage points higher (P=0.30), the rate of response to chondroitin sulfate was 5.3 percentage points higher (P=0.17), and the rate of response to combined treatment was 6.5 percentage points higher (P=0.09). The rate of response in the celecoxib control group was 10.0 percentage points higher than that in the placebo control group (P=0.008). For patients with moderate-to-severe pain at baseline, the rate of response was significantly higher with combined therapy than with placebo (79.2 percent vs. 54.3 percent, P=0.002). Adverse events were mild, infrequent, and evenly distributed among the groups.


CONCLUSIONS: Glucosamine and chondroitin sulfate alone or in combination did not reduce pain effectively in the overall group of patients with osteoarthritis of the knee. Exploratory analyses suggest that the combination of glucosamine and chondroitin sulfate may be effective in the subgroup of patients with moderate-to-severe knee pain. (ClinicalTrials.gov number, NCT00032890.). Copyright 2006 Massachusetts Medical Society.


Dan Hurley (Natural Causes) notes: “The new study was by far the biggest and best ever conducted on the substances...No statistically significant difference was seen between those taking any of the supplements and those taking placebo, but the study indicated why so many people think they benefit from it: a whopping 60 percent of those taking just a placebo said they felt better. The only sign of real benefit from the supplements came from an analysis of just the patients with moderate to severe pain, for whom those taking the glucosamine-chondroitin combination reported slightly less pain compared to those taking placebo. However, the number of patients in that category was relatively small, and experts have generally put little credence in such sub-group analysis, because one or another subgroups of patients in any study, if sifted through carefully enough, will turn out- simply by chance- to have fared better following a treatment."


The bottom line is that these are not the clear cut supporting threads of evidence supporting the use of oral joint supplements in animals suffering osteoarthritis. As more information trickles in, it could be that the weight of evidence swings positively for these supplements. On the other hand, initially favorable human studies later turned out to be far less accurate than assumed as more data came in. Additionally, these questionable joint supplements are among the most researched within the realm of the innumerable products available in the supplement industry. Indeed, a skeptical outlook remains the most prudent approach when encountering these products.


Justifying the amount of money spent on products claiming a medical benefit that have very little evidence backing them are of concern. Consumer choice in medicine needs to be limited to those modalities that have an acceptable level of evidence for efficacy demonstrable beyond placebo. Otherwise, often limited consumer funds, are directed away from those therapies that can do some good.

Wednesday, July 11, 2007

The tangled webs we weave…

Some of the more fascinating observations in medicine have to do with perception and interpretation. How patients and doctors cognitively process experiences can have rather huge implications toward the type of health choices they make. For example, some doctors can become easily convinced he or she might possess some innate healing power simply by talking and touching patients (fallacy of charisma). This can lead to other even less reality based practices. In the same way, a patient can perceive an improvement in their malady as associated with some other event (That fever went away when I drank that green pea soup- therefore green pea soup cures fevers…).


All humans innately create pattern associations as a natural matter of survival and this quality has deep evolutionary roots beyond the hominid line. That Homo sapiens have become so successful as a species is a tribute to the exquisite effectiveness these pattern associations have had in creating such social tools as language and culture.



In essence, humans are the children of non biological pressures (i.e., technology and social interaction) as much as they are of the biological ones (i.e., environmental pressures including climate change). One of the theories for our particular brand of intelligence and consciousness describes the inter play of pressures between ever more demanding technological advances and progressively more complex brain structure.



Whatever the case may be, the point here is that there has been a historically tenuous balance between the reality of the world around us and the “imagined” world we see in our heads. As time progresses, it seems humanity has been slowly tipping this balance in favor of realistic perceptions of reality over imagined ones.



That is, as information about the natural world accumulates and comes together in a larger “jigsaw” of associated pieces, humanity is being more careful of how it interprets perception. On the other hand, a tremendous chasm is growing between those who understand these realities and those who don’t.



So it is today in medicine. Whether we are doctors or patients, we tend to create a mishmash of imagined and real interpretations of disease and treatments. By understanding this and seeking out palpable realities- those put together through the laborious and careful work of so many- we can “keep our feet on the ground” and reduce the confusion between hope and false hope, effective healing and false healing. Even when there is little hope, authentic acknowledgement, companionship, and bonding will go much farther than anything our imaginations can muster.