A Peculiar Game of Chess

I received a nice crystal glass chess set for Christmas a little over a month ago, and I wish to show you an extremely peculiar arrangement of chess pieces, which happened by circumstance to end up organized in this special array, the 2^nd match I had ever played on this set. The chess pieces look as if they were arranged purposefully in such a manner, but I shall emphasize that the pieces ended up like this as a result of the vast complexity of chess and the myriad of endless permutations and possibilities for the pieces to be positioned. With the game’s constant “back-and-forth” maneuvering, occurring as a result of the interplay between each opponent’s respective offensive/defensive strategies, we (meaning my opponent and me) suddenly found ourselves at this resulting point in the match, to our amazement. The arrangement of pieces on each side was so unique that I absolutely had to document the occurrence by taking a snapshot of it.

But first, a side note on our modalities of chess play, this after having played chess against my boy Josh many, many times for well over a decade: Josh is very aggressive with using his queen to attack early on in the game, while I usually do not bring my queen out of hiding until the middle of the match, so let’s just say our queens were both eliminated very early on in this match via “equivalent exchange” LOL. Josh’s prized pieces are his 2 knights, so I almost always attempt to capture them early on in the game by setting up extremely elaborate traps, even at the expense of losing a seemingly “higher” ranked piece such as a rook or bishop. He is extremely adept at using the knight’s unusual “L-based” moving ability, as well as its capacity to jump over other pieces, using the two knights in conjunction with each other to setup traps and to cause inevitably forced capture of his opponent’s pieces. I, on the other hand, am not particularly skilled at using my knights, so I tend to use the horizontal/diagonal moving capabilities of my rooks/bishops, respectively, in concert, to attack my opponent.

Here is a "top-down" view of the arrangement of chess pieces as it appears about one half-hour into the match, and subsequently, a rotated "top-down" picture of the match as seen from my point-of-view. I have also included a picture with labeling of the pieces for ease of identification. I controlled the frosted pieces, while Josh controlled the clear glass chess pieces (you can click on each picture to get a larger view for better clarity):

The only pieces of mine which had been captured up until this point were 2 of my pawns, 1 bishop, and my queen, while I had captured 1 of Josh’s bishop, 1 knight, and his queen. So at this point in the match, you could say we were about even, as either opponent did not have any significant advantage in positioning or manpower over the other.

A few notes on the peculiarities of this match, starting with the arrangement of my pieces:

1. Note the arrangement of 5/6 of my pawns in the 4^th rank, creating a horizontal barrier to the advancement of Josh’s pieces. The barrier is relatively strong, but in retrospect probably not effective enough since I had previously described that Josh likes to use his horses, so he could easily penetrate the barrier by jumping over my pawns. As well, the weakness of such an arrangement is that I have no means of capturing pieces with pawns diagonally if the front-line of this barrier were to be breached (in other words, the pawns have no protection---note how Josh did this very well by placing his pawns in a diagonal array).

2. The position of one of my rooks behind the front-line of pawns. If any piece attempts to penetrate the barrier, my rook is waiting to pounce without any impediments located across the 3^rd rank.

3. One of my knights is in position to strike at the hole I left in my pawn-barrier, while still protecting the king. Movement of the knight allows my bishop to strike diagonally towards Josh’s left corner, although he has fortified his bishop well with a triangular arrangement of pawns, as I shall describe shortly. As well, my other knight is also within striking distance of Josh’s bishop-complex, although, again, his bishop is well protected.

4. My king and other rook had not been moved up to this point in the match, so I can still perform a “castle-kingside” move and bring my other rook out of hiding, waiting to attack up and down files (instead of ranks) if ever my pawn-barrier is again breached.

A few notes on Josh’s arrangement of pieces:

1. Josh also has a barrier of pawns along his 2^nd rank, with an “arm” of pawns coming off in a diagonal fashion, allowing protection of the leading pawns as I described above.

2. The amazing fortification of Josh’s bishop with the triangular array of pawns he has placed around it. At first I didn’t understand this move, as Josh is not very adept at using his bishops as much as his knights, although looking back, this makes sense now since although the bishop was protected well, it falls in-line with his style of play of not using his bishops much, as the bishop was relatively trapped in the back.

3. The positioning of Josh’s remaining knight, illustrating the fact that Josh loves to use his knights!! As you can see, it is the only piece he has up to this point which is actually active. Not exaggerating, he must move his knight literally twice as much as all other pieces combined.

4. Josh had also not moved his king or either of his rooks up to this point in the match, so he could still perform a “castle-kingside” move as well.

SO HOW IN THE WORLD DID THE MATCH GET LIKE THIS?!? Honestly, WE HAVE NO CLUE!! We were playing the best we knew how and simply ended up at this point in the match.

I do not recall whose turn it was next, however, as the match continued, my pawn barrier was slowly dismantled by me and chipped away at by Josh. With relatively few pieces remaining on either side, I ended up being able to get one of my pawns to Josh's 1st rank and that pawn was subsequently made into a queen. After this, I inevitably ended up checkmating Josh's king, although not without a few mistakes along the way, almost resulting in my loss and/or a stalemate (I absolutely SUCK at the end-game of chess, for some reason it is very difficult for me to realize the shortest amount of moves in order to checkmate my opponent and win the game, so a lot of times I accidently force a stalemate).

Via this example, I simply wanted to illustrate how intriguing chess can be, and in all the chess matches I have played in my life, I had never seen or played a match quite like this one!!

The COURAGE Trial: How the Media Misled the Public Concerning the Utility of Angioplasty and Stenting Procedures for Stable Coronary Disease

You may have heard a lot in the news recently about a recent study published in the New England Journal of Medicine concerning the use of percutaneous coronary intervention (PCI) procedures (aka angioplasty and stenting) in stable coronary artery disease. In this article, I will describe how the media has taken it upon themselves to present this study to the public in a misleading way, and how the study really does not tell us anything which we have not already known for years. It is also the public’s pre-conceived notion of how a heart attack occurs and of the utility of these procedures which is driving this hysteria, and I feel that in order to correct this misperception, they need to be properly educated on the basics of coronary artery disease and the utility of available interventions in treating it.
I want to preface this article by stating the following: A. I am not a cardiologist. B. This article is an opinion piece. Nevertheless, I obviously strongly believe in what I am stating here, as you will see shortly. As well, I feel as if the basic concepts behind this controversy are easy enough for a layperson to appreciate, as you do not need to be a board-certified cardiologist to understand it. Let us begin with a little background on this trial, and move on from there.
Results of The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial was released early through the New England Journal of Medicine’s website (www.nejm.org) on 3/26/07 as “Optimal Medical Therapy with or without PCI for Stable Coronary Disease” (direct link to article here). Although I won’t describe the trial in extreme detail, the concept of the trial is simple enough: the primary investigators randomized ~2300 patients diagnosed with stable coronary artery disease into a group that received PCI + optimal medical management and another group that received optimal medical management alone, and then followed them for several years to determine outcome (I explain what is meant by stable coronary artery disease below). PCI included angioplasty and stenting with bare-metal stents (this distinction is important, as drug-eluting stents are quickly becoming the standard). The primary outcome measured was a composite of both death from any cause + non-fatal heart attack (myocardial infarction, or MI).
The results of the study, for a reason I cannot for the life of me figure out, we’re deemed “SHOCKING”: There were essentially no differences in the rates of all-cause mortality and non-fatal heart attack between these 2 groups after a follow-up period of 2.5-7 years!! Seemingly, PCI + medical management of stable coronary disease was no better than medical management alone in preventing these outcomes!! The media immediately jumped on this, claiming that the results of the trial questions the utility of PCI with angioplasty and stenting. Accusations followed: interventional cardiologists were doing unnecessary procedures; the makers of the stents were making enormous profits at the expense of patients, so on and so on. In fact, here are some of the headlines spewed out over the papers and internet:

“Heart patients want answers after stent study”

“Heart study questions stent use”

“Heart experts question value of stent therapy”

“Stent Shocker: They Don't Stop Heart Attacks”

……The list goes on and on, and the fallout has only just begun as I’m writing this ~4 days after the study was released. I fear what might happen in the days to months ahead based on complete hoop-la!! Boston Scientific stock dropped more than 7% after this study was released (they make the Taxus drug-eluting stent). But the question that should be asked is this: “Did this study tell us anything which we didn’t already know?” Read on.
First of all, in general, the public does not understand what causes a heart attack in the first place. I’ve been complaining a lot about this fact for the last 2-3 years, and to be honest, prior to going to medical school, I misunderstood the mechanism as well. It is one of the greatest misperceptions in medicine. To understand this, you must comprehend the difference between stable and unstable coronary disease, and there are many.
Atherosclerosis, extremely simplified, is a process in which cholesterol is laid down in the inner lining of blood vessel walls. The process is complex, but over time, plaques form which can encroach on the hollow lumen of vessels, causing blockages. In other words, the pipes become clogged.
When this process occurs in a coronary artery, the territory of the heart muscle supplied by that artery can become ischemic (i.e. starved for blood and resultant oxygen). The heart is a muscle, and this muscle has a certain demand for blood. The coronary artery supplies the demands of the heart with needed blood. It is simple supply-demand economics. If the supply is too low to meet the heart’s demand, the heart suffers. Conversely, if the demand is too high for the available supply via the coronary arteries, the heart also suffers. This ischemia is manifested in humans through angina, typically in the form of chest discomfort, among other symptoms.
The process of atherosclerosis thus results in blockages, known in medical terminology as stenoses. A stenosis in a coronary artery can limit blood supply to the heart, although the heart can sometimes compensate for this in various ways, mostly by causing the affected artery to become wider (dilation). Thus, it adjusts its own supply to meet growing demands.
If the atherosclerotic process continues, and the stenosis worsens, eventually the heart can’t compensate for the reduced supply anymore, it becomes ischemic, and the symptoms of angina start to occur. This means that the heart is starving for blood supply.
A segment of the heart usually does not become ischemic until a stenotic plaque blocks approximately ~70%-99% of the affected coronary artery.
These plaques that cause 70-99% stenoses are usually stable. They will usually continue to grow as the atherosclerotic process continues, but a patient almost always will manifest anginal symptoms and present for treatment before this slow process leads to complete occlusion of the affected coronary artery. The symptoms help determine the problem. Stress the heart, and the angina may become more apparent, because the heart has a higher demand when it is stressed, and the supply of a severely stenotic coronary artery cannot meet this demand, even after dilating as a compensatory measure. Therefore, stable angina usually manifests itself as chest discomfort in the setting of stress upon the heart, such as exertion.
The 4 determinants of cardiac demand include heart rate, contractility, and the lesser known entities of afterload (related to the systemic blood pressure that the heart must contract blood against), and preload (related to the amount of blood the heart fills with). Change any or all of these 4 determinants enough, and the heart muscle will demand more blood. If it can’t receive it due to severe stable stenoses, stable angina occurs. In summation, it is a supply-demand mismatch problem.
THIS is what the COURAGE trial studied. It does not have ANYTHING to do with how a heart attack occurs. But THAT is the misconception. A majority of the public believes that it is this process which leads to a heart attack, and that fixing these stable stenoses will prevent a heart attack from occurring. They think that the stenoses keep worsening and worsening over time until the affected coronary vessel is 100% blocked, a heart attack occurs, and the heart muscle dies. That is NOT how it works. Let me set the record straight.
A classical heart attack is caused by unstable plaques. Unstable plaques are usually associated with stenoses in the 40-60% range, NOT usually the 70-99% stenoses, which tend to be more stable as described above. There are many determinants of an unstable plaque as compared to a stable one, which I will quote below directly from the published COURAGE trial manuscript.
Atherosclerotic plaques usually stabilize with something known as a fibrous cap, material which keeps the cholesterol core of the plaque from being exposed to the blood contained within the vessel. When this fibrous cap ruptures and the cholesterol-core is exposed to the bloodstream, the body attempts to seal it off with a thrombus (a clot). Sometimes this process can get a little out of control, and the clot grows and grows so much that it completely blocks the affected vessel. This is why aspirin and other anti-platelet agents, as well as blood-thinners like heparin, which affect the clotting factors, can help in these cases.
When an intracoronary thrombus occurs due to this plaque rupture, the coronary vessel can become 100% occluded extremely quickly, and the affected heart muscle’s blood supply is completely shut off. This can be catastrophic, especially if it affects one of the main coronary arteries. People can die suddenly due to electrical abnormalities (arrhythmias) which result from this lack of blood supply. Other times, the thrombus stops growing on its own, resulting in a plaque growing from 40-60% to say 80-95% within minutes. This is markedly different than the stable plaques described above. Needless to say, a person will experience unstable anginal symptoms if this happens, often while the patient is at rest, since the supply is severely limited by the resultant clot. As well, since this process is rapid, the heart cannot compensate with improving blood supply well in the short-term, as it can with the slow process of stable plaque propagation by growing new, small collateral vessels to the area around it.
In general, heart muscle starts to die within ~30 minutes or so after the affected coronary artery becomes occluded. Fortunately, the body’s own clot-busting system can re-vascularize (re-open) the artery by partially dissolving the clot. The process may cycle from here, as the clot shuts the vessel down, opens up, closes down, etc. The affected person may experience stuttering of anginal symptoms. This may go on for days, but it is an unstable condition. The unstable plaque will continue to be unstable until the body stabilizes it further with remodeling of the clot and fibrous cap over time, or until the worst happens, when the clot completely occludes the vessel, a full-blown heart attack occurs, and the affected heart muscle either dies or the patient seeks definitive treatment. Needless to say, after the whole affected muscle wall dies, the coronary artery can open up all it wants to re-perfuse its territory, but it won’t matter, since the muscle is dead.
This entire process is known as acute coronary syndrome (ACS). It is a spectrum of diseases encompassing unstable angina, NSTEMI, and STEMI, depending on how the supply of a coronary artery is affected by the formed clot, and the resultant muscle damage. In unstable angina, perhaps the clot is formed, cleared, formed, cleared, etc., but cleared in enough time to avoid death of heart muscle, or maybe the clot forms to an extent that it causes enough of a significant stenosis (70-99%) to cause symptoms, but not enough of an acute supply-demand mismatch to result in death of heart muscle. NSTEMI is caused when this aforementioned process does result in death of some heart muscle, as determined by reduced supply and increased demand, coupled with the time over which this mismatch occurs. STEMI is the classical heart attack, resulting from complete occlusion due to an unstable plaque rupture and subsequent intracoronary thrombus. The entire wall of the heart supplied by the affected vessel dies due to the lack of blood supply.
The difference between the entities of stable coronary disease and unstable coronary disease is KEY to understanding the COURAGE trial and its ramifications. Both the media (at least some of the media) and the public completely misunderstands this difference and also interchanges them. Although it is wrong, they believe that stable coronary disease leads to heart attacks, and thus if stable coronary disease is treated with PCI (angioplasty and stents) to relieve the resultant stenosis, it will prevent a heart attack from occurring. This is completely WRONG (although I do not place the blame on the public for this misunderstanding, as it is due to a lack of education).
Acute coronary syndromes are unpredictable events caused by unstable plaque rupture. The risk of it occurring can be reduced by lifestyle modification (diet and exercise) and specific medications. As well, the progression of acute coronary syndromes to a full-blown STEMI and resultant death of affected heart muscle, if they are caught in time (minutes to days, or even months to years, depending on the instability involved), CAN be prevented, none other than with medications and the same procedure which has been completely lambasted over the past several days, PCI, with better outcomes if stents are utilized!!
This has been PROVEN many many times, demonstrated by studies involving a huge amount of patients who received all manner of available procedures, including both bare-metal and drug-eluting stenting. Both angioplasty with bare-metal, and drug-eluting-stenting procedures save lives in this manner. They save thousands upon thousands of lives every year by treating unstable plaques. If a person is having a STEMI with a completely occluded coronary vessel and presents to a hospital that is fortunate enough to have the skilled professionals which can perform angioplasty and stenting (at all hours nonetheless), they will SAVE their heart (and maybe their LIFE). The faster they can get the procedure done and re-open the vessel, the more heart muscle is saved.
Within the medical community, it is well-accepted and has been proven multiple times that PCI in the setting of all acute coronary syndromes saves lives and reduces the rate of a resultant heart attack. Even if a patient presents with unstable angina (in which a vessel is threatening to shut down), PCI can prevent death and resultant NSTEMI or STEMI, as well as further anginal symptoms, if the unstable plaque can be treated with a balloon and stent before the vessel shuts down and a STEMI occurs.
The point is THUS: The fact that the COURAGE trial showed that PCI does not result in any survival benefit or prevention of heart attacks in stable coronary artery disease due to a stable plaque is ALREADY KNOWN. It has been studied before!! We KNOW that treating these stable plaques with angioplasty and stent only results in relief of stable anginal symptoms and improving exercise tolerance.
All of these considerations are in fact stated in the actual manuscript of the COURAGE trial as follows, in the introduction:

”PCI reduces the incidence of death and myocardial infarction in patients who present with acute coronary syndromes,^5,6,7,8,9,10 but similar benefit has not been shown in patients with stable coronary artery disease.^{11,12,13,14,15}” “Although successful PCI of flow-limiting stenoses might be expected to reduce the rate of death, myocardial infarction, and hospitalization for acute coronary syndromes, previous studies have shown only that PCI decreases the frequency of angina and improves short-term exercise performance.^11,12,15” (italics added)

Please notice the references quoted in the above statement. References 5-10 are from the previous studies that have already demonstrated a benefit of PCI in unstable acute coronary syndromes. Reference 5 itself is the ACC (American College of Cardiolgoy)/AHA (American Heart Association) guidelines on management of STEMI. The other references are from original studies or meta-analyses (which combine multiple studies into one) that show this benefit. So why is it that I am reading a headline that says “Stent Shocker: They Don’t Stop Heart Attacks”? You are right; they DON’T stop heart attacks if used in intervention of stable plaques, since stable plaques don’t cause the heart attacks in the first place!!
Also note references 11-15. They include some studies which compared stenting and/or angioplasty against medical management alone, similar to the COURAGE trial (although there were some differences). AGAIN, these trials showed a benefit in control of anginal symptoms in patients with stable coronary artery disease. Some of these studies (using angioplasty alone, before stents were on the market) are ~15 years old!!
Therefore, the so-called “surprising results” of the COURAGE trial are not a surprise at all!! They are anything BUT a surprise. We have known that PCI does not prevent heart attack or death in stable coronary disease for a very very long time. As well, given the background information I have provided above on the actual pathophysiology of the process, the studies are not a surprise at all anyways. They just prove what we already know via common sense. If I sat down and described to you this process of how unstable plaques lead to heart attacks, and how stable plaques lead to demand ischemic symptoms of stable angina, would you not, via common sense, hypothesize that placing a stent across an unstable plaque would prevent a heart attack from occurring? And that placing a stent across a stable plaque WOULD NOT prevent a heart attack from occurring, but just might help with anginal symptoms? Well, similar investigators thought the same thing (although this pathophysiologic mechanism was not entirely worked out when the first studies came out) and studied the question, confirming these hypotheses.
Therefore, I truly believe that the public is and will remain confused about how a heart attack occurs, and therefore they misinterpret the findings of the COURAGE trial, in still thinking that stable coronary disease leads to heart attacks. Granted, stable plaques may be a marker for other, more unstable plaques elsewhere, but themselves they do not lead to heart attacks. I don’t know how many more times I can say it. In fact, a far majority of stents are placed for acute coronary syndromes, NOT for stable coronary lesions.
Other commentators on this controversy point to inherit study flaws, such as the generalizability of the results (~85% of the study population were men), etc. However, THAT IS NOT THE POINT. The media and public are simply mixing up unstable (acute coronary syndromes) and stable coronary disease. The difference in between these is mentioned perfectly in the manuscript of the COURAGE trial itself!!:

“Our findings may be explained, in part, by differences in atherosclerotic plaque morphology and vascular remodeling associated with acute coronary syndromes, as compared with stable coronary artery disease. Vulnerable plaques (precursors of acute coronary syndromes) tend to have thin fibrous caps, large lipid cores, fewer smooth-muscle cells, more macrophages, and less collagen, as compared with stable plaques, and are associated with outward (expansive) remodeling of the coronary-artery wall, causing less stenosis of the coronary lumen.³⁶ As a result, vulnerable plaques do not usually cause significant stenosis before rupture and the precipitation of an acute coronary syndrome.³⁶ By contrast, stable plaques tend to have thick fibrous caps, small lipid cores, more smooth-muscle cells, fewer macrophages, and more collagen and are ultimately associated with inward (constrictive) remodeling that narrows the coronary lumen. These lesions produce ischemia and anginal symptoms and are easily detected by coronary angiography but are less likely to result in an acute coronary syndrome".^37,38

"Thus, unstable coronary lesions that lead to myocardial infarction are not necessarily severely stenotic, and severely stenotic lesions are not necessarily unstable. Focal management of even severely stenotic coronary lesions with PCI in our study did not reduce the rate of death and myocardial infarction, presumably because the treated stenoses were not likely to trigger an acute coronary event.” (italics, underlining, and bolding added)

Another point is to be made about the COURAGE trial, as I fear that people are going to start to refuse much-needed intervention with stents based upon this trial. Even if a patient does have stable coronary disease, the COURAGE trial suggests that there is no difference between trying medical management alone vs. PCI, and therefore, the patient might ask, WHY would I need a stent then? Justifiably, the question should be asked, right? For one it is a procedure, with its own risks, it costs much more than medicines, and also has some risk (although low) for in-stent thrombosis after it is placed, which leads acutely to a STEMI and sometimes, sudden death (Note: If you haven’t heard, there is another huge controversy involving this potential risk with drug-eluting stents, which I think is blown WAY OUT OF PROPORTION as well, and which would require a whole other article in and of itself).
Even if the patient understands their condition correctly, that they have stable coronary disease and that the COURAGE trial did not show “any difference” between medicines and PCI in management of this disease, they need to THINK (or be counseled) very carefully before they refuse PCI and elect to be treated with medication only. The consideration must be made in terms of the specific outcomes which are measured by the COURAGE trial. As we stated, the trial measures the rates of ALL-CAUSE DEATH and HEART ATTACK in each the medicine group and the stent + medicine group, and it was those outcomes which showed no difference. So how can one say there is no benefit at all in utilizing PCI even in stable coronary artery disease when stable coronary artery disease doesn’t lead to DEATH or HEART ATTACK in the first place? That is what this study attempted to measure, and again, the fact that there were no differences between the two treatment modalities is really no shock at all.
However, maybe there is a benefit after all in treating stable coronary disease with PCI (after all, I already stated that this is well studied and proven, as noted in some of the studies cited in the COURAGE trial as above), and that benefit would be control of demand-ischemia anginal symptoms. So there is still a benefit to PCI in stable coronary disease as compared to medications, in the control of anginal symptoms, and this has been KNOWN and is thus the indication for doing the procedure in the first place. But obviously, even prior to the COURAGE trial, I can say that most patients who received a stent to help treat their stable coronary disease likely thought that it was instead saving their life, or at least, preventing the ~80-90% lesion from progressing to a 100% lesion and (falsely deduced), causing a heart attack. I think it is also a failure on our part as physicians in explaining the true benefit of doing PCI in these cases, controlling their anginal symptoms.
I would still say that this is a noble benefit, and that is why, even in stable coronary disease, PCI definitely has a role. Anginal symptoms are uncomfortable and limit activity, and PCI can control these. I think the issue may be that interventional cardiologists are often quick to use PCI to control these symptoms, rather than trying medical management first in patients. Afterall, there is almost zero risk that the stable stenosis itself is inherently dangerous, since it doesn’t lead to heart attacks!!
Therefore, many patients could probably try medical management first instead of immediately receiving PCI, and we do choose this option for our patients in select cases, after considering the options, especially if we feel that undergoing an angiogram and subsequent PCI may be too risky to justify the benefits. Many of them do fine with no recurrence of symptoms, or if symptoms recur, they are controlled immediately with an under-the-tongue nitroglycerin tab.
Medicines can alter the dynamics of this supply-demand mismatch problem quite nicely. Nitrates and calcium-channel blockers can help dilate coronary arteries for more supply, and medicines which lower heart rate, contractility, and afterload (through blood pressure control) can help lower demand, and patients may remain symptom-free. Nevertheless, if they fail this medical management, PCI is definitive because it completely eliminates the supply-side problem (by opening the artery up completely, at least for a period time, i.e. months to years) of the entire supply-demand equation.
So the COURAGE trial measured a composite of all-cause death and heart attack rates as their primary outcome in comparing the two management strategies. However, as noted in many other studies prior showing a benefit in anginal symptom management with PCI for stable coronary disease, did the COURAGE trial also measure and show this benefit as well? In fact, they did measure this outcome as well, although not much is really mentioned about it (afterall, it has been proven already and this trial attempted to compare death and heart attack rates). In this study, they stated the percentages of patients that were “angina-free” in both the PCI + medicine group vs. the medicine-only group, at time points of 1, 3, and 5 years after enrollment in the study. The PCI + medicine group had slightly higher rates of being “angina-free” at both 1 year (66% vs. 58% of patients) and at 3 years (72% vs 67% of patient). Data for the measurement 5 years after enrollment of the study was not “statistically significant” (put simply, if there was a difference detected between the two management strategies, there is a risk that the difference was not true but simply due to chance, and at a risk that is considered unacceptable by the medical community).
Therefore, in line with previous studies, this study seemed to favor PCI even in control of anginal symptoms (at least in being “angina-free”). Particularly, it is EXTREMELY important to note that the trial was conducted with the use of bare-metal stents for stable coronary disease. Bare-metal stents have a higher re-stenosis rate than the newer drug-eluting stents, meaning that the stable plaque comes back after only several years as the body reacts to the foreign material in the stent and grows over it rapidly (although, some evidence points to the fact that occasionally the re-stenosis plaque can also be unstable). Therefore, this consideration must be taken into account when interpreting the benefit of PCI + medicines on anginal symptoms as compared to medical therapy alone, as the newer drug-eluting stents will allow a greater period of time to go by before a patient has recurrence of stable anginal symptoms and require a “re-do” PCI. If a similar randomized trial was conducted to evaluate drug-eluting stents + medicines instead of bare-metal stents as utilized in PCI vs. medical management alone, and the primary outcome measures were anginal symptoms instead of death and heart attack (as measured in the COURAGE trial), I hypothesize that it would suggest an even greater benefit with an even-wider spread between the percentages noted above, in terms of patients being angina-free at 1, 3, and 5 years. I am unsure however if a specific trial has addressed this clinical question as of yet.
Given everything I have mentioned up to this point concerning the COURAGE trial, I would like to discuss its ramifications. Not, in fact, the actual ramifications of the results of the trial, because again, I do not feel it added much, and it definitely didn’t shock me. I am speaking of the ramifications which are the result of those who misconstrue results of the trial, including the media, the public, and even surprisingly A LOT of physicians, many of them cardiologists (given this, I am sort of worried that I am missing something here, but I know I am not)!
The fall-out from this is just beginning, and to me, it is very frightening. My main concern is that some patients are sure to refuse a much-needed therapy because they do not understand how PCI benefits them immensely if they are having an acute coronary syndrome, due to an unstable plaque. The benefit of PCI in these cases is proven and recommended, but I know that some people will adamantly refuse the procedure because they are confused about the differences between unstable and stable coronary disease, or they will simply quote a headline or TV news segment they saw saying that there is “no difference” between PCI and medical management. There is absolutely no doubt in my mind that many will die or suffer great morbidity due to a heart attack because of this, those who would not have suffered these bad outcomes if they had not read the paper or turned on the TV and witnessed all of the over-blown hype concerning this trial. It is quite sad, and they need to be educated. Many patients may even delay seeking prompt medical evaluation in this regard.
I have already seen this concern manifested, only FOUR days after this trial was released. As I am on a cardiology rotation right now, earlier today a patient who presented with chest pain told us that if we found significant stenoses during his angiogram, he did not want PCI performed, but instead wished to end the procedure and discuss the possibility of medical management vs. PCI first (usually, PCI is performed at the same time as the initial angiogram, since going back and doing a 2^nd angiogram with PCI doesn’t make financial sense and opens up the patient to more risk with an additional procedure). HOWEVER, the patient had presented with symptoms which were more consistent with unstable angina (i.e. rest chest pain, and stuttering, intermittent chest pain), therefore worrisome for an unstable plaque!! Luckily, his angiogram did not show much disease, and therefore, hopefully his chest pain was due to some other cause. Nevertheless, it shows how this over-blown media coverage of the COURAGE trial is already affecting the decisions of patients, albeit in a detrimental way.
Another concern I have is that many physicians may misinterpret the results of the COURAGE trial, and thus the way they manage their patients may change for the worse. I doubt this will happen in hospitals, where access to cardiologists will result in the correct management a vast majority of the time. My concern is particularly with internists, who may see a patient in their office with symptoms consistent with unstable angina, and instead apply the results of the COURAGE trial and treat with medical management first. The results of this could be catastrophic, although I still trust that most internists understand the difference between acute coronary syndromes and stable angina.
To be fair, the COURAGE trial may result in many patients avoiding unnecessary PCI by trying medical management first for their stable coronary disease, and if that doesn’t work, they can subsequently undergo PCI for definitive treatment. Unfortunately, as I stated above, that would usually require two procedures (first an angiogram to diagnosis the stable coronary disease, and subsequently another procedure for the PCI) instead of one, thus more cost, risk, etc. As well, as above, we must still remember that PCI with a drug-eluting stent is likely to result in an even greater benefit of time in which the patient would be “angina-free” as compared to both bare-metal stents as studied in the COURAGE trial and medical management alone.
Another major concern I have is insurance coverage. Will the insurance companies (or Medicare) refuse to pay for PCI procedures in the management of stable coronary disease, unless medical management is tried first? While that may be justifiable, it shouldn’t be justified in light of the results of the COURAGE trial, because again, PCI has NEVER EVER been shown to lower the rates of death or heart attack in the first place, and that is what the COURAGE trial attempted to measure in comparing medical management alone to PCI + medicines. If everybody could just GET THAT THROUGH THEIR THICK SKULLS!!
I also pray that nobody loses their employment or is sued because of the results of this trial. That would truly be a tragedy, but it is bound to happen. Much of the fall-out is still unforeseen at this point in time. Like I said, even Boston-Scientific stock dropped ~7% because of this!! Those people who had invested in the company should get their money back, because people completely overreacted to the results of this trial and sold their stock!!
I think that I have ranted and raved enough on this matter. But in all seriousness, the COURAGE trial has really been blown completely out of proportion. The hysteria is both a result of a misinterpretation of what the trial intended to study in the first place, and in a lack of basic understanding of both how and what type of coronary disease actually leads to a heart attack. Physicians, the media, and the public are all to blame in this. Hopefully, patients will trust their doctors to do what is right for them, and I hope that they will receive proper education concerning what benefit PCI has for both stable and unstable coronary disease. We'll be watching eagerly as this story unfolds further....

You Won’t Get a Piece of Me

After you read what I’m about to say, you may find me a selfish person. But before you judge me, at least listen to what I have to say in this article, something I’ve wanted to say for awhile, but since the majority of society is against this, I was reluctant to speak on it. Nevertheless, I feel that as a doctor, I am in a special position to write about the subject of organ donation, as I have witnessed first-hand the death of patients and the subsequent process of donating their organs to an anonymous recipient.
Hopefully organ donation will be obsolete by the time I die, so that I may never have to make this decision in reality. Some people think that the decision to donate their organs requires absolutely no thought at all. After all, why wouldn’t you donate organs to save (maybe even) 6-7 lives, since you are dead and never coming back anyways? Let me describe my view on this.
A potentially self-centered statement: I will NEVER consent to donating my organs after I die. In fact, I am much more likely to donate either a kidney or a piece of my liver to a HLA-matched family member while I am alive then to give these organs to an anonymous recipient after I’m dead. Let me explain several reasons why, from both an ethical standpoint and an experiential standpoint. I won’t get too much into the altruism of donating organs, and I applaud those who would do such a thing. I honestly think though that many potential organ donors would rescind their wish to donate after they die if they had seen and learned what I have.
Organ donation is quickly becoming big big business. All of medicine and peripherally-related enterprises are big business, generating a mass amount of revenue, since the entire premise is to make people live both longer and with better quality of life, stemming from mankind’s survival instinct and drive to avoid pain and suffering, respectively. Both medicine and non-transplant surgery’s goal is to fix broken tissues and organs, or to delay the time it takes for them to break. This works to a certain extent, but it has been the dream of medically-inclined men to replace organs and tissues since the beginning of time. It has not been possible until recently. This is the main driver for the business of organ donation.
The process of creating and/or growing organs is a little ways off via genetic engineering techniques. Xenotransplantation, the process of transplanting organs from other species into humans, has also not panned out very well. Therefore, in the meantime, we must rely on donation of organs from other human beings until either of the aforementioned processes is more perfected.
Given this, and humankind’s desire to constantly extend life, human organs are in high demand these days, and will remain so for some time given rising incidence and prevalence of disease. Simple economical principles dictate that where demand exists, those who control and mediate the supply will benefit (i.e. profit). Since ethical principles forbid exchanging your organs for anything of monetary value, an attempt is made to make altruism the only factor involved in deciding to donate your organs. However, as stated, the mediators of this business control the supply and in turn, they benefit. Granted, the organ donation business is also largely motivated by altruism, and many organizations are non-profit. But since the demand for organs always outweighs the supply (for many reasons-ethical, medical, etc.), a system is setup in which certain people may skip mediating agencies and directly arrange donation to a desperate recipient, often for monetary gain (more for living-related donors, although also for families of deceased donors). There is no doubt that this exists, as there have been numerous reports of such transactions occurring, although it is uncommon. The process itself is regulated not only by ethical principles, but also by law, and this tends to reduce this problem. Therefore, I cannot dump on the whole organ donation business over this one specific fact, but nonetheless I feel I must state this as a background to my further objections over organ donation.
I feel that a lot of my main objection over organ donation is in the process of organ procurement itself. I think this stems from some technical aspects of the procurement process as well as a specific attitude of people in general and organ donation societies to the following sentiment: “After all, they’re dead!” Let me explain these issues in more detail.
Unfortunately, the time immediately after death is crucial in organ procurement. Once the heart and lungs stop, and the whole person is considered dead, the individual organs themselves only begin to die. Lack of blood supply and resultant lack of oxygen begins a process in which cells first become ischemic, and subsequently begin to necrose (put simply, decompose). Some organs degrade faster than others, but the point is, that the faster an organ is procured after the death of the whole person (cardiorespiratory arrest, as brain-dead people can at least have artificial ventilation and cardiac support), the more likely that the organ is viable in the recipient. Means such as freezing the organ may buy some time, as the tissues composing the organ become less metabolically active at a lower temperature.
Given this consideration, it is critical for a newly-deceased organ donor to present to the OR for harvesting of organs ASAP, if the organs are to even survive outside the human body and subsequently be transplanted into another human being. Whereas this is an unfortunate fact of organ donation, I feel it is one of the main driving factors in everything which is wrong with the organ donation process.
Warning: Here come my rants and raves about the horrors of organ donation. Imagine your parents are about to find out that you have died rather suddenly without warning, say in a car accident. You are rushed to the hospital, but are DOA (dead on arrival). Your personal effects are removed from your dead body, and it is noticed on your driver’s license that you have directives stating you would like to be an organ donor upon death. Let the circus begin.
Likely, the organ donation agency is called even before your parents are (TIME IS OF THE ESSENCE of course since somebody else is very sick and waiting for your organs, and your organs are starting to die NOW)! Your parents are called next, and they arrive 20 minutes later, completely distraught. I happened to be in the ER trauma unit when your body arrived, and I am trying to help your parents cope, offering support services such as a chaplain, etc. However, within 3-4 minutes of your parents just arriving to the hospital, I leave and direct an organ donation representative into the room. In the middle of this complete shock of losing you, your parents are gently asked if it was your wishes to graciously donate your organs to those who need them (of course, it doesn’t matter what they say, since you had previously specified that as your wish).
The staff may give your parents 5-10 minutes to visit with your body, say final goodbyes before seeing you again at your funeral, and then the organ donation representatives send a team in to take your body away for harvesting of your organs. Again, time is of the essence. Is that how you would like your distraught parents to experience the time immediately after your sudden death, with the topic of organ donation one of the first things to come up? Imagine if you hadn’t specified or told them of your wishes concerning organ donation, and they were left with making that choice, having to make a decision within minutes of arriving to the hospital.
I must ask about donation to newly-deceased patients’ families all of the time. It is usually #2 or #3 on my list of things that I must ask as required by Minnesota state law (another is addressing autopsy). Although I am almost always extremely uncomfortable in addressing it (especially if the death was unexpected), I cannot imagine what it would be like to be on the other end of that conversation. “You’re telling me my son (daughter, mom, dad, grandma, grandpa) just died and you’re asking me for their organs”? To be fair, many family members have no problem with this, and some actually like to answer that question, indicating that their loved one would have wanted to help save another life. However, that is only the beginning of this horrible process. I’ll describe the rest in a bit, after I detail other potential scenarios of how this can play out.
Brain death is a “special” kind of death in a way, part in due to the introduction of our own technology. A lot of times, brain dead people are young, and the brain death is due to some massive and final event such as a traumatic head injury or sudden stroke or brain hemorrhage. Brain dead people can be kept “alive” in the sense that machines can breathe for them if their brainstem is taken out. Alive in the sense that the patients’ families may consider them to be alive, because they are breathing and their heart is beating, but brain dead people are not alive. Their brain has lost all function, including rudimentary reflexes. Brain dead criteria is extremely strict, as rigorous tests must be performed to determine that even the most rudimentary brain functions have been lost.
Brain dead people are usually excellent organ donation candidates, as they tend to be younger and their main organs can continue to be preserved almost indefinitely with artificial life support. The ethics of the care and withdrawal of care from brain dead vs. nearly brain dead patients are particularly difficult. Nearly brain dead patients are those that have some rudimentary reflexes left, and thus do not meet specific criteria for “brain death”. Although futile, their lives can be prolonged by their families for years on end, with no “meaningful” function apparent. I will not go into my feelings on these ethical difficulties, whether to remove life support or not. However, problems come up when the subject of organ donation is approached. To be perfectly honest, although a lot of doctors claim to continue to treat these patients as they would any other with completely normal function, subconsciously, they do not. They see the futility of keeping a person alive who will never awake, who will never have quality of life. An ethical dilemma ensues. Even though it is the specific health-care proxies’ decision whether or not to remove artificial life support, this type of futile patient has viable organs. They are an “organ transplant candidate”. They can save others’ lives.
This can be extremely dangerous if these sentiments enter into the minds of those healthcare providers who are directly involved in the care of such a patient, either consciously or unconsciously. Care can be compromised. The physician may not work as hard in providing the adequate care the patient needs. They may subconsciously influence the family members concerning the fact that their loved one can save many lives by allowing withdrawal of life support and subsequent organ harvesting.
But who can blame them? In front of them is a perfectly good waste of human organs. Whereas these sentiments are common, they can lead down a very slippery slope. Where do we draw this line? There are people on both sides of personal and societal human interests, the family wishing to hold onto the hope that their loved one may one day respond to a novel therapy or that a miracle may happen, and the organ donation representatives and health-care team thinking about the sick who can benefit from this patient’s organs.
These arguments are hard to work through, but I think they illustrate how a major dilemma was introduced into the morality and ethics of humankind when transplantation technology was made available to them. I simply take the side against organ donation personally, because I see the organ donation representatives and their inherent biases against the deceased and their families.
Let us go back to the actual process of organ procurement. We have detailed how organ donation is addressed within minutes of a person dying, required by law. As stated, I think this is awful. It is as if I am coming to you and saying, “Oh yeah, I’m sorry about your family member dying, but now that he is dead, can we have his organs?!? They would save soooo many lives, wouldn’t he want that?” Is that not a loaded question in the first place? Since this article addresses a controversial viewpoint I hold, suffice to say I am the only one you or I know that would actually tell the organ donation representative to shove off! But even uncomfortably so in my case, as there is such pressure to donate, and to avoid disdain for being selfish.
Who else besides me would dare to say no to donate a deceased loved one’s organs to save others’ lives? If I say no, would they ask why? And my answer to this question would be exactly the point I have been trying to make, that they should not have asked me in the first place when I am in such utter grief having just learned my loved one has died. It is neither the place nor time to do so, but as we had previously outlined, if organs are to be viable in transplantation, that inherently the question needs to be addressed soon after one has died, as time is of the essence.
Let us move to the actual process of the harvesting. Does anybody even know what this is like when they decide to donate? Maybe they should watch a video of it first. An argument to this would be again, “who cares, you’re dead!” But imagine if your family watched your organ harvesting live within hours of learning you are deceased.
I have only witnessed one or two organ harvesting surgeries, and one corneal harvesting. Suffice it to say that the experience alone turned me off to ever consenting to donate. In scouring the internet for physicians with a similar viewpoint to mine, I found a post by an anesthesiologist in a debate on organ donation, the exact quote as follows:

“I am an Anesthesiologist on call, and my team was responsible for maintaining the brain dead patient's blood pressure, temperature and so on... The 17 year old beautiful young boy who had fallen and hit his head lay there on the OR table at once pristine and peaceful, then the next 30-60 minutes looked like a dead carcass on the African Serengetti, a victim of mindless tigers looking for spare parts. I have seen many procedures in my life but nothing, NOTHING is as DISGUSTING as the organ harvesting procedure. A vertical incision is made from crotch to throat, the Rib Cage is spread wide open and as quickly as possible, the organs tied off and removed, the BEATING heart stopped and grabbed out like Jack the Ripper, the Liver, Kidneys, Pancreas thrown on Ice and taken out in an Igloo cooler. Once this horrific process is done, It DOES NOT STOP! The next wave of Vultures fly in and take scalpels and cut out the EYES! Then all flesh was removed around the chest with nothing but bare RIBS exposed! The Once beautiful rosy cheeked 17 year old reduced to a pale Carcass. Absolutely the worst image I have ever witnessed. And who decides how the organs are used? Not the family, Not the Dead Patient. Why should One young boy be mutilated so another can live a few extra years? Society tries to extend the life of humans for whatever cost, the whole time I realized what really frightened me was the fact that I too will also be dead like that boy. He just made the transition tonight. Listen up....you all will die someday. Yes, you will! and instead of trying to prolong the inevitable why don't we accept that our time has come, and in so many instances self induced (ie..alcohol, smokes) So maybe you will get lucky and receive this kid's heart or maybe you will die waiting. anonymous Doctor.”

This is one person’s viewpoint of course, but I have talked to a lot of physicians, who witness this end of the organ donation process, and they are equally horrified about the whole process. From my (?biased) view, these organ donation people are absolute vultures. From what I have seen, they do not seem to care much or be appreciative of the deceased who donates. They only care about the end-point, that somebody else was able to live because they helped procure organs for them.
My viewpoint may change one day of course if I was in somebody else’s shoes, say for example if myself or someone I knew needed an organ to survive. I have even had some unusual encounters with patients that need a transplant to survive. Granted, they are in dire circumstances, and one should not generalize, but I have even seen patients praying that someone young (the most viable organs are from young healthy people) would have an accident and die so that they can receive their organ. Because organ donation exists, it creates this extreme demand, which can only come about if somebody in fact dies and donates their organs. I am not sure I would rather have the option available at all, as I think if I needed an organ, I would have wished that organ transplantation had never ever been developed in the first place. Death would seem far more preferable than the extreme ups and downs, anxiety, and unnatural thoughts of waiting for somebody to die to give me an organ.
On a quick side note, on the recipient's side, the entire transplant-waiting list process is also troublesome and rife with corruption. I have heard stories of V.I.P.’s (i.e. rich people, CEO’s, high-ranking governmental officials) mysteriously “jumping” to the top of the list to receive a specific organ. I will not even begin to start a debate on this. It is absolutely horrible to think that such things occur, but they do. Do you think if the president of the United States needed a heart transplant that he would actually be made to wait on the transplant list like everybody else, fairly and squarely?
I have also witnessed “games” being played with the health-care system and the transplant list for recipients. For example, when I was in the cardiac intensive care unit, we would occasionally admit heart transplant candidates that were awaiting a new heart. In the U.S., the candidates at the top of the list are divided into UNOS (United Network for Organ Sharing) status Ia and Ib. Status Ia candidates are at the top of the list, and are next to receive a heart transplant if a match is found. One of the main criteria in order for a patient to be moved from status Ib to Ia involves placement of a swan-ganz catheter (an invasive hemodynamic monitoring catheter placed in the neck) with continuous monitoring, and as well, initiation of an IV inotropic agent (an intravenous medicine which augments the heart’s pumping function for those with heart failure). The IV inotropic agents most commonly used include milrinone and dobutamine.
To my astonishment, I learned that it is quite common for transplant physicians to “manipulate” these criteria so that patients can be moved from Ib to Ia status. This occurred twice while I was in the CCU over 1 month. Patients were admitted in “heart failure”, saying that they required an IV inotropic agent, although in actuality they would be as stable as they had been when they were status Ib, with no actual change in their clinical status. We then were instructed to place a swan-ganz catheter in the patients’ neck (a procedure with potentially fatal risks, since it is floated through the heart chambers and subsequently up into the pulmonary vessels), and start the patient on an inotropic agent, and they would then be moved up to status Ia, sitting in the hospital and waiting for news that a heart is available for them. Even more blatant was the fact that we were instructed to start the dobutamine (the inotropic agent) at the lowest dose physically possible (since the patient didn’t really need it), practically just a “whiff”. There our patients sat, sadly and anxiously awaiting their new heart, but they never got it. They racked up 2 weeks in the CCU and a lot of anxiety. Are these games fair to those other people who are on the list and await a heart fairly?
As I've detailed, I have a lot of problems with this entire system of organ donation. After seeing what I have seen, I refuse to donate my organs after I die. You may still think that that is selfish, but you have not been in my shoes. Again, I have luckily never had anybody close to me need an organ transplant, and if I did, that life-changing event may change my perspective. But the moral and ethical dilemma of whether or not to donate your organs after you die is indeed a man-made one. There is certainly nothing "natural" about transplanting an organ belonging to one human being into another, but technology has made it a problem to consider for all of us after we die. All I know is that those who work for organ donation agencies seem like vultures to me after I have seen the way in which they latch on to a newly deceased patient's family so that they can "help" somebody else by securing their organs. Couple that with the obvious corruption that I have both heard about and witnessed first-hand involving which people actually get appropriated organs, and you may begin to understand where I am coming from.

Mind Freakin'

This post will FREAK your mind. I've never watched A&E's Mind Freak, but this guy Criss Angel is absolutely insane. I've never seen magic this good before. I can't for the life of me figure out how he pulls some of his stunts off. I'm definitely gettin' the DVDs of Season 1 and Season 2. Check these, the first one where he splits the woman in half completely shocked me when I first saw it. I was running around the apartment SCREAMING.....



He does it to himself as well:

What Causes a Hangover?

Hangovers suck. Millions of people out there probably woke up this morning with one, overdoing it slightly last night. I was luckily spared and have only a slight headache this morning. I've realized how much alcohol I can drink without feeling like utter crap the next day, cause let's face it, is it really worth it? Anyways, this gives me an opportunity to describe what biochemical processes actually lead to the development of a hangover, because I believe there is a mass misconception out there that hangovers are caused by dehydration, when that is only a small part of the whole process. Yes, alcohol is a diuretic, but do you really pee that much more when you drink? Read on.
A hangover is a complex process, but if you took biochemistry and learned the basic metabolic pathways that are involved in glucose metabolism, you can easily see why they occur. Let's explain a few basics.
First, you must go back to high-school chemistry and re-visit the concept of redox reactions. Redox is short for reduction-oxidation. It is slightly more complex than stated here, but you can think of reduction as the addition of electrons to an atom or molecule, and oxidation as the removal of electrons from an atom or molecule. These reactions occur together such that there is a net balance of reduction and oxidation in terms of addition-subtraction of electrons. I will explain this concept shortly. Particularly in biochemistry, there exist reduction and oxidation substances which donate and accept electrons in organic (carbon-containing) molecules in basic metabolism of food substances (carbohydrates, proteins, fats, and alcohols). These substances can oxidize or reduce intermediates in metabolic pathways to facilitate movement and further metabolism of the organic substance for energy storage and utilization. When these agents oxidize an organic molecule, they are in turn reduced themselves by accepting electrons from that molecule (hence the balance is preserved). Conversely, when these agents reduce an organic molecule by donating electrons, they are in turn oxidized themselves.
There are 2 main redox agents in the human body, nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). They are somewhat related to nucleotides chemically (DNA and RNA), and are synthesized from niacin, also known as nicotinic acid or Vitamin B3.
We will be dealing with NAD, since it is mainly involved in carbohydrate and alcohol metabolism (NADP is mainly involved in nucleotide and fat metabolism). When NAD is oxidized, we notate this as NAD+ (note that oxidation also refers to an increase in oxidation state of the molecule, the + sign indicating an oxidation state of +1). When NAD is reduced, we notate this as NADH. Therefore, NADH can donate electrons to an organic molecule, thereby reducing that molecule, and the NADH itself is thus oxidized to NAD+. The converse is also true.
Alcohol as contained within alcoholic beverages is ethanol (yes, the same exact substance which destroys so many lives is the same exact substance which may save the planet's energy crisis! As an organic molecule, it contains energy just like other foodstuffs!). The -ol denotes an alcohol group (-OH), and the ethan- just denotes the presence of a 2-carbon chain (i.e. methanol aka wood alcohol is an alcohol with a 1-carbon chain). The chemical structure of ethanol is as follows:

CH3CH2-OH

When you take in ethanol, it is metabolized in the liver as follows:

An enzyme known as alcohol dehydrogenase, in the presence of NAD+, oxidizes ethanol to a substance known as acet-aldehyde (aka ethanal) by removing the hydrogen (hence the enzyme is a de-hydrogen-ase) and converting the alcohol -OH group to a double-bonded aldehyde =O group. An aldehyde is a molecule which has a double-bounded oxygen on the carbon at the end of a chain (as opposed to a ketone which has a double-bonded oxygen somewhere in the middle of a chain).
NAD+, in turn, is reduced to NADH by accepting the hydrogen (and electrons) from ethanol, completing the redox reaction. This reaction can be notated simply as follows:

CH3CH2-OH + NAD+ + alcohol dehydrogenase <-> CH3CH2=O + NADH + alcohol dehydrogenase

Note that as an enzyme (i.e. a catalyst), alcohol dehydrogenase is not changed or consumed in any way, simply facilitating the reaction to occur much more quickly than it would occur spontaneously.

Acetaldehyde is toxic to the body, so the metabolization of ethanol continues in the liver. Acetaldehyde is further oxidized in the presence of NAD+ and another enzyme known as acetaldehyde dehydrogenase to form acetic acid (aka vinegar!), converting the aldehyde =O group to a carboxy acid group. Although I won't attempt to draw this reaction, it is analagous to the reaction above except the aldehyde is further oxidized to a carboxy acid.
Acetic acid can then easily be metabolized for energy in cells similar to other organic molecules such as carbohydrates, with the end result being CO2 (carbon dioxide), eliminated via respiration.
As you can see, the end result of the metabolization of ethanol in the liver is the harmless substance acetic acid, vinegar. However, as noted in the reactions above, the net result is also the reduction of TWO molecules of NAD+ to TWO molecules of NADH for every ONE molecule of ethanol that is metabolized. Continued metabolization of many ethanol molecules thus results in "tipping" the balance of NAD+ <-> NADH towards the reduced form as NADH. Thus, metabolization of an excessive amount of ethanol lead to an excess of NADH molecules within the body.
NAD+ <-> NADH is a delicate balance in the human body, since I previously stated that it is utilized in redox reactions involving metabolization of glucose, the main energy containing molecule in the body, and the preferred molecule to be metabolized by the brain.
Glucose is mainly metabolized an-aerobically through a process known as glycolysis (a word that simply means breakdown, or lysis of glucose). Glucose and subsequent products are successively oxidized repeatedly through various steps, resulting in a net generation NADH. This process generates some energy, but the end product of glycolysis, pyruvate, in the presence of a sufficient amount of oxygen, can further be metabolized aerobically in mitochondria via the Krebs' cycle to generate much more energy. Thus, glycolysis is an anaerobic process, no oxygen is utilized in this metabolic pathway.
This is partly why cells must switch from aerobic to anaerobic metabolism if you overwork yourself too much and you can't deliver enough oxygen to tissues to sustain the aerobic metabolism of glucose and other carbohydrates, and thus metabolism stops at the end of glycolysis in such cases.
The end product of glycolysis is a substance known as pyruvate. The chemical structure is as follows:












As stated, this substance usually enters the Krebs' cycle for aerobic metabolism, but if sufficient oxygen is not available (i.e. anaerobic exercise, sprinting, etc.), then it is further diverted to other substances, which we will see shortly!! The anaerobic metabolism of pyruvate to these other substances are different in different organisms. Where is this leading?
Well, the process comes FULL CIRCLE in yeast and various other organisms (yeast only extract energy through anaerobic glycolysis and have NO Krebs' cycle to metabolize glucose aerobically). Organisms such as yeast use glycolysis to metabolize glucose and other sugars to the end product of pyruvate too, but they have an "extra" step to extract the tiniest bit of more energy, a process known as FERMENTATION. They subsequently metabolize pyruvate into acetaldehyde and then into ethanol utilizing the same enzymes which our liver uses to reverse the process (ethanol -> acetaldehyde)! Yes, that is how your favorite alcoholic beverage is produced.....
Other organisms (such as animals and various bacteria) also have an "extra" step to further metabolize pyruvate anaerobically if sufficient oxygen is not available for pyruvate to enter the Krebs' cycle. Luckily, we don't act like yeast and convert pyruvate into ethanol (otherwise I would get smashed every time I ran the 100 meter dash LOL). Instead, in anaerobic conditions, we convert pyruvate into a substance known as lactic acid, the structure as follows:













Compare the structure of lactic acid to pyruvate above. Notice anything? The ketone =O group on pyruvate is reduced to an alcohol -OH group, forming lactic acid. HOW is this done? By our helpful redox agent, NAD. NADH reduces pyruvate to lactic acid, generating NAD+, in the presence of the enzyme lactate dehydrogenase (LDH).
What is the purpose of converting pyruvate to lactate or ethanol? Well, we are getting to the point, finally! Since pyruvate is reduced to lactic acid in humans, it helps to regenerate NAD+. If glycolysis simply stopped at pyruvate, NADH would build up quickly. Since there is a fine balance between red-ox agents (NADH <-> NAD+), if NADH builds up, NAD+ is depleted, and anaerobic glycolysis can't continue. NAD+ needs to be regenerated so that glycolysis can be continued in an anaerobic environment.
Lactate is subsequently shuttled from anaerobic environments such as skeletal muscle to the liver for metabolism back into glucose via a process known as gluconeogenesis. The gluconeogenetic pathway is not the exact reverse of glycolysis, however, the 1ST STEP involves oxidation of lactic acid back to pyruvate, which is the substrate the liver uses to begin gluconeogenesis. Just as the anaerobic fermentation process uses NADH to reduce pyruvate to lactic acid, the reverse happens in the liver, as NAD+ must be utilized to oxidize lactic acid back into pyruvate for entry into the gluconeogenetic pathway. This can't occur if there is an excess of NADH equivalents, and NAD+ is deplete. Therefore, an excess of NADH tends to favor conversion of pyruvate to lactate, whereas the liver needs to do the reverse in order to initiate gluconeogenesis. Thus, in summary, an excess of NADH impairs gluconeogenesis, and glucose can't be made by the liver.
And so we come back to ethanol metabolism, which we had previously stated also generates an excess of NADH molecules. Therefore, if you imbibe too much ethanol, an excess of reducing agent is produced in the form of NADH, and gluconeogenesis is impaired. This is the main effect producing the symptoms of hangover. As well, as previously stated, the intermediary step in ethanol metabolism, acetaldehyde, is also toxic to the body, and thus is further metabolized to vinegar. However, if an excess of ethanol is taken in faster than it can be metabolized through these pathways, acetaldehyde can also build up, further contributing to the unpleasantness of hangover. This notion is exploited in a particular treatment for alcoholics, a medication known as disulfiram (Antabuse). Disulfiram inhibits the enzyme acetaldehyde dehydrogenase, and thus acetaldehyde levels build up quickly when an alcoholic tries to drink, and they get sick. Sadly, it doesn't work too well.
It is therefore the excess of reducing equivalents in the form of NADH which contribute the most to the development of a hangover, through its inhibitory effect on gluconeogenesis. The biochemical processes involved are very much linked to metabolism of food through the glycolytic pathway, as seen in the creation of ethanol by anaerobic organisms, and our breakdown of this substance. So next time somebody tells you that "dehydration" causes a hangover, tell them that is only part of the story, and refer them to this article!

The State of the NBA

Given the recent brawl between the New York Knicks and the Denver Nuggets, my attention was turned to the current state of the NBA, and why I really do not follow this league or the NY Knicks anymore. This is in stark contrast to the past, in which I watched about ~95% of all the regular season and post-season games from the period of 1992-2000 (somewhere around 1000 games). This was the heyday of both the NY Knicks and the NBA as a whole, and I was lucky during that time to live in an area where we received every Knicks game on the Madison Square Garden (MSG) Network. I loved everything NYC during that time, including the Jets and Yankees, although I didn’t follow them as closely as the Knicks, as basketball to me was much more exciting than any other sport (I followed football a lot, but largely watched the Buffalo Bills at that time, whom I now represent over the Jets!). Besides the Knicks, the rest of the NBA was also exciting given the caliber of players that were in the game at that time (more on that later).

Although I didn’t watch this game live either, for those who missed it, here is a video of the Knicks-Nuggets brawl on December 16, 2006:

I was lucky to catch the video the morning after it happened on YouTube.com, but within ~24 hours, almost all of the video capturing the brawl was taken down from the website, with a disclaimer at the top of the page stating that the video was copyright by the NBA. Therefore, I apologize if the video is broken, but you can blame the NBA for that. I don’t see any other NBA footage being removed from the website, so one can only assume that the league singled out this “brawl” for removal rather than all of the highlights of their players performing spectacular moves, which remain on YouTube.com.

The NBA (Commissioner David Stern in particular) has obviously wanted to clean up its league’s image for quite some time now. This campaign largely started in response to the other infamous ”brawl” in recent years, the Detroit Pistons-Indianapolis Pacers brawl in November 2004. This brawl, initially involving Ron Artest and Ben Wallace, turned ugly quickly when the fans became involved in the fight:

Both the Knicks-Nuggets and Pistons-Pacers fights were similar in that both occurred towards the end of the game, starting with a flagrant foul upon the team that led by a wide margin (thereby obviously about to win).

Despite these numerous fights, I do not feel that it has much to do with the downfall of the NBA. Fights within professional basketball have been going on for a long time, and some of the legends have been involved in them as well (Dr. J vs. Larry Bird comes to mind).

The 2 biggest fights I had ever witnessed in professional basketball up until the Pistons-Pacers brawl both involved the NY Knicks. The first occurred in March 1993, and involved the NY Knicks and the Phoenix Suns. I remember that the game had been boring up to that point so I went up to take a shower and get ready for bed. Coming out of the shower, I went downstairs to see what the score was, but didn’t have my glasses or contacts on, so I couldn’t see much. Within a minute, a fight broke out between Doc Rivers (NY) and Kevin Johnson (Phoenix), and I had to sit within a foot of the screen to watch what transpired. The whole Knicks bench was cleared, and the result included Greg Anthony, who was injured and in street clothes at the time, going after K.J. and punching him in the face. It was the biggest brawl in the NBA up until that point, with tons of fines and suspensions.

The 2^nd biggest fight I had ever seen was the infamous NY Knicks-Miami Heat brawl in the 1997 playoffs. This fight got started when The Heat’s P.J. Brown BODYSLAMMED Knicks point guard Charlie Ward. That one act had the entire Knicks’ bench cleared in seconds, and everybody got into it, including Patrick Ewing, Larry Johnson, Allan Houston, and John Starks. The Knicks-Heat rivalry was pretty thick around that time in the NBA, after Pat Riley left coaching the Knicks to go to Miami, with some possibly shady deals occurring under the table to get Riley to leave NY.

Other notable NY Knicks fights I can remember occurred in the following season playoffs, continuing the previous brawl between the Knicks and Heat. I remember thinking that that fight was unusual because it involved former teammates Larry Johnson and Alonzo Mourning (both had previously played for the Charlotte Hornets). The bench-clearing occurred again but this time it ended with Knicks coach Jeff Van Gundy down on the court hanging on for dear life on Alonzo Mourning’s leg. He was pretty lucky he didn’t get trampled to death!

The Knicks-Pacers rivalry in the mid-90’s also produced some heated exchanges, many between John Starks and Reggie Miller (I HATED Reggie Miller!!), including the infamous fight that occurred when John Starks heat-butted Reggie Miller.

However, these fights are only a part of the problem the NBA faces these days, and as you can see, some pretty big fights occurred in the 90’s, when the NBA was in its prime. The issue nowadays is that there are no team dynasties and exciting players to follow anymore. There are a few great players, such as LeBron James and Kobe Bryant, but not one of them are as exciting as the NBA stars of the past, like Magic Johnson, Larry Bird, and Patrick Ewing.

And then we come to Michael Jordan. I never really appreciated him when he played, because he and the rest of the Chicago Bulls always thwarted the Knicks’ championship dreams in the early-to-mid 90’s. I HATED Michael Jordan with a passion back then, and so did most Knicks’ fans. But the Knicks-Bulls games always made for exciting basketball. Looking back, there is no doubt that MJ was the greatest player to ever play the game, and I’m not sure the NBA will ever return to those days, for 1 main reason: There were many exceptional players on many teams when MJ was playing, and this brought out the best in him. I honestly don’t think that MJ would be as amazing if he had played today, because the caliber of players overall is just not as good in the NBA.

I miss the NBA :( To me, it will never be the same. That’s why I pretty much stopped following the Knicks after Ewing left. They don’t have any franchise players in the league anymore, as free agency has also hurt the NBA (the only great players that have stayed with their original teams for a prolonged period of time is Kevin Garnett on the T-Wolves and Allen Iverson on the 76's-who at the time of this writing was just traded to the Denver Nuggets several days ago).

As a last plug against Michael Jordan and the Bulls, I will leave you with one of the greatest plays I had ever witnessed in all of my days watching the Knicks, by my favorite player of all time John Starks, THE DUNK: