Gout: a disease of humans or culture?

In medical school I was taught that gout was a condition caused by uric acid crystals that attack and inflame a joint. Thinking of these sharp crystals stabbing cells in joints such as the big toe still creates for me a mental image of extreme pain.

From Wikipedia

Uric acid is the end-product of purine metabolism.  Purines are organic compounds that are rich in foods such as meat (particularly kidneys, liver and brains) and alcohol.  Many people can have elevated uric acid levels without developing gout, but once the crystallization process begins, it is often a lifelong condition.  The primary cause, I was taught, was secondary to an under-excretion of uric acid by the kidneys, and the treatment was primarily to acutely decrease the pain and inflammation with medications such as colchicine, steroids, or non-steroidal anti-inflammatories, and then try to reduce the occurrence of gouty attacks with medications such as allopurinol.

Further, as it was more common with diets high in meat products, alcohol, obesity, insulin resistance and kidney disease, it was also advisable to treat these conditions as well.

And this is largely how I still treat gout.

However, I don't remember ever being taught (or myself asking) why we develop these uric acid crystals in the first place. In fact, humans are one of the very few organisms that develop uric acid crystals, or uric acid kidney stones or deposits of uric acid in joints, called typhi. Most other organisms have an enzyme called uricase, which destroys the uric acid, and thus they never have to worry about this condition.

In fact, this uricase enzyme in humans has been effectively disabled by genetic mutations. Why? Many scientists think that there may be many reasons for this.  Uric acid is a very strong anti-oxidant, and it may be beneficial in reducing reactive oxygen species (ROS) that can damage cells and cause premature aging.  It also offers neuroprotection.  Other scientists believe that at one time humans lived in a very low salt environment, and they adapted to this environment by disabling the uricase enzyme. This allowed humans to increase their production of uric acid, which allowed them to gently increase their blood pressure without the use of salt.

However, place these humans in areas with highly processed foods, high in calories and animal proteins, and environments prone to kidney disease (i.e., hypertension, diabetes, smoking), then they will under-excrete the uric acid. Indeed, gout was once referred to as the "disease of the kings" because only the rich could afford meals high in purines such as animal protein and alcohol, particularly wine.  Now, however, gout affects 4% of Americans and has doubled in incidence from the 1960s to the 1990s.  Further high uric acid levels (without actual gout) affect 20% of Americans.

Thus, maybe gout isn't a medical problem of the body, but rather ourselves and our culture not obeying the laws of the body. Maybe the body is trying to tell us to eat a low salt diet, drink plenty of water, and limit its intake of purine rich foods. Maybe we should listen to our body instead of constantly trying to "correct" its "mistakes."

What We Might Learn From Automobile Safety

One of the major advancements in public health has been the decrease in mortality from automobile accidents, as seen in this graph.

This achievement took action on part of engineers, behavioral psychologists, law enforcement, and countless other individuals working together to create a desired effect. For instance, below is a video from the National Highway Transportation Safety Administration (NHTSA) showing the result of a 1959 Bel Air automobile crashing into a 2009 Chevy Malibu. Although the Chevy Malibu is a smaller car, the passenger in the Malibu is much more likely to survive a crash than the passenger in the larger Bel Air. This occurred largely secondary to the impact of improved seat belts, improved crunch zones, and air bags.

Let’s break down how some of this achievement in decreasing automobile fatalities occurred. Here is a graph showing how seat belts (particularly shoulder-restraint rather than lap belts) saved lives, as well as the potential impact from air bags.

 

Further, behavioral modification changes such as greater criminalization of drunken driving have also decreased mortality.

We still have significant challenges, such as the increase in distracted driving by people texting or using their phone to search the internet, the potential increase in death rates from higher speed limits, the potential increase in marijuana-related accidents, and the challenge to decrease mortality from more fuel efficient cars that are often made with less steel. But these are seen as process-oriented problems with a hope for process-oriented solutions.

In short, this improvement in automobile fatalities occurred because many bright people from different fields worked together to help create a desired outcome.

But what would have happened if we just left the outcome to the individual buyer or driver of the car? Would the outcome have been as positive?  What if the buyer were given the option not to purchase that annoying beep when you don’t buckle your seat belt? Or if he/she could have paid a little less money not to have seat belts or air bags?

Yet when it comes to public health, we often state, “Well, it’s up to the individual.” Is this the best way to effect behavioral change? As a country, it is estimated that our obesity rate will be 42% to 50% by 2030. How will we pay for the increased health care costs that wlll result? If we have an outcome we desire as a population, for the individual and society, such as decreased obesity, why don’t we have thought leaders from many disciplines -– healthcare providers, industrial engineers, city planners, nutrition specialists, exercise physiologists, restaurateurs, farmers, basic scientists working on human homeostasis -- all work together to help generate the desired outcome?

Perhaps we may have better opportunity to effect the behavioral change desired if we create cities where people want to walk around, create communities that foster social interaction in healthy behaviors, create more nutritious fast food meals that are satisfying yet low in calories, and work together to decrease the burden for individuals and for society.

Help Your Provider, Help Yourself

I was eating dinner the other day with one of the healthiest appearing 62-year-old women I've ever met. She was vibrant, active and looked 15 years younger than her age. She said that she sees her doctor once a year and every year her doctor appears a little older, a little more harried, and little more distressed. She said, “I just want to give her a hug and tell her everything is going to be okay.”

The truth is that with decreasing reimbursements, liability concerns, office over-head expenses, personal debt concerns, more regulations, the need to see more patients in fewer hours, etc..., many providers feel quite frazzled. I believe some of this stress also occurs from the technological disruption which is occurring in the medical environment. Providers are not Luddites. Most providers I know love using their I-phone, and apps such as Epocrates which allows them to search medications or using web based resources such as E-medicine or Up-To-Date. However, many electronic medical records (EMRs) are not necessarily doctor-patient friendly. Rather, instead of the computer working for the patient and physician (as in the case of Epocrates and Up-To-Date), often providers feel they are working for the computer and they must adapt to it. For instance, here is a discharge note I received from an excellent cardiologist just last week. This is taken verbatim. “Please note that it is difficult to give the exact instructions of amiodarone on our electronic medical record system; but the fact that the patient will take 200 mg twice a day of amiodarone for 1 week followed by 200 mg daily has been explained to the patient and his family members.” It is not the fault of the drug or the physician, but the electronic medical record simply does not allow the input of such directions. Overall, it is a difficult transitions for many providers which I hope will work out for the best, particularly for the patient.

Lastly, new coding guidelines (called ICD-10) require such precision that in the future I am not sure how providers will be able to performs such tasks without either a medical scribe or a more enhanced artificial intelligence build into the medical record. To give an example, below I created a simple medical narrative and how it could be coded with the new ICD-10 guidelines. It could be funny, until you realize all the codes are real.

“John Doe drank a little and bet some money on the 2^nd Annual Llama and Camel Race at the Henderson Race Track. Unfortunately, he drank a little too much, tripped and fell on the driveway outside a local mobile home but was able to regain his balance before falling into a telephone pole and then, catching his balance, falling into it again. Undeterred, he decided to get on one of the llamas himself and ride off into the sunset, but was unfortunately hit by a 1994 Chevy Malibu. Thrown off the animal, he suffered a tri-malleolar fracture and appears to you dishelveled and slightly drunk.”

Now, CODE IT!

Y92024 Drive of mobile home as the place of occurrence of the external cause

W22.02XA Walked into lampost, initial encounter

W22.02XD Walked into lampost, subsequent encountered

V80.919 Hit by motor vehicle while riding an animal

S82.851A Initial encounter for closed fracture of tri-malleolar fracture

R46.1 Bizarre Personal Appearance

Such coding accuracy is often not taught in medical school or residency and requires a great deal of understanding and effort by the provider. Lastly, the simple basic medical narrative which tells of the patient's very real concernces and conditions can get lost.

So, in an effort to “do no evil” as Google might say, using Microsoft Word, my program director, Dr. Michael White, led a simple task force of myself and a college student to create a Microsoft Word template for an individual to construct his/her own medical summary. This can then be handed to the provider by the patient. It's a simple template which allows you to fill in your own medical history. Here is an example.

It can take a little while to accomplish depending upon your medical history but I believe it can be useful for both yourself and for the provider caring for you. One patient gave it to his doctor, and the physician actually started to cry because it was so useful for him and the medical record in general.

I do not know how to embed a formatable Microsoft Word document in Blogger, but if you would like to email me at delippman@yahoo.com with subject line, Medical Record, I will send you a copy for free.

Stress and Health

I am frequently asked if stress causes disease. Stress, I believe, has a huge psychological impact, and maladaptive behaviors in which we often engage in response to stress (such as smoking, overeating, excessive alcohol consumption, excessive rumination, etc...) can have extreme effects on one's physical health. Thus, potential treatment of stress may focus not only on reducing the stress-inducing events themselves, but also on one's response to such an event.

One of the organizations most interested in the physical and psychological impact of stress on the individual is the military. Military soldiers such as special operation forces who have a high probability of being behind enemy lines are often trained in intensely stressful situations with the hope of developing “stress inoculation.” Similar to vaccination theory, in which one is inoculated from a potential disease by vaccination with the virus and allowing one's immune system to fight it, stress inoculation hopes to build hardier soldiers to allow them to survive stressful situations associated with war.

One of the most stressful situations soldiers can experience is a course called Survival, Evasion, Resistance and Escape (SERE) at Fort Bragg's JFK Special Warfare Center. The SERE course is designed to simulate the evasion of an enemy, and if caught, to simulate a prisoner of war experience. Yale University's Dr Morgan, a researcher for the National Center for Post Traumatic Stress Disorder, studied 109 participants in the course.  Dr Morgan, et al. published their work with the title “Hormone Profiles in Humans Experiencing Military Survival Training” in 2000 in the Journal of Biological Psychiatry (2000:47: 891-901). They studied the salivary levels of cortisol and serum levels of testosterone at various stressful episodes of the training. Cortisol is a hormone released from the adrenal glands, which release carbohydrates for use by the brain. Testosterone is the primary male sex hormone.

In examining these individuals during stressful situations, researchers found that cortisol levels increased, while testosterone decreased. There was a change in the cortisol and testosterone during the escape and evasion, but the greatest changes in these hormones occurred when the soldiers were captured and underwent interrogation. During captivity and subsequent interrogation, testosterone levels could decrease to castration levels within 8 hours; the soldiers became effectively sterile during such episodes.

This study and others like it demonstrate that physical and psychological stress can have a profound biochemical effect on the body. It appears that this psychological impact is activated by a small walnut-sized organ in the middle of our brain called the amygdala. The amygdala analyzes for potential threats. If a threat is perceived, then messages are sent to the hypothalamus to release the fight or flight hormones.

From Wiki

It appears that there can be imprinting of a fearful event on the amygdala during a stressful situation. Thus, experiences that remind the amygdala (even unconsciously) of the stressful event can activate the amygdala to send a signal to the hypothalamus to release a cascade of fight/flight hormones. It is similar to someone who is having a panic attack. That person is convinced there is impending doom about to affect them. “Rationality” or “reason” are rarely effective during the acute attack, because one's body is currently being flooded by an activated amygdala subjecting oneself to a cascade of stress hormones.

People can respond to stressful events in different ways.  For instance, many smokers state that they smoke more in response to stress. Smoking releases dopamine, which is a “feel good” hormone. One can understand the desire for the cigarette in the effect that it has on dopamine release. However, when the dopamine wears off, the smoker often feels the need to smoke another cigarette to replenish the dopamine. This often creates a vicious cycle.

Are there other, more healthy means to decrease the impact of an activated amygdala? Actually, our frontal cortex is filled with inhibitory neurons, that, if activated, can calm an over-excited amygdala.  One activity that can help "turn down" the amygdala is meditation.  Meditation activates the inhibitory neurons from the prefrontal cortex and frontal cortex.  When functional MRIs (MRI scans that are performed with radioactive glucose that goes to areas of increased activity) are performed on skilled meditators, the activity in their frontal cortex and prefrontal cortex "light up."

There are various meditative techniques one can use to "silence the amygdala."  Often it is an attempt to decrease the constant inner voice chatter that occurs in our minds, most of which is negative, and allow a more contemplative, passive process.  Dr. Harold Benson, a cardiologist from Harvard, wrote The Relaxation Response in the mid-1970s and still has courses for physicians and other healthcare providers at Harvard.  His technique is at this website.  Christians may find Father Thomas Keating's Centering Prayer helpful; here is a website that offers PDFs that describe his process.  Thich Nhat Hanh, a Buddhist monk who has written extensively on meditation, has a short essay here on one of his simple, yet potentially powerful techniques.  

Center and Balance in Da Vinci's Vitruvian Man

Leonardo Da Vinci's Vitruvian Man has amazed me for at least the past 15 years.  Here is a little video I made to explain some of my reasons and perceptions, particularly from a functional anatomy point of view.

 

 

 

I am not the only individual to believe that there may be physical exercises within Da Vinci's drawings.  Michael Gelb has written several books, and this link has some of the exercises he has developed from the drawing.  http://www.signlanguageofthesoul.com/leonardo.html. 

 

My view is more static.  I simply ask the individual to stand in the "box" position for several minutes or lie down on the floor or the bed in the circular position for several minutes and to truly feel one's center of balance in the body.  Regardless of whether you engage in these exercises, Mr. Gelb's exercises, or simply a thought exercise, I hope the genius of Da Vinci shines through this little video.

Marlboro, Portion Distortion and Marketing Magic

Marlboro.

 

Whether you smoke or not, what do you think of when you hear that word? Cowboys and the American West, right? I grew up in 1970s suburbia and have been on a horse once in my life. I have more to with the American West than Marlboro!

Where does Marlboro come from? Marlboro is owned by a British corporation, Philip Morris. The name comes from a street in London called Great Marlborough on which its factory was first situated.  It originally started as a cigarette for women in the 1920s, and was known with the tagline, Mild as May, because their first “smokeperson” was not the Marlboro Man, but rather the famous movie star Mae West.

As can be seen in the ad, smoking was considered a feminine activity and not considered “manly.” In the 1950s, Philip Morris wanted to change their marketing to men and worked with Leo Burnett of New York  to create the Marlboro Man to market to men. The cowboy was chosen and the rest is history. Instead of thinking of a street in London, England, we associate Marlboro with the American cowboys. That is the power of advertising and brand identification.

Marketing does not take place on a billboard, on a television station, or in a magazine. It takes place in one’s individual consciousness. It creates a mental image that the viewer identifies with or wants to identify with.

As Al Reis and Jack Trout state in Marketing_Warfare (p . 44) “Marketing battles are fought in a mean and ugly place. A place that’s dark and damp with much unexplored territory and deep pitfalls to trap the unwary. The mind is the battleground. A terrain that is tricky and difficult to understand. The entire battlefield is just 6 inches wide. This is where the marketing war takes place. You try to outmaneuver and outfight your competitors on a mental mountain about the size of a cantaloupe. A marketing war is a totally intellectual war with a battleground that no one has ever seen. It can only be imagined in the mind, which makes marketing warfare one of the most difficult disciplines to learn.”

It is the power of advertising to effect behavioral change in an individual and a society that most interests me. Personally, I believe advertising has led to some remarkable changes in American life in terms of one’s health. From my perspective we can see this in how it has changed our social norms.

For instance, I believe the greatest cause of increase in our calories as a country is related to increase in portion sizes. Supersized meals and supersized sodas now look normal. A “typical” (based on RDA values) individual serving size now appears small. This is not because the serving size has changed, but because how we perceive them has changed. A great deal of this was accomplished through very successful marketing by different organizations.  For instance, as detailed in Greg Crister's Fatland. David Wallerstein, who was a director at McDonald's corporation, was first to suggest to the founder, Ray Kroc, to introduce supersized fries.  He argued that it was a values proposition.  People felt (and bought) that they were getting an increased value for the extra money they spent on the larger fries.  The consumer thus doesn't feel they are suffering from gluttony but rather they convince themselves they are being "frugal" shoppers by paying a little more for a much larger portion.  Meanwhile the franchisee is able to spend just a few extra pennies to create the supersized meal, with the extra charge being  primarily pure profit.

This has had a caloric effect on the individual consumer.  From Fatland, p. 28: "By the end of the century, supersizing --the ultimate expression of the value meal revolution -- reigned.  As of 1996, some 25 percent of the $97 billion spent on fast food came from items promoted on the basis of either larger size or extra portions.  A serving of McDonald's French fries had ballooned from 200 calories (1960) to 320 calories (late 1970s) to 450 calories (mid 1990s) to 540 calories (late 1990s) to the present 610 calories (2003).  In fact, everything on the menu had exploded in size.  What was once a 590-calorie McDonald's meal was now...1550 calories.  By 1999 heavy users -- people who eat fast food more than twenty times a month -- accounted for $66  billion of the $110 billion spent on fast food...Kids had come to see bigger everything -- bigger sodas, bigger snacks, bigger candy, and even bigger doughnuts -- as the norm; there was no such thing as a fixed immutable size for anything, because anything could be a made a lot bigger for just a tad more."

We can see this change from  the National Institute of Health Portion Distortion website, regarding how portion sizes have changed over 20 years from 1984 to 2004

Just look at the first picture of the coffee.  I believe it is almost impossible to view the coffee on the left as "small."  However, if we went back 20 years, we may have looked at the coffee on the right as "huge."  The latter view is probably a more correct one from a caloric perspective.  Here are some more examples of portion distortion

 

 

 

 

 

 

 

But how do we go back?  Our appetite in a variety of ways has fundamentally changed, and we've entered a "new normal."  This blog is not a criticism of brand marketing. Rather it is to help us become aware of its impact. We often state how hard it is to effect behavioral change, yet many companies are quite effective at creating it and we may have something to learn from them.

Perhaps we can use similar marketing techniques to create a healthier society, but the question is, how?  This post may lead to more questions in this regard than answers; however, I think it may be beneficial to study how marketers can move products and in so doing effect behavioral change.  It often requires an understanding not of rational concerns, but emotional ones.  We must be able to connect with the individual -- understand and appreciate his/her anxieties, fears and desires.  Perhaps, if we are honest with ourselves, we can learn a great deal from this marketing warfare to truly effect a healthier society.

Is It Cholesterol or Is It Oxygen?

I am virtually a vegetarian. (I eat pizza, which has milk, and had a meatball in New York last summer). However, my cholesterol is high, and I take cholesterol-lowering medication. Cholesterol comes from the animal family, and I eat virtually no animal products, so why would my cholesterol be high?

Approximately 75% of our cholesterol comes from what our liver produces, NOT from what we eat.   An enzyme called the HMG-CoA reductase is used by the liver to create cholesterol.  Medications called statins, which act on this enzyme, can lower one's cholesterol by up to 60%.   By contrast, medications that block cholesterol absorption from our diet will only lower cholesterol approximately 10%.

What exactly is cholesterol, and why, for many of us, does the liver produce so much of it?

To understand cholesterol, we must go back to basic biology and discuss prokaryotes and eukaryotes. Prokaryotes are cellular organisms whose cells do not have a nucleus, and eukaryotes are cellular organisms whose cells have a nucleus and other membrane-bound organelles. Prokaryotes do not have cholesterol, while eukaryotes use cholesterol to form the nucleus and other membrane-bound organelles. The cholesterol allows a stiffness and organization to the cellular membranes. The cholesterol also acts as a means of intracellular transport within the membrane itself. We humans, as well as all mammalians, are eukaryotes. 

Konrad Emil Bloch received the Nobel Prize for Medicine for his work on the biological synthesis of cholesterol in 1964. He noted that the creation of cholesterol required a great deal of energy and oxygen. The creation of cholesterol requires approximately 27 separate processes. He hypothesized that the utilization of oxygen to create cell walls and cholesterol walls was a complex organism's response to an oxygen-rich environment.  From this theory, we understand that cholesterol formation is an ingenious process of using the oxygen for the organism's benefit.

As we age, this cholesterol production can contribute to atherosclerosis through the process of developing an atheroma, or an intracellular lipid accumulation. Here is a nice picture of it from Wikipedia.

Cholesterol is insoluble in water and requires lipoproteins to transport it. Low Density Lipoproteins (LDL) deposit the cholesterol in plaques inside the arterial walls, while High Density Lipoproteins (HDL) act like scavengers and can help remove some of the plaques. The amount of LDL in the human organism is strongly related to cardiovascular risk.

However, it was discovered that it was not just LDL, but the degree of oxidized LDL that correlated with endovascular injury.  Oxidized LDL can damage the endothelial cells and allow cholesterol to build deposits in the subendothelial area (the space right below the endothelium lining the artery). This injury to the endothelial lining allows more cholesterol deposits to be created in the subendothelial area, creating more inflammation. White blood cells known as macrophages, which fight inflammation, try to repair the injury caused by oxidized LDL and consume them, causing “foamy macrophages.” This process is a very aggressive, angry, inflammatory process. If any of the area ruptures, then a blood clot can be formed, as stated in the prior post on coronary artery disease.

This process is known as “oxidative stress.” It is like rust on the bottom of an old car. Oxygen can be a very hungry molecule and has the ability to rip electrons off other nearby molecules. The molecules with the missing electrons are known as free radicals, and they can rip electrons off other nearby molecules, causing a free radical chain reaction.  As ferric oxide eats away at a car, so can this oxidative injury damage the endothelial lining of our cell walls.

As scientists understand more about this inflammatory, aggressive process, more unique treatments are being discovered. For instance, although powerful antioxidants such as Vitamin E and Vitamin C were not necessarily found to be beneficial for decreasing heart disease, other types called polyphenol antioxidants may be quite effective. In fact, in a study in the Journal of Clinical Nutrition, the use of pomegranate juice (a polyphenolic antioxidant) actually reduced atherosclerotic plaque in individuals with carotid artery stenosis. In a study in the journal Atherosclerosis, the addition of pomegranate extract to statins actually reduced macrophage foam cell formation and was felt to potentially decrease atherogenesis.

In short, cholesterol itself is amazing. It plays an essential role in the membranes of animal cell walls. It also is critical in the formation of molecules such as Vitamin D, steroid hormones and bile acids. But it appears intimately associated with oxygen.  Cholesterol may be created as a response to an oxygen-rich environment, and oxidative stress can impact the LDL receptors that carry it and contribute to the creation of atherosclerotic disease.  Perhaps in the future, we may become wiser about various lifestyles that may optimize the benefit of both oxygen and cholesterol without creating a disease process from them.