Tuesday, October 5, 2010

From "American Family Physician" - excellent review of vaccines and autism

AFP Journal Club
The Story Behind the Study

Autism and Childhood Vaccinations: Debunking the Myth
ROBERT DACHS, MD, FAAFP, Ellis Hospital Family Medicine Residency Program, Schenectady, New York

ANDREA DARBY-STEWART, MD, Scottsdale Healthcare, Scottsdale, Arizona

MARK A. GRABER, MD, FACEP, University of Iowa Carver College of Medicine, Iowa City, Iowa

Am Fam Physician. 2010 Sep 15;82(6):586-592.

Each month, three presenters review an interesting journal article in a conversational manner. These articles involve “hot topics” that affect family physicians or “bust” commonly held medical myths. The presenters give their opinions about the clinical value of the individual study discussed. The opinions reflect the views of the presenters, not those of AFP or the AAFP.

This Month's Article
Gerber JS, Offit PA. Vaccines and autism: a tale of shifting hypotheses. Clin Infect Dis. 2009;48(4):456–461.

Are childhood vaccinations associated with subsequent development of autism?

Bob: In 1998, a British gastroenterologist, Dr. Andrew Wakefield, published a report in the Lancet on eight children who developed symptoms of autism within one month of receiving the measles, mumps, and rubella (MMR) vaccine.1 Since then, the media, advocacy groups, and celebrities have promulgated the link between childhood vaccinations (particularly the MMR vaccine) and the development of autism. But, is it true?

This month's article clearly outlines the epidemiologic and biologic studies that should reassure physicians and parents that there is no connection between childhood vaccinations and autism.2 For the family physician, the data in this article are impressive and can be used to counter most parental concerns.

What does this article say?

Bob: This article reviews the three most commonly proposed hypotheses for vaccine-induced development of autism: (1) the MMR vaccine damages the intestinal lining, allowing the entrance of encephalopathic proteins; (2) thimerosal induces central nervous system toxicity; and (3) multiple vaccinations overwhelm and weaken the immune system. This article looks at the genesis of each theory and the data that debunk them.2

In regard to the MMR vaccine, Dr. Wakefield noted lymphoid nodular hyperplasia on endoscopy in eight children with gastrointestinal symptoms and signs of autism within one month of receiving the MMR vaccine. He then postulated that this intestinal inflammation allowed nonpermeable peptides into the bloodstream, subsequently affecting brain development.1

There are many holes in this argument. First, this was a self-referred cohort without a control group. Second, in Great Britain, approximately 50,000 children one to two years of age receive the MMR vaccine each month; this is a time when autism typically presents, making this likely a coincidental association. Third, the MMR vaccine has not been found to cause chronic intestinal inflammation. Fourth, no toxic encephalopathic proteins traveling from the intestine to the brain have ever been identified. Instead, genes that code for endogenous proteins, which influence neuronal synapse function, have been identified in children with autism.3

Mark: The most glaring flaw in the argument connecting an MMR-induced intestinal hyperplasia and subsequent autism development is assigning cause and effect to a potential association. Association should not be confused with causation.

Without a control group in the original study by Dr. Wakefield, it is imprudent to even suggest that there is an association between the MMR vaccine and intestinal lymphoid hyperplasia. Large-scale studies are often needed to demonstrate whether an association is statistically present.

Bob: The authors of this month's article reviewed 13 such large-scale studies that demonstrate no association between the MMR vaccine and autism.2 These are separated into three types of studies:

Ecologic (studies comparing vaccination rates with autism diagnosis). In California and the United Kingdom, the diagnosis of autism increased through the 1980s and 1990s, yet MMR vaccination rates remained stable during this time.4,5 In Quebec, Canada, autism rates increased despite a decrease in MMR vaccination.6

Retrospective observational (studies comparing vaccination status with autism diagnosis using national registries). The best study was one conducted in Denmark in which 440,655 children born between 1991 and 1998 who received the MMR vaccine were compared with 97,648 children born during the same years who were not given the MMR vaccine. There were no differences in autism rates between the two groups.7

Prospective observational (a long-term vaccination project allows researchers to prospectively record adverse events associated with the MMR vaccine). In Finland, 1.8 million children were prospectively followed after MMR vaccination, and no cases of vaccine-induced autism were recorded.8

Andrea: To further refine the concept of association and causation, there are times when an association does represent a cause and effect. A good example is smoking and lung cancer rates. Clearly, smoking is associated with increased lung cancer rates, and a randomized, placebo-controlled trial is not needed to prove this. The association between smoking and lung cancer meets all of the following criteria: strength and consistency of the scientific data; existence of a temporal relationship (between smoking history and lung cancer); existence of a biologic gradient (increased exposure results in increased risk); a scientifically plausible association; and experimental interventions that work (smoking cessation decreases cancer rates).9 However, in the case of MMR vaccine–induced autism, none of these criteria are present. The data, in fact, overwhelmingly support no association.

Bob: Let's briefly look at the second hypothesis of thimerosal-induced neurotoxicity. Thimerosal is an antibacterial agent that has been used in multidose vaccine preparations for more than 50 years. It is 50 percent ethyl mercury by weight. However, mercury poisoning has a distinctly different presentation than autism. The CDC has also demonstrated that the mercury in vaccines has not resulted in any subtle signs or symptoms of mercury poisoning.10 The authors of this month's article review seven large-scale studies—again, ecologic, retrospective, and prospective studies—all demonstrating no association between thimerosal and autism.2

Mark: And, by the way, live vaccines like MMR do not contain thimerosal.

Bob: The third and final theory suggests that the simultaneous administration of multiple vaccines overloads the immune system, triggering autism in a susceptible host. However, because of advances in protein chemistry and DNA technology, the immunologic load has decreased from more than 3,000 immunologic components in the seven available vaccines in 1980 to less than 200 in the 14 recommended vaccines today.2

Andrea: Two more points: (1) an infant's immune system is capable of handling the thousands of antigens it is exposed to early in life; and (2) autism is not an autoimmune disease. Therefore, this theory has no credibility.

Should we believe this study?

Bob: This month's article clearly provides the science and statistics to dispel the theory that childhood vaccinations induce autism.2 A Cochrane review came to the same conclusion in October 2005.11

Andrea: Large-scale studies, smaller studies, retrospective studies, prospective studies, and case-control studies (you name it) all come to the same conclusion: there is no connection between vaccines and autism. The only outlier is Dr. Wakefield's study, which suggests this possible link.1

Mark: Lo and behold, 10 of the 13 authors of Dr. Wakefield's Lancet article have since publicly retracted the interpretation they reported.12 The editor of the Lancet has acknowledged that, had they appreciated the full context of Dr. Wakefield's study, “… publication would not have taken place the way that it did.”13 On further review, the Lancet also recently published an official retraction of Dr. Wakefield's study (http://press.thelancet.com/wakefieldretraction.pdf).

What should the family physician do?

Bob: Get this month's article. It's an easy read. Keep it handy for when parents are apprehensive about immunizing their child.

Andrea: A national survey conducted in 2003 to 2004 indicated that more than one fourth of all U.S. parents were either unsure of vaccine safety or refused or delayed vaccination of their children because of safety concerns. However, the most important take-home point from that survey was that the parents who changed their minds and immunized their children did so because of information and assurance provided by their health care professional.14 Indeed, we do make a difference!

Mark: Understand the consequences if we just give in to fear and myths. In 2008, only three fourths of preschool children in the United Kingdom received two doses of the MMR vaccine. The result: measles infection rates have reached more than 1,000 cases per year, the highest since monitoring began in 1995.15

Main Points
There are no epidemiologic or biologic studies that support a connection between childhood vaccinations and autism.
EBM Points
An association does not confer causation.
Multiple criteria should be examined when considering if an association implies causation, including strength, consistency, specificity, temporality, dose-response relationship, plausibility, coherence, experimental evidence, and analogy.9

Address correspondence to Robert Dachs, MD, at dachsmd@aol.com. Reprints are not available from the authors.

Author disclosure: Nothing to disclose.

1. Wakefield AJ, Murch SH, Anthony A, et al. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children [retraction published in Lancet. 2010;375(9713):445]. Lancet. 1998;35(9103):637–641.
2. Gerber JS, Offit PA. Vaccines and autism: a tale of shifting hypotheses. Clin Infect Dis. 2009;48(4):456–461.
3. Sutcliffe JS. Genetics: insights into the pathogenesis of autism. Science. 2008;321(5886):208–209.
4. Dales L, Hammer SJ, Smith NJ. Time trends in autism and in MMR immunization coverage in California. JAMA. 2001;285(9):1183–1185.
5. Kaye JA, del Mar Melero-Montes M, Jick H. Mumps, measles, and rubella vaccine and the incidence of autism recorded by general practitioners: a time trend analysis. BMJ. 2001;322(7284):460–463.
6. Fombonne E, Zakarian R, Bennett A, Meng L, McLean-Heywood D. Pervasive developmental disorders in Montreal, Quebec, Canada: prevalence and links with immunizations. Pediatrics. 2006;118(1):e139–e150.
7. Madsen KM, Hviid A, Vestergaard M, et al. A population-based study of measles, mumps, and rubella vaccination and autism. N Engl J Med. 2002;347(19):1477–1482.
8. Peltola H, Patja A, Leinikki P, Valle M, Davidkin I, Paunio M. No evidence for measles, mumps, and rubella vaccine–associated inflammatory bowel disease or autism in a 14-year prospective study. Lancet. 1998;351(9112):1327–1328.
9. Simon S. Children's Mercy Hospitals and Clinics. Causation. http://www.childrens-mercy.org/stats/ask/causation.asp. Accessed January 8, 2010.
10. Thompson WW, Price C, Goodson B, et al.; Vaccine Safety Datalink Team. Early thimerosal exposure and neuropsychological outcomes at 7 to 10 years. N Engl J Med. 2007;357(13):1281–1292.
11. Demicheli V, Jefferson T, Rivetti A, Price D. Vaccines for measles, mumps and rubella in children. Cochrane Database Syst Rev. 2005;(4):CD004407.
12. Murch SH, Anthony A, Cassen DH, et al. Retraction of an interpretation. Lancet. 2004;363(9411):750.
13. Horton R. The lessons of MMR. Lancet. 2004;363(9411):747–749.
14. Gust DA, Darling N, Kennedy A, Schwartz B. Parents with doubts about vaccines and reasons why. Pediatrics. 2008;122(4):718–725.
15. Health Protection Agency. Measles figures soar. http://www.hpa.org.uk/webw/HPAweb&HPAwebStandard/HPAweb_C/1227774034336?p=1204186170287. Accessed December 6, 2009.
For more information on EBM terms, see the EBM Toolkit at http://www.aafp.org/afp/ebmtoolkit.

Copyright © 2010 by the American Academy of Family Physicians.

Saturday, September 4, 2010

Aspartame - harmless sweetener or destroyer of humanity?

A little while back, my dad forwarded to me the following e-mail and asked if there was “anything to it.” He called me “Dr. Science,” which is pretty exaggerated. Nevertheless--the e-mail:


In October of 2001, my sister started getting very sick.  She had stomach spasms and she was having a hard time getting around. Walking was a major chore.  It took everything she had just to get out of bed; she was in so much pain. 

By March 2002, she had undergone severaltissue and muscle biopsies and was on 24 various prescription medications.   The doctors could not determine what was wrong with her.   She was in so much pain, and so sick she just knew she was dying. 

She put her house, bank accounts, life insurance, etc., in her oldest daughter's name, and made sure that her younger children were to be taken care of. 

She also wanted her last hooray, so she planned a trip to Florida (basically in a wheelchair) for March 22nd. On March 19, I called her to ask how her most recent tests went, and she said they didn't find anything on the test, but they believe she had MS. 

I recalled an article a friend of mine e-mailed to me and I asked my sister if she drank diet soda?   She told me that she did.   As a matter of fact, she was getting ready to crack one open that moment. I told her not to open it, and to stop drinking the diet soda!   I e-mailed her an article my friend, a lawyer, had sent. 

My sister called me within 32 hours after our phone conversation and told me she had stopped drinking the diet soda AND she could walk!  The muscle spasms went away. She said she didn't feel 100% but, she sure felt a lot better. 

She told me she was going to her doctor with this article and would call me when she got home. 

Well, she called me, and said her doctor was amazed!  He is going to call all of his MS patients to find out if they consumed artificial sweeteners of any kind.   In a nutshell, she was being poisoned by the Aspartame in the diet soda... and literally dying a slow and miserable death. 

When she got to Florida March 22, all she had to take was one pill, and that was a pill for the Aspartame poisoning!   She is well on her way to a complete recovery.  And she is walking!   No wheelchair! This article saved her life. 


If it says 'SUGAR FREE' on the label;   DO NOT EVEN THINK ABOUT IT!    

I have spent several days lecturing at the WORLD ENVIRONMENTAL CONFERENCE on 'ASPARTAME,' marketed as 'Nutra Sweet,'  'Equal,' and  'Spoonful.' In the keynote address by the EPA, it was announced that in the United States in 2001 there is an epidemic of multiple sclerosis and systemic lupus.  It was difficult to determine exactly what toxin was causing this to be rampant. 

I stood up and said that I was there to lecture on exactly that subject. 

I will explain why Aspartame is so dangerous:   When the temperature of this sweetener exceeds 86 degrees F, the wood alcohol in ASPARTAME converts to formaldehyde and then to formic acid, which in turn causes metabolic acidosis. Formic acid is the poison found in the sting of fire ants.   The methanol toxicity mimics, among other conditions, multiple 
sclerosis and systemic lupus. 

Many people were being diagnosed in error.   Although multiple sclerosis is not a death 
sentence, Methanol toxicity is! 

Systemic lupus has become almost as rampant as multiple sclerosis, especially with Diet Coke and Diet Pepsi drinkers. 

The victim usually does not know that the Aspartame is the culprit. He or she continues its use; irritating the lupus to such a degree that it may become a life-threatening condition. We have seen patients with systemic lupus become asymptotic [sic, ?asymptomatic], once taken off diet sodas. 

In cases of those diagnosed with Multiple Sclerosis, most of the symptoms disappear. We've seen many cases where vision loss re turned and hearing loss improved markedly. This also applies to cases of tinnitus and fibromyalgia.   During a lecture, I said,  'If you are using ASPARTAME (Nutra Sweet, Equal, Spoonful, etc) and you suffer from fibromyalgia symptoms, spasms, shooting pains, numbness in your legs, Cramps, Vertigo, Dizziness, Headaches, Tinnitus, Joint pain, Unexplainable 
depression, anxiety attacks, slurred speech, blurred vision, or memory loss you probably have ASPARTAME poisoning!'

[The author goes on to attribute ADHD, Gulf War Syndrome, rage attacks and the obesity epidemic to Aspartame…]

* * * * *
My response:

Hey, Dad:

I wasn't ignoring you - it's just that my (apparent) reputation as Dr. Science (wow!) requires that I spend some time researching the evidence before I answer a question like this.  :-)  Here's what I found about the safety or toxicity of aspartame:

- A systematic review (considered the best kind of evidence in medicine - a systematic search of the medical literature available at the time, reviewed and summarized in a reproducible way) in "Critical Reviews in Toxicology" in 2007 found that:  a) even in the highest users of aspartame, the levels of use are far below the FDA and European Food Safety Authority maximum safe dose of 40 mg/kg body weight;  b) acute, subacute and chronic use studies in several mammalian species have shown no evidence of toxicity with doses up to 4000 mg/kg body weight/day;  c) studies of carcinogenicity reveal no evidence that aspartame is carcinogenic in humans, and a few comparison studies (users vs non-users) show no association of aspartame use with cancer;  d)  studies of aspartame and nervous system function show no compelling evidence that aspartame causes changes in human brain function, learning or behavior.
- Tests of genetic toxicity (tendency to cause genetic mutations) showed that, in bacteria and mice, aspartame MAY cause some DNA breakages and mutations, but both saccharin and another sugar substitute called ASK caused more genetic damage than aspartame.  The relevance to these studies in humans is unclear.
- One interesting study in 2005 in the American Journal of Gastroenterology showed that, in patients with alcoholic liver disease, a dose of aspartame FIVE TIMES that consumed by the average person did not cause any adverse effects in liver function, brain function or methanol accumulation.  Why they did this study, I have no idea.
- There are a couple of small studies showing that exposure to aspartame before birth may induce genetic mutations...in mice embryos.  Again, hard to know how applicable this is to human beings.

Overall, I think this story is probably hokum.  There's been a controversy surrounding these sweeteners since their invention, mostly motivated by mistrust toward things that are "artificial" and therefore unfamiliar and scary.  So far, there's no good evidence that aspartame in amounts used by people in food and drinks has any harmful effects on health.

Then again, I could be wrong.  :-)


Tuesday, August 17, 2010


Medical Meanderings 21 May 2008


“[John R. Brinkley and Mrs. Brinkley are] two of the finest people and the greatest benefactors to mankind on earth…I wear goat glands and am proud of it.”
U.S. Senator Wesley Staley (D - CO), 1922

By 1930, John Brinkley was the millionaire founder of the Brinkley Institute of Health (containing the Brinkley-Jones Hospital, Brinkley-Jones Associates, the Brinkley Research Laboratories and the Brinkley Training School for Nurses) in Milford, Kansas, and host of the “Medical Question Box” on KFKB, the most popular radio station in the United States. He had powerful friends, including the Vice President of the United States, and was considering a run for governor of Kansas.

He was also the most dangerous charlatan in America. Brinkley, born in 1885, had at first attempted to go to medical school in Chicago in 1908. At the time, the idea of standardized medical training was far from widely accepted. Although experimentally-based, “allopathic” physicians were dominant in America, there were dozens of other schools teaching the gospels of osteopathy, chiropractic, homeopathy, herbs and more. Brinkley settled on the Bennett Eclectic Medical College. Eclectic medicine relied largely on herbs and taught several ideas ahead of their time, but also included a lot of pseudoscientific guesswork. After dropping out due to excessive drinking and leaving his first wife, Brinkley had several false starts including a stint as an “electro-medic” in South Carolina and as a general practitioner in Arkansas (after buying a medical diploma from the Eclectic Medical University of Kansas City). Finally, his big break came in 1917.

One strong trend of American quackery in the early 20th century was “gland therapy” for that most perennial of human afflictions—sexual inadequacy. The thinking ran thus: animals like chimpanzees and goats are sexually…vital. If we can take the animal’s testicle and get it into the human body, it will make its recipient similarly vital. I am not kidding. So, people who would not buy a second-hand Model A Ford without skeptical evaluation were gullibly risking their health ingesting and injecting goat glands. Brinkley saw an opportunity. A farmer named Stittsworth complained of “no pep.” Brinkley surgically implanted goat testicles in Mr. Stittsworth’s scrotum. The farmer paid and went home. Two weeks later, the farmer returned with a smile and new vigor, and word spread. Dr. John Brinkley’s goat-gland practice was born.

Author Pope Brock tells Brinkley’s full, incredible story in his excellent new book, Charlatan: America’s Most Dangerous Huckster, the Man Who Pursued Him, and the Age of Flimflam. Brinkley’s dubious career was paralleled by that of Dr. Morris Fishbein, associate editor of the Journal of the American Medical Association, who determinedly crusaded to bring Brinkley down and in so doing became the most famous “quack-buster” of his day.

Brinkley’s career ended on March 30, 1939, when he lost a lawsuit against Fishbein during which his scams and hokum were fully exposed. When he died in 1942, Brinkley had killed 42 patients at his hospital, not to mention those who were discharged and died later, nor those harmed or killed by his bad advice and fake remedies sold on the radio. He was still one of the most popular men in the United States. In our age of weight-loss remedies, sexual tonics, various gurus pushing supposed cures “your doctor won’t tell you about,” and other nonsense, Brinkley’s story should be cautionary for all of us.


Medical Meanderings 9 January 2008

Snip, Snip

This was the most unkindest cut of all.
William Shakespeare, “Julius Caesar,” Act III, scene ii

Vasectomy is a safe, permanent method of birth control for men. It is also one of the few suggestions that will send the most macho, grizzled tough guy running for the door. Still, it’s not uncommon: one in five American men over age 35 have had vasectomies, and about four million are performed each year worldwide.

But before we get into details, a quick anatomy review. Sperm are made in the testicles, which hang out (literally) in the scrotum. New sperm move into the epididymis, a convoluted network of tubes on top and behind the testicle. In the epididymis, the sperm are mixed with fluid from the seminal vesicles to make semen. During ejaculation, the semen is pushed out of the epididymis, up the vas deferens, through the prostate and out. The vas deferens (or “vas,” but never “the v.d.”!) is a long, thin tube, about the size and consistency of a piece of half-cooked spaghetti. It runs from the epididymis, into the pelvis, behind the bladder, through the prostate and, finally, into the urethra and out. Long trip, but the section through the scrotum without exits or U-turns gives us a great spot to put in a roadblock.

During a vasectomy, a small amount of anesthetic is injected with a tiny needle into part of the skin of the scrotum. When the skin’s numb, the doctor finds the vas and holds it steady with one hand while making a tiny incision in the skin over the vas. A loop of the spaghetti-like vas is brought up through this tiny hole and a section clipped out. The ends are then either clipped with small staples or burned with electrical current (which doesn’t hurt). Then, the vas is put back and the skin closed up if needed (sometimes a stitch isn’t even necessary). It all takes about 30-45 minutes. The man is then sent home wearing a jock strap to hold his equipment steady (and to help his sense of manliness). Most guys can go back to work the next day with some limits, and are back to normal in a week.

Now for the weird part. In the eight weeks following the procedure there are still some sperm in the plumbing. So, another form of birth control has to be used. To clean out the pipes, the fellow has to ejaculate about 20 times before his follow-up visit. Then, he goes to the doctor where he gives a semen sample to make sure no sperm are left.

Once the plumbing is clear, vasectomy is a highly effective form of birth control—the failure rate (that is, pregnancy rate) is less than one in a thousand. For those guys not persuaded by statistics, how about money? Vasectomy costs half as much as tying a woman’s tubes (not to mention being a safer procedure), and is about the same cost as a two-year supply of birth control pills.

So, guys…think about it. It’s quick, cheap, effective and not all that painful. It won’t make you sing soprano, hurt your sex drive or make you more likely to ask for directions. Real men get vasectomies.


Medical Meanderings 12 September 2007

Testosteroni: The Elderly Man’s Treat?

I think age is a very high price to pay for maturity.
- Tom Stoppard (1937 - )

It’s likely that anyone reading a weekly medical column has heard of menopause, or “the change” as many women call it. Menopause is the normal, age-related process of decreasing estrogen levels in the woman’s body, causing classic symptoms like hot flashes (or flushes), thinning of the bones, and lack of menstrual periods. Recently, however, there has been talk in some medical circles of an “andropause,” or male menopause, caused by declining testosterone levels in older men. Is there anything to this idea of “andropause”?

As men age, the level of testosterone in their blood normally decreases to some extent. Unlike menopause, however, there’s not a huge drop in hormone levels and, so far, the symptoms caused by this change aren’t clearly defined. Nevertheless, believers in “andropause” seem to think backward. They reason as follows: since many symptoms of aging in men are similar to symptoms of low testosterone in young men (called hypogonadism), it is reasonable to assume that low testosterone may cause many of the symptoms of aging. This is a tricky bit of flawed reasoning (called “argument by analogy,” for you logic buffs), and the link has not been supported by scientific evidence so far. Just because low testosterone and aging have similar results does not mean one causes the other.

Then the question arises: Even if it’s not an obvious disease, if we can, shouldn’t we fix problems such as age-related loss of bone, loss of sexual function and loss of muscle mass and strength? If an older man has declining testosterone and these problems, shouldn’t giving him some testosterone help get back his strength and mojo? Not necessarily. The available medical studies (and there aren’t that many) on testosterone treatment show that making the hormone level normal does NOT improve bone density, sexual function, quality of life, muscle strength or physical function.

Not only is aggressive testosterone replacement in older men apparently ineffective, it may be harmful. Both prostate enlargement and prostate cancer depend on testosterone, so giving more can worsen these problems. Testosterone treatment also worsens sleep apnea, increases the percentage of red cells in the blood (which may increase risk of heart attack) and lowers good cholesterol. It’s no magic elixir of youthful manliness.

Just as recent studies have made us doctors seriously question whether we should be trying to undo the changes that women experience as they go through menopause, it may be time to reconsider testosterone replacement in older men. It should probably be reserved only for those patients with severe, proven hormone problems, not for those older men who would just like more pep (or a younger girlfriend). In fact, it may be time for us all to reconsider the common view that aging is a disease that needs to be cured. Just as we don’t try to stop the changing of the seasons or the falling of the leaves, perhaps we shouldn’t stubbornly try to reverse those inevitable signs that our bodies have been around for awhile.

Lesch-Nyhan Syndrome

Medical Meanderings 15 August 2007


“I take you where you want to go / I give you all you need to know / I drag you down, I use you up / Mr. Self-Destruct…” - Nine Inch Nails, “Self Destruction”

In 1964, a pediatrician named Dr. William Nyhan and his medical student assistant, Michael Lesch, published a report bearing the esoteric title: “A familial disorder of uric acid metabolism and central nervous system function.” In it, they described a horrifying disease affecting little boys that caused them, around 6 months of age, to move spastically, twitching and involuntarily jerking their limbs. Then, as the disease progressed, these little boys would develop self-mutilating behaviors. Their hands would fly to their mouths, where they would bite off parts of their fingers, all the while screaming for help, unable to stop. They would bang their heads into walls, stab themselves, burn themselves, unable to stop.

In earlier times, such horrifying behavior would have doubtlessly been attributed to demonic possession or witchcraft. But Lesch-Nyhan syndrome, as it is now known, is due to the buildup of a simple chemical in the areas of the brain that control movement, the basal ganglia. The culprit is uric acid, a byproduct of the metabolism of DNA in our diet. Uric acid is familiar to anyone with gout—it is this chemical that builds up and crystallizes in the joints, causing inflammation and pain.

When Drs. Nyhan and Lesch discovered the uric acid was the cause of the bizarre syndrome, they attempted to treat affected children with allopurinol, a medication used to lower uric acid levels in gout patients. However, this medication, and no medication so far, has been able to change the course of the disease. As it turned out, the high uric acid levels and the self-mutilating behavior are both symptoms of a separate underlying problem.

That problem is a misspelling. Patients with Lesch-Nyhan syndrome are born with one letter misplaced in one gene in their entire genetic program. That gene, which is carried on the X chromosome, codes for an enzyme, hypoxanthine-guanine phosphoribosyltransferase (HPRT). Since boys have only one X chromosome, while girls have two copies, this abnormal gene and thereby the disease, shows up predominantly in boys.

What does it mean that a single gene can cause a person to chew off his own fingers against his will? How can any of us believe in “free will” (whatever that means) if a random, simple DNA misspelling can make someone destroy his own life if left unrestrained? Lesch-Nyhan syndrome raises interesting questions, not just about the brain and our body’s complex chemistry, but also about our easy assumptions about our behaviors and choices. Do we control our brains, or do our brains control us? Does that question even mean anything?

Dr. Nyhan, now 81 years old, still works with patients affected with the disease at the University of California – San Diego. His younger colleague, Dr. Lesch, is now Chairman of the Department of Medicine at New York’s St. Luke’s-Roosevelt Hospital. The disease named for them is fortunately rare, affecting only a few dozen people worldwide. But the questions about human nature it raises affect us all.

Monday, August 16, 2010

John Snow

Medical Meanderings 18 July 2007

Water From The Well

And I would have stayed up with you all night / Had I known how to save a life…
The Fray, “How To Save A Life”

London, England, in the 1850s, was a rather miserable place to live on a good day, and positively deadly at less fortunate times. In a world of no sewers, no water purification plants, no germ theory and no antibiotics, the “terrorist” most feared was cholera. Cholera is an infectious disease rarely encountered in modern America, but it remains the most common cause of death for children in the developing world, and over 60 countries have outbreaks each year.

The first known epidemic of cholera occurred in 1817 in India, but like West Nile virus in our time, it quickly spread around the world, reaching England in 1831. In 1853, with approximately 1.5 million people living in London, cholera killed 10,675. (To give you perspective, this death rate would be the equivalent of a bioterrorism attack killing 16,000 people in present-day Denver.) In late August 1854, a woman dumped a pail of water in which she’d been washing her ill infant’s diapers. The wash water, carrying cholera bacteria, percolated through the broken brick lining of the Broad Street water well.

The Broad Street well was a popular source of clear drinking water for a neighborhood of 25,000 people living packed together at 300 persons per acre. But clear doesn’t mean clean. From August 31st to September 9th, 700 people died of cholera from drinking Broad Street water. Entire families died together in one room, and only a rare family survived without losing at least one member. It was the most concentrated loss of life from cholera in English history.

Adding to the terror of the epidemic was the fact that no one in the 1850s knew about germs. The best scientific minds thought that cholera was transmitted by “miasma,” or bad, stinky air. There was plenty of stinky air in a big city with horses, cattle and humans sharing crowded living conditions with no sewer system. Miasma theory had a strong hold on the medical establishment for centuries, and like pseudoscience today, it was advanced by strong opinions based on no facts.

That all changed when a general practitioner named John Snow looked at the problem. Snow--a 34 year old expert in the use of the anesthetic ether--had already published a study in 1849 arguing that cholera was not caused by bad air, but by contaminated water. His idea was not noticed. But during the 1854 outbreak, by doing the hard medical detective work now known as epidemiology, Snow concluded that the pump was the source of the outbreak. He had the pump handle removed, saving untold lives. Incredibly, Snow never knew about the existence of the cholera bacterium. He solved the mystery just by observation, and put the dangerous nonsense of miasma to rest.

Next time you flush your toilet or get a drink of water from your tap, take a moment to think of John Snow and be grateful that, because of his work, your toilet water won’t end up in your glass.


Medical Meanderings 30 January 2008

Sweet as Honey

Instead of dirt and poison we have rather chosen to fill our hives with honey and wax; thus furnishing mankind with the two noblest of things, which are sweetness and light.
Jonathan Swift (1667 – 1745)

For thousands of years, honeybees have provided human beings with what, until modern times, was our only source of sweetness. Of course, they gather flower nectar, fan it with their wings to evaporate water and concentrate the simple sugars fructose and glucose, and store the sugars in their hexagonal wax cells not for us, but for themselves and their eggs. Nevertheless, we learned to domesticate bees and use their honey for food and flavoring.

Honey has its fair share of medicinal uses as well. Honey was used very early in recorded history to make and to flavor alcoholic beverages, which were much safer to drink than water. The Egyptians used honey as embalming fluid, to stop decay and prepare their dead. Honey was also the first antibiotic ointment. The extremely high sugar concentration and lack of water in honey greatly impairs the growth of bacteria in wounds. In fact, it is still used today to prevent infection of minor burns.

Now, those of you who know me (or have read this column for long) know that I’m not a big fan of so-called “alternative medicine.” (Mainly because I’m a huge fan of science and evidence.) However, honey has recently become a proven alternative to our over-the-counter cough remedies.

In December 2007, Dr. Ian M. Paul and his colleagues published a study in which they compared buckwheat honey (a dark type of honey) to both a honey-flavored preparation of dextromethorphan (the “DM” in Robitussin DM and other cough medicines) and to no treatment. The dosages of both treatments were half a teaspoon for two- to five-year olds, a full teaspoon for six- to eleven-year olds, and two teaspoons for twelve-year olds and up. (Honey should NOT be given to infants younger than one year old because of a small risk of botulism, a rare type of food poisoning.) The treatments were given to 105 children with coughs from colds, and the children and their parents were asked about the severity of the cough before and after treatment.

This was a well-designed experiment and good science: The kids were randomly assigned to a treatment, and they and their doctors didn’t know which kid was getting which treatment until after the experiment was over. The treatments both tasted like honey. Finally, there was a control group—the kids that had no treatment.

Honey won hands down. Dextromethorphan was as useless as no treatment at all—a result that has been seen in multiple other studies of cold remedies. In other words, there is no evidence that the “DM” works. But honey does. It significantly reduced cough, probably by a combination of soothing the throat, antioxidant activity and perhaps antibacterial action. It’s safe, effective and tasty—another incredible gift from our pollinating insect friends. Following close on the heels of the FDA’s warnings against cold remedies for children, this news is certainly sweet.

Brain Day

Medical Meanderings 18 October 2006

It’s All In Your Head

“… art thou but a dagger of the mind, a false creation, proceeding from the heat-oppressed brain?”
William Shakespeare, “Macbeth”

When your alarm clock rings in the morning, the sound enters your auditory cortex of your brain, located just under your ears on the sides of your head. The auditory cortex sends the information to your reticular formation, a very primitive area at the top of your brainstem, stimulating multiple areas of the brain. You become conscious, dreams disappear, and another day starts.

You, in every way that we can understand, are contained in a three-pound lump of grayish-brown tissue in your skull. This wrinkled lump consumes 20% of your body’s energy and is an unimaginably complex network of some million billion connections, containing and creating your every memory, emotion, decision, sight and sensation.

As you shower, shave and brush your teeth, your frontal lobe, the newest part of your brain (in evolutionary terms) thinks about your day. Simultaneously, your motor cortex and sensory cortex--both inch-wide strips, running side to side, across the top of your head—coordinate and execute the complex behaviors of getting ready for your day. These activities occur with almost no input from your conscious, active frontal lobe.

You head out to the garage to go to work and, without looking, grab your keys out of your pocket or purse. Your sensory cortex, located just above your ears, effortlessly identifies the right key by its shape. You back out of the garage and your cerebellum, sitting just behind the brainstem, coordinates all the complex movements of your feet on the pedals, hands on the wheel and eyes on the rearview mirror. Suddenly, your visual cortex notes a dark shape move behind the car in the rearview mirror. Within milliseconds, the information is interpreted and sent to the motor cortex, and your feet hit the brakes. A second or two pass before your higher brain areas catch up, and you interpret the shape as the neighbor kid recklessly riding by on his new bike.

All day at work, as you concentrate on your job, a small area of the brain located a few inches behind your eyes regulates your heart beat, your rate of breathing, your body temperature and your appetite. Every new fact that enters your mind is processed by the hippocampus, a little seahorse-shaped area deep in the brain at the level of your temples. The hippocampus decides, like a master filing clerk, what facts are worth saving in long-term memory and what’s worth forgetting.

Procedural memory--the kind used to brush your teeth or ride a bike—is stored mainly in the cerebellum and motor areas of the frontal lobe. This kind of memory allows you to cook supper after work while using your attention to talk to a friend on the phone. Nothing gets dropped or burned. Your reticular formation, in concert with the tiny, melatonin-making pineal gland near the center of the brain, starts making you feel tired. Time for bed. You climb in, turn out the light and, as portion after portion of your brain enters sleep…another busy day ends.

Bacterial Resistance

Medical Meanderings

The Monsters We Made

Although the Cold War is over, there is still an arms race going on. This arms race is with an invisible enemy who seems able to invent new defenses almost as fast as we can invent weapons. So far, we are winning the race on most fronts, but many experts predict that in the very near future, this won’t be the case. Our enemy may become impossible to kill.

Bacteria are quick learners. Alexander Fleming invented penicillin in 1928, and at first, many medical experts declared that the Era of Infectious Disease was over. Humanity had won the war against the germs. Now, almost 80 years later, penicillin is rarely used because so many bacteria are resistant to it. And its cousins, the cephalosporins. And erythromycin. And, and, and… There have even been reports in recent years of bacterial infections resistant to one of our most powerful antibiotics, vancomycin, which was one of our biggest weapons. The bacteria are learning, and they really like to share.

How does a bacterium “learn” to resist penicillin, or any other antibiotic? There are several ways. In all cases, bacterial resistance is a wonderful example of evolution in action. There is a population of, say, a million bacteria. In that million, there may only be one that, by chance, has a slight mutation of its genetic code that changes protein X in its microscopic body. However, it just so happens that protein X is the target for an antibiotic. The antibiotic is introduced, and most of the million are killed by it, but that one mutant survives, because it alone is unharmed by the antibiotic. The survivor starts to reproduce, and soon we have a population of a million bacteria that can resist the antibiotic.

Humans, of course, aren’t stupid. We have invented countermeasures that can overcome bacterial resistance, brand new antibiotics that have new targets, and we’ve learned to use combinations of antibiotics together. Although we’re not stupid, sometimes we aren’t wise. We give millions of pounds a year of antibiotics to cattle to enhance their growth. We give antibiotics to millions of people each year who have only a cold or viral bronchitis, which antibiotics cannot touch. We make antibacterial soaps to fight imagined contamination. We’re giving the bacteria every chance we can to learn how to fight back.

Because they are such quick learners, many of our old enemies are coming back. We thought, for example, that we had defeated tuberculosis. Now, in many countries, treatment of tuberculosis requires three different drugs given together for several months. Many of our hospitals in America (including our own) fight MRSA, methicillin-resistant staphylococcus aureus, a difficult-to-treat common germ. Bacterial resistance is a fact of life now, and our enemies will not unlearn what we have taught them. We can only hope to stay a step ahead.


Medical Meanderings 5 July 2006

Oxygen Addiction

I can feel you breathe / Just breathe… - Faith Hill, “Breathe”
Would somebody help me breathe? - Nickelback, “Breathe”
Everything is alright / if I just breathe… - Michelle Branch, “Breathe”
So cradle your head in your hands / And breathe, just breathe… - Anna Nalick, “Breathe”

Evidently, breathing is important to musicians. (Wonder why so many of them smoke?) While you read this article, I dare you to hold your breath and to find out it’s pretty important to you, too. Politicians are worried about our national addiction to oil, but what we’re really addicted to, as a species, is oxygen.

What does oxygen do for us? On a molecular level, oxygen is the molecule that is “the final electron acceptor at the end of our mitochondrial electron transport chain”. What?! Said more simply, we have to have oxygen for our cells and tissues to manufacture energy to keep all of our life processes going, from brain cell firing to toenail growing.

Oxygen is transported to our tissues in the blood, mostly attached to hemoglobin in our red blood cells. Hemoglobin has a crispy protein shell with a chewy iron center. (Hemoglobin is dark bluish red without oxygen, and a bright red with it.) The trick of hemoglobin is to be “sticky” to oxygen in the lungs, but not so “sticky” that it won’t let oxygen free in the tissues that need it. (Still holding your breath?)

Our red blood cells pick up oxygen (and drop of waste carbon dioxide) in the lungs, which do an efficient job of drawing in air through increasingly narrow pipes to tiny microscopic air sacs called “alveoli”. The alveoli sit at the end of the air pipes like grapes in a bunch. If the air pipes plug up (as in bronchitis and asthma) or spasm (as in asthma), it’s called “obstructive” lung disease, because as the person tries to exhale, the airways collapse and airflow out is blocked.

Asthma is a common and complicated problem caused by both inflammation (swelling and mucus production) and spasm of the air passages in the lungs. It is a disease partly caused by genetic (hereditary) factors that cause an over-active immune system and by outside factors that cause inflammation of our airway tissues. The narrowed airways cause wheezing and coughing, especially at night. The feeling of an asthma attack is like breathing through a tiny coffee stirrer; or like taking a breath in, only exhaling half of it, then trying to take another breath.

The airway spasm of asthma is treated with “bronchodilators” like albuterol (fast-acting but short-lasting) or salmeterol (slow-acting but long-lasting), which stimulate the muscle cells of the air tubes to relax and open. The inflammation of asthma is treated with steroid inhalers (all slow-acting and long-lasting) like fluticasone, which turn off the immune system’s attack on the airways. Asthmatics are also helped by avoiding “triggers” for their asthma such as cigarette smoke, cats, cold weather, exercise or strong emotion.

The American Lung Association’s motto is “when you can’t breathe, nothing else matters,” and they’re right. If you’ve held your breath while reading this, you know how right they are. Okay, you can breathe now.


Medical Meanderings 5 August 2009

All Good Things… ©

To everything there is a season, a time for every purpose under the sun. A time to be born, and a time to die…
- Ecclesiastes 3:1-2

Each of us starts out in life as a ball of cells called a blastocyst. You may notice, however, when you look at (most of) your friends and neighbors, that they are not spherical. How do we grow from a ball into two-legged, two-armed, one-headed adults? Of course, the first thing needed is growth—through cell division, over and over, tissue is added. Second, cells have to become differentiated. That is, groups of cells start to specialize into nerve or bone or muscle cells. Each cell switches certain genes on or off, like a handyman selecting what tools he’ll need for a job and putting others away. Once transformed into a certain type of cell, the identity is permanent.

The third process that must occur for us not to become giant human spheres is called apoptosis (ay-poh-TOE-sis), or programmed cell death. Apoptosis is derived from the Greek “apo-,” meaning “away from” and “ptosis,” meaning “to fall.” That is, cells undergoing apoptosis are falling away, like autumn leaves. These cells essentially commit suicide in a very organized fashion, right on time. This allows certain tissues to shrink as others grow, shaping our organs and limbs, even our brains.

Apoptosis can by triggered from outside the cell, when chemical messengers attach to “death receptors” on the cell surface, or from inside the cell, due to damage from chemicals and radiation. In either case, the control center of the cell, the nucleus, starts the self-destruction as DNA clots together and breaks apart. Then, a series of enzymes is activated, leading to a cascade in which the cell’s own proteins are digested. Through this process, the membrane of the cell, its “skin,” is kept intact. This keeps the cell contents from leaking out into the surrounding tissue, thereby avoiding a huge mess to clean up. Finally, the cell corpse (scientists actually call it that) is ingested and digested by surrounding cells.

Not only is apoptosis vital for normal growth and development, it is important in the proper function of our immune system’s defenses. When you get an infection, the white blood cells replicate and swell their numbers in order to fight the battle against invading bacteria or viruses. However, once the battle is over, the extra troops can’t be sent home (to where?), so they self-destruct. After all, we don’t want millions of extra white blood cells floating around with nothing to do. Apoptosis plays a role in autoimmune diseases such as lupus and rheumatoid arthritis in an opposite way—white blood cells active in inflammation fail to self-destruct as they should, instead hanging around causing mischief in healthy organs.

All good things must come to an end, including living cells. The wisdom of our bodies’ tissues shows us that not only is it important to know when to prosper and grow, but that there comes a time, even for individual cells, when it’s time to bid good-bye.


13 May 2009 Medical Meanderings

When Good Brains Go Bad ©

Your crystal ball is where you chase the dragon / She said, now bring me home his head inside a sack…Got to get that monkey off your back…
- Aerosmith, “Monkey On My Back” (1989)

Unlike plants, we animals get to move around. Because those that apathetically sit and wait for food, water and mates generally die or get eaten by competitors (at least until modern times), we have inherited brain systems that motivate us to seek out what we need for survival. When we satisfy these hard-wired, inborn drives, it gives us pleasure and makes us more likely to repeat the behavior.

Several brain circuits handle these complex motivational tasks, but one of the biggest drivers is a cluster of nerve cells called the nucleus accumbens (uh-KUM-bins). When we do something rewarding (eating, sex, etc.), the nucleus accumbens is stimulated, causing signaling of several further areas of the brain, including the areas that encode memory, enable movement and direct attention. These circuits ensure that we’ll remember what felt good, how we got it, and that we’ll look for another opportunity in the future.

Addiction hijacks this necessary brain circuitry. The word “addiction” has a very specific medical meaning: the continued, compulsive drive to use a substance despite serious adverse consequences to the user. Despite financial ruin, damaged relationships or medical illness, his brain’s reward circuitry has changed in such a way to undermine voluntary control and drive him only toward the next “fix.” In the addicted brain, the usual levels of neurotransmitters have been altered, which results in craving and the misery of withdrawal. Areas providing impulse control and direction of attention are less active than in normal brains, impairing the addict’s “willpower” and ability to see the bigger picture. Laboratory rats will press a lever to dose themselves with addictive drugs, neglecting food, water and mating until they die. The smoker puffing through his tracheostomy hole, the malnourished alcoholic or meth user, the gambler who loses his daughter’s college fund, on and on…we do much the same.

Genetics contribute about 40-60% to an individual’s risk of addiction. For example, genes linked to an increased or a decreased risk (depending on the mutation) of addiction to alcohol, nicotine and codeine have been found. However, genetics are certainly not the whole story—environment, exposure and the choice of repeated use have equally large role in addiction.

As scientists understand more about what goes wrong in the addicted brain, we have more tools to assist those who want to end their addiction. Unlike rats, we humans have huge brains we can also employ to break free of addiction, though “cure” is elusive. Medical help is sometimes necessary to prevent serious withdrawal illness, or to ease the transition. Several medications have become available in recent years to block drug-induced reward and lessen withdrawal. Support groups and addiction counselors can also help the addict re-wire his altered brain, learn new ways to think and live without the drug, and regain control over his attention, memory, mood and life.


Medical Meanderings - 16 April 2008

My Forehead

I am beautiful no matter what they say / Words can’t bring me down…
- “Beautiful,” Christina Aguilera (2002)

Sebaceous (suh-BAY-shus) glands are spread across my skin, including my forehead, attached to each of my hair follicles. About two weeks ago, due to excessive rubbing of my forehead with a towel, or my dog Ludwig’s aggressive licking of my face, or a casual scratch or rub of my forehead, a few dozen dead skin cells were pushed into one of my 150,000 hair follicles. This specific sebaceous gland and follicle was located about 3 inches above the lateral edge of my right eyebrow. A very visible bit of real estate.

The skin cells were full of a protein called keratin (which also makes up the shafts of my hair and my fingernails) a flexible, gummy kind of protein. This caused a keratin plug in the curving tube leading from the hair root and gland opening to the surface of the skin. Since the opening was plugged, the greasy sebum made by the gland could not work its way out onto the surface of my forehead. Sebum is made of a mixture of fats, cholesterol and wax (yes, wax) that is broken down on its way to the surface by bacteria (they gotta make a living, too) called Propionibacterium acnes.

As I went about my daily life, the plugged sebaceous gland kept on producing sebum, and the bacteria kept chomping on it, but the oily stuff just accumulated. At this point, if the skin-and-oil plug reached the air at the surface of my skin, the plug surface would have oxidized like a bitten apple in the open, turning the plug black. This pleasant phenomenon is the classic “black head,” which is not (as alleged by many parents of teens) dirt. It’s oxidized fatty acids. Yummy.

However, if the oily plug didn’t quite reach the surface, but rather pushed up a thin dome of skin cells over the gland opening without being exposed to air, the plug would still look white. These little beauties are called “white heads,” and they’re not full of pus, but only pent up skin oils.

My sebaceous gland didn’t follow either of these relatively harmless, cosmetically benign courses. No, no. Instead, the pressure in the gland built up, the bacteria kept working, and finally the walls of the sebaceous gland burst. Sebum and bacteria exploded into the surrounding skin. Loose sebum in the skin is very irritating, and my immune system responded—white cells started cleaning up the damage, releasing chemicals that dilated my skin capillaries. Increased blood flow to the damaged area of my once pristine forehead caused swelling and a bright, attention-grabbing redness.

Unfortunately, at this point, I made a horrible misjudgment. Upon noticing this developing insult to my self-image in the mirror, I decided to help the life-cycle of the beast along…by squeezing it. So, I applied digital pressure to each side of the swollen, red nodule. Then more pressure. Nothing. All I had done is push the bacteria-laden oily goo further into my normal skin, worsening the inflammation and dooming myself to a week of an extremely noticeable forehead flaw. Acne strikes again. Physician, heal thyself.

Monday, July 19, 2010

Anatomy Lab

Medical Meanderings 10 June 2009

Cutting Up ©

“He lived for others, he died for us.”
Common epigraph written on dissection tables circa 1900.

I clearly remember the first day of anatomy class, the second day of medical school in the summer of 1995. A large group of us, mostly new college graduates, stood nervously outside the anatomy lab doors. Although no one had told us to be quiet, we whispered with strangers who would soon be our lab partners. After a brief introduction from our professor regarding the layout of the anatomy lab, the textbook we’d be using, the location of the bathroom and so on, the big doors were opened and we filed in.

My three partners and I found our “humidor”: the metal table with two heavy, hinged doors in which the cadaver was kept. The doors were unlatched and carefully swung downward under the table. On the table was a white body bag with, obviously, a body in it.

When instructed, one of us (not me) unzipped the body bag, loosing a strong whiff of phenol and formalin preservative. The thin plastic was rolled back, and the petite 73-year old woman, whom we would come to know intimately, was exposed. She was on her back, naked, with face, hands and feet wrapped in moistened gauze to preserve them until that part of dissection—and to preserve our emotions for now. Her hair was shaved off, a fact that surprised me until I reflected on its necessity here. Her skin had an unnaturally firm, plastic look from the embalming process, which had also created many wrinkles as it dissolved some of her scarce body fat.

We started with her upper extremity—the arm. Two of us dissected each arm, one reading instructions and the other cutting. The first cuts were unnerving—we expected her to flinch, or bleed, or cry out, but of course skin is simply a material thing when life has left it. In a few days, we became comfortable learning to separate skin from muscle, ligament from tendon, nerve from artery. The details were overwhelming, the names foreign and functions complex. It didn’t take long to become so absorbed that we often forgot the arm we were exploring had hugged and waved goodbye.

From the upper extremities, we moved on to the chest and the back (which required the unexpectedly difficult task of turning her face-down). The head and neck required dissection of the face, another emotionally troubling task. Finally, we explored the pelvis and the lower extremities. Our cadaver was slowly disassembled into her component tissues, which were meticulously kept together. Finally, when we had learned all we could and passed the final examination, her 73-year old remains were cremated together, and given to her family for burial at a yearly ceremony held at the medical school.

Why, in this age of computer simulation, must doctors-to-be dissect human bodies? Because the feel of a nerve compared to an artery cannot be well-simulated. Because human beings vary more than books or programs can comprehend. Finally, because to help the living, the presence of death must not be as unnerving as it was to all of us uninitiated novices on that first day.


Medical Meanderings

Rub A Dub Dub (c)

In 1847, a young medical professor in Vienna, Austria, named Ignaz Semmelweis went to visit a sick friend. His friend, Jakob Kolletschka, was near death with a high fever, rapid pulse and sweats. Jakob had become sick soon after knicking one of his fingers while doing an autopsy and as Ignaz stood by his friend’s bed, watching him die decades before germ theory and antibiotics, Ignaz had a stunning insight: He had seen this disease before…in pregnant women.

Semmelweis had been troubled for years by the high death rate from “puerperal fever” in pregnant women in his hospital, where 13% of those admitted in labor died before hospital discharge. In a nearby obstetrical hospital run by midwives instead of physicians, the maternal death rate was only 2%. Now his friend Jakob had an illness very similar to puerperal fever from dissecting a dead body, and Semmelweis made a connection that would change medical practice forever.

Semmelweis had noticed that medical students would move from the autopsy room to the delivery room, wearing the same clothing and without washing their hands. On a hunch, he set up a policy: No one will be allowed to deliver a baby without first cleaning his hands in a chlorine solution. The death rate from puerperal fever on the labor and delivery ward dropped quickly to two percent.

Hand washing is the most basic weapon in the war against infectious disease. When done correctly, it can reduce the spread of many diseases. Unfortunately, it is rarely done correctly—in one study, 90% of hospital staff washed their hands for less than 10 seconds, instead of 15-30 seconds recommended by the Centers for Disease Control. Even in study situations, where people are being observed for compliance, only 40% of hospital staff washed their hands as they should have. Also, frequent hand washing is tough on the skin, causing changes in the types of germs present, and damaging the skin, possibly leading to a higher risk of transmitting infection.

Nowadays, alcohol hand rubs are becoming more widely accepted as the best way to clean hands. Alcohol hand rubs containing kill 90% or more of bacteria, viruses and fungi on the hands and reduce the risk of disease transmission from 92% with hand washing to 17%. Alcohol hand rubs work by breaking apart proteins in germs, and they work almost immediately. Also, they save time—whereas hand washing takes up to 30 seconds, the average alcohol hand rub is used in only 10 seconds. If you clean your hands five times a day, you will save 10 hours per year with a hand rub—that’s more than a full work day (or a good night’s sleep!).

Either way, by soap or by alcohol rub, in this season of colds, flu and strep, clean your hands early and often. Make Semmelweis proud. His insight, after all, eventually got him fired when the hospital administrator felt the policy change to be a criticism of his management. Science marches on, office politics doesn’t.

Ear Wax

Medical Meanderings 15 October 2008

Waxing Eloquent ©

If your head is wax, don’t walk in the sun.
Benjamin Franklin (1706-1790)

Ear wax is beautiful stuff. Medical types call ear wax “cerumen,” from the Latin word “cera,” meaning wax. Cerumen is a complicated mixture of secretions and debris produced by the outside third of our ear canals. The secretions include sebum, the same oily chemical that, when eaten by bacteria in our armpits, gives us the distinctive odor of locker rooms. Also, specific glands called ceruminous glands secrete the long chains of fat molecules that make ear wax so…waxy.

The sebum and wax mix with whatever passes by in the ear canal, including dead skin cells, bacteria living on our skin, water and occasional hairs. This mixture can range in texture from liquid to a rock-hard, and in color from a reddish-black to white. The characteristics of our cerumen depend on its specific composition and on how long it’s been sitting in the ear canal. The texture and color of our ear wax, however, doesn’t necessarily tell us much about how the ear canal is working.

The wax is moved outward from the ear canal by a lining of hair cells, by the movement of the tissues around our jaw joint, and by the normal growth of skin in the canal. The point of knowing this is: we do NOT need cotton-tipped swabs! The ear canal comes with standard equipment that moves the wax out, unless we do something (like sticking in a swab) that destroys the lining cells or packs the wax in more deeply or tightly. All we do with those swabs, toothpicks, paper clips or whatever else we stick in our ears is damage the system that would clean our ears out all on its own.

Cerumen has several important roles in keeping the ears healthy. First, it traps dust, skin, hair and insects that would otherwise plug up our ear canals in a few months, and moves that garbage out. Second, it absorbs water that would, if allowed to stay in the canal, form a home for bacteria to grow and infect us. Third, it is thought to have acted as an insect repellant back when our ancestors slept on the ground.

Getting rid of impacted ear wax is not something to try at home. Serious, sometimes permanent damage can be done to the ears during botched attempts to dig ear wax out. Leave it to the professionals, who have several methods of attacking this difficult problem. Drops that soften ear wax (e.g., mineral oil) are helpful. We will use cerumen spoons or curettes to carefully pull wax out. Water irrigation often works, and if all else fails, suction devices may work. There is no scientific evidence that “ear candling” is useful in removing ear wax, and it cannot be recommended.

The easiest way to maintain the health of your ear canals is to leave them alone. If it’s too late for that, then simply placing two drops of mineral oil in each ear once a week, occasional irrigation of the ear in the shower, and avoiding cotton swabs is all you need to do.

Saturday, July 17, 2010

Legionnaire's Disease

Medical Meanderings 14 October 2009

Philly Mystery (c)

“In solving a problem of this sort, the grand thing is to be able to reason backwards…but people do not practice it much.”
- Sherlock Holmes, in “A Study in Scarlet” (Sir Arthur Conan Doyle)

In July 1976, the Pennsylvania chapter of the American Legion, a non-political organization of military veterans, met in Philadelphia. Ten thousand men attended, but within days of returning from their convention, a dozen attendees were dead, and several others were hospitalized, due to a mysterious respiratory illness. Those affected were suffering with a rapidly-progressive pneumonia and fevers exceeding 107 degrees Fahrenheit.

The summer of 1976 was not very different from the summer of 2009. The country was primed with a fear of an infectious epidemic. The Ford administration was preparing to vaccinate the public against an unusual, spreading strain of influenza called “swine flu.” The media fed the fear, with Michael Crichton’s novel “The Andromeda Strain,” about the terrifying spread of a devastating pathogen, becoming a best seller. Then the news broke in early August about the new, fatal “Legion disease” in Pennsylvania, the cause of which had not been found.

Pennsylvania state health workers had initially responded to the epidemic by preparing for a medical disaster while reassuring the public that the crisis was under control. Help was soon requested, and the Communicable Disease Center (now the Centers for Disease Control and Prevention, or CDC) sent twenty federal disease investigators to assist dozens of state investigators. The CDC’s investigators were members of the Epidemiology Intelligence Service, the federal government’s “rapid response team” of physicians and public health scientists sent to do the detective work in any potential epidemic.

By the end of the epidemic, the disease had infected 221 Legionnaires and killed thirty-four. The medical investigators had spread across Pennsylvania, reviewing hospital records, attending autopsies and investigating the sites involved in the July convention. Initially, influenza was suspected, but none of the victims tested positive for the influenza virus. The investigators followed several other false leads, including the possibility that the Legionnaires had been exposed to a toxin, heavy metal or poison.

It took six months to identify the culprit of this epidemic, a newly-discovered bacterium that was named (in honor of this outbreak) Legionella pneumophilia (meaning “preferring the lungs”). Legionella prefers to live and grow in standing water. It had contaminated the plumbing within the convention hotel, then infected its victims through shower heads and faucets.

Legionnaire’s disease, as it is now known, is still relatively common, causing up to 10% of severe pneumonia with high fevers. Frighteningly, it has been found in up to 70% of hospital water systems in some geographic regions! However, we have diagnostic tests and antibiotics available to diagnose and treat Legionnaire’s disease that were not available in 1976. Nevertheless, there are lessons to be learned in the story of Legionnaire’s disease. The confusion and chaos of media-driven public fear can hinder progress and lead to irrational panic. On the other hand, the effectiveness of medical detective work and the scientific method is clear.

Locked-In Syndrome

Medical Meanderings 28 October 2009

The Horror ©

“A corpse with living eyes...”
- Alexander Dumas, “The Count of Monte Cristo”

Your eyes flutter open and slowly adjust. You hear voices in the distance, and something beeping in a regular rhythm. You try to sit up. No go. Okay, okay, you tell yourself--take it slow. To your right, just inside your peripheral vision, is a glowing monitor with colorful, squiggly lines and numbers, and a clicking box with a bag of water hanging above it. Toward your feet but above you, a television flickers. Directly in front of your face, a corrugated plastic tube seems to emerge from your face and stretch away somewhere. To your left, a sliding glass door beyond which uniformed men and women move briskly about. The answer comes: you’re in a hospital.

Again, you try to sit up without success or even movement. You try to raise your head. Nothing. Move your hand. Nothing. You try to call for help, to get someone’s attention. No movement, no sound. Then you realize you can blink, but you cannot move your eyes. You hear intermittent hissing of air through the tube which you now realize is in your throat, and the beeping of the monitor.

Soon, an older man in a long white coat and a young woman in bright scrubs enter your room. “Sad thing,” says the nurse. What happened? you want to say. “No obvious stroke on the CT scan, yet,” answers the doctor, “but sometimes big strokes can take awhile to show up.” A stroke? you think silently. I had a stroke? I don’t remember. “Well, at least the heart, liver, kidneys...everything seems healthy,” says the nurse. That sounds like good news, you think. “Yes, true. Hopefully some good will come of this,” the doctor answers. “I’ll go speak to the family about organ donation.”

What?! you want to scream. No, I’m here! But you cannot speak. Your eyelids can flutter, but you cannot speak, nor move, nor make a sound. You have indeed suffered a small stroke, but to a very important area of your brain. As a result, you have a rare neurological syndrome appropriately called locked-in syndrome.

Locked-in syndrome was first described in 1966. It is a state in which the connections between the higher regions of the brain (thinking and language) are severed from the regions, called the midbrain and pons, that carry impulses to the spinal cord. The result of this devastating injury is a patient who is fully conscious and awake, but unable to speak or move. It is vital that physician differentiate between locked-in syndrome and more common brain injury states such as coma (in which the patient is unmoving and unconscious) and persistent vegetative state (in which the patient can move but is unconscious). If not, an awake, thinking patient may end up an unwilling organ donor.

This Halloween, though, no need to fear that one day you will wake up unable to move or speak--appearing, essentially, to be brain dead. It wouldn’t, it couldn’t happen to you...right?

Protein Folding

Medical Meanderings 4 November 2009

Know When To Fold ‘Em ©

“The Universe is not only stranger than we imagine, it is stranger than we can imagine.”
J. B. S. Haldane (1892-1964)

If a mad scientist were to want to create a living human cell (and some non-mad scientists are working on this), he (women rarely become mad scientists) could not simply pour all the chemical ingredients into a blender and expect a good result. Most biological chemical reactions are so slow that they essentially don’t happen at all on their own. How do our own cells, then, manage to coax these molecules to react, thereby staying alive and keeping us alive?

The answer is the miracle of proteins. Every one of our cells contain millions of different proteins, which are the most versatile molecules known, the multi-function Swiss Army knives of biology. One class of proteins, called enzymes, are responsible for taking two different molecules and marrying them in the chemical reactions needed to maintain life. Enzymes are so efficient in this role as catalysts that they can increase the rate of a chemical reaction a billion- or trillion-fold. Each enzyme has a small pocket into which specific molecules fit snugly, like a plug into a socket, allowing the enzyme to do its chemical work.

What allows an enzyme to use this kind of key-in-lock specificity? Every protein is made of a long chain of building blocks called amino acids, which are linked together, like a string of pearls, in a particular order determined by a length of DNA. The chain of amino acids is called the “primary structure” of a protein. However, amino acids have positive and negative charges, so we can imagine a string of magnetic pearls which, far from hanging simply around a graceful neck, would stick to each other according to the rules of magnetic attraction. Amino acid chains tend to morph into spirals or crinkled sheets called the protein’s “secondary structure.” The sheets and spirals then bend sharply, stick together, fold into each other. All this folding and bending results in the protein’s “tertiary structure,” a specific three-dimensional shape, more complicated than paper origami, which determines the function of the protein enzyme.

Now we can see why a change (mutation) in a particular gene might have major effects in the body. The DNA sequence of the gene decides the order of amino acid building blocks, but if even a single pearl is changed, the string folds up in a completely different way, and that enzyme will function very differently. The lock changes, and maybe the key fits better, maybe it doesn’t fit at all. Depending on the protein, the change can be helpful, neutral or catastrophic.

Scientists are beginning to better understand the effects of protein folding on the development of embryos, various diseases (such as “mad cow” disease and sickle cell anemia) and the overall course evolution has taken. The complicated path from gene to amino acid to protein folding is becoming clearer, and it will be exciting to see how the future...unfolds.

Friday, July 16, 2010

Medical Meanderings is back!

After an eight-month hiatus due to a lair location change, Meanderings is back! The Committee on Meanderings Authorship (comprising the world's top literary and medical minds) and distinguished Editorial Board (members of which have sworn an oath of secrecy and anonymity) cannot guarantee that Medical Meanderings will be released weekly, but we will do our best to provide the world with interesting, entertaining and factually accurate reflections on an intermittent basis. Enjoy, Dear Readers!

P.S. To get the proverbial ball rolling, the CMA has posted a few oldies but goodies.