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.