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.