Sunday, February 28, 2010

2/28/2010

Insomnia is a common sleep complaint, yet many people don’t realize simple things that can be easily done to optimize sleep. Much of the tips below are intuitive, some are not. A few are simply incompatible with some life styles. Business travel and being on call were two factors in my own life that played havoc with my sleep.

It’s important to establish a set time to go to bed and precede this with a ritual, such as brushing your teeth and changing into comfortable sleepwear. Part of a good sleep routine is to establish a regular wakeup time that allows for sufficient sleep. Once in bed, or just prior to going to bed, practice relaxation techniques, such as yoga.

Avoid naps. This is probably one of the easiest factors to control if you are employed. Although alcohol may relax you, it has a rebound effect that disrupts sleep when the blood level burns off. So avoid it 4-6 hours before bedtime. Likewise, avoid caffeine in any form (including chocolate) 6 hours before bedtime. Heavy, spicy, or sugary foods close to bedtime may keep you awake, especially if you suffer from GERD.

Your bedroom should include comfortable bedding. (I love the Sleep Number mattress). Keep the room well ventilated and at a comfortable temperature. Block out distracting noises. We mask city noise with a white noise generator. Several good ones can be found on the Internet for under $75. Use the bed only for sleeping or sex and not for reading or watching TV.

Evaluate the effects your medications may have on sleep and, if possible, take those with sedative side-effects within 30 minutes of going to bed.

Thursday, February 25, 2010

2/25/2010

Many people consider sleep a passive process -- probably because most the time we are motionless. Actually, sleep is an active brain process. There is no well defined “sleep” center in the brain like there is a visual center. Instead, various areas of the brainstem are responsible for producing sleep stages. In humans sleep can be studied by attaching recording electrodes to the scalp, over the chest, and over limb muscles. In other words by monitoring brain waves, heart rate, breathing, and muscle tone.

As we enter the first stages of sleep the EEG begins to slow along with our breathing and heart rate. This is termed Slow Wave Sleep (SWS). We progress through four stages of SWS (stages are judged by the amount of slow waves) several times a night. Although we may dream during these periods, the dreams are less vivid and well formed that during REM sleep. From SWS we can move into Rapid Eye Movement Sleep, or REM sleep. The name derives from the observation that during this phase of sleep the eyes move together in rapid random jerks as if the person were scanning a picture. Of note is that during REM periods, the nerves from our spinal cord to our arms and legs are actively suppressed so that it’s as if we are paralyzed. (The nerves to the muscles controlling breathing and swallowing are not affected). Watch a dog sleep and you can see REM periods – you see the eyes move under the lids and, if you watch closely, you may even see the paws twitch. It’s appealing to think the dog is dreaming of chasing the neighborhood cat. It is during the REM periods that we have our most vivid dreams. As we sleep through the night, the periods of REM become more frequent at the expense of SWS. We periodically awaken during the night but normally return to SWS.

Various sleep disorders result when the normal sleep mechanisms malfunction. Narcolepsy is a chronic problem that causes excessive periods of daytime sleep in people who otherwise should be well rested. Cataplexy, on the other hand, is a disorder in which emotion triggers severe weakness of the limbs for a period of seconds - as if the centers that suppress muscles during REM sleep are inappropriately activated. Sleep walking may result from not suppressing leg muscles during REM sleep.

It’s not known for certain why we sleep. But it is known for certain that sleep is crucial to our well-being and may play a role in laying down long-term memory. On the other hand sleep deprivation is deleterious to health. Mild deprivation results fatigue-related problems such as work place errors. As deprivation increases so does the severity of side effect and in its most severe form can result in psychosis and seizures. Not everyone requires the same amount of sleep per day, but most of us need at least 6 hours.

Tuesday, February 23, 2010

2/23/2010

I chair the Institutional Review Board that oversees all research on human patients at a local Seattle hospital. Our job it to protect the rights of patients. This is not to suggest any evil intent on the part of the doctors. The problem is that clinical research involves risks and rewards. The risks are not always obvious, like the side effects of a drug. Much of what we do is cancer studies. Frequently, part of these protocols is the establishment of central tissue repositories for future research. Okay, what does that mean? Let’s say Mr. X has lung cancer and is referred to Dr. Y, a cancer specialist, who happens to be part of a multicenter trial evaluating the effect of apple juice on lung tumors. During X’s evaluation, his lung is biopsied. Some of this specimen is examined microscopically to confirm the diagnosis but some is left over. Should this excess biopsy material be thrown in the trash or should it be stored in a tissue bank for future research?

If you were Mr. Smith, what would you do? If you’re like many people, you may think, “Sure, I’d allow that. After all, it may end up helping medical science.” But here’s the rub: A piece of tissue in isolation may not very useful. Its value often comes from the personal health information attached to it, such as the donor’s sex, age, diagnosis, smoking history, medications, etc. Would you be comfortable allowing this type of personal information to be released to someone you don’t know for undefined purposes?

And what if Dr. Xu holds several thousand shares of a company that uses the repository to develop a hugely successful monoclonal antibody treatment that earns him a large profit? Is this what you envisioned when you donated tissue? Perhaps it makes no difference. Perhaps it does.

And what if, two years from now, a marker for a fatal disease is identified and your material tests positive for it? Would you want to be notified? Is the researcher obligated to do so?

Ideally tissue repositories are set up so that specimens are “de-identified.” Meaning they cannot be linked back to any one person. However, our individual genetic code is as specific as fingerprints. Given enough genetic mapping, any specimen can eventually be traced back to the donor.

Along with medical advances come weighty ethical issues.

Friday, February 19, 2010

2/19/2010

Ever wonder what information is contained in “brain waves,” (the EEG, electroencephalogram)? An EEG is a snapshot of brain electrical activity and is obtained by gluing small electrodes in a set pattern over the scalp in much the same way as EKG (electrocardiogram) electrodes are pasted on the chest. Most EEGs are recorded for only 30 minutes or so and therefore represent a small sample of what actually occurs during a 24 hour period.

Brain waves change with our level of alertness. They slow considerably during most stages of sleep and speed up during periods of extreme concentration. When we are awake but not involved in a mental task they idle within a fairly constant range. The EEG has characteristic patterns associated with different levels of sleep (for example during periods of dreaming). Because dream sleep is characterized by rapid eye movements this is called REM sleep. For this reason all night EEG recordings can be useful in diagnosing various sleep disorders.

Different drugs affect EEG patterns, so the test can be helpful in determining the cause of coma in patients. Complete loss of brain electrical activity is one factor in diagnosing brain death – the state in which the brain is irreversibly and totally damaged.

Some forms of epilepsy have specific patterns of activity associated with them. For this reason, the EEG is commonly used in diagnosing and treating seizure disorders. However, because these characteristic patterns come and go (as do the seizures) any EEG may miss their occurrence. Thus, although the presence of epileptic activity in an EEG is helpful in diagnosing the disorder, the absence of epileptic activity does not rule out the disorder.

Monday, February 15, 2010

2/15/2010

Last night I saw a TV ad for a device that claimed to be “clinically proven” to help back pain. Because of my own back problems it caught my attention. Know what? I couldn’t find any information about their clinical trial. Not only that, but the treatment isn’t FDA approved. So, to me their claim is meaningless.

How do we know if a medical device (or drug) is effective? By testing it in a well-designed clinical trial. Okay, so what’s a clinical trial? It’s a scientific experiment designed to show that the new treatment is more effective than what is available.

Let’s say hypothetical company, XYZ Inc, wants FDA approval for a whiz bang therapy for back pain. They must first document all previous science supporting that their drug has a reasonable chance to be effective. This usually includes evidence from laboratory animals. The FDA may then allow the company to conduct a small (feasibility) study on limited number of people to show that the treatment is safe. Because feasibility studies are typically small, usually they are not sufficient to prove efficacy. If the treatment appears safe, the next step is a larger, pivotal study to prove efficacy.

Why do patients agree to be experimented upon? Is it altruism? No. It’s because they hope the new treatment offers more benefit than what is already available.

Implicit in this agreement is the assumption the volunteers are completely informed of the risks. But this hasn’t always been the case. Between 1932 and 1972 an experiment in Tuskegee, Alabama purposely withheld treatment from African-Americans infected with syphilis in order to document the disease’s natural progression. Even worse, the subjects were never informed of the risks. Since then, sweeping changes in medical research have occurred.

On July 12, 1974 the National Research Act was signed into law. In 1979, after the Belmont Report summarized guidelines for the ethics of human experimentation, the Office for Human Research Protections (OHRP) was established. Now, human experimentation is carefully monitored by special review boards.

Occasionally I hear complaints about the glacial speed of the FDA. However, the agency has provisions to fast-track new therapies that address problems which have no other effective treatment. Balancing clinical need against due diligence is sometimes difficult. I can remember the FDA being criticized for not releasing the drug thalidomide to treat morning sickness in pregnant women when it had already been approved in Europe and Canada. It was then determined to cause severe birth defects.

Friday, February 12, 2010

2/12/10

My sister died from cancer this last December, at home. Four decades earlier we’d seen our mother die slowly and painfully from wide spread metastatic disease. Maybe that’s why she signed the papers that would allow her to legally end her life.

In November 2008 the voters of Washington State passed Initiative 1000 – the Death with Dignity Act modeled closely on a decade-old Oregon law. It allows physicians to prescribe lethal doses of medication to terminally ill patients who have been diagnosed as having less than six months to live. The law went into effect in March 2009. I voted for it.

The intent is humane; to allow a person the option to die quickly and peacefully instead of slowly and painfully.

As the law went into effect, hospitals and clinics scrambled to make institutional policies as to whether to op in or out. About a third of the hospitals are participating, meaning they're letting each individual doctor, pharmacist, and caregiver decide whether to participate. About a third of the state's hospitals have opted out. That means caregivers operating in their facilities or on their behalf are forbidden from helping a patient die, and their pharmacies may not dispense the medications. Another third seem to be somewhere in the middle. That could mean a hospital might forbid doctors and pharmacists from prescribing and dispensing lethal medications on its premises. But the hospital could let its doctors prescribe a lethal dose to an outpatient.

But here’s the rub. If you’re you meet requirements for a prescription (usually Seconal, a potent barbiturate), you must find a pharmacy that will fill it and you must show up in person to collect it. In my sister’s case, by the time she was sent home for terminal hospice care she was too sick and frail to get out of bed and move further than a bedside commode. The law that allowed her to exercise her right to end her life paradoxically denied her the option.

Wednesday, February 10, 2010

2/10/10

Another brain related topic to recently catch the attention of the popular press is the association between epilepsy (seizure disorder) and sudden death. Again, this is not really news because the risks associated with seizures have been well known for years.

First of all, what is epilepsy? It’s the condition when a person has chronic recurring seizures, or a seizure disorder. Okay, so what’s a seizure? It’s what happens when a part of the brain has a period abnormal activity. Picture a large auditorium full of students, all of them busy with taking an exam. Suddenly, one guy jumps up and shouts for a few seconds. Everyone stops what they’re doing and looks at him. He’s disruptive, but if everyone ignores him and goes back to work, not much happens. If this were an area in the brain it would be the equivalent of a small, focal seizure. If, on the other hand, all the other students follow his lead, pandemonium results until either someone stops it or they just get tired and go back to work. This is the equivalent of a generalized seizure. The reasons some neurons develop this kind of abnormal activity are multiple and can range from metabolic problems to scar tissue that is the result of damage, such as a small stroke.

Just how a seizure effects a person depends upon what brain circuits are involved. A very short seizure within the centers for consciousness may appear as only a brief blank stare. One involving motor control centers may result in arm and leg jerking. A seizure that storms through the area regulating the heart rate can cause cardiac arrest and death. This catastrophic effect is, fortunately, very rare. The majority of people with seizure disorders live normal lives.

There are numerous prescription drugs that can help control seizures. And for some patients whose seizures are the result of a small scar on the brain surface, surgery can remove the seizure-producing tissue.

Friday, February 5, 2010

2/5/2010

A recent Washington Post article titled, 'Brain activity detected in ‘vegetative state,’ reported research by a University of Cambridge neuroscientist which showed evidence of consciousness-like brain activity in a few patients in a persistent vegetative state. (The study itself was published on line in the February 3rd New England Journal of Medicine). Persistent vegetative state is a condition of patients with severe brain damage who were in a coma, but then progressed to a state of wakefulness without detectable awareness. In other words their eyes may be open but they are otherwise unresponsive. PVS results from severe head trauma or prolonged periods no oxygen (for example, when the heart stops for minutes).

One of the Cambridge patients was able to correctly answer yes or no questions by activating different parts of his brain. The activation was measured by functional MRI. (f-MRI is a very sophisticated way of using MRI scans to show changes in brain activity that occur during a mental task – see a previous post.)

This study is important for several reasons. One being that it could theoretically be a way to communicate (albeit very slow and rudimentary) with some patients who cannot move a muscle, not even their eyes, on command.

But each apparent breakthrough has its downside. In this case the fear is that the Cambridge findings will be taken out of context and generalized to all long-term unresponsive patients, and that this, in turn, will reignite the bitter fights like the Terri Schiavo case (the Florida woman in a PVS whose family sparked a national debate over the right-to-die issue.)
It should be emphasized the Cambridge patients had PVS from traumatic brain injury instead of brain damage from lack of oxygen, (as was the case with Terry Schiavo). Although interesting, the changes seen in these patients do not prove consciousness as we know it. As stated in the NEJM editorial that accompanied the article, “The mind is an emergent property of the brain and can not be ‘seen’ in images.”

Monday, February 1, 2010

2/1/2010

Dementia is a condition in which a person is losing, or has lost, cognitive abilities. Although Alzheimer’s Disease (AD) accounts for 50 -70 % of all cases of dementia there are several possible reasons why a person might be suffering from dementia. Some are treatable, some are not. Therefore, all cases of dementia need a careful evaluation.

Just like our bodies change with age so does our brain. Some begin very early, while others occur later. Reaction times, for example (the time it takes to react to a stimulus), begins to slow in our late teens and early twenties and continues to slowly decline with age. This is one reason most top athletes, for example tennis players, peak at such a young age.

All of us, at one time or another, have blocked on recalling a well known word or name. We know what it is, but just can’t bring it to our consciousness even though we may even know the first letter of its spelling. Psychologist call this the tip of the tongue phenomenon (http://en.wikipedia.org/wiki/Tip_of_the_tongue ). Throughout our lives this happens to all of us, but its occurrence seems to increase as we pass from the late 50s to early 60s.

Regardless of age, any decline in cognitive abilities in the form of memory loss and confusion can be a sign that brain cells are failing. There may be many reasons for brain cells to fail. Most commonly, it’s from not enough oxygen and nutrients flowing to brain areas. Because some of these causes can be reversible, anyone who shows signs of dementia should be evaluated. A thorough work-up begins with the doctor taking a careful history – is there a family history of dementia? How rapidly is the onset of symptoms? Are there signs of depression? (Severe depression can appear similar to dementia.) Chronic drug or alcohol abuse can also cause symptoms that mimic dementia. An evaluation should include complete blood studies to look for treatable abnormalities, such as Vitamin B12 deficiency. Finally, imaging studies (discussed in a previous blog) can document some causes, such as a brain tumor. If all the studies are negative, the imaging may show signs of brain shrinkage do to loss of cells. The diagnosis of AD or any other type of dementia is made only by putting all this information together and is not based just on the imaging studies alone. If no other cause for dementia is determined, then it’s likely due to AD.

A German physician, Alois Alzheimer, first described it in 1906. If we look microscopically at the brains from AD patients we see two abnormal structures – plaques and tangles. Plaques are deposits of a protein fragment called beta-amyloid. Tangles are twisted fibers of another protein called tau (rhymes with “wow”).

In the process of aging, everyone develops some plaques and tangles. But people with AD have many more than would be normal, especially in areas that are important for learning and memory.

Plaques and tangles are thought to block communication among nerve cells and are the equivalent of nerve cell tombstones left over from dead cells. The build up of amyloid in cells may be the result of a malfunction of the cell’s ability to produce and use energy (a function of the mitochondria). Preventing or slowing this build up is likely to be where future treatment will be effective.

Until recently no drugs were available to treat AD, but Aricept®, a recently released drug, appears to slow symptom progression. Unfortunately, it does not reverse the damage that took place before the starting treatment.