Wednesday, October 31, 2012

Alzheimer's Disease

     Alzheimer's Disease is a progressive dementia that causes a steady, virtually irreversible loss of social skills and intellectual skills, and eventually impairs the sufferer's ability to carry out the ordinary activities of daily living. There have been many studies purporting to show an external cause, or successful drug treatment or beneficial  interactive treatment, but no clinical intervention has been demonstrated to make a permanent difference in the course or incidence of the disease. Since the disease can only be definitely diagnosed by autopsy of the brain, it remains a diagnosis of exclusion, and since the diagnosis is a horrific one for the patient and his/her family, every effort should be made to look for a reversible cause of the person's dementia. The best book of which I know that discusses the stresses of being an Alzheimer's caregiver is "The 36 Hour Day", which describes what it is like to be the caregiver on a 24/7 basis of someone who's mind is being progressively ravaged. .

     It has been my experience that AD patients fall into one of two categories. Some (like my father who had it for five years) appear to be unaware of their condition. They slowly develop a childlike dependence on the caregivers, and cause little or no fuss as they regress to a point where they lie in bed all day and are unable to feed themselves. Others are aware that something is wrong and get frustrated, angry and paranoid and become hostile to caregivers. They are therefore much more difficult to nurse, because they are usually inaccessible to gentle reason.  Drug treatment of this latter  condition usually involves major tranquilizers, is seldom successful in the long run, and can have unacceptable side effects. On occasion physical restraints are necessary. Their caregivers are under major stress, and usually are mentally holding their breath, hoping that the latest outburst will be the last one. A special problem arises when the AD patient tells a relative that the aide has physically abused him/her, and the relative cannot tell if the patient is speaking the truth or succumbing to paranoid ideation. I know several families who have changed aides monthly.

     One problem that arises is guilt on the part of the immediate family members, especially a spouse or a child. They may feel that they have not done enough, or been sufficiently perceptive or supportive. They feel guilty if they cannot be with the AD patient 24/7, and I have to reassure them that caregivers need rest also, and that there is a reason that interns, truck drivers, and airline crews have strict limits on the number of consecutive hours that they are allowed to serve. An early point of stress is the family decision to remove driving privileges from the AD patient. The primary caregiver also often feels uncomfortable about  being more than one or two hours from the AD patient in case "something happens", let alone taking a weekend trip or an extended vacation.

     Then there are the well-meaning friends and relatives who bombard the caregiver with forceful suggestions about taking the AD patient to a special diagnostic or treatment center, or to a geriatric specialist. Again, the reversible causes of dementia are well-known to all competent internists, family doctors and neurologists, and are diligently looked for. One diagnosis that is occasionally overlooked is the pseudo-dementia of depression. And there is no good clinical evidence that intellectual interaction and stimulation affects the course of the disease. The main advantage of a day-care center for the AD patient is that it gives the caregiver a well-needed rest.

     All AD patients have some degree of memory loss and impairment, most commonly in short-term memory. As we get older, the transfer of information from short-term to long-term memory becomes less automatic and requires more effort,so that while in our 20's we remember our friends' phone numbers and addresses automatically, as we get older we write it down more and more often or log it into our smartphones. If you walk into a room in your 20's and say "where did I put my car keys", you curse yourself for being an idiot, but the same activity in your 60's immediately makes you concerned about AD, It has been my experience that a significant sign of serious memory loss is the inability to find one's way home after a walk or a drive, especially if the person  took an unfamiliar route to get someplace. And if you want to find something after you put it down, you will be most successful if you place it at eye level.

Thursday, October 18, 2012

Are Annual Physicals Beneficial?

     I have received a number of questions about the latest Cochrane report about the purported uselessness of annual physicals, so I thought I should analyze the report for my readers. (My earlier thoughts were posted in an earlier blog, entitled The Annual Physical.) For those of you who are not familiar with the Cochrane system, it is similar in concept to the group of French mathematicians who have published articles for over 50 years under the pen name Bourbaki. The Cochrane group is an international non-profit organization. It  has a fluid makeup and a number of different participants, and devotes itself to finding the best proven treatment or diagnostic process for a given disease or symptom, based on clinical studies. They publish a book each year under the auspices of the British Medical Journal, and when you read the book you are led to realize how few of our medical methods are well-grounded in clinical fact. As I have often mentioned before, what seems "obvious" often does not stand up under clinical studies, e.g. the proper treatment to reduce the number of calcium oxalate kidney stones you  produce is to INcrease the amount of calcium in your diet, not to decrease it. I should also mention that the calcification of your coronary arteries proceeds independently of the amount of calcium in your diet.

     A good summary of the Cochrane report to which I refer was published online by Med Page Today on October 16, 2012, at The study was a meta-analysis (and see my previous blog on that subject with an analysis of the weaknesses of such a study) of 16 clinical trials involving over 180,000 patients. The endpoint they looked at in 8 studies was cardiac mortality and in 8 studies was cancer mortality.  They found that patients who had regular health checkups died from both causes at the same rate as those who did not have an annual physical, and they also did not have less disability.

     There are several logical errors in this analysis. To begin with, since the mean time of the studies  was 9 years, they could not test for total mortality, i.e. extension of one's lifespan. Secondly, many patients go for  screening studies such as a pap smear and a mammogram without having an annual physical. Thirdly many patients take themselves to cardiologists of their own accord, and periodic cardiology visits were not counted as a regular health checkup any more than was a visit to one's gynecologist. The conceptual problem with all the studies is that no attention was paid as to how a potentially fatal disease or condition was discovered. We do know that certain interventions save lives, so that people who see a doctor, even aperiodically, live longer than people who never see a doctor. Therefore the questions devolves upon when and how often a patient should be examined by a doctor, and whether the schedule of the visits should be rigidly time-ordered, or one should wait for the patient to come in. At what time interval does a periodic physical exam of a patient with no complaints begin to save lives? This is the basic unanswered question.

Tuesday, October 16, 2012

West Nile Virus

     This has been an exceptional year for West Nile Virus infections in the U.S., especially in Texas where the majority of infections, permanent disability and death have been reported. As always, the most accurate and up-to-date information is available from the Center for Disease Control, whose website is Since this RNA virus is spread almost exclusively by bites from infected mosquitoes, the best way to avoid infection is to minimize exposure to these insects, recalling that they are most likely to bite at dawn and at dusk. Some of the standard instructions include wearing long-sleeved shirts and pants, using mosquito repellent, and not venturing outside at times of maximum exposure. However the Asian tiger mosquito, which has also transmitted the infection in the United States, is a daytime feeder.

     The infection is now endemic in the United States in birds that perch. Most birds are just carriers, but crows and robins are often killed by the virus. In fact, the first case reported in the U.S. came from isolation of the virus from a dead crow in New York City, so it is advisable not to handle dead birds but rather to report them to your Board of Health.

     The virus was first reported along the Nile River in Uganda in 1937, but now has spread to all tropical and temperate climates throughout the world. It can infect mammals and reptiles, and most hosts show no signs of the disease. There is no vaccine against the disease, and no available anti-viral medicine for it,
so the only treatment for serious cases is support of vital signs in an ICU. It is diagnosed by tests of the blood or of CSF fluid from a spinal tap. It has been spread by blood transfusions, so banked blood is now tested for this disease. It can also be transmitted from pregnant women to the fetus,  from nursing women to their children, and by organ transplant. There has been no evidence of people-to-people direct infection.

     The majority of humans bitten by infected mosquitoes show no signs of the disease--- 80% have no symptoms at all. Of the remaining 20%, most just show mild symptoms of a viral infection, which can include fever, malaise, rash, swollen lymph nodes, muscle aches and lack of appetite. A few unlucky patients (about 1%) develop infections of the central nervous system, either meningitis or encephalitis, and these may be left with permanent disabilities or have a fatal outcome. The incubation period is 2 to 15 days.

     Those at highest risk for CNS infection are the very young, those over 50 years of age,  pregnant women, and patients with a weakened immune system, e.g. from cancer chemotherapy, AIDS, or immunosuppression after an organ transplant. Additional risk factors appear to be male sex, diabetes, and hypertension, and some patients may genetically be at higher risk for neurological complications. Some patients may have symptoms for 60 to 90 days, and there have been case reports of chronic fatigue persisting for one to two years after infection.

Sunday, October 14, 2012

Epidural (spinal) Injections and Fungal Meningitis

     There have been so many articles written recently about the outbreak of fungal meningitis secondary to spinal injections with a steroid that I thought I should make a few clarifying remarks. Most of what I say here is taken from the Morbidity and Mortality Weekly Report, or MMWR, published by the Center for Disease Control. Their statement is contained in their early release dated October 12, 2012, and their website is

     Steroids (in this case methylprednisolone) can be used to  relieve the inflammation of swollen nerves and joints, and are often given by injection epidurally (that is, near or into the spinal canal) to relieve the pain caused by sciatica or other neuritis. This can break the cycle of  pain causing  muscle spasm which in turn can pinch the nerve that travels through the muscle and perpetuate the pain. There have been various studies of the efficacy and permanence of the relief caused by this treatment, but a discussion of that is outside the scope of this blog.

     The potential problem with steroid injections lies in the fact that it suppresses inflammation in part by suppressing the local release and local action of white blood cells. So if the steroid solution itself is contaminated with bacteria or  fungi, you are not only inserting a pathogen into a very susceptible region of the body but you are also directly inhibiting the body's response to and elimination of the pathogen. In the recent epidemic, the contaminant was a fungus.

     Now fungi reproduce vary slowly, so it can take weeks for the implanted infection to manifest itself. (In the recent outbreak the time between injection and the development of symptoms ranged from 1 to 42 days.)  Because fungi reproduce slowly, the time necessary to treat fungal infections is measured in months, not in days or weeks, since  most antifungals work by attacking fungal DNA after it has uncoiled to reproduce. And because fungi have sterol compounds in their cell membranes, ordinary antibiotics cannot penetrate the cell and therefore do not work. In addition, because the two-drug combination suggested by the CDC to treat fungal meningitis has serious side-effects, one does not give prophylactic antifungals as a rule.

     Fungal meningitis is not contagious, and there has been no record of people-to-people spread. The contamination occurred at the factory where the steroid was compounded. For various legal reasons, such compounding facilities are NOT under FDA control, and therefore the production process is neither inspected nor sampled for absence of contamination by the federal government. A recall process has been instituted by the Massachusetts manufacturer under the auspices of the CDC, and over 90% of the patients who received injections from the contaminated lots have been reached and notified with the assistance of the local Boards of Health. IMHO, this does not mean that one should avoid epidural steroid injections, but it would be prudent to make sure that the supplier was  "reputable", i.e. the drug came from a drug company whose name you recognized, since they would have much more to lose if their product were found to be unsafe.

Wednesday, October 10, 2012

Diet, Health, and Longevity

     This blog was stimulated by a front page story in the New York Times of Saturday, October 6, 2012. It described the response of tens of thousands of high school students this fall to the new federal mandate that school cafeteria lunches be "healthy". The students are throwing the lunches away, or boycotting the cafeteria, or buying their food from vending machines. The same children who wouldn't eat their spinach as two year olds will not eat rice cakes and whole wheat pizza when they are sixteen. Come to think of it, neither would I (don't rice cakes really taste like styrofoam?). And the food pyramid that students are taught to guide their healthy eating habits in schools today is the inverse of what we were taught as students: What we were taught should be at the top of the food pyramid is now placed on the bottom, and our bottom is now their top.

     Do we really know what "healthy" food is? Do we really know which diet is "best" for us? What should be the nature of our diet to maximize our life span? Do we know if optimal health requires us to eat three meals a day rather than two meals or six meals? And at what time of the day should we eat our largest meal?  Is salt really bad for you, or sugar? How much or little fluid should we drink, and of what kind? Is it safe to fast for 24 hours?  What do we do with the fact that human skeletons from 9,000 B.C. when humans were hunter-gatherers and ate mostly meat  show no signs of tooth decay, while skeletons from 6,000 B.C. when humans began to cultivate grain and ate carbohydrates show extensive tooth decay and jaw abscesses? (saliva turns starch to sugar in your mouth, but only can break meat down into its proteins) What about the many benefits of coffee (described in an earlier blog), or the benefits of moderate alcohol consumption or dark chocolate? Should we eat until we are no longer hungry, or stop when we are only partially filled? Is the Japanese diet responsible for their high rate of stomach cancer or for their  longevity? or both? or neither? Isn't the reason that everyone likes ice cream due to the fact that it is really flavored frozen mother's milk, rich in sugar and fats?

     I will now list the top countries for life expectancy, first from birth, and then from age 40. There is a slight variation because infant mortality enters into the total life expectancy from birth: For instance the Unites States rates 49th in life expectancy from birth, but 33rd in life expectancy from age 40. If diet affects total health (as opposed to the amount of food or calories eaten at a single sitting) then we would expect a clustering of countries from the same area of the world who consume approximately the same diet, and we will see that this is not the case.
     Life expectancy from birth in descending order: Japan, Singapore, Australia, Canada, France, Sweden, Switzerland, Israel, Iceland, New Zealand, Italy.  Life expectancy from age 40: Japan, Switzerland, Australia, Italy, Israel, Iceland, Spain, France, Canada, Singapore, New Zealand . I have included 11 countries rather than 10, because I am not certain if Singapore should be classified as a city rather than as a nation.

     Japan and Australia rank #1 and #3 in both lists, and they have totally different diets and eating habits. The French paradox pops up, of course. Israel and Canada both rank high, and again they have radically different dietary habits. So if we look at total longevity, it is difficult to draw any conclusion about the benefit of any particular diet. I should also mention that the longest lived people born in America are Asians, so it would seem that genetic heritage might be more important than diet in determining longevity. As far as I am aware, no substantial research has been done on the country-wide genetic contribution to longevity, but we do know that there are many genetic factors which are common to people of a given country. As a trivial example, all 100% Inca indians from Peru have type O blood, but very little research has been done on the effect of a blood type on one's health. We know that almost every female Pima Indian from the American southwest has severe gall bladder disease and a cholecystectomy by age 18. The Parsees in India, who are descended from the Zoroastrians (who believe in a God of good and a God of evil) who were expelled from Iran and Iraq, have an exceptionally high rate of breast cancer. Much more research has been done on disease incidence and risk factors than on the incidence of health and longevity factors, for obvious reasons: Disease is immediately obvious, but the absence of disease is more difficult to measure, and longevity requires waiting for a life span to ensue.

     The problem in recommending a "healthy" diet is one of insufficient information. We only have biomarkers which are surrogates for health and longevity. A white laboratory rat reproduces every 30 days, so in six months I will have studied six generations of rats and have a fairly good idea of which diets are beneficial or harmful for them. Humans reproduce every 25 years (on the average) and the longest detailed interventional diet study was 5 years, with a few tracking studies of 10 years and the Framingham study also available. So we just don't have enough diet data to advise healthy people (except the trivial advice to not get fat, not to smoke, and to have a glass of wine three days a week). And we have gotten burned with misplaced advice: Vitamin E supplements were shown to increase the rate of heart disease, and  the anti-oxidant beta carotene was shown  to increase the incidence of lung cancer in smokers. Finally, there is absolutely no evidence that diet is more important than the genetic makeup in a country's overall longevity.