Monday, April 30, 2012

Medical Statistics and Medical Errors, Part I

     The field of medical statistics is poorly understood by many doctors and by most patients. An article in the New England Journal of Medicine that surveyed over 100 articles published in reputable medical journals stated that over 50% of them used medical statistics incorrectly, and furthermore stated that this misuse invalidated the clinical conclusions of many of these articles. In this blog I will not discuss esoterica such as when to use a two-tailed t-test rather than a one-tailed test, or the uses and misuses of the Cox regression analysis. Instead I will try to point out fallacies in reasoning and statistics that should cause you to doubt a result quoted in the journal or in the newspapers.

     Let me begin by saying that except for out-and-out charlatans, no physician deliberately lies or misuses statistics in a paper. However, it is very easy to delude oneself when doing research. A classic example occurred to a physicist in France in the 1920's and 1930's who claimed to see special rays, called "N-rays" when a beam was passed through an aluminum prism. Only he was able to see these rays, which were subsequently proven to be nonexistent when an American physicist named Wood surreptitiously removed the prism and the rays were still seen by the French scientist. More recently, we can recall the Utah scientists who claimed to have produced "cold fusion" with a table-top experiment. In the distant past, I can refer you to the European horse, "Clever Hans", who was claimed by his owner to stamp his hoof four times when asked for the sum of two plus two, and was also observed to answer similar  arithmetical questions. It was later shown that the horse was (subconsciously) interpreting minute muscular twitches of his master when the number of hoof stomps reached the desired answer.

     Medical error can reach unimaginable heights. The Nobel Prize in Medicine was awarded to Dr. Egas Moniz in 1949 for work he did before WWII claiming to show that prefrontal lobotomies calmed and cured schizophrenic patients. There was no control group cited, and except for the surgery in "One Flew Over the Cuckoo's Nest" it is rarely if ever performed today. But schizophrenia was such a treatment-defying mental disease that the doctors became desperate to seize upon any procedure that seemed to promise a cure, including insulin-induced hypoglycemic shock. Again let me emphasize  that the doctors believed that they were helping the patient, even though a true blinded clinical study had never been done.

     I have already blogged twice about the statistical errors  inherent in meta-analyses of clinical studies, and have published a critique of meta-analysis in the Volume 81 edition of "Chance", a statistical journal published by the mathematics department of Middlebury College, Vt. The point I want to make is that the proper use of meta-analyses is to suggest hypotheses which then should be tested in a proper double-blind clinical study. It is irrational and a violation of statistical theory to combine a number of non-significant clinical studies and thereby to claim a statistically significant clinical result. I can assure my readers that no such approach was ever taken to decide the speed of light or the mean distance of the earth from the sun.

     I cannot emphasize enough the importance of paying attention only to articles and reports of clinical studies that are published in a refereed medical journal. The referee (and I have been both  a referee and an associate editor for both physics and medical journals) wants to ensure that only statistically accurate clinical reports are published. This is a valuable filter because the referee has no axe to grind, and (should be) free from any bias. Thus the referee ensures that the article makes sense, is statistically and scientifically accurate, has enough patients in the study to make the result clinically important as well as statistically correct, and contains enough information that any other medical scientist could repeat the exact study.

     Whenever you see a newspaper report about a medical study, you should try to at least get an abstract of the paper. The abstract is almost always available through, a library journal listing service managed by the National Institutes of Health. Many many times the newspaper, in an effort to simplify the scientific facts, misstates the results of the study. Needless to say, any TV interviews with a doctor should be taken with a large grain of salt, especially if he or she is publicizing a recently written book. Again, the gold standard is a refereed paper published in a reputable medical journal. And let us not forget how many times the clinical conclusions of a published article were refuted by the next clinical article that dealt with the same medical problem. That is why I always tell my patients to wait for and look for a second confirming article, and not to believe any medical "progress" that is written up in the National Enquirer.  

     As a final point, let me re-iterate the importance of differentiating between relative risk and absolute risk. The absolute risk is the benefit or risk you gain when compared with the total population of patients,  while the relative risk compares you to other patients with your identical clinical problem(s). Anticoagulation can reduce the risk of a stroke in patients with atrial fibrillation. The absolute risk of stroke in patients without anti-coagulation may be 5% in two years, and the absolute risk of stroke for patients who are anti-coagulated may be 2.5% in two years. You can therefore claim, with equal validity, that anti-coagulation reduces the absolute risk by 2.5% in two years, or reduces the relative risk by 50% in two years and most newspaper results and PR results will quote the 50% relative risk reduction because it is a larger number and therefore sounds more significant to the uninitiated.

     Let me close by citing verbs that should alert you to a non-scientific conclusion: if the results "suggest that", "can be interpreted as", "might mean that", "leads doctors to believe that", "indicates that",  "can support no other conclusion", then run for the nearest exit, because such phrases never precede a statement in a physics journal about the measured  half-life of the mu meson (2.2 microseconds at rest  for those of you who are interested in the result).






Tuesday, April 24, 2012

Some of my Thoughts

     Below are some of my medical observations, some recalled facts from journal articles, and some of my thoughts and speculations. As do many other people, I tend to generalize, so if I write "men" or "women", please mentally substitute "the majority of", or "most". Some of these comments have appeared in earlier blogs.

1) It is not true that turning the thermostat up as high as it will go will heat your house faster.

2) Similarly, it is not true that if you are running low on gas you should drive faster to get to a gas station before your gas runs out.

3) When you are dating, you are on your best behavior. So if something about the other person bothers you, do not expect it to improve.

4) The Federal Highway Safety Board (see its Congressional testimony) knew from experiments with crash test dummies  that airbags could  be lethal or injurious to young children fastened in carseats in the front passenger seat, but they were so anxious to get the carseat law passed that they omitted this from their testimony.

5) In almost every state where mandatory seatbelt laws were passed, the death rate for pedestrians increased the first two years.

6) When I asked one of my children how getting a driver's license changed his life, he replied that he was now a much more careful pedestrian because he realized how difficult it was to see them.

7) There is a higher death rate for pedestrians who cross against the light in the middle of the block rather than at the corners, because drivers subconsciously look for pedestrians at the corners.

8) In an informal poll, over 90% of adults questioned who liked chocolate ice cream as a child could curl their tongues, and those who preferred vanilla could not. Why and how the motor XIIth cranial nerve is connected to the taste part of the VIIth (anterior tongue)  and IXth (posterior tongue)  cranial nerves is a mystery.

9) We don't know why some people sneeze violently as they leave a dark movie house during the day and emerge into bright sunlight.

10) Your fingernails and hair do NOT grow after your death: skin retraction secondary to dessication just makes it appear that way.

11) The majority of women who do the family wash throw out their husband's t-shirts if  they have holes in them, and the husbands don't know why.

12) The women applauded and the men were shocked when Geena Davis threw the baseball game to her sister in "A League of Their Own". A male player would not even throw a professional game to his identical twin brother. And Early Wynn, a fastball pitcher for the Cleveland Indians who was known for his brushback and knockdown pitches was quoted as saying that he would even pitch his mother high and tight if she got a hit off him.

13) School rules are made by women for girls, and work rules are made by men for men and boys.

14) When a man tells another man or woman "I'll call you", it is generally understood by the other man but not by the woman that he means sometime between the present and his deathbed.

15) "Men are expected to be emotionally shallow"---Jerry Seinfeld.

16) In a study done at Cook County Hospital in Chicago, by looking only at blood types, it was found that in 10% of the live births it was medically impossible for the husband to be the father of his wife's child.

17) Why do schoolgirls usually have much neater handwriting than schoolboys? They both have equal manual dexterity.

18) Could Abraham Lincoln be elected president if he ran for that office today?

19) Pacific tuna is pink (as you see when you order sushi or sashemi tuna in a Japanese restaurant). Atlantic tuna, or albacore, has white flesh. Pink tuna was sold for years before white tuna came on the market, and people shied away from buying tuna with this new color. Then the white tuna sellers came up with a killer ad: "Our tuna is guaranteed not to turn pink in the can".

20) Brakes stop the tires, but the tires' friction with the pavement has to stop the car.

21) In my years in the Emergency Room of Columbia-Presbyterian I never saw a Cadillac driver with a fractured leg from an automobile accident, but I did see plenty of Volkswagen drivers. Moral: drive the biggest, heaviest car you can, such as an SUV. Probably half of your accidents are caused by the other driver, so you want him to bounce off you. In the same vein, I told all my children that I would never let them ride or own a motorcycle, and for the first six months after they got their driver's license I had them drive an old, heavy, Buick Estate station wagon.

22) No doctor ever got sued for doing an (unnecessary?) test, but many have been sued for not doing one.

23) Lawyers can charge for telephone advice. Doctors cannot, but they can be sued for giving bad advice over the phone. Some doctors refer all patients who call to the ER and/or tell them to come right away to their office for just this reason. In some states it is a violation of "sound medical practice" to give any medical advice if you have not seen the patient.

24) Why are seatbelts not mandatory in all schoolbuses in all states?

25) Did your money manager predict the 2008 bank crash? If not, why are you still allowing him/her to manage your money?

26) It is illegal to sell organs here, but not in India. Many patients with kidney failure both here and in England fly to India to buy a kidney and pay for the transplant.

27) On the island of Anguilla, there are five medical clinics: one family medical practice, one dental, and three plastic surgery.

28) New Jersey residents take their driving test in a parking lot. They do NOT take the test on a road with real traffic. To this day I have patients who will not drive on NJ highways because they never learned how to merge at high speed.

29) Why not mandate that the horn of any car in reverse sounds a beep-beep-beep as most trucks do?

30) All of us have emotional inertia, and hope/pray that the stresses of our job or our marriage will get better
without our doing anything about it.

Sunday, April 22, 2012

How to Interpret Medical News and Tests

     There have always been and will always be news articles and TV news stories about the results of medical tests. Some of these articles will quote (usually incompletely and incorrectly) from a study published in a refereed journal, some will quote from a talk given at a medical conference, and some will be derived from an interview with a doctor whose research has come to their attention. One major problem, of course, is that the non-scientist  has no way to judge the medical significance of such news reports, let alone whether or not the reported work fulfills certain basic requirements of scientific rigor. In this blog I will present some guidelines to help such readers and viewers evaluate the news report or interview.

     Firstly, there are no real secrets in medical treatments. Everyone publishes their research, and, if it is significant, tries to get on Oprah's show. Failing that, the PR department of their hospital will issue news releases to local and national newspapers and magazines as well as to the TV media. All of us would like to become famous, respected by our peers, and rich, no matter what our field of endeavor, and keeping our successes secret is not the proper avenue to achieve this. For instance in the field of cancer, each hospital has its weekly tumor board meeting where interesting, challenging or puzzling cases and/or results are presented and discussed. Then in most large cities there is a monthly oncology get-together. There also are quarterly meetings around the country as well as an annual meeting, which meeting is always well-attended by the media.

     Secondly, be careful about placing too much credence in any single report of a talk or paper delivered at a medical meeting. Such a report may or may not be clinically accurate, but until it is submitted for consideration to a refereed journal and is published, it is just one doctor's opinion. In my prior field of physics we recently had  newspaper reports of an experiment which purported to show that neutrinos traveled faster than the speed of light, but a careful re-analysis of the data showed that they did not.

     Third, it is essential to understand and appreciate the difference between relative risk and absolute risk. Absolute risk compares you to the entire world, e.g. you have a 10% chance of going bald if you are a man. Relative risk compares your subset to others in your group: if you are an American male, you have twice the chance of going bald than if you are Chinese. Researchers and reporters use relative risk to over-emphasize their results, and sometimes to stampede you into a certain behavior:  the relative risk number is always larger than the absolute risk number because a subset (the denominator in risk calculations) is always a smaller number than the entire set of humans. If your chance of being hit by lightning is 1/2,000,000, or one in two million, and I can reduce your risk to 1/1,000,000, the absolute statement is that I reduced your absolute risk by 1/1,000,000 , or 0.0001%. OTOH I can say with equal validity, that I reduced your relative risk by one-half, or 50%. Always look to see the absolute number, because only that number has immediate relevance to your case.

   Fourth, in connection with the degree of risk protection, we have the "number needed to treat", or NNT. That is, how many patients, based on the statistics of the study, would have to be treated by the drug or intervention in question in order to get one positive result (i.e. cure one patient, diagnose one disease, save one life, etc.). And note that they NEVER quote the NNS, or the number needed to treat to have one patient get  a side effect, and usually the NNS is quite smaller than the NNT. Would you take a pill to prevent a heart attack if they had to treat 10 people to save one person from a heart attack? What about 100, or 1,000, or 10,000 or 100,000? And would you still agree to treatment if the NNS were 2, i.e. 50% of those taking the medicine or other treatment suffered a side effect?

     Fifth, those patients who enrolled in a study group are probably not typical of the average patient, and the results quoted for them may not apply to you. The study group patients are highly motivated,  have a strong interest in staying healthy, and are committed to seeing the doctor when scheduled. Also their reporting of side effects may not encompass all possible side effects if a question about the possible effect is not included on the questionnaire. A case in point is that  a few men who took Viagra reported seeing a bluish tint to their field of view, a reaction that certainly was not looked for until it was first reported.

     Then we have the case of honest error. Many clinical studies are not borne out when they are repeated by another researcher or research group. This is in part due to the fact that with commonly accepted statistical medical analysis there is at least a 5% chance that the beneficial conclusion was reached by error.
Or it may be simply that the second study group differed in some important way from the first. There are many, many cases of the New England Journal of Medicine, or Lancet publishing back-to-back articles which come to opposite conclusions about a seemingly identical clinical treatment of the same medical problem.

     You should also be aware of the placebo effect. Many studies have demonstrated a placebo effect of 30% across the board. In other words, taking a sugar pill or an injection of normal saline can produce a beneficial effect.
This may be related to the fact that almost all patients feel instantly better as soon as the doctor walks into the examination room wearing a white coat. The human brain is a marvelous organ, and the mind-body interaction is always occurring, either on an unconscious or subconscious level. Believing can sometimes make it so, but we don't know how to engender that believing on a consistent basis.

     Finally, distrust all medical advertisements about the wonderfulness of the doctor or clinic or hospital doing the advertising. If they were that wonderful, they would not need to advertise. I especially dislike the ad (hospital name deliberately omitted) "Cancer. Where you're treated first can make all the difference." The insidious suggestion is that if you do not go to them for treatment and your cancer spreads you only have yourself to blame!!!

Monday, April 16, 2012

Reduce Illness by Irradiating Food

     I was listening to a lecture yesterday given by the discoverer of the West Nile virus, and he mentioned a topic that I have discussed before: The fact that irradiation of food would greatly reduce food-transmitted illness.
I would like to expand on that topic here, discussing it both as a physicist and as a physician. It is important to realize that gamma radiation at the energies we would employ canNOT make the food radioactive.

     There are three types of radiation: alpha rays,. or helium nuclei (two protons plus two neutrons), beta rays, or electrons, and gamma rays, or photons, which we know as visible radiation, infrared radiation, ultraviolet radiation, microwave radiation, radio waves, television waves, or xrays (the label varies depending on the wavelength and energy of the radiation, but they are all photons, or packets of energy). At energies below several  Mev (and xrays are in the Kev range, or 1,000 times less energetic) a nucleus cannot be made radioactive. All that Kev radiation can do is to disrupt the nucleus of the cell and fragment its DNA, thereby either killing the cell or rendering it incapable of reproducing. But the food we eat is already dead or dying, and disrupting the nuclei of a leaf of lettuce will not kill it twice over---dead is dead. And the vegetable nucleus cannot absorb the gamma radiation and release it when we eat it; such a process is impossible by the laws of physics, which are much more accurate and precise than the laws of medicine.

     The people who got harmed by gamma radiation were people directly exposed to high energy Xrays, such as those at Hiroshima and Nagasaki, as well as many of the people around Chernobyl and  Fukushima. The irradiation of the food would take place in processing plants, far away from us, and in a lead-lined shielded room. The radiation would kill viruses (no hepatitis transmitted by the lettuce you eat) bacteria, (no E. Coli from the hamburgers you eat), and parasites (no tapeworm or trichinosis from the ham you eat).

     As a public health measure, this process is inexpensive and tremendously protective, but there is an irrational fear of "radiation". Apparently we would rather risk becoming ill by ingesting possibly contaminated food, than expose ourselves to irradiated food. I was also reminded that MRI, or Magnetic Radiation Imaging was initially called NMR, for Nuclear Magnetic Resonance, which is an accurate label of the physics involved, but the "powers that be" pandered to the fear of the word "radiation" by changing its name.


Friday, April 13, 2012

Medicine and the Scientific Method

     The scientific method was  pioneered by Galileo Galilei who did the first recorded gedankenexperiment (thought experiment) as well as the first experimental test of a physical law. He kept detailed records of his thoughts, experiments, and observations, including the observation while in  church that a hanging lamp with a longer chain had a longer period and swung more slowly than a similar lamp with a shorter chain. Through a series of experiments he also determined that the period of the pendulum was independent of the mass of the lamp, that the period varied directly as the square root of the length of the chain, and that the period was independent of the length of the arc. (This latter statement only holds true for arc angle lengths for which the sine of the angle is approximately equal to the angle, expressed in radians, i.e. up to about 10 degrees, which is why grandfather pendulum clocks are tall and thin.)

     Now let us address the science behind medical diagnosis and treatment. Almost all correct medical treatments and predictions were arrived at by observation and induction,and almost all the  incorrect treatments arrived at by deduction or using false analogies. Induction (pace David Hume) is the reasoning that says that since the sun has risen in the east for over 10,000 years, it will rise in the east tomorrow.  Deduction is the reasoning that says that the proper way to prevent calcium kidney stones is to decrease the amount of calcium in the diet (a statement which has been shown to be false: clinical studies have shown that you should INcrease the amount of calcium in the diet). We have to rely on induction because the "laws" of biology and life cannot be expressed by mathematical equations, and there are few if any axioms from which medical "laws" can be deduced.  We also sometimes have difficulty defining what we mean by "normal", and how "abnormal" you have to be before a doctor declares that you have a "disease".

     And let us not forget the male analog of a tree falling in a forest and making no sound because there is no one there to hear it: Many men feel that you are only sick if a doctor tells you that you are sick, so if you never see a doctor.............then you are never sick. This is one reason why men get so depressed when they have a heart attack---their denial has crashed into the wall of reality. They then also  often become extreme believers in the virtues of a healthy diet, weight loss, and daily exercise.

     We also have a macro/micro problem: If I want to improve the overall health of a nation of 10 million people, and lengthen the average life expectancy of its citizens,  I would recommend certain tests, but for a given individual, since I have no advance way of knowing the ultimate cause of his/her death, I cannot recommend those same tests with the same degree of certainty. I have a number of elderly patients who have refused annual mammograms, and a number of patients (curiously enough not the same people) who have refused an annual stool for occult blood and periodic colonoscopies, and so far none of the first group has developed breast cancer, and none of the second (with one exception) has developed colon cancer. (The exception was a female who had had lymphoma, and did agree to annual pap smears.) In addition, to the best of my knowledge, none of my patients who refused the flu vaccine have died from influenza.

     The basis of medical reasoning by induction is that if a certain treatment for a certain disease diagnosed by a certain method "cured" more patients than did non-treatment,  then  the same treatment for the same disease (if indeed you do have the same disease as the treated group) will cure you. We are here generalizing that we are all human beings, and deliberately neglecting all differences in sex, age, weight, height, hair color, skin color, ethnic background,  geography, living conditions, time of year, religious belief,  overall health, and prior medical history. Whether or not any of these conditions makes a difference for the particular treatment for a particular disease has not, in general, ever been looked at, and we are also  assuming that if a drug  is given it will have  the same chemical constituents and potency as the medicine used to treat the cured group. This is a very large assumption. We also conveniently ignore the fact that the test group was not on any other medicines, since the test group is almost always pharmacologically null, and most patients over the age of 50 are taking at least three prescription or over-the-counter drugs. To show you how disease outcome predictions have changed, I just read a medical summary of the third patient to survive an infection of the brain with the rabies virus, which we were taught as recently as 10 years ago is 100% fatal.

     I am forever reminding my medical residents that common diseases occur commonly, but can occur with uncommon symptoms. For instance, an acute attack of (ocular) glaucoma can present as intense abdominal pain. If a brunette says she is coughing up red hair, then you should check her mediastinum for a dermoid cyst. If a patient complains of red urine or blood-like red strands in the stool, inquire about recent ingestion of beets. If the computer says that a female patient has severe diabetes because she is spilling sugar and protein in her urine, has an elevated blood sugar,  and has not had her period for two months, you must first rule out pregnancy, because in most computer disease diagnostic trees, pregnancy is not listed as a disease, and therefore the computer cannot recognize the constellation of symptoms for what it really signifies.

     The field of medicine is an art as well as a science. A well-trained physician can look at a patient, recall the last seen visage of the patient and decide that "this patient looks sick", using some internal heuristic and gestalt.
Unfortunately that is not an acceptable computer diagnosis, so we are forced to invent a disease that fits.

     I tell my residents that if the admitted patient is alive when I come in to do my morning rounds, then they have succeeded in the first part of their job, which is to ask for each and every symptom and abnormal test  "what disease or condition can the patient have that can kill him/her if I don't make the diagnosis, and how can I diagnose and treat it?". This requires applied induction, because the resident must ask him/herself what condition that he/she has either seen or read about that can evince these symptoms. I might add that the real challenge is to know which abnormal tests should be ignored, because they are not clinically significant to the presenting case.

     As a final note, a physician's ego should never interfere with the treatment of the patient. A patient's disagreeing with either the diagnosis or proposed treatment is never a reason for the physician so show anger or disbelief. I have many, many male diabetic patients who should be taking insulin but they refuse: if they take insulin they really have diabetes, but if they only take pills then they just have "a sugar problem".





Friday, April 6, 2012

How Does a Doctor Determine That You Are Dead?

     The concepts of this blog are largely taken from the book "The Undead", by Dick Teresi, which raises serious questions about the possibility that some organ donors may have a functioning cerebral cortex and therefore be aware (and possibly also feel pain) as they are cut into and their organs are harvested for transplant, and this book should  be referred to for further information and references.

     Disclaimer: I am not opposing organ transplantation here, but merely showing what the legal definition of death is in our present time.

     What do we mean by "dead"? There is more than one answer to this question. There is what you would think is or should be the definition, what most doctors think, what many philosophers think, what various religious leaders think, what the law says, and finally, how the law is applied by doctors. Without editorializing, I will describe how the definition of "dead" has changed (I hesitate to use the word "evolved") over the history of man. Our acceptance of the definition is modified by at least three factors: (a) the normal ego cannot conceive of its own non-existence,  (b) none of us wishes to be buried while still "alive", and (c) it's easier to say and think that "they" know what they are doing when a doctor declares a patient to be dead.

     First, some fundamental facts. The cortex of the brain, which is what we see in our minds when we think of a brain, generates electrical and magnetic impulses while you are alive and thinking, dreaming, processing sensory input from the world, etc. These electrical signals can be detected by an ElectroEncephaloGram, or EEG, and the flow of blood and metabolic activity can be measured by a functional MRI, or fMRI as well as a PET scan.The brain stem controls breathing as well as reflexes that involve the cranial nerves, such as the corneal or blink reflex, the gag reflex, and a positive response to the apnea test---more about these tests later. Finally, the heart has its own pacemaker(s) and can beat by itself and circulate blood even when the brain stem has been totally destroyed.

     I am not going to discuss the various definitions of death that operated in different societies, or before WWII, or in fact before 1968. Up until that time, it was generally felt that if your heart stopped beating (no pulse), AND you were not breathing (no signal to the diaphgram from the brainstem), you were considered to be dead. In certain cases of deep coma, some doctors insisted on a "flat line" EEG, i.e. no electrical evidence of cortical activity from the thinking part of your brain. Even then it was recognized that there were exceptions to that rule: certain drug overdoses such as glutethamide (Doriden) or cold water suffocation (drowning and a core body temperature below 95.0 degrees F) could mimic the state of death, and those patients, especially drowned children, could be revived with no apparent aftereffects.

     Anesthesiologists often say that a deeply anesthetized patient is in a near-death state, in that they have to mechanically breathe for the patient. In the case of open heart surgery, the still, pulseless heart is shocked back into "life". If the anesthesiologist observes an acute increase in pulse rate or blood pressure during surgery, his/her immediate assumption is that the patient is feeling pain, and a narcotic is injected to suppress the putative pain, i.e. the anesthesia is deepened. Only if the elevated pulse and/or blood pressure does not respond to additional pain medication does he/she inject medicine to lower the pressure and the pulse. So the point here is if the pulse or blood pressure rise as an operation is being performed, the cortex of the brain may be perceiving pain.

     In the August 5, 1968 of the Journal of the American Medical Association, the Harvard Committee, which contained psychiatrists, neurologists, and ethicists, but NO cardiologists issued their new guidelines for declaring death. They gave several reasons for the need for this new definition. Two of them were the need to free up ICU beds for patients who could better benefit from them, and to reduce the controversy over obtaining organs for transplantation. The conditions were (caps added by me): an unreceptive and unresponsive patient, no movements or breathing, no reflexes, and TWO FLAT EEG'S  taken 24 hours apart. They reiterated the importance of this last test. Note that no mention was made of an absent pulse or a flat line EKG, but then again there were no cardiologists on the panel(!).

     Then the federal government stepped  in, passing the Uniform Determination of Death Act (UDDA) 1n 1981. This is now the law in all 50 states, The UDDA states that the ENTIRE brain must cease to function, irreversibly, and again it notes that drug overdose and hypothermia must be ruled out. However, unlike the Harvard statement, there is no requirement for flat-line  EEG's, and certainly no requirement for a flat-line EKG. It is important to note here  for the non-doctors in my reading audience that all the tests of reflexes, including calorics, doll's eyes and ciliospinal are only tests of brain stem activity or the lack thereof. There is NO reliable test  for the absence of  higher cortical function if an EEG is not done. No reason was given for dropping the last requirement of the Harvard Committee.

     Let me close by noting that there are two well-recognized near-death neurological states in which the patients can think and sense the outside world, but doctors are unable to determine that the patient has a functioning brain. In each state, there have been cases of patients recovering and becoming fully conversant with their doctors, and describing what they felt like. One is the Locked-In Syndrome, and the other is the Persistent Vegetative State. In the locked-in syndrome the brain stem is permanently damaged or destroyed, but the cortex is fully functioning. In the persistent vegetative state, there are brain waves, a sleep-wake cycle, and spontaneous breathing. The precise definitions are unimportant except to note that such patients can recover.

     P.S. Karen Ann Quinlan lived for over 10 years after she was disconnected from her respirator.


Monday, April 2, 2012

Diabetes---Part I

     This blog will discuss adult-onset, non insulin-dependent diabetes, otherwise known as Adult Onset Diabetes (AODM), or Diabetes II. The "M", of course, stands for "Mellitus", which is Latin for "sweet", since diabetic urine usually tastes sweet because of its sugar content (there should be no sugar in your urine). This discussion is not meant to be exhaustive, but will cover what I feel to be the essential topics of the disease.

     Every cell in your body needs sugar (usually glucose) to function at peak efficiency. All cells can ingest a little glucose by passive absorption, but the absorption is greatly facilitated by the presence of insulin in the bloodstream along with the glucose. Two groups of metabolically active cells can absorb enough glucose without insulin to continue their normal processes: red blood cells and brain cells. If this were not the case, then all diabetics would die very rapidly. I should mention here that cancer cells have a higher metabolic rate than non-cancerous cells, and therefore have an accelerated uptake of glucose. This is the basis for the PET scan, which replaces one O-16 oxygen atom in glucose with O-17, a radioactive oxygen atom that emits a positron (hence Positron Emitting Test) and is thereby converted to N-17, an isotope of nitrogen.

     Most diabetic patients have one or both of two defects: either their pancreas does not secrete enough insulin,  or their tissues are resistant to the action of insulin. In either case, their blood  sugar is higher than is normal for their given metabolic state, and some sugar may spill over into the urine. The urine test for sugar can have several false positives, so by itself the urine test canNOT be used to diagnose diabetes, but only to suggest its presence. I should  mention here that the metabolism of the liver is also affected by the presence of insulin, because the liver requires insulin both to suppress its generation of glucose and to enhance its absorption of triglycerides, so that most diabetics have elevated fasting triglyceride levels.

     What is a "normal" level of glucose in your blood? There are at least two definitions: the numerical  definition which defines a "normal" range, or the clinical definition which states the level at which clinical intervention, i.e. treatment, either extends the patient's life or prevents damage to any organ. I will not consider here the subset of diabetics with congestive heart failure, except to note that blood is a non-Newtonian viscous fluid, and that the shear resistance to blood being circulated by the heart rises abruptly at sugar levels above 250, so that a patient with a glucose of 300 may be in heart failure while the same patient can be brought out of heart failure by lowering the blood glucose to 200.

     It is universally accepted that a glucose level greater than 200 measured two hours after a full dinner denotes diabetes; this may be quantified by repeating the measurement two hours after the patient ingests 75 grams of glucose on an empty stomach. It is also generally agreed that a fasting (i.e. 8 AM blood test with no food for the previous 8 to 12 hours) blood glucose of less than 100 means that there is no fasting diabetes. Inbetween these two numbers there is some leeway and much argument. It used to be that a fasting glucose of over 140 was called "impaired glucose tolerance" or "pre-diabetes" and some interventions (e.g. with metformin) reduced the risk of progression to full diabetes. Then the "pre" level was lowered to 125, then 110, and then to 100, with the major result that many more patients were labeled "pre-diabetic) and had to pay higher premiums for life insurance and/or long-term care insurance.

     When the blood glucose level is above 200 in most patients, two irreversible events occur. The first, which causes lasting damage, is the deposition of sorbitol, a non water-soluble molecule, into the membranes of the capillaries of some but not all the organs of the body. This renders a capillary bed incapable of transporting oxygen and soluble nutrients across its boundary from the blood  to the affected organ. The second, which is of diagnostic import, is an increased creation of glycosolated hemoglobin, or glycohemoglobin (HbA1c) in your bloodstream. When glucose diffuses across the red blood cell membrane, a small percentage of it forms a stable complex with the hemoblogin molecule that all red blood cells possess to carry their oxygen. Since red blood cells have an average lifetime of 120 days in your blood stream, the concentration of glycohemoglobin is an indirect  measure of your average blood glucose for the past three months. HbA1c concentrations in excess of 7.0 are considered to be indicative of, or even diagnostic of, diabetes mellitus. (Even this test is not 100% accurate because heavy daily users of aspirin will have an elevated level of HbA1c, since acetylated glycohemoglobin is eluted more rapidly.)

     In all individuals, fat cells require insulin to process the conversion of triglycerides to fat molecules. When you become fatter, the number of fat cells does not increase, but rather each fat cell swells. Therefore, the heavier you are, the greater is the total area of fat cell membranes that is exposed to the circulating blood, and the more insulin they will extract from your circulation. This is why as you gain weight you become more and more "pre-diabetic", and why the first advice given to all overweight diabetics is to lose weight. Unfortunately, as I have indicated in earlier blogs, the only method of weight loss that is guaranteed to work  is operative reduction of your stomach volume and food capacity, either by stomach banding or by gastric bypass surgery. I should also mention that daily exercise (about 30 minutes non-stop) is also beneficial, because exercise promotes the cellular uptake of glucose from the bloodstream, and this effect lasts for longer than the 30 minutes you spent exercising. When you exercise, it is sufficient to exercise at such a rate that at the end of the 30 minutes you feel that you  have had a workout; your pulse rate is immaterial.

     P.S. Although elevated blood sugar is pathognomic of diabetes, it is NOT true that eating sugar or carbohydrates will make you diabetic, unless it also makes you gain weight.