Monday, January 31, 2011

Preventing Hypertensive Stroke

     This blog is rather short, because the basic facets and results are quite clear. The biggest risk factor for stroke in the general public is high blood pressure. The first anti-hypertensive to conclusively demonstrate a reduction in stroke risk was thiazide diuretics. They apparently work by lowering the total amount of salt in the body. We also know that thiazide diuretics are synergistic with every other anti-hypertensive medicine, in that diuretics potentiate the effect of every other hypertensive treatment. In fact, if you are on two anti-hypertensive drugs, one of them should be a diuretic, unless you have some very unusual medical condition.

     So the message of this blog is that diuretics prevent strokes. I raise this point because recent medical studies have been trumpeted in the newspapers as being more effective or more potent than thiazides in lowering blood pressure. But the question to ask your doctor is if this new and "better" anti-hypertensive treatment has been shown to lower the risk of stroke. If it hasn't, then either ask him to add a diuretic,  or see a specialist in hypertension, to see if yours is a special case.

     This is a small example of substituting an endpoint for a clinical result. We have seen similar problems in whether or not lowering cholesterol prevents heart attacks, or if lowering CPR is beneficial. To use my favorite analogy, just because you have a better "tool" for returning the arrow over the elevator to the lobby than simply pushing the lobby button, it doesn't mean that your tool will get the elevator down any faster.

Tuesday, January 18, 2011

Helping Patients to Improve Their Health ?

     There has been a lot of press and discussion about how giving patients more information about their health and healthy habits in general will improve their health, but I have never seen much evidence of this. In fact, a recent 13-month study of Taco Bell, which posts the calorie count of each item in its menu, showed that customers did not decrease their total caloric intake. It's somewhat similar to smokers smoking a greater number of low-nicotine cigarettes to get the same total nicotine effect, or people eating more of a low calorie food. I also can't see how having all their electronic medical records will give them healthier habits.

     Every adult knows (or at least is told by his doctor and government authorities) that he/she can become healthier by stopping smoking, losing weight, and exercising, with very little effect on their habits. In all my years of practice I have  never been able (even with the help of a nutritionist) to get any overweight new onset diabetic patient to lose weight, even after I told them that the loss of 20 pounds would probably reverse their diabetes. In fact the only patients I have ever seen voluntarily and efficiently lose weight is men after their first heart attack. The heart attack removes their denial that they could ever get seriously ill. Most of them immediately go on a diet whose major component is eating fish 7 days a week. This works, but after 6 months I have to check their blood for toxic mercury levels. The only healthy habit my patients willingly follow is that of having a glass of wine daily, fish oil twice a day, and dark chocolate. This is probably because two of the three taste pretty good, and none of it seems like real medicine.

     The basic problem is that the human brain seems to be geared to avoid a life-threatening problem only if it is perceived to be imminent, i.e. to occur in the next 10 seconds, but not if the threat is 10 or 20 years in the future. So not every driver belts in, every cigarette smoker (and they know cigarettes are also called "coffin nails") intellectually believes that cigarettes may be dangerous, but also believes that the particular cigarette being smoked at this minute will not be lethal. Every adult understands the dangers of unprotected sex, but 25% of my college student patients (male or female) have unprotected sex at least once during college, usually when they are having sex with someone who is not their usual partner.

     When I am medical ward attending, I poll my residents to see how many of them actually  finished the prescribed number of days for their last antibiotic prescription, and the answer is always fewer than 75% of them. I then ask them to sit down and talk with the next ward patient who refuses a test or a prescription and try to understand their reasons and motives, rather than immediately call for a psychiatry consult. Similarly, I have regular patients who have never had a mammogram, a colonoscope, a flu vaccine, etc. However, I can usually get them to take a tetanus shot every 10 years after I explain that tetanus is usually fatal. (The same applies to yellow fever vaccine, but not always to malaria prophylaxis.)

     Many patients also try to appear healthier than they are. I usually have my diabetic patients initially do fingerstick sugars fasting in the AM and 2 hours after dinner in the PM 3 times a week. Once the  HgbA1C blood test became available (for you non-doctor readers, this is a measure of the average blood sugar for the previous 3 months) it was immediately evident that most diabetic patients either wrote down a lower number for their blood sugar than the test showed, or kept on re-doing the test until they came up with a number they liked.

     We all have patients that try to reduce (on their own) the amount of blood pressure or asthma medicine that they take, because they think that the more medicine they take, the sicker they must be. I explain that the important aim is to achieve control of the problem, and it is not sensible to expose themselves to the possible side effects of any medicine unless they take enough medicine to achieve our mutual goal. Sometimes they will skip some of the medicine and not tell me, hoping that it will not show up on my examination.

     In line with the above, patients with unhealthy habits know that their habits are unhealthy, and that their refusal to alter their habits is illogical. It is precisely because their behavior is not logical that telling them more than once or twice to change their habits is non-productive, and only causes bad feelings on the part of the advisor or advisee or both. Confrontation never works in such situations. The only exception I have ever seen is when an alcoholic  man's boss tells him to go and dry out for 30 days or else he will lose his job, the man dries out and stops drinking. This is because his job is intimately entwined with his ego. 

     This subject will be continued in a future blog.


Saturday, January 15, 2011

Urine Drug Tests

     I have not read any articles recently about urine drug tests, so I thought I might discuss it here. A useful article with many excellent references was written  by Karen Moeller, in the Mayo Clinic Proceedings: If you are an old-timer such as myself, you probably remember the Yippie Handbook: "Steal This Urine Test".

     The problem for the tester is the existence of false negative tests, and of course the problem for the testee is false positive tests. As a compromise, all tests have a cutoff, above which the test is considered positive. The urine tests are almost always a screen by immunoassay for either the parent drug or a metabolite. Since, as we shall see, many OTC as well as Rx drugs can give a false positive for various "drugs of abuse" (a technical term comprising amphetamines, cannabinoids, opiates, cocaine, and phencyclidine), for legal purposes any positive screening urine drug tests must be confirmed by gas chromatography-mass spectroscopy. The immuno screening test is used because it is rapid, not labor intensive, and cheap, much in the same way that the VDRL test is used to screen for syphilis, and the FTA to confirm it. As an example of the problem with a false positive screening test, since Lyme Disease is caused by a spirochete, just as syphilis is, many patients with Lyme disease will test positive on a blood screening test for syphilis.

     One immediate problem occurs with the amphetamine assay. There are 2 chiral isomers of methamphetamine: d-methamphetamine and l-methamphetamine. The (d) and (l) prefixes stand for (dextro) and (levo) respectively. The d-isomer if dissolved in water will rotate the plane of polarization of polarized light to the Right, and the l-isomer will rotate it to the Left. Louis Pasteur showed over 100 years ago that (almost always) chemical syntheses make an equal amount of the (d) and (l) isomer, but animal enzymes will usually act on one and not the other (he used tartaric acid for this demonstration). Thus your body usually uses only d-sugar isomers (hence dextrose), and the 8 essential amino acids for protein synthesis are all l-isomers. In fact if you were fed only d-amino acids by IV, you would starve to death.

     Now even gas chromatography is not sensitive enough to distinguish between d-methamphetamine and l-amphetamine. The d-isomer works as a CNS stimulant and produces euphoria, and the l-isomer produces peripheral vasoconstriction, and thereby relieves cold symptoms. Of course the OTC drugs used for cold symptomd such as pseudoephedrine, phenylephrine, and phenylpropanolamine will produce false positive tests. Most stimulant drugs used for ADD (such as Ritalin) and most diet drugs (such as phentermine) will also produce a false positive test. More amazingly, the following are some of the Rx drugs that will give a false positive methamphetamine urine screening test: Amantadine (used for the flu and for Parkinson's Disease), Wellbutrin (buproprion), Zantac (ranitidine), Trazodone, Desipramine, Trimipramine, Labetolol (for blood pressure), Chlorpromazine, and Isoxsuprine.

     False positive tests for cannabinoids (marijuana metabolites) can be produced by Efavirenz (an anti-viral used to treat AIDS patients), ANY of the NSAIDS ( Motrin, Alleve, Celebrex, etc.), Tolmetin, and any of the proton-pump inhibitors (Nexium, Prevacid, omeprazole, etc.).

     False positive tests for phencyclidine ("Angel Dust") can be produced by Effexor (venlafaxine), Tramadol,, Advil/Motrin/Ibuprofen, Robitussin DM (dextromethorphan), Benadryl (diphenhydramine), Doxylamine, Imipramine, and Ketamine.

     False positive tests for opiates: Robitussin DM (again!), Benadryl (also again), poppy seeds, quinine, Rifampin (used to treat TB, and also occasionally added to the Rx for severe staph infections), and ALL of the quinolones (Cipro, Levaquin, etc.).

     As far as is known, no OTC or Rx drug produces a false positive test for cocaine, unless the Rx itself contains cocaine.

     For completeness, I should add the length of time that drugs of abuse can be detected in the urine:
 Amphetamine---48 hrs., Barbiturates----short acting---24 hrs, long acting (e.g. phenobarb)---3 weeks, benzodiazepams-----short acting (e.g. Ativan/lorazepam)---3 days, long acting (Valium/diazepam)---30 days(!), cocaine metabolites----2 to 4 days, Phencyclidine---8 days,  Marijuana---once---3 days, 4 x a week---5-7 days, daily use---10-15 days,  long term heavy smoker---more than 30 days.

     I should also mention that some urine tests also use indirect testing methods, such as testing  for the presence of a diuretic, which was taken by the testee in order to dilute his/her urine and cause a false positive test.  If your company wants to see if you are a smoker, they will test your urine for the presence of cotinine, a metabolite of nicotine. Unfortunately, many vegetables such as tomatoes contain a high concentration of cotinine naturally, so if you are a true vegan, you may have a "true" false positive test for tobacco use, in the sense that the chemical is really in your urine, but was only derived from your diet.

     BTW, the ingestion of ethyl alcohol will produce a positive urine test for 7-12 hours.

Wednesday, January 5, 2011

Weight loss (#3)

I think it is time to describe how to lose weight as simply as possible, and to examine how to apply these results to everyday life. From a biophysical viewpoint, if the energy input (calories) is less than the energy expended in daily motion and metabolism, we will lose weight. It is also important to remember that it takes metabolic energy to digest, process, and burn or store food, so that although fat contains 9 calories/gm, carbohydrates contain 5 cal/gm, and the average protein 4.5 cal/gm, the energy yield of each is less than this, because of the metabolic work that must be performed to make it useful to the body. Don't forget that, for instance, swallowing and peristalsis both  use muscles, and these muscles require energy to function.

Again, if you ingest fewer calories than your daily expenditure, you will lose weight (and probably feel hungry throughout the process). The only painless way to lose weight is by cigarette smoking, and we deduce  this from inverse data: Everyone who stops smoking gains about 10 to 15 pounds the first year, and women usually gain more than men. From this we infer  that smoking not only assuages hunger, but raises our metabolic rate. And it has to be smoking, because the use of nicotine gum or patches does not lead to weight loss.

I might here mention that as far as I can see, antidepressants do not invariably lead to weight gain. Rather, depressed patients usually become vegetative, and lose interest in eating, sleeping, exercise and sex. As they become less depressed by the use of medicine, all their appetites increase.

I should also mention that most women find it impossible to lose the last 5 pounds they put on after they become pregnant and give birth. I am convinced (without any supportive evidence) that there is a permanent endocrine/metabolic change in their bodies.

Now, how can we ensure losing weight? The only method that always works (and cures adult onset diabetes as well, secondary to its enforced weight loss) is gastric banding or gastric bypass. The operation works by severely restricting the part of the stomach that can receive food at a given feeding. The patient's eating habits do not change, but if too much food is eaten at one sitting,  the stomach pain is excruciating, so that patients learn to eat much, much less, and typically lose 100-150 pounds. On rare occasions, liver failure occurs 6 months to 2 years after the bypass surgery, and the failure is reversed by reversing the surgery. I have had 3 such patient, and since their fundamental eating habits were never changed, they quickly ballooned up to their previous weights.

I should also mention that between the ages of 25 and 75, your metabolic rate decreases by the equivalent of 3 to 4 pounds per year, so to paraphrase what the Red Queen told Alice in Wonderland you have to run faster or eat less each year  just to maintain your current weight.

There is no evidence that posting the calories next to a food choice enables people to lose weight. All it does is spoil the pleasure of eating a hot dog at a ballpark, because you really don't want to know how many calories you are eating when you are eating for fun. It requires a lot of mental discipline to lose weight, and the human brain is not geared to avoid problems 10 years down the road, but only the dangers that are 10 seconds away. (Just as a cigarette smoker knows that cigarettes are dangerous, but feels confident that the particular cigarette he is about to smoke will not kill him.) I have told countless adult-onset diabetic patients that if they lost 10 to 20 pounds they would no longer have elevated sugars and I could stop their diabetic medicine. In all my years of practice not one has ever achieved this, even after being referred to an endocrinologist and a nutritionist. 

Insofar as carbohydrates are concerned, it is wise to avoid foods with a high glycemic index. If you are dieting you should NEVER eat white potatoes or any bread (bread is really composed of "useless" calories, and white bread is the worst). It is OK to eat pasta, but never have seconds. Rice is the safest carbohydrate to eat to lose weight. In fact, many civilian captives of the Japanese in their prison camps during WWII lost a goodly amount of weight, and their diabetes went away. Before insulin, the standard nutritional treatment for diabetes was to limit the carbohydrates eaten to just rice. I should also mention here that in paleontologic excavations, skeletons from 9000B.C. when man was a hunter-gatherer show no evidence of tooth decay, but as soon as man started to cultivate carbohydrates, the later skeletons showed caries.

So how do we lose weight? I am ignoring exercise for the time being, except to note that most college graduates gain weight the first year they are working, because instead of running all over the campus and up and down stairs, they are sitting behind a desk for 8 to 10 hours each day. Again, we have to eat less, and exercise portion control. I don't believe in special diets, because few patients can keep them up forever, and it is easier  to  lose weight on diets that you like. I tell my patients no white potatoes or white bread, to weigh themselves on Sunday, and to re-weigh themselves the next Sunday. If no weight has been lost, I tell them to eat smaller portions  any way they choose to, and to weigh themselves again the following Sunday. Repeat the process until weight is lost, and then maintain that diet with those portions. The weight loss always plateaus, because the brain is persnickety and loves the status quo, so  as you lose weight, the body's metabolic rate decreases, so it becomes harder and harder to continue the weight loss. (Don't worry, the same thing happens in reverse as well: if you gain weight, the body's metabolic rate increases.) The main fact to remember is that you burn fat most readily when you feel hungry, and your liver usually has a 6 hour supply of glycogen, or animal starch. So if you feel hungry after dinner, you will start to burn fat in 6 hours, but if you don't feel hungry you start to burn fat 6 hours after you do feel hungry. So the best way to ensure fat loss is to feel hungry all the time, which most people cannot do.

The most successful at losing weight are marathoners and other long-distance runners, and anorectics. So at the extremes, both hard exercise and not eating will help you to lose weight. This shows that weight loss is definitely achievable, but no one knows how to motivate people to lose weight, any more than we know how to motivate them to stop smoking or drinking. I don't know if the dieters or the smoke-enders know themselves how or why  they changed their habits.

I do think that daily exercise is part of weight loss. When I was young, we all ate "junk food" Bonbons, Dots, Chuckles, Banana splits Milky Way, Twizzlers, etc, but we ran around playing games in the school yard for 3 hours each day until dinner, and all day Saturday and Sunday. Today's children have after-school studies, practice, scheduled play dates, etc, so they have less of a chance to burn off the calories they ate. I assume they have the same food appetites that we did, so how can they lose weight without exercise? I should also mention that weight loss is especially problematic for poorer people, because protein is always more expensive than carbohydrates.
One final point: Why don't adults say to themselves "Hey, I should lose some weight" the first time their pants waists  increase from 30 to 32 inches or their dress size increases from 6 to 8?  Until we can answer that question I don't think we will ever solve the problem of how to help people lose weight.

And we all like ice cream because it's components are that of mother's milk: sugar and fat!