How much sleep do we need?

or how do I get my teenager up for work on a summer morn'?

Generally he gets his own darn self up, but this a.m. was an early start, and early start and summer and teenager are not necessarily part of the same sentence. When I first woke him up, it was clear that no one was home behind his eyes. After I poured water on his head, it was clear that an angry but wakeful human had taken charge.

Here are some observations from a recent article in ScienceNOW Daily News(1) about how much sleep animals need in the wild and why that may or may not apply to humans and the subset of humans known as teenagers:

1. "Animals sleep less if they need to graze extensively--as with herds of horses." This is a tough one, he already grazes extensively. The problem must be, however, that if all the grass...er food...is right there in the 'frig, he doesn't need to spend much time doing so. Note to self: Empty out 'frig.


2. "Animals that sleep in groups, such as herds of grazing animals, get less sleep than species that live alone." Scientists theorize that this is based more in eating habits of herd animals rather than the herdiness of it all. M. certainly has quite a sociable herd to graze with, but, again, the good grazing is apparently too close at hand.

Perhaps when he moseys back down the road to school, no more 'summertime, and the grazing is easy. This kid has a 9 a.m. class this fall; I hope the living is lean and dangerous at school. Or maybe not...
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(1)http://sciencenow.sciencemag.org/cgi/content/full/2008/722/2?etoc

Deplin testimonial

I posted some time ago about Deplin, a glorified B vitamin (methylated folate to be exact) that may supplement antidepressants by promoting the production of neurotransmitters in the brain. I've prescribed it to some people not on antidepressants and found that many of them have a positive response with respect to energy and focus. Check out this e-mail from a patient with MS who struggles with low energy and lack of focus:

This new addition to my Rx. closet has made an incredible difference. I feel human, actually went for a walk with my dog last night (1st time in 10 years), feel more alert, have terrific energy and life is suddenly colorful.

Who's the pain in the butt here?

My patient has a pain in the butt. Not 'is a' mind you, but 'has a'. I've never seen anything like it. Her sit bones (ischial tuberosities) are painful to sit upon. She's o.k. with standing or lying, but her sitting hours are intolerably painful so, therefore, seriously curtailed.

I didn't know what to do with her (my father's advice from my childhood regarding things medical that were problematic --"Don't look at it for three days and it will go away"-- didn't work). Ibuprofen and such made no difference. I had to send her to a specialist, and believe me, it was hard to know just what specialist to use.

The orthopedist ordered an MRI of her butt. It showed minimal inflammation of the spot where the hamstrings insert onto the butt bones, but treatment for tendonitis, including cortisone injections, was useless. The neurologist was clueless, the physical therapist energetic but likewise without results.

We finally sent her to a pain management specialist. If you can't beat it, treat it. She was frantic to travel (out of the question) or simply to read a book in the seated position (if you're like her, reading while lying down is a recipe for sleep).

He listened to her story. Don't know if he examined her butt. He suggested Tylenol (heavens, Doc, been there/tried that already!). When she asked him what else could she do to once again achieve comfort in her life, he answered "Just stand up!"

I kid you not, that's what our pain specialist recommended.

The ups and downs of being a doc

Life and a road trip recently took me through Rawlins, Wyoming. Hours of driving through the monotony of southwest Wyoming dictated the need for a pit stop; time to eat and rest glare-weary eyes.

We found a little restaurant, actually the only diner on Main St. that teemed with life and advertised breakfast served all day. Several stuffed animals graced the entryway, real stuffed animals including a bobcat caught for all eternity mid-leap as he brought down a fleeing pheasant. The women's room sported, of course, the title 'Cowbelles' and the men's merely 'Cowboys.'

The meal was so-so, they were out of blueberry muffins and I passed on the alternative biscuits and gravy. As we finished our meal, a tall and sunburned man strode by, balding head shaved close, a slight potbelly protruding over his turquoise studded belt buckle and a beeper hanging off the belt. Most heads turned as he passed, a wide variety of townfolk waved and called "Hi Doc."

Ah, a diner in a town where everybody knows your name. I longed to jump up too and yell "I'm a Doc" and have them all laugh with delight that this dusty aging hippie in coffee-spotted capris and a t-shirt was a colleague to their own dear Doc.

Anyway, Doc Rawlins got to the counter to pay his bill, and I waited to see if they would offer him a bag of blueberry muffins to add to the bag already on his waistline. But instead, the older woman at the register started in on a long story about her bowels and her trip to the regional hospital. Not that I was eavesdropping, but shoot, we were sitting nearby, and I was hoping, at least, for some wonderful tale about how the Doc had saved her aging aunt.

Then I remembered that I live in a neighborhood and shop at a grocery store where many know my name. Why one patient one day described her vaginal woes to me in produce, and another pulled down her lower eyelid in paper goods to ask me whether or not her bloodshot, oozing eye was conjunctivitis. It was. I called in a prescription right then and there to the pharmacy located just east of aisle 18.

On my second day back to work after our Wyoming tour, the nurse practitioner asked me to look at a cat bite, or rather a young woman's hand with four cat bites on it one of which had penetrated her thumbnail. In the day since the feline's attack, the hand had swelled some, the thumb turning pink and puffy. Cat bites are nasty affairs; think for a moment what sorts of fishy things go in that mouth. I told the NP to call a hand surgeon and confirm that oral antibiotics would suffice for a now.

Several minutes later, she returned, sadly shaking her head. "No go, Chief," she reported, "I couldn't get past the front desk with my question. They offered me an appointment for next Tuesday."

What sort of nonsense was that? I strode to the phone and pulled the officious "This is Dr. P, I need to talk to your on-call physician now about a patient."

"Just a moment, I'll get Dr. W," the receptionist said. A moment later she returned to ask "Would this be about a cat bite perhaps? We just had a patient call here for advice a moment ago."

The hand surgeon came on the line shortly thereafter and confirmed the NP's plan as a good one. I realized then, once again, the value of the title and the ease with which it takes me right to the top. Maybe someday it will get me blueberry muffins as well.

Payback time for moms

The female brain is a dynamic structure, which expresses its plasticity most readily following reproductive experience.
---from the Department of Psychology-Neuroscience, University of Richmond

According to research out of the University of Virginia(1), there may be psychological compensation for all those sleepless nights, saggy breasts, and stretch marks that accompany motherhood. Those tedious months of pregnancy, suckling, and pup-rearing...oh right, we're talking rats here.

Neuroscientist Dr. Craig Kinsley and colleagues proved that mother rats adapted better to the stress of confinement in a Plexiglas restraint tube than their female colleagues who'd not yet coped with the demands of ungrateful offspring. Did they consider that lady rats--married, with children--may have just been grateful for the relative peace and quiet afforded by those Plexiglas walls? Speaking from my current perspective of mom to one teenager on site for summer, I would easily adapt, right here, right now, to voluntary confinement at an air-conditioned hotel.

The researchers conclude: "The data suggest that reproductive (hormonal) and/or maternal (pup exposure) experience may inure a female and her brain to stress, rendering her less susceptible to the behavioral-or other-disruptions that stress sensitivity can produce."
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(1)Wartella, J et al. Single or multiple reproductive experiences attenuate neurobehavioral stress and fear responses in the female rat.Physiol Behav 2003 Aug;79(3):373-81.

Lab test for ovarian cancer

A friend/patient of mine was recently diagnosed with Stage IV ovarian cancer. That, of course, is one of the most difficult aspects of ovarian cancer, namely that it is relatively symptom-free until it reaches an advanced stage.

In retrospect, she identified certain vague abdominal symptoms in the months prior to diagnosis (constipation, bloating, the development of a small 'middle-aged' pouch in the midriff), most notable and puzzling to her through the winter and spring was the increasing agitation of her devoted dog. The dear but scruffy mutt would scarcely leave her side, and no sooner did my friend lie down, but the dog would lay paw or muzzle on her abdomen. Most dramatically, the dog would eye her directly with long and beseeching looks.

An article in the June, 2008 edition of Integrative Cancer Therapies(1) may explain her canine's consternation. Swedish researchers in collaboration with members of the Working Dog Clubs of Sweden and Hungary theorized that dogs could be trained to recognize the characteristic odor of ovarian cancer. They not only found that the scent of an ovarian tumor in a doggy sense is different from that of other gynecological cancers (e.g. cervical or uterine) but that these cancer-screening pooches correctly sniffed out early-stage and borderline tumors as well as big, advanced ones.

The authors wrote: "Our study strongly suggests that the most common ovarian carcinomas are characterized by a single specific odor detectable by trained dogs, and while we do not believe that dogs should be used in clinical practice, because they may be influenced during their work [now what, really, could distract a dog?]... still, under controlled circumstances, they may be used in experiments to further explore this very interesting new property of malignancies."
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(1)Horvath, Gyorgy, et al. Human Ovarian Carcinomas Detected by Specific Odors. Integrative Cancer Therapies Vol 7 Number 2 June, 2008.

It took all my education...

A man came in today worried about a red area on his arm. The spot was about the size of a quarter and had two raised bumps within its circumference. He told me that he'd had two similar areas recently, one on the other arm and one on his back, both now resolved. All of them itched.

And they pay me for this?

Tumor necrosis factor

This sounds like a good thing, right? Produced by cells of the immune system, this protein's name implies that it is a sort of cellular "ace-in-the-hole," inducing death in wayward cells and their mutant offspring before a cancerous tumor is formed.

When first discovered in 1975, tumor necrosis factor (TNF) was noted to induce death in malignant cells in laboratory studies. Unfortunately, it is most complex in its actions, proving toxic to healthy cells and actually promoting the growth of certain kinds of cancer. TNF in the wrong place at the wrong time causes unwanted inflammation. This little troublemaker is a destructive party crasher in the joints of persons with rheumatoid arthritis, It also has destructive, pro-inflammatory effects in Crohn's colitis, smoking-related lung disease, atherosclerosis, Alzheimer's disease, and doubtless much more of that which ails us. It contributes to the profound wasting of AIDS and induces fever and shock in the face of overwhelming bacterial infections.

TNF is a good thing if you happen to do battle with a saber-toothed tiger, accidentally drive a Folsom point into your leg, or fall off your bicycle and scrape your knee. TNF is known as an 'acute phase reactant'; as the body's own EMT, it is one of the first responders at the scene of injury or infection. Produced by activated white cells and the endothelial cells that line blood vessels, TNF attracts bacteria-killing white cells known as neutrophils, promotes the passage of these cells through the blood vessel lining into damaged tissues, alerts the liver to produce pro-inflammatory molecules such as c-reactive protein or CRP, suppresses appetite, and promotes fever.

If TNF and company are activated, however, by cigarette smoke, doughnuts, McDonald's french fries, or too much waisted fat, this same immune response sets off a world of trouble in our arteries. Likewise, auto-immune diseases such as lupus or rheumatoid arthritis cause TNF inflammatory responses in joint spaces and other body tissues.

Body balance or homeostasis depends on equilibrium between troubleshooters such as TNF and peacemakers such TNF inhibitors. Therapies directed against TNF have changed the long-term outlook for patients with rheumatoid arthritis. These new drugs include TNF antibodies such as Remicade and Humira, and proteins that fuse with TNF such as Embrel. Early suppression of the joint-destroying inflammation associated with RA can prevent skeletal deformities and pain, markedly improving a patient's quality of life. Unfortunately, blocking a bad actor such as TNF which also has essential immune functions is not without problems. For one thing, TNF has an active role in the body's response to mycobacterial infections. As a result, cases of active tuberculosis have been reported with the use of anti-TNF agents.

Optimal vitamin D doses

I thought everyone had heard the news about the widespread deficiencies in vitamin D, yet the majority of people whose D levels I check measure way, way low in this essential vitamin. Even those who take a daily multi-vitamin with 400 units of D per tablet (the current RDA) are failing to top 30 ng/ml, the lower end of the desirable range.

Doctors in Beirut studied two groups of adolescents over 16 weeks. Half took 1400 units of D3 per week (the RDA for this age group is 200 units) and the other half took 14000 units per week. By study's end, the high dose group had a significant upward change in their serum D levels, but, better yet, demonstrated "substantial increments in lean mass, bone area, and bone mass."(1)

Many of my patients take 400 units of D3 per day, the amount present in most multi-vitamin pills. Per Toronto's Dr. Reinhold Vieth and colleagues "Supplemental intake of 400 IU vitamin D/d has only a modest effect on blood concentrations of [vitamin D], raising them by 7–12 nmol/L [2.8-4.8 ng/ml], depending on the starting point."(2) So if you're skidding along in a pasty white fashion, no sun plus one multivitamin pill/day, and your vitamin D level is around 11 (like so many of my patients), adding one more 400 unit D tablet per day will only get you up to 15, still terribly deficient.

Experts recommend supplementation in the neighborhood of 2000 units per day. Studies suggest that fracture risk falls with D levels of 30 ng/ml, and the improved outcomes not only result from stronger bones but also from greater muscle strength.
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(1)Maalouf J, et al "Short term and long term safety of weekly high dose vitamin D3 supplementation in school children" J Clin Endocrinol Metab 2008; DOI: 10.1210/jc.2007-2530.

(2)Vieth, R et al. "The urgent need to recommend an intake of vitamin D that is effective" American Journal of Clinical Nutrition, Vol. 85, No. 3, 649-650, March 2007

Dr. Ed Hepworth, Denver, CO

Credit where credit's due. I know that people search for patient reviews of physicians, so here's one from a woman who had complicated sinus surgery with Dr. Ed Hepworth here in Denver:

This guy's incredible. Man, he's good!

Lipotoxicity

Here's the new lipocentric news! What is not news, of course, is how lipocentric we're all getting, our fat or lipid-filled midriffs featured front and center in a pregnant abdomen sort of way. Researchers now, however, are theorizing that the fat load we carry as a result of overeating and undermoving is the primary metabolic driver behind the current epidemic of type 2 diabetes. Dr. Roger Unger of the Touchstone Center for Diabetes Research concludes in a recent JAMA editorial that "If this is in fact the case, [high blood sugar] should be corrected by eliminating the lipid overload."(1)

Want the skinny on fat overload? Check out: Lipotoxicity for the details.
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(1) Unger, RH. Reinventing Type 2 Diabetes. JAMA, March 12, 2008, Vol 299, No 10.

Designated Listener, Part II

Seems like there's a run of bad health luck in the lives of those around me here recently. I found myself, once again, sitting in as designated listener for a loved one (LO) during an important consultation. This time, I noticed a few eye-openers about the way my colleague conducted the visit, so here's three rules for MDs in the consultation room:

1. Doctors who don't get appropriate touching should skip touching altogether.
   This guy often stood with hand on LO's shoulder or occasionally sat with hand on LO's knee. I prayed that LO would not haul off and smack him. Honestly, it was not the time or place for such touching, and, in any case, LO exudes 'don't touch me' from every pore of his body.
2. Explain your thoughts, but don't dither.
   The doc was clearly puzzled by the situation and was thinking on his feet. As he mused about the possibilities in a roundabout, back-and-forth, sort of way, he finally came up with what I thought were three appropriate theories. LO concluded, not inappropriately, that this physician was fairly clueless about LO's condition.
3. Explain, but don't over explain.
   The physician gave so many simplistic 'for examples' that he came off as patronizing. Patients may need simplification, but, here I completely agree with LO, this was WAY too much dumbing down.

As an aside, our consultant stood through most of the visit in a stance appropriate to a college defensive back. I assume that at some point in his career he was just that, but it was a little strange there in the examining room.

Blood vessels love grape juice

They're not just passive pipes anymore. Blood vessels, or rather the single layer of cells known as the endothelium that line these passages, actively regulate blood pressure, blood flow, clotting, inflammation, and the immune response. And endothelial cells love purple grape juice whether it's fermented or not.

Persons with arterial disease such as hypertension or atherosclerosis are known to have endothelial dysfunction. In other words, their blood vessels are unable to expand normally in response to such things as exercise and cannot, therefore, efficiently increase blood flow and oxygen delivery when needed. Researchers are able to measure the health of the endothelium and its ability to increase blood flow by a simple test called flow-mediated dilation (FMD).

This test uses ultrasound technology to measure the diameter of the brachial artery at the elbow. A blood pressure cuff is then inflated on the forearm to the point where blood flow through the area is stopped. When the cuff is released, blood surges back into the forearm. Ultrasound is again used to the brachial artery, and the state of blood vessel health can be judged by the post-test expansion of this artery.

Fifteen patients with proven coronary artery disease were hooked up with daily grape juice over the course of 2 weeks(1). Prior to being juiced, these patients, as expected, demonstrated impaired FMD. After 14 days of Welches (and this must be concord grape juice), their FMD tripled. No such changes were observed in other studies conducted with OJ or grapefruit juice.

Grape juice kind of makes my skin crawl, but I drink it anyway. Pair it up with dark chocolate and oatmeal, and your endothelium will be relaxed, your arteries surging with blood.
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(1)Stein, JH et al. Purple grape juice improves endothelial function and reduces the susceptibility of LDL cholesterol to oxidation in patients with coronary artery disease. Circulation. 1999 Sep 7;100(10):1050-5.

Designated listener

Unfortunately, I was the designated listener for a good friend yesterday. I sat through the doctor's appointment with her and took notes while she more or less heard the words that would change the course of the rest of her life.

The doctor did a wonderful job with a most difficult task. She started the conversation with "I am so sorry that you have to come see me today." She spent nearly an hour and a half with us, explaining and also doing a fair amount of listening herself.

Afterwards, we went out to lunch. Shortly after ordering, the waiter returned to the table. "I'm afraid I have some bad news," he said. "We're out of the foie gras."

She and I didn't know whether to laugh or cry. Bad news indeed!

The benefits of Deplin

I wrote about Deplin recently. Billed as a 'medical food,' it is an fancy new methylated version of folate that easily enters the brain. Being a good sport and an inquiring mind as well as a doctor, I thought I'd give it a try.

The downside of Deplin is that it does indeed interfere with sleep. On the plus side, however, I have noticed an increased ability to focus on loathsome tasks involving numbers. My theory is that I have been borderline low on norepinephrine, the lack of which makes me inattentive and anxious. This new source of methylated folate is, perhaps, hard at work promoting norepinephrine production in my aging brain.

I have not yet heard back from several patients whom I have started on Deplin. I hope that it will improve their response to antidepressants and decrease that lethargy that sometimes accompanies the use of SSRIs. This side effect may be due to a down-regulation of norepinephrine receptors in the brain.

I said...MOVE YOUR REINDEER!

You may be surprised to discover that reindeer herding is a hazardous, noisy profession, what with all those braying reindeer and roaring snow mobiles. However, Finnish researchers have found that hearing loss among the herders is not just about nerve damage from noise exposure. Those tundra hands who escaped job stress through smoking, particularly those indulging in more than 144,000 cigarettes (a pack a day for 20 years), had significantly more hearing loss than their non-smoking herd-buddies.

Lest you think this danger does not relate to your daily life, this finding was repeated in a study of 1,500 Japanese office workers exposed to nothing more than the ringing of phones and computer games, There, the risk of high-tone hearing loss among heavy smokers was more than two times greater than those who abstained.

No wonder our pleas to our smoking friends to quit sometimes fall on deaf ears.

"Etiquette-based medicine"

Patients ideally deserve to have a compassionate
doctor, but might they be satisfied with one who is
simply well-behaved? ...A doctor who has trouble feeling
compassion for or even recognizing a patient's suffering
can nevertheless behave in certain specified ways that
will result in the patient's feeling well treated..
---Michael Kahn, MD

Dr. Kahn calls for a good manners curriculum in medical education in the latest edition of the New England Journal of Medicine.(1) He provides an example of a behavioral checklist that clinicians should follow to promote civility and respect in our patient encounters, including:

1. Introduce yourself.
2. Shake hands.
3. Sit down.
4. Smile if appropriate.

I'm sure you've all had encounters with physicians who were less than polite. My Mom's first doctor at the nursing home, shortly before I fired him, spent five minutes in her room during which he never looked at her once nor addressed a single remark to her. I saw a dermatologist a few years back who walked in one door of the exam room, moved slowly past me looking closely if briefly at the area of concern on my forearm, then scurried out the door at the other end of the room. Period. End of encounter.

I agree with Dr. Kahn. If you can't teach all medical students compassion, pass along a few basic rules of etiquette, and train them to shake hands and sit a spell.
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(1)Kahn, MK. Etiquette-Based Medicine. NEJM. Volume 358:1988-1989.

Post-vaccination syncope

Early in my medical school career, some brave pediatrician rounded up a group of us to observe a circumcision. The mom among us (brave soul had a young son at home) turned white as a sheet mid-procedure and sank to the floor in a faint.

This loss of consciousness as a result of undergoing an unpleasant experience is called vasovagal syncope. Completely involuntary, changes in automatic body functions after an intense experience result in overactivation of the parasympathetic nervous system (drop in heart rate) and withdrawal of sympathetic tone (dilation of blood vessels with a subsequent drop in blood pressure). Blood flow to the head diminishes (thus white face), and down she goes.

Actually, she is not completely accurate. The most common vasovagal reactions we see at the office are young men swooning after blood draws. Per the May 2nd Morbidity and Mortality Weekly Report, however, there's a new trend in fainting--teenage girls going to ground after vaccinations.

Experts theorize that the upswing in adolescent girls getting shots due to the rise in recommended vaccines such as the Gardasil series against HPV has caused this surge in syncope. While sinking to a prone position restores blood flow to brain, the worry here is that the young lady will injure herself while sinking, or will take out others if she sinks and drives.

Last year, one of my neighbors, a girl of 15, came to my office from her nearby school to get her tetanus shot. No one likes to be needled, but K was particularly dramatic about her distaste for the task. Nevertheless, she finally received her shot, and fifteen minutes later, we headed for my car as I was done with work and had offered to take her home. Halfway there, K complained of dizziness, and when I looked over she was out like a lightbulb, twenty-some minutes post-vaccine.

Our experience underlines the importance of the Advisory Committee on Immunization Practices' (ACIP) recommendation: Keep the drama mamas and the papas under observation for 15 or more minutes after they twitch their way through their ordeal.

Aspirin and breast cancer

I am often asked whether or not I'd recommend the daily use of aspirin. Specifically, with respect to heart disease prevention, 2003 guidelines suggest that those at 10% risk of a heart attack in the next 10 years do just that. Wondering if that's you? Check out Risk assessment tool. Some suggest that the 10% threshold be raised to 15-20% 10 year risk to avoid putting every man over 70 on aspirin due to the risk of bleeding in the GI tract.

Doctors at the National Cancer Institute checked out questionnaires from over 127,000 female AARP member with respect to NSAID usage (aspirin, ibuprofen, and other anti-inflammatory analgesics) and breast cancer incidence over six years(1). While the use of non-aspirin NSAIDs did not affect the risk of breast tumors, the daily use of aspirin dropped the risk of estrogen-receptor positive cancers (the most common type) by 16%.

Just yesterday, a patient asked me if she would experience pain if daily aspirin use was irritating her stomach to the point of bleeding. I have had three patients over 25 years of practice with catastrophic hemorrhages from aspirin use. Two of them started vomiting bright red blood as their first sign of trouble. The third walked into the office on shaky legs, weak and white as a sheet from blood loss over the previous months. He did not realize that black stools were a sign of blood loss through the GI tract. Pepto-Bismol users, don't freak out. PB makes stools black too!

Do I take a daily aspirin? Yes, I do. I've done so every since the Nurses' Health Study results showed that 20+ years of consistent aspirin use, at least 4-6 times per week, cut the risk of colorectal cancer by 46%(2). This study was published in 1995, so I've got 7 years to go to reap my rewards.

Please note, this post is for informational purposes only. Decisions such as daily aspirin use should be made in consultation with your personal physician who is familiar with your health history.
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(1)Gierach, G et al. Nonsteroidal anti-inflammatory drugs and breast cancer risk in the National Institutes of Health-AARP Diet and Health Study. Breast Cancer Res. 2008 Apr 30;10(2):R38 [Epub ahead of print].
(2)Giovannucci, E et al. Aspirin and the risk of colorectal cancer in women. N Engl J Med. 1995 Sep 7;333(10):609-14.

Deplin

see also Deplin Testimonial for a report on Deplin from a patient with multiple sclerosis

The PamLab drug rep is moderately annoying. I hate to think that the messenger would affect my interest in the message, but, alas, it did for months. He finally staged a lunch 'n learn,* but also, much more importantly, he brought in an article by Dr. Stephen Stahl that caught my attention big-time.

Dr. Stahl is Dr. Psychopharmocology. He literally wrote "The Book" also known as Essential Psychopharmocology. If ever you suspected that the use of psychoactive drugs is a lot of baseless hooey, check out this tome.

Unfortunately, this world is a fast-paced one that demands more attention, energy, and multi-tasking than many can manage. As a result, there's a lot of overwhelm and depression going around. One could only wish that antidepressants were unnecessary, but a lot of people struggle to get a grip on their mood while being bombarded with the pressures of modern life. As a result, these drugs can be lifesavers, or at least change surviving into thriving.

That said, antidepressant medications aren't perfect. In many cases, some relief is obtained, but it's either not enough or marred by the side effects of the drugs. So patients find themselves limping along with ongoing fatigue, inertia, decreased concentration, or other symptoms that impair their quality of life.

The search continues, therefore, for 'augmenting agents' that improve response to antidepressants. Enter Deplin, billed as a 'medical food' which falls somewhere between food and drugs per the Food and Drug Administration who will soon need to change their name to the Food, Medical Food, and Drug Administration. Per them, Deplin aka L-methylfolate--an active form of folate--is so classified because it is:

...intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation.(1)

Now how good is this?!? A new drug, er medical food, that's a glorified vitamin, that has great science behind it for the treatment of depression which is at least half my practice. And being a child of the '60s, always willing to pop a pill to alter mood, I've tried this product myself, and I'm impressed with the results after just a few days of use. But this post is long enough, check out methylfolate and depression for more information on how Deplin works.
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*And lunch was a Subway sandwich on a stale roll and a liter of Diet Pepsi. After the luncheon, he left but hurried back in to grab the leftover pop. So don't think he bought my interest with a fancy meal!
(1)Food and Drug Administration/Center for Food Safety and Applied Nutrition. Food Safety and Applied Nutrition, Medical Foods. Available at: http://www.cfsan.fda.gov/~dms/medfguid.html.

Lovely Confections in Denver

Sometimes a person has just got to indulge. When it's that sort of time, I tell my patients to make sure those calories are really worth it.

Lovely Confections at Colfax & Steele didn't get Westword's Best of Denver award for cupcakes for no reason. These little cakes are so rich and good they sent shivers up my spine. Alas, sharing two with a teenage boy meant less than one for me.

Paxil and the blahs

Paxil (paroxetine) used to be my favorite choice of medications for the longterm control of anxiety. It worked quickly, and rapid relief of anxiety is a good thing.

I've mentioned before, however, how some people experience a dulling of emotion on Paxil. One patient yesterday called it 'robot mode.' That 'whatever dude' sort of attitude may be a welcome relief from all overwhelm all the time, but patients like this lady eventually want more from life than just freedom from fretting. In particular, she hated the inertia she felt at days' end when choosing between attending her kids' sports events versus sitting quietly doing nothing at all.

Unfortunately, in her case, no drugs at all is not a choice. Job, kids, financial worries, and her serious generalized anxiety disorder just don't work out together. Adding Wellbutrin didn't help; we're trying Effexor now.

A dark patch on the skin

A thirty-something year old lady came in today for her physical. Among other things, she complained of a dark patch on the outside of her left ankle along with pain in the same spot. Dark patch and pain, no connections so far.

So I check it out. The patch is slightly irregular and brown with faint overtones of red. It looks like nothing familiar so far, not fungal, not eczema, not psoriasis. Not tender to touch nor hot in an inflamed sort of way.

The pain occurs while walking, so I ask to see her walk barefoot across the room. Bingo. We have a too many toes sign signaling flat feet, flatter left than right. No wonder her collapsing left ankle hurts. But what about the dark patch?

Does it itch? You bet, she says. Do you scratch it? Are you kidding, she counters, all the time. Ah ha, it's that hyperpigmented Iscratchtoomuchandirritatemyskin chronic skin change sort of look. I see that lots in the middle of the back in older people still limber enough to reach around to scratch.

Patches of skin near the spine itch due to a radiculopathy (now how good a word is that) meaning that a little nerve branch going to the skin called a radicular nerve gets pinched as it passes out of an arthritic spine. The skin supplied by this nerve starts to itch or burn, the patient scratches it lots, and the skin gets dark from chronic irritation. Then I look like an amazing medical intuitive when I ask if that area bothers them.

The brown discoloration of chronically scratched at skin is caused by hemosiderin. This pigment is a breakdown product of hemoglobin. As people dig at itchy spots over time, tiny blood vessels rupture and release hemoglobin into the skin. This iron-carrying molecule from blood is deposited into the space between cells and is subsequently broken down into hemosiderin, leaving a permanent discoloration to the skin. You often see this same blotchy brown residue in the lower legs of elderly persons with varicose veins who develop an itchy condition known as stasis dermatitis.

Godspeed Vernice Griffin

I attended a memorial service this weekend for a remarkable woman/friend/patient. The service itself was remarkable as Vernice had prepared a slide show set to music of her life. But truly wonderful was the woman who outlived her 3 month pancreatic cancer prognosis by 2 years.

In 2006, Vernice had returned to work as a visiting nurse. As she drove through northeast Denver, a gunman walked in front of her car when she pulled up to a stop sign. He looked her in the eye, arm rising and gun cocked in hand, fully prepared by his cold and mocking gaze to shoot. He leveled his gun, and Vernice told me that she considered whether or not this was an easy way out of her battle with cancer. In what must've seemed like a lifetime but perhaps was a second or less, she chose life and ducked. The bullet took out a piece of her wild mane of auburn hair, but Vernice lived on for another year and a half as if her pancreatic cancer was nothing more than a chronic annoyance.

Now that's grace under fire! Good-bye Vernice, you will be missed.

Oxidative stress in feces

While reading a book recently called Vitamin E & Health published by the New York Academy of Sciences, I came across something entirely new for us to worry about. Here's the scoop on stressed-out stools:

Dr. Charles Babbs of Purdue University made the "chance discovery" that one part feces in 10,000 parts liquid generated detectable quantities of highly reactive hydroxyl radicals." (I wonder what he was doing when he accidentally stumbled on that little pearl of wisdom?). In other words, the bacteria in poop makes such great quantities of these bad actor hydroxyl molecules, it is as if the rotting wad that daily traverses your colon had been exposed to 10,000 rads of gamma irradiation! And you do NOT want highly reactive slop making its way through your abdomen, messing with your colonic DNA.

So how do we keep from harboring such a molecular time bomb within our colons? No surprises from a book about vitamin E--take vitamin E...and avoid dietary iron and fat. Why not iron?

Iron is an essential part of the hemoglobin molecule which transports oxygen to our tissues. No iron, no life. Excessive iron intake, however, may rust out your lungs, your bowels, and your pancreas, at least if you happen to be a rat from the South or an aging woman from Iowa.

Data from Tennessee rodents showed that dietary iron increased oxidative stress in feces, and stressed-out stools, as noted above, increases risk of DNA mutations and cancer in colon cells. Midwestern investigators found that postmenopausal women in the Iowa Women's Health Study with high iron diets were more likely to get lung cancer, colon cancer, and type 2 diabetes, especially if they drank alcohol.

I recommend multi-vitamins WITHOUT iron to all my patients (and the rats that love them) who are no longer growing or losing blood through their monthly cycle.

Does housework improve your health?

Could be per London researchers who published their study in the British Journal of Sports Medicine. When I read, however, that their data suggested as little as twenty minutes per week of straightening up could straighten up attitudes, I thought "You must be joking."

The doctors sent out questionnaires to nearly 20,000 Scots over an eight year period. They asked participants to: 1) Report on their usual level of physical activity, and 2) take a little quiz assessing their current mental health. They found:

1. Those who puttered 'bout the house and garden for 20 minutes 1-3 times per week were 24% less likely to be in psychological distress.

2. Subjects who upped the putter to 4-5 sessions weekly were 16% less distressed, suggesting perhaps there's a limit to how much time you can muck in the clutter and benefit from having done so.

3. Best of all, no surprise, were those who increased intensity of activity; their bursts of sports rewarded them with 33% less angst.

Well yeah, we know about endorphins and all that; regular hot and sweaty stuff has just got to be good for the mood. But what about this stab or two per week at tidying the home? Does the satisfaction of stacking magazines and emptying waste baskets feed back to a brighter mood?

This, of course, is the rationale behind cognitive behavioral therapy; play like you care and then you start to care. I've mentioned Fly Lady before, the balabusta* who urges women overwhelmed and undermotivated to start the first day of the rest of their lives by cleaning the kitchen sink each night. If you get a grip on one small spot in your chaotic life, next thing you know, you'll be wiping around the kitchen sink, sweeping the floor, combing your hair, and taking on the world.** Hard to believe, however, that those persons spending just long enough each week to conquer the sink and perhaps the stovetop could be experiencing either enough endorphin high to boost their moods or getting cognitively motivated to become undepressed.

My experience with persons in psychological distress is that they simply don't do housework. Period. And those persons not in psychic trouble straighten up their houses as a matter of course.

Makes you wonder about the quality of the medical research that drives our beliefs.
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*That's Yiddish for super-woman; she cooks, she sews, she works, she raises children, and does it all in style.
**Sort of a "If You Give a Mouse a Cookie" approach to mental health.

Risk factors for gout

About once a month, some aging fellow (sorry guys, it's more prevalent in men than women) hot foots it into my office with a hot foot. Gouty feet do not like to be touched; that joint at the base of the big toe--the most commonly affected site--is red, hot, swollen, and strictly hands-off on exam.

Gout is an inflammatory arthritis caused by the precipitation of uric acid crystals in the tissues in and around the affected joint. Uric acid is a metabolic waste product produced during the breakdown of purines which are compounds present in foods such as meat and seafood.* High intake of these foods in susceptible individuals can increase the risk of a gout attack; one study of middle-aged health professionals found that those who chose beef, pork, or lamb as a main dish 2 or more times weekly doubled their risk of gout vs. the group that hardly ever ate meat. On the other hand, those old guys who drank low-fat milk thrice daily were half as likely to suffer from gout attacks compared to those who had none. No mention made of those individuals who both ate meat and drank low-fat milk.

I've just learned about another dietary risk factor for this painful condition, namely sugar-sweetened soda. Now no one ought to be drinking this garbage, and here's another reason why. Investigators made another pass at the health professional data with respect to pop preference. Compared to those who never drank the stuff, those who consumed one can daily were half again more likely to get gout and those who had two or more servings daily nearly doubled their risk.

I ask a lot of people about what they eat and drink, and, believe it or not, two sodas per day is not that unusual.
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*Purine-rich vegetables such as peas, beans, and mushrooms do not increase risk of gout.

Lotrel

Twofers --pills that include more than one blood-pressure lowering medication-- are a good choice for the treatment of hypertension even when the patient's blood pressure is not that hyper. Not only does the combo form eliminate one prescription co-pay and improve patient compliance, attacking hypertension with two different therapeutic approaches often achieves better control.

A popular and effective twofer pill called Lotrel has now become one of those 'stop the study' pills--therapy so effective that they stopped the study as it was no longer ethical to withhold the drug from the control group. This medication, now available in some strengths as a generic, combines an ACE inhibitor called benazepril (Lotensin) with a calcium channel blocker called amlodipine (Norvasc). Each of these drugs works in a different way to cause relaxation of the blood vessel walls. As a result, the same fluid volume (that would be the circulating blood) moves through a larger space causing a drop in pressure.

Here's what the Avoiding Cardiovascular events through Combination therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial accomplished. Over 11,000 hypertensive subjects, all of whom were over 55, obese, and many were diabetic were put on one of two different twofer drugs: Lotrel or lotensin plus a diuretic. Those patients who took Lotrel were 20% less likely to end up with a stroke, heart attack, unstable angina, or a need for procedures to open their coronary arteries over the first 3 years of the study. These results were highly significant in this high risk group, and may well change our standard protocols for treating hypertension which has, until now, started with a diuretic then added on an ACE inhibitor.

Per ACCOMPLISH investigator Dr. Michael Weber: Right now, there is a recommendation that when you're putting together combination treatment for hypertension you need to normally include a diuretic as one of the two agents. I'm sure that recommendation will change.

My medical partner and I have long been impressed with the efficacy of Lotrel in hypertension control.

"My little toenail looks gross!"

I came back in the room after my patient was dressed for the last word on her physical. She had shoes and socks off, a sure sign that she'd just remembered some foot issue.

Her toenail did indeed look gross. The toenail was split all the way down, and the skin around it was heavily calloused. Not a wart, as she theorized, but the result of narrow shoes smashing her 5th toe beneath her 4th.

I asked her to stand up with her bare foot next to her stylish brown leather heels. There was no relationship whatsoever between the shape of her foot and those lovely stilettos. I indicated my stumpy black Merrill's, suggesting that a better match between shoe shape and foot would heal up that toenail. Not only was the shoe too narrow, but the height of the heel was forcing her forefoot to be solidly crammed into the pointy toe.

She stopped short of gagging at my footwear choice and agreed to seek a more practical shoe.

What's going around, March, 2008

What better way to pass the viral misery than to think of ways to corrupt other people's songs. Too sick to sleep, too sick to read, too miserable to watch TV, here's my creation:

Croup

(Croaked to the refrain of Joni Mitchell's "Both Sides Now")

I've looked at croup from both sides now,
As doc and victim, still somehow,
It's cough/chills/aches that I recall,
I've got no time for croup, at all.

Wise words from an orthopedist

My patient was worried about her knees. Pain prevented her from getting down into a squatting position. Shoot, I haven't been able to do a deep knee bend for years, but I certainly could relate to fretting over aging joints. So I sent her off to Western Orthopedics where she met with Dr. Raj Bazaz.

He checked out her knees and declared them fit for service for years to come. His best advice to her? Don't do deep knee bends.

She was delighted with the visit.

Recurrent urinary tract infections

Phone calls in the night are a surefire way to set my heart racing. Death, destruction...or a patient with a urinary tract infection? I try to be understanding at 2 a.m., and heaven knows I do understand the agony of dysuria, that urgent, can't-be-quenched, fire of an infected bladder that sends a woman back and forth to the bathroom. And all too often, the middle-of-the-night episode is just one in a series of pesky infections.

What's up with recurrent urinary tract infections (UTIs)? Similarly plagued St. Louis rodents are providing clues as to why some UTIs are so hard to beat.
Washington University researchers induced UTIs in a group of volunteered rodents down at the lab. The rest reads like a science fiction story.

As expected, the e. coli bacteria invaded the epithelial cells lining the mousy bladders. Once inside the cells, the microbes set up housekeeping, forming a "biofilm" around themselves and their offspring. This protein shell protected them against attack from both antibiotics and the mouse's immune system. The growing colonies of bacteria, encased in their armor of protein, formed pods that pooched out from the bladder wall into the cavity of the bladder. Occasionally, the pods ruptured and spilled bacteria into the urine, thus creating another round of midnight misery for the mice. The Washington investigators theorize that if humans also experience attacks from the bacterial pod people, this would explain the recurrence of some UTIs after treatment.

And why my phone rings in the wee hours of the day.

On the dangers of not drinking

This from Dr Jane Østergaard Pedersen National Institute of Public Health, Copenhagen:

Another important finding is that physical activity can reverse some of the adverse health effects associated with alcohol abstention. People who did not drink but whose physical activity was moderate or high had a lower risk of IHD [ischemic heart disease] than the inactive nondrinkers.

I just told a group of nurses yesterday that while moderate alcohol intake (from 1-14 drinks/week) decreased risk of heart disease and raised levels of HDL-cholesterol, we were not yet recommending that non-drinkers consider drinking. These Danish researchers analyzed 20 years of data from nearly 20,000 persons enrolled in the Copenhagen City Heart Study. They found that mortality from ischemic heart disease and all cause mortality dropped with physical activity or moderate drinking, but dropped most with those Danes who celebrated their post-exercise glow with a beer or two.

Pedersen concludes: "The lowest risk of death from all causes was observed among the physically active moderate drinkers and the highest risk as seen among the physically inactive non- and heavy drinkers."

So drink a little, move a lot. And if you don't drink, you gotta' move!
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1. Østergaard Pedersen J, et al. The combined influence of leisure-time physical activity and weekly alcohol intake on fatal ischaemic heart disease and all-cause mortality. Eur Heart J. 2008; DOI:10.1093/eurheartj/ehm574.

Tart cherries, arthritis, and all that ails you

How good are Montmorency cherries? Well suffice it to say that at a certain point, I just had to stop reading the bushels of cheery cherry news in order to get this post written.

First of all, they're a wicked good source of melatonin. So much so that Dr. Russel Reiter, the so-called 'dean of melatonin research,' has now become the darling of U.S. cherry growers. Dr. Reiter has proven in his Texas neuroendocrinology lab that eating tart cherries replete in melatonin will make you replete in melatonin.

Hard to say what's next best about cherries. Probably their anthocyanin content. These cherry compounds are potent cyclooxygenase (COX) inhibitors. If that term rings a bell, it's because COX-2 inhibitors have been big news lately, first as miracle compounds that decrease arthritis pain without bothering the stomach, then as pharmaceutical villains for the faint of heart who wonder if Vioxx and Bextra caused their hypertension or heart attacks. For heart-safe and stomach-safe COX-2 inhibition, eat cherries.

After Michigan State University investigators patented a process to separate cherry from anthocyanin, the folks at Overby Farms used this technique to make cherry little dog biscuits for arthritic pooches. You will enjoy HipBones. The MSU investigators subsequently discovered that humans may lose weight, lower cholesterol, and increase insulin production with high anthocyanin-content foods, so buy some of those biscuits for yourself.

And now this final word about cherries from Iowa's Dr. Raymond Pohl, and then I'm plum cherried out. He writes that the perillyl alcohol in the fruit "shuts down the growth of cancer cells by depriving them of the proteins they need to grow. It works on every kind of cancer we've tested it against."

For a world of testimonials from aching humans and their canine companions, look around the web.

*This is the advertising slogan for "Tart is Smart" cherry juice. Check out tartissmart for more information on cherries than you could ever hope for, plus retail locations where you can buy this good red stuff. For those of you in Colorado, visit your local Albertson's!

Gross hematuria

Well I suppose anytime you see blood in your urine it's kind of gross. Scary too. In a medicalspeak sort of way, however, gross hematuria means enough blood in urine that anyone could see it by just taking a peek before they flush. Microscopic hematuria, on the other hand, refers to hidden blood which is only found when the urine is examined under the microscope. The clearly visible sort of bloody pee is always a problem, but here's an instance where the problem was out of the ordinary.

This patient came to me doubled over in pain. He explained that he had a history of kidney stones, and had begun experiencing the typical pain from flank to groin earlier that day. The pain of kidney stones is reputed to be one of the worst pains imaginable. Sorry to be a cynic, but I felt half sympathetic AND half skeptical about the truthfulness of his story. But he brought records from another state that confirmed two previous episodes.

Most persons with a kidney stone develop microscopic hematuria, so I asked him to leave a sample of urine for analysis. He limped dramatically off to the bathroom, and emerged after awhile with a grossly bloody sample. Bright clear yellow urine shot through with strands of blood as if he might have drawn blood from his arm and squirted it into his fresh sample. I have no doubt this fellow had kidney stones in the past, and no doubt that he developed a liking of the strong narcotic pain relievers prescribed for these episodes. I invited him to head over to the ER if he was in that much pain for I was unable to help him.

Real honest-to-goodness gross hematuria is always a cause for investigation and solution. Many women have had the alarming experience of seeing blood in their urine, accompanied by the characteristic burning and urgency of a bladder infection. Some runners can bleed into their urine after extreme workouts. Otherwise, gross hematuria is quite worrisome for urological cancer and requires a careful workup.

Tips from a pro

She's the professional patient who's not always patient. After a lifetime of cystic fibrosis and two double lung transplants, Tiffany Christensen knows her way through a medical maze. Her recent post on the top ten tips for navigating same includes a most important piece of advice:

Here’s the greatest irony of illness: when you are at your worst is exactly the time when you need to be at your best! If you aren’t up for self-advocacy, bring some one who can do it for you.

Check out the rest of her list at Navigating the medical maze. And if you happen to be facing a serious illness, know and love someone who is, or think you might someday be so challenged, her book "Sick Girl Speaks" is essential reading, and a mighty good read at that.

Pink urine

Two encounters from another day on the front lines as a PCP:

1. Pale pink urine, prettiest pee I've ever seen, like a fine rose wine. Beets, it turns out, really do turn urine pink.

2. On another note, to my patients if you're reading my blog, do NOT bring in used tissues to prove the color of that which you are coughing up. I will take your word for it.

Traumatic brain injury

You do not want to knock your noggin, not even a nudge!

Used to be, if a head-injured patient didn't lose consciousness, we didn't call it a concussion. Increasing evidence confirms, however, that any blow to the brain, including those that seem relatively minor, can lead to serious problems.

Canadian researchers looked at 69 traumatic brain injury (TBI) patients*. While the investigators measured injury severity by the depth of coma or degree of altered consciousness, they soon found out that even those who had walked out of the ER post-trauma demonstrated significant changes on MRI scanning one year after the fact. And, surprisingly, these high resolution scans showed that the white matter --that deep portion of the brain that contains crucial connections between nerve cell bodies-- sustained the biggest tissue loss in the walking wounded as well as those who were down for the count.

White matter matters have been a been a matter of some attention since MRI technology has come into vogue. White matter injuries that show up as bright spots on the brain are common with aging and correlated with cardiovascular risk factors such as hypertension. The more that's the matter with a person's white matter, the more likely they are to have trouble carrying out complex mental tasks. This same sort of cognitive difficulty is seen in post-TBI patients, and now we know why.
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*Levine, B, et al. Neurology, March, 2008.

Idiopathic hypersomnia (IS)

Think perpetual teenager. As in back in the days when you were one or parented one, holding mirror to Rip Van Winkle Jr.'s nose at 2 p.m. to see if you/he could still be counted among the living. Only this Sleeping Beauty is no longer a teen, and snoozes on even if it means losing a job or failing a course while remaining oblivious to the wake-up bells and whistles going off around him.

I hate these idiopathic diagnoses. This one is basically a fancy way of saying the patient sleeps too much and we don't know why. Now how is that going to make a person feel better about not only sleeping too much, but once up, being so out of it that he or she can't even remember what was said or done in those first few hours of the day? Well, if misery loves company, this diagnosis says you sleep too much, we don't know why, AND there are other people just like you sleep too much in the same way so it's a syndrome and not just you.

The symptoms of IS include excessive daytime sleepiness, tendency to nap, long nighttime sleep durations, difficulty awakening, and confusion on finally getting up which is also known as 'sleep drunkenness.' And don't mistake these people for healthy hypersomniacs or those people who thrive on a long night's sleep and then function perfectly well by day.

So what do you do with a drunken sleeper who's had no drinks at all but just seems that way? Per Medscape author Muhammed Faisal Hafeez Khan, MD of Duke University, you ply them with the same sort of stimulant medication that persons with ADD use. In addition to Dexedrine, he recommends a trial of Provigil (modafanil) which, if used at bedtime, promotes morning wakefulness. This drug was originally developed for narcolepsy and is now approved to rally shift workers and persons with sleep apnea to full alertness.

Medial epicondylitis or Snow-shoveler's elbow

I'm told that I hold a snow shovel wrong. Who's to say really what's right or wrong when it comes to wielding a snow shovel? My spouse claims the proper way is to grip the snow shovel with the left hand by grabbing it fingers down. That, unfortunately, requires that you have a brachioradialis muscle on the top of your forearm with which you can both grip and lift pounds and pounds of snow. I was not issued one of those muscles.

So what's a spaghetti-armed doctor to do? Exactly what my mush-armed patient did--grab the shovel handle in an underhanded sort of way, which brings the trusty biceps into play along with the pronator teres, flexor carpi radialis, and palmaris longus muscles on the palmar side of your forearm. After moving mountains of snow, these overused muscles which attach on the inner aspect of the elbow, start screaming with pain. This is known as medial epicondylitis, golfer's elbow, or, for all of us who weathered this difficult winter season, Snow-shoveler's elbow.

Those scoopers who favor the overhand shovel technique, however, would overuse the brachioradialis muscle causing pain at its tendinous insertion on the outer aspect of the elbow. This is known as tennis elbow, or Snow shoveler's elbow.

I assured my patient today that the orange crocuses were in bloom in my garden, and the end of the snow surely cannot be far behind. Tendinitis starts to heal when the patient stops bothering the tendon. While extraordinary repetitive motion creates tendinitis, ordinary daily activities like lifting kids, books, grocery bags, and suitcases can perpetuate the problem.

BRCA genes and the women who worry about them

Tumor suppressor genes are worthy bits of genetic info that produce DNA-repair proteins. Left uncorrected, broken DNA can lead to cells no longer subject to orderly growth and development. Unfortunately, tumor suppression genes are also subject to mutated DNA which then produces faulty proteins unable to do their fix-it jobs. Persons who inherit abnormal copies of BRCA1 or BRCA2 are particularly susceptible to ovarian, breast, or prostate cancers.

Women in Denver with a strong family history for either of these cancers can sign up for care through the Rocky Mountain Cancer Center's High Risk Breast Cancer Clinic at Rose Hospital. Drs. Dev Paul and Michele Basche along with genetic specialists evaluate risk and may recommend adding MRI surveillance to annual mammograms as well as genetic testing for BRCA mutations.

According to the Myriad model based on my family history and ethnic background, my risk for a BRCA mutation was 16%. My insurance approved genetic testing (although they will doubtless end up paying far less for it than I will), and I was eager to know the outcome. Fortunately, my test was negative.

One of the things that makes BRCA testing more appealing than other genetic inquiries, say one into Alzheimer's risk, is that something can be done if the test is positive. A newly published study* in the Journal of Clinical Oncology confirms that the current strategy of removing the ovaries of BRCA-mutation positive women is beneficial to their long-term outcomes.

When the researchers compared women with BRCA1 or BRCA2 mutations who either underwent oophorectomies or not, those who chose surgery had a significantly reduced risk of cancer compared with the control group. Specifically, risk reducing oophorectomy was associated with an 85% reduction in BRCA1-associated gynecologic cancer risk and a 72% reduction in BRCA2-associated breast cancer risk.

One of my patients with a BRCA2 mutation (2 sisters, a mother, and a cousin all dead or dying from cancer) was in yesterday, completely satisfied with her decision to undergo this surgery. She had a laparoscopic removal of the ovaries with Dr. Michael Moore in Denver, and declared him "the best."
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Kauff, N, et al. J Clin Oncol. 2008 Feb 11 [Epub ahead of print]

New blood test for ovarian cancer

First it was 'Kathy's story,' an e-mail that circulated for several years about Kathy and her tragic bout of peritoneal cancer. The moral of her story was get a CA125 test. I read the latest header on the latest CA125 e-mail as my patient set it on the desk in front of me today, 'Do not take no for an answer.' Another day, another woman wishing we had a decent test to detect early ovarian cancer.

I would never deny a woman this test, but I do emphasize to those who ask that it is a terrible screening test for ovarian cancers. Believe me, I wish both personally and professionally that we get a good test, both sensitive (picks up ovarian cancers reliably when they're present) and specific (only positive when there actually is a tumor), and let it be found ASAP!

Coincidentally, this headline news came across my screen tonight. So put this in an e-mail and circulate it to all your girlfriends!

"Blood test detects early stage ovarian cancer with 99 percent accuracy"

Yale researchers went looking for unique proteins shed by ovarian tumors. Since these proteins are only made by ovarian cancer cells, their presence in a patient's blood is diagnostic of a tumor. Apparently, however, it takes a heap of a lot of cancer cells to raise protein levels to detectable levels, so the first test attempt based only on tumor proteins was not sensitive for early cancers. On a second pass, the New Haven scientists added an assay for proteins made by a woman's body in response to the foreign tumor tissue.

Score! Four tumor proteins plus two immune-response proteins equals this new highly sensitive, highly specific test. The test now enters phase III clinical trials--the last step before applying for FDA approval--through the Early Detection Research Network (EDRN) of the National Cancer Institute (NCI)and LabCorp.

Bystolic and stress

All stressed out and nowhere to run, no one to punch out. I was at a meeting yesterday, one of the most stressful meetings I've ever attended. My heart was pounding, I'm sure my face was red, and I had no recourse but to listen politely to the proceedings. If ever there was a stress test for my aging heart, that hour-long ordeal was it.

My forty-something year old patient lives a perpetual stress test. Caught in a years long legal battle with a former business colleague, he lives his life in a never-ending nervous fit. His heart pounds along at a resting heart rate above 110, his blood pressure is high, but the worst symptom, the one that brought him in 2 weeks ago, is how very, very hot he feels. He can scarcely stand indoor heating; his secretary suffers the open office windows while his wife piles on the covers in their breezy bedroom.

I have seriously entertained the notion that this poor fellow has an adrenal tumor, so intense are his symptoms. While waiting for his first round of tests to come back, I wondered if we might give him, his secretary, and his wife a break with beta blockers.

Originally developed for blood pressure troubles, beta blockers have since been tapped to control abnormal heart rhythms, protect heart muscle after a heart attack, and to combat performance anxiety. They work by competitively blocking cellular receptors for beta-sympathetic adrenal hormones such as norepinephrine which set off the 'fight or flight' response. As such, they can slow down the pulse and blood pressure response to stress. The problem with earlier versions of beta-blockers is that they blocked both beta-1 receptors responsible for cardiovascular changes and beta-2 receptors which, among other things, relax smooth muscle and dilate the airways (so you can get more oxygen to run away from lions, tigers, and meetings, oh my).

As my patient also has asthma in addition to more stress than any human should have, I needed a beta-1 selective agent that would not contribute to an asthmatic constriction of his airways. Lucky for us, the sales rep from Forest Pharmaceuticals had just left a big supply of Bystolic (generic name nebivolol) in our drug closet. I gave him a bottle and hoped that there would be no unexpected beta-2 blockade.

Here's the phone message I received 2 days later:

Said the pill you gave him works wonders. His heart rate went from 160 to 78, no more body heat, has not been using his inhaler, and his BP has gone down. He also has been working all day.

Now that is a wonder drug! I wonder why I didn't take one before the meeting from hell.

Flow-mediated vasodilation

They're not just passive pipes anymore. No longer do scientists view our blood vessels as mere conduits that carry blood from heart to bod and back again. The worthy endothelial cells that line our arteries and veins not only respond to signals from the kidneys and adrenal glands to dilate and constrict, they actively produce substances themselves that affect their functioning.

One way that researchers test the health of blood vessels is through an indirect method called flow-mediated vasodilation (FMV). This test, an indirect measure of the ability of the arterial system to respond to increased demand, is performed by pumping up a blood pressure cuff on the subject's arm to some intolerable level for a few minutes, releasing it, and then calculating the subsequent surge of blood flow through the brachial artery at the elbow with ultrasound technology.

A small study from Italy looked at the effects of a high-fat meal on blood vessel reactivity in ten postmenopausal women. The ladies were invited down to the lab for an 'oral fat load,' doubtless a large piece of tiramisu. At two hourly intervals thereafter, their FMV was measured. At baseline, the ladies sent nearly 8% more blood coursing through their fingertips after the cuff was removed. Two hours after the high-fat treat, this number fell by two-thirds, meaning that their blood vessels' capacity to dilate in response to increased blood flow fell by over 60%.

Theoretically, then, a high fat meal, whether consumed in a fast food joint or as part of an Atkins diet, can wreak havoc in an individual with unsuspected coronary artery disease. A burst of activity after the feast, say a sprint up the block to catch a bus, calls on diseased arteries to provide extra blood flow at a time when they are clamped down from a load of Nacho Belle Grande. When blood supply can't keep up with demand, the oxygen-starved portion of the heart can be damaged.

Air pollution, cigarette smoke, and early morning hours all can muck up your FMV. Vitamin E, oatmeal, dark chocolate, green tea, JuicePlus, and ACE inhibitors (a class of blood pressure meds that includes lisinopril and enalopril) all support your endothelial cells to expand on demand.

A new drug for alcohol dependency

College campuses are filled with kids who drink for kicks. Statistics suggest that some of these early drinkers will go on to become alcoholics for the feel good, addictive thrill of it all. The majority of adult alcoholics, however, drink to relieve stress and anxiety.

Currently, two drugs are available that are supposed to alter a drinker's response to alcohol in a way that makes ongoing use less appealing. Naltrexone is an opioid receptor blocker believed to prevent the release of dopamine (a feel-good neurotransmitter) that occurs with drinking. A 2006 study reported in JAMA found that naltrexone plus behavior therapy was significantly successful in preventing relapse in abstinent alcoholics. On the other hand, this same study found no benefits from Campral, another drug used for abstinence support. Campral is believed to block the effects of glutamate on brain cells. Glutamate is an activating neurotransmitter which, in some individuals, promotes anxiety and agitation.

So what can be done for alcoholics who drink to calm themselves? Researchers at the U.S. National Institute on Alcohol Abuse and Alcoholism went looking for other substances that would modulate stress reactions in the brain. They pulled LY686017 off the back shelf of drugs tested for depression but discarded for less than perfect efficacy. Ex-alcoholics who scored high on anxiety scales were given LY686017 or placebo, then given questionnaires about just how much they craved alcohol. Those plied with LY686017 were notably less likely to long for a drink.

But these Maryland scientists did not just stop with questionnaires. They subjected the subjects to mock interviews and math tests with scowling assistants in intimidating white coats. Afterwards, the group was tested for levels of the stress hormone cortisol. All subjects also got to sniff and caress a vial of their favorite beverage and were asked just how badly they wanted to drink it. Again, LY686017 triumphed, squelching the hormonal stress reaction as well as the urge to drink.

Says neuroscientist Selena Bartlett of the Ernest Gallo Clinic and Research Center at the University of California, San Francisco, "It feels like we're heading for a sea change for new therapies for alcoholism."

Excess weight and cancer risk

I woke up later than usual this a.m. (my morning lark has migrated south these gray, snowy days). The thought of racing around to get ready for step aerobics was nearly more than I could face.

Face it I did, and this research report from the current issue of The Lancet(1) makes me glad that I ventured forth. Epidemiologists from the Universities of Manchester and Bern knew that obesity increased the risks of some cancers. Using 41 years of data found on MEDLINE and Embase, they correlated incidence of 20 cancers with BMI(2).

They found that the risk of excess poundage relative to cancer varied with sex. For the overweight guys, every 5 point increment in BMI significantly raised the risk of esophageal, thyroid, colon, and renal cancers. For women, esophageal, gallbladder, endometrial, and renal cancers were most strongly associated with increasing weight.

Lest you think achieving a 5 point drop in your BMI is a daunting task, I accomplished that 6 years ago with a single one hour kickboxing class per week. Just sixty minutes of a hot, sweaty workout each week. Research suggests that the best way to shake pesky, longterm fat off is with high intensity exercise.
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1) The Lancet 2008; 371:569-578.
2) To calculate your BMI, divide your weight in kilograms by your height in meters squared. Got it? If that is too much for you to face this snowy Sunday, let someone else do it at BMI calculator.

What's going around?

Illness #1: Starts with a tickle or tiny cough. Patient thinks must've been exposed to perfume, smoke, cat, smog, or perhaps a minor illness. Within hours to two days, patient develops sore throat, hoarseness, and a cough that is painful, compelling, deep, possibly productive of small amount of yellow guck. Body feels toxic, aching all over and fatigue so severe that patient debates with self whether or not it's worth getting up to bathroom or perhaps better just to hold it. No one wants to be around patient, including doctor.

Illness #2: Rather abruptly develops deep cough, body aches, chilling, fever, headache. Maybe sore throat. Eyes are glassy and no one doubts patient is ill. No one wants to be around patient, including doctor.

One illness is probably croup, the other influenza. Both are nasty and highly contagious. The flu shot, as you may have heard, was not a good match for the circulating strains of influenza this season. The viral part of these illnesses lasts for a week or more, the cough lingers for weeks (or even months in Denver's cold, dry, dirty air). While we can sort of take the edge off the misery with codeine cough syrup and Advil, antibiotics won't help a bit.

Getting better involves a slow return of energy. Remember, the cough may well outlast the illness by weeks. If you succumb to one of these bad actors, look out for phase 2 of the illness. If a week or more into the illness, you feel worse instead of better, and that which you cough or blow out is colored and disgusting, you may be developing bronchitis or sinusitis. We can talk about antibiotics.

If this onslaught keeps up, I may start wearing a mask during close encounters of the contagious kind. Please don't take it personally!

Concierge service AND medical care

I was nearly out the door today (quiet schedule due to the weather and Valentine's Day) when my middle-aged patient dropped in. I treat her for high blood pressure and high cholesterol, both of which are well-controlled. This afternoon, however, she began experiencing chest discomfort, shortness of breath, and dizziness.

Her blood pressure was up but her pulse below sixty. She was nervous and breathing rapidly. On EKG, she had evidence of a lack of oxygen to the front wall of her heart. To the ER, I said, Now! But I've got a brisket in the oven at home, she countered, and no one to turn it off. It hardly seemed prudent to let her drive home through the cold to save the brisket at the expense of her heart. So I dropped her off at the ER, then went to her townhouse and turned off the oven, leaving the brisket to cool on the counter.

The report so far is so good--her cardiac enzyme levels do not indicate any damage, but her story so suspicious for angina that they will keep her overnight and stress test her tomorrow. My only regret? The thought of that delicious smelling brisket spoiling uneaten on her kitchen counter.

A patient came in today wondering if an inexpensive test would tell her the state of her coronary arteries. When asked why she wondered about her heart, she replied that she experienced an unpleasant pounding sensation in her chest for hours each day and worried that she would soon have a heart attack. In fact, she'd recently been exploring some difficult past experiences with her therapist who had suggested she consider medication for her depression and anxiety. She was afraid, as so many people are, to try antidepressants.

I told her it was possible that she might not even know what it's like to live without anxiety as she'd apparently not been free of it for her adult life. I wished I'd had a copy of this poem with me to share with her. Here's an excerpt; it's written by a man who is undepressed for the first time in his life after starting Paxil:

I feel more like myself,
a feeling that can hardly be true
after 60 years of prowling
outside the fence, with the gates
locked, or scarier still, open,
swinging and I would stand there
paralyzed, afraid to step in
my feet starved for affection
and serotonin shooting itself
in the foot each time a foot perked up
and started to dance. But that can
hardly be true, the way I feel today,
so vividly myself, so grounded
you might say the first draft is done.
I'm in the process of revision.

Metabolic syndrome a lifesaver

Metabolic syndrome and lifesaver are rarely seen in the same sentence. The metabolic syndrome is a cluster of high risk conditions which greatly increases the chances of developing diabetes and heart disease. If you've got waisted fat, your silhouette more apple than pear, plus two of the following:

• Elevated blood pressure
• Low serum HDL-cholesterol
• Elevated fasting serum triglycerides
• Elevated fasting glucose

it's time to undertake serious lifestyle changes. My middle-aged patient clearly had trouble in a metabolic syndrome sort of way--she came to her appointment late last year in overalls because she'd packed so much fat round her middle that jeans were yesterday's dream. Her problem, however, was upper right abdominal pain.

There was no telling whether or not she had a mass in her abdomen as her central fat mass was as round and tense as a full-term pregnancy. Her lower right ribs were tender to touch, and I concluded that she was suffering from the same sort of ribcage discomfort as an expectant mother might have just before giving birth. But this lady was so uncomfortable that I felt we'd best do a CT scan to check for an internal problem such as gallstones.

The CT results were bad news--she had a large mass on her right kidney. A cancer was found at surgery, completely contained within the kidney, with no evidence of spread. She was cured by a nephrectomy. But a month later she was back in the office, her abdominal pain unchanged from her original visit. The pain, in fact, was from her expanding waistline pressing out on her ribs. The kidney cancer was a most fortunate 'incidentaloma' found in passing by a just-to-be-sure-we're-not-missing-something CT.

A rare complication of MRIs

I had an MRI last year as a screening test for breast cancer. MRI scanning with a contrast material called gadolinium is the best screen currently available for the cancer, and I received my negative results with a deep sense of satisfaction that, for the moment, I was free and clear.

While I have an internist's enthusiasm for ingested substances*, I have an abiding distaste for things injected. I will think long and hard about getting another MRI--I didn't mind the noise, no problem with the confined space, and I don't really mind IVs, it's the thought of another IV injection that stops me cold. And now, here's news of a new disease, rare but icky, we've created with gadolinium imaging technology.

Nephrogenic systemic fibrosis (NSF) was first described in 1997. Case series confirmed that NSF was confined to patients with renal insufficiency (diminished kidney function), and later determined to affect only those kidney patients who had undergone radiological imaging with gadolinium in the several months prior to developing hardened leathery skin. The fibrosis or connective tissue thickening and scarring associated with NSF binds up joints, lungs, heart, and diaphragm as well as the skin. The systemic involvement can be fatal.

By the time your kidney function is low enough to be at risk for NSF, you have already come to the attention of a specialist. Hopefully, no cases of NSF will appear in people not known to be at risk. This emerging syndrome reminds me, however, that there's no such thing as diagnoses for nothing' and MRIs for free**.
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*Coupled with a coming-of-age-in-the-'60s mentality
**Sorry Dire Straits!

Oncotype DX Breast Cancer Assay

Many years ago, two of my patients in their early 40's had abnormal mammograms. In both cases, the films showed suspiciously clustered spicules of calcium. The biopsy on one showed invasive ductal carcinoma; her subsequent work-up confirmed no spread of the cancer to lymph nodes or beyond. The other one's biopsy was negative.

Prevailing wisdom at the time was to administer adjunctive chemotherapy to nearly all patients no matter whether their cancer was localized or not. My previously well patient, a professor at a local university, underwent chemo and died from an infection shortly after receiving her first dose. The other lady was found to have the exact same suspicious cluster of calcifications on her mammogram several years later (the first biopsy had missed the area) and underwent another tissue sampling which was positive for cancer. She had a lumpectomy, but no chemotherapy was recommended. Now two-plus decades later, she just retired from her law practice.

Fast forward to two months ago. Another abnormal mammo followed by another biopsy on another lady. This cancer was also localized by all tests, but her tissue was then examined for hormone receptors and genetic content post-lumpectomy. This DNA analysis known as the Oncotype DX Breast Cancer Assay revealed that the chances that her cancer would return without follow-up chemo were "off the charts." No dithering over whether or not chemo is appropriate; in her case it is essential and life-saving.

On average, the outlook for most women with node-negative, estrogen-receptor positive breast cancer treated with estrogen-blockers post-surgery looks good. Overall, these patients have a 15% risk of recurrence in the 10 years after diagnosis. This means that 85% of the women who underwent a course of chemotherapy for this diagnosis in the past could, in fact, have skipped these difficult treatments and still done well. Up until recently, however, we had no good way to counsel these women about which path to pursue.

In 2004, the Oncotype DX test was developed to test for the active expression of tumor-related genes in breast cancer surgical specimens. The results were used to develop a Recurrence Score which predicts the likelihood that the tumor will return in the future. Now women diagnosed with estrogen-receptor positive breast cancer are candidates for more individualized treatment based on these 'biomarkers of recurrence.'

To develop this test, the researchers sorted through 250 candidate genes from a DNA library of genetic material. They then analyzed clinical studies of cancer patients and the genetic nature of their tumors looking for a correlation between the expression of these 250 genes and the likelihood of cancer relapse at a later date. The scientists chose a panel of 21 genes for the final assay based on the strength of association between their expression and risk of recurrence. The Recurrence Score also correlates with the length of time until relapse and overall survival.

The test was lauded at the time by senior investigator JoAnne Zujewski, MD as having "the potential to change medical practice by sparing thousands of women each year from the harmful short- and long-term side effects associated with chemotherapy." Furthermore, those who could benefit most from opting for chemo, like my current patient, can feel more assured that they've made the right decision.

Marijuana withdrawal

Using marijuana (way, way back when and never,ever inhaling!) made me as fumble-mouthed as an evening news anchor and rather forgetful, so I gave it up before college. I've been surprised to learn, however, in my role as privileged exam room confidante that quite a few people continue to smoke up daily. Before they even go to work! Very few express any desire to quit, and no wonder considering new evidence from Johns Hopkins University researchers.

In a small series, the Baltimore psychiatrists found that subjects withdrawing from regular marijuana use suffered from withdrawal symptoms equivalent to those which occur on giving up cigarettes. The symptoms included irritability, anxiety, difficulty in focusing, and insomnia.

The problem I've come up against in helping those few who'd like to walk away from the marijuana habit is a lack of available medical adjuncts to shore up their will power. We have alternative nicotine delivery systems such as patches, lozenges*, and gum for those giving up cigarettes. A newish drug called Chantix* acts as a weak nicotine analogue in the brain, working on nicotine receptors to release a little bit of the feel-good neurotransmitter called dopamine but not so very much as to perpetuate the addiction. Naltrexone helps alcoholics give up drinking, as, theoretically, does Campral although efficacy data on the latter is not so very convincing.

But, alas, there are no legal marijuana analogues on the market FDA-approved for withdrawal purposes. Marinol (generic ronabinol) is a synthetic version of the active compound in marijuana called delta-9-tetrahydrocannabinol or THC. It is indicated for suppression of nausea associated with cancer chemotherapy or as an appetite stimulant for persons with AIDS. Its use could perhaps supply THC to marijuana addicts in much the same way that Nicoderm provides nicotine to withdrawing cigarette smokers.

Acomplia*** or rimonabant is an endocannabinoid receptor blocker which was developed to help persons with a prediabetic condition called the metabolic syndrome get a grip on their elevated blood fat levels and weight. It would probably take the fun out of smoking marijuana as the THC could not meet up with its receptors if Acomplia was already sitting in place, but it is not available in the US.

The bottom line is that quitting addictions is a lot of unpleasant work. I quit smoking 30 years ago this month, and I'd never care to have to motor my way through another withdrawal experience.
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*A patient recently told me about a nicotine lozenge called Ariva. Sold behind the Walgreen's cigarette counter, 20 lozenges for about the same price as a pack of cigarettes, Ariva was very helpful in her quest to quit. I gave a pack to a near and dear one who wished to cut back on his habit, and the product set off powerful and painful gagging. Great, gagging or smoking, which would you pick?

**A pesky little post-release problem with Chantix has the FDA re-examining safety data. Apparently partially blocking nicotine receptors sets off suicidal depressions in some people.

***Acomplia is also linked with suicidal depression. Apparently, you can't block the body's feel good receptors without making some people feel bad.

Lap banding in Denver

...if I were going to have a weight loss operation...there's no doubt I'd have the lap band. Why? Cheaper, safer, faster, doable as an outpatient procedure, quicker recovery, equal weight loss in the long run.
---Sid Schwab, MD, from his Surgeonsblog

During laparoscopic gastric banding, an inflatable silicone band is places around the upper portion of the stomach. This creates a pouch above the band just beneath the point at which the esophagus enters the stomach. After the first few bites of a very small meal, this little sack of stomach is full, overweight eaters feel satisfied, and they begin to lose weight.

Doctors down under recently found in a small series that morbidly obese patients with diabetes who underwent a lap band procedure for weight loss lost significantly more weight than a control group who followed a diet and exercise plan. And 2 years post-op, 22 of 30 in the lap banded band had their type 2 diabetes go into remission compared with 4 of 30 in the control group.

And if I were going to have weight loss surgery in Denver, I think I'd sign on for banding with Dr. Matthew Metz. This surgeon is not only a genuinely nice and personable fellow, he was also a bariatic surgery fellow at the Cleveland Clinic. He's a bariatric surgery nerd (that's what you want in a specialist), fully trained in all the latest surgeries and completely ready to repair and revise out of date bypasses that no longer work.

Check out Coloradobariatric.com.

The dewy glow of a morning lark's skin...

My son called me at 6 a.m. today. Lest you think 'what an early bird that teen!', let me tell you he'd not yet been to bed. He'd just pulled one of those college all-nighters, and was calling me to request a noon wake-up call so that he wouldn't miss his 12:30 class...yet again.

Researchers have devised an innovative way of finding out whether folks are morning larks or night owls (as opposed to, say, just asking them). European biochemists recruited a group of willing subjects* who self-identified as morning or evening persons. The scientists then nipped a couple of skin samples from the group and cultured the cells in the lab. They then minced up a few fireflies, and inserted the gene that makes the insects glow into the gene that regulates the internal clock of human skin cells.

The purpose of melding human DNA with that of fireflies was to get a visual on the cells' 'inner slave clocks', that part of our body that responds to the brain's call to bounce out of bed or snooze onward. Indeed, these skin samples began glowing like a Midwestern summer's eve at a time determined by the subjects reported biorhythms. Now how bizarre must that have been--these cell communities in petri dishes switching on and off there in the lab based on the behavior of their previous human owners.

Interesting, but what's the point? Says chronobiologist Achim Kramer who helped design this study, "Pinpointing individual clock cycles could pave the way for personalized sleep and drug therapies." If they can pave a way to get my son up in the a.m., that is scientific progress at its best.

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*I used to dub them volunteers, but discovered in a recent New Yorker article that many of these experimental subjects are 'professional guinea pigs,' often making an adequate living from payments for participation in studies like this.

Male commuters walk on the wild side

Here's an interesting item from Science Magazine comparing bus-riders living dangerously to strutting peacocks:

Oxford psychologists Robin Dunbar and colleagues observed 1,000 men and women waiting for the bus over a three month time period. Their more pedestrian conclusion was that men were more likely to cut it close with respect to catching the bus, often arriving at the bus stop at the absolute last moment before departure.

More dramatic, however, was the jaywalking behavior of the bus-riding men. When observed by women, the scoff-laws were much more likely to make risky dashes through traffic on their way to the stop. The article doesn't say whether or not near death by squashing ruffled the riders' feathers, but the investigators did compare the feats to mating displays.

One problem with Paxil...

and Prozac, Zoloft, Celexa, and Lexapro

Several years ago, I treated a teenager with Paxil for show-stopping anxiety. He came back two weeks later no longer feeling much anxiety. In fact, he wasn't feeling much of anything. In his words:

I couldn't get my shoes tied this morning. It wasn't that I didn't know how to tie my shoes, I just didn't much care whether they were tied or not. It seemed like too much trouble.

This blah sort of feeling (other patients have variably described it as a lack of emotions, loss of joy, inability to cry, being wrapped in cotton, and viewing life from a fishbowl) is a big problem with this class of drugs known as SSRIs or selective serotonin reuptake inhibitors. My psychiatrist colleagues tell me as many as 40% of patients will experience this dulling of emotion.

While patients may initially welcome the resolution of depression and anxiety, this inability to feel quickly becomes a problem. My patient who called me a saint post-Cymbalta prescription had this problem as well with the SSRIs. More later on why Cymbalta and Effexor are not so dulling, and why Cymbalta may have it over Effexor.

Phone follow-up

Even as I found the phoned request for a two week time-out in a rest home amusing due to the enormity and impossibility of the task, I did recognize that this lady was at her wits' end. A single mother of tweenaged girls, she is struggling with extraordinary fatigue, even more than expected for a single mother of tweenaged girls.

I'm not sure which came first, the depression or the fatigue, but I do know she is seriously depressed. We have since had a long phone discussion about her faltering mood, and have a plan in place--albeit short of a two week vacation--that will address her troubles.

Here's the kind of patient phone message that makes my day:

Cymbalta has changed my life. You are a saint!

Check here later for information on why SSNRIs made her feel good and me look good.

Dr. Smak is the queen of the outrageous patient calls, including the following:

Please write letter on letterhead stating that patient is unable to do work of any kind for 3, 6, or 12 months.

Call and leave message on machine when complete. Patient will be gone all day hunting.

Here's my 'did-they-really-say-that?' phone message of the day:

Patient is having a lot of stress with her kids and her health. She would like to check into a Health & Wellness Center for 2 weeks. 'A place where I can be monitored and relax.' Advise.

Beyond Zetia

This Zetia business seems to be rocking the cardiology world just like the Women's Health Initiative blew up conventional wisdom on hormone replacement therapy.

Cholesterol in the body comes from two sources: one pool manufactured in the body, and the other from the diet. Zetia is a drug that lowers LDL-cholesterol levels by partially blocking the absorption of cholesterol from the small intestine. Statins such as Zocor and Lipitor, on the other hand, decrease some of the activity of an enzyme that is important in the body's own cholesterol production. Zetia has been heavily marketed as a good drug for persons with high cholesterol who either can't tolerate statins or who don't reach their goal LDL-cholesterol levels on statins alone.

The ENHANCE trial found that persons taking the Zetia-Zocor combination for 2 years (aka Vytorin) did no better than those on Zocor alone with respect to unwanted thickening of their carotid arteries. As a result, not only are cardiologists taking sides in the Zetia/no-Zetia debate, now they're wondering if lowering LDL-cholesterol is even an important goal in the war against heart disease. Consider these varied opinions from the nation's top heart specialists:

The idea that you're just going to lower LDL and people are going to get better, that's too simplistic, much too simplistic.
Dr. Eric Topol, Scripps Institute

The message for me is not that lowering LDL cholesterol doesn't work to prevent disease progression or to prevent clinical events. The important thing to remember is how the cholesterol levels are lowered...There are many advocates out there who espouse lowering LDL cholesterol by any means possible. But let's be clear: 95% of the studies that form the basis for the cholesterol hypothesis are based on studies of statins
Dr. Steven Nissen, Cleveland Clinic

Anytime you can lower LDL-cholesterol levels safely, you are going to see reductions in the risk of clinical events.
Dr. Patrick McBride, University of Wisconsin

Per Dr. Nissen, the bottom line here is that statins not only lower LDL-cholesterol, but they also can raise HDL-cholesterol (a weensy bit), decrease triglycerides, and lower c-reactive protein or CRP. CRP is a pro-inflammatory molecule in the body; when present in elevated amounts, CRP not only is a marker for risk of coronary artery disease, the substance actually causes trouble in arteries whose walls are streaked with fat.

The Premarin drug rep started sneaking through our door after the 2002 WHI results were released, sheepishly bearing samples and M&M's. The Avandia reps don't even come around anymore. Come to think of it, haven't seen the smiling face of the Vytorin rep in the last week either.