Dr. Allan Conney and his colleagues went looking for a way to provide hairless mice with a safe summer glow.

Caffeine-laced lab water increased the mice's ability to kill off precancerous cells in their icky white skin by 100% as did regular work-outs on the exercise wheel. But go-getter mice who indulged in caffeine AND exercise between sessions with the UV lamp were nearly 400% more effective at policing their sun-damaged DNA.

The researchers were hopeful that this simple formula for sun protection would work for humans as well. They issued, however, this final note of caution:

Don't go out and exercise and drink a lot of coffee and assume you're going to be protected. Keep in mind that these are studies in mice.
--Allan Conney PhD, Rutgers cancer researcher

Oscar the Cat

You've doubtless heard by now of Oscar the death-sniffing cat. He made my local morning newspaper; I'm sure he was in yours as well. Oscar lives at the Steere House Nursing and Rehabilitation Center in Providence, Rhode Island. He senses when the residents there are on their way out. Here's an excerpt from a day in his life as published in the latest New England Journal of Medicine(1):

Oscar arrives at Room 313. The door is open, and he proceeds inside. Mrs. K. is resting peacefully in her bed, her breathing steady but shallow. She is surrounded by photographs of her grandchildren and one from her wedding day. Despite these keepsakes, she is alone. Oscar jumps onto her bed and again sniffs the air. He pauses to consider the situation, and then turns around twice before curling up beside Mrs. K.

One hour passes. Oscar waits. A nurse walks into the room to check on her patient. She pauses to note Oscar's presence. Concerned, she hurriedly leaves the room and returns to her desk. She grabs Mrs. K.'s chart off the medical-records rack and begins to make phone calls.

Within a half hour the family starts to arrive. Chairs are brought into the room, where the relatives begin their vigil. The priest is called to deliver last rites. And still, Oscar has not budged, instead purring and gently nuzzling Mrs. K. A young grandson asks his mother, "What is the cat doing here?" The mother, fighting back tears, tells him, "He is here to help Grandma get to heaven." Thirty minutes later, Mrs. K. takes her last earthly breath. With this, Oscar sits up, looks around, then departs the room so quietly that the grieving family barely notices.

I was at my mom's today. She is suffering from a series of small strokes, and today was a particularly bad brain day. I think both she and I would have welcomed Oscar's ministrations this afternoon, but cat attendant or no, today was not the day.
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1. Dosa, DM. NEJMVolume 357:328-329 July 26, 2007 Number 4.

Exhausted arteries

My mom lives in a condominium complex with a beautifully landscaped central area, complete with pond. As you walk the grounds, a background roar suggests the wind or sea but is, in fact, the traffic noise of I-25 just behind the high wall surrounding the complex. Out of sight may be out of mind, but the arteries within may never forget that highway nearby.

German researchers studied nearly 5,000 subjects living in the industrialized Ruhr area(1). The participants underwent electron-beam computed tomography or heart CT scans to determine their degree of coronary artery calcification (CAC) which indicates the level of cholesterol build-up in arteries. The investigators found a significant correlation between CAC scores and the proximity of the nearest highway to the subjects' homes.

Immunologists at UCLA determined the underlying mechanism of this relationship between urban air pollution and risk of heart disease(2). In both human artery tissue samples and in mice, these California docs determined that diesel particles plus LDL-cholesterol leads to more severe atherosclerosis than either soot or cholesterol alone. Both arterial irritants cause the release of 'free radicals' or reactive oxygen molecules known to be highly damaging to human tissue.

My guess is that the summer air here in Denver that hangs visibly through the trees on a hot summer day is the equivalent of living next to I-25 with respect to our heart's health.
_____
1. Hoffmann B et al. Residential Exposure to Traffic Is Associated With Coronary Atherosclerosis Circulation. 2007;0: CIRCULATIONAHA.107.693622
2. Nel a et al. The cellular impacts of diesel exhaust particles: beyond inflammation and death. Eur Respir J. 2006 Apr;27(4):667-8.

...the only funeral you can be sure your physician will attend will be that of his or her own.
--George Lundberg MD, Editor-in-Chief of MedGenMed

Not me. I try to attend all the funerals of my patients who die, every one. I not only love a good funeral, I need a good funeral to come to grips with the loss of these dear people who trusted me with their life...and death.

J was a fifty-something year old lady who had a chronic pain thing that defied explanation or treatment. A bright psychologist, she was her own best advocate. At the beginning of each visit, she would hand me a typed agenda for the appointment. We often covered her latest round of specialist visits which ultimately included a complete evaluation at the Mayo Clinic. A dear woman, but I dreaded her visits, in part due to our mutual frustration over the lack of progress.

She died suddenly and unexpectedly one day while napping in her rocker. Her funeral was packed with people from varied walks of life. The music? J's own recordings, her voice so beautiful it makes me shiver still to recall its full-bodied beauty. Did I know she sang? Sadly, I did not.

E, who struggled in the end with a vicious cancer after years of diabetes and congestive heart failure, was stunning in her pictures displayed at the funeral, pictures from a much younger time before I ever knew her. At K's funeral, a poster board displayed the glorious sunrise pictures shot by her young nephew on the day of her death BEFORE he even knew she was gone. At D's funeral, I met her baby granddaughter whom D met briefly at the end of her life. At MJ's funeral, his family came back to where I sat and insisted I move up to the family row. R's funeral was hardest of all--she had died of an overdose of medication I gave her to ease her intractable pain.

I would have missed an important part of my patient's journey here on earth if I'd missed a single one of these and other sad good-byes.

A 17th century pitch for exercise:

Better to hunt in fields for health unbought
Than fee the doctor for a nauseous draught.
The wise for cure on exercise depend;
God never made his work for man to mend.

--John Dryden

Ziana

One of the benefits of aging is the end, finally!, of acne. That doesn't mean that zits are not a topic of discussion in the household here, so I read with interest that a new twofer gel is available for those of us young enough to still breakout.

When I got my first zit, unkindly pointed out by Susan Millicent on a 6th grade field trip, the best my pediatrician had to offer was a suggestion to leave soapsuds on my face for a minute each evening. Red and scaly became the order of the decade, whether from soapsuds, sunlamps, or Retin-A. No matter the cause, though, red and scaly always preferable to pustules.

Enter lyrically labeled Ziana. Google Ziana, and you will find she will read your Tarot cards OR it will cure your acne. Per Dr. Wortzman of Medicis Pharmaceuticals, the gel version was more effective and produced less erythema and skin scaling as well as patient-reported burning and itching in clinical trials than use of its component parts. "Very little skin irritation," says he.

Ziana combines the antibacterial punch of topical clindamycin with the zit-digging power of tretinoin (Retin-A). Pricey though per one dude on acne.org:

Well guys...ixnay on the Ziana. I just found out that not only does it cost $250 WITH the $35 rebate the derm gave me, but that my parent's health care plan won't cover it because it's too damn expensive!!!

Sick Lit

Whatever you've got, chances are good that someone else has not only been there, suffered that, but that they've also written about it, painted it, or filmed it. For an extensive catalogue of hundreds of works of art and literature with medical connections, check out The Literature, Arts, and Medicine Database.

Chlorthalidone for blood pressure

I'm not joking about this issue. It is easier for doctors to write HCTZ than to write chlorthalidone, even though study after study has shown that chlorthalidone is a better drug...if you want to prescribe chlorthalidone, you have to write out all 14 letters.
---William Elliott, MD Rush Presbyterian St. Luke's Medical Center in Chicago

So are we docs really that lazy that 10 letters come between us and better care for hypertension? Sort of, that and habit--always have written for the water pill HCTZ (hydrochlorothiazide) and always will. Also the lack of recent literature on the superiority of chlorthalidone (man I don't even like typing that sucker) AND the fact that all the standard twofer drugs for hypertension as in two drugs in one tablet are HCTZ plus whatever. Except for Tenoretic which is now known as atenolol/chlorthalidone which is even a bigger drag to write out.

At least three large studies have shown that patients on CTD (there, see, it can be abbreviated) have better outcomes than those on HCTZ with respect to blood pressure control and, more importantly, 58 percent less coronary heart disease and 41 percent fewer deaths.

Am I going to start writing for CTD? Not only does that mean all those extra letters all day long, it means pulling out the other med (lisinopril, Diovan, Cozaar to name a few) and writing out all those letters in a separate script along with the one for CTD plus asking patients to cough up an extra co-pay as the twofer becomes two.

Where did humans get the extra energy to support their large brains?

Actually, I've been wondering some busy afternoons where I'm going to find the energy to hold my head up much less support the brain within. Harvard University primatologist, Richard Wrangham has been wrangling, however, with this long-standing riddle in human evolution, namely what allowed Big Head Todd and friends to rise from the lower primates in order to paint in caves, play rock music, and blog on the Internet.

One word, per Dr. Wrangham: Cooking. Big old brains require big time energy; a resting adult's noggin uses 25% of his/her total energy output. If you have to spend the day picking nits out of each other's fur for supplemental protein, you hardly have time to work with your opposable thumb or to invent Folsom points.

On the other hand, if you cook the nits you pick, you in effect predigest your food, so less energy is spent on digesting and more sugar is available to the brain. Per Wrangham, cooking paved the way for the dramatic expansion of the human brain. He notes:

No human foragers have been recorded as living without cooking, and people who choose a 'raw-foodist' life-style experience low energy and impaired reproductive function. The possibility that cooking is obligatory is supported by calculations suggesting that a diet of raw food could not supply sufficient calories for a normal hunter-gatherer lifestyle.
_____

Wrangham R etal. Comp Biochem Physiol A Mol Integr Physiol. 2003 Sep;136(1):35-46.

More produce does not produce more cancer protection

No more bolting more blueberries which, when eaten in a hurry and underchewed, come out looking about like they did going down. Apparently the daily five as in five servings of fruits and veggies is good breast cancer prevention, but more is not better.

While my medical partner is a star when it comes to packing a little lunchbox full of baby carrots, cherries, grapes, etc., my produce produces mold and turns to slime in my crisper bin. I was pleased, therefore, to read the results from this study of 3,000 breast cancer survivors. One group followed the five per day formula while the other half were schooled in the more the merrier philosophy of vegan fare. There was no statistically significant difference in breast cancer recurrence between one group or another.

Lead author John Pierce of the University of California, San Diego concluded "You don't need to go overboard." He did note that daily exercise remains clearly associated with better outcomes in breast cancer survivors. And, as Susan Gapstur of Northwestern University adds, "At the end of the day, it's never wrong or bad to eat healthfully."
_____

Pierce JP et al. JAMA July 18, 2007.

Courtesy waves

I wrote two days ago about warm glow motives. This warm and fuzzy feeling occurs when the ventral striatum deep within the brain lights up with activity as you do unto others as you would have them do unto you.

Well what better way to follow the Golden Rule than to allow some chump trying to get out of a driveway a chance to enter your lane of traffic. Life's contentious enough, and little traffic niceties might make everyone's day a little easier. I've discovered, however, no electrical hum generates out of my ventral striatum unless said chump gives me a little wave as he zips in front of me. No wave, no glow.

If courteous drivers have no dopamine flowing out of the ventral striatum, road rage follows. Remember to give a little sign to your fellow drivers that you appreciate their help.

Where's the Acomplia?

This drug, generically known as rimonabant, is an endocannabinoid receptor blocker. Do you recognize that word in there--cannabis as in marijuana?

All that is pleasurable in an illegal sort of way mimics some function in the body that causes good vibrations through the central nervous system. As some of you who once inhaled your way through your youth may remember, marijuana not only feels good but causes enormous craving for and pleasure in eating. Block those cellular receptors that hook up with marijuana, and research suggests you can mash the munchies and lose the weight.

Acomplia looked like just what the doctor ordered for those expanding midlife waistlines resulting from years of overeating. Studies suggest that not only can weight be lost, but the metabolic syndrome, a dangerous body state contributing to diabetes and heart disease, can be reversed as well through use of this drug.

Unfortunately, we've got endocannabinoid receptors for more reasons than just enjoying the occasional funny cigarette. Data now suggests that blocking those feel-good receptors increases risk of depression and suicide. The FDA continues to investigate these unwanted outcomes of the drug, and Acomplia's approval is not expected in this country any time soon.

The glow of giving

My friend J enjoys paying for the person behind her in line at the Starbucks drive-through to the everlasting delight of her daughters. If she carried a function MRI machine in her van, a recent study out of Oregon(1) suggests that we could see the girls' brains light up with philanthropic pleasure.

This neuroeconomic study stuck volunteers in just such a machine and scanned their noggins while they played a 'dictator game.' The subjects received $100 and then made decisions about whether or not to donate money to the game's food bank.

The investigators correlated the subjects' self-reported satisfaction of giving with activity in their ventral striatum, a structure deep within the brain known to produce a feel-good sort of reward response. The area was fired up whether or not the giving was voluntary vs. mandatory taxed transfers, but glowed hotter when the altruism came from the heart and not the government.

The researchers dubbed this response the warm-glow motive. This may explain, they say, the economic puzzle: If money is a good, why are people willing to give it away?
_____

Harbaugh WT et al. Science 316 (2007)1622-1625.

Posterior tibial tendon dysfunction

Overstretched and going to ground. Doesn't that about sum up this aging thing? Well here's another thing going wrong in the half-century set.

The posterior tibial tendon basically comes from the calf around the back of your inner ankle bone where it stretches over the inside edge of the foot and holds the arches up. Injure yours through overweight, overstress, or just plain too many years of living, and the little darling stretches or tears and poof! arch hits the floor. The loss of the arch stresses your ankles and drags your knees inward along with the feet and the ankles. The result? Foot pain, lateral knee pain, and an inability to stand on your toes.

Shoot, who knew? If you're wondering about the state of your arches, check out your wet footprint. Or look for the "Too many toes sign." Get a buddy to stand behind you and look at your feet. A positive 'too many toes sign' is present if more than the pinky toe can be viewed from the back. This toeful look is created by the outward splay of a foot caving inward due to a fallen arch.

And it's not necessarily just the midlife women suffering from PTTD. The other day, a phys.ed. teacher, male, 30 y.o., came in complaining of right ankle pain. This developed after he walked all day long on a trip in flip flops (no arch supports in those) carrying a backpack. Sure enough, this young fellow had 'too many toes' on his right foot and had injured his posterior tibial tendon through overuse/misuse during his daylong trek.

Practicing what I preach

Well it wasn't exactly stalking a saber-tooth tiger across the tundra. But it was a whole lot like air-boxing to overloud music with a bunch of women half my age.

I've signed up for a trial membership at 24-Hour Fitness, and went today to their Turbo Kickboxing class. Very humbling--I consider myself fit enough, but these women, especially the buff little instructress, have taken fit to entirely new levels.

Here's wise words by FW Booth from the Journal of Physiology:

In sedentary cultures, daily physical activity normalizes gene expression towards patterns established to maintain the survival in the Late Paleolithic era.

The cute little membership rep asked me what my goals were for my 24 Hour Fitness work-outs. I told him "Staying alive," and I meant it.

A bad pancreas day

That would be yesterday. Three patients in for discussions on their newly diagnosed type 2 diabetes, and two more for the 'you're on the way there' talks.

I gave them all my 'right genes/wrong eon' lecture. Basically, here's the scoop when our 'Ice-Age genome' meets the 21st century:

• The human genome evolved within an environment of high physical activity.
• Our cultural evolution has proceeded too rapidly for genetic accommodation.
• This mismatch between biology and lifestyle fosters development of chronic disease such as diabetes and heart disease.

In other words, our physiology was perfected during the Ice Age for cold, famine, and high activity. Now, we're not cold, we're not hungry, and we're triumphant if we park the car at the far end of the grocery store lot before we go 'hunting' through the aisles to supply our family with food.

Our bodies, meanwhile, are storing our extra calories for the coming famine which never comes. All that fat to waist sets up a metabolic nightmare that takes high intensity physical exercise to unravel. Those of us whose ancestors were clever enough to take down mammoths (and that would be all of us) are most likely to go down this road.

This diabetic news was not news to any of my patients with whom I spoke yesterday. They all had screaming warning signs for years on their lab printouts and around their midriffs. If you have elevated triglycerides as in more than 150 on a fasting sample, an abnormal fasting blood sugar (100 or above), and/or your waistline is the first part of your anatomy to walk through the door, don't wait for a bad pancreas day, eat less and move more now.

MD: How's your blood pressure been?
Pt: Good, as far as I know.

This means patient hasn't checked it.

MD: How often are you getting out for exercise?
Pt: Not as often as I should.

This means not at all.

The upside of bipolar disorder

I had a delightful young lady in my office today. She caught my eye in the waiting room even before I called her name due to her engaging smile, the kind of person you'd like to hire to work your front desk and win over your public.

She, however, was not particularly happy today, having been recently diagnosed with bipolar depression. Despite her successful career in public relations, she worried that her future would be bleak due to her condition.

I assured her the upside of bipolar was the creative energy and outgoing personality she brought to her life, her work, and her relationships, all qualities easily visible during our brief encounter. I just e-mailed her the following quote from Dr. Peter Whybrow of the Department of Psychiatry and Biobehavioral Sciences at UCLA. He is responding to the question as to why genes for bipolar disorder would persist in the human genome:

I think there is much in the energy and excitement of what one considers hypomania* that codes for excellence, or at least engagement, in day-to-day activities. One of the things that I've learned over the years is that if you find an individual who has severe manic depressive disease, and you look at the family, the family is very often of a higher socioeconomic level than one might anticipate. And again, if you look at a family that is socially successful, you very often find within it persons who have bipolar disease...

So I think there is an extraordinary value to those particular genetic pools. So you might say that if you took the bipolar genes out of the human behavioral spectrum, then you would find that probably we would still be -- this is somewhat hyperbolic -- wandering around munching roots and so on.
_____

*Hypomania is the high energy state short of outright mania that can be seen in persons with bipolar tendencies in the course of their normal functioning

Builds stronger bodies 2 ways

If I had it to do over again, which thankfully I do not, I would take two specific supplements during pregnancy along with the old standby prenatal vitamin: vitamin D and omega-3 fatty acids.

The former improves bone health in a woman's offspring. British researchers studied nearly 200 children for bone mineral content at age 9 years correlated with their mother's vitamin D levels during pregnancy.(1) Those with D-ficient moms (defined as blood levels of 25(OH) vitamin D <11mcg/L) had significantly lower lumbar spine bone density compared with children of D-replete moms (vitamin D >20).

As most women get most of their bone mineralization in place by age 20, D supplementation in pregnancy can improve peak bone-mineral acquisition, perhaps reducing the risk of osteoporotic fractures in later life.

So D covers the bones, and omega-3 fatty acids improve developing brains. We're all fat-heads insofar as 60% of our brain is made up of lipids. Intake of DHA or docosahexaenoic acid during pregnancy, especially during the final trimester, pumps that baby's brain full of DHA which becomes an integral part of the neuronal or brain cell membranes. Rat moms rave about the cognitive and attentional abilities of their DHA-primed offspring.(2) Evidence suggests that such a strategy works well for humans too.
_____


1. Javid MK et al. Lancet. 2006;367: 36-43.
2. Levant B et al. Lipids. 2006 May;41(5):407-14.

No MAM

There are so many reasons to dread the onset of menstruation--crabby, irritable, teary ones. For many women who suffer from migraines, those plummeting estrogen levels associated with the start of the flow also bring on a menstrually associated migraine or MAM.

One strategy to duck the MAMs has been to use birth control pills continuously over three cycles, cutting a year's load of periods from 12 to 4. Several pill types are currently available specifically designed for this purpose, including Seasonique which includes a small amount of estrogen in the pills taken during the quarterly week off.

Endo Pharmaceuticals has just completed another Phase III clinical trial on Frova, an Imitrex-like drug typically used to rout a migraine in the early stages. When Frova is taken twice daily beginning three days before the usual onset of a MAM and continued for six days total, study subjects experienced less intense MAMs, or no MAMs at all!

Thyroid dosing: Too low is too slow

I definitely learned that initiating thyroid replacement therapy in persons profoundly hypothyroid should be done slowly and carefully to avoid heart complications. I never learned, however, the proper starting dose for your average, semi-sluggish, hypothyroid woman. This is important as statistics suggest that 15% of adult women ultimately become low in thyroid.

Leaving no problem left unstudied, Dutch docs conducted a study that compared a full starting dose of levothyroxine (1.6mcg/kg which is the equivalent of a .1 mg Synthroid or Levoxyl tablet for a 130 pound woman) to a weensy, sissy little dose of .025 mg with respect to the speed with which thyroid levels returned to normal on follow-up testing.(1)

Whether or not the 50 study participants received the big deal or the teeny bit, no one complained of palpitations, chest pain, nor keeled over dead of a heart attack.

The notable difference between the two groups, however, was that nearly half the full dose group was euthyroid (normal levels) within 2 months of the study's start but only 3 in the low and slow bunch had achieved normalcy by then. In a way, it matters not one way or the other as quality of life with respect to symptoms improved at the same rate in both groups.

On the other hand, each dose adjustment requires a trip to the lab to check levels followed by 3 to 4 frustrating calls to the physician's office to get the results and get the new prescription called in, so aggressive dosing may work better for all in the short and long run.
_____
Roos A, et al. Archives of Internal Medicine 2005;165: 1714-1720.

I recently had a slim and fit sixty-something year old lady come in for a discussion on her elevated cholesterol. While her total and LDL-cholesterol were notably high, her protective HDL-cholesterol levels were elevated as well in a satisfying sort of way.

The first step in determining whether or not she should be on cholesterol-lowering meds involved totaling up her risk factors for coronary artery disease according to guidelines issued by the National Cholesterol Education Program(1):
__________

Major Risk Factors (Exclusive of LDL Cholesterol) That Modify LDL Goals

* Cigarette smoking
* Hypertension (BP greater than or equal to140/90 mmHg or antihypertensive medication
* Low HDL cholesterol (<40 mg/dl)*
* Family history of premature CHD (CHD in male first degree relative <55 years; CHD in female first degree relative <65 years)
* Age (men greater than or equal to45 years; women greater than or equal to55 years)

* HDL cholesterol greater than or equal to60 mg/dL counts as a "negative" risk factor; its presence removes one risk factor from the total count.
__________

According to our calculations in her situation, she had zero risk factors as her HDL-cholesterol of 87 canceled out her age of 62. Her goal LDL-cholesterol was less than 60, and the recommended level at which to use medication was greater than 190.

Her LDL-cholesterol was 197. She, as so many people are, was reluctant to start drug therapy. Off she went, instead, to Colorado Heart & Body Imaging for a $395 CT scan of her heart. The news was not good--she had a fair amount of calcifications in her coronary arteries, correlating with more plaque in those vessels than 90% of women her age.

She started treatment with Lipitor yesterday.

_____
1. See NHLBI, ATP III At-A-Glance for the complete algorithm.

Physician Self-disclosure

Rochester MDs wondered about the extent to which primary care docs take the Enough about you, what about me? attitude during office visits. In addition, they investigated whether or not physician self-disclosure (MD-SD) has a positive effect on patient/doctor interactions(1).

They analyzed 113 undisclosed 'standardized patient' visits with 100 volunteer physicians for the number and content of MD-SDs. One-third of the investigational visits contained an MD-SD. Of these, 40% were unrelated to the topic under discussion and a mere 21% of the visits returned to the previous conversational thread after the MD burst in with his/her information.

Whoa, this is sobering food for thought. I certainly have been known to bring up personal or family information when I feel it is pertinent to the visit at hand, particularly when something about that experience may help the patient to feel less odd about their symptoms or less nervous about trying a therapeutic strategy. In particular, I've brought up my experience with panic attacks while driving on the highway in order to decrease the patient's suspicion that I am easily dismissing their panic-driven symptoms as 'all in their head.'

Occasionally, however, I must admit that I go too far with what I consider a particularly amusing or fascinating story of a personal nature, but always related to the topic at hand. I recall telling myself "Time to shut up and listen," on more than one occasion.

The authors of this article conclude: There was no evidence of positive effect of MD-SDs; some appeared disruptive. Primary care physicians should consider when self-disclosing whether other behaviors such as empathy might accomplish their goals more effectively.

Point well taken!
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1. McDaniel, SH, etal. Physcian Self-disclosure in Primary Care Visits. Arch Intern Med. 2007;167:1321-1326