Social genomics and loneliness

The term social genomics is a new one to me. The fact that social factors influence health is not.

I wrote some time ago about the effects of self-described loneliness/social isolation has on the health of older adults. UCLA researchers examined the white cells of persons who were highest of the "high-lonely" vs. those "low-lonely" (socially connected) subjects.(1) A total of 209 genes showed different levels of expression between the two groups. Over 4 years of study, the lonely crowd over-expressed genes that resulted in inflammation and under-expressed those involved in antibody production against bacteria and viruses.

These DNA effects of social isolation were very specific to three groups of genes. The first group of affected genes are involved in the early phase of the immune response wherein the body revs up inflammation as a first response to injury or infection. I have written numerous times about the blessing/curse of inflammation insofar as appropriate levels are essential to a successful recovery from infection but too much (think cytokine storm in influenza pneumonia) or wrong place at the wrong time (say in an arterial wall that has cholesterol build-up) can be counter-productive or downright destructive.

The other two groups of immune genes that respond to the lonely soul's transformed internal environment are those that stimulate the production of interferon (a molecule that amplifies immune response against viruses) by lymphocytes and those that stimulate production of antibodies by B lymphocytes. The activity of both these types of genes is diminished in people who are less connected to friends and family.

The psychological literature abounds with studies in which socialization is correlated with susceptibility to viral illness. In another one of those 'who the heck volunteers for these things' type of study, researchers at Carnegie Mellon University assessed 193 subjects for PES (positive emotional style) vs. NES (negative emotional style of course) and then sprayed rhinoviruses/ common cold or influenza viruses up their noses to see who got sick.(2) Those NES-positive individuals, described as anxious, hostile, and depressed were 3 times as likely to succumb to the influx of nasal virus compared to all the PES prone Pollyanna types who were happy, lively, and calm.

Per Steve Cole, co-author of the study on white cells and loneliness: Research in social genomics has now clearly established that our interpersonal world exerts biologically significant effects on the molecular composition of the human body.(3) What remains to be seen is how attitude adjustments of the cognitive or pharmocological variety can affect how our DNA gets activated.
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1) Cole SW, et al. Social Regulation of Gene Expression in Human Leukocytes. Genome Biol. 2007;8(9):R189.
2) Cohen S, et al.Positive emotional style predicts resistance to illness after experimental exposure to rhinovirus or influenza a virus.Psychosom. Med. 2006 Nov-Dec;68(6):809-15. Epub 2006 Nov 13.
3) Cole SW. Social Regulation of Human Gene Expression. Current Dir. In Psych. Sci. 2009 Vol 18 No 3.

To Elaine Calzolari 12/30/50-11/8/09

Astolat. Public art by Elaine Calzolari

My friend and sister-in-law Elaine Calzolari died early this morning. A sculptor whose innovative work with stone revolutionized the field, her favorite work was Astolat, named after the legendary home of the fair maiden Elaine of Arthurian legend.

It is my privilege to have shared her life and death along with her daughter Miranda Paley. We should all be so blessed to exit earth with such a brave and loving soul as Miranda at our side. Elaine's favorite poem was "Witnessing" by Gary Miranda, the perfect tribute to this mother/daughter team. Godspeed Elaine!

Witnessing

Beneath the leaves of a plant, that's named for milk
that bleeds milk, we search for chrysalides,
things that I've never seen, but whose name I like.
And I think as I look of all the things

you've taught me to name--larkspur, loose-
strife, sea lavender, plants called hens
and chickens, butter and eggs, your eyes
bright with such knowledge and solid as nouns.

Just so, you tell me now of creatures
who choose the underbelly of these leaves to make
wombs of, studded with gold, from which emerge
Monarchs that range the length of the Atlantic

in hordes--one more fact I must have missed
by skipping the fourth grade. And when, today
we find no trace of anything resembling this
miracle you mention, and I'm about to say

you made it up, you bend down, break a pod,
and blow unlikely butterflies in the sky's face-
not black and orange like Monarchs, but cloud-
thought white, or like the way I mark my place

when I read your eyes, which witnessing claim:
This is the world. Try to learn its name.
Witnessing.

Vitamin D and blood vessel health

I'm sure you know by now that vitamin D is the new darling of the vitamin world. If you're not taking extra, where have you been? UK investigators(1) tested blood vessel health in type 2 diabetics by an indirect method called flow mediated vasodilation or FMV and added yet another reason to consider letting a little sunshine onto your pasty white skin. And if your skin is not white, all the more reason to make an extra effort to get extra D by sun or by supplement-- darker skin is known to be more resistant to the effects of UV radiation with respect to the production of viratmin D.

First a review of FMV. This rather simple test measures the ability of the brachial artery located in the elbow to dilate in response to increased flow. A pressure gauge measures the force of blood flowing through this upper extremity vessel. A blood pressure cuff is then placed on the subject's arm and pumped up high enough to stop blood flow to the arm below. When released, the surge of blood returning to the artery causes the vessel to expand, accommodating an increased flow to the (briefly) oxygen-starved tissues of the lower arm.

This dilation is the mark of a healthy vessel. People with diabetes and hypertension have blood vessels that don't respond normally when tested--and also, unfortunately, in real-life situations such as exercise. Researchers, therefore, use this test to evaluate certain interventions like medications, vitamins, or dietary strategies that tend to normalize the wacked-out FMVs of those with such chronic conditions.

So Dr. Sugden and his colleagues took a group of sun-starved, diabetic Scots in winter and gave them a single whopping dose of D--100,000 units--testing their FMVs before and 8 weeks after the bolus. All of these subjects had D levels <50 ng/ml prior to the trial, and the D supplement raised their levels on average by 15. Darned if that D didn't do the duty! FMV levels rose significantly at follow-up.

Have you D-cided to up your D yet?

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( 1)Sugden, JA et al. Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low vitamin D levels. Diabet Med. 2008 Mar;25(3):320-5. Epub 2008 Feb 13.

Small thigh circumference and cardiac risk

Here's a new take on body build and health! We are all familiar with the apple/pear thing in that those who carry their weight around the waist in an apple-ish silhouette are at greater risk of heart disease than those whose excess pounds hang on their hips. These Danish researchers took the measurements one level lower(1); here's what they found:

Professor Berit Heitmann and company from Copenhagen's Research Unit for Dietary Studies took tape measure to thigh on over 2800 legs still attached to as many Danes, then followed the group for 12+ years checking out incidence of heart disease and death. Pipe cleaner thighs that fell short of 60 cm. (23.6 in.) in circumference were an independent risk marker for both unfortunate endpoints.

So what's the problem with skinny thighs? Two of our biggest muscles are contained therein, namely the quadriceps and the hamstrings. A loss of muscle mass could be a marker for inactivity or chronic disease such as COPD that prevents exercise. In fact, a Canadian study found that loss of mid-thigh muscle mass as measured by CT scanning was a better predictor of mortality in chronic pulmonary patients than a low body mass (both indicative of the wasting associated with lung disease).(2) Less muscle mass is also known to predispose to insulin resistance and type 2 diabetes as demonstrated by the elevated fasting blood sugars and cases of diabetes that we unexpectedly see in scrawny old ladies.

So should we be measuring thighs along with waistlines, blood pressures, and pulse rates (and also asking about physical activity, sleep habits, diet histories and domestic violence in the leftover minutes of annual physicals)? Says Australian epidemiologist Dr. Ian Scott in an editorial accompanying the Danish study: "Will this association help clinicians predict risk in individual patients more accurately than they already do using readily accessible and validated risk calculators? The answer is — we do not know."

I, for one, shall pass for now.
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(1) Heitmann, BL et al. Thigh circumference and risk of heart disease and premature death: prospective cohort study. BMJ. 2009 Sep 3;339:b3292. doi: 10.1136/bmj.b3292.
(2) Marquis, K et al. Midthigh muscle cross-sectional area is a better predictor of mortality than body mass index in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2002 Sep 15;166(6):809-13.

Idiopathic erythema

My friends used to worry that my father, a psychiatrist, was secretly diagnosing their psychopathology when they'd stop by the house. On average, one word--adolescence--was all that was needed to label our deviance from normal behavior during those formative years.

Sometimes, I like to play 'guess the diagnosis' when I'm out and about in public. During PTA meetings at my daughter's high school, I'd sit and wonder why another parent's face was so red (the meeting content, as you may guess, was simply riveting!). I never did figure it out, nor do I have the slightest idea what happened to the man in the years since last we met. I was disturbed, however, to come across an item in a medical journal that suggested that his diagnosis may not have been benign.

Idiopathic erythema is a fancy way of saying the skin is red and we don't know why. One of my fellow residents during training had allergic dermatitis (eczema) as a cause of his not-so-idiopathic erythema. Those patients who are red for unknown reasons tend to be male (73%) and older (average age 69 years in one study).

Out of 218 Singaporeans studied by dermatologists there, 18% were ultimately found to have cancer. Dr. Steven Thng and his colleagues concluded, "We recommend close follow-up with reevaluation for malignancy even if the intitial investigation had been negative."

I hope this fellow is doing well, ruddy but cancer-free. But I now have something new to think about when a patient complains "Boy is my face red!"

Vitamin D, influenza, and old ladies

Many epidemiologists now believe that flu is seasonal because vitamin D levels fluctuate seasonally. Vitamin D is a potent immune modulator; individuals tend to have higher levels during summer months with higher exposure to UV radiation and, therefore, are less likely to contract the flu while sun-kissed.

Researchers followed the seasonal health adventures of 208 post-menopausal women over three years as correlated with their monitored intake of D.(1) The results, shown in the bar graph above, were as follows:

• Those ladies in the placebo group (lightest bars) got cold and flu symptoms all year long, but especially in the winter.
• The test subjects (intermediate shaded bars) who received 800 units/day of supplemental D were as likely to get sick in the summer as winter, but were far less likely to take to their beds than their D-ficient colleagues.
• In the final year of the study, the test subjects were plied with 2000 units of D each day. Only one lady (as represented by the itty-bitty dark bar in summer) got sick while D-eeply dosed with the vitamin.

Presumably D same benefits accrue to old guys too.
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1)Aloia JF, Li-Ng M: Epidemic influenza and vitamin D. Epidemiol Infect 2007; 135: 1095–1096.

Big-time kyphosis

When some of my older female patients lie back on the exam table, their heads drop backward, necks extended, due to a forward curve in their thoracic spine between the shoulder blades. This hunchback thing is an exaggeration of the kyphosis or the gentle curve normally present in this area. It can result from weakness of the upper back muscles aggravated by poor posture but it becomes particularly prominent in women suffering from osteoporosis.

The lady in the above x-ray* has a helluva kyphosis based on osteoporosis. Her T score which compares her bone density to the ideally mineralized skeleton is -4.2 (normal range is greater than -1). This means that she has lost 42% of her bone mineral density and is severely osteoporotic. As a result, her normally block-shaped vertebral bones have collapsed anteriorly and become wedge-shaped due to compression fractures. She has lost height; her head and upper body have permanently sunk forward as her spine curled.

She no longer has room for her abdominal organs which have pooched out as her ribs sank into her pelvic bones (yes, that's bowel gas just below her chin--she is permanently gazing at her navel!). Worse yet, her thorax is severely shrunken, and her lungs can no longer fully inflate. She presented to the ER in respiratory failure as she could no longer exchange high CO2 exhaled air for high O2 inhaled air. She died during this hospital admission.

You do NOT want this collapsing spinal column thing. Lie on the floor--does your head flop backwards due to the forward curve of your upper spine? Are you uncomfortable without a pillow when lying flat on your back? Get your bone density checked. Find a physical trainer to nag you about your posture and work on your upper back strength. Take extra D and calcium!
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*Blechacz, B. Images in Clinical Medicine. NEJM 6/12/08.

The Teeming Team from Palliative Care

My friend was making some tough decisions. She was in the hospital for shortness of breath, and a lot of fluid had been drained from the area around her lungs earlier that afternoon. These effusions from her metastatic cancer would soon return; the question under consideration was what to do next.

Yet another knock on the hospital door heralded yet another helper with an agenda. No, not one helper, but rather a bevy of young, white-coated women bustled in.

"Hi," chirped one, "I'm Ms. Whatever from the Palliative Care Team. Your doctor asked us to come visit with you."

Oh heavens. This well-meaning crowd was about as welcome as a flock of Grim Reapers. Right time, right place, but WAY too many of them in the room, all eyes trained sympathetically on my friend lying in bed. The one next to me with Something, MD embroidered on her lapel (didn't have my reading glasses on) leaned forward, hands on knees in the sort of poise you'd use to peer down at a small child, and outlined the services the team could offer.

After a brief and strained conversation, E. sent them packing. Great idea, nice people, but they should crowd into a conference room and review their M.O.

Prostate Cancer Risk Screening

"Should I get a PSA test?" My patient was giving me a run for his money during his annual exam last week. We'd already discussed the pros and cons of undertaking treatment for blood pressure, and he'd asked for the evidence why one medication was preferable to another. He wanted to know if the data I presented was from studies sponsored by dirty drug company money. Finally, he threw out this challenge to conventional wisdom on prostate cancer screening, and a very good question it was.

Men anticipate prostate cancer screening with all the dread that women bring to Pap tests. Screening is generally limited to men over the age of 50 (unless there is a history of early prostate cancer in a father or brother) and consists of an exam of that part of the prostate that can be reached by a probing finger plus a blood test for prostate specific antigen or PSA.

The problem is that the PSA, while being the only cancer marker test currently available for screening purposes, is not specific. In other words, most men with an elevated PSA do not have cancer. The digital exam is even less specific as many aging men have enlarged prostates without harboring cancer. Other screening deficiencies in our current approach of one blood test and one finger exploration include:

• Most men with prostate cancer (85% in one study) detected by PSA screening could avoid therapy. Per another study, one would have to screen 1400 men and perform 50 prostatectomies to prevent one death from prostate cancer.
• There is no PSA level below which the risk of cancer is zero. The Prostate Cancer Prevention Trial (PCPT) found cancer in 6.6% of men with PSAs below .5 and 12.5% of those men had aggressive cancer.
  
• Other factors seem to affect PSA levels, e.g. obesity and statin use lower PSA.

So what's a guy to do? One study over nearly 9 years showed a 20% decreased risk of cancer death with PSA screening every 4 years vs. none at all. Another concluded that testing every 6 years with digital exams every 4 made no difference whatsoever. Dr. Eric Klein notes(1): "All cases of prostate cancer are clinically relevant in that they can cause anxiety or can lead to treatment-related morbidity." In other words, we are detecting a large number of sub-clinical tumors--i.e. no symptoms suggest a prostate cancer brewing--with our screening, many of which would never cause a problem. We know that 90% of men with low-grade prostate cancer choose treatment which can cause incontinence, impotency, or death.

Dr. Klein suggests one approach to screening that uses seven variables to predict a man's risk of currently having prostate cancer. This test can be found at PCPT risk calculator.
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1. Klein, EA. What's new in prostate cancer screening and prevention? Cleveland Clinic Journal of Medicine. Vol 76 August 2009 439-445.

Doc of Ages now on Twitter

I'm going to give this a try for all the little pearls I come across in medical magazines that can be delivered to you in 140 characters or less. No updates on where I am, what I ate for breakfast, or how much sleep I got, just the latest in medical knowledge from the cutting edge.

You can sign-up at twitter.com/docofages. All my blogs will continue to be published on a more or less regular basis.

Is Multitasking Bad for Your Brain?

This morning I was perusing an August issue of Science. My husband walked into the kitchen and switched the radio on to NPR's Car Guys, then began grousing about what idiots they were and what bad advice they gave. So there I am, reading, drinking coffee (I don't suppose that counts), listening to those Car Guys yuk it up, and degrousing the spouse (that's what you do when you acknowledge someone's rants with sympathetic murmurings of assent). Oddly enough, in one of those 'bloggable moments' that those of you who blog know so well, the magazine article I was reading was "Multitasking--Bad for the Brain?"(1).

A word or two first about multitasking--I don't know when the word was coined, but in this day and age of electronic devices, the skill ranks right up there with missing sleep to multitask as one of the characteristics of New Age success. The ability to text, talk on the phone, work on the computer, and troubleshoot simultaneously is the mark of a modern manager (and that, Jean C, is why we pay you the big bucks!). More than once I've cited 'inability to multitask' as one of the job requirements that a patient applying for disability can no longer perform.

I personally go into what I call overwhelm mode if called on to multitask too long. Bi-tasking I can do, fielding an urgent message say in the middle of an exam, or mixing pancake batter while talking on the phone. Well actually, the latter has proven problematic in the past. But layering calls from the ER, prescriptions, annual exams, work-ins, and a kid crisis in a single afternoon puts me over the top with agitation.

So here's what Stanford scientists found when they compared 19 heavy habitual media multitaskers with 22 persons who generally limit their electronic input. The subjects were tested for their ability to filter out irrelevant environmental information as well as "irrelevant representations in memory." In addition, all the volunteers were also tested for the ease with which they switched tasks. Those heavy duty multitaskers (IM'ing, skyping, texting, gum-chewing fools no doubt) were more distractible and less able to switch tasks midstreams than their colleagues who characteristically uni- or bi-tasked.

The obvious question that arises from this study: Do multitaskers scramble their brains in the multitasking or are they just a flighty, distractible bunch from the get-go who are attracted by nature to a 3-ring cognitive circus?

My reaction to my a.m. over-stimulus? I excused myself ASAP to go blog, taking my IPhone along so I could respond to a text that just came through from Jean C.
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(1) Ophir, E, et al. "Cognitive Control in Media Multitaskers." Proc Natl Acad Sci USA. 2009 Aug 24.

Verbal fluency exercises

Verbal fluency or the ability to find the right word at the right time in a timely fashion is one of those front brain skills that lags with age. Add dwindling hormone levels, social isolation, and/or a history of even a mild concussion, and you may end up as fumble-mouthed as an evening news anchor.

We know that reading, working crossword puzzles, and interacting with friends are all ways to support brain function and verbal fluency. To heck with all that, how 'bout still another way to waste time on the Internet? Try lumosity.com, a web-site full of games that do both--bolster your brain and while away time you don't have. In particular, have a go at Word Bubbles which not only tests your verbal fluency but your typing and spelling skills as well.

And thanks, or no thanks, to my niece Miranda for the loss of many an hour!

Weekly H1N1 flu update

As an internist and primary care provider, I expect to be on the front lines during the upcoming flu season...whatever it may bring. Here's my first weekly flu report; stay tuned for future updates concerning the H1N1 vaccine, the latest in H1N1 research, and ways that you, your family, your friends, and co-workers can stay healthy through the fall and beyond!

A few words about seasonal flu

Influenza viruses are identified by their surface proteins that allow the little buggers to 1) stick to the cells of your throat and 2) thrive and multiply in your airway. H is for hemagluttinin, a protein that hooks the virus up to you, and N is for neuraminidase, a protein that promotes the release of newly made flu virus particles from the infected cell to its uninfected neighbors.

The reason that flu is such an ongoing nightmare is that the virus remakes itself every year with novel H and N proteins so that many people, even those who have previously had flu, aren't immune to the new variety. Every year we try to anticipate what this slippery little devil is going to do with respect to H's and N's and then develop a shot to promote immunity in all vaccinated persons. We particularly target those who are very young, very old, or otherwise affected with a chronic disease which would make them more susceptible to a complicated and dangerous case of the flu.

What's all the fuss about H1N1?

This past spring (late in the flu season) a new strain of flu emerged--first identified in Mexico--with novel H and N proteins. The strain was first traced to pigs--new influenza strains often start in pigs--thus the original name 'swine flu'. This name was dropped after pigs were unfairly targeted as the infectious source of the disease, but now we know of course that you cannot get H1N1 flu from eating pork.

The scary things about this new flu were that 1) it showed up in the Northern Hemisphere at a time when flu should be winding down, and 2) it appeared to be particularly severe or lethal in healthy, young adults, a group generally not at risk for flu complications or death. We are concerned, of course, that this H1N1 flu could cause another worldwide, devastating pandemic like the outbreak of 1918 which was also caused by an H1N1 type of influenza. Bird flu,incidentally, is typed as H5N1.

Lots of research is being done on this new strain, but the findings of flu expert Dr. Peter Palese and his team at Mount Sinai School of Medicine in New York are reassuring. They agree with CDC data that estimate only 10% of household contacts of patients with H1N1 will become infected which suggests that this bad actor is not as tough or transmissible as we originally feared.

Tuna casserole deficiency or cardiac arrest?

Manytuna Casserole
2 tuna-fish-can-sized cans of the cheapest tuna
1 package broad noodles
1 can condensed cream of mushroom soup
1 package of frozen green peas

Precook the peas. Precook some (not all) of the noodles. Mush together in the pot
you just cooked the peas in (after draining off some of the water): the peas, the tuna
fish, the cream of mushroom soup (just as it comes out of the can), and the following
seasonings: salt pepper paprika oregano and garlic salt
Beginning with the noodles, alternate in your casserole dish layers of cooked noodles
and mush-mixture, ending with mush-mixture. Sprinkle a little paprika on top for local
color. Bake at 350 degrees for 20 minutes or so (there being no cheese to melt in this recipe).

I was never deficient in tuna casserole after my mom sent me "The Impoverished Students' Book of Cookery, Drinkery, & Housekeepery." And a good thing too as medical research confirms that ample tuna casserole (or omega-3 fatty acids in any other form) is a good way to ward off death. Here's what researchers at the University of Washington found:

They gathered blood samples from 300 unfortunates who had pitched over mid-life from sudden cardiac arrest. They then minced up the red cell membranes from the dearly departed, analyzed them for omega-3 fatty acid content. This measurement of omega-3 fatty acids in red cells--specifically DHA and EPA--is called the omega-3 index and measures the levels of these worthy fats as a percentage of total fats in the cell membrane.

The omega-3 indices of the fallen were compared to those of a control group from persons of similar age who were still alive and well. This upstanding group--who doubtless loved tuna casserole or rare tuna steaks or anchovy pizza--were far more likely to own red cells with at least 5% omega-3 content.

A preventive cardiology group at the University of Munich crunched omega-3/risk of death numbers and came up with these compelling statistics for downing capsules even if they make your breath smell like a dead mackerel:

"A review of the literature, expanded by measurements of the omega-3 index, indicates that the risk of sudden cardiac death correlates inversely with the omega-3 index. For persons with an omega-3 index <4%,>8%.

So omega-3 fatty acids, specifically EPA and DHA (read the label on your fish oil supplement selections and choose the capsule with the highest content of these two components), have anti-atherosclerotic (prevents build-up of cholesterol plaque), and anti-arrhythmic (prevents your heart from beating too fast, too slow, or too irregularly) properties. Furthermore, that fishy oil in the red cell membranes makes them less likely to glump together in a clot and more likely to squish through narrow places.

What's your excuse for sneering at tuna casserole?

Cankles

Not a pretty sight, and certainly not one you want to see below your knee on a trans-Atlantic flight. On average, it's a bad thing that airplane seats on such journeys are so close together that you can hardly reach your feet to pull off your shoes, but a good thing insofar as inspecting your ankles is difficult. But when I finally got my lower leg into viewing range on the leg of the trip from Madrid to Philadelphia, it was strictly Exhibit B for me!

This would be a good time to review venous return from the lower leg and all that might interfere with it during a summer flight. Consider blood and its journey from toe back to heart after its load of oxygen has been delivered to these nether regions. Each heartbeat sends a surge of blood through the elastic arteries which expand as the blood pushes by and then contract in a springy sort of way to amplify its forward progress. By the time the blood passes through the teeny weeny capillary bed back to the leg veins, however, it's a different story.

The veins which carry blood back to the heart are neither elastic nor springy. When the blood arrives in the venous system, that pulsing kick from the heart's action is much diminished. In the upright or seated position, gravity is tugging that old deoxygenated blood downwards. The veins have valves on their inner walls that open to partially prevent this gravitational backwash, and activation of the leg muscles helps to further squeeze venous blood in its upward course.

Think for a moment, then, about a middle-aged lady(MAL) stuck in a seat for 9 hours watching "Bride Wars" and "Marley and Me" and eating salty airline meals. Actually, the movie choices have nothing to do with our cankle tale here, but believe me, these were dismal ways to pass time. So the MAL has already walked too much through the hot Spanish sun with her venous system dilated from the heat and saggy with age. She's retaining water from the high salt food. Furthermore, as she sits motionless in steerage, two 90 degree turns in her leg veins (at the knees and the hips) further slow the flow.

Oh gad, methought, those are NOT my ankles (or more precisely, where are my ankles?). For those of you wondering when your ankle bones will re-emerge from the inflight edema, mine took two days and I've seen it take up to two weeks in some of my patients.

Limbrel--new option for osteoarthritis

I wrote some time ago about licofelone, a new analgesic for osteoarthritis (OA) that was then in Phase III clinical trials. Not only does this new agent decrease pain and inflammation from OA without stomach irritation (a la ibuprofen, naproxen, etc.) or cardiovascular complications (a la Vioxx and Bextra), it also demonstrates potential in actually slowing down joint destruction. Alas, while new reports on its dual action efficacy--analgesia AND disease modification--continue to appear, I can find no information on a release date.

I was pleased, therefore, to learn today about a new drug for osteoarthritis--a medical food actually--from a patient. Limbrel is all phytochemicals which should delight the aging hippies in all of us that search for the natural in the drugs we take to keep old body hooked to mellowing soul. It's made from those two lovely plants pictured above: Scutellaria baicalensis and Acacia catechu.

So here's the scoop. Arachidonic acid(AA) is a polyunsaturated fat that's necessary to body functions when it is appropriately converted to chemicals that protect your stomach lining, dilate blood vessels, promote proper blood clotting, and repair tissues. Too much AA in the wrong place at the wrong time is a bad thing whether it's derived from cellular injury or diet (think twisting your ankle as you eat a Big Mac for a double load of AA). Per Dr. Barry Sears: "...if you inject arachidonic acid into... rabbits they are dead within three minutes. "

As you get older, injured, have an inherited predisposition to arthritis, and eat too much fatty red meat or egg yolks, all that piled up AA gets churned along by the COX-1, COX-2, and 5-LOX enzyme systems into a world of inflammatory molecules and reactive oxygen species which set off a process by which your cartilage is destroyed and your bone overgrows into treacherous spurs.

You can inhibit COX-1 by aspirin or NSAIDs or inhibit COX-2 by Celebrex, but unless you turn down your 5-LOX as well, the resultant imbalance creates other problems. Scientists have sorted through more than a thousand plant-derived molecules looking for flavonoids with favorable suppressive action on these inflammatory pathways. Apparently those pretty posies posing above won the competition, proving both safe and efficacious in decreasing the pain of osteoarthritis.

While licofelone has been shown to slow down the cartilage destruction that leads to permanent joint deformities in osteoarthritis, Limbrel makes no such claims. Whether this is due to a lack of research supporting this function, or simply that it doesn't work in that way is not clear. Limbrel, however, is available here and now whereas licofelone is still churning along on the slow train to FDA approval. I've requested samples from the company, and look forward to working with those of you with the gnarly hands and aching knees of osteoarthritis to see what we think about this one.

Patellofemoral pain, arthritis, and exercise

First off, an explanation. What's Martha Raye with her toothsome bedentured smile doing in a post on aging knees? If you have patellofemoral arthritis, I think you can relate.

The patella (kneecap) sits in front of the lowest part of the femur (thighbone) at the knee joint. Patella slides over femur as we bend at the knee, and when all is young and working correctly, the cartilage-covered surface of one slides over the cartilage-covered surface of the other.

So with age, cartilage breakdown, misalignment, and saggy old quadriceps (large muscle on the front of the thigh in charge of getting us off chairs and toilets), the patella starts slamming into the front of the femur, and the cartilage frays, tears, and wears away down to bone. So as we squat, plie, rise up, and sit down, one bone grates on the other bone, and...just like Martha Raye fielding a seed between denture and gum...we wince with pain.

Well, that's me. Deep knee bends are yesterday's move, squats out of the question, and I channel Martha Raye during lunges. The first thing I told a personal trainer during a trial session is "I don't do lunges. Period." But she is not taking no lunges for an answer, noting as I have that flexing the weight-loaded knee to heave the rest of me up and down (assuming I'm not in a wheelchair) is what I must do for the rest of my life if I care to remain independent. Is this all about being under 30 and not appreciating how it feels to work-out on aging knees, or is she on to something?

She will feel smugly vindicated when I show her a Dutch study(1) that indicates exercise beats other strategies for relieving patellofemoral pain. The sports medicine practitioners at Erasmus University Medical Center in Rotterdam signed up 131 patients with up to twice that number of painful knees to undergo a 12 week supervised exercise program directed at quadriceps strengthening, flexibility, balance, and coordination or an equal number of weeks under 'usual care' from their physicians. The latter, I'm guessing, means this control group was told "You should do leg lifts and take Advil (or whatever the Dutch equivalent is) and get over it. Next."

On comparing the exercised group with those who motored on without supervision, the researchers found significant improvement in pain and function scores in the former not only at the end of 12 weeks but also on follow-up 12 months later. One can assume that diminished pain means improved alignment and quadriceps strength have improved the tendency of bone to grate on bone and, as a result of this supervised exercise program, wear-and-tear degeneration has been halted.

My trainer has cleverly disguised lunges as other exercises where I hop from bent leg to bent leg as she throws things at me (well, a ball actually), or stand on one bent leg while I do distracting maneuvers with weights in hand, and, well, I hate to admit it but my knees feel better.

So I guess I'll channel Erma Bombeck instead and let Martha Raye rest in peace.
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1. American College of Sports Medicine (ACSM) 56th Annual Meeting: Abstract 570. Presented May 27, 2009

I'll be doggone!

I was scribbling away on my patient's chart during the initial part of her annual exam. As I wrote her latest information, she began to pant.

My first doctorly thoughts before I looked up: "Good heavens, she's in metabolic acidosis," "She has a sucking chest wound," and finally "She's lost her mind!"

As I turned my gaze towards my patient, I noted that she looked neither distressed nor hypoxic. And...the panting was coming from near her feet!

"What on earth is that noise?" I asked.

She leaned down sheepishly and unzipped her large bag. A small silky-haired dog popped out and made my day by sitting in my lap for the remainder of the interview.

A biological reprieve from life in a shoe

There was an old woman
who lived in a shoe,
she had so many children
she didn't know what to do.
She gave them all broth
without any bread;
she whipped them all soundly
and put them to bed.
--Mother Goose

Have you ever considered that menopause may be a biological boon to get us out of such sticky shoe situations? Seriously though, what is Mother Nature's point with this mixed, menopausal blessing?

Craig Packer, a professor of ecology at the University of Michigan, considered the evolutionary advantage to animals of such programmed senescence, where the ovaries quit years before the rest of the body. He first looked for a 'granny effect', a survival advantage for those young animals with living grandmothers capable of assisting in their care. Baboon grandkids survived just as well whether grandma was dead or alive. Lion cubs only benefited from Grandma Lioness's attention if granny could nurse the little darlings because she herself remained fertile (heaven preserve us from that!).

So why don't the females of various species just keel over at menopause? Packer concluded that the answer could be found in ''prolonged maternal investment," the dependence of young mammals on the presence of a mother who's neither frail, shoe-bound, nor dead. Baby baboons need that mother's touch through their second birthday, and it is fortunate then that a baboon mom typically lives five years past her final birthing.

On the other hand, lion cubs are independent and good to go after just one year, so mama lionesses live less than two years past the end of ovarian function. Packer then assumed that human children need their moms until age ten (what kids has he been around??), and guessed that our maternal ancestors ideally would have lived until age sixty--ten years past the end of reproductive cycling--in order to see the last little darling out the door.

And now, with current advances in medical care and nutrition, we can anticipate successfully nurturing our children until they themselves are sixty!*
_____
*Or more. My 90 year old patient spent the first half of her annual exam appointment two weeks ago fretting over her 70 year old son who still walks from his house next door to hers each evening for her home cooking. Gad.

The oriented-in-space place

Drawing a mental blank is a drawback of a busy day; being unable to draw a mental map of your current location is a red flag for trouble. While getting lost in your work rates high performance reviews, getting lost while driving maybe a sign of dementia.

Arriving safely at home at the end of our day requires the proper functioning of an oriented-in-space place in our brains located just behind and above the ear. This medial superior temporal area (MST) is charged with personal global positioning, providing our brain with continual updates on our current location in space.

Unfortunately, the MST is particularly vulnerable to the cellular destruction associated with Alzheimer's Disease(AD), leaving its victims unstuck in their once familiar world. This deficit has been dubbed 'motion blindness'; the the resultant inability to navigate, even through one's own home, leads to a tragic loss of independence.

Here's another scary consequence. While early AD victims may remember street names and the basic rules of the road, there are certain driving skills that lapse early in the course of the disease based on MST dysfunction. I remember an office visit where my elderly patient arrived slightly late for her appointment. She sat down in the chair with a sigh, then proceeded to recount her harrowing drive over during which, per her report, she sideswiped several cars on both sides of the narrow streets near my office while trying to guide her car down the middle of the road. She had no sense at all of where her car ended relative to those parked by the curb.

I don't know what was more disturbing--her zigzag navigation of a potentially lethal weapon or her relative indifference to destruction that she left in her path.

What's the scoop on the flu?

Every year, the influenza virus reinvents itself. In the countryside and farms of Southeast Asia, this bad actor mixes up genetic material with its viral cousins, producing brand new strains that then spread throughout the world in the throats and lungs of international travelers. And every year in turn, epidemiologists try to anticipate the new flu variants in order to produce an effective vaccine in time for the next flu season.

But now, as all of you know, the pesky pathogen has performed a new sort of quick change trick. This latest viral transformation apparently occurred in the pig farms of Mexico, and the resultant strain strings together genetic material from human, swine, and avian sources into a novel hybrid to which none of us are immune. This 'swine flu' has produced serious illness in its country of origin, and now the whole world watches in nervous anticipation as it continues its spread.

Let's get the good news out right up front. First of all, flu is seasonal, and the season here is nearly over. While this new strain of flu may resurface next winter, its current run could well be brief. And scientists will have time to develop an effective vaccine before its next world tour. Secondly, the cases thus far identified in the US and abroad have generally been mild and self-limited.

And finally, this swine flu is sensitive to two standard anti-virals--Tamiflu and Relenza. Remember, however, that not only can influenza pull off genetic mixology to produce an entire new strain, it also can acquire the genes for immunity to these drugs. If enough of us twitch and take Tamiflu at the first sign of any viral illness, be it flu, croup, or the common cold, this acquired resistance will be a sure thing. So don't call your doctor for a 'just in case' prescription; Adele and I will say "NO!"

The flu is highly contagious; it's effectively spread by tiny respiratory droplets which remain suspended in air and settled on surfaces for some time after an unrestrained sneeze or cough. Good prevention practices include:

• Cough or sneeze into your sleeve. Using your hands or a tissue to contain your explosion just makes more objects infectious.
• Better yet, stay home with your secretions when ill, and don't expect affected employees or co-workers to crawl on in to work when they are unwell.
• Wash your hands frequently, and don't touch your face or handle food after touching shared surfaces until you've washed up.
• Practice good health habits to enhance your overall immunity and resistance.
• Ask your doctor to check your vitamin D levels, and then discuss supplements with her/him to bring yours up to the ideal range. Influenza is increasingly considered a vitamin D deficiency disease!

For an amusing look at keeping your mucous to yourself, check out this video.

Of linens and proteins...*

And stressful situations in closets and cells.

I've mentioned before that I suffer a weensy bit from disposophobia or the inability to part ways with stuff. Old towels are no exception. My linen closet bulged (past tense due to recent reform efforts) with tattered towels and sheets too short for current mattresses. As I dug deeper in search of bath accessories with the most residual fluff, the rifled remaining towels took up more and more space, threatening the hinges on the closet doors. I desperately needed an unfolded towel response (UTR).

Enter the towel-like equivalent of body clutter, namely unfolded proteins. Not only do your cells need to string the appropriate sequence of amino acids together to form proteins, but they also must pull a little proteinaceous origami trick to get them into the right spatial configuration for proper functioning. Unfolded proteins are the bane of an aging cell's existence--witness all that rumpled beta-amyloid protein that gums up old neurons in Alzheimer's disease.

Hurrah for evolution! Enter the unfolded protein response (UPR), nature's way of sensing a haphazard pile of proteins on the cellular floor. And if the UPR can't straighten up the protein closet--wadded proteins stacking ever higher--then the UPR just makes some sort of nasty enzyme that explodes that cell and its proteiny mess right then and there.

Alas, as Dr. Dale Bredesen of the Buck Institute for Age Research points out, the UPR is no different than a lot of other body responses to dysequilibrium: "The initial response is protective, but the late response is destructive." He and other neurobiologists are hoping to unlock the secrets of UPR in order to keep this organizing principle on our side.
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*Check out Menopause Moments for a review of a book with one theory how misfolded proteins may be the infectious basis for Alzheimer's Disease.

"The Power of Two"

After my mother's craniotomy for a subdural hematoma several years ago, she made rapid progress and was transferred to the rehab unit. Unfortunately, shortly after playing several hands of bridge with visiting friends, she developed a fever and chills and was diagnosed with c. diff sepsis.

The hospitalist came right over, started IV fluids and antibiotics, and breezed on out. My friend Brenda, the unit's only RN, and I looked at one another.

"Are you okay with her staying here?" I asked.

"It's just me and 20 patients," she replied. "I don't think I have time to give her the care that she'll need."

Fortunately, I caught up with the doctor, and he agreed to transfer Mom to the ICU. A good thing too as bacterial sepsis is not a rehab floor matter. I wondered what would've happened if I hadn't been there at the time. And I wondered that again several days later when the specialist missed the fact that Mom was going in and out of atrial fibrillation on the ICU monitor. And I marveled how anyone survives a hospitalization without an advocate on hand.

We are fortunate, therefore, that Brian and Gerri Monaghan have written a moving account of their own journey through life-threatening illness and advocacy, "The Power of Two". Not only is this book a compelling, entertaining, and (at times) tear-jerking account of love and loyalty in sickness and in health, it is a step-by-step, tip-by-tip, how-to manual for all of us who will face a serious illness or care for someone in that situation. And, through my life roles as doctor, wife, daughter, mother, and friend, I can tell you that will absolutely be all of us.

I'd like to say that I'm going to keep this book on my shelf for my next advocacy adventure, but I plan to give it away to a friend who was diagnosed last week with cancer. With the Monaghans on their team, and this guidebook in hand, she and her family will be able to stand up and advocate for what they need.

In praise of Dr. Anthony Laporta

My friend/patient did not look well. She came in on Friday of last week looking gray and tearful, still battling the abdominal pain that she'd called me about the previous week. Not only was she 7 pounds lighter than her usual weight, she had scary lymph nodes on the side of her neck.

One of those moments when I puzzle over what to do with my face as I launch into Dr. Scheduler, working to get her a CT scan and an appointment with a general surgeon for a biopsy. All ASAP! Within two hours, both appointments were made for the beginning of this week.

So here it is Tuesday p.m., and I've just gotten off the phone with Dr. Anthony Laporta whom I've never met and never spoken to before yesterday. My friend and I agree that this fellow is the best. He was on his cell phone, the sounds of his son's lacrosse game in the background. He had the the CT results to me within 2 hours of the Monday's scan. Post-op, per him: "I walked down to the lab to have a look at the slides from the biopsy." No unnecessary waiting for my pal--"My goal," per Laporta, "is to get things done as quickly as possible to minimize the time spent worrying about the unknown."

So tomorrow a.m., she will see the oncologist--on her way to an action plan within five days of her first appointment! I recommend Dr. Laporta with pleasure to all those facing the scary prospect of surgery.

Fretful and friendless raises risk of dementia

Just untangling the conclusions of this Swedish study was a brain workout in its own right, a downright 'how much wood would a woodchuck chuck..." sort of puzzle:

Neither high neuroticism nor low extraversion alone was related to significantly higher incidence of dementia. However, among people with an inactive or socially isolated lifestyle, low neuroticism was associated with a decreased dementia risk (hazard ratio [HR] = 0.51, 95% confidence interval [CI] = 0.27-0.96). When compared to persons with high neuroticism and high extraversion, a decreased risk of dementia was detected in individuals with low neuroticism and high extraversion (HR = 0.51, 95% CI = 0.28-0.94), but not among persons with low neuroticism and low extraversion (HR = 0.95, 95% CI = 0.57-1.60), nor high neuroticism and low extraversion (HR = 0.97 95% CI = 0.57-1.65).(1)

Got it? So do we fret and socialize, stay home and calmly knit, or placidly go out drinking with our buddies? Don't freak out while you discuss this conundrum with your friends because, as you will see once you sort out the various possibilities here, being a Buddha of a buddy is your best bet for the brightest brain.
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Wang, HX, et al. Personality and lifestyle in relation to dementia incidence. Neurology. 2009 Jan 20;72(3):253-9.

Flector patch--the first NSAID patch for pain

So what does a NSAID patch have to do with this piece of exercise equipment? Let me explain.

It's called a Trikke (as in trike for grown-ups). You use all your balance and leg strength to power this in a skating sort of fashion. Is this the appropriate gizmo for a middle-aged female? No, no, not me, I wouldn't be caught dead on this thing--probably would be dead if I tried. My intrepid medical partner Adele, however, has been seen 'skating' on a Trikke down Montview Blvd. here in Denver, and one day she met the pavement beside her trike, her hamstring muscle ripped from its pelvic attachment.* She healed to skate (and ride, and do Pilates, and lift weights again), but the scarred muscle is not as flexible as it used to be which in turn puts stress on her pyriformis muscle.

So last week she was running from exam room to exam room working her healing magic while occasionally clutching her piriformis muscle which was in spasm whilst whining softly with pain (check out where the pyriformis muscle is and you'll know what she was grabbing). The King Pharmaceuticals rep coincidentally showed up with info and samples of the Flector patch.

A word or two about diclofenac, the active ingredient in this medicated patch indicated for topical use for pain control of acute injuries such as strains, sprains, and contusions. Diclofenac, formerly known as Voltaren, is a dandy non-steroidal anti-inflammatory (NSAID) which reaches high concentrations in joint spaces. It's generic, cheap, works well, AND causes stomach inflammation with bleeding, possible liver toxicity, and can reduce blood flow to kidneys, particularly aging kidneys.

So, Novartis developed Voltaren Gel to smear on arthritic joints; used regularly it significantly decreases pain without bothering the stomach, the liver, or the kidneys. And now King Pharmaceuticals brings us diclofenac in patch form with very little systemic absorption--also safer for use particularly in older souls with acid gastritis and aging vascular systems.

Adele, being the sort of sport that she is and really distressed by her pain in the butt, slapped a patch on the offending area. Perhaps this was not the best Flector patch trial as it became quite wrinkled given the anatomy of the area and the wearer reported it was a little like having an ongoing wedgie. Nevertheless, Flector is a good idea (but a really stupid name) and I look forward to handing them out to persons with sprained ankles, shoulders, or back to see how they fare.
_____
*My bro' Reality Man uses one too, but so far he's remained upright in his exercise endeavors.

How do crossword puzzles help my brain?

Check it out at Menopause Moments.

YogaToes revisited

I've mentioned before that this product has relieved most of my foot pain coming from falling arches and mid-foot impingement syndrome (along with arch supports in the shoes). Just noticed a coupon code in Health Magazine for $15 off--go to YogaToes.com and enter coupon code H3X9.

Can NSAIDs prevent Alzheimer's Disease?

Alzheimer's disease (AD) gums up the brainworks with tangled neurons and protein plaques. Much of the damage occurs, however, as a result of an inflammatory response to these changes. Scientists theorized that the regular use of anti-inflammatory drugs such as Advil, naproxen, or Celebrex (also known as non-steroidal inflammatory drugs or NSAIDs) could slow down or prevent this degenerative disease.

The Alzheimer's Disease Anti-inflammatory Prevention Trial(1) enrolled over 2,000 seniors aged 70 years and older and followed them through 7 years of life correlating the use of NSAIDs (naproxen 220 mg. twice daily, Celebrex 200 mg. twice daily, or a look-alike placebo with no anti-inflammatory properties at all). All participants had a family history of AD and were thus considered to be at increased risk for developing the disease.

Made no difference what the septuagenerarian subjects took--naproxen, Celebrex, or no drug at all--with respect to their subsequent tendency to drift towards dementia. In fact, there was 'weak evidence' for a detrimental effect of naproxen.

The problem, however, is that this really wasn't a preventive trial at all. By the time old folks enter their eighth decade, they may well already be on the road to AD. Chemopreventive studies--i.e. those research trials seeking substances that actually protect against the development of AD through a neuroprotective substance-- would need to be undertaken on younger subjects over a longer period of study, an approach that is prohibitively expensive. The studies that suggest that NSAIDs are indeed useful in AD prevention are largely observational and/or retrospective; large populations are quizzed as to their health habits and medication usage, and these reports are correlated with present or future health outcomes. And if you've ever quizzed an old person about their drug use now and in the past, you may well wonder as do I how accurate those self-reports really are.

While the jury's still out as to whether NSAIDs are useful against AD, there is evidence that they may lower the incidence of cancer, and they certainly are good for pain. On the other hand, a recent study(2) showed a strong link between their use in patients also on anti-depressants such as Prozac or Lexapro (aka SSRIs) and gastrointestinal bleeding. Those on this pharmaceutical duet were 4.8 times more likely to bleed from their upper GI tract.
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1. ADAPT Research Group. Cognitive Function Over Time in the ADAPT: Results of a Randomized, Controlled Trial of Naproxen and Celecoxib. Arch of Neur. 2008;65(7): 896-905.
2. deAbajo FJ, et al. Risk of upper GI tract bleeding associated with SSRI and Venlafaxine therapy: Interaction with NSAIDs and effect of Acid-suppressing agents. Arch of General Psychiatry. 2008;65(7):795-803.

Kefir and breast cancer

(thanks to Dr. Jacob Schor once again for bringing yet another health topic to my attention; check out his web-site at denvernaturopathic.com to subscribe to his newsletter)

Human beings have a self-preservation mechanism in the gag reflex; when something unexpectedly unpleasant in taste or texture hits the mouth, the entire upper digestive system reacts quickly and violently to eject to the offender. The first time I learned about this survival mechanism, I had just taken a large mouthful of buttermilk with my childhood friend Jean's encouragement. She raved about how tasty it was when, in fact, it was vile. I laughed hard and gagged simultaneously, sending the buttermilk through my nose.

Decades later, I accepted a small jar of homemade kefir from my patient V who took a bottle of the worthy stuff to work every day along with a container of home-cooked stew. As she is absolutely one of the healthiest people I know and care for, I was eager to start a kefir habit of my own. But oh heavens, it's surprisingly tart and foul, worse than buttermilk, and I spit the stuff out. New research suggests, however, that it may be the latest and greatest chemopreventive agent against breast cancer. Maybe chocolate syrup can enhance the taste. Check this out:

Canadian nutritionists cultured human breast cells--both cancerous and not-- in the lab, then fed the little colonies extracts of kefir, yogurt, and plain old pasteurized milk in various concentrations and checked out who thrived and who died(1). Kefir depressed tumor cell growth in a dose dependent fashion--the more kefir present, the fewer the cells. A .63% kefir extract dose (now perhaps even I could handle that) decreased tumor cell numbers by 29% and the 2.5% formula felled those cancerous bad girls to 56% their pre-kefir numbers. The yogurt also suppressed tumor growth, but less vigorously than the kefir. And the milk stimulated both lines of breast cells--normal and malignant--at concentrations as low as .31%!

Do I want to wait for more info, more studies? I think not. I'm calling V tomorrow for her kefir recipe. After all, if I fully expect it to taste sour and slightly carbonated, I can overcome the urge to cough it out through my nose.
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(1) Chen, C et al. Kefir extracts suppress in vitro proliferation of estrogen-dependent human breast cancer cells but not normal mammary epithelial cells. J Med Food. 2007 Sep;10(3):416-22.

Updated colon cancer screening guidelines

When I was an intern, we had a standard 'scut list' of tasks that no one loves but only an intern (or medical student if you were lucky enough to have one around) would do. Every admission, no matter what time they rolled through the ER door, needed a complete work-up by the time morning rounds began, and that work-up included a gram stain of that which they were coughing up if coughing was one of their presenting symptoms. This involved getting a phlegmy sample, teasing out spit from the real deal gunk within, then spreading the mess on a slide and processing it appropriately. Needless to say, it was gross.

What does that have to do with colon cancer screening? Well it's to let you know that I'm okay with digital rectal exams and testing stool samples thus obtained for blood because it's a walk in the park compared to the above. Nevertheless, I welcome the latest screening guidelines(1) from the United States Preventive Services Task Force (USPSTF) that do not include rectal finger probes for those brave souls who get their every 10-year colonoscopy exams.

Colonoscopies are the best cancer screening tests we have with respect to cancers ducked (as pre-cancerous polyps are removed) or cured (tiny cancers found before they spread). That said, they're expensive, time intensive, and not without rare but serious complications. Someday we'll have a better way, but meanwhile they are still on the A list for those over 50 at average risk. On the other hand, the USPSTF says that colon CT scans are not yet ready for prime time screening purposes. More info needed, they declared, to support its routine use because thus far, this easier and less expensive scanning technique produces too many 'false positives' (looks like a polyp but not a polyp just a hunk'a stool clinging to the colon wall).

For those who cannot stomach (or perhaps cannot colon) the thought of a colonoscopy, or just plain can't afford it, the panel supports yearly high-sensitivity fecal occult blood testing (FOBT) or every 5 year sigmoidoscopy with FOBT in between. Used to be that FOBT was about equivalent creepy to sputum gram smears--requiring that the testy testee fish around in the toilet water for their 'specimen,' then to use a junior-sized popsicle stick to apply it a little card, do this three days in a row, then mail the cards off to the MD office where a testy assistant had to open the crusty old card and test it for blood. Now, the MD or patient takes darling little grooved stick from a teensy tube, gently rubs it in the residual stool on the exam glove finger or a used piece of toilet paper (if doing test at home), and reinserts stick in tube. Testing is then carried out with a treated paper strip and no further person/fecal interaction is required.

Alright, that is a wee bit gross as well, but all this colon cancer seeking is important stuff for persons of age.
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1) Preventive Medicine 2009: The Annual Meeting of the American College of Preventive Medicine (ACPM). Session 30. Presented February 13, 2009.

Breast cancer and hormone therapy

I believe that the most important influences driving our medical decision making process are our personal beliefs, both our worst fears and our fondest hopes. These belief systems are powered by our own medical histories, those of our family, the things that we read, and our personal experience. Sometimes my exam room is crowded to overflowing as Suzanne Somers argues with Dr. Susan Love in the corner as Dr. Andrew Weil tries to get a word in edgewise. Meanwhile my patient's mother and her best friend's cousin are lurking just behind her clamoring to add their opinions on the magazine articles spread out on the desk in front of us.

I would be foolish to discount these many voices; if they're important to my patient, they need to be a part of our discussion. I like to think my worst fears are highly informed ones, yet I am highly influenced by my family history of dementia and completely freaked out by the latest news on breast cancer and HRT in the latest issue of the NEJM(1). Here's the scoop:

The Women's Health Initiative randomized over 16,000 women to receive either combined postmenopausal hormone replacement therapy (Premarin plus Provera) or a look-alike placebo, then followed each group with regard to health outcomes, particularly the incidence of cardiovascular disease and breast cancer. The trial was abruptly halted in the summer of 2002 (what menopausal internist can forget that?) when it was clear that harm outweighed benefit with respect to heart attack, stroke, and breast cancer risk.

The study has come under attack for applying data obtained from a somewhat older group of women (average age 63) many of whom were overweight, hypertensive, diabetic, and smokers to a younger group of women just entering menopause and looking to improving their quality of life with HRT. Several studies, both trials concluded and some still underway suggest that, in fact, this latter group of 50-somethings may actually receive cardiovascular protection from the use of hormones particularly so-called bioidentical estrogen delivered in a non-oral fashion (such as via a skin patch).

I'm good with all that but note please that cardiovascular disease is not high on my to-worry list although I certainly recognize that many of my patients are at risk for same. And as losing my marbles is number one on my future frets, and estrogen is a top neuroprotective agent for aging female brains, I'm choosing to motor on with my HRT choices.

When the WHI data came out, some drug company or other provided me with graphics on this breast cancer thing. One thousand little grey female stick figures were lined up on the top of the page three of whom were colored orange. These unfortunate orange ladies were the number per year of new breast cancer victims in 1,000 post-menopausal ladies not on hormones. At the bottom of the page, another 1,000 skirted sticks queued up, 996 clad in grey and 4 in blue. You've got it: the blues were new cases of breast cancer per year in 1,000 post-menopausal hormone users. The absolute risk was huge; a 33% increase in breast cancer amongst hormone users but the relative risk small, namely one additional breast cancer per thousand users.

BUT...consider that 4th blue lady, her life turned upside down with biopsies, chemo, radiation, and a world of worry even though her chances of actually dying from that cancer are small. And if your worst fear is that cancer-induced world upheaval, then you will choose to discontinue therapy or never start it in the first place.

And now the doctors of the WHI bring us this new news to add to the evidence behind our worst fears, namely that the incidence of breast cancer which nearly doubled in the hormone users over the 5.6 years of the study decreased rapidly in the two years after the study coinciding with a marked drop in the use of combined hormones by the subjects. The busy slide at the top of this post illustrates this in the upsloping solid red line on the left which represents cancer incidence during the study and the soothing downward solid blue line on the right as fewer women got the bad news in the 2 years following the study's end. The black and white graph that follows is the interesting and contrasting data from a Scottish study that also notes the drop in hormone use over a similar time frame (the two plunging lines) but the more or less straight line at the top shows that Scottish women did not experience the drop in breast cancer rate with falling use of HRT.

Argh, what's an aging woman on hormones or contemplating their use to think? Estrogen is a growth-stimulating hormone, and thanks for the boost when it comes to bone, muscle, connective tissue, skin, vaginas, and brain. I love my brain power, I worry often about dementia, and I don't mind the youngish looking skin, so here's to hormones! But, breasts that aren't prepping to feed a developing babe don't like to be stimulated, and the more you goose your breast cells years after pregnancy is nothing but a distant memory, the more likely you are to stimulate a cancer. I don't want cancer, no not one bit, I know one woman who got cancer within 1 1/2 years of starting HRT, so to heck with hormones!

Well, Ms. Suzanne Somers staring out the cover of "The Sexy Years" like you just rolled out of a bed in which you were not alone, what is easy about this decision? Absolutely nothing. Per Dr. Morris Notelovitz, a venerable old menopausal researcher, every year a woman and her doctor should review her hormone therapy decision (and every other medical decision she makes per me!). If she is using HRT, why? If she is not using HRT, why not? What are the experts and your secretary's aunt saying? What do you believe is best for yourself?
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(1)Cheblowski, RT et al. Breast Cancer after Use of Estrogen plus Progestin in Postmenopausal Women. NEJM. Volume 360:573-587 Feb. 5, 2009.

Pilates, back pain, and Denver's old spines

I see a lot of older women going to ground--their spines telescoping downward and often acquiring notable, painful curves in the journey south. Unfortunately, got one of those backbones myself. I've tried a lot of things to shore it up but none more useful than my lessons with Dana Dreifus, a wonderful Pilates instructor in central Denver. She has an incredible intuition for that which you need to balance and strengthen, and she's quick with adjustments to the standard postures in order to accomodate your ability and level of fitness.

But you don't have to be old and degenerating to enjoy Dana's careful attentions and enthusiasm. If you're new to Pilates or wish ongoing instruction, you could not do better than to call her at: 720-936-3667.

L-carnitine for your hair

Those of you who follow my Menopause Moments blog might already be taking this stuff to boost your brain. So here's good news from TheDermBlog.com that this supplement may stimulate hair growth.

Hair follicles go through cycles wherein hair grows (anagen) and then falls out (telogen). Hair aging badly becomes thinner, finer, and more colorless with each cycle. Progesterone promotes glorious hair (think hair during pregnancy) and precipitous drops in this hormone cause hair loss (think hair after pregnancy or during menopause). Testosterone causes hair loss in a characteristic pattern (those thinning temples and shiny pink crowns of aging men and some women). Minoxidil or Rogaine improves circulation to hair follicles and sort of helps men and women hold onto their hair. So what does l-carnitine do?

When hair follicles were cultured in the lab (if they can grow 'em in a dish, why can't they grow 'em on our heads?) in the presence of l-carnitine, researchers at the University of Hamburg observed several positive things: the growth phase lasted longer, fewer hair matrix cells keeled over dead, and more matrix cells proliferated. At a molecular level, less TGFbeta2 factor, less TGF-beta II receptor protein, and falling levels of caspase 3 and 7 confirmed a more-growth-less-death environment for the hairy little cell community(1).

The German dermatologists summed it up thus: "l-carnitine, a frequently employed dietary supplement, may stimulate hair growth by increasing energy supply to the massively proliferating and energy-consuming anagen hair matrix." Whoa, I would like to use "massively proliferating" and "my hair" in the same sentence. How do you say "Please don't hate me because I have beautiful hair" in German?
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1. Foitzik, K et al. L-carnitine-L-tartrate promotes human hair growth in vitro. Exp Dermatol. 2007 Nov;16(11):936-45.

Moxxor

From an e-mail I received this week:
I was wondering your thoughts on Moxxor. I pasted below an email I got from a friend who is helping promote it. Please let me know your thoughts.

Oh dear, another product about which I know nothing but upon which I am asked an opinion. The standard dilemma--do I write back and say "This is Dr. Paley's secretary. Thank you for your query but unfortunately the doctor is unable to answer individual e-mails." Or do I look it up and give it my best guess. Well that's what I did.

Moxxor is a supplement made of oil d'green-lipped mussels. The thought of eating bi-valves always brings to my mind "The Walrus and The Carpenter" poem from Alice in Wonderland; the first poem I ever memorized (one of three lifetime poems by rote for me) wherein a walrus and carpenter entice little oysters to scurry from their beds for a walk along the beach and ultimately eat them all(2).

Back to Moxxor, just letting you know I'm a little uncomfortable right up front with its origins. I am, however, very pro-omega-3-fatty acids, and Moxxor's green-lipped mussel variety is, per glowing Internet reports, a particularly fine one. GLM-omega-3's are purported to have potent anti-inflammatory properties. One fellow who actually met the guy who developed Moxxor (a toothy, widely grinning fisherman from New Zealand) took his first dose, worked out like mad at the gym that afternoon, then woke up the next day pain-free from his exercise session.

Now if you can wait long enough for the graphics to load (which I did not), mymoxxor.com tells you how you can become an independent distributor of the stuff. Right there that's enough to make me want to write back to this lady about what a silly scam it all is--just buy the 3 for 1 omega-3's at puritan.com. But I looked in on PubMed.gov and learned a thing or two about the health benefits of GLM's.

UK Scientists did a meta-analysis of studies treating osteoarthritis with GLM(1). They concluded "The data... suggests that GLM may be superior to placebo for the treatment of mild to moderate OA. As a credible biological mechanism exists for this treatment, further rigorous investigations are required to assess efficacy and optimal dosage." The credible mechanism is provided by numerous studies that show that GLM's have unique poly-unsaturated fatty acids with significant anti-inflammatory activity.

Whoa, I'm down for that; I've got a finger, two thumbs, a knee, and a foot in serious need for significant anti-inflammatory activity. Maybe I could become a Moxxor dealer and get out of primary care. I'll let you know if I ever get past the graphics delay and my bi-valve aversion to actually order this stuff.
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(1) Brien, S, et al. Systematic review of the nutritional supplement Perna Canaliculus (green-lipped mussel) in the treatment of osteoarthritis. QJM 2008 Mar;101(3):167-79.

(2) Here's the part that's put me off my Oysters Rockefeller:

*'But wait a bit,' the Oysters cried,
'Before we have our chat;
For some of us are out of breath,
And all of us are fat!'
'No hurry!' said the Carpenter.
They thanked him much for that.

'A loaf of bread,' the Walrus said,
'Is what we chiefly need:
Pepper and vinegar besides
Are very good indeed --
Now, if you're ready, Oysters dear,
We can begin to feed.'

'But not on us!' the Oysters cried,
Turning a little blue.
'After such kindness, that would be
A dismal thing to do!'
'The night is fine,' the Walrus said,
'Do you admire the view?'

'It was so kind of you to come!
And you are very nice!'
The Carpenter said nothing but
'Cut us another slice-
I wish you were not quite so deaf-
I've had to ask you twice!'

'It seems a shame,' the Walrus said,
'To play them such a trick.
After we've brought them out so far,
And made them trot so quick!'
The Carpenter said nothing but
'The butter's spread too thick!'

'I weep for you,'the Walrus said:
'I deeply sympathize.'
With sobs and tears he sorted out
Those of the largest size,
Holding his pocket-handkerchief
Before his streaming eyes.

'O Oysters,' said the Carpenter,
'You've had a pleasant run!
Shall we be trotting home again?'
But answer came there none --
And this was scarcely odd, because
They'd eaten every one.

Pedometer-based walking intervention

I love these names--if I recommend pedometers, and I do, then I am conducting pedometer-based walking interventions. Visions of two wild-eyed pedometer experts swooping unannounced into your workplace, grabbing you one arm apiece, and carrying you out to the parking lot where they install a pedometer on your waistband and drag you screaming, half-walking/half-kicking around the parking lot until you hit 10,000 steps.

Anyway, scientists from the Dept. of Family Medicine conducted a meta-analysis of PBWI's which means that they not only searched six electronic databases for weight loss outcomes in nine different studies that compared the pedometered with the pedometerless to see who lost the most weight, but they also contacted real-life pedometer experts just in from field interventions to interpret the results. Their conclusion?

Pedometer-based walking programs result in a modest amount of weight loss. Longer programs lead to more weight loss than shorter programs.

I trust the experts were pleased.

Statins and infection control

I have any number of patients who take statin drugs(1) to lower their cholesterol levels in order to reduce their risk of unwanted cardiovascular outcomes such as stroke or heart attack. I would prefer, in an ideal world, that these patients control their risk factors with healthy habits in diet, exercise, and weight control, but, alas, this is not a perfect world but rather one in which many lack time, will-power, and resources to make these changes in a timely fashion.

In addition to their ability to reduce cholesterol production and increase LDL clearance by the liver, these drugs are known to reduce inflammation in the body. Inflammation is a good thing as a first responder to infection or injury, but inflammation gone amok is part of the pathological process that increases tissue destruction in Alzheimer's disease, athersclerosis (hardening of the arteries), cancer, arthritis, and severe infections.

Danish and American researchers theorized that the anti-inflammatory effects of statins could improve outcomes for patients admitted to the hospital for pneumonia; those persons protected from over-exuberant inflammation by statins might be more likely to walk out of the hospital rather than being rolled out through a basement door on a gurney. They examined the hospital records for nearly 30,000 patients over 7 years looking for pre-admission statin use as correlated with the risk of sepsis and death associated with serious pulmonary infections. Indeed, those patients currently on statins had a 31% better chance of being alive 90 days after their pneumonia diagnosis compared with those in a statin-less state.

Wondering why? Dr. Kasturi Haldar of the Center for Rare and Neglected Diseases (I kid you not) informs us in an editorial in the same Archives issue that it's all about G proteins. Statins block the isoprenylation (whatever that is) of small G proteins. This decreased prenylation business protects against Alzheimer's disease because the beta-amyloid guck that gums of the brainworks in the disease depends on the breakdown of amyloid precursor protein, a process which in turn counts on prenylated G proteins.

In infections, little G proteins increase the inflammatory response which can fill the patient's airway with fluids and white cells instead of the air upon which we depend. G proteins might also promote the bacteria's ability to enter cells and prosper therein. As in Alzheimer's, as statins decrease the prenyl pool upon which G protein function depends, the decreased inflammatory response may reduce the inflammatory response.

So if you are ever called upon to weigh the decision of statins or not in your future health care plan, consider this side benefit of the use of these drugs.
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(1)Lipitor, Crestor, simvastatin, lovastatin, fluvastatin
(2) Thomsen, RW, et al. Preadmission Use of Statins and Outcomes After Hospitalization With Pneumonia. Arch Int Med Vol 168 (No.19), Oct. 27, 2008.

Skinceuticals C E Ferulic

So what's Arlen Specter doing on my blog? Well, he's got those pouchy things going on on either side of his mouth. And that's my newest obsession--my little pouchy things where acne scars are coalescing with wrinkles. I googled Arlen Specterish pouchoid look and found TheDermBlog.com Well, actually not, I don't exactly remember what I googled but it was some combination of Vitamin C serum and aging skin. Topical vitamin C is known to stimulate collagen production, and collagen is the fibrous tissue that keeps your cheeks off your chin and your chin off your collar. And Dr. Benabio's excellent blog noted that this fern-derived antioxidant called ferulic, when combined with topical C, stablizes the latter and allows it to penetrate better into damaged skin. And he said someday soon, topical C plus ferulic would be available.

I am computer woman, see me google. Off to vitamin C AND ferulic arriving at Skinceuticals C E Ferulic Sample Size . What the heck, thinks I, it was on sale in December, so for $25, why not?

Fast forward to three weeks later, a patient told me today my skin looked great. "Good color," she said, "You look healthy!" Need I say more?

September, 2009 update: Still using CE Ferulic. A little goes a long way--one tiny sample body supplies nightly face application for over a month. Skin looking so good that my 20-something year old daughter noticed it and took one of my bottles for herself! Get your own CE Ferulic my dear!

Fat or not, the fit live longest!

I mentioned in my previous post that exercise promotes immunity, just one more reason to dance as if your life depends on it. Exercise scientists set out to study the association between cardiorespiratory fitness, extra weight, and the predisposition to keel over dead in older adults. They enrolled 2600+ adults aged 60 or older in the Aerobics Center Longitudinal Study, poked, prodded, measured, and then watched their subjects' survival stats over 22 years. Here's what they found:

In conclusion, in this prospective study of adults 60 years or older, low fitness predicted higher risk of all-cause mortality after adjustment for potential confounding factors, including adiposity. Fit individuals had greater longevity than unfit individuals, regardless of their body composition or fat distribution...It may be possible to reduce all-cause death rates among older adults, including those who are obese, by promoting regular physical activity, such as brisk walking for 30 minutes or more on most days of the week which will keep most individuals out of the low-fitness category(1).

So here's what I hear: "I'm so discouraged. I've been working out for a month now and I haven't lost any weight." A couple of points: 1) Working out at the rate of 20 minutes on a treadmill 3 days per week is insufficient to promote fitness or weight loss, though theoretically it's better than nothing at all, and 2) If you are on the road to fitness with sufficient cardiovascular workouts, you are promoting good long-term health--and survival--whether or not you lose weight. All-cause mortality is just that, death from any cause whether it be heart attack, stroke, cancer, or sepsis from an overwhelming infection with some nasty, multi-drug resistant bacteria.

What's on your New Year's resolution agenda?
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(1) Sui, X, et al. Cardiorespiratory fitness and adiposity as mortality predictors in older adults. JAMA 2007 Dec 5;298(21):2507-16.