Will walk for feedback

I ask all my patients about their personal exercise routines. They often answer that while they do no exercise, they are "extremely active" all day at work. I encourage them to wear pedometers in order to gauge just how active they are. One dismayed lady tried it out, then wailed in a follow-up email "There are only three steps between my desk and the file cabinet!". Not such a whirlwind at work after all.

Researchers in New Zealand decided to see if sedentary seniors could be persuaded to move more if equipped with encouragement and a pedometer(1). One group of geezers (geezettes too!) were given step-counting gadgets along with exercise counseling and follow-up phone calls to set ever greater step-counting goals. A control group were counseled and called but were not issued any freebie pedometers.

At the end of a year, both groups had significantly increased their leisure walking, proving that mere encouragement and phone calls are useful interventions. The pedometered seniors, however, doubled their extra walk-time compared with the unmetered oldsters. Blood pressures dropped in both groups. No surprise--this step-counting strategy works in middle-aged ladies as well(2).

I've been through multiple pedometers in multiple years. I've lost more than a few--in a cab, a nail salon, into the toilet. I've tossed out several due to inaccuracy; so sensitive to motion, they registered any shift of position. I currently wear a Fitbit designed to remain true to step count even if stuffed in a pocket. It also has a flower that gains more leaves the more active you are.

If the Fitbit is too pricey for you, I encourage you to invest in a mid-range device. The Yamax SW701 Digi-Walker Pedometer has been trial-tested for accuracy.

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1) Kolt, GS et al. Healthy Steps Trial: Pedometer-Based Advice and Physical Activity for Low-Active Older Adults. Ann Fam Med May/June 2012 vol. 10 no. 3 206-212.

2) Hultquist CN, Albright C, Thompson DL. Comparison of walking recommendations in previously inactive women. Med Sci Sports Exerc. 2005;37(4):676–683.

Of Dreams and Dendritic Cells

"His dream was to use his discovery to cure cancer and infectious diseases like HIV and tuberculosis. It's a dream that's pretty close." Michel Nussenzweig on his fellow researcher Ralph Steinman.

When my mom was newly diagnosed with lung cancer, I brought her a bunch of "Conan the Barbarian" balloons with an encouraging note calling on her immune cell to rally to the job of eliminating the cancer (which she ultimately bested, living on another 18 years!). At the time, however, she was less than amused and huffily informed me that "There is nothing wrong with my white cells."

Immunotherapy, wherein a patient's own immune cells are primed to attack their invasive cancer, is a rapidly advancing area of cancer research. Due to a wide array of ploys with which cancer cells hide from the immune system coupled with various host deficiencies in mounting the appropriate defense, cancer therapy has for years centered instead on chemotherapy. These toxic chemicals are designed to be more lethal to the rapidly dividing cancer cells than on normal tissue. Unfortunately, normal often falls along with the malignant.

One of the giants among researchers in immunotherapy is Ralph Steinman who ironically died September 30th, three days before winning the Nobel Prize in medicine earlier this week. In a further twist of fate, he died of pancreatic cancer, living much longer than most unfortunate souls with this disease perhaps because he applied his own discovery to his personal case.

Dr. Steinman's contribution to this important research was the identification of a unique little player in the immune cascade that he dubbed a dendritic cell due to its tree-like branching configuration reminescent of the dendrites of neurons. The dendritic cell is one of the initial workhorses of the immune system, processing foreign material such as viruses and then presenting it to T cells which are activated in turn to attack the unwelcome invaders.

Dr. Steinman isolated his dendritic cells, exposed them to his pancreatic cancer cells, and thus instructed his T cells to recognize those bad boys as unwanted visitors. A former student, now a collaborator, had this to say, "We'll never know [whether it worked] ...but one thing is for sure: he was able to make T-cells specific for his cancer. It obviously didn't cure him, but it may have prolonged his life."

Walking across Virginia

Wondering where I've been? Well, busy for one, very busy. For those of you who didn't get the mailing, we've moved our office. From our vintage little office building that was originally built by my pediatricians in 1949 to sleek revamped office digs on the old Children's Hospital medical campus. If you can get through on the phones and find the darned office (still a few glitches to work out!), I think you'll be pleased to see that Adele and I are business as usual under the auspices of Exempla Healthcare here in Denver.

In my spare time, however, I've been walking across Virginia. Well not really walking across Virginia which would doubtless be even hotter than Denver and logistically problematic. I'm talking traversing in a virtual sense. I urge my patients to find an exercise activity that engages their interest as well as their heart. Used to be Jazzercise for me, step aerobics too, but that was years and a lot of knee cartilage ago. Walking with a dog is a personal joy, but I've got no pooch on-site with whom to mosey. So instead, I'm walking solo across the United States with an eye on the West Coast by 2020.

Wanna' come along? Check out the TransAmerica Trail (aka Tools to keep you active) at http://exercise.lbl.gov/index.html. Sign me up as your partner--they'll put you on my map and me on yours at the same starting point. I'm walker number 65471 about to enter Kentucky but happy to join you back on the Virginia coast.

Sesame oil may be some kind of cure-all!

This just in from my favorite naturopath, Dr. Jacob Schor. This news is particularly important for persons who are hypertensive, have high cholesterol, are diabetic, carry weight around their middle, or travel that overweight road to all of the above.

According to an article penned by Dr. Schor in the current issue of Natural Medicine Journal (1), just a spoonful of sesame oil (actually 2.4 tablespoonfuls/day) makes the blood pressure/cholesterol levels/blood sugar/waistline go down. He cites results from a group of scientists from India's Vinayaka Missions University about the remarkable results of daily sesame oil use in a group of 60 diabetics followed over 2 months. One third downed oil alone, one third used oil plus a diabetic medication called glyburide, and the remaining subjects took glyburide alone.

While those on drugs plus oil did best of all, the oil-alone group fared fairly well as well. The glucose-lowering effects of combo therapy were downright remarkable with blood sugar dropping by 36% and HbA1c (a value that reflects an averaged blood sugar over the prior three months) by 43%! All oil-users also had significant drops in total cholesterol, LDL-cholesterol, and triglycerides plus a bonus rise in HDL-cholesterol.

The Vinayaka group conducted a similar study on locals with high blood pressure who took one of two commonly used anti-hypertensive drugs--hydrochlorothiazide or atenolol. Over a study period of 45 days, the subjects used sesame oil for all their cooking needs and blood pressures dropped to normal. The next 45 days were spent sans sesame supplementation, and blood pressures rose to pre-study levels. Body weight, body mass index, and waistline measurements dropped as well.

I plan to recommend this strategy to my patients willing to give it a try; I'll let you know what results we get. I personally have used sesame oil each a.m. for almost two years in an ayurvedic quest for oral health(4). That morning spoonful theoretically draws out nasty toxins and is meant to be spit out post-pull. Perhaps thereafter, I should consider actually swallowing a swig for the rest of me.
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(1) http://www.naturalmedicinejournal.com/article_content.asp?article=113
(2) Sankar, D et al. Sesame oil exhibits synergistic effect with anti-diabetic medication in patients with type 2 diabetes mellitus. Clin Nutr. 2010 Dec 15. [Epub ahead of print]
(3) Sankar, D et al. Effect of sesame oil on diuretics or Beta-blockers in the modulation of blood pressure, anthropometry, lipid profile, and redox status. Yale J Biol Med. 2006 Mar;79(1):19-26.
(4) Asokan S. Oil pulling therapy. Indian J Dent Res 2008;19:169

Sarcopenia or why we install railings by toilets

I attended a funeral last Friday. There was a fair amount of rising and falling to feet and to seats what with religious moments and a standing, whooping, foot-stomping ovation to Megan and her life well-lived. I've written before about funerals, and how I love a good one, but that is not the subject of this post.

My pew-mate was an older woman who carried more than a little extra weight and who struggled mightily to stand each time we were called upon to do so. In front of me sat a skinny woman, still older yet, who did not even attempt to get upright until it was time to leave the chapel. Two elderly friends of Megan, each losing physical ground in her own way, one to excess adiposity and osteoarthritis of knees and hips perhaps, the other to fraility and sarcopenia. The inability to rise from a seated position, however, be it in a kitchen chair, a living room recliner, or a toilet seat, is a big step on the road to dependence and demise.

Aging is filled with -penias as in osteopenia (loss of bone mass short of osteoporosis) and sarcopenia or loss of muscle mass. There are many factors that contribute to this age-related wasting away of muscles some of which not yet elucidated but not the least of which is inactivity brought on by injury, arthritis, and illness which in turn leads to weakness and fatigue which in turn fosters more inactivity.

In order to repair, regenerate, and develop muscles to propel ourselves up out of a chairs and off to the 'frig (or the gym!!), we depend on 'satellite' stem cells that reside on the surface of our muscle fibers. Reduced numbers of such cells coupled with their decreasing ability to do their job is the biological basis of sarcopenia. I've had patients seek out human growth hormone and human chorionic gonadotropin in order to boost muscle mass and reverse aging, but rats and researchers in Washington state and Israel have recently published findings that suggest a simpler, less expensive, more accessible way to get myogenic satellite cells. One word: Exercise!

Rodent models suggest nothing but bad news from aging satellite cells. Satellite cells are usually in a resting state in older animals but can be activated to repair and renew muscles after injury and illness. But satellite cells are more likely to generate fat (the lady next to me!) or fibrous connective tissue (the stringy, skinny lady in front of me!) than muscle fibers as they grow old. So what happens if rats work out instead of veg in front of the TV set?

The researchers confirmed that the older the rat, the fewer the satellite cells on their calf muscles. However, when the four-legged geezers were persuaded to hit the exercise wheel, this aging effect was corrected, and both males and females greatly increased the number of myogenic--muscle producing--cells. Better yet, this cellular change had a visible effect on the old coots with a favorable shift in their lean-to-fat content and on their level of "spontaneous locomotion." Svelte, toned, AND disinclined to sleep the day away in the wood shavings!

One of the ways I assess how my patients are faring is to greet them first in the waiting room. First of all, it's a good way to start the visit, but, in addition, I can watch them rise from their chairs and walk across the room and up two stairs to the hall. I am daily appalled by the way some of my long-time patients increasingly struggle with the task, even moreso by their seeming indifference or inattention to their inability to move with ease. Check out the way you spring from your pew, your toilet, your desk chair. Don't take "can't do it easily" for an answer.
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1) Shefer, G et al. Reduced Satellite Cell Numbers and Myogenic Capacity in Aging Can Be Alleviated by Endurance Exercise. www.plosone.org.

Swiss chard and lung cancer

If R is you or more specifically your DNA in charge
of cell proliferation, the CH3 or methyl group is your
potential road to ruin.

In the spring of 2008, one of my patients came back from a vacation to Mexico with "pneumonia". But I didn't really think it was pneumonia--the shadow on her x-ray wasn't quite pneumonia-ish, and her symptoms of fatigue and a non-productive cough weren't exactly right either. Anyway, we optimistically tried a course of antibiotics without any change in that infiltrate, and, alas, it was lung cancer after all. Mother of two boys still at home and an ex-smoker for more than a decade, my patient died at home six short months later.

Sometimes rogue DNA--perhaps damaged by aging, smoke, or an errant sunbeam--just gets the best of you despite all that water and veggies and walking at dawn. Still, a person keeps trying to do what she can to avoid the brick wall of mortality, and a recent study in the journal Cancer Research (1) further supports the value of leafy greens. But before we discuss the goodness of greens, a word or two on gene promoter hypermethylation events which are nothing you want occurring in your DNA.

Genes are minute strips of DNA. During a typical 'business-as-usual' day in the life of a normal cell, they are activated by external and internal events and transcribed via RNA to produce worthy proteins that carry on normal activities that include damage repair and control of cell proliferation. If, however, one instructional molecule of the DNA gets permanently tangled up with a methyl group, the entire gene is silenced and its work remains undone. Worse yet, as that cell with its load of methylated DNA replicates itself because no gene product was there to tell it not to, all its offspring cells are also methylated. As a result, an out of control, methylated mass of cells continues to grow unchecked. Sounds like cancer, doesn't it?

So once hypermethylated, can you become demethylated? Such a demethylation process is the dream of scientists looking for chemopreventive strategies. As opposed to chemotherapy drugs which seek and destroy cancer cells, chemopreventive agents act to repair or prevent malignant change. Researchers from the University of New Mexico sorted through sputum from smokers (both current and ex-) seeing if certain dietary strategies were associated with lower levels of methylated genes in expectorated DNA.

Some 1,100 subjects dutifully hawked up their secretions and completed Harvard Food Frequency Questionnaires. As a result, the New Mexican docs were able to identify leafy greens (and we're not talking lettuce here), folate, and multivitamin use as three strategies that correlate with less methyl-generated mess. They proposed that further study might verify these and other agents as ways to reprogram our genome for life without cancer.

Now I'm all for this sort of research as a doctor and an ex-smoker. My problem is that a pile of steamed chard (or kale or greens) is an unappealing mess all its own. Any suggestions of different ways to prepare an appetizing, chemopreventive side dish of greens?
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1) Stidley, CA et al. Multivitamins, folate, and green vegetables protect against gene promoter methylation in the aerodigestive tract of smokers. Cancer Res. 2010 Jan 15;70(2):568-74.

Best personal trainer deal in Denver

Please note the corrected dates for this program

I have struggled mightily with back pain from scoliosis and degenerative arthritis. Thanks to a program of core strengthening courtesy of two knowledgeable young women--one a Pilates instructor with a strong background in physical therapy and yoga, the other an athletic trainer with a gift for modifying her workouts for older, less flexible non-athletes--my spasms and debility are yesterday's news.

I've put a lot of time and money into this program figuring properly that any bottom line beats crippling pain and decreased mobility. I am pleased to announce now that my trainer Tanya Martelli (Dr. Sykes goes to her too!) has assembled a low cost solution for those of you displeased with your aging spines.

She will be conducting a three class workshop for five participants Oct. 8, 15, and 22 at our office from 4-5 p.m. The focus will be on posture and core power, and at the end of the sessions, each person will have a home program to continue progress made during the class. The cost is $45. If these times do not work for you, Tanya plans another three week session mid-day Tuesdays at the end of this series.

You do not need to be our patient to attend these classes. Interested? Contact Tanya at tlyaskoff@mac.com to sign-up or inquire about future classes. She just designed a home program for me that I took on a recent road trip to California--worked just perfectly to keep me upright and buff while away from home. She could do that for you too!

Rose Kelly

Rosellen Kelly, 8/20/52-7/31/10

I lost my dear friend Rose yesterday to cancer. Mom, wife, friend extraordinaire, writer, artist, and Assistant Head of School at St. Anne's Episcopal here in Denver, she was a treasure to all who knew her. She collected friends like an endless strand of pearls--like the ones she wore at a time when our generation was mostly through with such traditional adornment.

Gracious, hilarious, and soothing, she told me that she viewed death as "just showing up for my next assignment. An angel in life, she has ample experience for her upcoming gig.

Window of Opportunity of Estrogen Therapy for Neuroprotection

Those of you who find this topic one of interest should check out the newest post at my other blog: Menopausemoments.blogspot.com.

Fractures and Fosamax

Dang, what was this 60-something year old lady(1) doing that resulted in her femur breaking like a branch across a gardener's knee? The unsettling answer? Nothing. She just felt a "giving away" sensation in her leg and then she gave way and went to ground. Of note, however, she had been taking medications for 17 years to prevent osteoporosis: first Fosamax and then Boniva.

Our bones are in a state of constant turnover. Breakdown of bone matrix by cells called osteoclasts is balanced by a corresponding build-up of bone mass undertaken by osteoblasts--a process that continually replaces old bone with new. In adults, bone formed equals bone broken down as osteoblasts fill areas along the bone surface previously resorbed by osteoclasts. Such dynamic restructuring in response to the forces of gravity and activity is essential to bone strength. In addition, this active bone metabolism repairs micro-traumas caused by everyday wear and tear as well as macro-traumas such as fractures.

As we grow older, we tend to breakdown faster than we build-up (well duh!). Ongoing osteoclastic activity is no longer countered in kind by reciprocal action from aging osteoblasts especially in women who are estrogen-deficient, inactive, on steroids, or deficient in calcium and vitamin D. Now bone resorbed by osteoclasts exceeds bone built by osteoblasts resulting in bones that are not only thinner but also architecturally unsound. As a result, vulnerable areas such as the hip, the vertebrae, and the bones of the forearms lose strength and fracture easily.

One strategy developed to combat this scenario is a class of drugs called bisphosphonates (Fosamax, Actonel, Boniva, Reclast, and others) which inhibit normal bone-remodeling through inhibition of osteoclasts. Since bone resorption triggers bone formation, these drugs are better suited to slowing loss rather than gaining mass. While population studies show decreased risk of fractures in persons using bisphosphonates, disturbing patient histories, such as that from the unfortunate lady pictured above, suggest that extended use of Fosamax and friends may result in bone fragility through the accumulation of microdamage in bones weakened by a loss of the normal reparative functions.

Texas researchers had a look at bone chips from persons who had spontaneous--i.e. no antecedent trauma--fractures while on Fosamax(2) most of whom had delayed or absent healing at the site of the break. Scary stuff on microscopic exam--many of the patients showed "markedly suppressed bone formation" with little or no osteoblastic activity and diminished mineralized bone. Even those patients on concurrent estrogen therapy demonstrated decreased bone formation. While Fosamax was the first bisphosphonate 'out of the gate' and thus most likely to be associated with fractures related to long-term use, scientists believe that this brittle bone thing may well be found with ongoing use of the other agents in this class.

Well yikes, is it time to boycott Boniva? Act not on Actonel? Consider first, this meta-analysis of several bisphosphonate trials.(3) These scientists from four different countries supported by Merck (Fosamax) and Novartis (Aredia, Zolmeta) analyzed data from three large studies looking for risk of fractures of the femoral shaft (considered atypical when compared with the more common fractures of the femoral head) as they were associated with use of bisphosphonates. Most reassuringly, they found such drug-related breaks to be rare, occurring at a combined rate of 2.3 per 10,000 patient-years. In other words, of 1,000 women using a bisphosphonate for 10 years, 2.3 would have an unexpected fracture of their thigh bone. There was no elevated risk of this type of fracture between those on Actonel and those on placebo, and a relative risk of 1.5 for women on Zolmeta (an IV bisphosponate most often used in serious situations such as in women with metastatic cancer where the drug slows down the spread of the tumor through the bones).

In an editorial that accompanies this study(4), Dr. Elizabeth Shane of Columbia University emphasizes that such atypical fractures are extremely rare, and particularly unlikely in persons on bisphosphanates. In fact, she cites studies that show, on average, that these femoral shaft fractures are more commonly caused by osteoporosis than the medications that treat the condition, and high adherence to this drug regimen more often decreases the risk of this type of bone breakage. She concludes: "many more common and equally devastating hip fractures are prevented by bisphosphonates than are potentially caused by the drugs."

Several authors have suggested that women on bisphosphonates be given a drug holiday in order to allow for a time of normal bone remodeling. Bisphosphonates bind to bone and are slowly released by osteoclastic activity. Fosamax is present in the body long after its use is discontinued--one study found bone turnover suppressed for three years after five years of regular Fosamax use. There are no official guidelines to follow with respect to intermittent bisphosphonate use, but one year off does not seem to diminish the positive effects on fracture risk.

What should you do? Talk with your doctor about taking a drug holiday (no, not THAT kind of drug holiday) if you've been on bisphosphonates for more than five years.
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(1) X-ray and case history from:
Goddard MS, et al. Atraumatic Bilateral Femur Fracture in Long-Term Bisphosphonate Use. Orthopedics. 2009 Aug;32(8). pii: orthosupersite.com/view.asp?rID=41933. doi: 10.3928/01477447-20090624-27.
(2) Odvina, CV, et al. Severely suppressed bone turnover: a potential complication of alendronate therapy. J Clin Endocrinol Metab. 2005 Mar;90(3):1294-301. Epub 2004 Dec 14.
(3) Black, DM, et al. Bisphosphonates and Fractures of the Subtrochanteric or Diaphyseal Femur. Published Online March 24, 2010 (DOI: 10.1056/NEJMe1003064).
(4) Shane, E. Evolving Data about Subtrochanteric Fractures and Bisphosphonates. Published at www.nejm.org March 24, 2010 (10.1056/NEJMe1003064)

The changing face of primary care

My medical partner and I are facing big decisions about the future of our medical practice. I urge all of you--particularly our patients--to head over to Denver Doc Online and read about our dilemma and leave your thoughts behind.

Morton's Foot

Dr. Dudley Morton practiced in the 1930's, first describing a number of foot ailments including Morton's foot (aka Morton's toe), and Morton's neuroma. Morton's foot is a common but dysfunctional variant of foot structure occurring in more than 25% of the population. By the time one hits middle-age, however, the instability caused by this condition can lead to pain and an inability to walk pain-free into the golden years.

Check out the sketch below from The Trigger Point Therapy Workbook for a look at Morton's Foot which is also known as short first metatarsal syndrome. The metatarsals are the longish bones beneath each toe, and the first metatarsal meets up with the big toe at a most critical juncture known as the 1st MTP (metatarsal phalangeal) joint which should be one of the primary weight-bearing areas of your foot.

If you've been issued a stumpy first metatarsal (arrow B), your weight is transferred to the 2nd MTP joint (arrow A) beneath your 2nd toe (arrow C). As a result, your weight can wobble inward towards the arch or outwards towards the little toe which has been likened to 'walking on ice skates'. The 2nd toe may extend beyond the big toe in persons with this Morton's business; while some call this long 2nd toe a sign of nobility. In my experience, it's a sign that you may give up walking for exercise.

Then look out, it's like a veritable aging house of cards cascading down your midline. The arches fall, a bunion may pop out, the ankles hyperpronate (see below), your calf muscles start working overtime to hold up your body,your knees knock together in the midline causing arthritis and collapse of your lateral knee joint,


you start to hate walking, gain weight, and plummet into old age way before your time.

So if that info knocked your socks off, check yourself for Morton's foot thusly:By pulling your toes downwards, you'll be able to see the locations where the metatarsals end and Morton's mayhem begins.

Got Morton's? I do. Custom-made orthotics and Pilates have changed my life. If you've been short-changed on your first metatarsal and are starting to hobble with pain, a trip to the podiatrist is definitely worthwhile. For more information, check out Mortonsfoot.com.

Milk thistle for liver protection

I had a patient in yesterday whose medical records show a long history of elevated liver function tests. These enzymes, namely aspartate aminotransferase (ALT) and alanine transaminase (AST), are part of routine blood test panels often ordered to screen for disease. Normally present in liver cells, elevated levels in the blood can indicate disruption of the cells by inflammation or disease. Even minor elevations are taken seriously if they persist over time as progressive destruction of the liver from hepatitis or other disease can occur without major changes in the transaminase values.

Further testing indicated she might be suffering from auto-immune liver disease wherein a misguided immune response against one's own tissue can cause damage to the organ. She wondered what she could do to promote liver health while pursuing a definitive diagnosis with a specialist. I recommended milk thistle only to read the following today on the Consumer Lab web-site.

Consumer Lab is an independent organization that tests nutritional supplements for quality, assuring that these products are pure, contain what they claim, and are free of contamination. The nominal yearly subscription fee is well worthwhile if you are a fan, as am I, of supplements. One of their recent reviews covered milk thistle.

Only one brand was found on testing to contain the amount of active ingredient indicated on the label. Furthermore, the evidence that milk thistle changed the course of chronic liver disease caused by hepatitis or alcohol was weak. The research suggesting that the herbal preparation protects against liver toxicity from acetaminaphen and anti-seizure meds was stronger. The active ingredient in milk thistle--silibinin--has been the subject of recent cancer research and seems to have some promise as a chemotherapeutic agent.

I don't feel quite so enthusiastic about my recommendation now. If you're considering milk thistle supplements, have a look at the ConsumerLab site to choose the best brand.

Rheumatoid arthritis, disability, and dismay

One of my favorite patients struggles mightily with the pain and disability of rheumatoid arthritis. Unfortunately, she got hooked on Oxycontin that she started taking for the pain of infected foot ulcers brought on by the immune-suppressive drugs she takes to control her disease.

Each time I see her, I'm dismayed with 1) how quickly life can unravel due to disease and disability, and 2) how difficult it is to be taken seriously when you take too many pain meds no matter how legitimate your need for same. I spent over an hour on the phone today with the patient and a pain specialist she consulted last month. The latter never even examined her when she came to his office seeking help with pain control and narcotics withdrawal. "I could have you committed," he told her, "for your illegal use of drugs. What on earth did he think he'd accomplish with nonsense like that except to drive her to tears (which he did).

So now she's fallen and sustained four compression fractures of vertebrae made thin from steroid use. The orthopedist she sees for degenerative disk disease never mentioned to her that her new, dreadful pain was due to fractures. I have no idea what my colleagues think they're doing here. But I do know if you're malnourished, angry, and you look older than you are due to the ravages of pain and illness, it's extraordinarily hard to be taken seriously.

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.