Wednesday, September 30, 2009

Can Prednisone make me feel crazy?

If you've ever taken it, you already know the answer is an emphatic YES!! Here's a visual from my friend and artist Rose Kelly about her trip to the "Prednizone" while undergoing chemo.

Sunday, September 27, 2009

Advanced glycation end products

That which is truly tasty, like make the hair stand up on your neck and shiver over the full delicious tastiness of it all, may prematurely age your blood vessels, your nerves, your kidneys, and your joints.

These advanced glycation end products or AGE are the end-products of reactions that bond sugar to protein in the absence of water. Think sugar steaks (too bad you won't want to try one at Bastien's Steak House on Colfax after reading this), the brown sugar/Jack Daniels crust on baked ham, browned cookies, the caramelized surface of creme brulee. So let's just say you avoid AGE in foods, and I'm not necessarily saying you should because, after all, life is meant to be enjoyed, well turns out you can glycate your own darn sugar once its ingested or produced. And fructose (that which sweetens your bottled drinks) is very prone to glycation.

So AGE along with ALE (that would be advanced lipoperoxidation end products or metabolized fat) are very proinflammatory molecules. AGE hooks up with specific cellular receptors called RAGE and the combo acts as a 'master switch' that activates nuclear factor kappaB(1) and creates high levels of dysfuntional proteins among other things. The sort of dysfunctional proteins that gum up your brain, your peripheral nerves, and your arteries.

Well we're all going to rust and glycate and peroxidate eventually, and we may as well do it with the satisfied smile of the occasional gourmand. But, as in all things, a little is good but a lot is not, and if you want to keep your cells functional, some things are best done in moderation or not at all.
1) NF-kB is a good thing if you happen to be injured or infected as it amplifies the immune response but a bad thing if you happen to drink Coke and eat browned chocolate chip cookies on a regular basis.

Tuesday, September 22, 2009

New Diagnoses, New Behavior

Can't look for what you might find
Once more you're running around in circles just to prove
You knew the answers all the while
Can't figure why no matter what you say or do
Things stay the same you will remain
Day late a dollar short
Day late a dollar short
--The Acro-Brats(1)

There's nothing like a new diagnosis of diabetes to get a patient's attention. Suddenly, all those discussions about diet, exercise, weight loss, soda consumption, etc. make sense. Well better late than never (perhaps The A-B's have a song about that too) but there's also the day late dollar short thing too because this is a condition that you are far better off without.

Yale scientists actually set out to prove what I already knew from years of consultations with the newly diagnosed. They checked out data from the Health and Retirement Study panel on over 20,000 people who were overweight or smokers.(2) The odds of weight loss or smoking cessation were hugely increased among individuals newly diagnosed with serious illnesses such as diabetes, smoking, heart disease, or COPD. Those who'd just learned they had heart disease were 5 times more likely to throw away the smokes than persons just counseled to do so just because it was the right thing to do, and new diabetics sent their BMI's plunging compared to the merely overweight.

Can't figure why no matter what I say or do
Things stay the same patients will remain
Day late a dollar short
Day late a dollar short

(1) I actually listened to this song on You-Tube. Definitely not my thing--the metallic thrum made my amygdala cringe-- but I appreciate the edgy frustration expressed by the Acro-Brats. I feel it myself, everyday, in exam room encounters.
(2) Keenan, PS. Smoking and weight change after new health diagnoses in older adults. Arch Intern Med. 2009 Feb 9;169(3):237-42.

Sunday, September 20, 2009

Too close for comfort?

I recently attended my 40th high school reunion. I talked for awhile with one old friend I hadn't seen in years. But I was distracted during the entire conversation by her preferred conversational distance which was close, darned close! Not a breath problem--hers was fine and apparently mine was too--just my problem with her 'in my face' proximity. A new study may indicate why, and it implicates my overactive amygdala.

I've mentioned before that the amygdala, an almond-sized region at the base of the brain, is nerve cell center for coordinating response to threat. If yours is on overdrive like mine, you may over-respond to horror movies, scary books, and phones ringing in the night.

Neuroscientists had the opportunity to study the biological underpinnings of personal space in a patient known as SM. She had a genetic disorder that took out her amygdala, and as a result, she could not recognize fearful facial expressions in others, and was very outgoing and far more trusting than average. And she cozied up in conversational situations such that she--Ms. Red above--let an experimenter get twice as close to her as the other Ms. Blues did without expressing any discomfort in the situation. (1)

Scientists went on to study preferred conversational distance with functional MRI scanning.(2) They socked away average persons with intact amygdalae in the machine, then got closer and closer to the subjects, measuring their brains for activity. When they invaded that person's comfort zone, the amygdala lit up with activity.

"Our findings support the idea that the amygdala functions as the brakes in social interactions, If you take away the amygdala, it seems like you are less tuned to ... social [behaviors] that can cause discomfort," says neuroscientist Richard Davidson of the University of Wisconsin.(1)
1) ScienceNOW Daily News, August 31, 2009
2) Kennedy DP et al. Personal Space Regulation by the Human Amygdala. Nat Neurosci 2009 Aug 30.

Thursday, September 17, 2009

Antibiotic resistance and beyond

Almost all the drugs that we consider as our mainline defense against bacterial infection are at risk from bacteria that not only resist the drugs but eat them for breakfast.
--George Church, geneticist, Harvard Medical School

What's eating you may eat drugs too! Church and company dug up this unhappy piece of news while digging in a cornfield fertilized with manure from antibiotic-fed cows. They compared the locals (soil microbes) in the corn patch to their bacterial colleagues from the dirt of a pristine forest and several other locales more or less contaminated with druggish waste.

So you'd expect those bugs inured to manure to be antibiotic resistant and the au naturel bunch to die when cultured with drugs, right? Unfortunately, wrong. Bacteria from every sampling included strains that could survive "with nothing to eat but antibiotics." Not only did these little hummers not die from the drugs, they devoured them.

For those of us who think antibiotic resistance is not a huge and looming danger, Gerry Wright, a chemical biologist from McMaster University, sums it up in words that can't be ignored: "Soil bacteria pass around resistance-conferring genes like teenagers swap downloaded music files, and pathogenic [disease-causing] bacteria could likewise pick up antibiotic-digesting genes, particularly from a closely related microbe.


Tuesday, September 15, 2009

Health care debate

If you live in the Denver area, consider attending the Great Debate on Health Care this Thursday, Sept. 17th at South High School. Conservative talk show host Hugh Hewitt and C.U. law professor Paul Campos, both articulate proponents for their respective sides, will debate current proposals for health care reform. You can order tickets online at or purchase tickets at King Soopers.

Denver Doc now on Twitter

I've made the technological leap to Twitter for those medical pearls of wisdom from me to you that fit in 140 characters or less. No updates on my dentist appt. or the weather here in Denver, just good health-related information from reliable sources. This blog will continue to be published on a regular basis as well.

If you're interested in Twitter updates from Denver Doc Online, you can sign-up at Thanks!

Monday, September 14, 2009

The amygdala and PTSD

I can hardly bear to watch violent or scary movies. I walked out on The Ring the moment the dried-up little girl was found in the closet (thankfully, the movie was 'showing' at the time in our living room). And the opening scene of The Exorcist in which Father Merrin finds the creepy little statue, the wind blows, and a couple of dogs fight still can interfere with a good night's sleep for me.

Research suggests that an overactive amygdala (the brain's VP in charge of processing emotional experiences and fear) may predict how an individual handles stress, be it in pictures or for real. Israeli scientists used functional magnetic resonance imaging (fMRI) to scan the brains of 18 year old subjects undertaking training as paramedics(1). They scanned the trainee's brains while showing them photographs of graphic medical scenes specifically looking for activation in the amygdala region. They also screened the recruits for stress symptoms including anxiety and insomnia.

After 18 months and a grisly load of combat experience, the researchers found that those paramedics with the largest increases in stress symptoms were the ones with the greatest amygdaloid activity on the initial scan. Study co-author Talma Hendler says that the amygdala may be an "a priori biological marker" for individual susceptibility to post-traumatic stress disorder.

Rather than use a fancy, expensive fMRI as a screening test for fitness under fire, I suggest a less expensive showing of Inglorious Basterds. Check the subjects' heart rate and blood pressure by the movie's end, and you'll know who's ready for the field and who should stick to the office.
1. Proc Natl Acad Sci USA. 2009 Aug 18;106(33):14120-5.

Thursday, September 10, 2009

H1N1 vaccine--one dose will do!

This just released today on the New England Journal of Medicine web-site. Results from the H1N1 vaccine trials indicate that one dose of the soon-to-be-released shot results in a good response from most adult subjects. Furthermore, no serious adverse effects occurred--just the usual sore arm and the vague flu-ish sort of feeling that is commonly occurs as a result of the immune reaction to the shot.

Vaccine demand is expected to exceed supply through the fall, so this one shot news is good news indeed.

Monday, September 07, 2009

Who should get Tamiflu for H1N1 flu?

If this past weekend is any indication of phone calls to come, I will be busy fielding requests for Tamiflu for suspected 2009 A(H1N1) which is what we're calling swine flu these days. Patients are understandably nervous for themselves and their families with regards to the spread and severity of influenza illness.

There are 2 available antivirals which are active against 2009 A(H1N1)-- oral Tamiflu (oseltamivir) and inhaled Relenza (zanamivir). For some reason, I've always reached for Tamiflu, and a brief search for a comparison of one antiviral to the other suggests that I am just another victim of an effective marketing campaign by Roche Pharmaceuticals. Nevertheless, be it Tamiflu or Relenza, one of the biggest fears per flu-ologists is that the novel H1N1 flu will become resistant to these worthy drugs, and they will be rendered powerless against the bug.

So what does the CDC have to say on the subject? They along with the WHO (the World Health Organization, that is, not the '60's band) recommend that antiviral treatment be undertaken in accord with the following guidelines:
  1. Treatment is recommended for all hospitalized patients with confirmed, probable or suspected 2009 H1N1 or seasonal influenza.
  2. Treatment generally is recommended for patients who are at higher risk for influenza-related complications.
  3. Treatment should be initiated empirically when the decision is made to treat patients who have illnesses that are clinically compatible with influenza. Treatment should not await laboratory confirmation because laboratory testing can sometimes delay treatment and because a negative rapid test does not rule out influenza.(1)
In other words, if the patient is sick enough to be hospitalized with flu-like illness, initiate treatment immediately. While these antivirals work best if initiated in the first 48 hours of illness, evidence suggests that hospitalized patients with seasonal flu fare better with respect to risk of death and length of hospitalization if Tamiflu therapy is started even if it's more than 48 hours after onset. Those known to be at higher risk of flu-related complications include pregnant women, persons who are immunocompromised (undergoing say chemotherapy or treatment for rheumatoid arthritis), or those with underlying medical illnesses such as diabetes, asthma, or heart disease. And finally, if we providers determine that a patient meets one of these criterion, get 'em going on it and don't wait for final proof!

These recommendations highlight the urgency with which certain subgroups of flu victims should be treated. The CDC, therefore, goes on to make further suggestions as to handle the upcoming flu season and the avalanche of requests for antiviral medications. These include:
  1. Provide information for patients at higher risk for influenza complications about signs and symptoms of influenza and need for early treatment after symptom onset.
  2. Ensure rapid access to telephone consultation and clinical evaluation for these patients as well as patients who report severe illness.
  3. Consider empiric treatment of patients at higher risk for influenza complications based on telephone contact... if this will substantially reduce delay before treatment is initiated. In selected circumstances, providers may consider giving a prescription for an influenza antiviral to selected patients who are higher risk for influenza complications.
  4. Request that patients at higher risk for influenza complications contact the provider if signs or symptoms of influenza develop, obtain the medication as quickly as possible and initiate treatment.
  5. Counsel patients about influenza antiviral benefits and adverse effects, the potential for continued susceptibility to influenza virus infection after treatment is completed (because of other circulating influenza viruses or if illness was due to another cause).(2)
What about antiviral chemoprophylaxis wherein antivirals are given to at-risk persons exposed to someone who is fluish? Please note in no case do these recommendations include giving Tamiflu to any old person traveling and worried regarding flu exposure except as outlined in the 3rd guideline above.

  1. Persons who are at higher risk for complications of influenza and are a close contact of a person with confirmed, probable, or suspected 2009 H1N1 or seasonal influenza during that person’s infectious period.
  2. Health care personnel, public health workers, or first responders who have had a recognized, unprotected close contact exposure to a person with confirmed, probable, or suspected 2009 H1N1 or seasonal influenza during that person’s infectious period.
  3. Antiviral agents should not be used for post exposure chemoprophylaxis in healthy children or adults based on potential exposures in the community, school, camp, etc.
  4. Chemoprophylaxis generally is not recommended if more than 48 hours have elapsed since the last contact with an infectious person.
2. This is an abbreviated list. See above web-site for the full printed version.

Friday, September 04, 2009

H1N1 and severe respiratory failure

Scientists are ferreting out clues to the ferocity with which this new swinish flu attacks the lower airways in some of its victims. Ferrets demonstrate a susceptibility to influenza A very similar to humans and therefore are used as an animal model in flu investigations.

The above picture(1) shows microscopic sections of ferret airways (that is not a goose!), comparing seasonal H1N1 flu (the usual variety that circulates each winter season) on the left to tissue infected by the 2009 A/H1N1 flu on the right. Violet coloration indicates affected surface cells, and both varieties make a mess out of noses with sloughing sheets of dead nasal tissue full of violet-colored intruders as seen in the top pair of slides.

Moving on down to the trachea (which is the largest central airway lined with rings of cartilage that you can feel in the front of your neck), the ferret with seasonal flu middle picture on left is free of viral invasion but the swine-flu ferret victim on the right has dots of violet flu violation throughout its trachea. Finally, and of importance to this discussion, slides from the bronchioles of both ferrets are pictured at the bottom. This tissue was obtained from the smallest airways that go directly into the alveolae or air sacs that hook up oxygen with blood. Seasonal Flu Ferret has normal bronchioles, flu bug free, but Swine Flu Ferret's tiny air passages are teeming with the little buggers.

What's this got to do with the upcoming flu season? One of my patients, an ICU nurse, shared a disturbing report with me yesterday. She said that her unit has been busy this entire spring to summer with youngish patients suffering from severe swine flu-related bronchiolities (inflammation filling these airways with fluid) requiring ventilator support until the infection started to clear. Her information jibed with an August report from the World Health Organization entitled "Preparing for the second wave: lessons from current outbreaks." Per the WHO document:

"Clinicians from around the world are reporting a very severe form of disease, also in young and otherwise healthy people, which is rarely seen during seasonal influenza infections. In these patients, the virus directly infects the lung, causing severe respiratory failure. Saving these lives depends on highly specialized and demanding care in intensive care units, usually with long and costly stays."

This information highlights not only the importance of widespread immunization against the 2009 A/H1N1 flu (which creates so-called herd immunity, slowing down or preventing the lateral spread of flu from person-to-person due to the large number of vaccine-protected people) but also the paramount importance of immunizations for persons with underlying illnesses, particularly asthma, cardiovascular disease, diabetes, and immunosuppression.
(1) Munster, VJ, et al. "Pathogenesis and Transmission of Swine-Origin 2009 A(H1N1) Influenza Virus in Ferrets." Science 24 July 2009: Vol. 325. no. 5939, pp. 481 - 483.

Tuesday, September 01, 2009

Why should I get a flu shot?

Well, there's a hack of a lot of flu coming our way. Consider this:

  • Flu viruses reproduce every 8 hours.
  • That's a three times daily opportunity to meet and mate with other influenza viruses in the neighborhood.
  • If seasonal A(H1N1) rolls in the tracheal hay (that's your airway!) with swine-origin 2009(H1N1), the latter could develop an even more effective way of passing from human to human.
Conclusion? You do NOT want these bad actors fooling around together in your nose and throat. In order to prevent such airway orgies, you need two shots. The CDC currently recommends that you get the seasonal flu vaccine now to prevent crazy long lines in late October when the swine flu vaccine rolls off production lines and into your neighborhood Safeway. So roll up your sleeve, and get shot 1 now.