Tuesday, November 27, 2007

No free rides

And antidepressants are no exception. The class of antidepressants known as SSRIs-- Prozac, Zoloft, Paxil, and others--have absolutely revolutionized the treatment of depression and anxiety in the last 20 years. Research published this year in the Archives of Internal Medicine, however, suggests that which is good for the brain is bad to the bone.

Canadian researchers studied a group of 5,000 some adults over 50, following their health outcomes over 5 years for incidence of falls and fractures. In particular, they were checking for 'fragility fractures' or those broken bones resulting from minimal trauma such as falling out of bed.

Those subjects who were under treatment with SSRIs were 1.5 times more likely to pitch over in a fall and 2 times more likely to break a bone--not necessarily related to those increased falls--than their colleagues who were toughing out the modern world without the support of medications.

This adds another tough decision in our 'better living through chemistry' kind of lives. SSRIs can literally be life-saving, and their benefits most definitely enhance life's journey for many. As the authors note: "These risks must be balanced against the benefits gained by the treatment of depression with SSRIs."

Sunday, November 18, 2007

Transient Global Amnesia (TGA)

For the third time since spring, my Mom experienced TGA. She was sleeping deeply when I arrived at the nursing home; attempts to rouse her for lunch were unsuccessful. I sat reading by her bedside until she started to stir. As she came to, I chatted with her idly about the events of my day. She looked at me with no particular alarm or recognition; her first words several minutes later were "Who are you?".

As the hospice social worker put him, I am 'letting go of letting go,' so I've long ceased concluding rapidly that 'this is it,' call the family, she's on her way out. Instead, I chatted on, casually reorienting her, none of which stuck.

So which parts of her brain were out of blood? Studies using fMRI and PET scanning, both of which are functional scans which indicate what part of the brain is actively metabolizing sugar and receiving blood flow, indicate that brain areas involved in memory function are short on blood during TGA. Specifically, the thalamus, amygdala, and hippocampus are affected. The amygdala is also involved in emotional arousal, and its hypoxic state may have explained why she did not demonstrate the sort of alarm that you'd think someone would feel about coming to in a world that made no sense.

Monday, November 12, 2007

The Electrical Basis of Consciousness

The posterior parietal cortex (PPC) is connected to the medial temporal lobe (MTL) is connected to the prefrontal cortex (PFC) all of which is goosed from below by the ascending reticular activating system (ARAS) rising up out of the brainstem. This crosstalking network keeps us alert and oriented. Per neuroscientists in Georgia and Tennessee, disruption of these circuits can take out IQ points in old folks and the seriously ill. Furthermore, if you happen to be both old and critically ill as in eligible for the ICU, the disruption of these connections takes delirium (temporarily out-to-lunch) and turns it into dementia (permanently out-to-lunch).

The matter with old gray matter is that it starts to dry up. The PPC, MTL, and the PFC all atrophy with age, leaving the ARAS in charge of activating increasingly balky connections. Pain medication, sedatives, and overwhelming systemic illness, however, cause the ARAS to falter. Once the critical threshold of normal functioning is passed, the very sick and the very old lose their tenuous hold on reality. Dr. Max Gunther and his colleagues theorize that this may be why delirium is common in the ICU.*

And I always thought it was the perpetual fluorescent lights, equipment alarms, and overhead pages that put patients over the ICU edge.
*Gunther, ML et al. Medical Hypotheses Volume 69, Issue 6, 2007, Pages 1179-1182

Saturday, November 10, 2007

Spice curries favor with aging brains

My turmeric has arrived. No ethnic cooking with these 300 capsules of East Indian spice, however, because they're brain food for me. Every so often I come across research so compelling that I shut down the word processor and search the web for the best price on a priceless new product. And 150 days worth of turmeric for $9.00 at www.puritan.com seems like a bargain. Here's why.

Alzheimer's disease causes the accumulation of an abnormal protein called beta amyloid (Abeta) in the brain. Great glumps of Abeta destroy brain cells, perhaps by setting off an inflammatory process in much the same way that cholesterol deposits lead to the destruction of blood vessel walls. Anti-amyloid agents theoretically could prevent this degenerative process.

Enter curcumin or turmeric, the yellow curry pigment which is already known to possess antioxidant and anti-inflammatory properties. Scientists working on mouse brains (both inside and outside the mouse) found that curcumin was a potent inhibitor of Abeta aggregation. In other words, a dash of spice on a mucked-up mouse brain prevented little Abeta clumps from growing into big nasty plaques. Furthermore, Tg2576 mice--bred to be particularly susceptible to senility--with advanced amyloid guck in their brains actually reversed their Abeta plaques when Indian curry replaced their standard American chow.

The authors of this UCLA study published a few months ago in the Journal of Biological Chemistry concluded: "These data suggest that low dose curcumin effectively disaggregates Abeta... supporting the rationale for curcumin use in clinical trials preventing or treating AD." They are currently undertaking just that to see if curcumin can improve mental status in patients already affected by Alzheimer's disease.

Topical pain relief for arthritis

This is a topical topic indeed for an aging population trying to stay active yet leery of the side effects of pain-relieving drugs. As you are well aware, non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and aspirin are a mixed blessing of benefits and detriments. While relieving the pain of inflamed joints, these drugs also interfere with the lining of the entire GI tract raising risk of gastritis, ulcers, diarrhea, and colitis. In addition, NSAIDs can restrict blood flow to the kidneys and cause loss of kidney function, and acetaminophen (aka Tylenol) is also known to be toxic to the liver.

I have any number of patients who are unable to take NSAIDs for the above reasons. One middle-aged teacher with severe osteoarthritis had a stomach hemorrhage from aspirin taken for her chronic headaches. We keep seeking alternative relief for her--unfortunately, the latest attempt at using Cymbalta (an antidepressant AND a chronic pain reliever) to control her pain caused her blood pressure to soar. Another teacher/patient developed Stage I renal insufficiency from ibuprofen. We have developed a more or less satisfactory pain program for her with low dose, long-acting narcotics.

So the recent FDA approval of Novartis's Voltaren Gel may be the very thing for joints on fire. The topical application of this longtime NSAID produced significant relief for hand and knee pain in clinical trials. Because it is absorbed and works locally, there may be less potential for the kind of systemic side effects noted above. Per rheumatologist Raymond Flores, MD: "The advantage to this preparation [compared with oral painkillers] is that it seems like it's providing comparable relief but with little systemic absorption."

Tuesday, November 06, 2007

Blood Pressure Shot?

This is something entirely new and different under investigation. The problem with blood pressure medication is that it must be taken daily and forever. Daily and forever is rough, and people are reluctant to comply with this D&F business. And even if you do take those BP pills each morning, they are often long gone by the early a.m. hours of the following day when blood pressure rises in readiness for upgetting. As a result, early a.m. hours are the most common time for strokes and heart attacks, especially early Monday a.m.'s.

A Swiss company that apparently specializes in searching for vaccines for all that ails you (nicotine addiction, obesity, Alzheimer's, melanoma, etc) has developed a vaccine against angiotensin II, that pesky little molecule that constricts your blood vessels and causes a rise in blood pressure. Now if you happen to be dehydrated or hemorrhaging or slogging through the mall the day after Thanksgiving looking for Christmas gifts, a little angiotensin boost to the blood pressure assures that you will stay alive long enough to get water, blood, or a seat at Cinnabons. But if your kidneys are a little misguided and working overtime in the mistaken impression that your blood pressure is low, poof! angiotensin II is not a good thing.

Enter CYT006-AngQb (well they're going to have to come up with a new name, aren't they, if this shot ever has a shot at market popularity). This is a "viruslike particle-based conjugate vaccine that targets angiotensin II" meaning that it presents an angiotensin-ish sort of look-alike molecule to your immune system that then learns to personally dispose of too much of this bad boy.

In phase II trials, CYT006-AngQb was safe, well-tolerated, AND effective. Blood pressure fell a modest 5.6/2.8 points by day in the vaccinated group compared to those who got a painful placebo shot. That means those with elevated blood pressures of say 140/90 fell to about 134/87, a drop that would produce significantly less risk of heart attack and stroke over time. Better yet, the ones who got a real shot at the real shot experienced a wee hours BP drop of 25/13 so that those same hypertensives who registered BPs of 140/90 at study's start were mellowed down to 115/77 in the early a.m. 14 weeks later.

Ideal blood pressure is 115/75. Cardiovascular risk starts to rise with anything more than that. In case you were still laboring under the impression that 120/80 is okay, sorry, they've changed the rules on you! But soon, perhaps, you will have a shot at normal blood pressure, and you'll perhaps only need a booster every 4 months or so.

End stage renal disease and EGFR

Well who really gives their kidneys a thought? Patients all worry about cancer, and rightly so, and everyone is finally heeding the call to worry about their hearts. But headline news at medpagetoday.com alerts us that baby boomers are entering the age of end-stage kidney disease.

This coincident with the addition of a new lab value on routine lab printouts--EGFR. This stands for estimated glomerular filtration rate which is a fairly accurate estimate of the efficiency of kidney function. The National Kidney Foundation encourages that all persons "know their GFR number," so now we've got another number to add to our blood pressure, blood sugar, and serum cholesterol statistics. If you know your creatinine (a measure of waste in the blood included on most standard lab panels), you can know your GFR with this handy tool: EGFR calculator.

My discussions with patients about their routine lab work has, therefore, acquired a new level of complexity. The lowered thresholds for fasting blood sugar and optimal cholesterol already require extra time to interpret, but no way to explain EGFR and its implications in a sentence or two.

Results of this screening test are divided into normal (>60), and low. The things that make GFR drop are prevalent in an aging American population, and include hypertension, obesity, diabetes or even prediabetes, and the overuse of analgesics such as Tylenol and Advil. Regular use of diuretics can also contribute to diminished kidney function.

There is information that routinely passes right over the heads of most of my patients (extra weight is bad for you) and some results that finally cause them to sit up and take notice (you have diabetes). Unfortunately, 'you ought to lose weight,' when ignored for years, result in 'you have diabetes.' 'Your kidney function is low' is turning out to be an eye-opening phrase and is one best heeded while lifestyle changes can turn the trend around.