Archive for September, 2012

What's the best way to prevent a stoke?

Tuesday, September 25th, 2012

The carotid arteries are a main line of supply for your brain

Last January the Center for Medicare and Medicaid Services convened a meeting to discuss what's the best way to handle carotid artery disease (CA-D). Those vessels are a major supply of blood to our brains and, as we age , smoke, don't exercise, have high blood pressure, diabetes, high cholesterol, get obese, or develop other risks factors they can be narrowed by atherosclerosis (AKA hardening of the arteries).

Obviously if we can stay young (we can't), keep our weight normal, have normal blood pressure (start by consuming less salt), and never smoke, we have a better chance of less changes in our blood vessels.

Well that's just not the case for much of our population, so then the question arises should our medical folk look for CA-D on a routine basis? Except for being 71 years old, I'm at relatively low risk with normal lipids, a weight approximating what my 8th-grade scale would have shown and a BP of 118/68. I only smoked for four years and quit for good over 40 years ago. So  my physician listens to my neck for an abnormal sound called a bruit, but otherwise hasn't suggested any other tests for CA-D.

How about the rest of her patients, or for that matter, all of you who are adults. If you have risk factors, and I should include a family history of stroke, you may or may not have symptoms of CA-D. Those could include, but aren't limited to, blurred vision, weakness in one part of your body, problems in speaking or understanding others, memory issues or being confused.

Then your physician has a host of tests she or he can order: those include an ultrasound to see if you have normal blood flow, angiograms, or even CAT scans or MRIs. Ultrasound (the fancy term is a carotid duplex Doppler study) is noninvasive, so nobody has to stick an artery or inject a dye. Angiograms, also called arteriograms are invasive and there's an added risk if the dye is can cause damage to your kidneys. CAT scans expose you to x-rays and MRIs may be tough if you're claustrophobic (although the chamber was much more open the last time I had one).

So most docs will be very judicious in picking which patients get which tests.

But what if you don't have CA-D symptoms and either physical examination or testing reveals significant disease? An Australian neurologist, Dr. Anne L Abbott has been a significant figure in opposing the current high rate of carotid artery procedures. Roughly 125,000 Americans per year have either carotid artery surgery or angioplasty with stent placement (inserting a balloon catheter  which is inflated to open the artery and a mesh tube designed to keep it that way).

This is what a vascular stent looks like


There's a heated debate going on among physicians who are experts in vascular disease and thirty-eight of them wrote an open letter to Medicare opposing the manufacturers who want the government agency to expand insurance coverage to include stent placement in patients who have no symptoms at present.

On the other hand, a May 2010 article by an interventional Cardiologist, Dr. Cristopher White from the Ochsner Institue in New Orleans, examines in great detail the results of a variety of studies done in the United States and in Europe. He mentions that stroke is our third leading cause of death; that of the 3/4th million who have one in this country per year, many are left with significant disabilities; and of adults over 65, one in twenty to one in ten have significant carotid artery narrowing (50% or more) without having symptoms.

Stroke risk is clearly related to how much atherosclerotic disease is present; more is bad. The article I mentioned above was written by and perhaps slanted toward stents and compares surgical and non-surgical interventional approaches. What is not clear is how much screening should be done in patients without symptoms and what the outcome of modern medical therapy would be compared to either invasive procedure.

I'm very interested to find out more, but have no intention at present of having more tests without better data.





What are those?



Mast cells, immunoglobulins and our dog Yoda

Saturday, September 22nd, 2012

We just lost a beloved family member, our ten-year-old Tibetan terrier Yoda, to a malignancy that I'd never heard of, an enormous mast cell tumor. It made its initial appearance only eight days previously while I was in Memphis at a 90th birthday celebration. My wife called me and said Yoda had swelling in his neck and a cough.

She took him in to the multi-veterinarian clinic where he's been going for ten-plus years and they were puzzled. They were unsure of which of four possible diagnoses was causing his problems. He got an antihistamine and a broad spectrum antibiotic and improved considerably. When he lost his appetite  on a Sunday afternoon, we spoke to the on-call veterinarian who felt he should be seen early on the next morning.

By then his neck was swelling again and we were promptly referred to the CSU Veterinary School's hospital. They got him into their urgent care system, aspirated some cells from his neck and told us he had a mast cell tumor. The literature they supplied said these are extremely rare in humans, but common in dogs.

a tropical frigate bird with his pouch inflated

A short while later his neck was swollen to the point where he needed to be intubated in order to breathe. The only creatures I had ever seen with a similar appearance were  great frigate birds in the Galapagos. In their case, the pouch is inflated by the male birds to attract a possible mate; in Yoda's case the malignant mast cells had "degranulated" releasing histamine and other mediators of immunity.

Our surrogate son, now in his second medical career, had never seen a mast cell tumor and both of us had to return to memories of our freshman years in medical school (mine considerably before his) and to Google the term to remember exactly what a mast cell is and what physiologic role it plays.

I went back to the Web and read about mast cells and their companions in allergic inflammation; it was a highly technical article written for allergists and immunologists, so I struggled a bit. Let's start with the immunoglobulins, our antibodies. There are five classes of these chemicals which are manufactured by the body in response to foreign substances (antigens) such as pollen, bacteria, or cancer cells. Three of them, termed IgA, IgG and IgM were familiar to me.

IgA antibodies protect our body surfaces (e.g., nose, digestive tract, eyes & ears) that are often bombarded with outside antigens. IgG antibodies are the smallest, the only immunoglobulin that can pass through the placental barrier to a fetus, and make up nearly 80% of all of these immunity chemicals. They help protect us against bacterial and viral infections. IgM antibodies are much larger, play an important role in our initial line of defense versus infections and are produced, to a large extent, in the spleen.

IgD was the mystery antibody for many years; recently it has been felt to be a surveillance system, binding to one kind of blood cells and setting off an intricate series of protective processes.

So that left IgE whose connections with allergic reactions was clear. Along with blood cells known as basophils and eosinophils and "tissue-based" mast cells, IgE is a crucial factor in inflammation associated with allergy.

I mentioned that mast cells are tissue-based; they're not something you'd see in a normal CBC (complete blood count), but "hang out" in association  with blood vessels and on epithelial surfaces (your skin is classed as such, but epithelial tissues also line the cavities and surfaces of structures throughout the body, and also form many glands). Mast cells are "cousins" to basophils, similar in appearance and function, and containing histamine and heparin, but are thought to be generated in the bone marrow from different precursor (ancestor) cells.

They have a highly significant part in the inflammatory process and team up with IgE which coats their outside surface. They have key roles in asthma, a variety of itches, and allergic rhinitis (one form of this disorder would be "There's pollen in the air so my nose gets clogged up and I sneeze."). They're also crucial in immediate hypersensitivity, severe kinds of allergic reactions that can be life-threatening. One example of this would be a person who has a severe, potentially fatal reaction to a bee sting. The medical term for this is anaphylaxis.

A human mast cell cancer; the dark-staining areas are filled with malignant tumor cells.

Mast cells can cause diseases in people; one type leads to pigmented skin areas that when stroked develop hives. Rarely do human mast cells lead to malignancies. I talked to a physician friend who had seen one case in her career and found an online series that had a total of three cases.

In dogs, on the other hand, mast cell tumors are relatively common, but most are lumps that can be removed surgically. A smaller number of canines develop larger tumors and a few have even more malignant disease.

Unfortunately, our dog Yoda had one of the bad kind. His was the largest, most rapidly-growing mast cell cancer the Vet School's senior oncologist had ever seen.

We'll miss him. He was an important and much-loved part of our family.







Almost everything about blood except for mast cells.

Friday, September 21st, 2012

I started a post on mast cell tumors in humans and dogs, having learned about them the hard way...our dog died this week.

When the Colorado State University Veterinary Hospital first mentioned mast cells to me, three days ago, I had to struggle to remember what they were. I don't think the term has come to my attention since my freshman year in medical school, nearly fifty years ago.

These are typical red blood cells

I realized if I was going to write about them, first I needed to read about them and then I needed to write about blood and white blood cells in general and get to mast cells in humans and dogs in another post.

So let's start from scratch. I weigh 150 pounds, so my body contains roughly  ten and a half to twelve pounds of blood, about four and a half to five quarts worth. My blood performs a number of vital functions, especially those of transporting oxygen to my cells and getting rid of carbon dioxide. Those tasks are allotted to my red blood cells which make up 40 to 50% of my total blood volume (the percentage for men is a little higher than for women).

Most of us know something about red blood cells and since our blood has a red color it's easy to ignore its other blood components. But those are crucial as well: roughly 55% of our blood is a fluid called plasma. Over 90% of that is water, but there's some sugar, fat and even proteins (actually about 500 kinds of proteins). In addition, vitamins, minerals, hormones and enzymes as well as  thirteen blood clotting factors help make up plasma.

That doesn't leave much room for two other absolutely essential kinds of cells: platelets and white blood cells. Platelets are tiny, roughly a third the size of red blood cells, but they work together with the blood clotting factors to enable us to plug wounds. Sometimes they're too effective in causing clots; they apparently have their peak activity in the AM, so is presumably why strokes and heart attacks are somewhat more likely to occur then.

That brings us to white blood cells which only form about one percent of our blood volume, but are crucial to our survival. They are also found elsewhere in our bodies, especially in our spleen, liver and lymph nodes. When you have a CBC, a complete blood count, you should have 4,500 to 10,000 white cells in every milliliter of your blood. Over half of those are neutrophils, white blood cells that rush on ahead of their colleagues to gobble down bacteria, viruses and other infecting organisms. They're called neutrophils because when a typical microscopic examination of blood is done they don't pick up much of the stain used to show granules containing chemicals.

T-cell lymphocytes attacking a cancer cell

The next biggest chunk ( a quarter to a third) of your white cells are lymphocytes which come in three "flavors." NK or natural killer cells are a part of the innate immune system and play a major role in defending the host from both tumors and virally infected cells. T cells are involved in cell-mediated immunity whereas B cells are primarily responsible for humoral immunity (relating to antibodies). The function of T cells and B cells is to recognize specific “non-self” antigens. Once they have identified an invader, the cells generate responses that are tailored to maximally eliminate pathogen (invaders such as bacteria) or infected cells. B cells work by producing large quantities of  antibodies which then neutralize foreign objects like bacteria and viruses. In response to pathogens some T cells, called T helper cells produce chemicals called cytokines that signal other cells and, in doing so, help that direct the immune response while cytotoxic T cells produce enzymes which induce the death of infected cells.

Now we're down to small percentages, but some highly significant white cells: Eosinophils, whose granules strain red, and basophils with blue-staining granules. The eosinophils typically make up about 3% of your WBC count and mediate allergic reactions. Basophils amount to less than 1% of the WBCs in normal healthy people and their granules contain histamine, important in allergy, and heparin, an anti-clotting chemical, as well as other mediators of body reactions. When tissues are damaged, basophils can help bring about inflammation, essential to healing, and increase blood flow to the injured area.

So what about mast cells? They hang out elsewhere and I'll write about them tomorrow.

Guillain-Barre strikes nearby again

Friday, September 14th, 2012

Patients with GBS frequently need a respirator, for a while.

For the second time, someone I know has had the misfortune to contract Guillain-Barre Syndrome, (GBS) sometimes called "ascending paralysis."

The first was a good friend who was an Air Force colonel, a former SR-71 pilot, athletic, slender and tall...he had been our Center Vice Commander when I led a small military hospital, then we kept in touch after he retired. Several years later a mutual friend called to tell me he was on a respirator in an ICU unit.

He made good progress over the next few months and eventually returned home, but with a markedly altered gait due to residual leg weakness.

That was my real-time introduction to Guillain-Barre which otherwise had been an obscure entry in a medical textbook. We saw that friend two months ago and his weakness is stable. Then two days ago I heard that a member of my men's book club, a retired professor, had the same syndrome, had been hospitalized locally and, as of yesterday, was undergoing rehab in the same facility where my wife and I have gone to for physical therapy.

GBS is an autoimmune disorder, meaning our own immune system, instead of attacking a target that is foreign to us, like a bacterium or virus, turns on us and attacks part of our body. The tissue involved varies with the disorder. Examples include Type 1 diabetes, rheumatoid arthritis, lupus and multiple sclerosis. Notice I'm not calling these illnesses as a group diseases although some are more familiar to me under that title. So what's the difference?

Some people use the terms disease, disorder and illness interchangeably. But the way I was taught, a disease has a specific cause, often an infectious one, and the body's normal function is impaired. So typhoid fever is a disease. In contrast you carry some bacteria in your bowel normally, without them causing any problems. There are certainly diseases that don't (according to our current knowledge) have a direct bacterial or viral cause; coronary artery disease would be one such.

My take on medical diagnoses that are termed disorders is they are not associated with a known infectious organism, are not communicable (certainly not all diseases are)  and may have an unknown cause. The metabolic disorders, e.g., diabetes or hypothyroidism, would fit into this category.

GBS often follows a minor infection, can occur at any age, but is more likely to be seen in people who are 30 to 50 (this may be changing as more older patients have been noted in recent years)and, in most cases, the condition starts with muscle weakness in the legs which then spread upward (i.e., ascending paralysis). It can worsen very quickly, but most frequently does so over a period of days. If a patient's chest muscles and diaphragm are affected, they may need  to be on a respirator.

Many have to learn to walk again.

There is no cure for GBS, but most people survive and, with appropriate medical care, eventually recover totally. In most series of patients, less than a third are left, like our former SR-71 pilot friend, with longterm weakness after three years.

There are treatments that appear to be helpful. An excellent review of GBS Rehabilitation Outcome and Recent Developments was published in a 1999 edition of the Yale Journal of Biology and Medicine. A series of 37 patients with GBS with a mean age 62 (see what I said about older patients) were followed for an extended time period. Fourteen required mechanical ventilation for 38 days (plus or minus 10), but all were eventually weaned off the ventilator successfully. None of this group of patients died, but overall mortality rates in larger series of patients have ranged from 3 to 18 %.

The clinical picture of GBS is changing and the Yale article gives lots of important concepts starting with the definition of the syndrome: a polyneuropathy (a disorder affecting multiple nerves) with an acute onset of bilateral motor weakness, absent (or severely diminished) reflexes and specific pathology features. It's the most common acute (as opposed to chronic) neuropathy in the developed world, but is still relatively rare with about four to five cases a year in a town like Fort Collins with a population of ~150,000.

Most who develop GBS have had a preceding illness or event (flu-like illness, diarrheal disease with Campylobacter being the most usual cause, upper respiratory tract infection or perhaps a vaccination (this is a hotly debated topic; the CDC review of the proposed link between vaccinations and GBS concludes there's little evidence to support a causal association with the possible exception of the 1976-77 swine flu immunization).

It's important to seek medical care early if symptoms of GBS develop; doing so may save your life.

Prostate Cancer Controversies

Friday, September 7th, 2012

A prostate cancer awareness symbol

Prostate cancer is the most common cause of cancer death in older men. A few years ago most of us males over the age of forty (it seldom occurs before that) were periodically screened for the disease using the PSA test (a blood test for a prostate-specific antigen) and had digital rectal exams to check the size and consistency of our prostates whenever we had our yearly appointment for a physical and also had comprehensive lab work done.

Then things changed: the annual medical exam was discarded by most physicians in favor of a targeted examination, which in my case, with my history of high blood pressure, includes a nurse taking my BP and my doc listening to my heart and lungs. Not much else, unless I have a specific complaint. I'm 71 and haven't had a digital exam for five years. I had a PSA done when blood was drawn for other reasons and it was 0.7, well under the level that would have raised any concern about my prostate.

In October, 2011, the Harvard Health Blog provided two points of view on pending new recommendations for prostate-specific antigen (PSA) testing from the U.S. Preventive Services Task Force. A panel of experts after a thorough review of the literature on prostate cancer had concluded, that for men over 50, screening using the PSA test offered a low benefit to risk ratio. A huge controversy broke out with the American Urological Association arguing against the proposed new concept. Other physicians noted that an elevated PSA doesn't always mean cancer and, much more importantly, doesn't  distinguish which cancers of the gland are likely to be fast-growing and life threatening.

Oncologist, Dr. Marc Garnick, editor of Harvard's "Annual Report on Prostate Diseases," noted that the new testing recommendation was not a blanket statement fitting all men: those at higher risk (African-Americans and men with family history of cancer of the prostate) may still be suitable candidates for annual PSA testing. He later published an article in Scientific American mentioning that the use of regular PSA testing had led to over a million men having treatment for prostate cancer since 1985 and many thousands of men having complications of prostate surgery or radiation therapy (impotence, incontinence, rectal bleeding).

Dr. Garnick basically agreed with the task force's conclusions; felt the evidence supporting regular PSA testing was flimsy, but thought that the procedure gave important information after a cancer of the gland has been diagnosed.

Garnick was interviewed by a senior editor of the magazine and the resultant February 8, 2012, piece supplies audio comments from Dr. Garnick which detail some of the issues. One such concerns a man who has had his malignancy removed by a total (radical) prostatectomy. His PSA should plummet down to undetectable levels and, if it doesn't, either not all the cancer was excised or there has been spread beyond the local area (metastases).

I was reading my email a few days ago and noted one from my friend Rick with a link leading to an article from the Fred Hutchinson Cancer Research Center in Seattle titled "Prostate Cancer: 6 things men should know." There were six myths rebutted and I especially noted four conclusions: eating tomato-based foods and products doesn't prevent the malignancy; high testosterone levels don't correlate with risk of this tumor; omega-3s don't lower the risk (actually very high blood levels in one study were associated with higher risk); dietary supplements (selenium and vitamin E) don't prevent the disease.

At age 50 and above, this was on my schedule; at age 71 it's not

Another online publication from the Hutchinson Center gives background information on prostatic cancer. They note the frequency of the disease increases in men over 55, that obese men have a higher risk of developing an aggressive form of the disease, as do smokers. Those who drink red wine (four 4-ounce glasses a week) were noted to have a 60% lower incidence. Older men may receive unnecessary surgery; in this group the malignancy, often small and slow-growing, may not be life-shortening.

The need for screening in the general population of men is an ongoing medical controversy. We'll likely hear much more about PSA testing, but many would concede that a new type of evaluation needs to be developed.

I agree and for now I don't plan to have any more PSAs drawn.