Mini Med School 2006 Information and Answers to Questions

Anatomy and Physiology

CU-Boulder Q: I have heard the buildup of lactic acid is an indicator of fibromyalgia, is this the case?

The cause of fibromyalgia is still unknown and hotly debated; there is no animal model so research has to proceed slowly. Good, reliable information about it is not easy to find, but the National Library of Medicine has done a fine job of assembling a list of trustworthy Web resources at http://www.nlm.nih.gov/medlineplus/fibromyalgia.html

CU-Boulder Q: Does Lub-Dup count as one beat or two?

One beat. Lub is the closing of the “backward” valves as the ventricles begin to contract; Dup is the closing of the forward valves to prevent backflow into the ventricles as they start to relax.

Montrose Q: Is the lipid collection in coronary arteries a result of inflammation? Which comes first--lipids or inflammation?

Tough question with no answer at this time. There are theories that accept both models, so more work is needed. But there is much to be found out. In the past few years, it’s been found that blood levels of something called CRP correlate well with risk of coronary artery disease. CRP levels have been know for years to be a marker of inflammation. The American Heart Association has an interesting article at http://www.americanheart.org/presenter.jhtml?identifier=4648

Montrose Q: What long-term changes (vital signs, increased respiratory rate) does the body make when a person moves from sea-level to high altitude?

These will be variable; a growing person is able to make more profound adaptations that an oldster (kids in Leadville have bigger chests). In general, tidal volume (the amount we inhale, on average) may increase a bit, while the initial rapid breathing settles down. The most important change is this: Sensors in the kidney )remember, it gets to look at a lot of the heart’s output) detect lowered oxygen content and secrete erythropoietin, the hormone that makes the bone marrow ramp up its production of red blood cells. So people at high altitude have higher red cell counts (“hematocrit”, the % of blood volume that is red cells may go from 35% to 50%).

Greeley Q: What is the function of the CORACOACROMIAL ligament and what happens when it is destroyed during rotator cuff surgery?

According to Gray’s Anatomy: “This ligament, together with the coracoid process and the acromion, forms a vault for the protection of the head of the humerus.” It goes from the coracoid process to the acromion, both of which are prominences on the scapula, one in front and the other behind. In some operations (fewer in recent years) the ligament is cut to offer better access to the area needing repair. There are some reports that the shoulder can be less stable if the ligament has been cut. It’s worth a careful assessment of shoulder strength and mobility. For people interested in what the rotator cuff is, and surgery to repair it, there is a very clear interesting site at http://www.medicalmultimediagroup.com/pated/shoulder_problems/cufftearold.html

Montrose Q: What other dietary/supplemental changes can a person make to increase acidity for high altitude adjustment?

Plums, coffee, grapefruit, orange juice, lemonade and limeade, yogurt, buttermilk.

Montrose Q: What generates the electricity in the body?

As we said, it’s the movement and separation of charged ions like potassium (K+), sodium (Na+) and chloride (Cl-). Membranes have pores and channels and can pump one or the other of these ions selectively, creating a charge difference across the membrane, like a capacitor. The nature of membranes is such that when the charge begins to flow across the membrane it is rapidly propagated along the length of the cell, Some nerve cells are a meter or more long, so an electrical excitation can move rapidly, say, from the brain to the knee, causing local muscles (which are triggered by the same sort of electrical events) to contract.

Montrose Q: What causes clots?

Platelets, the tiniest cells in the blood, adhere to sticky or cut surfaces and become activated, exposing molecules on their surface that interact with the cascade of clotting proteins which are abundant in blood. The proteins are changed from an inactive to an active state, eventually resulting in the conversion of soluble fibrinogen to insoluble polymeric fibrin, the essential backbone of a clot. Rough surfaces can cause clotting (possibly the surfaces of atherosclerotic blood vessels), as can slowed flow in veins (deep vein thrombosis as sometimes seen in travelers sitting for extended periods), and turbulent flow (for example around damaged heart valves).

Montrose Q: What is the latest technology or research for treatment of macular degeneration? Is there at this time any drug or procedure that can restore some vision loss from macular degeneration?

I don’t know enough about this to give you a full answer. but there is an excellent web site from the National Eye Institute (NIH) at http://www.nei.nih.gov/health/maculardegen/armd_facts.asp

There is some buzz about the use of a new treatment, Avastin, in macular degeneration. Ask your ophthalmologist.

Cell Biology

Boulder Q: Do organelles have any genes within them? How are they made?

Mitochondria have a small set of genes within them, which make some of the special products expressed only in these little powerhouses. What is exciting is that most scientists believe that mitochondria are derived from bacteria that may have gotten inside some primitive cell and become a symbiont. The mitochondria DNA has certain similarities to ancient bacterial DNA.

Montrose Q: How does radiation or chemotherapy stop cancer cells from replicating?

The energy from radiation can be absorbed by DNA directly, or it can interact with cell water to create activated atoms called "free radicals." In either case, energy is transferred to DNA resulting in chemical changes, like the formation of glued-together thymines called thymine dimers. These cannot unwind during DNA replication, so the cell dies when it tries to divide. Many cancer chemotherapy drugs cause similar damage to cancer cell DNA. More on this during our Cancer lecture.

Boulder Q: Is DNA more easily damaged by industrial chemicals as opposed to UV light exposure?

Like most things in biology, it depends. First, many industrial chemicals are not particularly "genotoxic." They may be irritants or cause damage some other way, or they may be relatively harmless. Then, it is a question of dose. Many chemicals are known to damage DNA only at much higher doses than are ever achieved in the environment. PCBs are an example; no one is sure if they are harmful at the very low exposures the average person receives. UV is dangerous, but as we'll see in the Cancer talk, there are many events that have to take place before that sunburn results in a skin cancer.

Boulder Q: In multiple births, how common is it for one of the babies to be born with a birth defect (for example, Downs Syndrome) when the other is not? Is this only possible in fraternal births, or is it possible in identical ones as well?

Down syndrome is usually caused by the fetus having an extra copy of chromosome 21 in some or all of its cells. The chromosome is normal but the extra copy unbalances metabolism and several pathways do not perform or develop normally. It is usually the result of an abnormal sperm or egg contributing to the fetus (the sperm or egg has the extra chromosome, due to imperfect division in the process called meiosis). Sometime the fertilized egg begins correctly but one of the first cell divisions results in one of the chromosome 21s going to a daughter cell it shouldn't have. So it is seen in both fraternal and identical twins, though more commonly in fraternal twins, since the abnormal egg or sperm cause is by far most common. It can be more difficult to diagnose Down syndrome before birth in a twin pregnancy.

Aurora Q: What mutation of the genome is most widely considered to be the to be the reason for White blood cells attacking pancreatic islet cells in type I diabetes?

There isn't just one. Probably the most significant is the HLA gene group, which regulate normal immune responses, especially those of T cells. Certain HLA types are more associated with Type 1 diabetes than others, but it is by no means absolute. Next in importance is the insulin gene itself, though why is not clear. After that, at least 15 other genes play some role in determining whether a person will get Type 1 diabetes. And the role of the environment may well trump that; genetics change only slowly but the incidence of juvenile diabetes is increasing alarmingly worldwide.

Microbiology

Boulder Q: Are there common, easily available, inexpensive, masks that people might wear?

A very nice mask is the N95, which has pretty good efficacy at blocking oral spread of viruses. They used them in Toronto during the SARS outbreak. They cost about $1 each. But note, hand washing has been shown to be more effective in stopping spread of respiratory viruses.

Boulder Q: What's the best type of waterless hand sanitizer for the average person to use if they can't be near a sink at all times?

Look for something that has at least 60% alcohol, Purell is a common brand. Avoid cut-rate products, some have as low as 40% alcohol and are not effective. These things do not generate resistant bugs, as they are physical membrane disrupters. They are good to use when there is some risk of the hands being contaminated (having held onto the stair rail for 4 flights in the hospital, say, or played with a snotty baby). They shouldn't be used excessively just for the sake of feeling clean.

Boulder Q: Why shouldn't people who have had Guillan-Barre disease get a flu shot?

We think that Guillan-Barre syndrome is a post-viral infection abnormality, possible due to autoimmunity. Because of this, many doctors are reluctant to give a "live" virus vaccine to someone with G-B history. Flu vaccine (injected) is not live, but there are reports of G-B in people after flu shots anyway, so we tend not to do it, as a precaution against a very rare event.

Pueblo Q: Would you recommend a flu vaccine for a 20 month old child?

Yes. The CDC this year lowered the recommended age for flu immunization to 5 months. Note that these little ones require 2 shots to become fully immunized, so make a plan with your health care provider. Flu can be very hard of little kids (higher morbidity and mortality than in adults).

Boulder Q: Can you explain how you can use viruses to fight bacteria?

Most kinds of bacteria are susceptible to "bacterial viruses" called bacteriophage, or phage for short. The idea of using phage as a weapon against bacterial infection was ridiculed in this country for years, but the Russians did some very interesting experiments. The appeal is that bacteria that have become resistant to almost all antibiotics should still be susceptible to phage. The problems are drug delivery: How do you efficiently get the phage to the bacteria in the infection? How do you avoid the patient becoming immune to the phage? And how do you sell this strange idea to the public?

Aurora Q: Is it your opinion that a many viruses are delivered through a bacterial vector? If so, can antibiotics effectively treat viruses by killing the vector by which they invade?

Nice idea, but we don't think so. Most viruses are very specific for their hosts, whose metabolism they must take over and convert to virus production. So it is impossible to infect a human cell with bacteriophage, and impossible for measles to grow and reproduce in yeast or bacteria.

Pueblo Q: Some individuals are avoiding getting the flu shots claiming the vaccine causes early onset of Alzheimer's disease. Is there and what is the basis of this concern?

I (JJC) can find no scientific data that even hints at a connection between the two. But that doesn't mean there aren't dozens of Web sites that claim a connection. Most are what I would call "quack" sites, and come from conspiracy theorists. In many cases people are making what's called the "post-hoc fallacy;" if one thing happens after another, it must be that the first thing caused it. Mother gets a flu shot and two years later is diagnosed with Alzheimer's; the shots must have caused it.

Montrose Q: Do antioxidants actually boost the immune system and how does this work?

There is no evidence to support a specific effect of antioxidants on immunity. In the lab it is easy enough to show that if you remove all antioxidants from a system things, including immune things, don't work right; or if you flood the system with reactive oxygen species, things go badly. But that is a far cry from saying that in people eating a regular diet, supplementation with antioxidants will have some sort of tonic effect on immunity. I wish it were so but there are no data.

Boulder Q: A Denver cardiologist is promoting the use of mega doses of Vitamin C for the treatment of West Nile Virus. What is the basis for this theory?

This is based on a model from a clinic in California, which recommends up to 120 GRAMS of Vitamin C a day! That's more than even poor Linus Pauling, when he was getting confused, would have recommended. There is nothing in this idea at all, that I can see. When you see a web site promoting something, it sometimes helps to notice whether it ends in ".com"

Boulder Q: Is there any work going on towards developing vaccines in cultures besides eggs, since many people are allergic to eggs, and therefore can't be immunized?

Yes, a lot, both for your reason, and to increase vaccine yield and shorten the time to make it. Viruses may be grown in cell culture instead of eggs, so many people are trying to optimize that process. Also, just the key antigens can be expressed in harmless bacteria or yeast which make them and release them into the medium. Many drugs are already made this way.

Boulder Q: Should one who has had a chicken pox vaccine periodically be tested to see if the immunity continues?

In the best of all worlds we would do that, and custom-deliver boosters. But it isn't all that easy to test this type of immunity, so usually we don't bother. The CDC recommends a booster only for people with special risk factors.

Pueblo Q: Is there a connection between immunizations and autism?

No. This has now been conclusively demonstrated, after many children needlessly suffered serious viral illnesses and a few died, because their parents did not get them vaccinated; or the government suspended vaccine programs (Sweden, Japan).

Pueblo Q: Having West Nile Virus, why does it effect people different? My friend was paralyzed from the waist down for 6 weeks, why?

We don't know why there are such different responses to the virus. Older people in general get worse disease.

Denver Q: There is so much work being done on genomes. Can you help distinguish the differences between some of the different ways this mapping of the genome is being developed. For example, cloning, stem cells, and so forth. Are these all good?

Mapping the genome does not involve stem cells. You just need one nice healthy cell, say a white blood cell or a skin cell. Using molecular biology techniques, all the DNA in it is amplified (replicated) millions of times until you have enough to work with. Then it is broken into manageable bits and the nucleotide bases in it are sequenced by automatic machines that can do hundreds of thousands in a day. Then the hard part is stringing together these individual sequences into a whole (like reassembling a book from its loose, scrambled, unnumbered pages). Once that's done and redone and checked, you have a genome. The next step it to look at differences between many people, and try to make associations: Do all redheads have ATG here, while brunettes have ATT? If so, what is that gene, and how does it dictate that difference? Is there a consistent gene difference ("allele") in people in whom aspirin works but ibuprofen doesn't? And so on. Cloning is just growing more cells from a single starting cell. Most cancers are clones. A stem cell, when it is cloned, can produced "differentiated" cells that can do something the stem cell itself can't. Thus the hematopoietic stem cell can give rise to platelets, red cells, and white blood cells.

Immunology

Denver Q: Despite the 200 year time lapse, please compare the medico-ethical difference between the Jenner testing of cowpox/small pox and the experiment with Bubble David’s bone marrow transplant. Is there really a difference? Both patients were minors and legally not competent to consent.

That’s true, but in both cases someone who was a parent or in loco parentis gave permission, in a manner approved by the standards of the time. I think in David’s case, it was understood that all due care was being taken, that the treatment was state of the art, and that the family wished treatment that might have freed David from the bubble forever, knowing that there was a risk that it would not work and could be fatal. Is it so much different from allowing the surgeons to repair a heart defect in a child nowadays?

In Jenner’s case, though, the child was not ill and you could argue might never get smallpox, so he was put at considerable risk by the experiment with an uncertain benefit. Nowadays we would not test a vaccine on a child unless there were extensive data showing it was harmless in the best animal models, or it was similar to known substances that were harmless, or something like that.

Denver Q: If someone is already affected by an auto-immune disease, does that make them more susceptible to develop another kind of auto-immune disease since their immune system has already made a mistake, is more prone to reacting the wrong way?

There is pretty good evidence for autoimmune diseases clustering in families, and also for one person having more than one (thus, “Rupus,” with characteristics of both rheumatoid arthritis and lupus). The risk is not high, and reminds us that for these diseases, you need a genetic predisposition (not fully worked out) as well as an environmental cause (not fully worked out).

Denver Q: My other question concerns the environment in the trigger of an auto-immune disease. It has been established that, for example, type 1 diabetes occurs when there is a genetic predisposition combined with environmental factors, such as a virus, that triggers the actual onset. Would it be theoretically possible that if an individual who developed type 1 diabetes would have been in a different physical environment at the very time of the start of the auto-immune attack, then that person would not have developed type 1 diabetes?

You would have to think so, though it would be hard to test. In animal experiments, certain triggers will result in autoimmunity, and if the triggers are withheld, the animals stay healthy.

Boulder Q: Is there such a thing as a homeopathic vaccine for measles or mumps?

I found this statement on “Shirley’s Wellness Café,” a site whose reliability I cannot vouch for: “Homeopathy can be used successfully to prevent and treat smallpox, measles , whooping cough, chickenpox, and other ailments.” Of course, this is a secret the homeopaths seem to be keeping from the rest of us.

Boulder Q: How does the thymus gland relate to your immune system?

It is the site where developing T cells rearrange the gene segments that code for their receptors for antigen. Since these rearrangements are random, some of the receptors end up being “anti-self,” so in the thymus, if they bind “self” at this immature stage, they die by apoptosis.

Montrose Q: How does homeopathy work? or does it?

There is no evidence that it does. It is based on a belief that chemicals leave behind mysterious “vibrations” in water as they are diluted; in fact, the more dilute the stronger, and the best are solutions so dilute there will not be even one molecule of the chemical in the bottle you buy. This idea has been tested in vigorously controlled experiments and found to be useless. Drexel University College of Medicine, a new name just a few years ago, is the descendent of the homeopathic Hahnemann Medical College of Philadelphia. They no longer teach homeopathy.

Boulder Q: If someone had a smallpox vaccine 45 years ago, would there be any immunity now? How about 25 years ago?

There may be some. We know that about half of people have easily measurable immunity after 25 years. But in the absence of smallpox, we don’t know how a lab measurement would relate to real-world resistance to an epidemic. I’d guess that if there were an epidemic, those of us who were once immunized should stand back and let naïve people get the first shots.

Boulder Q: In leukemia, what effect does the overgrowth of white blood cells actually do that is harmful to the person?

They can replace normal cells simply by outgrowing them, or they can get between them and prevent their normal interactions. Also, some tumor cells release factors that inhibit immunity, possibly in an attempt to ensure the survival of their own “selfish DNA.”

Pueblo Q: Does a tonsillectomy as an adult pose a higher risk or longer recovery time versus having the procedure as a child?

Oy, everything is harder when you’re older.

Pueblo Q: Is the immune system affected by the procedure? Any precautionary measures?

Probably not, or we’d be reading scientific papers about it by now.

Boulder Q: Evolutionarily speaking, do cowpox and smallpox have a recent common ancestor?

There is enough genetic sequence difference to suggest that the separation was not very recent. Cowpox is, curiously, a rat virus; both the cow and the human are “incidental hosts.”

Boulder Q: Why do some viruses stay dormant (mono) while others re-emerge (AIDS?)

Not completely known. The latent viruses of the herpes family, like mono and chicken pox, actually turn off almost all gene expression so they make the least amount of antigen for the immune system to see. When something happens to decrease immunity they can wake up and make a productive infection. HIV is an RNA virus that gets into a cell, makes a DNA copy of itself, and inserts it somewhere in the cell’s DNA genome. It carries a “promoter” region which responds to the factors made by the cell when it is activated; when the cell gets turned on, so does virus production. Nasty.

Boulder Q: If a person gets the flu, do they become immune at all to the flu? Why is it necessary to continually get flu shots?

It wouldn’t be if this weren’t among the most mercurial of viruses; it changes virtually from person to person by random mutation (“drift”) and it also can exchange huge hunks of DNA with another flu virus all at once (“shift”). So this year’s virus may be only slightly related to last year’s and you need a new shot.

Boulder Q : Why doesn’t the US use live tuberculosis vaccinations like the ones that are used in Asia? Aren’t they more effective than dead vaccines?

Yes they are. But there are population differences related to gene frequencies, and some studies have show poor efficacy of TB vaccine in US populations. I think a new vaccine for all of us is imperative, and a number of good labs are hard at work on it.

Montrose Q: Antibodies vs. dendritic cells: Are antibodies only activated in disseminated infections and dendritic cells activated in localized infections?

Dendritic cells get activated in local infections and, if the disruption is strong enough (technically, if the local cells release enough cytokines and chemokines) the dendritic cell will leave the area, go to the nearest lymph node, and show what it’s seen to the T and B cells there, resulting in a systemic immune response.

Pharmacology

Montrose Q: What is your opinion on the Wal-mart proposed $4.00 generic cost? How will that impact other chains and independent drug stores?

It could be good or bad. Good, if we are really being overcharged by everyone else (but it’s hard to believe so when you are paying $10 for 30 pills which are the product of some very complicated chemistry and testing). But if WalMart is selling below cost to increase store traffic (already known to be happening in Florida) then they may be helping to put smaller pharmacies and chains out of business, and that could be bad

Montrose Q: Why don't MDs consult with a pharmacist more when prescribing or diagnosing a patient's care?

They could in some cases do a better job of it, it is true. One of the problems is that reimbursements to physicians are so low now, that time spent doing that is time banns money lost, according to the administrators, so it is not encouraged. Again, with better electronics, maybe that will get better.

Montrose Q: The media has recently said that it can cause irreversible liver damage to take too much ibuprofen either in one dose or over time. What is the maximum safe dose of ibuprofen at one time and over time?

See FDA article at http://www.fda.gov/fdac/features/2003/103_pain.html

Also an article in Hepatitis Magazine: http://www.hepatitismag.com/storydetail.asp?storyid=37

Greeley Q: What is the mechanism by which grapefruit juice affects various medications?

There is a chemical in grapefruit that blocks one of the P450 enzymes in liver that “detoxifies” many chemicals in our diet, as well as certain drugs. If it is inhibited, the drug persists longer and higher, sometime even dangerous, levels are achieved. It takes a fair bit of grapefruit to do this, however, so if you accidentally have a swig don’t panic.

Montrose Q: How long do students in Med School study pharmacology?

One very long formal course, and then as appropriate in just about every other course from second year on.

Montrose Q: Are doctors encouraged by drug companies to prescribe drugs without knowing all the potential complications?

Let’s say that when you talk to a drug company rep, the first thing they stress is not the complication rate. But they don’t lie, and the training of a doctor is supposed to help her or him make intelligent decisions based on facts.

Montrose Q: What do you see in the future for a geriatric pharmacist in light of our aging population?

I guess this means a pharmacist who specializes in older patients! We need many more of these, just as we need doctors who do that. A burgeoning field, interesting and hardly explored.

Montrose Q: Why are Western Medical Practitioners so reluctant to acknowledge or even research the use of herbal remedies for treatment of disease?

No money in a product that can’t be patented. It costs hundreds of millions of dollars to test and get a new drug approved. If there was one that really looked good, the NIH would test it (it has for a few preparations, like saw palmetto).

Boulder Q: I've always taken Lipitor in the mornings, you said it should be taken at night. Why?

The manufacturer says “Lipitor is taken once a day. It can be taken with or without food, day or night. It's helpful to remember to try and take Lipitor at about the same time every day.” A lot of practitioners think that most drugs have fewer side effects when taken in the evening, though.

Human Behavior

Pueblo Q: As a PhD student in Psychology, I am not always in agreement with children hitting certain benchmarks by a certain age. I believe that children can learn so much more and comprehend more than we give them credit for. What are your views on this?

Absolutely agree. Although some benchmarks are essentially “hard-wired” and it is amazing to see kid after kid first learning to roll front to back, then a month later back-to-front, and so on. An experienced child practitioner can usually tell a kid’s age to the month by watching them long enough. But intellectual development is variable and I also think we don’t ask enough of kids. In some countries students start on a second language in 1st grade, on Latin in 3rd grade, and so on. Kids learn so much more readily than do adults, they should at least get the chance to try. That’s why the home environment is so important.

Greeley Q: What do you mean when you say that girls write diaries to separate from their mothers?

To have a little piece of their mind that is secret, in which they can try out ideas and thoughts without fear of adult censorship or worse, ridicule. It’s why parents should never read a kid’s diary unless it is an absolute emergency.

Pueblo Q: How do you feel about teaching children to use sign language before they speak? Do you think it holds any merit that a child will excel at a quicker learning rate?

Probably not. It has been shown that children who learn to sign from signing parents begin by “babbling” with their fingers, at just the age that speaking kids babble out loud. So it could sharpen some skills, I guess, but maybe not more than a second spoken language introduced along with the first one (as happens in many bilingual families).

Montrose Q: Why are identical twins more disposed to have problems? Are both twins equally disposed and if not, why?

Sorry for the confusion. Identical twins share all the same genes; fraternal twins share about half, like any other siblings. We want to know if there is a genetic component to schizophrenia. We ask one of each pair of 100 identical twins, and one of each pair of 100 fraternal twins, if they are schizophrenic. 10 in each group say yes. Then we ask them about their sibling. We find that only one of the fraternal twin’s siblings is also schizophrenic, but 6 of out 10 identical twins with schizophrenia also has a twin with schizophrenia. This would indicate that there is a strong genetic component to the disease. It's one of the reasons we study mice so much: inbred mice are all like identical twins, and if you find such a strain that in which all have, say, lupus, you know it's a genetic disease and can begin to unravel the genes involved.

Montrose Q: How does a doctor determine if medicine or counseling should be used to treat depression?

In general, “major” depressions respond only to strong medication. “Minor” or “reactive” depressions (due to terrible events) often respond best to counseling, sometimes with help from tranquilizers or other medications. It's not always simple to know into which category your patient fits, and psychological testing can be useful for helping make the diagnosis.

Cancer

Boulder Q: What are your thoughts about chelation therapy, that is often touted as the only answer for very ill individuals?

Chelators are chemicals that bind and thus inactivate certain ions, including calcium and heavy metals like mercury and lead. They are used as drugs for treating acute heavy metal poisoning. They are dangerous and must be used by trained practitioners, since the blood concentration of calcium is critical to normal heart function. Alternative practitioners have used this therapy for atherosclerosis and for heavy metal poisoning that is not detected by the usual standards (and therefore may be fictional). There is no evidence for its efficacy in either of these applications and they are disapproved by the relevant medical boards.

Montrose Q: What ongoing research is your lab working on?

Taking a breather while I work on the Black Death, and public education and outreach events, like the Mini Med School, the Café Scientifique, and Art in Science/ Science in Art.

Boulder Q Why is a test for ovarian cancer – early detection – so elusive and what will it take to develop a sensitive and specific test for it? i.e.: either a blood or cytology test?

To develop a good blood test for any cancer, we need to identify a protein released into the blood that is unique to that tumor type. Currently the best example is probably PSA, prostate-specific antigen. No all tumors seem to make a unique product. Ovarian cancer often makes a protein called CA125, for which there is a test available. The problem is, in recent large trials, although the test was in fact able to detect people with very early stage ovarian cancer, it missed other cases at the same stage. Worse, it had a high “false-positive” rate, meaning the test was positive in a woman without cancer. What must one do with a positive test? The results were that too many women were being exposed to potentially risky operations on the basis of a positive CA125 test, even when they did not have cancer. There is a lot of work going on to develop non-invasive tests (ultrasound, for example) to be done on a woman with a positive test before resorting to surgery. At present, therefore, CA125 screening is not generally advised. Many labs are looking for new, alternative tests.

Boulder Q: How does a doctor detect digestive cancers?

Symptoms are important: unexplained weight loss, pain, altered bowel function, and so on. A routine colonoscopy every 5 years, more often if there is family history or polyps have been found. If there is a high degree of suspicion, a blood test for CEA is done (it has false positives, like CA125, so it’s reserved for when there is other evidence for a problem). Finally, barium meals or enemas, CAT scans, MRI, and exploratory surgery may be required.

Greeley Q: Referencing your chart entitled "5 year survival rate by stage," what is the comparison of survival rates for "with treatment" vs. "without treatment?"

Hard to say. “Without treatment” is not an option in a medical setting, so the only controls for new treatments are the currently-recognized best treatment. The best we can do is compare now to decades ago, when (we know now) treatment was not very effective, and see the improvement in survival.

Montrose Q: Why are we told not to BBQ very much?

Meat heated to charring temperatures generates nitrosamines from its amino acids, and that family of chemicals is carcinogenic. So, barbecue is OK in moderation and if you limit the charring (inside cuts). Vegetables have so much more water and less protein that charring in the BBQ is less of a worry, though don’t overdo it. Charred veggies are often bitter as the char is carb-char, like burnt toast.

Email Q: It seems that certain types of tissues do not develop cancers (or, at least, I've never heard/read about such cancers). Muscles, eyes and hair follicles would be examples of cells that seem to be cancer-free. Do these cancer-free cells have some protection that might constitute a clue for cancer treatment or prevention?

There are tissues that develop cancer more rarely than others. One thing that limits cancer development is cell division rate. If cells in a tissue do not divide, they cannot lock in mutations in a new clone. So the lens of the eye, whose cells do not have nuclei, never develops cancer. Other eye tissues unfortunately do, and neuroblastoma developing in the retina is a genetic tumor of children. There are muscle cancers called rhabdomyosarcomas (striped muscle) and leiomyosarcomas (smooth muscle). Skin tumors do develop in hair follicles too. Tissues where the cells normally divide a lot are most prone to cancer (breast, for example, whose ductal cells grow and die with each hormonal cycle).

IMAX Q: Are pheochromocytomas hereditary?

From Dale Cassidy, 2nd year medical student who researched this question: A small minority (about 10-20%) of pheochromocytomas arise because a person has an inherited susceptibility to them. Inherited pheochromocytomas are associated with four separate syndromes: Multiple Endocrine Neoplasia, type 2A (MEN2A); Multiple Endocrine Neoplasia, type 2B (MEN2B); von Hippel-Lindau disease (VHL); and Neurofibromatosis type 1 (NF1). Individuals with pheochromocytomas as part of any of these four syndromes usually have other medical conditions as well. People with MEN2A often have cancer (usually thyroid cancer) and other hormonal problems. Individuals with MEN2B can also have cancer and hormonal problems, but also have other abnormal physical features. Both MEN2A and MEN2B are due to genetic alterations or mutations in a gene called RET, found at chromosome 10q11.2. Individuals with VHL often have other benign tumors of the central nervous system and pancreas, and can sometimes have renal cell cancer. This syndrome is caused by a mutation in the VHL gene, found at chromosome 3p25-26. Individuals with NF1 often have neurofibromas (benign tumors of the peripheral nervous system). NF1 is caused by mutations in the NF1 gene, found at chromosome 17q11.

Email Q: At the end of your lecture you were describing systemic treatment, specifically chemotherapy. You mentioned various agents and how they work/the type of tissues they affect. I don't have my notes in front of me but for example I think that Vinblastine was described as a cystoskeletal agent (I think). I am a cancer registrar and I know "some" things about chemotherapy agents. I want to learn more about the different categories of chemos that are out there and what tissues these drugs work on, and exactly how it is determined which ones to use. My question to you is: Do you know of a good resource to refer to (internet site, books, etc.) I can learn more about this? Or where I might find out?

The best guide to cancer drugs is the American Cancer Society's: http://www.cancer.org/docroot/cdg/cdg_0.asp

Medline Plus from the National Library of Medicine offers a very rich directory of Chemo resources, all of them checked for accuracy, at: http://www.nlm.nih.gov/medlineplus/cancerchemotherapy.html

And Wikipedia is also quite complete on chemotherapy: http://en.wikipedia.org/wiki/Chemotherapy