February is American Heart Month. Sponsored by the American Heart Association, American Heart Month is a time to battle cardiovascular disease and educate people on what they can do to live heart-healthy lives. Heart disease, including stroke, is the leading cause of death for men and women in the United States.

How much do you know about the condition of your heart? Heart health awareness typically focuses on heart disease in older adults caused by an unhealthy diet and a lack of exercise. But what if you could be at risk for cardiac arrest and sudden death even though you are young and in shape?

Image credit: Heart arrhythmia via Shutterstock

Long QT syndrome (LQTS) is one of several sudden arrhythmia death syndromes, a class of conditions affecting the heart’s rhythm. People can be born with an inherited form of the syndrome or acquire it during their life. LQTS can cause sudden, uncontrollable, dangerous heartbeats in response to exercise or stress. LQTS can arise from mutation of one of several genes, including Potassium Channel, Voltage-gated, KQT-like Subfamily, Member 1 (KCNQ1); Potassium Channel, Voltage-gated, Subfamily H, Member 2 (KCNH2); and Sodium Channel, Voltage-gated, Type V, Alpha Subunit (SCN5A).

LQTS is common; approximately one in every 2,500 people has the disorder [1]. Some people don’t discover they have LQTS until the sudden unexplained death of a family member. However, if identified, LQTS can be treated with medications, limited physical activity, or, in some cases, medical devices or surgery [2].

Dr. Brian Delisle, a faculty member of the University of Kentucky’s College of Medicine, is studying the genetic form of LQTS in order to identify new treatments. According to Delisle, there are several types of the genetic form of LQTS, each caused by a different gene mutation. One form of LQTS syndrome, LQT2 (which involves mutations of the human ether-a-go-go related gene (hERG), also known as KCNH2), is caused by a mutation in a gene that codes for potassium channels in the heart’s cells. The mutation prevents the potassium channels from being transported to their proper place at the cell’s surface. As a result, the potassium channels cannot function properly.

In a recent study published in the American Journal of Physiology Cell Physiology, researchers from Delisle’s laboratory found that a distinct cellular compartment in cardiac myocytes (heart cells) negatively regulates the production and movement of LQT2 [3]. Delisle said:

We do have a series of drugs that can correct this … in cell systems. But the problem right now is that most of the drugs that do this actually cause the acquired form of Long QT.

Delisle hopes that by better understanding the mechanism preventing the proper transport of the potassium channels to the cell’s surface, other therapeutic approaches can be identified to correct this problem.

About the author: Julianne Wyrick is a senior biochemistry major at Asbury University. A 2011 Kentucky Academy of Sciences award winner for scientific research, following graduation Julianne plans to enter a health and medical journalism graduate program.

References

1. Long QT Syndrome. Sudden Arrhythmia Death Syndrome (SADS) Foundation. Accessed 2012 Jan 28.
2. Long QT Syndrome. Mayo Clinic. Accessed 2012 Jan 28.
3. Smith et al. Trafficking-deficient hERG K? channels linked to long QT syndrome are regulated by a microtubule-dependent quality control compartment in the ER. Am J Physiol Cell Physiol. 2011 Jul;301(1):C75-85. Epub 2011 Apr 13.
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Most of us like a great steak, but may not want to think about how it arrives on our plate. Similarly, we want medicines, vaccines, antibiotics, surgery and diagnostic tools when we’re sick, but we may not care to know how exactly these treatments make it into our hospitals and pharmacies. Well, chances are, scientists developed them with the help of laboratory animals. Nearly every medical breakthrough involves animal research. From antibiotics to blood transfusions, dialysis to organ transplantation, vaccinations to chemotherapy, bypass surgery and joint replacement, practically every drug, treatment, medical device, diagnostic tool or cure we have today was developed with the help of laboratory animals. Each day, dedicated scientists study animals to find new cures for diseases and conditions that are currently incurable.

Discoveries and cures happen when scientists study diseases in living systems — first in animals and then in people. Scientists cannot simply plug a formula for cancer into a computer and test drugs’ effectiveness with computer modeling. Instead, the only way scientists can work toward real treatments is to examine how each genetically unique cancer behaves in a living animal system. This enables them to see which cancer treatments will work best for both people and animals, the latter of which get many of the same types of cancer as people.

An exciting example of animal research is happening now at the Masonic Cancer Center at the University of Minnesota. Doctors have developed a vaccine for a deadly brain cancer called glioblastoma multiforme. Glioblastoma is a terminal cancer that both people and dogs get. Even after surgery, radiation and chemotherapy, this aggressive brain tumor grows back rapidly to kill the person usually within one to two years, while dogs normally die within one month. Doctors recruit pet owners to enroll their dogs with brain cancer into a study. After removing the tumor from a dog’s brain during surgery, the doctors create a cancer vaccine using that dog’s unique tumor cells. They inject the dog with several rounds of vaccination and eventually the dog builds up immunity to the cancer. Their immune cells act like an army to kill the foreign invader, the brain tumor. This vaccine is extending dogs’ lives dramatically and many dogs become tumor-free. After perfecting the vaccines with dogs, doctors are now conducting a clinical trial with human brain cancer patients. These patients are also receiving personalized vaccines made from their own tumor cells and hopefully they will have the same life-extending results in people as they are having in the dogs. What the scientists are gleaning from this cancer research helps not only man’s best friend, but also may help human brain cancer patients facing a grim prognosis. One day in the near future, this immunological approach to treating cancer could replace standard treatment methods such as radiation and chemotherapy.

Animals are our allies in the war against cancer and other deadly diseases. Laboratory research with dogs and fish gave us insulin to treat diabetes. The polio vaccine was developed following research with mice and monkeys. Clams and rats helped researchers illuminate the power of the MRI. The HPV vaccine was developed with rabbits. People with Parkinson’s are benefiting from deep brain stimulation that was perfected with monkeys. Ferrets have been crucial in the development of the bird flu vaccine. Most recently, scientists discovered spinal cord regeneration techniques because of rodent models. That means some day in the foreseeable future, some paralyzed people may be able to get out of their wheelchairs.

What breakthroughs are next? Perhaps cures for diseases like breast cancer, AIDS, Alzheimer’s disease, Lou Gehrig’s disease, multiple sclerosis, arthritis, diabetes, cystic fibrosis, depression and glioblastoma are on the horizon. The cures we dream of will be possible because scientists are studying diseases in animals. Animal research is saving and extending both human and animal lives.

About the author: Liz Hodge is the Director of Media & Marketing Communications for the Foundation for Biomedical Research (FBR), the nation’s oldest and largest organization dedicated to improving human and veterinary health by promoting public understanding and support for humane and responsible animal research. A non-profit foundation, the FBR works to inform the news media, teachers, students and parents, pet owners and other groups about the essential need for lab animals in medical and scientific research and discovery.

Right now, more than 107,000 Americans wait for a life-saving organ transplant. The list grows with another name every 11 minutes, and every day, 18 people on that list die.

One organ donor can save eight people’s lives and a tissue donor can help up to 50 others. The fact remains, however, that there simply aren’t enough organs to save everyone on the waiting list.

Signing up to become a donor is easy — most Americans can designate themselves as donors when they get their drivers license and, in many states, that designation transfers their information to a state database. In the event of their death, organ donation professionals access that database, which begins the process of saving lives.

Making the decision to become a donor is different; it requires a clear understanding of the way donation works — which can prove difficult, given various persistent myths about donation.

Organ donation and transplantation, like any other health-based decision, should be made based on facts, not fears. So here’s the truth:

1. Organs which can be donated include the heart, lungs, liver, small intestine, pancreas and kidneys. Numerous tissues can be donated, including corneas, bone, skin, tendons, ligaments, heart valves, veins, arteries and more.

2. All major religions in the United States support organ donation. Many consider it the highest form of charity and — even if there is a religious rule or law about what should be done with someone’s body after they die — that rule becomes secondary if the possibility of saving someone else’s life exists.

3. It is possible to have an open casket funeral after organ and tissue donation. For example, donated skin is recovered from the back of the body. Organ recovery occurs like any other surgery, in a hospital’s operating room.

4. There is no cost to the family if their loved one becomes an organ and tissue donor.

5. Organ donation occurs as a result of a head trauma — such as a car accident or stroke. An individual who has been brought to the hospital after such injury must be declared brain dead in order for donation professionals to proceed with the donation process.

   Brain death is not the same thing as a coma or a persistent vegetative state (PVS). A coma is a state of ongoing unconsciousness and not necessarily permanent. PVS results in the destruction of the higher functioning portions of the brain and is permanent. In both cases, the individual is still very much alive. Brain death, however, is the complete cessation of all brain function; when the brain swells to the point where it receives no blood or oxygen supply, the person will die.

6. The physicians who determine brain death are not the same physicians responsible for the organ donation process. Hospital staff is obligated to do one thing: exhaust every measure necessary to save someone’s life. Donation becomes a possibility when each measure fails.

7. Upon arriving in the emergency room with a serious head trauma, patients are typically placed on circulatory support. This is because the brain — responsible for telling the body what to do — has suffered an injury, and supportive machines will keep the rest of the body functioning while the brain recovers. But that support can’t repair brain damage. If the brain dies while the patient is on support, the machines can continue functioning for a short time; therefore, the organs will continue receiving blood and oxygen. Those organs can then be donated to save the lives of others.

8. Organ donors can also become tissue donors, but becoming a tissue donor does not require brain death. At the time of tissue transplantation, there are actually no living cells in the donated tissue.

Brain death doesn’t occur that often. In fact, less than 1% of deaths in the United States are brain deaths [1]. And not every person who suffers such a fate designated themselves as organ donors.

Those waiting for life-saving transplants can’t be compared to people with other illnesses. End-stage organ failure isn’t worse or better than cancer or heart disease, but it’s different because the cure lies in selflessness. People on the waiting list depend on the generosity of others in order to survive.

If you’ve already designated yourself as a donor, you may wonder what else you can do to help save lives. The answer is simple: tell others. Tell your family and friends what you’ve decided and encourage them to learn more, as well. Additional information is available — and the opportunity to sign up as a donor — at www.donatelifeamerica.net.

About the author: Rebekah Apple is the Public Affairs Coordinator at the LifeLink Foundation, a non-profit community service organization dedicated to the recovery of life-saving and life-enhancing organs and tissue for transplantation therapy. Her goal is to share the truth about the donation process and allow everyone the opportunity to make an informed decision.

References

1. Understanding Death Before Donation. The Gif of a Lifetime. Accessed 2010 Aug 25.

Experts agree that diet and nutrition can reduce risk of many diseases, including different types of cancer and chronic disease. A recent update to a 2007 report by the American Institute for Cancer Research/World Cancer Research Fund (AICR/WCRF) concludes that breast cancer deaths can be prevented by physical activity, breast feeding, a healthy diet and other preventative measures. The study is an update to the breast cancer chapter of Food, Nutrition, Physical Activity and the Prevention of Cancer: a Global Perspective [1]. Earlier conclusions were based on data from 873 studies evaluating the relationship between diet, physical activity, obesity and cancer [2]. The 2009 update includes evidence from an additional 81 studies.

The report estimates that over 70,000 breast cancer cases in the U.S. — 40% of cases every year– could be avoided every year by simple lifestyle changes. The update reinforces the following AICR recommendations:

• Due to the link between excess body fat and cancer, people should aim to be as lean as possible without being underweight.
• Be physically active for at least 30 minutes daily.
• If you drink, limit alchohol consumption to two drinks a day for a man and one for a woman.
• Mothers should breastfeed exclusively for up to six months after birth.

The report did not examine other protective factors that may overlap and contribute to breast cancer, such as the effect of taking postmenopausal hormone therapy and oral contraceptives, or risk factors, some of which cannot be avoided, such as genetic background or certain environmental factors.

The AICR recommends a mostly plant-based diet with limited consumption of salt, red meats and alcoholic drinks. The report does not provide a decisive picture of particular food groups that can reduce the incidence of cancer. As of 2006, the largest ever clinical trial of low-fat diet showed that longer term follow-up was needed to determine whether reducing total fat intake had a signficant impact on the incidence of breast cancer [2].

Even so, following the AICR’s recommendations can lead to better prevention practices: a study from Johns Hopkins University School of Medicine found that obese women are less likely to undergo regular mammography, which is key to screening breast cancer and lowering mortality rates [3]. The National Cancer Institute provides risk profiles and other tools that examine multiple factors that impact your risk to develop breast cancer.

The AICR/WCRF report — Food, Nutrition, Physical Activity and the Prevention of Cancer: a Global Perspective — is the most comprehensive report on diet and cancer ever compiled. Over 7,000 studies were independently reviewed, compiled and presented to an expert panel of 21 world-renowed scientists, who evaluated the data and developed recommendations for cancer prevention.

The report on breast cancer is part of the Continuous Update Project, which continuously updates the findings of the AICR/WCRF 2007 report [1]. This allows for cancer prevention information that is always based on the latest research. Breast cancer is the first type of cancer researchers have reviewed evidence on as part of the update project. They have started reviewing data on colorectal cancer and prostate cancer, and the results are expected early next year. The long-term goal of the Continuous Update Project is to continually update evidence on all types of cancer.

About the author: Allison Bland is a communications fellow at Research!America and a graduate of McGill University with degrees in English and History of Science. She is interested in science and health communication on the web.

References

1. Food, Nutrition, Physical Activity and the Prevention of Cancer: a Global Perspective. World Cancer Research Fund/American Institute for Cancer Research. 2007 Nov 1.
2. Prentice et al. Low-fat dietary pattern and risk of invasive breast cancer: the Women’s Health Initiative Randomized Controlled Dietary Modification Trial. JAMA. 2006 Feb 8;295(6):629-42.
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3. Maruthur et al. Obesity and mammography: a systematic review and meta-analysis. J Gen Intern Med. 2009 May;24(5):665-77. Epub 2009 Mar 11.
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A recent study in the Proceedings of the National Academy of Sciences (PNAS) hints at a future where a daily multivitamin could be replaced with a personalized vitamin that would work with the unique genetic makeup of an individual’s genome [1]. Studies have repeatedly cast doubt on the effects of vitamins for the prevention of cancer and other diseases, and doctors and scientists are mixed in their recommendations for taking these supplements. A doctor may prescribe vitamins to cure metabolic diseases, but the enzymes that do this metabolic work in our bodies vary from person to person because of genetic mutations that cause them to function slightly differently.

There are over 600 enzymes that need vitamins or minerals to work properly, and researchers at the University of California Berkeley tested one of them. Using the MTHFR enzyme, which requires the B vitamin folate to do its part in building DNA molecules, they found 14 variants of the enzyme based on the genomes of over 500 people. When the mutated enzymes were expressed in yeast cells, which imitate the human metabolism, they found that four of the variants affected the way the enzyme functioned in the cell. But by adding folate to the yeast cell’s diet, four of the five mutated enzymes became fully functional again.

Personal genome screening is on the verge of popularization, but the focus is still on disease identification. A complete personal genome screening that takes into account such subtle variants in our enzymes would allow for a “fine-tuning” of a person’s metabolism. From the PNAS paper [1]:

Extrapolating to 30,000 proteins in the proteome, every individual would harbor 250 deleterious substitutions considering only the low-frequency variants.

Such genetic variation suggests that there could be a significant physiological impact to enzyme function. Based on the results of the MTHFR study, this could be corrected with individualized vitamin or mineral supplementation. According to the primary author of the study, Nicholas Marini, Ph.D. [2]:

Our studies have convinced us that there is a lot of variation in the population in these enzymes, and a lot of it affects function, and a lot of it is responsive to vitamins. I wouldn’t be surprised if everybody is going to require a different optimal dose of vitamins based on their genetic makeup, based upon the kind of variance they are harboring in vitamin-dependent enzymes.

For more information on using vitamins to promote general wellness and avoid deficiency diseases, visit MyPyramidTracker.gov. The website allows you to track your intake of these nutrients based on your body type and dietary guidelines, as well as assess your physical activity.

About the author: Allison Bland is a communications fellow at Research!America and a graduate of McGill University with degrees in English and History of Science. She is interested in science and health communication on the web.

References

1. Marini et al. The prevalence of folate-remedial MTHFR enzyme variants in humans. Proc Natl Acad Sci U S A. 2008 Jun 10;105(23):8055-60. Epub 2008 Jun 3. DOI: 10.1073/pnas.0802813105
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2. Personal genomes may lead to personalized vitamin supplements. University of California Berkeley press release. 2008 Jun 2.

Warfarin (brand name Coumadin) is one of the most commonly used anticoagulants (meaning a medication that thins the blood). It is used in a variety of medical situations, including atrial fibrillation, blood clots and when there is an increased risk of blood clotting due to genetic predisposition. When a patient is on warfarin, they need frequent blood draws to measure blood thinness and frequent dose adjustments until they have reached a stable level of blood thinning.

However, clinicians realize that each patient’s warfarin dose can be highly variable for any number of reasons, including genes, diet and concurrent medical illnesses. Sometimes it can take many weeks or months to get a patient to the right warfarin dose, and during that time the patient’s blood can either be too thin, putting them at risk of bleeding, or too thick, placing them at risk for developing blood clots. A more refined way of dosing warfarin is needed that takes into account individual patient factors.

An article published recently in the New England Journal of Medicine by the International Warfarin Pharmacogenetics Consortium seeks to address these concerns [1]. The authors include 21 research groups from around the world, representing a broad group of patients and investigators. Initially, they looked at 4,043 patients who were at their target warfarin dose, and looked back at a variety of clinical and genetic characteristics, including:

• demographics
• the stable therapeutic dose of warfarin
• the International Normalized Ratio (INR), used to monitor the effectiveness of blood thinning drugs, achieved with a stable warfarin dose
• the desired INR
• the use of other medications
• Cytochrome P450, subfamily IIC, polypeptide 9 (CYP2C9) genotype variants
• Vitamin K epoxide reductase complex, subunit 1 (VKORC1) genotype variants

Genotype variants called single nucleotide polymorphisms (SNPs) of CYP2C9 and VKORC1 are strongly associated with warfarin responsiveness [2]. The researchers were not able to include information on diet or smoking status. From this information the scientists created a mathematical model which predicted the optimal warfarin dose. They called this the pharmacogenetic algorithm. They then applied the algorithm to 1,009 patients to see if the model predicted the final dose of warfarin used. They compared the result to a model that used only clinical (non-genetic) data and to a second model that had every patient taking an initial dose of 5 mg of warfarin daily (which, in clinical practice, is a common place to start warfarin dosing).

The pharmacogenetic algorithm predicted a lower dose of warfarin (8.3 mg/day) then the clinical algorithm (10 mg/day) or the flat dosing approach (13.3 mg/day), and was closer to the ultimate maintenance dose of warfarin achieved. The largest differences in doses were noted among patients who ended up requiring either very low or very high doses (in essence, those patients at greatest risk of bleeding or clotting when a physician is starting them on warfarin). This represented 46% of the patients in the study — a substantial number.

What is unknown is whether using this algorithm translates to better outcomes for patients, such as less bleeding or clotting, or even fewer blood draws. Although one assumes that will be the result, a study should be performed to confirm this. Also, this investigation was done retrospectively and should be confirmed with a prospective study (meaning in real time), which is a study design that is less subject to potential bias. In that setting, the impact of diet and smoking on warfarin therapy should also be assessed.

This study is one of a growing number demonstrating how pharmacogenetics can be used to individualize and optimize drug therapy. This is a promising application of “personalized medicine”, whereby drugs and drug doses will be safer and more effective for patients because they will be selected based on an individual’s genetic makeup.

Additional resources can be found in the Personalized Medicine category of the Highlight HEALTH Web Directory.

About the author: Noelle K. LoConte, M.D. is an assistant professor of medicine at the University of Wisconsin. Dr. LoConte’s clinical interests lie in gastrointestinal cancer and geriatrics. She has authored numerous studies on gastrointestinal cancer and has been interviewed by several media outlets about her expertise in this area. She blogs about current research, trials, treatments and issues in the hematology/oncolgy field at HemOnc Today.

References

1. International Warfarin Pharmacogenetics Consortium. Estimation of the warfarin dose with clinical and pharmacogenetic data. N Engl J Med. 2009 Feb 19;360(8):753-64. DOI: 10.1056/NEJMoa0809329
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2. Cooper et al. A genome-wide scan for common genetic variants with a large influence on warfarin maintenance dose. Blood. 2008 Jun 5. [Epub ahead of print]
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