How Winner Cells Kill Loser Cells: New Perspectives

There are literally many trillions of cells in the human body. Every day, 20 to 70 billion of those cells die while others continue to survive and proliferate. Some cells die spontaneously through programmed cell death, a process known as apoptosis.

Specialized cells known as phagocytes, which act like vultures, then engulf and consume the byproducts of dead cells.

Some cells are actively destroyed by other cells. The cells that are victorious can be referred to as winner cells and those that die off can be referred to as loser cells. In many ways, cellular life is like real-world animal life, with daily competition where the strongest and/or best survives. Cellular competition is important because it helps get rid of deficient or damaged cells (caused by mutations) that can cause harm to the organism.

In a recent article published in BioEssays, researchers from Spain discussed recent results of cellular competition studies. They reinterpreted previous models of cell competition where winner cells were believed to be the ones that killed and engulfed the remains of loser cells. In the reinterpreted model, the winner cells identify kills the vulnerable loser cells (like an assassin of predator would) but recruit other cells to engulf their remains.

The article discussed how cell competition involves cells comparing their fitness status. In other words, the cells size each other up like two animals in the wild and the unfit cells are labeled with a molecular code that describes it as such. It as if these cells each have a sign on them saying “I’m a problem cell.” It is not precisely known how this code is recognized by other cells but in the end, the fit cells try to eliminate the unfit type.

While a defective cell can be eliminated by fit cells around it (akin to being someone being ostracized from a group) there are other times when a supercompetitor cell can overtake those around and spread (akin to an alpha male who destroys his surrounding competition and then spreads his lineage).

In some cases, however, such as cancer, the defective cells are protected by a special protein so that they are not eliminated. In this way, unfit cells can eventually overtake fit cells. In this way, disease can overtake the human body. For example, cancer is an abnormal growth of new tissue characterized by uncontrolled growth of abnormally structured cells that have a more primitive form.

Suggested reading: Molecular and Cell Biology For Dummies

Reference: Lolo FN, Tintó SC, Moreno E. (2013, in press). How winner cells cause the demise of loser cells: Cell competition causes apoptosis of suboptimal cells: Their dregs are removed by hemocytes, thus preserving tissue homeostasis. Bioessays.

Kim Kardashian: Exercise, Over-exertion, and Miscarriage Risk in Pregnancy

Kim Kardashian has been in the news lately for medical reasons. Specifically, the 32-year-old socialite and TV personality, who announced that she is pregnant on 12/31/12, has been receiving criticism from medical doctors and health commentators that her recently reported miscarriage scare (based on flu-like symptoms) could be due to an excessive exercise regimen combined with a busy schedule.

Some media reports have cited guidelines for exercise during pregnancy and emphasized that it is important to exercise in moderation to avoid exhaustion, dehydration, and overheating. There are numerous guidelines available regarding exercise during pregnancy. The most cited guidelines are those by the American College of Obstetricians and Gynecologists (ACOG) in 2002 which state that in the absence of either medical or obstetric complications, 30 minutes or more of moderate exercise a day on most to all days of the week is recommended for pregnant women.

One problem with the ACOG guidelines is that they do not define moderate exercise. Some have interpreted them to mean that it is exercise that leaves one feeling energized and refreshed but not exhausted. However, this is subjective and the exercise intensity to achieve these feelings can vary greatly from person to person.  This has led some to develop more recent guidelines in 2011, which state that increasing the amount of vigorous exercise and physical activity expenditure is an important goal for pregnant women, especially for those who are overweight or obese.

To do this, the researchers who proposed these guidelines (Zavorsky & Longo, 2011) suggested walking 3.2 kilometers per hour (1.98 miles per hour) for 6.4 hours a week or preferably exercising on a stationary bike for 2.7 hours a week. They stated that the best health outcome will come from vigorous exercise at greater than or equal to 60% of the heart rate reserve (HRR). HRR is the difference between the measured maximum heart rate and resting heart rate.  The maximum heart rate is the highest heart rate one can achieve without severe problems during exercise. Some measurement devices of exercise intensity will measure the percent of HRR. If unable to access this information easily, the researchers suggested exercising at 70 to 75% of the maximum heart rate.

In short, the problem in Kim Kardashian’s case does not necessarily have anything to do with her exercising most days a week or 7 days a week because that is recommended in the guidelines. One simply needs to use common sense on not exercising in excess, particularly when there are extensive stressors present in one’s life such as divorce proceedings and a busy travel schedule.  Higher stress levels increase levels of cortisol (a type of hormone) in the body, which can elevate other chemicals in the body that lead to miscarriage, premature contractions, and premature labor.

Lastly, there are numerous contra-indications to exercise during pregnancy such as lung disease, persistent bleeding, heart disease, and many others. Pregnant women should discuss their exercise regimen with their doctors before proceeding. This is particularly the case since large Danish study several years ago showed that exercise in early pregnancy is associated with an increased risk of miscarriage (Madsen et al., 2007). The authors of that study, however, suggested caution in interpreting the results however because limitations of the study design may have contributed to the association.

Suggested reading: Mayo Clinic Guide to a Healthy Pregnancy
 
Related blog entry: Anti-depressants in Pregnancy: What are the Risks?

References:

The American College of Obstetricians and Gynecologists. Committee on Obstetric Practice. Exercise during pregnancy and the postpartum period. (2002). Int J Gynaecol Obstet.  99, 171–173.

Madsen M, Jørgensen T, Jensen M, Juhl M, Olsen J, Andersen P, Nybo Andersen A. (2007). Leisure time physical exercise during pregnancy and the risk of miscarriage: a study within the Danish National Birth Cohort. BJOG.114:1419–1426.

Nascimento SL, Surita FG, Cecatti JG. (2012). Physical exercise during pregnancy: a systematic review. Curr Opin Obstet Gynecol. 24(6):387-94.

Zavorsky GS, Longo LD. (2011). Exercise guidelines in pregnancy: new perspectives. Sports Med, 41:345–360.

Decreased Child ER Visits after LA Lakers Title Games

There are many situational factors that can potentially affect why people bring children to the Emergency Room (ER). One such factor is major sporting events, such as the Super Bowl, World Series, and NBA Championship Games. That is, if people are pre-occupied watching these games or celebrating afterwards, they may be less prone to take children to the ER and will perhaps wait the next day to follow-up with a pediatrician.

A recent study in Pediatric Emergency Medicine explored the ER census over a five year period (2006-2010) in relation to the three major sporting events mentioned above. The study times were 4 hours before each event and 8 hours after the events began, divided into 2-hour increments. The comparison group study times were one week after the major sporting event during the corresponding time periods. The study site was the Emergency Department in Loma Linda University Medical Center which means all the times were in the Pacific time zone.

Results of the study generally showed that there was no significant difference in the ER census before and after any of these sporting events compared to the control periods. This is good news because if there is a true emergency, then children should be taken the ER whether there is a major sporting event going on or not. However, 6 to 8 hours after the NBA Finals there were more children taken to the ER in the study group versus the control group.

Because the study was performed in a city close to Los Angeles, the researchers performed further analyses to determine if there was any specific effect related to the Los Angeles Lakers being in the NBA finals. Results showed that there was a decreased use of the ER for children 6 to 8 hours after the games when the Los Angeles Lakers were in the finals. When the Lakers were not in the NBA Finals, there was no decrease in children going to the ER compared to controls in the 6 to 8 hour post-game period. Of course, it is possible that that the decreased ER visits after Lakers wins were related to some other unknown factor, so the topic will require further study, especially since there were a small number of children in the ER during that time period (sleeping hours). 

Suggested reading: The Los Angeles Lakers Encyclopedia

Related blog entry: Who Uses the Emergency Room Most? The Answers May Surprise You?

Reference: Kim TY, Barcega BB, Denmark TK.(2012). Pediatric emergency department census during major sporting events.Pediatr Emerg Care. 28(11):1158-61.

Daylight Saving Time Change May Increase Heart Attack Risk

When people go to bed tonight, at 2:00 am, an hour of sleep will be lost due to daylight savings time. Last year, in a prior blog entry, it was discussed how sleep deprivation on the Monday following a shift to spring daylight savings time results in a small increase in fatal car accidents.

A new study reported in a recent issue of the American Journal of Cardiology provided evidence to show that daylight savings time shifts might briefly and modestly affect the incidence and type of acute (sudden) heart attacks.

In the study mentioned above, there were 935 patients (59% men and 41% women) whose electronic medical records were reviewed at two emergency centers in Michigan. The researchers studied the incidence of sudden heart attacks that presented to the hospital the week after daylight savings time and after the autumn switch to standard time. There were 328 patients studied during that time frame. A comparison group was also studied, made up of 607 patients with comparable diagnoses who came to the hospital two weeks before and two weeks after the shift to daylight savings time. 

The main finding that reached statistical significance was an increase in a type of heart attack after the transition to daylight savings time compared to patients who were studied two weeks before and after the shift to daylights savings time. This was noted for the first day (Sunday) after the transition to Spring.

The increased heart attack risk is theorized to because of the biological effects of decreased sleep length and sleep quality. For example, partial night sleep deprivation is associated with increased levels of certain chemical related to cardiac function such as norepinephrine. It can also increase the rate of firing of nerve cells that regulate heart rate. Increased blood pressure and narrowing of blood vessels was suggested as another possible cause of acute heart attack after sleep deprivation.

While the results of this study are interesting, they cannot definitely prove that transition to daylight savings time causes acute heart attacks because it is based in a retrospective chart review (preventing the researchers from controlling other factors that could influence the results), is based on association (associations do not prove causation), and because there were not enough heart attacks per day to strengthen the power of the statistical analyses. More research is still needed to determine if the increased risk indicated in this study is real and if so, how to decrease the risk. Until that time, common sense would indicate that trying to get extra sleep during the daylight savings time transition is a smart thing to do, especially if you have risk factors for heart disease.

Suggested reading: Mayo Clinic Healthy Heart for Life!

Reference: Jiddou MR, Pica M, Boura J, Qu L, Franklin BA.(2013). Incidence of myocardial infarction with shifts to and from daylight savings time. Am J Cardiol., 111(5):631-5.

Helicopter Pilots: Associated Diseases and Sicknesses

Research studies have shown that pilots are more prone to numerous adverse health conditions related to chronic exposure to high altitudes (where there is less oxygen), and high speeds, temperatures, vibrations, and noise levels.

However, many of these studies lump airplane pilots together with helicopter pilots but the groups may be susceptible to different conditions due to different flight characteristics. For example, helicopter pilots do not fly as high and as fast as airplane pilots. Thus, studying helicopter pilots separately may be helpful.

In the current issue of Aviation, Space, and Environmental Medicine, researchers from China performed such a study to study the types of diseases helicopter pilots suffered as well as their sick leave time. The study involved a random sampling of 516 pilots between the ages of 20 and 52. Their medical records were reviewed to obtain medical diagnoses and sick leave time for each diagnosis.

Results of the study showed that the top three organ systems in helicopter pilots affected by disease are the digestive system, cardiovascular system, and the musculoskeletal system. The top three organ systems associated with the longest sick leave durations were the digestive system, musculoskeletal system, and the nervous system. Conditions in these organ systems accounted for 66% of sick leave time combined.

The three most common medical conditions for the helicopter pilots were fatty liver (9.88%), hyperlipidemia (high fat levels in the blood; 6.98%), and polypoid gallbladder lesions (3.42%). Fatty liver is a reversible condition where fat accumulates in the liver. Polypoid lesions of the gallbladder are types of polyps in the gallbladder. Polyps are a type of growth that projects from the lining of mucous membranes. A mucous membrane is one of four major types of thin sheets of tissue that line or cover various parts of the body. The gallbladder is a small, pear shaped sac, located under the liver, which helps store and transport bile to the first part of the small intestine. Bile is a bitter, yellow-green substance released from the liver that carries away waste products.

The three diseases associated with the longest sick leave periods in helicopter pilots were ground syncope (fainting; 7.23%, 157 sick days), chronic gastritis (inflammation of the stomach lining; 6.68%, 145 sick days), and lumbar (lower back) disc herniation (protrusion) (4.19%, 91 sick days). Lumbar disc herniation could have been related to chronic sitting in helicopter pilots. The authors suggested more efforts be made on controlling and preventing this problem in the future.

The study also showed that the helicopter pilots rarely suffered from specific aerospace related diseases/problems (e.g., hearing loss, loss of consciousness) that airplane pilots do, likely because of the differences in their flight characteristics.  However, the ground syncope was a significant concern which led the authors to suggest better training to tolerate high altitudes and speeds. It is not altogether if there is something specific about being a helicopter pilot that makes one prone to fatty liver, hyperlipidemia, and polypoid gallbladder lesions or if some other factor was the cause.        

Suggested reading: Pilot Medical Handbook: Human Factors for Successful Flying

Reference: Xiao, D., Li, H., Wang, X., Wang, B., Yan, Y. & Men, K. (2013). Prevalence of Disease Spectrum and Sick Leave Time Associated with Illness in Helicopter Pilots. Aviation, Space, and Environmental Medicine, 84, 3, 234-236.

Cholesterol Lowering Drugs Slows Progression of Clogged Arteries

Cholesterol is a waxy, fatty substance found only in animal tissues. High-density lipoprotein (HDL) cholesterol is called "good cholesterol" because it helps prevent cholesterol from building up in the arteries. An artery is a blood vessel that carries blood away from the heart.

Low-density lipoprotein cholesterol is called "bad cholesterol" because together with other substances it can form plaques (hard, thick deposits) in the walls of arteries, leading to blockages. When this happens it is known as atherosclerosis.

Atherosclerosis can cause damage to large blood vessels, which is a major cause of stroke and coronary artery disease. A stroke is a burst artery (a type of blood vessel that carries blood away from the heart) or a blockage of an artery in the brain. Coronary artery disease is a narrowing of coronary arteries, which supply the heart with blood. The narrowing of coronary arteries causes heart damage.

There are many different types of drugs that lower bad cholesterol levels, the most commonly used of which are known collectively as statins. There is evidence from research studies that randomly assign patients to different treatment groups that statins decrease atherosclerosis but little is known about whether the finding from these studies applies to other settings.

In an upcoming issue in the journal, Arteriosclerosis, Thrombosis, and Vascular Biology, researchers from Norway published the results of a 13-year follow-up study designed to answer this question. Specifically, they took commonly used measures of atherosclerosis in the right carotid artery (an artery in the neck that supplies blood to the brain) in 2965 people (1442 men and 1532 women) via ultrasound scanning. Ultrasound scanning is a procedure that uses high-frequency sound waves to produce images of internal body structures.

Results of the study showed that long-term use of cholesterol lowering drugs (more than 5 years of use) had a protective effect on the right carotid artery by lowering the total plaque area and decreasing the thickness of the arterial wall. Non-chronic use of cholesterol lowering drugs had a weaker protective effect on these measures.

Suggested reading: Controlling Cholesterol For Dummies

Reference: Herder M, Arntzen KA, Johnsen SH, Eggen AE, Mathiesen EB. (2013, in press). Long-Term Use of Lipid-Lowering Drugs Slows Progression of Carotid Atherosclerosis: The Tromso Study 1994 to 2008. Arterioscler Thromb Vasc Biol.

Five Ways to Protect Medical Websites and Blogs from Marketing Scams

If you run a popular medical website or blog (or any website/blog for that matter) you will inevitably be contacted by people who want to advertise on your website to market their brand name or product. Sometimes you will be contacted a company representative but other times you will be contacted by freelancers or other third parties who work to promote businesses on the internet.

Fortunately, most of the people who contact website/blog owners represent legitimate and reputable companies but this is not always the case. To maintain a popular and trustworthy website, it is crucial that you protect it and your readers from dubious advertisers and marketing scams. Below are five tips to help prevent you do this based on personal experience.

1. Do a News Search: Simply take the name of the company and search for it in the news section of a major search engine. You are looking to see if the company is involved in some sort of significant controversy or receiving some type of negative press. For example, I was once contacted by someone who wanted to place an advertisement for a rehabilitation facility. A Google News search revealed that the company had been in the news for using controversial and scientifically unproven techniques that resulted in several deaths.  I had not heard of the facility previously and would not have not have known without the search. A good example of how a little investigation can go a long way.

2. Do a General Search: Not all companies will be involved in controversy significant enough to have caught the eye of the media to warrant a news story. This is where a search on a major search engine’s main page can come in helpful. For example, I was once contacted by a freelancer who was selling advertising for a company offering test preparation guides. Nothing turned up on a news search but a regular internet search revealed that all user reviews were negative, accusing the company of selling a fake product with wrong answers and refusing to issue refunds. True or not, this was not a company that would be advertising here.

3. Go to the Company Website: Evaluate the company’s website. Does it look professional? Would you feel comfortable being directed to it from a website you trust? Does it seem like the website is making outlandish or dubious claims that may put your readers at risk for deception?  Does the website seem exploitive in any way? Look for names of who runs the company and do a search for them as per above. Is the site run by someone who lost their license for malpractice and/or involved in recurring media controversies or is it run by an established physician(s) well-regarded by his/her peers? Answers to these questions will help guide decisions about advertising placement. 

4. Do NOT Install Code Files from Third Parties: You should not install code files (e.g., source code) on your website/blog provided to you by third parties because you can unknowingly be placing malicious content on your website/blog that can spread viruses and malware.The one exception to this would be source codes for ads provided by reputable advertising programs such as Google Adsense.

5. If it Does Not Seem Right, Go with Your Instinct: This part is more difficult to describe because it is the most subjective but if something seems suspicious, trust your instinct and stay away. For example, I was once contacted by an advertising agency requiring a signed contract (which is unusual). Upon asking the agency rep the name of their company and website, the company name provided could not be found on any search engine, it was claimed that the website was down for repairs, and the link provided to a supposed new website looked like it was created in a few minutes and consisted only of a bar across the middle of the page with a few words.  Another advertiser once asked to purchase 10 text links of short phrases scattered anywhere throughout the page, even in tiny font. This is a very odd request and a little investigation revealed it to be a company with a bad reputation.

Suggested Reading: The Con: How Scams Work, Why You're Vulnerable, and How to Protect Yourself

Remember the Joys of Sleeping

Sleep is one of the most important things we do as human beings. Without proper sleep, the rest of our life can be negatively affected. With about one in every fifteen Americans suffering from sleep apnea, it's not only important to get sleep, but also to get good sleep. Here are some of the new and effective treatments for those diagnosed with sleep apnea:

Mask/Device Therapy

A very common and affordable treatment offered by many sleep treatment centers, such as WakeUpToSleep, is mask and device therapy. This type of therapy will allow users to sleep better than they have in a long time, give them more energy throughout the day and may even help with other health issues, such as high blood pressure or weight loss. 

A popular type of mask treatment is called Continuous Positive Airway Pressure (CPAP) therapy. This type of sleep machine offers a mask to cover the nose and mouth and one that only covers your nose. It will take time to get used to the machine, but research shows this type of treatment can help with daytime sleepiness, lower blood pressure and, in most cases, is a better option than other non-surgical treatments of sleep apnea.

Expiratory Positive Airway Pressure (EPAP)

One of the newest treatments, recently approved by the FDA is a single-use device place over the nostril before going to sleep. It allows the free movement of air and increases the pressure in the airway to help keep it open. The device is capable of reducing snoring and daytime sleepiness and is a good alternative for those unable to tolerate CPAP.

Oral Devices

Another option proven to help with snoring and allow for better sleep is an oral device. These types of devices help to keep the throat open during sleep. CPAP and EPAP are considered more effective treatments, but oral devices are often much easier to use. For those suffering from mild to moderate sleep apnea, an oral device prescribed by a dentist can help.

Surgeries

If home treatment won't do the trick, surgery is the next type of treatment. Depending on the individual and the condition, one of four surgeries may be recommended. These include tissue removal, jaw repositioning, implants and a tracheostomy (creating a new air passageway). 

Tissue removal often works for those unable to tolerate a CPAP therapy. The doctor will remove tissues from the back of your mouth, along with your tonsils and adenoids. However, this isn't the most successful type of treatment and only works in some cases.

Jaw repositioning helps to enlarge the space behind the tongue and will require the help of an oral surgeon. Often this type of treatment is combined with other sleep apnea treatments for better success.

Implants are plastic rods inserted into the soft palate under local anesthetic. Those suffering from mild sleep apnea are often the best candidates for this type of treatment.

A tracheostomy is the last option a surgeon will recommend. If nothing else has worked, they may perform surgery to create a new air passageway. Only when the condition is life threatening or severe, will this procedure be used. 

Whether you suffer from mild or severe sleep apnea, a treatment can help you get a good night of sleep every night. Consult a doctor before choosing a treatment, as they will be able to best diagnose the severity of your condition and match the right treatment for you.

The above entry is a guest blog post.

Bariatric Surgery in Obese Persons Does Not Reduce Long-Term Health Care Costs

One type of drastic treatment for obesity is bariatric surgery (also known as weight-loss surgery).This involves surgically reducing the stomach size, removing a part of the stomach, or removing and re-directing the small intestine to a small stomach pouch. The latter is referred to as gastric bypass surgery. The small intestine is the part of the intestine that takes in all of the nutrients that the body needs.

The surgery is known to help with weight loss and improves overall health. An example is remission of diabetes mellitus. In diabetes mellitus, the body is not able to effectively use a natural chemical called insulin, which quickly absorbs glucose (a type of sugar) from the blood into cells for their energy needs and into the fat and liver cells for storage.

While bariatric surgery has health benefits, it is also associated with frequent complications such as bloating and diarrhea after eating, infections, leaks at the surgical site, hernia (tissue protrusion) through the incision site, and pneumonia. Pneumonia is inflammation of the lungs due to infection.

With health care reform a reality, an increasing focus of insurers will be if the surgery actually reduces long-term health care costs. The surgery is currently approved by insurance companies due to the potential to improve health care costs.

In an upcoming article in JAMA: Surgery, researchers published a study designed to analyze the long-term health care costs associated with bariatric surgery. The study followed-up 29,820 patients who underwent bariatric surgery between 2002 and 2008 under a BlueCross Blue Shield insurance plan across the U.S, making it the largest study of its kind.  The patients were compared to a matched control group that did not undergo surgery but who had obesity or diagnoses closely associated with obesity (e.g., diabetes mellitus).

Results of the study showed that total healthcare costs were greater in the bariatric surgery group during the second and third years after surgery but were similar in the later years. In specific areas, the bariatric group had higher inpatient care costs which offset lower costs for prescriptions and office visits. The authors concluded that bariatric surgery does not reduce overall health care costs in the long-term and that there was no evidence that one type of bariatric surgery was more likely to reduce long-term health care costs.

In an accompanying article in the journal, Dr. Edward Livingston (Deputy editor of JAMA) noted that bariatric surgery should only be offered to highly selected patients: those in whom there is an overwhelming probability of long-term success, who have complications of obesity that can improve with weight loss surgery, and who have history of demonstrated medical and dietary compliance.

Suggested Reading: The Obesity Epidemic: What Caused It? How Can We Stop It?
 
References: Livingston EH. (2013, in press). Is Bariatric Surgery Worth It?: Comment on "Impact of Bariatric Surgery on Health Care Costs of Obese Persons". JAMA: Surgery.

Weiner JP, Goodwin SM, Chang HY, Bolen SD, Richards TM, Johns RA, Momin SR, Clark JM. (2013, in press). Impact of Bariatric Surgery on Health Care Costs of Obese Persons: A 6-Year Follow-up of Surgical and Comparison Cohorts Using Health Plan Data. JAMA Surgery.

Prescription Medications for Children’s Headache Are Generally No Better than Placebo

Similar to adults, headache is one of the most common symptoms that children (including adolescents) report. Patients are often treated with numerous trials of medications to reduce headaches. Many times, they report that none of the medications have helped. Although some patients report reduced headache after using prescription medicine, this does not mean that the medicinal powers of the medication actually caused the reduction. That is, the improvement may have been due to the placebo effect.

The placebo effect is when someone reports or shows improvement in a health condition when given a treatment they are told is genuine but is actually not. An example would be telling one group of patients that they are being given a medication to treat headaches when they are only swallowing a sugar pill that does not actually treat headaches. In this example, the sugar pill is known as a placebo. If the placebo group reported significant improvement from the sugar pill treatment then this improvement is known as the placebo effect.

If drug studies do not include a placebo group for comparison purposes then there is no way to tell if any reported improvements from genuine medical treatments are due to actual medicinal effects or due to the powers of suggestion (placebo effect). When studies include a placebo group it is known as a placebo-controlled study.

Unlike placebo treatments, actual medications have potential side effects. Some parents may not want to run the risk of such side effects if the medication prescribed has not been proven to be better than placebo. In an upcoming study to be published in JAMA Pediatrics, researchers reported on the results of statistical analyses based on an extensive literature review to determine the effectiveness of headache medications in reducing headache the frequency and severity of headaches in children (less than age 18). After an literature search revealed 2918 articles for review, only 13 were placebo controlled studies that randomly assigned patients to groups.

The results were startling in that only two medications (topirimate [Topamax] and trazodone) had limited data supporting their effectiveness in treating episodic migraine headaches. Migraines are moderate to severe headaches that are associated with nausea, vision disturbance, vomiting, and light sensitivity. Other commonly used prescription medications for headaches showed no evidence supporting their use in children in adolescents.

What treatment did the study find that was clearly effective at treating headaches? The placebo. The authors noted that since there were so few studies on this topic with placebo comparison groups that more research is needed and that firm conclusions cannot be made at this time. Nevertheless, one is left to wonder whether it would be a good idea for physicians to initially treat children who report headaches with a placebo to see if this works before treating with prescription medication. This is a controversial approach, however, although many physicians use placebo treatments in clinical practice and only a minority view it should be prohibited due to ethical reasons. Note that this study did not review the effects of over the counter pain medications compared to placebo.

Suggested reading: Heal Your Headache: The 1-2-3 Program for Taking Charge of Your Pain

Related blog entry: The Stomach Bug/Flu in Children: What Works & What Doesn't

Reference: El-Chammas K, Keyes J, Thompson N, Vijayakumar J, Becher D, Jackson JL. (2013). Pharmacologic Treatment of Pediatric Headaches: A Meta-analysis. JAMA Pediatrics.

Increased Risk of Sudden Hearing Loss in HIV

Common signs and symptoms of HIV (human immunodeficiency virus) includes weight loss, fever, and a sickly appearance even though these are not universal problems in those infected with the condition. Hearing loss is usually not one of the first symptoms that comes to mind when thinking of HIV but is can happen in between 21 to 49% of cases.

There are three types of hearing loss. The first type is sensorineural hearing loss, which is caused by damage to the auditory nerve that transmits message to the ear, damage to the inner ear, or damage to parts of the brain that process sounds. When this occurs suddenly (over a period of a few hours to 3 days), it is known as sudden sensorineural hearing loss (SSHL). When it has been present for a long time, it is known as chronic sensorineural hearing loss. The second type of hearing loss is conductive hearing loss, in which there is a problem conducting sound waves anywhere along the path through the outer ear, eardrum, or middle ear. The third type of hearing loss is mixed-type hearing loss, which is a combination of the first two types.

The main causes of hearing loss in people with HIV are the direct effects of the virus (or other opportunistic infections) on the brain or auditory nerve and side effects of medications used to treat HIV. The sudden form of sensorineural hearing loss (SSHL) is believed to be rare in HIV but there has been no large scale study to on the topic in the English scientific literature.

In an upcoming study to be published in JAMA: Otolaryngology – Head and Neck Surgery, researchers performed such a large scale study with 8,760 HIV patients and 43,800 people without HIV over about a 6-year-period. The study participants were all from Taiwan. The results of the study showed that HIV patients between ages 18 and 35 had a 2.17 higher incidence of HIV compared to controls. The increased risk of SSHL was found to be especially true for men. No increased risk of SSHL was found in the HIV group for patients ages 36 or older for unclear reasons.

Suggested reading: The First Year: HIV: An Essential Guide for the Newly Diagnosed

Related blog entry: Contraceptive Use in Women with HIV

Reference: Lin C, Lin SW, Weng SF, Lin YS. (2013). Increased Risk of Sudden Sensorineural Hearing Loss in Patients With Human Immunodeficiency Virus Aged 18 to 35 Years: A Population-Based Cohort Study. JAMA Otolaryngol Head Neck Surg. 21:1-5.

Milk and Yogurt, but Not Cream, Improves Bone Density

The benefits of dairy consumption are often touted because calcium intake increases bone mineral density (BMD) which is a fancy way to refer to bone thickness. Increased BMD is important for growing youth and also for the elderly, especially to decrease osteoporosis in the latter. Osteoporosis is an abnormal loss of bone thickness and a wearing away of bone tissue.

Although dairy products are a good source of calcium, as pointed out in a prior blog entry, too much supplemental calcium can lead to heart problems in men. In addition, not all dairy products are created equal. In an upcoming study in the Archives of Osteoporosis, researchers at Northeastern University studied the association between various dairy products and BMD in 3212 people over 12 years. Specifically, they examined yogurt, milk, cheese, most dairy (total dairy without cream), and fluid dairy (milk and yogurt).

The study results showed that milk and yogurt were associated with hip BMD but not spine BMD. Milk and yogurt intake also showed a marginally significant protective effect but that this effect needed confirmation with future studies. However, study results also showed that cream might lower BMD. Cheese intake did not improve BMD. The authors concluded that not all dairy products have equal benefits on the skeleton, likely because of different nutritional profiles.

Suggested reading: The Complete Book of Bone Health
 
Reference: Sahni S, Tucker KL, Kiel DP, Quach L, Casey VA, Hannan MT. (2013). Milk and yogurt consumption are linked with higher bone mineral density but not with hip fracture: the Framingham Offspring Study. Arch Osteoporos. 8(1-2):119.

Vision Insurance Should be Part of Regular Health Insurance

Vision loss affects millions of Americans, sometimes due to significant eyes disease. The main eye disease causing vision loss includes glaucoma, age-related macular degeneration (ARMD), and cataracts. Glaucoma is a condition in which increased pressure in the eye can lead to gradual loss of vision.

ARMD is a loss of vision in the center of the visual field (the macula) because of damage to the retina. The retina is an area at the back of the eye that is sensitive to light. Cataracts is a darkening of the lens in the eye. The lens is an organ located between the colored part of the eye, that bends light as it enters the eye.

The best way to prevent permanent vision loss from these and other conditions is early detection and treatment, which can be accomplished by periodic eye checkups. People may avoid early screenings if they do not have symptoms, which can happen when a good eye compensates for a bad eye. It is also likely that people will be less likely to go for preventive vision screenings if they do not have vision insurance. Many people have regular health insurance but do not have vision insurance because it is a separate insurance benefit. In efforts to lower healthcare costs, which is increasingly happening due to healthcare reform, vision coverage is often dropped.

In an upcoming issue of JAMA Ophthalmology, researchers reported on the results of a large study with 27,152 adults (ages 40 to 65 years) examining the likelihood of an eye care visit within the past year and of self-reported visual impairment in those with vision insurance versus those who did not have vision insurance. Of the adults studied, 3158 (11.6%) had glaucoma, cataracts, and/or ARMD.

About 40% of the overall sample and those with eye diseases did not have vision insurance. The researchers found that people with vision insurance were more likely than those without vision insurance to have eye care visits, to report no difficulty recognizing friends across the street, and to report no difficulty reading printed material. Those who had an eye care visit from the total sample and eye disease sample reported being better able to recognize friends from across the street and had no difficulty reading printed material.

The researchers concluded that lack of vision insurance interferes with eye care services, which may lead to permanent vision damage. The researchers argued that preventive eye car should stop being a separate insurance benefit and should be a mandatory part of all health plans. I agree with them and would also say the same thing for dental insurance…put them all under one comprehensive plan.

Suggested reading: Reader's Digest Guide to Eye Care: Common Vision Problems, from Dry Eye to Macular Degeneration
 
Reference: Li YJ, Xirasagar S, Pumkam C, Krishnaswamy M, Bennett CL. (2013, in press). Vision Insurance, Eye Care Visits, and Vision Impairment Among Working-Age Adults in the United States. JAMA Ophthalmology.

When “Mad Cow Disease in Humans” is Misdiagnosed

Mad cow disease is also known as bovine spongiform encephalopathy (BSE). This is because the word “bovine” refers to cows (and other related animals) and the last two words refer to this being a disease of the brain and spinal cord (encephalopathy) that causes it to have a spongy appearance (spongiform). 

Mad cow disease is a deadly condition caused by an abnormal protein known as a prion, which enters the body when cows are fed the remains of other cows or infected sheep. The prions that cause mad cow disease are highly resistant to heat and are very difficult to kill. 

When humans eat cow meat infected with mad cow disease, the prions can enter the body and cause a similar disease in humans. When this happens it is known as variant Creutzfeldt–Jakob  disease (vCJD). The condition presents as a rapidly progressing dementia with hallucinations. Dementia is a progressive loss of cognitive and intellectual functioning without loss of consciousness. A hallucination is a strong sensory perception that one has of an object or event while awake, when no such object or event exists.

There are two other kinds of CJD. One is called familial CJD (fCJD), in which the patient inherits a genetic mutation (abnormality) that leads to the formation of prions that cause the condition. Lastly, there is sporadic CJD (sCJD), in which people develop the condition without any known risk factors. In other words, there is no evidence that they consumed contaminated meat and the condition does not appear inherited. The sporadic form is the most common form of CJD. This has sometimes been referred to as “mad cow disease in humans” (hence the title of this blog post) even though the two are believed to be unrelated.

Sporadic CJD can be very difficult to diagnose because it is such a rare condition. However, a rapidly progressing dementia is the first tell-tale clue. Diagnosis can be made by integrating the clinical history with the results of diagnostic studies such finding the abnormal 14-3-3 protein in a sample of CSF (cerebrospinal fluid, a cushiony fluid that protects the brain and spine and helps distribute nutrients to these structures), finding characteristic spikes on an EEG (electroencephalography, a test that measures electric brain waves), and finding bilateral abnormalities in the basal ganglia on a brain magnetic resonance imaging (MRI). MRI scans produce extremely detailed pictures of the inside of the body by using very powerful magnets and computer technology. The basal ganglia is an area of gray tissue deep inside the brain that controls movement.

In the current issue of JAMA Neurology, researchers from the University of California San Francisco reported the results of a study designed to examine how often patients with sCJD were misdiagnosed, who misdiagnosed them, what conditions they were misdiagnosed with, and when the correct diagnosis was made. The study involved 97 patients eventually proven to have sCJD based on a microscopic analysis of brain tissue.

The results of the study showed that only 18% of patients with sCJD were correctly diagnosed on the first evaluation and when this happened the diagnosis was almost always made by a neurologist.  However, the doctors  who most often made the wrong diagnosis were also neurologists as well as primary care physicians.  The average time from disease onset to correct diagnosis was 7.9 months, which was about two thirds of the way through their fatal disease course.

The study found that the top five misdiagnoses for sCJD were viral encephalitis (inflammation of the brain caused by a virus), paraneoplastic disorder (a disorder that mimics cancer but is not actually cancer), depression, peripheral vertigo (spinning sensation while sitting still), and Alzheimer’s disease (the most common form of dementia).

Suggested reading: The Pathological Protein: Mad Cow, Chronic Wasting, and Other Deadly Prion Diseases
 
Reference:  Paterson et al (2013, in press). Differential Diagnosis of Jakob-Creutzfeldt Disease. JAMA Neurology.

Too Much Calcium Can Hurt Men’s Hearts

It seems that everywhere you look in the grocery store these days, you will find food and drink manufacturers touting that their product is a great source of calcium or that it contains a calcium supplement. Orange juice is a good example where you can purchase brands with added calcium in it.

For people who want more calcium, they can easily purchase individual calcium supplement pills. The reason that many people want to add more calcium to their body is because calcium helps make bones stronger. This is an especially important benefit to the elderly, whose bones become more brittle and are more susceptible to breaking.  This is a big reason why 50 to 70% of the elderly are known to use calcium supplements.

While there can be benefits to bone strength by increasing calcium, this does not necessarily mean that the added calcium is beneficial for others parts of the body, specifically, the heart. That is, evidence has come to light that use of calcium supplements is associated with heart attacks, death from heart disease, and stroke. A stroke is a burst artery (a type of blood vessel that carries blood away from the heart) or a blockage of an artery in the brain.

In an upcoming study in JAMA Internal Medicine, researchers presented results from a very large study involving 388,229 older adults (ages 50 to 71) in 10 states. The study examined the association between the use of individual calcium supplements and calcium in multivitamins with cardiovascular disease/death.  The subjects were followed-up over a period of 12 years.

In men, the study found that high intake of supplemental calcium was associated with a higher risk of death from cardiovascular disease (particular from heart disease but not stroke). No negative cardiovascular effect of supplemental calcium intake was found in women and no negative cardiovascular effect of dietary calcium intake was found for men or women. Overall, you may want to consider talking to your doctor about the results of this study if you are a man older than 50 who uses a high level of supplemental calcium.

Suggested reading: The Complete Book of Bone Health

Related blog entry: Pale Skin and Vitamin D

Reference: Xiao Q, Murphy RA, Houston DK, Harris TB, Chow WH, Park Y. (2013, in press). Dietary and Supplemental Calcium Intake and Cardiovascular Disease Mortality: The National Institutes of Health-AARP Diet and Health Study. JAMA Intern Med.

Adult Psychiatric Effects of Childhood Bullying

Unlike decades ago, today there are significant efforts in place to decrease bullying in school. This mainly takes the form of bullying prevention programs that teach children to be friendly to one another, to pledge not to be a bully, and to take a strict disciplinary approach to a child who physically or emotionally bullies another child.

RECOMMENDED BOOK: Bullying Prevention and Intervention: Realistic Strategies for Schools

While these efforts are laudable, bullying can extend beyond school grounds where school officials have limited to no influence. In some instances, such as cyber bullying, school officials can sometimes intervene, but in other cases such as bullying at the neighborhood playground, there may be nothing they can do. While parents should take responsibility to prevent bullying, there are too many broken households and irresponsible parents who do not effectively teach their children right from wrong. In fact, children’s anger regarding issues related to their parents (e.g., witnessing domestic violence, being the victim of parental abuse, parental divorce) is part of what can lead some children to become bullies towards others to release their own anger.

I have always firmly believed that childhood experiences are critical to developing our personalities and that the effects of these childhood experiences typically last into adulthood in some way, shape, or form. Although we are all born with a certain biological temperament, childhood experiences affect the way we learn to interact with others (e.g., outgoing versus shy), how we think about others (e.g., trust or mistrust), our motivational desires (e.g., to fit in or stand out), and shape our self-identity.

Since it is also known that victims of bullying and being a bully are associated with increased risks of psychiatric problems in childhood, there is good reason to believe that such problems extend into adulthood. In an upcoming research study to be published in JAMA Psychiatry, researchers tested this hypothesis with 1420 young adults who had been assessed for being the victim of bullying and/or being a bully four to six times between ages 9 and 16.

The results showed that the effects of being bullied are direct, have multiple effects, last into adulthood, and that the worst effects were for people who were both victims of bullying and bullies (bullies/victims). Specifically, victims of bullying and bullies/victims had increased rates of psychiatric disorders in childhood and adulthood as well as family hardships.

The researchers found that even after controlling for the effects of childhood psychiatric illness and family hardships that victims of bullying had higher rates of agoraphobia, generalized anxiety disorder, and panic disorder in young adulthood. Agoraphobia is fear of being in places or situations from which escape may be difficult (or embarrassing) or in which help may not be available in the event of having a panic attack or panic-like symptoms.

Even after controlling for the effects of childhood psychiatric illness and family hardships, bullies/victims were at increased risk for young adult depression, panic disorder, suicidality (males only), and agoraphobia (females only). How about bullies only? They were more likely to develop antisocial personality disorder. Antisocial personality disorder is a more serious behavioral and emotional disorder that involves a pattern of disregarding the rights of others since age15. Overall, these results show that being a victim of bullying has more negative psychiatric effects (particular those associated with being anxious, which make sense) than being a bully.

Related Blog Entry: Cyber Bullying to a Dying Child with Huntington's Disease: A New Low for Society

Reference: Copeland WE, Wolke D, Angold A, Costello EJ. (2013, in press). Adult Psychiatric Outcomes of Bullying and Being Bullied by Peers in Childhood and Adolescence. JAMA Psychiatry.

Using Computers to Improve Eye Socket Fracture Surgeries

Eye socket fractures commonly occur after traumatic injuries to the face such as motor vehicle accidents, assaults, and falls. For many reasons, they are among the most complex fractures to surgically reconstruct. For example, precise surgical skill is required to avoid damaging the eyelid and the eyes, the surgical work space is narrow, and viewing the entire bone fracture is usually impossible.

Adverse outcomes can result from attempts to surgically reconstruct the eye socket. The most common adverse outcomes include double vision, posterior displacement of the eyeball within the orbit, and decreased eye sensitivity. Some people need a second operation due to complications from the first, which is another adverse outcome. To avoid these complications, it is essential to restore the orbital (eye) bones to their correct structural position. These days, computer assisted technology can aid the surgeon to achieve this goal.

One such computerized technique is referred to as mirror image overlay (MIO). This technique extracts an image of the non-traumatized eye socket on the opposite side of the face and superimposes it onto an image of the fractured eye socket. This provides the surgeon with better information about what the normal bone structure should look like in the individual. It also provides the surgeon real-time feedback of the position and shape of a surgical implant in relation to the correct structural position of the natural bone. The MIO images come from a CT scan. CT scanning is an advanced imaging technique that uses x-rays and computer technology to produce more clear and detailed pictures than a traditional x-ray.

In an upcoming article in JAMA Facial Plastic Surgery, researchers from the University of Washington Harborview Medical Center explain this computerized technique in more detail and report on whether it improves outcomes in 113 consecutive cases of complex orbital fractures. Of these cases, 56 surgeries were performed with the MIO computerized technique and 57 were performed without it. The results of the study showed that surgeries using the computerized technique resulted in decreased double vision and a greatly reduced need for a second surgery. The authors recommended the use of this computerized-assisted surgical technique for complex eye socket fracture repair.

Suggested reading: Face The Facts: The Truth About Facial Plastic Surgery Procedures That Do and Don't Work

Reference: Bly RA, Chang SH, Cudejkova M, Liu JJ, Moe KS. (2013,in press). Computer-Guided Orbital Reconstruction to Improve Outcomes. JAMA Facial Plast Surg.

Salivary Stones: The Mouth’s Version of Kidney Stones

Most people have heard of kidney stones (technically referred to as renal calculi) but not many people have heard of salivary stones. The formation of stones in the salivary glands is technically referred to as sialolithiasis.

These stones (pictured above) are most commonly found in the submandibular glands (also known as submaxillary glands) which are located below the floor of the mouth. These glands produce about 70% of saliva. Salivary stones can also occur in the parotid glands, which is the largest of the salivary glands.

The most common signs and symptoms include mouth pain (usually in the floor of the mouth) and intermittent swelling in the area of the gland. The diagnosis is usually made after the doctor has performed a physical examination and obtained a clinical history but imaging techniques provide a more definitive indication. The most commonly used imaging techniques to diagnose salivary stones are x-rays, ultrasound scanning, and sialograms (a special x-ray technique of the salivary glands). Ultrasound scanning is a procedure that uses high-frequency sound waves to produce images of internal body structures. There are various surgical and non-surgical options available to remove the stones.

About 97% of cases of salivary stones occur in adults but rarely, these stones also occur in children. One such case is soon to be published in an upcoming issue of the Archives of Disease in Childhood. The case is that of a 14-year-old boy with a 6-year history of intermittent swelling on the right side of the neck, associated with pain on swallowing. It would last for several hours and then go away. Initially, his doctor thought that he had a swollen lymph node and treated him with antibiotics. This is a common initial diagnostic error. However, when the antibiotics did not work, the doctor felt the stone upon physical exam, confirmed the diagnosis by x-ray, and removed it through surgery.

Suggested reading: Salivary Gland Disorders and Diseases: Diagnosis and Management

Reference: Liu NM, Rawal J. (2013). Submandibular sialolithiasis in a child. Arch Dis Child.

Use of Smartphone Apps to Diagnose Skin Cancer: Beware

These days, it seems that there is a smartphone app for just about anything. The medical field is no stranger to apps, including ones that check for medication interactions, those that help people learn anatomy, and those that check for the possible reasons for various signs and symptoms. There are several apps that exist for patients that allow them to take a picture of a mole and have it analyzed to determine if it is likely benign (non-cancerous) or likely to be cancer.

Cancerous skin lesions are referred to as melanomas. Some moles are describes as dysplatic nevi, meaning that they are usually benign but may resemble a melanoma.

It is essential to detect dysplatic nevi and melanomas early so they can be removed before skin cancer spreads throughout the body. This requires going to a dermatologist for a full body skin check, typically about once a year. However, many people do not do this because of time pressure, financial stress, lack of health insurance, difficulties finding a dermatologist (skin doctor) in their area, and embarrassment about needing to remove their clothing during the physical exam. For such people, free or low cost medical apps can be an appealing alternative.

The problem, however, is that such apps are not subject to any type of regulation or oversight. The app makers protect themselves legally by requiring the user to accept a disclaimer saying they are only meant for educational purposes, but many patients will still likely rely on the results as medical advice. If the results of such apps are typically wrong, however, this can lead to a very dangerous situation in which patients believe that a melanoma is actually non-cancerous and do not have it evaluated by a dermatologist until it has worsened and spread throughout the body. In some cases, this can potentially lead to death.

In an upcoming issue of JAMA Dermatology, researchers from the University of Pittsburgh Medical Center tested four smartphone apps designed for melanoma detection with existing photographs. The pictures submitted were those that had undergone tissue analysis and were reviewed by a board certified dermatologist. In total, 188 images were used, 60 of which were melanomas. The others were benign.

The first three apps used algortithms to classify the images. Application 1 determined if the image was “problematic” or “okay.” Application 2 determined if the image was a “melanoma or if it “looks good.” Application 3 determined in the image was “high risk,” “medium risk,” or “low risk.” The fourth app did not use an algorithm but sent the image to a board-certified dermatologist for evaluation and provided results within a day. This app classified images as “atypical” or “typical.” Each app also classified images as unevaluable in some way, if necessary.

The results of the study were very concerning because there were too many false negatives (classifying abnormal results as normal) for the three automated programs. Even the best of these classified 30% of melanomas as benign. One of these programs only had a sensitivity of 7%, meaning that it only correctly identified 7% of melanomas as abnormal. This program was the most specific (94%) meaning that it correctly identified benign lesions as normal, but this is hardly reassuring since the program classified almost all images (including melanomas) as normal. The three other programs had specificities ranging from 30 to 39%.

The most sensitive program of the four was the only one that used a physician to review the images. This program only falsely classified 2% of melanomas as benign. The cost of this increased sensitivity was increased price of the product, as it was the most expensive of the four, costing five dollars per image analysis and a 24-hour turn-around time for results. The other programs were free or $4.99 for unlimited use and provided immediate results. As the saying goes “You get what you pay for.”

The critical statistics for classification accuracy are the positive predictive values (PPV) and negative predictive values (NPV). PPV indicates the proportion of positive test results that are true diagnoses. All four apps performed poorly in this regard, with PPVs ranging from 33 to 42%. For the app using the physician, this is because it classified many normal images as abnormal. The NPV for this app though, was 97%, meaning that 97% of negative test results were correct. The other programs had NPVs of 65 to 73%.

Suggested reading: Beating Melanoma: A Five-Step Survival Guide
 
Reference: Wolf JA, Moreau J, Akilov O, Patton T, English JC, Ho J, Ferris LK. (2013). Diagnostic Inaccuracy of Smartphone Applications for Melanoma Detection. JAMA Dermatol. 16:1-4.

Lionel the Lion Faced Man: A Case of Hypertrichosis

Abnormalities in human variation sometimes provide shocking visual examples of various medical conditions. At the MedFriendly Blog, the extremes of human variation have previously been highlighted here, here,  here, and the case of the lady who grew horns. Another good example is the little known case of Stephan (Stephen) Bibrowski, known by his sideshow name “Lionel the Lion Faced Man.”

As you can see from his shocking visual appearance, Lionel was covered with hair, so much so that he could actually comb the 8-inches of hair on his face to completely cover his nose and style it in a way to appear lion-like. He had about four inches of hair hanging from other parts of his body besides the face. The only parts of his body that were not covered with hair were the soles of his feet and the palms of his hands.

Lionel was doing what he could to deal with a very difficult medical condition known as hypertrichosis.
Hypertrichosis is a technical term that refers to an abnormal amount of hair on the body. While we all probably know of people who are abnormally hairy, Lionel had a more extreme version of hypertrichosis, which is often referred to as werewolf syndrome because it can cause people to take on the appearance of a werewolf. Unlike lions and werewolves, many people with hypertrichosis have few teeth, which was the case for Lionel.

Children born with extreme versions of hypertrichosis face rejection from society, including from their own family. For example, Lionel’s mother  rejected him and gave him to a show manager at age four, who named him Lionel the Lion Face Boy at the time and showed him around Europe as a circus freak . He later wound up on display at Barnum and Bailey’s circus in the early 1900s. Although many would naturally feel sorry for him, he reportedly enjoyed his fame. He was known to be shy, polite, and intelligent, able to speak five languages fluently. He died at age 41, although there are varying accounts as to the cause.

Some people like Lionel are born with hypertrichosis and in those cases, there is no cure. In other people, the condition is acquired over time and can be treated if the cause can be found (e.g., a reaction to medication). In some people, like Lionel, the excessive hair growth covers nearly the entire body whereas in other people the excessive hair growth is localized to one area of the body.  Various hair removal techniques are available for temporary and permanent hair removal.