Genetics in Medicine: A Game of Odds

Each of us begins life as a single cell. The chromosomes within, formed out of long chains of DNA called genes, carry all the information necessary for the formation of a human being. The entire complement of  DNA, including long segments that have no known function, must replicate itself billions of times over the course of development of the baby and the life of the individual who emerges from the womb.  If there were never any errors in the original DNA,  if there were never any errors in replication of DNA, and if genes did not turn on and off in response to environmental factors, aging would not occur and human misery would be confined to infectious diseases and trauma. Now that the human genome has been decoded, can we look forward to a disease free world and to extension of the seemingly fixed lifespan of 110-120 years? Not likely, but the focus on the genetic contribution to disease will change medicine, for better and for worse, in the years to come.

Visible genetics: the family history

Doctors have always taken a family history as part of the initial evaluation of a patient. Physical features, health and ailments that run in families are visible genetic information. Height and body shape, nose shape, bunions, baldness, premature white hair all “run in” families. So do a variety of illnesses. Family history tells the story of genes that have expressed themselves already. Laboratory analysis of an individual’s genes attempts to predict what may happen in the future.

Laboratory genetics

In a few rare illnesses such as cystic fibrosis, sickle cell disease, and some devastating neurological degenerative disorders resulting from errors in very small parts of the genetic code, the genetic information is clear cut – the individual has an abnormal gene, and they have or will eventually show signs of the disease. These diseases, along with problems of chromosome breakage or duplication such as Downs syndrome, are the object of prenatal screening tests.  For the most part, however, genetic results are statistics – the odds that a problem will eventually appear. Potentially damaging treatments applied to healthy people, based only on future odds,  is the “for worse” change that may come with the addition of genetic information in the practice of  everyday medicine.

 The problems with statistical medicine 

Statistical predictions apply to large numbers of people, not to individuals. Not all people who have a gene associated with Alzheimer’s dementia will get the disease, but since more people born with that particular gene will develop Alzheimer’s than those born without it, the gene is said to increase the risk for the Alzheimer’s disease. The prediction of a strongly hereditary trait – one associated with an 85% likelihood that some kind of illness or cancer will appear by a given age – gives the impression that the illness is almost inevitable for every member of the family. But from the standpoint of an individual within the family, the risk is always 50%.  Either they will or will not be affected.

The importance of treatment availability when disease risk is high

What does knowing that there is an increased risk of suffering a given disease do for you? If there is a treatment that prevents the evolution of the disease, and it has no adverse effects, then it would be reasonable to gamble on undergoing treatment based on worry that the disease will appear, rather than waiting to see if one is in the lucky percentage that escapes. Women who undergo removal of their breasts and or ovaries because they have a genetic trait that greatly increases risk for cancer in these organs have made this judgment.  (They also must accept the minuscule risk that breast or ovarian cancer can still occur even after surgical removal of the organs.)

In the case of the devastating brain degeneration known as Huntington’s disease (HD), people usually know they are at risk because one parent has developed the characteristic dementia and movement disorder in midlife. Because of the so called dominant inheritance pattern of HD, half of the offspring of the parent, statistically, will also be affected.  But no one knows which children carry the gene unless testing is done. Now available and definitive, the genetic test for this disease is a double-edged sword. Life is normal for the carriers of the gene until middle age. The knowledge of what is coming might convince the bearer of the gene not to reproduce, but also make living a full and happy life seem out of reach.

The role of genetics in common diseases

What about the prediction of increased susceptibility to more common diseases, such as heart disease and some cancers?  This aspect of genetic testing may help people with their motivation to lose weight, exercise, eat well and get their routine colonoscopies. Genetic analysis of cancers that have already developed is already proving helpful in the design of specific treatments for specific tumors. All tumors of lung or liver or brain are not alike and “one size fits all” treatments, the only type available in the past, will give way to individualized plans and drugs. An individual’s responses to drugs for conditions such as high blood pressure and heart disease, including both desired and to adverse effects, is also based on genetic makeup.  Personalized treatments are already increasing for these problems.

Genetics and aging

Genetic studies are also teasing out at least some of the pathways involved in aging. Will advances someday lead to immortality? Very unlikely, and a bad social idea anyway. But understanding the way the genes gradually fail in their the mission of cellular repair may well lead to better old age. The key will be to use the knowledge early in life. So far it looks like preventing the errors in DNA replication that contribute to the diseases of old age depends on the same old things that your grandmother might have advised – eating modest amounts real food, preferably from fresh sources in all food groups, avoiding sugar and other refined carbohydrates, drinking little alcohol, avoiding sunburn, keeping in motion, sleeping enough, and most importantly,  avoiding the biggest DNA error trigger of all – cigarette smoke.  Of equal importance is recognizing that no matter how much we know and try to prevent, life will eventually wind down. Living one’s individual allotment well and fully is as important as avoiding cancer – and may actually help genes replicate correctly.

(For readers especially interested in how the genetic code works, Francis Collins’s The Language of Life, and Matt Ridley’s Genome: The Autobiography of a Species in 23  Chapters are good starting points.)

 

Carpal Tunnel Syndrome

 

Wrist splints are common sights. You see them on cashiers and typists, on hairdressers and bank tellers. They reflect the frequency of a problem called carpal tunnel syndrome. The carpal tunnel is an anatomical structure inside the palm of the hand at its base, and the syndrome is a collection of symptoms related to the nerve that passes through the tunnel on its way from the forearm to the hand.  The nerve is the median nerve, and it is accompanied by nine tendons that connect the muscles of the forearm to the fingers.   At times, lack of space puts pressure on the median nerve, causing aching pain in the wrist, forearm and even upper arm, and numbness or tingling in the thumb, index, third and the half of the ring finger closest to the thumb. With enough pressure the thumb muscles weaken and shrink.  Any combination of these symptoms, when caused by pressure on the median nerve in the hand, adds up to carpal tunnel syndrome.

Nerves tell you they are in trouble

Pressure on nerves that run close to the surface of the body slows conduction of the electrical impulses that carry sensory information about pain, temperature, position and touch. When your foot or arm “falls asleep,” the culprit is pressure on the nerves that carry sensory information. Pressure symptoms from the median nerve in the base of the hand are so common that many people experience them transiently when they grip a steering wheel tightly over a long period of time, or pound or push with the base of the hand. Instinctively, they respond to the feeling of fingers tingling or going to sleep with re-positioning or shaking of the hand. Only when pressure is sustained do nerves become damaged enough to cause the muscles they supply to weaken. The median nerve is a common site of chronic pressure because of the anatomy of the tunnel it must pass through to the hand.

Tunnel anatomy

The roof of the carpal tunnel is an arch of bones at the base of the hand.  The floor is a horizontal span of several tendons and ligaments between the bones on the thumb side and the little finger side of the hand. The bony arch changes shape with hand movements, especially with bringing the thumb across to the little finger side, flexing the wrist and extending the wrist.

Who gets carpal tunnel syndrome?

Because the carpal tunnel is smaller in women than in men, they are more frequently affected by symptoms from pressure on the median nerve, particularly during pregnancy when hands commonly swell.  Some medical conditions like heart or kidney failure, diabetes and growth hormone producing brain tumors may cause pressure to increase in the carpal tunnel. Inflammatory conditions like rheumatoid arthritis may also bring out symptoms. While carpal tunnel syndrome seems common in people whose occupations involve repetitive hand motions or hand pressure, such as hairdressers, typists, bakers, and jackhammer operators, rigorous studies do not fault the activities alone, but the activities combined with the individual anatomic structure, and with underlying medical conditions,  if present.

The reason for those wrist splints

Since the anatomy of the hand is responsible for carpal tunnel syndrome, relief comes from maximizing the space between the ligaments and bones. When symptoms begin, the first line of treatment is a splint that keeps the wrist aligned in a neutral position – neither flexed nor extended. It also keeps the thumb from falling in toward the ring finger. The splint’s design allows for use of the fingers and thumb and it can be worn during most activities. The crucial time for keeping it on is during sleep. When we sleep our hands naturally fall into a posture of wrist and finger flexion, and some people exaggerate this pose by tucking their hands beneath them, and even unconsciously clenching them.  Hand position at night often brings carpal tunnel symptoms to light, especially aching in the forearm, and tingling in all the fingers except the pinky.

Stretching the tunnel

Stretching the base of the hand during the day is also helpful. One good stretch is accomplished by  placing the hand flat on a wall at about shoulder height, turning the body perpendicular to the wall and stepping far enough away to straighten the elbow as much as possible. Then rotate the “eye” of the elbow, its inner bend, up to face the ceiling as much as possible. Hold the stretch for up to thirty seconds at a time.

Advil doesn’t change the anatomy

Anti-inflammatory drugs like Advil can help reduce swelling of tendon sheaths if the problem with the hand is related to injury or an underlying inflammatory condition like rheumatoid arthritis, but chronic use of anti-inflammatory drugs has not been shown to help typical, uncomplicated carpal tunnel syndrome.

When conservative measures fail

If conservative measures like splinting and stretching do not resolve carpal tunnel symptoms, surgery to expand the canal is generally successful. Some surgeries are performed through a small incision, using a scope and tools inserted directly onto the tunnel to cut away the connective tissue surrounding the nerve and tendons. Other cases require an open incision in the palm.

Diagnosis

Diagnosis of carpal runnel syndrome is relatively easy from the history alone. Conservative measures can be attempted without any other tests, provided that there are no underlying medical conditions suspected to be causing the symptoms. However, if conscientiously applied conservative measures fail, or if there is muscle weakness at the time of diagnosis, then a test called a nerve conduction study and electromyogram (EMG) will almost always confirm the diagnosis. The pressure on the nerve in the carpal tunnel causes a current applied to the nerve to be delayed in its passage to the hand, easily picked up in the nerve conduction study. Tiny needles that measure activity in the palm of the hand pick up signs of loss of nerve supply to muscles.  Muscle nerve loss does not respond as well to conservative measures as sensory symptoms like numbness and tingling do, so if the EMG demonstrates muscle nerve loss, surgery is usually recommended.

 

 

A Primer on Steroids

Ask around among your friends and you will find that many of them, at one time or another, have been given “steroids” by their doctors. They have taken pills, inhaled the drugs, had injections, smeared creams on their skin, dropped liquid into their eyes, or received the drugs in an enema. They may have been treated for pain, swelling, rashes, cancer, slipped discs, vision problems, arthritis, colitis or vasculitis.  At the same time, you hear stories of athletes “doping” with “steroids” to enhance athletic performance and losing titles they won for having done so. You read ads for body building “steroids” and see the results in pictures of massively muscled men – and women. And sometimes you hear that testosterone, widely advertised for aging men, is a “steroid.” Are these all the same drugs? Yes, and no.  They are all manufactured versions of human steroid hormones.

What makes a steroid hormone?

All steroid hormones begin as molecules with the same core structure made from cholesterol. Various carbon, hydrogen and oxygen combinations added to the core make different chemical structures with different functions in the body. Those steroid hormones made in the testes and ovaries are called sex hormones. Those made in the adrenal glands are called corticosteroids and mineralocorticoids. Steroid hormones trigger a large number of different and vital chemical responses throughout the body.

Which steroids are used for which problems?

The steroids you hear about most frequently are synthetic versions of some of the adrenal glands’ corticosteroid hormones. Because they block immune system function, they are very powerful anti-inflammatory agents, commonly prescribed for allergic responses, autoimmune diseases, catastrophic situations involving trauma and shock, some cancers, and pain problems in which inflammation is thought to be the culprit. The steroids used for body building and performance enhancement are usually derivatives of the male sex hormones, or are nutritional supplements which are thought to increase the body’s own production of the male hormones.

Catabolic and anabolic effects: breaking down and building up

The first corticosteroids used in humans were animal adrenal gland extracts. They were lifesaving treatments for shock in people who had lost adrenal gland function. Incidental observations about their powerful anti-inflammatory effects propelled their widespread use and the Nobel Prize in Medicine in 1950 went to the men who elucidated their physiologic effects. With increased use, however, corticosteroids proved to have many serious long term effects because they are catabolic hormones, achieving their results by breaking down the body’s proteins and diverting them for different purposes.

The male sex steroids are anabolic hormones because they signal the body to build proteins. They have much narrower medical applications than the adrenal corticosteroids do. Anabolic steroids are useful in patients who have impaired male hormone production for reasons such as pituitary gland (the master gland) failure or testicular failure. But anabolic steroids are not medically needed in healthy people, and their use in amounts required to increase muscle mass above the body’s natural endowment courts significant risks. They are not medically available for healthy people. The male hormone testosterone is sometimes prescribed for men who have low testosterone levels later in life, with the aim of restoring libido and maintaining muscle mass, though there is some controversy about the risks versus benefits of this practice.

Powerful drugs with powerful side effects

Side effects of adrenal corticosteroids are related to the dose, delivery mechanism and especially to length of time used.  With oral and intravenous delivery, changes in glucose metabolism shift the pattern of fat storage in the body to the trunk, the neck and the face, producing the characteristic “moon facies” of someone treated with steroids over long periods of time, in relatively high does. Skin thins. Muscles shrink. Bones lose calcium and may fracture. Cataracts commonly develop. Insomnia and sometimes a form of mania signal brain effects. Suppression of the immune system, the source of the powerful anti-inflammatory effects of the corticosteroids, allows some infections to blossom. And very soon after steroid treatment starts, the adrenal glands begin to curb their own production of steroids, making stopping the drugs dangerous unless they are slowly tapered, a process that sometimes takes months.

Injections of corticosteroids into painful, presumably inflamed areas cause breakdown of the collagen structure of in connective tissue. Injections directly into tendons can cause enough degeneration at the site to lead to tendon rupture, causing some orthopedists to ban steroid injections anywhere near the Achilles tendon. Steroid inhalation for asthma and chronic obstructive lung disease is similar to topical use for skin problems – very effective at relieving inflammation, and not associated with much absorption into the body, so not as likely to produce adverse effects.

Some of the side effects of anabolic, male hormone steroids are related to their androgenic properties – the ability to produce and enhance male characteristics, and at the same time to shut down the body’s own production of testosterone in the testicles. Female users have deepened voices and develop acne and facial hair, but lose scalp hair. Males develop decreased sperm counts and shrunken testicles and also get acne and lose scalp hair (remember how many bald cyclists there were in the Tour de France during the height of the doping scandals?) But the most dangerous side effects are not visible: they include heart disease, liver cancer, anger, aggression and irritability and depression, as well as abnormalities in liver and kidney function.

Exercise caution in legitimate use of steroids and avoid illegitimate use

Alternate day dosing schedules for corticosteroids may help prevent side effects, as will the development of newer, more targeted versions of the drugs. But steroids should always be approached with caution, and used with great care. The most important things for doctors and patients to consider are the certainty of the diagnosis and likelihood that the condition will improve with less risky treatment. For instance, if orthopedic pain comes from muscular imbalance and not from inflammation, steroid injections will not help. If the condition being treated – say a bad case of poison ivy – will resolve with other types of care, steroid risks are unnecessary. Always remember that some severe steroid side effects can occur with just a few weeks use.

Sidebar: Case History illustrating Risk/Benefit Judgment in Corticosteroid Use

A 60 y.o. woman undergoes successful surgery for a benign brain tumor, but awakens with a paralyzed facial nerve, a well-known and feared complication of surgery in this type of tumor.  She has a severely drooping mouth and lower eyelid. High dose steroids over the next week reduce the swelling in the nerve, resolving the facial nerve paralysis. But the treatment also causes degeneration of the tops of the hip bones – a well-known steroid complication called aseptic necrosis. She then needs two hip replacements. Was the side effect worth the treatment result? In this case, most people would say yes. But if the steroid treatment had been for something that would have resolved with other treatment, the hip complication would have been much harder to accept.

Your Discs Are Bulging—Does it Matter?

Have you been told that you have bulging, degenerated discs in your spine? If so, you are not alone. Millions of Americans undergo X-rays, CT scans, and MRI scans of their backs and necks each year and receive the same news. As a result, multiple millions of dollars are spent on medications, physical therapies, surgical procedures, and spinal manipulations in an effort to treat back pain. The people undergoing all this diagnosis and treatment might imagine that other, luckier people have normal spinal discs, but they might be surprised to learn that bulging discs are so common that they may be considered a normal part of aging. Most often, they cause no symptoms or problems, and it pays to be cautious about embarking on courses of investigation and treatment based simply on these “degenerative changes.” But it also pays to know when and why discs do cause trouble.

What and where are spinal discs?

The spine is a column of thick, circular bones—also called vertebral bodies—that in terms of anatomy is divided into three major sections: the cervical (neck) spine, thoracic (mid-back) spine, and lumbar (lower back) spine. The vertebral bodies have flat tops and bottoms, and they sit atop one another, separated by discs that cushion the spine and allow for the compression, rotation, and bending of the entire spinal column. The arches of bone on the back sides of each of the vertebral bodies line up with each other to form a bony tunnel, which surrounds the spinal cord and the nerves that connect it to the body. Pairs of these nerves exit from the sides of this canal below each vertebral body.

Spinal discs are a lot like flattened cream-filled doughnuts, with a soft center called the nucleus pulposus and a tougher perimeter called the annulus. Each annulus is attached to the ligaments that run the length of the spine and hold it together. Every day, gravity squeezes so much water out of each disc that an average adult shrinks by more than one-half inch between morning and night. As a disc loses water and flattens, it may protrude beyond the edges of the vertebral bodies located above and below it. Under these conditions, the ligaments bounding the disc tend to bow outward to accommodate the flattening, and the result is the classic “bulging” discs often seen on back scans. Is such bulging a cause of pain?

When bulging becomes cracking and herniation

Judging by the number of people who have bulging discs and no pain, the answer to this question is, not very often. But discs can cause pain if they are damaged. Cracks can develop in the back part of the annulus, especially in the lower neck and lower back, and are sometimes caused by sudden movement or excessive loading of the neck or back or sometimes with no readily identifiable cause. Risk factors for the development of cracks include age, smoking, and heavy weight lifting. When cracks form in the annulus, nerve fibers send out distress signals which feel like deep back pain that sometimes radiates down the legs. Symptoms usually improve over a period of six to eight weeks, but if the tear is extensive enough, it may open a path for part of the soft nucleus pulposus of the disc to work its way through, becoming a so-called herniated or “slipped” disc.

Location determines  symptoms

Extruded far enough, a herniated disc bulges straight backward into the bony tunnel that houses the spinal cord or off to either side, where it squeezes into the narrow canal that should hold only a spinal nerve root passing out to the body. Depending on the location and the extent of the disc herniation, pain in the back or neck might be accompanied by a set of neurological symptoms including numbness, tingling, and a sense of weakness in an arm or a leg. Symptoms may improve over time with no treatment or with relatively modest treatments, like physical therapy or cortisone injections, as the disc shrinks. But there is potential for the worsening of symptoms, so careful physical evaluation and follow-up are important.

More than 95 percent of disc problems occur in the lumbar spine. Here, as in the neck, discs tend to slip off to the side, compressing single nerves and causing pain to run down a leg or arm or weakness in corresponding muscles. Definite loss of strength in a muscle group controlled by the nerve under pressure most often calls for surgery to decompress the nerve. Sometimes scans indicate that a fragment of disc has broken off and lodged itself under a nerve. Unlike nonfragmented disc herniations, which may gradually shrink and relieve symptoms, symptoms caused by fragmented discs tend to be persistent unless the fragment is removed.

Disc herniation in the upper spine

When discs slip straight back into the central spinal canal, symptoms can range from none to neurological deficits that require immediate decompression surgery. Serious central disc herniations are uncommon in the neck and quite rare in the thoracic spine but in both locations may cause symptoms from the spinal cord itself that include pain, balance problems, weakness in the legs, and an inability to control the bladder.

Disc herniation in the lumbar spine

In the lumbar spine, because the spinal cord does not reach down this far, central disc herniations put pressure on the so-called cauda equine, or “horse’s tail” of nerves that travel down the spinal canal from the spinal cord to their exit points at different lumbar levels. Symptoms here often consist of a confusing array of pain, numbness around the groin and legs in a pattern that traces an area where a saddle would make contact with the body, leg weakness, fecal incontinence, and trouble initiating urination. This combination of symptoms requires immediate surgical decompression.

Surgery or not?

While surgery for severe symptoms is an easy decision and while many disc removals are done with microsurgical techniques and small incisions and are less invasive than in the past, the decision to try to improve back pain alone by operating on a bulging disc is not as easy. To improve the likelihood of good results, studies like disc injections are sometimes done. The dye used helps visualize the disc, and, if the injection reproduces the patient’s pain, confidence that the disc is the source of the back pain increases. Injections can be helpful in determining which of several bulging discs might be the source of pain.

Caution in the decision

Disc removal for pain alone or for pain combined with sensory symptoms that come and go should be approached with caution. First, every attempt should be made to improve the strength of the muscles that support and move the spine, to improve overall posture, and to lose excess weight that the spine is asked to support. Back and neck pain arise from many different structures—muscles, ligaments, tendons, bones, and nerves—and can improve dramatically with improved strength, flexibility, and posture—bulging discs or not.

 

What is Macular Degeneration?

eye

To understand age-related macular degeneration (AMD), the most common cause of legal blindness in older people, you need to understand the macula.  First, think of the eye as a hollow globe made of three layers.  The white, outside layer is the sclera. Inside the sclera is a middle layer called the choroid, which contains networks of tiny blood vessels called capillaries. The inner layer, called the retina, contains pigment-filled cells that absorb light, light receptor cells call rods and cones that change light into electrical information, and nerve cells that transmit that information to the brain. In the center of the retina, there is a tiny yellow spot about the diameter of a pencil eraser called the macula lutea (Latin for yellow spot).

What does the macula do? Try looking at a star to find out.

The macula contains only cone receptors, which detect color, and is responsible for sharply focused vision. If the macula degenerates, visual clarity is lost. The other 96% of the retina contains mostly rods, non-color receptors that perceive dim light and movement and are responsible for peripheral vision.  When you look at stars, you see them only with your peripheral vision. Trying to focus on a single star makes it disappear because the macular cones require more light than the night sky offers.  Imagine the disappearance of anything you try to focus on, in any kind of light, and you have some grasp of what macular degeneration is like.

When the macula degenerates

Age-related macular degeneration moves slowly, with many years between the first visible changes in the retina and the onset of symptoms. The first symptoms come from decreasing visual sharpness. Reading speed declines. Reading glasses no longer work for fine print. Road signs look blurred. With progression, dark patches or blank spots appear when patients focus on faces or print, and sometimes straight lines appear wavy. Legal blindness (best corrected vision less than 20/200) comes later and is never total because peripheral vision is spared, even though some of the same degenerative changes affect other parts of the retina. The macula is simply so tiny and so specialized that small areas of damage interfere with the ability to see clearly.

What’s the cause of macular degeneration?

No one knows for certain what causes macular degeneration but ophthalmologists suspect that the vascular anatomy of the retina plays a significant role. While the macula looks yellow, the rest of the retina has a reddish hue because of an overlying bed of capillaries, branches of the retinal arteries and veins which spread like a tree over the retinal surface. The tree stops at the macula and this vital region depends solely on blood flow through the network of tiny capillaries in the choroid layer for oxygen and nutrients and for clearing away the products of its high rate of energy use. The first changes that signal possible AMD, visible long before any symptoms appear, occur in the microscopic space between the choroid layer and the retina and are called Drüsen.

Signs of deterioration

Drüsen are yellowish accumulations of fats and proteins and inflammatory substances.  Small, sharper edged patches called hard drüsen are commonly seen in other parts of the retina and do not interfere with vision, but larger, fluffy patches, especially in the area of the macula warrant more frequent follow-up exams because people who have them sometimes, but not always, develop symptoms of AMD.  If visual symptoms occur and drüsen are present, the diagnosis is dry macular degeneration. In about 10-20% of cases of dry macular degeneration, new tiny blood vessels poke through to the retinal layer from the choroid, a process called neovascularization. When this happens, the diagnosis becomes wet macular degeneration which reflects the tendency of these blood vessels to leak and bleed, causing more cell destruction and separation of the retina form its underlying supporting layers.

Who’s at risk for macular degeneration?

The primary risk factors for macular degeneration are age, smoking and increased body mass index. A family history of macular degeneration also increases the chances of its occurrence, but so many different genes are involved that predictive genetic testing is not useful. Diabetes and vascular disease can accelerate the degenerative process. On the positive side, diets rich in green leafy vegetables, particularly those containing abundant antioxidants called carotenoids, as well as diets rich in Vitamins C and E, and those rich in zinc have been associated with lower frequencies of macular degeneration.

Other eye problems are more common

Fortunately, AMD is much less common than other age-related visual problems like presbyopia (poor near vision) and cataracts, both of which are eminently treatable. AMD affects about 2% of people in their 70s. Prevalence jumps to about 14% in Caucasians who reach their 90s, but remains at about 2% in other races. Legal blindness typically does not occur until the eighties.

Treatment

There is no treatment for dry macular degeneration.  The positive correlation between dietary antioxidant consumption and lower rates of AMD has led to the development of the “eye vitamins,” and while studies have shown some slowing of the degenerative process when these vitamins are consumed, there is no evidence that taking them prevents the onset of the disease.

The first line of treatment for wet macular degeneration is injection, directly into the eye, of drugs which block new blood vessel formation. This slows the disease process, but does not cure it. Another treatment is photocoagulation, or the injection of drugs which, once activated by light aimed at the new blood vessels causes them to shrivel.  Laser treatment of troublesome blood vessels is commonly done, but it destroys the retina in the area treated, so its aim is prevention of new problems.  Surgery is sometimes required to drain fluid accumulations or reattach retinal tears.

Preliminary studies suggest that high dose cholesterol lowering drugs (statins) may shrink drüsen, but one worrisome study of data from a large managed care group suggested that statin use for over a year increased rates of progression of dry AMD to wet AMD. Long term prospective studies are needed, and eye exams should be routine for anyone taking statins.

Useful Macular Degeneration websites

https://nei.nih.gov/health/maculardegen/armd_facts

http://macularhope.org

http://www.aao.org/eye-care-for-older-adults

http://www.amd.org/

Broken Heart Syndrome: The Octopus Trap

“Doctoring her seemed to her as absurd as putting together the pieces of a broken vase. Her heart was broken. Why would they try to cure her with pills and powders?”  Leo Tolstoy, writing about Kitty’s heartbreak over Vronsky in Anna Karenina

 

Sometimes people say that a spouse who dies unexpectedly within hours to weeks after the partner’s death has “died of a broken heart,” though a variety of different medical conditions are responsible for the increased death rate among grieving partners, who are often elderly. In 1990 a paper appeared in the Japanese medical literature that described a peculiar heart problem, documented by modern technology, that the popular press seized upon as a possible explanation for the correlation between grief or fright or other emotional stress and sudden, unexpected death. The cardiomyopathy the authors described was an abnormality in the heart muscle of the left ventricle, the chamber of the heart that pumps blood out to the body. That part of the heart acted as if it had been “stunned” into inactivity and caused pain and other symptoms commonly associated with heart attacks, but the patients did not have any coronary artery disease.  These facts seemed fit neatly into the concept of a “broken heart.”

Why an octopus trap?

The ventriculograms, or dye studies, of the hearts of the Japanese patients described in the 1990 paper showed peculiarly dilated left ventricles, ballooned at their tips so that they resembled octopus traps – narrow-necked, flask-shaped contraptions that are easy for the tentacled animals to enter but hard to escape. In the Japanese language an octopus trap is a takot-subo and by the mid-2000s the name Takotsubo cardiomyopathy, or TCM, was widespread and many more cases had been described. Risk factors for the stress-induced cardiomyopathy were both physical and mental and included stays in ICUs, near drownings, major physical injuries, bad medical or financial news, legal problems and natural disasters, and, of course, unexpected death of a loved one. Cases have also been attributed to cocaine and methamphetamine use, as well as to exercise stress testing. These patients who acted as if they had had a heart attack were most often women and they had no history of heart problems prior to the events that hospitalized them.

Who is at risk? What are the symptoms?

Takotsubo syndrome is not common, but also not rare. It accounts for 1-2% people who have symptoms initially thought to be caused by regular coronary artery disease. In women, some people estimate that as many as 5% of heart attacks are actually TCM.  Most TCM patients are Asians or Caucasian, over 90% are post-menopausal women and most cases come to attention because of heart attack-like symptoms such as acute chest pain and shortness of breath.  But unusual presentations also occur as a result of the effects of the poor heart muscle function. When it’s pump action fails, the heart sends hormonal signals that affect water and salt balance in the body.  Fluid retention occurs in some people. Low sodium levels cause symptoms of profound fatigue in others. Clots may form in the poorly contracting ventricle, break loose and cause strokes. Lethal complications such as ventricular fibrillation and actual rupture of the impaired ventricle are very rare, but have occurred.

What’s the cause?

Diagnosis of Takotsubo syndrome requires new abnormalities in the electrocardiogram, absence of coronary artery disease and no evidence of heart inflammation from an infection or autoimmune disease. While the enzyme markers for a heart attack may rise, they do so earlier and fall back to normal more quickly than they do in a routine heart attack. In addition, the muscle abnormalities in the left ventricle can’t be mapped to the territory supplied by one coronary artery as they can when a blockage is responsible for the damage. Doctors who make a TCM diagnosis must also make certain the patient does not have a tumor called a pheochromocytoma, which produces stress hormones.

Most patients recover completely

By now TCM is known to be transient, with supportive care leading to complete recovery within 1-2 months in over 95%of patients. Recurrence is extremely rare. However, the actual cause, or mechanism by which the transient heart damage occurs, remains unknown. A number of theories have been proposed and all of them have something to do with a temporary derangement in function of the cells of the inside layer of cells of the left ventricular chamber of the heart. In these cells normal energy production from fatty acids is halted. The area of the heart involved happens to have a high concentration of receptors for catecholamines (adrenaline like hormones), perhaps making it susceptible to overstimulation and damage by severe stress. The high preponderance of postmenopausal women in case reports suggests that perhaps sex hormones are somehow protective factors.

Do people really die from broken hearts?

But is the Takotsubo syndrome responsible for deaths that seem to come from emotionally broken hearts? The mortality rate in cases of Takotsubo syndrome that come to medical attention is low. Recovery rates are high. Broken heart deaths most often occur in older people who have multiple health problems which might play a role. For example, when singer/actress Debbie Fisher died as she was planning her daughter Carrie Fisher’s funeral this year, a NYT reporter speculated about the cause of death being the Takotsubo syndrome. But Debbie Fisher had suffered several strokes in recent years and had high blood pressure. Later stories attributed her death to a fatal stroke related to high blood pressure.

Grief and stress do raise the risks of dying for the bereaved, but the causes of death are many and varied and mostly related to longstanding health problems.  The pills and powders Kitty scorned for her broken heart in Anna Karenina have a place in the treatment of the many other problems that occur in the setting of grief, especially depression. While it is tempting to attribute sudden, unexpected deaths in emotionally stressed people to an odd and mysterious heart problem named after an octopus trap, science requires objectivity and evidence.  So far the evidence about sick hearts that resemble octopus traps suggests that, at least in the people in whom the diagnosis is made, death is a very rare outcome and complete recovery is the rule.

Chilly Treatment

Large scale studies of survival after cardiac arrest have produced dismal statistics, with survival to hospital discharge of 17.6% when the patient is already in the hospital at the time of the arrest and only 6.1% when the arrest occurs outside the hospital.  The development and widespread deployment of portable automatic external defibrillators (AEDS) in public places has increased the number of people who make it to the hospital after cardiac arrest.  However, the survivor’s longer term outcome depends in large part on how much brain damage occurs during the arrest and whether or not the restoration of circulation damages the brain further, a phenomenon called reperfusion injury.  Because the odds of initial survival have improved, and because lowering the core temperature of the body appears to lessen reperfusion injury, the subject of hypothermia has emerged as a vibrant area of research and therapeutics.

Therapeutic hypothermia is an old idea

Hippocrates (460-370B.C.) recognized the value of cold temperatures in the outcome of soldiers with head injuries and in people suffering from tetanus. In the 1800s, Napoleon’s surgeon used ice to prepare limbs for amputation because it numbed pain and reduced bleeding. Over much of history, miraculous recoveries were reported in victims of cold water submersion. But not until the late 1950s did therapeutic hypothermia become a routine part of some surgical care, when experiments in animals demonstrated its value in protecting the brain during the open-heart surgery.  Despite some attempts to cool patients for other problems such as cardiac arrest, strokes and head injuries, the number of problems encountered in during cooling and in the re-warming phase put a damper on the use of the technique. Now, however, we are in the middle of a revival of interest in therapeutic hypothermia.

How does cold help?

Cold protects the brain because the biochemical reactions that sustain life are influenced by temperature. If the heart stops, the brain runs out of fresh supplies for energy production in two minutes. A downward spiral toward brain cell death begins unless blood flow is restored within the next two minutes. When blood flow is restored (reperfusion), a cascade of potentially damaging chemical reactions begins in cells that have been deprived of oxygen. The longer the period of arrested circulation was, the more damaging these reactions are.

The body at different temperatures

Changing the body’s temperature changes the speed and efficiency of its chemical reactions.  At temperatures over 105 many processes fail completely. As body temperature falls below normal, chemical reactions slow down.  Between 92 and 89.6  the damaging chemical responses that come after blood flow returns are blunted enough to improve outcomes significantly.  By 90, pulse and respirations slow and peripheral circulation shuts down. By 86 the patient may still be alive, but looks dead. This level of deep hypothermia is used for some long, difficult cardiac and neurosurgical procedures.

Lowering temperature is now routine, sometimes

Since 2005, the American Heart Association has recommended therapeutic hypothermia as a routine part of patient care after a cardiac arrest in circumstances that depend on the reason for the cardiac arrest, the speed of the resuscitation, and the state of the patient after circulation is restored.  Some medical centers are also experimenting with the technique in the treatment of certain types of strokes and head injuries.

How do you lower someone’s core temperature?

How do you cool a body that normally maintains a constant temperature that hovers within a few tenths of a degree of 98.6?  Any environment with a temperature less than body temperature provides a gradient for heat loss.  Deliberately making someone hypothermic means increasing that temperature gradient. In the presence of a gradient, heat radiates away from the body. Heat is also conducted away when the body is in contact with any colder substance; when the colder substance such as air or water is in motion, heat is lost even faster, by convection.  Heat is also drawn away by evaporation of perspiration on the skin’s surface, where the sweat keeps the microclimate humidity at 70% even when you think you are dry.   Heat also dissipates when warm moist air is exhaled from the lungs.

Several internal and external ways of changing the temperature gradient  exist: ice packs applied to the head, neck, axillae, groin, where large blood vessels are close to the surface; cooling blankets that house cold water circuits; closed catheters through which cold saline circulates inserted into large blood vessels; ice water balloons in the bladder.    These methods are directed at the core temperature of the body – the temperature of the internal organs and the brain. They do not cause problems like frostbite, seen commonly with accidental hypothermia, because the ambient temperature is not freezing and the skin is protected from direct exposure to ice packs being used for cooling.

The body resists lowering the temperature

Normally, we protect ourselves from falling temperatures by putting on more clothes and increasing activity, and by shaking and shivering, which produce heat.  A patient who has suffered a cardiac arrest will not engage in the normal behavioral responses, but he will shiver and perhaps become agitated, both of which are counterproductive to getting the temperature down. Sedation and even muscle paralysis are therefore necessary for the period of cooling.

Despite problems,  therapeutic hypothermia is here to stay

Current therapeutic hypothermia protocols call for maintenance of temperature between 32-34 (89.6-93.2) for 18-24 hours, followed by passive re-warming over the next 24 hours. Overshooting and undershooting of temperature are both common, as are difficulties maintaining electrolyte and sugar balance. Some complications like pneumonia and bleeding problems are more common than in similar patients not being treated with cold temperatures. Much work remains to determine the best timing for induction and maintenance of hypothermia after cardiac arrest, but it is clear that “the sooner the better” is the general rule and that the revival of interest in therapeutic hypothermia is here to stay.

No more posts.