Stem Cell Treatments: Hope and Hype

In the early 1920s, John Romulus Brinkley, an entrepreneurial Kansas physician with dubious professional credentials, ran a lucrative business implanting goat testicles under the skin or in the scrotum or abdomen of patients who sought his help for any one of twenty-seven ailments, including flatulence. He was one of many medical hucksters who took advantage of an unregulated medical world in the United States at that time and made fantastic claims for their medical treatments, potions, and elixirs. Eventually, Brinkley’s medical license was revoked by the state of Kansas, and he moved south to Texas, where he advertised his services via a folksy radio station broadcasting from just over the border in Mexico. His station’s powerful antenna beamed his ads and promises all the way to the Canadian border, drawing patients south for his “treatments.” In the end, Brinkley is said to have made millions of dollars before a federal grand jury indicted him in 1941 for postal fraud. He died, bankrupt, in 1942, before he ever stood trial.
Fast-forward to a well-regulated medical world in December 2014. A famous ex-hockey player suffers a stroke and travels to Mexico for stem cell treatments. His family claims great results, and his therapists corroborate the reports, leaving many who read the story to wonder whether their brain-damaged relatives could also benefit from this therapy and why they would have to travel to Mexico to get it. Is this the same type of treatment being offered, without FDA approval, at the new stem cell clinics popping up in many American cities? And why is stem cell treatment not FDA approved? The answers require some understanding of stem cell research, clinical trials of new therapies, and the reasons why the FDA exercises caution when approving novel therapies.

What are stem cells?

Stem cells begin in a fertilized human egg, which splits into two cells, then again into four, and again into eight, and on and on. The first few dozen cells have the potential to become any type of cell in the body and are called embryonic stem cells. As the fetus develops, cells begin committing themselves to different roles, shaping a human body with all its complex organs. Some cells in each organ, however, retain enough of their primitive character to serve as a reservoir of cells for the repair and growth of the organ. These cells are called adult stem cells. The term “stem cell treatment” might refer to procedures involving either type of stem cell, but the stem cell therapies being offered commercially are adult cells.

The hope of stem cell therapy

The promise of adult stem cell therapy is based on the hope that stem cells can be harnessed to perform on demand and develop into mature cells to replace aging or damaged cells. In an ideal world stem cells could be coerced to act like the stem cells residing in bone marrow do naturally and regularly. Marrow stem cells make new blood components continuously – red blood cells, white blood cells, and platelets. They must do so because blood cells have life spans of only a few weeks.
Bone marrow transplants were the first stem cell treatments. They were used successfully in treating blood cancers and worked by replacing the patient’s bone marrow with that of a healthy donor. Bone marrow contains many types of blood and immune cells, but it is the stem cell component that repopulates the patient’s diseased marrow after it has been wiped out by chemotherapy. Originally, drugs were needed to keep the body of a recipient of a bone marrow transplant from rejecting the foreign cells, but advances in doctors’ ability to separate healthy stem cells from all the other bone marrow components now make it possible for physicians to give the patient his or her own cells, making antirejection drugs unnecessary.
The discovery that stem cells existed in many different tissues widened research horizons and raised hopes that stem cells could be used to repair and regenerate more tissues than just bone marrow. A wide variety of stem cell experiments aimed at treating a number of diseases, including multiple sclerosis and heart disease, are now being conducted. Ongoing clinical trials at academic medical centers are enrolling patients under strict protocols. Such trials are the only objective way to establish the safety and efficacy of stem cell treatments compared to standard care and to placebos. But so far, these trials are still ongoing, and the FDA has only approved marrow and umbilical cord blood stem cell use for the treatment of blood diseases like leukemia and lymphoma.
The hype: what are stem cell clinics selling?

But what about the stem cell clinics in the United States that offer treatments for a wide range of diseases related to aging, including diseases such as Parkinson’s disease, Alzheimer’s disease, chronic lung disease, and cardiac disease? These clinics are entrepreneurial ventures that operate without FDA approval. Stem cells are not considered drugs because they are harvested from the patients own body for re-injection into it; therefore, the FDA has no jurisdiction over the hundreds of stem cell clinics operating in the United States. If trouble occurs in these clinics (and it has, including death) then state medical boards are responsible for policing the people providing services until some kind of FDA regulation is put in place.

Fat is the usual stem cell source

Today’s stem cell clinics appeared after the discovery that fat was one of the richest sources of adult stem cells. With the purchase of a cell separator and participation in a weekend seminar, any doctor can open a stem cell clinic. During stem cell treatments, fat is harvested from each patient through a version of the liposuction process. The stem cells that reside deep in the fat, near blood vessels, are concentrated in the cell separator and mixed with the patient’s plasma to cause the stem cells to begin to divide and grow. Some clinics also obtain marrow stem cells through a large needle inserted into the bone of the hip, and, in some clinics, lasers are used to activate the stem cells and raise them from a dormant state to a reproductive one. Treated cells are then injected back into the patient, into the bloodstream, under the skin, into a joint, or into the spinal fluid. In theory, these cells find their way to the targeted, ailing tissues, turn into the desired cell type – such as knee cartilage – and heal the problem. Some practitioners, however, believe that the stem cells may not propagate themselves but only stimulate the body’s natural repair processes.


Stem cell clinic literature often gives the impression that these procedures are risk free, but, in fact, all invasive medical procedures carry some risks, like infection and adverse effects such as dizziness. Recently several patients became blind after stem cell injections aimed at curing threating the macular degeneration in their retinas. Risks and side effects should be disclosed to every patient, even if their rates of occurrence are low.

No long-term follow-up studies available

Stem cell treatment is so new that there have been no long-term follow-­up studies done on large numbers of patients, the type of studies that are used to uncover unexpected trouble with new procedures. Since stem cells are meant to reproduce and grow and since manipulating them outside their natural environments and injecting them into patients presents a risk of changing the programming that keeps their reproduction under control, long-term follow­ up studies over many years are essential. While some stem cell clinics purport to do studies on patient outcomes, they demand that their patients pay for their treatments, and no legitimate study would require payment for the patients to be involved. Furthermore, the studies done in these clinics do not include control cases to assess placebo response or control groups to compare results with standard treatment.

Over-regulation or protection against charlatans?

With advertising claims being made that stem cell therapy rejuvenates aging body parts, with many people suffering from painful joints and other ravages of life, and with the FDA restricting stem cell treatment approval to specific blood conditions, what is the interested potential patient to think? That in the last one hundred years we have overreacted to charlatans and are using regulatory agencies to unnecessarily restrict useful medical therapies? Or that the injection of stem cells into the body with the expectation that these cells will reach the correct destination and perform just the repairs needed is a bit like trusting the promises John Brinkley once made about his goat testicle therapy? Desperation may drive some people to try what is easily available (though very expensive), but the safest course at this time is to stick to FDA­ sponsored stem cell studies for any attempted treatment. And to remember that placebo effect of any medical treatment, even antibiotics, accounts for 30% or more of the positive  responses in studies of efficacy. Glowing reports from friends and relatives don’t necessarily mean that demonstrable changes occurred in their bodies.  Research on stem cell treatments continues, but there is still a very long way to go.

Skin Cancer: Common and Commonly Curable

Babies arrive in the world with soft, smooth, and usually flawless skin. Old men and women leave the world wrinkled, mottled, spotted, and scarred. In between, the skin replaces itself many hundreds of times and in the process accumulates enough DNA damage to make skin cancer the most common of all cancers, with more than 2 million cases occurring in the United States each year. Fortunately, most skin cancers stay put in the locations where they start. They don’t invade nearby tissues and don’t spread through the base of the skin to travel to other parts of the body. Skin cancer is largely curable by removal alone.

Different skin cells and different skin cancer names

The three most common types of skin cancer arise from cells that grow in the epidermis, or outermost layer of the skin. The inner layer of the epidermis is made up of basal cells. Basal cells regularly reproduce themselves in order to make squamous cells, which are replacement skin cells and form a middle epidermal layer. This layer also contains cells called melanocytes. Melanocytes produce melanin, the pigment that gives skin its color. The outer layer of the epidermis consists of dead skin cells that are constantly being shed. The most common skin cancers come from these three types of skin cells: basal cells, squamous cells, and melanocytes. All three types of cancer are more common in fair-skinned, light-haired, light-eyed people. All three are also related to lifetime sun exposure.

Basal cell skin cancer

Basal cell cancer is the most common type of skin cancer, accounting for 80 to 90 percent of reported skin cancer cases. It is also the most benign skin cancer. Basal cell cancers begin with errors in a cell’s DNA, which serves as instructions for building squamous cells from basal cells. The abnormal cells that are created by this damaged DNA form a tiny area of skin that is different from surrounding normal skin. Typically, it looks like a little dome, with a waxy, pale appearance. Over time it may develop tiny blood vessels around it. It might bleed easily or develop a sunken center or a crusted top. Sometimes the color may be a little darker or rosier than that of the surrounding skin.

Basal cell cancers grow slowly and very rarely travel to other parts of the body. That said, they can invade nearby tissues, and the earlier they are removed, the less likely they are to recur (and the smaller the scar caused by their removal will be). Basal cell cancers occur most commonly on areas of the body exposed to the sun, especially the scalp, forehead, and corner of the nose. They are also more common in people who have been intermittently exposed to the sun without protection. Basal cell cancers take many years to develop, and by age sixty-five, about 50 percent of the population will have developed at least one such cancer. Within five years of treatment of one basal cell cancer, one-half of patients will develop a second one. Because of the popularity of tanning, both indoors and out, basal cell cancers are now appearing in some people before middle age.

Squamous cell skin cancer

Squamous cell cancers can occur in areas of the body that are not generally exposed to the sun, like the mouth and the genital region. However, when squamous cell cancers appear on the skin, they typically develop in areas that show other signs of sun damage—wrinkling, freckling, mottling, thinning, and sagging. They may also evolve from solar, or actinic, keratoses, which are considered precancerous markers of sun damage. Usually appearing as small red spots (under a quarter of an inch in diameter), solar keratoses have some white scaling on their surfaces. Some are sore and tender, and thickening with increased tenderness can indicate a progression to a skin cancer. Squamous cell cancers can be flat and scaly patches of skin or firm, red nodules or non-healing sores. Unlike basal cell cancers, squamous cell cancers, particularly those on the lip, can penetrate deeper layers of skin and travel to other parts of the body by way of the lymphatic system, though this spread is uncommon. If many precancerous lesions are present, treatment with chemotherapeutic creams helps prevent cancer development.


Like basal cell and squamous cell cancers, melanocyte cancers, which are known as melanomas and appear similar to moles, more commonly occur in fair-skinned people and are also related to sun exposure. It is no coincidence that the highest rates of melanoma in the world are in Australia and South Africa, two highly sunny areas colonized by fair-skinned people who are genetically better suited to the gray skies of northern climates.

Melanomas must be distinguished from normal moles, which develop in virtually all people. The average adult has twenty-five moles with varying degrees of pigmentation. Many “rules” exist for helping physicians decide whether a mole might be cancerous. For example, moles that are asymmetrical in shape and color, have irregular margins, and are larger than a pencil eraser are often considered suspect. However, none of these “rules” is a reliable way to tell if a mole is cancerous. More reliable suspicions are generally based on observations concerning mole development. The development of a new mole, particularly on the back or the legs, that grows over a number of years is definitely something that should be discussed with a physician.

A full 70 percent of melanomas are what are termed superficial spreading melanomas and are curable if caught when they are less than 1mm thick. Another 7 to 10 percent of melanomas, those that are deep blue-black or purple nodules, tend to spread more readily to other parts of the body. Rarer yet are melanomas in odd locations like the eye, under a nail, on the palm of the hand, or on the sole of the foot. These, too, are more dangerous.

Like basal cell and squamous cell cancers, the treatment for a melanoma is removal. There are a variety of different ways to remove skin cancers, ranging from scraping and cauterizing to a surgical excision with microscopic monitoring to find the edges of the tumor. Cure rates are high—in the 98 percent range, particularly when the tumors are small. If a tumor does spread to nearby tissues, it can still be cured, though with more surgical scarring. Metastatic melanomas do not respond well to conventional cancer treatments as a rule but may react differently to newly developing targeted immunological treatments.

Screening for skin cancer: no controversy 

In contrast to the confusion surrounding screening tests for some other types of cancer, clarity is the mark of medical advice about skin cancer. It helps if you know what to look for and to seek a medical opinion about any suspicious skin spots. Most often, doctors will recommend biopsy of a suspicious lesion as the surest way to make a diagnosis, and patients can expect that removal will be part of the cure for any cancers that are found. You won’t ever regain the skin of a newborn, but you do not need to have skin cancer.


Your role in skin cancer prevention

• Beginning early in life, protect your skin, particularly the skin on your face, scalp, ears, lips, back , arms, and hands. Use hats, shirts, and sunscreen (at least 30 SPF) to help block the harmful rays of the sun.
• Avoid prolonged sun exposure when the sun is high in the sky.
• At least once in middle age, have a professional examination of all your skin. If you are fair-skinned, and/or have sun damaged skin, heed your physician’s advice if he suggests more regular checkups. The American Academy of Dermatology sponsors free screening exams every May.
• Keep an eye on your skin and have new, enlarging, color-changing, non-healing or bleeding spots checked by a professional.

Fever: Resetting the Thermostat


Humanity has but three great enemies: fever, famine, and war; of these by far the greatest, by far the most terrible, is fever.
―William Osler, MD

    In Dr. William Osler’s world of the late 1800s, doctors had not yet seen antibiotics rescue people from death caused by infectious diseases. Osler, one of the founders of Johns Hopkins Hospital routinely saw children die from meningitis, scarlet fever and diphtheria. He watched adults die from wound infections and cholera and the threat of mortal infection loomed over every surgical procedure. Fever was an unwelcome herald of trouble that often ended in death.

However, since antiquity fever was also thought to be therapeutic for some ailments of the brain, including melancholy and seizures. In the 1920s, a German psychiatrist, Julius Wagner-Jauregg, attempted to use the recurring high fevers of malarial infection to treat syphilis, then an incurable disease that eventually robbed patients of their minds and motor coordination.  Wagner-Jauregg was a eugenicist and later a Nazi sympathizer, and gave his patients malaria without their consent, but the fact that six of his nine patients recovered earned him the Nobel prize in medicine in 1927. He remains the only psychiatrist ever to be so honored in that discipline. Fever asylums popped up in many locations on both sides of the Atlantic in the 1930s, but were relegated to history by the discovery of antibiotics in the next decade.

How does the body temperature rise?

Fever begins when a “pyrogen” – some kind of viral or bacterial protein, or a protein made by the body as part of an inflammatory response — stimulates a tiny, deep part of the brain called the hypothalamus.  There, “warm sensitive neurons,” normally responsible for keeping the body temperature stable, act as if the temperature has fallen and slow their firing rates, triggering physiologic responses throughout the body that produce more heat. The incipient fever sufferer feels cold and sometimes begins to shiver. Blood vessels in the skin clamp down, sacrificing their flow to the core of the body in an effort raise the temperature. Heart and breathing rates go up, core temperature rises and the forehead begins to feel warm to the touch, even though the patient still feels chilled.

Definition of normal and abnormal body temperatures

Normal body temperatures vary over the course of the day and from individual to individual, within a degree above or below 98.6°F (37°C). Oral temperatures are about a degree lower than ear and rectal temperatures.  Fever is defined in adults as 100.4° orally or 101°F (38.3°C) rectally, and 101° orally in children. These elevated temperatures seem to work, along with the body’s immune system, to undermine the success of an invaders like viruses and bacteria……up to a point. Temperatures rising to 103-104° begin to have deleterious effects on cells, making their membranes unstable and triggering faults in the workings of cellular machinery. Organ failure can result, complicating already serious illness with kidney and liver problems.

Why do babies and little children get fevers so often?

Babies and small children, who are at the beginning of their life experience with infections, develop fevers more often than adults do. Their fevers may be the first or only symptoms of illness, and the illness may be brief and self-limited. Fevers which indicate worrisome problems in children are accompanied by other symptoms like rash, stiff neck, lethargy, breathing difficulties or abdominal pain.

Adult fevers 

In adults, other symptoms of trouble often come before a fever and point to a body part in some kind of trouble.  When fever occurs along with GI symptoms like abdominal pain, nausea, vomiting and diarrhea, a significant abdominal problem requiring medical or surgical attention may be present. Fever along with cough and sputum production may mean a bacterial pneumonia. Fever that develops as a part of the flu is usually accompanied by profound fatigue, muscle aches and pains and headache.

What causes fever?

About 75% of elevated temperatures come from infections. What causes account for the other 25%?  This “non-pyrogenic category” includes fevers from some cancers, from inflammation of all kinds, from brain injuries like hemorrhages and strokes, and from major bodily injuries with crushed or otherwise damaged tissues. In addition, overactive thyroid glands elevate body temperatures. Some drugs, particularly the neuroleptics used for depression and other psychiatric disorders can cause fever, as can some genetic problems.  Familial Mediterranean Fever comes from mutations in genes that control inflammation responses. Malignant hyperthermia, a potentially fatal rise in temperature in response to anesthetics, comes from a muscle gene mutation.

To treat or not to treat fever?

Treatment of fever is straightforward – body temperature drops in response to an antipyretic drug such as acetaminophen (Tylenol) or aspirin. But fever appears to be an evolutionary response in almost the entire animal kingdom, aimed at protecting the body from invasion by other living forms. In other words, fever induced by infection may be helpful.  Why try to normalize the temperature during the illness?

Most of the time, with temperatures in the 101-102 range, treatment beyond making the patient comfortable is not necessary. But the deleterious effects of raising body temperature begin to show up in the 104 range, and perhaps sooner in people who have underlying medical problems that affect their ability to tolerate higher heart and breathing rates or to maintain adequate hydration. Fever makes demands upon the body that young and otherwise healthy people can tolerate, but older, sicker people may not. Elevated temperatures in heat stroke from a hostile environment or from excessive exertion without adequate hydration serve no useful purpose and should always be treated promptly, with external cooling and hydration.

In the modern age of medicine, antibiotics have reduced Osler’s greatest enemy to a symptom of illness. But it is a symptom that deserves respect. When fever is present, something is wrong and the wrong thing usually involves and invasion of the body by another living form, or a significant area of tissue inflammation or decay. Careful evaluation of other symptoms is the first priority in discovering the cause of fever, for that is what needs treatment more than the fever itself. Should we overuse antibiotics and render them ineffective against our most common infections though, Osler’s great enemy will regain its fearsomeness.

Polar Moods

Bipolar disorder, previously called manic-depressive disease, is a not a new diagnosis. But it is one being made with increasing frequency, particularly in children and young adults. In psychiatry diagnoses are legion, but they all fall into one of three categories: disorders of mood, thinking, or personality. Bipolar disorder is a problem in the sphere of mood, described in the 1880s by Emil Kraepelin, the German psychiatrist whose Compendium der Psychiatre was the world’s first systematic classification of mental disorders. At the time, psychiatrists recognized separate illnesses called mania and melancholia, but Kraepelin was the first to see that some patients cycled between these opposite poles of mood. Over time, the term cyclical insanity gave way to manic-depressive disease, and finally to bipolar disorder, type I or type II (the milder variety). Melancholia is now called unipolar depression and mania is no longer a diagnosis but rather a  behavioral symptom in all kinds of psychiatric disorders.

Normal ups and downs in mood


Everyone has ups and downs in mood. Mood involves both  subjective feelings and  outward behaviors. It is clear from “normal” mood  swings that both internal and external factors influence ups and downs. Many of those factors, such as sleep, stress, physical activity, diet, and abuse of alcohol, nicotine and drugs, also affect general health.

The definition of mood disorder

Normal ranges of mood vary greatly from person to person, so the psychiatric definition of “mood disorder” rests on the degree to which disrupted behavior interferes with carrying out the normal activities necessary for functioning at a given stage of life. Clearly abnormal symptoms like hallucinations, which define the thinking disorder schizophrenia, may also appear in bipolar type I. New genetic work suggests that mood and thinking disorders are not as separate as our classification systems try to make them, so it is not surprising that symptoms at times overlap.

The down side of the mood spectrum

Depression, the low side of the mood spectrum, robs a person of interest and joy in his activities. He has little energy, sleeps more than usual, or may be unable to sleep through the night, waking up anxiously at two or three AM. He may gain or lose weight. He tends to ruminate, repetitively chewing over negative thoughts. Sadness permeates his world. Of course these  same symptoms  can be completely appropriate responses to terrible life events that cause profound grief.  A depressed mood becomes abnormal when it occurs or persists unrelated to circumstances, blocks the activities necessary for normal life, and/or includes persistent thoughts of death or suicide.

The up side

At the other end of the mood spectrum, mania, the mind speeds up. Thoughts are rapid, distractibility is high, speech is pressured, and ideas become grandiose. Sleep isn’t necessary. The manic person engages in risky behaviors and feels invincible. He undertakes grand schemes, spends money with abandon, and becomes obsessed with projects or ideas. When the exuberant moods are still under some control (hypomania), they can be very productive. The afflicted individual seems lively and charismatic, the life of the party. But when mania spirals out of control it can become life threatening. As mentioned above, mania not confined to bipolar disorder. It is a symptom that can happen in mood, thinking and personality disorders.

Bipolar: more down than up

Most patients with true bipolar disorder spend far more time on its depressive side, experiencing few manic phases. In fact, it is now felt that many cases unipolar depression, with no history at all of hypomanic or manic episodes, actually represent bipolar mood disorders, making diagnosis tricky. Correct diagnosis is important. In unipolar depression, the response to conventional antidepressant therapy takes weeks, but in bipolar depression, the same drugs can tip the patient into a manic state quickly. It is possible that the reported cases of suicide shortly after antidepressants are started may be related to this phenomenon.

The danger of wrong diagnosis

In our current medical and economic climate, the threshold for using antidepressants is very low. Frequently the drugs are prescribed by non-psychiatrists, without concurrent talk or behavioral therapy, and without adequate follow-up. So it is imperative for patients who are given antidepressants to understand that a rapid response, within days to a week, and feelings of agitation or irritability might mean that the diagnosis of unipolar depression is wrong. For bipolar patients, the drug of choice is a mood stabilizer, which calms manic states and can prevent return of depression.

Stabilizing the mood

The most effective mood stabilizer is lithium. Lithium is a simple chemical element in the same family of elements as sodium, potassium, calcium and magnesium, rather than a complicated molecule like other psychoactive drugs. Its mechanism of action remains elusive, though it is thought that it makes the neurochemical transmitter norepinephrine less available and less effective in the brain. Lithium must be monitored carefully, with urine levels performed regularly. Toxic side effects include diarrhea, tremors, thirst, weight gain, drowsiness, and impairment of kidney and thyroid function.
If lithium is ineffective or poorly tolerated, drugs normally used for treatment of seizures may work as mood stabilizers. One, valproate, is particularly effective for people who also have substance abuse problems, a not uncommon occurrence. Antidepressants may also be necessary at some point, but not without concurrent use of mood stabilizers. Bipolar disorder is a lifelong problem that requires careful monitoring, variable amounts of drug therapy, and simultaneous counseling aimed at development of cognitive skills and habits that help blunt the effects of mood swings on behavior.

Are we creating more lifelong psychiatric problems with drug treatment?

Some psychiatrists feel that the widespread use of antidepressants and other mood altering drugs to treat poor behavior or reactions to life’s inevitable problems changes brains enough to change the way true psychiatric problems now evolve. These days, we have increasing numbers of bipolar diagnoses. Compared to past decades, bipolar patients now cycle more rapidly between highs and lows. While the increasing frequency of bipolar disorder diagnosis may represent increasing labeling of behavioral problems, we also must consider the disturbing possibility that temporary alteration of brain activity with drugs is leading to long term psychological and behavioral changes. Readers who are interested in more extensive discussion might want to read Anatomy of an Epidemic: Magic Bullets, Psychiatric Drugs, and the Astonishing Rise of Mental Illness in America by Robert Whitaker, Broadway; (August 2, 2011).

Sleep Debt: The Hidden Costs

Everyone has a sleep bank. Each night your accounts get credited with 7-8 hours of the physical and mental benefits of sleep and each day the accounts pay out those benefits in the form of emotional, intellectual and physical energy. Just like in any bank account, withdrawals can’t exceed deposits without incurring debt. Sleep debt, though, is easy to ignore because physical activity keeps alertness high. As long as you move around instead of reading or watching TV, you won’t nod off and you can keep thinking that 5 or 6 hours of sleep a night meets your needs. But covering the debt with activity is like keeping a bank balance out of the red by borrowing money and paying interest. Sleep debt exacts a toll on the body that goes beyond depressed mood, irritability and lack of ability to concentrate and learn, not to mention the potential for causing motor vehicle accidents.

The biological clock

As sleep debt mounts, the body’s biologic clock goes awry. This clock, located deep in the brain, controls circadian rhythms – regular ups and downs in behavior, body temperature, appetite, hormone production, alerting mechanisms, and the urge to sleep. When the clock malfunctions chronically, the results show up in the form of weight gain, high blood pressure, diabetes and diminished immunity to infection.

Setting the clock

Regular periods of darkness are required to set the brain’s internal clock to keep the body in synch with the 24-hour day set by the sun. Sleep researchers have shown that, when living in a research setting where there are no external clues about time of day or night, subjects’ internal clocks actually work on a 25-hour cycle. Normal peaks of sleepiness and alertness work themselves into the wrong time of the  24-hour day and night outside the sleep lab, producing weeks of daytime sleepiness and nighttime insomnia in the research subjects. Over time, the peaks cycle back into synchrony with day and night producing several weeks of normal daytime alertness and nighttime sleepiness.

Laboratory settings may exaggerate these patterns, but most people know that during some weeks they simply perform better during the day and sleep better at night  than during other weeks, indicating that in the modern, artificially lit world, the 24-hour day is more like a 24-25 hour day as far as the body’s natural rhythms are concerned. This clock drift is very sometimes very evident. Cyclical insomnia and daytime sleepiness are in common in blind people, in people at very high latitudes where the summer sun circles the sky for almost 24 hours, and in shift workers who are up all night in brightly lit environments. These problems, while distressing, respond to maintaining regular sleeping schedules and closing out all light during sleep periods, which resets the clock.

Why the clock matters

The internal clock is easily disrupted by one or two day episodes of sleep deprivation that people experience for reasons as varied as extra work loads, exams, brief periods of emotional upheaval, or any of the other myriad problems that keep people awake, but studies have repeatedly demonstrated that a few days of “catching up” on sleep restore the body to normal rhythms, contributing to a widely held impression that sleep deprivation, while responsible for serious accidents, doesn’t cause real health problems.
However, bigger problems do come from disturbing circadian rhythms more chronically. In recent years research attention has shifted from short term sleep deprivation to the chronic, partial sleep deprivation that is so common in our modern society, where nodding off during monotonous and sedentary activities like reading or watching TV are almost expected. Many people think they need no more than 5-7 hours of sleep at night, but while a few truly short sleepers exist, most people require around 8 hours of sleep each night to achieve maximal alertness throughout the day. Chronically shortchanging sleep by even an hour a day changes the timing and levels of multiple hormones, causing other metabolic changes and weakening the immune system.

Lack of sleep wreaks havoc on hormones

One of the first hormonal changes produced by chronic short sleep involves cortisol, the stress hormone produced by the adrenal gland. Normally cortisol levels decline during late evening hours, but without enough sleep, production continues unabated, Cortisol then begins to contribute to immune stress and to insulin resistance, which leads to diabetes and fat deposition. A second contributor to insulin resistance is a change in growth hormone secretion from one large burst during sleep to two, smaller bursts before and after sleep. A third change comes from failure of the pituitary gland to produce its normal night-time rise in thyroid stimulating hormone, the stimulus for the thyroid gland to produce more thyroid hormone. All of these changes are consistent with the fact that as little as one week of 4 hour sleeping nights can convert healthy young people to a pre-diabetic state. Observational studies do show higher rates of diabetes in chronically sleep-deprived women.

Lack of sleep and obesity

If these hormone changes are not enough to convince a short sleeper to turn out the lights earlier, studies on the appetite influencing hormones leptin and ghrelin, produced by fat tissue and the stomach respectively, might help. Leptin, which signals when to stop eating, diminishes markedly after 6 days of four- hour sleeping nights, despite no change in caloric intake. Ghrelin, which stimulates appetite, particularly for high carbohydrate foods, goes up when sleep is short.

Sleep debt is all around you

    All of these hormonal factors are significant in society where people lead overscheduled lives in stimulating, loud and bright environments without regard to natural day and night. We do not need sleep studies to tell us that we are in an age of significant sleep debt – just count the number of people, including children, asleep on planes and buses, over books and newspapers, and on couches in front of TVs. If you fall asleep regularly under these circumstances, you are in chronic sleep debt. Given the increase in obesity and diabetes over the last few decades, sleep is another potential therapeutic avenue – a fruitful and inexpensive area of health over which we have considerable control.

Managing the sleep budget: factors under your control

1. Take the television out of the bedroom.
2.Darken the room completely, or wear a comfortable, opaque eye mask.
3. If noise is a problem were soft ear plugs.
4. Keep the temperature low at night and invest in a comfortable mattress that does not move.

1. Keep the biologic clock in sync with the sun by getting outside regularly.
2. Get regular exercise like walking, but avoid exercise in the last 3-4 hours before bedtime.
3. Keep naps short – 45 minutes or so – and confined to early afternoon hours.
4. Avoid heavy meals and alcohol in the last 4 hours before sleep.
5. Aim for the same bedtime every night, well before midnight, and develop a quiet bedtime ritual

Internal factors
1. Empty your bladder right before getting in bed.
2. Seek medical treatment for heartburn if causes frequent awakening. Ditto for urination.
3. Evaluation for sleep apnea is a must for someone who snores and suffers from daytime sleepiness.
4. Treatment of arthritis with exercise, physical therapy and medications, if necessary.
5. Try to get weight down to normal: sleep apnea, heartburn, and arthritis pain all benefit

More On Shingles

Readers wanting to know more about some topics  pose very good questions. My original magazine column about immunization to prevent shingles (September 2011) generated enough reader mail to warrant another column sharing some of the answers.

Recognizing recurrent shingles episodes:

One reader had suffered through an eruption of ophthalmic shingles, which involves the nerve that carries sensation from the eye, including the cornea, from the skin around the eye, and also from the forehead. The reader wanted to know “What are the signs and symptoms for a re-occurrence of the zoster virus in the eye so I would know what to look for if I am getting an attack?”  As in other areas of the body, symptoms that come before the rash erupts  in the eye and the face are sensory  – tingling, burning, itching and pain. Warning sensations in ophthalmic shingles might also include irritating dryness and a sense something lodged in the eye. Our reader understood that taking an antiviral drug early in the course of an eruption might lessen the likelihood of scarring of the cornea, so paying attention to early symptoms has therapeutic consequences.   If an abnormal sensation persists for several hours without explanation or response to simple measures like rinsing the eye out, then the symptom is worth bringing to the attention of the doctor. That said, the use of antiviral drugs early in the course of a shingles outbreak does not prevent the eruption from progressing, but it may shorten the duration and lessen its intensity.  When the surface of the eye is involved, anything that can be done to prevent corneal scarring is of some value.

Drugs that make the virus awaken

The same reader also wanted to know what drugs might predispose her to another eruption, and how to avoid them. The drugs that put people at most risk for a herpes zoster outbreak are the ones that suppress the function of immune cells in the body. The most common offenders belong to the steroid class on anti-inflammatory drugs, and have names like prednisone, dexamethasone, decadron, and prednisolone.  They are used to treat conditions like multiple sclerosis and lupus and rheumatoid arthritis and when used for periods longer than a week, they begin to impair immune response.  Sometimes they are part of a chemotherapy regimen for cancer. Other chemotherapy drugs and radiation also impair immune cell function, so shingles eruptions are not surprising in patients undergoing cancer treatment.  Paradoxically, steroids are part of the treatment for shingles – but they are used for only a short time, to decrease inflammation.

Vaccine questions

Another reader wrote:” My husband never had Chicken Pox and yet he did have a severe case of shingles and he was in his 40’s when they occurred. At that time we were told the opposite of the article…we were told he got shingles because he had never had Chicken Pox.  This was over 20 years ago so perhaps research has changed that.  Does the fact he had shingles mean he cannot get the vaccine?” There are many people whose childhood chicken pox was so mild that they have no memory of the disease. Blood testing will show whether or not there is any trace of immunity to the virus in people who think they did not have the disease. An adult who contracts chicken pox for the first time has a rash that involves much more of his body than the shingles rash does.  He is also extremely sick, much more so than a child with the disease. So if an adult develops what is a typical shingles rash, it is considered proof that he has had chicken pox in the past.

You probably did have chicken pox

Age 40 is on the young side for shingles, but there are many idiosyncrasies in the immune system, with some people have worse immune “memory” for specific viruses than others do. Having had a shingles eruption does not prevent this reader’s husband from getting the vaccine, and given that it is now over 20 years since the last time the virus stimulated his immune system, immunization might be a very good idea.  Guidelines for vaccine administration also do not exclude people who think they did not have chicken pox as a child, even though, in theory, a vaccine made from a live, weakened virus could cause a full blown case of chicken pox in a chicken pox virgin (more on different vaccine constructions below).  It is estimated that 99% of people in the US have had chickenpox, whether or not they are aware of it.

Being refused the vaccine

Getting an immunization proved difficult for another reader. He went to his county health department seeking a shingles immunization, but he was turned down because he has non-Hodgkin’s lymphoma, a form of lymphatic system cancer. While his disease is in remission and his blood work indicates good immune cell function, there is a theoretical risk that the vaccine, which contains a live, weakened version of the virus, will reactivate the line of white cells that caused his lymphoma. Many people face this type of risk-balancing problem in choosing whether or not to get a vaccine, and each individual case requires weighing risks versus benefits. In some cases, for example someone with AIDS who has good white blood cell tests and is not sick, the patient’s doctor may advise getting the vaccine because the risk of the effect of a shingles outbreak is greater than the risk that the virus in the vaccine will cause trouble. In the case of people with history of cancers that arise directly from immune system cells, however, no one wants to take a chance of triggering cells to become cancerous by the introduction of a live virus in the form of a vaccine.  In addition, no one wants to  introduce an infection that the immune system cannot control.  These problems are the reason that researchers have pushed to develop a new vaccine, just becoming widely available in in 2017-18, which does not contain any live virus.

The old and the new vaccines

Lastly, several readers inquired about the frequency of the zoster vaccination.  Immunizing for shingles is relatively new, and recommendations may change, but right now, Zostavax, the old vaccine, is recommended for all people over age 60,  as a one time shot. Zostavax cuts the rate of shingles by 51% and the development of post-herpetic shingles pain by 65%.  The new vaccine, Shingrix, is recommended beginning at age fifty and in tests improves these prevention rates to 98% and 85% respectively. Shingrix requires two separate doses. The effectiveness of the vaccines does wane over time, and there is more experience with the old one. Currently there are not any guidelines about repeat administration, but there are no contraindications to getting the new vaccine for people who have already had the old one.

Where to get immunized

Immunizations are available at pharmacies, grocery stores, county health offices, and walk in clinics and all of these facilities have guidelines which will exclude some people.  Anyone excluded by general criteria should review the reason with a doctor who cares for the problem that caused the exclusion.

New Knees and Hips: Making the Leap

In these days of angst about health care and its costs, I am reminded of a medical school professor who told his students that all surgery was optional. Without surgery, he said, some people would die prematurely and some would have miserable lives, but the human race would survive.  He was right. Surgery benefits individuals, not populations, and all surgery falls into one of two categories – those procedures, like appendectomies and C-sections, which rescue individuals from premature death, or those like joint replacements, which improve individual quality of life.

Artificial joints

The forerunners of joint replacements were wooden legs – the crude mechanical approximations of limbs torn asunder by accidents and war.  Fast forward a few hundred years, through remarkable developments in materials science, anesthesia and infection control, and we have slick titanium or ceramic implants that replace joints worn down by modern life. Hip and knee replacements, procedures which began in earnest in the 1960s, are safe and effective. Currently it is estimated that over 300,000 hips are replaced in the United states alone each year. In most people, even the very elderly, they return mobility and help maintain independence.

Costly and difficult substitutes for nature

As good as these artificial parts are, they are still less than perfect substitutes for your native joints.  Joint replacement is irreversible, initially painful, and potentially risky.  Good results require serious commitment to rehabilitation – more exercise than some people have ever engaged in.  Already major consumers of the health care dollar, hip and knee replacements are set to explode budgets as our obese population ages and wears out weight bearing joints.  Between 1997 and 2004, private insurance layouts climbed from $1.1 billion to $3 billion for new hips and from $1.46 billion to $4.64 billion for new knees. These figures don’t include Medicare expenditures, which are the principle source of payment, and constitute over 20% of Medicare outlays.  Limits may be imposed by available surgeons trained to do these procedures, a number already in decline and not expected to increase over the next decade. If you are in possession of good joints, try to hang on to them for as long as possible. Maintain normal weight, don’t smoke, and work on strength and flexibility of trunk and limbs.

Deciding to replace a joint

The decision to replace a hip or knee usually comes after years of declining physical activity and escalating anti-inflammatory and pain medication use. At times a decision is forced on a patient as treatment for a hip fracture, but ideally the surgery is an elective procedure decided upon by a patient, along with a doctor who knows him well and understands all his other medical problems. Time spent researching surgeons and hospitals and settling upon those with good results is worthwhile. Sometimes a decision can be delayed by opting for steroid injections, but they weaken connective tissue and cannot be repeated indefinitely. Delaying too long, however, might influence results. Some studies show worse functional outcomes after knee or hip replacements in more debilitated patients.

On the replacement road

Whatever way it happens, once the road to hip or knee replacement is undertaken, the orthopedic team and patient travel as close companions. Careful adherence by the patient to all instructions and advice insures the best possible outcome, and good communication from the doctors, nurses and therapists encourages patient cooperation. Work starts well before the surgery. Painful knees and hips are often housed in bodies that are overweight and out of shape. The difficult job of getting a new joint moving is easier if muscles have been in training pre-operatively.  And the more weight that can be shed ahead of time, the less the strain on bone and muscle as they attempt to hold a new joint in place.

Immediately after surgery, mobilization begins. First comes sitting up, getting out of bed, and walking with assistance – as soon as tolerable and with whatever restrictions needed to protect the new joint. Supervised therapy sessions, starting within the first few days, aim at moving the new joint through larger ranges of motion without endangering its stability. Every encouragement to move and every caution about how one moves (such as the prohibition against leg crossing) is important.

Potential problems

The push to get patients moving and the precautions about how they move are important for preventing two of the biggest complications of lower extremity joint replacement: blood clots in the legs (with potentially catastrophic migration to the lungs) and dislocation of the hip (slipping of the ball of the new hip out of the socket).  The most feared complication, infection, prompts meticulous wound care and surveillance for other infections. A brief stay in a transitional care facility, if recommended, is beneficial. Therapy occurs in well-equipped spaces several times a day and gets the long-term recovery off to a good start, and medical supervision is close at hand. Most people will also need home help for a month or more, as well as continued outpatient physical therapy.

The long run

If joint replacements are so advanced and helpful, why suffer with bad knees and hips at all? There are many joint replacements being done at younger and younger ages, but the fact remains that artificial joints have a limited  – though quite long – life span,  in the range of 15-20 years, though as advances are made, these figures may stretch out. Some people are still walking well on their first new joints at the 25 year mark.  But artificial materials  will eventually suffer wear, and there is an additional problem of the prosthesis loosening in the bone, a process that is not entirely understood. Replace a joint at age 65 and it may well last until life’s end. Replace one at 45 and you may be looking at a second period of disabling pain followed by a redo of the replacement, but this time in an older bone already altered by the first procedure. Opting for a new knee or hip is a decision that warrants careful, educated and open-eyed assessment of short and long-term risks and benefits, but as quality of life surgery goes, these procedures are among the most useful.

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