Nov
05
2014

How To Cope With Time Switches

This review is about how to cope with time switches. In Europe daylight saving time begins on the last Sunday in March and wintertime starts on the last Sunday of October. Here in North America we start daylight saving time on the second Sunday of March and end it on the first Sunday of November each year.

With the time switch just last weekend I thought it would be worthwhile to comment in a blog how our bodies, particularly our hormones suffer from this.

You may have heard about the circadian rhythm with respect to hormones. The changes of the sun causing the day/night cycle have profound influences on our hormones, called the diurnal hormone changes or the circadian rhythm.

How do circadian rhythms work?

In the morning when you open your eyes, light enters our eyes and the hypothalamus registers this in the suprachiasmatic nuclei (see Ref.1). There are also links from the hypothalamus to the pineal gland, where melatonin is synthetized and stored. The light signal stops the secretion of melatonin from the pineal gland, although it is still being produced during the day in the pineal gland, but stored there until the evening hours set in. You may have noticed that you start yawning when the light dims in the evening. That’s when melatonin is released into your system to let you know its time to go to sleep.

Of course, we have electrical light and can turn night into day if we choose to! This works for a limited time, but eventually tiredness sets in, and melatonin wins the upper hand. Melatonin is the master hormone of the circadian rhythm.

Cortisol and melatonin are natural opposites

It is interesting to note that cortisol does exactly the opposite. Cortisol is the adrenal gland hormone that helps us cope with stress. When we are fully awake, we need cortisol to cope with stress. Melatonin inhibits cortisol secretion and cortisol inhibits melatonin secretion, so they are natural opponents working together for your common good. This is part of the circadian rhythm. We can measure these hormones and this is how researchers have found out how this works.

How To Cope With Time Switches

How To Cope With Time Switches

Time switches affect the circadian rhythm

When we switched time back by one hour on our wristwatch and clocks, the internal time in our body did not accept that right away. The body needs to gradually adjust to this by reading the external signals: when are we opening our eyes? What is the light intensity when we get up, what is the light intensity when we go to sleep?  Some people find it easy to adjust; others find it very difficult to adjust. Some individuals breeze through the adjustment process in a day or two. For others it can as much as 1 or 2 weeks before the hormonal adjustment is completed.

Symptoms of problems adjusting the circadian rhythm

Symptoms due to time switch are a feeling of hangover on the first one to two days after the switch. This is despite you having gotten enough sleep, but the quality of sleep was not the same as before the time switch. Your head feels heavy, you are irritable, and you may feel mildly depressed. You also may find it more difficult to concentrate on one thing and you experience fatigue. Some experience insomnia. What is behind this is a disturbance of your cortisol levels. Your cortisol level is normally highest in the early morning hours, just before you wake up. As a male your testosterone level is also highest when you wake up thanks to the circadian rhythm. Both cortisol and testosterone recover their hormone storage during your deepest sleep.

Our hormones are linked to the internal diurnal clock

In women the ovarian hormones have not only a monthly rhythm, but also a 24-hour diurnal rhythm, based on the internal 24-hour clock. The hypothalamus and the pituitary gland have an intimate involvement in both sexes regarding this diurnal rhythm. They are in communication with the pineal gland that produces melatonin to regulate all of the major hormone systems. So, when we switch our watch back by one hour in the fall or forward by one hour in the spring, our body clock is out of sync with the new time that rules the world. This state of being out of sync may last for a few days. We still get tired according to the old time and we still wake up according to the old time until our internal clock has readjusted. People have genetic differences on how quickly they readjust.

Jet lag

When we travel eastward or westward through time zones a phenomenon of being “out of sync” occurs as well, very similar to what happens with time switches. It is the same re-adjusting process of the internal circadian rhythm that our bodies have to come to terms with. Some people are affected more when they travel west though time zones, and it may take them longer to adjust to it compared to traveling east. But other people complain that for them it is just the opposite, and traveling east is the problem for them. North-south travel does not cause jet lag as the internal time and the external time remain synchronized. A very similar phenomenon is happening with the spring and fall time switches. Some people find it nervier when in spring the clock is advanced by one hour and others complain that fall is their difficult time when the time is switched back by one hour. There are genetic differences of how we adjust with our internal clocks.

Shift workers

Shift workers experience problems with the circadian rhythm as well. The switch between working day shifts and night shifts leads to a condition called “shift-work sleep disorder” (Ref.3). Similar to jet lag this is due to the fact that there is a disruption of the synchronization between the body’s inner clock and external cues. The work rules do not allow enough time for recovery. It would be much more cost effective, if unions and employers allowed those who are naturally born to cope with night time shift to work those shifts and allow those who are sensitive to shift-work sleep disorder to work only day shifts. We live in an age of political correctness, but we tend to overlook how our bodies work.

What you can do to ease yourself into the time switch

1. As there is a lack of deep sleep with the time switch, it is not a bad idea to take a short nap when you feel tired during the day. Catch a nap on the weekend or on a day, when you are off work! It’s good for you! This will build up your adrenal gland hormones and give you the extra surge of energy you are craving for.

2. At the end of the day though, you need to go to bed according to the new time to train your pineal gland and your entire hormone system about the new time situation. Your body needs the cues from you, when you start and end your day, so that it can sync your internal clock with the outside time.

Melatonin restores the circadian rhythm

3. A simple remedy that fits right into your hormone rhythm is to take a melatonin tablet (about 3 mg for an adult), available at your health food store or drugstore 30 minutes before bedtime. Ref. 2 states that melatonin “restores the circadian rhythm “. This helps your circadian hormone rhythm by giving it an evening boost of melatonin. This tells your system it is time to go to sleep. At that time when you close your eyes the signals  through the optic nerve shut down. This gives the circadian rhythm yet another signal about what time it is. In just a few days (for very sensitive people in 1 to 2 weeks) your entire hormone system including the circadian 24-hour undulations will be reset. Now your internal clock has been reset and is in sync until the next time switch.

More about hormones: http://nethealthbook.com/hormones/introduction-hormones/

References

1. Melmed: “Control of Hormone Secretion” in: Williams Textbook of Endocrinology, 12th ed.Copyright 2011 Saunders, An Imprint of Elsevier

2. Rakel: Integrative Medicine, 3rd ed. Copyright 2012 Saunders, An Imprint of Elsevier

3. Daroff: Bradley’s Neurology in Clinical Practice, 6th ed. Copyright 2012 Saunders, An Imprint of Elsevier

Feb
15
2014

Melatonin More Than A Sleeping Aid

Melatonin has been available to the public in the US since 1992. It is usually used as a sleeping aid or for jet lag related sleeping problems. However, in the last decade much more data about melatonin has come out that has proven that melatonin is a major hormone. The pineal gland contains another brain hormone, serotonin, which is converted into melatonin within that gland. Melatonin is a key hormone that regulates the sleep/wake cycle. It works in concert with cortisol, which has the highest level in the morning while melatonin has its highest level in the evening and during the night. Melatonin also regulates the menstrual cycle and determines when women get into menopause.

Lately new information has come to the forefront showing that there are connections to Alzheimer’s disease, Parkinson’s disease, stroke size and recovery from strokes. Even traumatic brain injury can be minimized when enough melatonin is present. In addition melatonin is an important anti-oxidant.

Finally, there is evidence that melatonin helps to determine how well we age.

In the following I like to review some of the evidence for all of these claims.

1. Melatonin as a hormone

Melatonin levels were found to be very low in breast cancer and prostate cancer patients. It has been determined that the immune cells have melatonin hormone receptors and need melatonin for stimulation. Because of the immune stimulatory effect of melatonin, it is often given as a cancer adjuvant treatment to other cancer treating modalities. Ref. 1 describes that melatonin regulates the female hormones (LH, FSH), which then determine when a woman has her menstrual period and also when she eventually enters menopause. The pineal gland is the master gland for the diurnal hormone rhythms.

Melatonin More Than A Sleeping Aid

Melatonin More Than A Sleeping Aid

2. Melatonin levels decline with age

Melatonin levels in both men and women decline as we age. This figure shows that the highest melatonin levels are reached by the age of 10; by the age of 40 only 15% of the youthful levels remain while by the age of 55 only 5% or less of the original youthful levels are left. This explains why older people are more prone to infections (missing immune stimulation) and why the sleep pattern in older people is changed (shorter periods of sleep, less restful sleep). Ref. 1 points out that with insulin resistance (from diabetes or due to excessive sugar and starch consumption) cortisol levels are chronically elevated, which in turn inhibits melatonin production.

3. Melatonin protects from neurodegenerative diseases

A newer application of melatonin is as a preventative in the neurological field, particularly in the area of Alzheimer’s disease, Parkinson’s disease and the prevention of strokes. With respect to Alzheimer’s disease studies have shown that patients with Alzheimer’s have much lower melatonin blood levels when compared to age matched normal controls. In ischemic stroke patients it was found that stroke patients had much lower melatonin levels when compared to normal age-matched controls. Other studies have shown that pineal gland calcification was associated with low melatonin levels and a high risk for ischemic stroke. This risk was even higher when the patients had high blood pressure, diabetes and high cholesterol/triglycerides. When a stroke has occurred, it is important that the free radicals are removed as quickly as possible, which is where the antioxidant properties of melatonin fit into a rehabilitative program. The presence of melatonin enhances brain plasticity. However instead of using melatonin after a stroke, it is much better to use melatonin regularly before a possible stroke, as this gives a better chance reducing the size of the stroke. This in turn will lead to a faster and more complete recovery after a stroke.

Another important disease of the elderly is Parkinson’s disease. Melatonin helps to prevent oxidative damage to the dopamine producing cells in the basal ganglia thus preventing Parkinson’s disease. As with Alzheimer’s disease, there is a correlation of low melatonin levels and this neurodegenerative disease, which goes beyond the age-related reduction of melatonin levels. In experimental Parkinson’s disease models in mice melatonin was highly effective in preventing deterioration of Parkinson’s disease.

4. Melatonin may extend life

The combination of being a free radical scavenger, an immunostimulant and an integral key hormone allow melatonin to have beneficial effects in the aging process. When melatonin supplements are given, the stimulation of the immune system can cut down infection rates in the elderly, prevent and mitigate degenerative diseases of the brain (Alzheimer’s, Parkinson’s), re-establish sleep/waking rhythms and help reduce arthritis.

Conclusion

Melatonin is a widely used sleep aid. As it is practically absent in people beyond the age of 55, it makes sense to supplement with melatonin in that patient group. However, there are side effects particularly in people on blood thinners as coumadin competes with melatonin in getting eliminated through the cytochrome P450 liver enzyme system. This will result in longer bleeding times in patients on blood thinners who also take melatonin supplements. It is important that patients discuss this with their doctors. However, given all of the benefits described above, for the vast majority of the baby boomers melatonin supplementation would be very beneficial. Doses as a sleep aid vary between 1mg and 5mg at bedtime for most people. Cancer patients require higher doses (10 to 20 mg per day).

More information on melatonin, which is at the center of the circadian hormone rhythm as the key hormone switching from day to night and welcoming the day by switching its secretion from the pineal gland off in the morning: https://www.askdrray.com/how-to-cope-with-time-switches/

Reference

1. Datis Kharrazian: “Why isn’t my brain working?” Copyright 2013, Elephant Press, Carlsbad, CA, USA (pages 306-310).

Last edited Nov. 7, 2014

Sep
28
2013

Sleepless Nights

Sleeping problems (insomnia) are very common. About 10% of the population suffers from chronic insomnia; 30% of the population suffers from occasional sleep problems. In a large outpatient population of a clinic consisting of 3500 patients who had at least one major clinical condition, 50% complained of insomnia, 16% had severe symptoms, 34% had mild symptoms (Ref.1). Insomnia is more common among women, and older people as well as in people with medical or psychiatric illnesses. Long-term studies have shown that the same insomnia problems persist throughout many years. It is not possible to offer a simple remedy for insomnia, because insomnia is a complex problem. Here I will discuss some of the causes of insomnia and also discuss some of the treatment options.

Symptoms of insomnia

The person who suffers from insomnia will usually state that they have problems falling asleep. Worries of the day suddenly circulate through their thoughts and they toss and turn nervously looking at the clock from time to time and getting more and more anxious that they cannot sleep. Others fall asleep OK, but in the middle of the night they wake up perhaps to visit the restroom, but then they cannot go back to sleep. Others wake up 2 hours before their normal alarm clock time and they feel their stomach rumbling making it impossible to fall back to sleep. Older people with chronic diseases and general poor health suffer more from insomnia. In this setting insomnia may be more related to the underlying disease rather than old age. Psychiatric disorders also are associated with more insomnia. Treat the underlying psychiatric illness, and the insomnia disappears.

Although insomnia is a sleep disturbance during the nighttime, people who are affected with this complain of daytime fatigue, of overstimulation, yet they catch themselves making frequent mistakes, and their inability to pay attention gets them involved in accidents and falls. Longitudinal studies have shown (Ref. 1) that people with chronic insomnia are more likely to develop psychiatric disease, such as major depression,  anxiety disorder and alcohol and substance abuse. Unfortunately these disorders can by themselves again cause insomnia, which reinforces chronic insomnia. Insomnia leads to poorer social and physical functioning, affects emotions, leads to a lack of vitality and physical endurance, contributes to worsening of pain and can affect general and mental health.

Research about insomnia

Much has been learnt from sleep studies using polysomnography monitoring during a full night’s sleep. These studies have been used mainly as a research tool. In such studies eye movements, brain wave activity, muscle activity, chest movements, airflow, heart beats, oxygen saturation and snoring (with a microphone) are all simultaneously recorded. This way restless leg syndrome, sleep apnea, snoring, seizure disorders, deep depression etc. that can all lead to insomnia can be diagnosed and separated from insomnia. The stages of sleep (wakefulness, stage 1 to 3 sleep and the REM sleep stage) can also be readily measured using polysomnography (Ref.2). According to this reference the majority of insomnia cases do not need this complex procedure done.

Sleepless Nights

Sleepless Nights

Causes of insomnia

Traditionally insomnia cases are classified into primary insomnia and secondary insomnia. Secondary insomnia is caused by all of the factors discussed below. When they are dealt with, we are left with cases of primary insomnia.

The following medical conditions can cause insomnia: heart disease, pulmonary diseases like asthma and chronic obstructive pulmonary disease (COPD); gastrointestinal disease like liver cirrhosis, pancreatitis, irritable bowel syndrome, ulcers, colitis, Crohn’s disease; chronic kidney disease; musculoskeletal disease like arthritis, fractures, osteoporosis; neurodegenerative disease like MS, Parkinson’s disease, Alzheimer’s disease; endocrine disease like diabetes, hyper- or hypothyroidism, adrenal gland fatigue and insufficiency; and chronic pain conditions. Also, psychiatric conditions like major depression, schizophrenia and anxiety disorders can cause insomnia.

This list in not complete, but it gives you an idea of how complex the topic of insomnia is.
The physician who is seeing a patient with insomnia needs to rule out any of these other causes of insomnia to be certain that the only condition that is left to treat in the patient is insomnia itself. The other diagnoses have to be dealt with separately or else treatment of insomnia will fail.

Ref. 1 points to a useful model of how to think about causation of insomnia: there are three points to consider, namely predisposing, precipitating, and perpetuating factors. Let’s briefly discuss some of these.

Predisposing factors

We are all different in our personal make-up. If you are well grounded, chances are you are not susceptible to insomnia. Anxious persons or persons who have been through a lot of negative experiences in life will have personality traits that make them more prone to insomnia. Lifestyle choices such as late nights out, drinking with the buddies in a bar (extreme circadian phase tendencies) will have an impact on whether or not you develop insomnia.

Precipitating factors

A situational crisis like a job change or the death of a loved one can initiate insomnia.  However, there could be a medical illness such as a heart attack, a stroke or the new diagnosis of a psychiatric illness that has become a precipitating factor. Sleep apnea and restless leg syndrome belong into this group as well as would the stimulating effect of coffee and caffeine containing drinks. Jet lag and nighttime shift work can also be precipitating factors.

Perpetuating factors

Daytime napping to make up for lost sleep the night before can undermine sleep initiation the following night, which can lead to a vicious cycle. Similarly, the use of bedtime alcoholic drinks leads to sleep disruption later that night and can become a perpetuating factor, if this habit is maintained. Even the psychological conditioning of being anxious about whether or not you will fall asleep easily or not the next night can become a perpetuating factor.

I will return to this classification and the factor model of causation of insomnia when we address treatment options.

Drugs that can cause insomnia

One major possible cause for insomnia  can be side effects from medications that patients are on (would belong to the ‘perpetuating factors’ among causes). Physicians call this “iatrogenic insomnia”. The antidepressants, called selective serotonin reuptake inhibitors (SSRI’s) like Prozac are particularly troublesome with regard to causing insomnia as a side effect. Other antidepressants like trazodone (Desyrel) are used in small doses to help patients with insomnia to fall asleep. Some asthmatics and people with autoimmune diseases may be on prednisone, a corticosteroid drug. This can cause insomnia, particularly in higher doses; so can decongestants you may use for allergies; beta-blockers used for heart disease and hypertension treatment; theophylline, an asthma medication and diuretics. Central nervous stimulants like caffeine or illicit drugs can also cause insomnia. Hormone disbalance in general and hyperthyroidism specifically as well as Cushing’s disease, where cortisol levels are high will cause insomnia.

Treatment of insomnia

So, how should the physician approach a patient with insomnia? First it has to be established whether there is secondary insomnia present due to one of the predisposing, precipitating or perpetuating factors. In other words, is there secondary insomnia due to other underlying illnesses? If so, these are being addressed first. Lifestyle choices (staying up late every night) would have to be changed; alcohol and drug abuse and overindulging in coffee or caffeine containing drinks needs to be dealt with. Cognitive therapy may be beneficial when mild depression or anxiety is a contributing factor to insomnia.

The remaining insomnia (also medically termed “primary insomnia”) is now being treated.

The following general points are useful to get into the sleeping mode (modified from Ref. 3):

  1. Ensure your bedroom is dark, soundproof, and comfortable with the room temperature being not too warm, and you develop a “sleep hygiene”. This means you get to sleep around the same time each night, have some down time 1 hour or so before going to bed and get up after your average fill of sleep (for most people between 7 to 9 hours). Do not sleep in, but use an alarm clock to help you get into your sleep routine.
  2. Avoid caffeine drinks, alcohol, nicotine and recreational drugs. If you must smoke, don’t smoke later than 7PM.
  3. Get into a regular exercise program, either at home or at a gym.
  4. Avoid a heavy meal late at night. A light snack including some warm milk would be OK.
  5. Do not use your bedroom as an office, reading place or media center. This would condition you to be awake.  Reserve your bedroom use only for intimacy and sleeping.
  6. If you wake up at night and you are wide awake, leave the bedroom and sit in the living room doing something until you feel tired and then return to bed.
  7. A self-hypnosis recording is a useful adjunct to a sleep routine. Listen to it when you go to bed to give you something to focus on (low volume) and you will find it easier to stop thinking.

Drugs and supplements for insomnia

1. In the past benzodiazepines, such as diazepam (Valium), lorazepam (Ativan), fluorazepam (Dalmane), temazepam (Restoril), triazolam (Halcion) and others were and still are used as sleeping pills. However, it was noted that there are significant side effects with this group of drugs. Notably, there is amnesia (memory loss), which can be quite distressing to people such as not remembering that someone phoned while under the influence of the drug, you promised certain things, but you cannot remember the following morning what it was. Another problem is the development of addiction to the drugs with worse insomnia when the drugs are discontinued. Many physicians have stopped prescribing benzodiazepines.

2. There are non-benzodiazepines drugs that are used as sleeping pills (hypnotics), such as Zaleplon (Sonata), Zolpidem (Ambien) and Eszopiclone (Lunesta).  They seem to be better tolerated.

3. Ramelteon, a melatonin agonist, is available by prescription in the US. It probably is the best-tolerated mild sleeping pill and works similar to melatonin, but is more expensive. Chances are that your physician likely would prescribe one of the non-benzodiazepines drugs or Ramelteon for you as they do not seem to be addicting.

4. However, there is an alternative: Many patients with insomnia tolerate a low dose of trazodone (Desyrel), which is an antidepressant with sleep restoring properties. A low dose of 25 to 50 mg at bedtime is usually enough for insomnia. This allows the patient to fall asleep within about 30 minutes of taking it, and sleep lasts through most of the night without a hangover in the morning. Many specialists who run sleep laboratories recommend trazodone when primary insomnia is diagnosed. However, this is still a drug with potential side effects as mentioned in the trazodone link, but 50 mg is only ¼ of the full dose, so the side effects will also be less or negligible.

5. I prefer the use of melatonin, which is the natural brain hormone designed to put us to sleep. Between 1 mg and 6 mg are sufficient for most people. We know from other literature that up to 20 mg of melatonin has been used in humans as an immune stimulant in patients with metastatic melanoma with no untoward side effects other than nightmares and some tiredness in the morning. A review from the Vanderbilt University, Holland found melatonin to be very safe as a sleeping aid. There are several melatonin receptors in the body of vertebrates (including humans), which are stimulated by melatonin.

6. Other natural methods are the use of L-Tryptophan at a dose of 500 mg at bedtime, which can be combined with melatonin. It is the amino acid contained in turkey meat, which makes you tired after a Thanksgiving meal. GABA is another supplement, which is the relaxing hormone of your brain, but with this supplement tolerance develops after about 4 to 5 days, so it is only suitable for very short term use. Herbal sleep aids are hops, valerian extract and passionflower extract. They are available in health food stores.

Conclusion

A lack of sleep (insomnia) is almost a given in our fast paced lives.

When it comes to treatment, all of the other causes of secondary insomnia need to be treated or else treatment attempts would fail. What is left is primary insomnia. This is treated as follows:

We need to review our sleeping habits, lifestyles and substance abuse. Remove what is detrimental to your sleep. Start with the least invasive treatment modalities such as self-hypnosis tapes, melatonin, L-Tryptophan or herbal extracts. Should this not quite do the trick, asks your doctor for advice. The non-benzodiazepines drugs or Ramelteon would be the next level up. It may be that an alternative such as low dose trazodone would be of help. Only, if all this fails would I recommend to go to the more potent sleeping pills (keep in mind the potential for addiction to them).

References

1. David N. Neubauer, MD (John Hopkins University, Baltimore, MD): Insomnia. Primary Care: Clinics in Office Practice – Volume 32, Issue 2 (June 2005)  © 2005, W. B. Saunders Company

2: Behrouz Jafari, MD and Vahid Mohsenin, MD (Yale Center for Sleep Medicine, Yale University School of Medicine, New Haven, CT, USA): Polysomnography. Clinics in Chest Medicine – Volume 31, Issue 2 (June 2010), © 2010 W. B. Saunders Company

3. Jean Gray, editor: “Therapeutic choices”, 5th edition, Chapter 8 by Jonathan A.E. Fleming, MB, FRCPC: Insomnia, © 2008, Canadian Pharmacists Association.

Last edited Sept. 28, 2014

May
01
2008

Tree Pollen Connected With Mood Disorders

Seasonal affective disorder (SAD) does have its grip on people who react to a lack of sunlight in the winter month. As a result depression in the winter season is not uncommon. Some people just report it as feeling “down” and “tired” or report a lack of energy. Despite all the reports about SA, epidemiological studies have shown that the rate of depression is not the highest in dreary months like January or February but it spikes in the months of April and June. Dr.Teodor Postolache, a psychiatrist at the University of Maryland made a recent presentation at a meeting of the American Acadamy of Allergy, Asthma and Immunolgy delving into the reason for this finding. He compared the exposure of tree pollen which triggers a cytokine release to a tsunami.Virtually no outdoor allergens are present in the winter months, but with the release of tree pollen people who are vulnerable to allergies are exposed to massive amounts of allergens. The released cytokines may affect brain function and behaviour, resulting ultimately in changed cortisol levels and an altered serotonin metabolism. After breathing the cytokines are already released in the nose and they can continue their action in the prefrontal brain area where the centers for mood, anxiety and impulsivity are located. Dr. Postolache and his colleagues confirmed that individuals with a history of allergy and asthma had a 2.5 fold of suicide compared to controls and those with allergic rhinitis had a 1.7 fold higher risk.

Tree Pollen Connected With Mood Disorders

Tree Pollen Connected With Mood Disorders

For the first time it could also be demonstrated that cytokine levels in suicide victims were significantly elevated in the orbitofrontal cortex, the brain area that affects mood. Intranasal corticosteroids in the form of nosedrops can bring significant relief to allergy sufferers, and Dr. Postolache and his team will examine the benefits of intranasal corticosteroids closer  in a clinical study. Whereas systemic corticosteroids have shown a negative impact on mood disorders and depression, the local application of a nasal spray or drops is geared to abolish the pathways from the nose to the brain for the inflammatory cytokines.

More information on seasonal rhinitis: http://nethealthbook.com/ear-nose-and-throat-diseases-otolaryngology-ent/nose-problems/allergic-rhinitis/

Reference: The Medical Post, April 1, 2008, page 1, 34

Last edited November 3, 2014