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July 19, 2014

Ear Injection of AM-101 May Stop Tinnitus

Phantom ringing of the ears also known as tinnitus is an extremely frustrating condition that afflicts many people. Often triggered by hearing nerve damage, there's no good treatment to fix this condition once it sets in.

Until possibly now... 

AM-101 made by Auris Medical is an experimental drug containing esketamine hydrochloride embedded within a hyaluronic acid gel formulation. It works by blocking the NMDA receptors of the cochlear inner hair cell.

Normally, when there is trauma sustained by the cochlea whether it be loud noise or viral infection, excess amount of a neurotransmitter called glutamate gets release. The problem is that too much glutamate also triggers hearing nerve death due to over-excitation via the NMDA receptor. When these hearing nerves die, it leaves the brain cells responsible for hearing in a permanently switch-on state leading to tinnitus, even if there's no sound present.

AM-101 is hypothesized to block the NMDA receptor from being over-stimulated by the glutamate neurotransmitter thereby preventing hearing nerve death.

But, does it work?

According to one small prospective, double-blind, randomized, placebo-controlled study involving 248 patients, it DOES work to a significant degree.  42% reported their tinnitus was half as quiet as before compared with 14% in the placebo group. After 90 days, 57% of those taking the active gel said their tinnitus was 'much improved' or 'very much improved'.

Of course, the trick is to administer the drug before nerve death has set in after which it would be too late. In the study, only patients with onset of ringing within 3 months were eligible to participate.

Patient also need to realize that the drug is administered by injection through the eardrum and into the middle ear space. This injection technique is commonly used in the treatment of sudden nerve hearing loss where steroids are injected. Watch video of this injection method below.

Unfortunately, AM-101 is not available except under research protocols currently and is undergoing FDA clinical trials. The preliminary results are very promising however.

Efficacy and Safety of AM-101 in the Treatment of Acute Inner Ear Tinnitus—A Double-Blind, Randomized, Placebo-Controlled Phase II Study. Otology & Neurotology: April 2014 - Volume 35 - Issue 4 - p 589-597

Dr. Chang Quoted in Slate Magazine Article

Dr. Chang was quoted several times in a Slate Magazine article regarding some strange things the body does. The article organized in a question and answer format, includes several ENT questions for which Dr. Chang provided answers to.

Such answered questions by Dr. Chang included:
  Occasionally my hearing will ‘go out’ and everything will go dull.. and then a high pitched frequency screeches for a few minutes. No one else hears it and everything else seems really hushed while it's happening. Maybe it's the aliens.

  I can make a loud rumbling sound in my ears at will without moving any muscle in my face. I have no idea what this is called but it kind of sounds like when you put your ear to a seashell at the beach.

  Once in a while when I eat something sugary I get a really sharp pain under/around my ears. like really sharp. It sucks. I did some reading on it, I think it has something to do with the salivary glands?

  Tonsil stones or “Tonsillolith”. They're small white/yellowish blob that randomly comes out of my mouth sometimes... And they smell extremely bad.
Read the magazine article for the answers!

Why Does Your Body Do These Strange Things? Slate July 2014.

July 13, 2014

Botox Injection Severe Side Effects Treatment

Side effects from botox injections are not uncommon and even expected to some degree in the region where the injection was performed. For example, when botox is injected into the voicebox for spasmodic dysphonia, normal and expected side effects include hoarseness and dysphagia.

However, in very rare instances, more severe side effects may occur that may even appear to be life-threathening including stridor, shortness of breath, profound difficulty swallowing, etc.

In such situations, beyond supportive care and ruling out more serious conditions like a heart attack, treatment with pyridostigmine can be quite effective in alleviating if not outright reversing the severe botox side effects.

Pyridostigmine is a drug that prevents the body from breaking down the chemical mediator (acetylcholine) that causes muscle contraction. Given botox works by preventing the release of acetylcholine, it makes sense that by preventing the body from breaking this hormone down, more of it is around to activate the muscle.

Put simply, pyridostigmine increases acetylcholine levels to counteract the botox effect of decreasing acetylcholine leading to a net zero effect theoretically. But does it work that way? According to one research paper, it certainly appears to do so!

In cases of stridor due to bilateral vocal cord paralysis or other severe side effect, an initial treatment of 300 mg of pyridostigmine x 2 doses separated by 6 hours followed by 30 mg 3x per day is recommended. Symptom improvement occurs fairly rapidly.

In less dire situations, simply starting a patient on pyridostigmine 30 mg 3x per day without an initial loading dose is sufficient.

Otherwise, behavioral support alone is recommended for less severe botox side effects.

Pyridostigmine for Reversal of Severe Sequelae From Botulinum Toxin Injection. Journal of Voice. 2014 Jul 5. pii: S0892-1997(14)00091-5. doi: 10.1016/j.jvoice.2014.04.010. [Epub ahead of print]

July 08, 2014

Does Sinus and/or Nasal Surgery Help with Sleep Apnea?

Bluntly, the answer is not really... Although it may make sense that improving nasal airflow should help with obstructive sleep apnea, the reality is that it does not make a profound difference. Indeed, there was a study in 2014 that looked into this question.

In this study, 3 groups of patients were looked at divided into patients with mild, moderate, or severe obstructive sleep apnea (OSA). These patients underwent sinus surgery, septoplasty, and turbinate reduction.

What was found was that patients with severe OSA with a mean AHI of 52 would go down to 43 (normal being less than 5) after surgery. Moderate OSA with a mean AHI of 22 down to 20. Patients with mild OSA did not have any significant changes to AHI at all.

In other words, for patients with moderate or severe OSA, although the AHI does decrease somewhat, it does not decrease enough that it really makes any clinical difference. Patients with moderate or severe OSA still had OSA... and still would need to use a CPAP or equivalent machine after surgery to correct their sleep apnea.

Although at first blush, these results may not make sense, it actually does make sense when you consider sleep apnea to be a multi-level disorder affecting not just the nose, but the throat as well.

For example, the back of the tongue may fall backwards obstructing the airway causing sleep apnea. Correcting nasal factors would have absolutely ZERO impact on tongue factors of OSA.

In order to determine where these other anatomic factors may be that may contribute to OSA, a sedated or sleep endoscopy is often performed. Watch the video below.

Granted, patients may STILL wish to pursue sino-nasal surgery due to discomfort with their sinuses and nasal breathing... but patients need to be aware that their OSA may still remain essentially unchanged!

Sino-nasal surgery may also help with CPAP compliance as lower pressures may be required to address OSA compared to before surgery. Why? Because the nasal passages are more open after surgery so it is easier to push air into lungs when using CPAP.

Effects of Endoscopic Sinus Surgery and Nasal Surgery in Patients with Obstructive Sleep Apnea. Otolaryngol Head Neck Surg. 2014 Mar 31;151(1):171-175. [Epub ahead of print]

July 02, 2014

CEO of JPMorgan has Throat Cancer

Image from Wikipedia by Steve Jurvetson
The CEO and President of JPMorgan, Jamie Dimon, announced that he has throat cancer and is currently undergoing treatment at Memorial Sloan Kettering Cancer Center in Manhattan for the next eight weeks. According to a letter he sent to shareholders on July 1, 2014:
"I wanted to let you know that I have just been diagnosed with throat cancer. The good news is that the prognosis from my doctors is excellent, the cancer was caught quickly, and my condition is curable. Following thorough tests that included a CAT scan, PET scan and a biopsy, the cancer is confined to the original site and the adjacent lymph nodes on the right side of my neck. Importantly, there is no evidence of cancer elsewhere in my body." [link]
Based on this information, he has a Stage 3 or 4 (out of possible 4) throat cancer. Stage 1 is the early and best stage to have. It is less clear exactly where the throat cancer is whether it be tonsil, tongue, oropharynx, or some other location. Based on probabilities, he most likely has squamous cell carcinoma which is the most common type of cancer of the head and neck including the throat.

Although he states the prognosis is good, it is not as good compared to patients where no neck mass is present (Stage 1 or 2) where chemotherapy may not even be necessary.

He also mentions the word "curable" which I am leary of when he has just started treatment. Even if no cancer is detectable at the end of treatment, throat cancer, especially stage 3 or 4, has the potential to come back.

Recall the case of actor Larry Hagman of Dallas fame... He had throat cancer and was declared "cured" 8/29/12. Than on 11/24/13, he died of cancer recurrence and complications.

The risk of cancer recurrence is highest within the first 2-3 years after treatment completion, and markedly decreases after 5 years.

Typically if cancer has not come back after 5 years, the word "cure" may than be used, but even than, such patients are seen yearly for the rest of their life for cancer monitoring.

Because the risk of cancer recurrence is so high in the first few years after treatment completion, patients are seen frequently for the first 2-3 years after treatment.

Every 2 months for the first year. Every 3-4 months in the 2nd year. Every 4 months in the 3rd year. Every 6 months in the 4th year. Yearly starting at 5 years after treatment.

This type of follow-up applies to all head and neck cancer.

JPMorgan CEO Jamie Dimon has cancer. USA Today 7/2/14

JPMorgan CEO Jamie Dimon's letter to shareholders. USA Today 7/1/14

June 19, 2014

Why is Allergy Present More Now than in Past? Hygiene vs Hapten Hypothesis

It is pretty much well-established fact that there are more people with food and inhalant allergy now than in the past. Two main theories have been proposed to try and explain this unfortunate phenomenon that is affecting more kids with each new generation.

Keep in mind the explanations provided below are significantly simplified for lay public understanding. One can go into cytokines, Th1 and Th2 responses, and other techno-jargon, but not here.

Perhaps the most popular explanation is the "Hygiene Hypothesis" which mainly states that major improvements in public health and medical technology have led to a cleaner home environment with less infectious and parasitic disease burden, resulting in less stimulation of the immune system and a consequent predisposition to allergic disease.

This hypothesis helps to explain why 3rd world nations which have poor sanitation and greater microbial/parasitic diseases do not suffer nearly as much allergic problems as well-developed nations. Basically, the dirtier and more disease ridden people grow up in, the less allergies they have because the immune system is preoccupied with fighting "real" infectious problems. In the absence of such immune stimulation, the immune system essentially gets "bored" and starts treating normal things like pollen as an infection that needs to be eliminated.

The alternative explanation is the "Hapten Hypothesis." Before explaining further how this theory works, first a little immunology instruction. Haptens are very small molecules which are able to easily pass through skin and mucus membranes with ease and by themselves cause absolutely no problems whether immune or allergy. However, when such haptens attach to a carrier protein, it may elicit a profound allergic immune response. Keep in mind that the carrier protein itself may also not elicit an immune response. It is the combination of hapten and carrier protein together that causes the problem.

According to the Hapten Hypothesis, persistent low-grade exposure to environmental haptens via the skin and oral routes at key times during human development – namely, pregnancy and the first year of life – can lead to allergy development. Dietary hapten intake may interfere with oral immune tolerance mechanisms while repeated skin exposure to haptens may promote elevated allergy responses.

What are some of these oral and skin haptens?

• Preservatives
• Nickel
• Cobalt
• Vanillin
• Pesticides
• Drugs (antibiotics and others)
• Industrial chemicals
• Food emulsifiers
• Food colorants
• Flavour enhancers
• Antioxidants
etc etc

Arguments promoting the Hapten Hypothesis over the Hygiene Hypothesis goes as follows:

#1. The biggest reduction in infections came at the end of the 19th century with improvements in sanitation and nutrition – not in the second half of the 20th century, when the greatest increase in allergic disease began – so why didn't they occur together??? However, significant exposure of haptens to the human population on a recurrent basis occurred on a major scale during the 20th century.

#2. The Hygiene Hypothesis states that our immune system does not get stimulated enough by infections. But technically, that's not true... Vaccination programs are the deliberate exposure of our immune system to a whole host of diseases including polio, tetanus, diphtheria, and measles, all by the age of 1 year. Disease burden is not a factor according to the Hapten Hypothesis.

#3. Studies have repeatedly shown that respiratory infections are associated with the development of allergic disease... but according to the Hygiene Hypothesis, the opposite should occur. According to the Hapten Hypothesis, drugs like antibiotics are haptens and can actually promote allergy development.

So is there a definitive answer here?

Unfortunately not, though there are very smart people working on this.

My hunch is that the final answer may be a combination of both hypothesis.

At the very least, there really may be something to the organic movement which promotes eating/drinking foods that contain no pesticides, preservatives, or chemicals and the use of skin products which also contain only "organic" ingredients.

However, keep in mind that the BIGGEST impact towards the prevention of allergy development are actions taken while a woman is pregnant through the infant's first year of life. After that, interventions may be too little, too late according to the Hapten Hypothesis.

I personally like the Environmental Working Group website to check if certain products are "organic" or not because I certainly don't have the time to check every consumer product myself.

When it comes to food, try to make all baby food from scratch. Next best would be to purchase baby food that is sold refrigerated (avoid baby food sold on regular shelves).

Does hapten exposure predispose to atopic disease? The hapten-atopy hypothesis. Trends Immunol. 2009 Feb;30(2):67-74. doi: 10.1016/ Epub 2009 Jan 8.

Food-provoked eczema: A hypothesis on the possible role of systemic contact allergy to haptens present in both cosmetics and foods. Estetol Med Kosmetol 2011; 1(1): 35-40. DOI:

The importance of hapten-protein complex formation in the development of drug allergy. Current Opinion in Allergy and Clinical Immunology 2014 Jun 17;
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