Archive for December, 2013

There's Silver in Them There Pills

Wednesday, December 25th, 2013

Like most medically-trained people (and hopefully many of the rest of us), I've been highly concerned about the rise of drug-resistant microorganisms, bacteria that can't be treated with our standard antibiotics. A recent article in The Wall Street Journal with the intriguing title "Antibiotics of the Future" offered considerable hope, but let look at some background on the subject first.

The WSJ article said that two million patients each year in the United States develop infections that doctors can't combat with our normal antibiotics; earlier in the year, the CDC in a report titled "Antibiotic Resistance Threats in the United States 2013" estimated that at least 23,000 of them die. They divide the microorganisms, all bacteria except for Candida (a fungus), into three groups: those whose threat levels are considered urgent, serious or concerning. The three in the urgent category include Clostridium difficile, which causes severe, life-threatening diarrhea, often in patients who have been hospitalized and are already on antibiotics, and leads to a quarter-million infections, 14,000 deaths and a billion dollars in medical expenses yearly. Then there are the carbapenem-resistant Enterobacteriaceae,  abbreviated as CRE (the carbapenems are powerful antibiotics considered the "drugs of last resort," used when all other old and modern antimicrobials fail or are thought to be likely to fail; Eneterobacteriaceae are bacteria that are part of the normal gut flora.)

CRE infections most often happen in patients getting treatment for other serious conditions. They may be on a respirator, have a long-term catheter in their bladder or have been on other antibiotics. One estimate says there are 9,000 CRE infections a year and they cause at least 600 deaths. Patients in intensive care units not infrequently have IV catheters placed in large veins in the neck, chest or groin to allow hospital personnel to give medications and draw blood sample for a prolonged period of time. If these get infected they can cause a bloodstream infection (sepsis is the medical term). About half of all hospital patients who get CRE that goes on to cause a bloodstream infection die.

The third infectious urgent threat level is the bacteria, Neisseria gonorrhoeae, that causes the STD gonorrhea. The CDC estimates more than 800,000 cases occur yearly in the United States and 30% of these are resistant to some antibiotic, but almost all can be treated, at this time, with a two-drug cocktail. Gonorrhea causes severe reproductive system complications and the CDC says it "disproportionally affects sexual, racial and ethnic minorities."

Then there is MRSA, methicillin-resistant Staphylococcus aureus. This bug is classified as serious, not urgent, yet there are roughly 80,000 severe MRSA cases a year and over 11,000 of these patients die. Most major MRSA cases are seen in healthcare setting among patients with weakened immune systems (e.g., those on hemodialysis or receiving cancer therapy) but less serious MRSA  can case problems in otherwise healthy people, including athletes who share towels or razors, children in day-care and members of the military in cramped quarters. Some of these infections, usually of the skin, can become severe and life-threatening.

The CDC piece, except for Candida, excludes non-bacterial diseases, but I received a reader comment a while back from a person whose website ( has a post on Deadly Viruses.  Like parasitic diseases, e.g., malaria, viruses through the ages have killed simply enormous numbers of people. Now we're facing a future when bacterial illnesses could overtake their status as the prime infectious threats to mankind.

An article in the December 23, 2013 online version of the New York Times described an increased death rate among dolphins, with many dying of viral disease. A number of them also showed evidence of antibiotic resistant bacteria, presumably from environmental contamination. Dolphins have been termed the modern equivalent of the canary in the coal mine, a biological early warning system analogous to the times when miners used to carry caged canaries while at work; if there was any methane or carbon monoxide in the mine, the canary would die before the levels of the gas reached those hazardous to humans.

The New England Journal of Medicine in January, 2013published an article titled "The Future of Antibiotics and Resistance." The lead author, Dr. Brad Spelberg, works where I did my research fellowship. He and two colleagues mention that antibiotic-resistant bacteria are considered, in a major yearly publication by the World Economic Forum  (WEF), to be a leading risk to human health.

The World Economic Forum's (WEF) 2013 publication on Global Risks analyzed fifty possibilities (e.g., economic disparity, religious fanaticism, rising greenhouse gas emissions, terrorism, water supply crises), examining their likelihood over the next decade, the impact if they actually happen and how interconnected they were to each other.  It used those to generate analyses of three major risk cases: one was on the threats to economic/environmental systems, a second on so-called 'digital wildfires" from misinformation, and  The Dangers of Hubris on Human Health, devoted to antibiotic-resistant bacteria.

In a study done in Europe, 50% of French patients experiencing a flu-like syndrome (FLS) expected their physician to prescribe an antibiotic; FLS may be caused by influenza virus or other viruses and antibiotics are not of any use against these viral diseases. The WEF piece mentioned an article reporting 98% of Chinese children seen in a Beijing pediatric hospital for common colds were given antibiotics.

Huge quantities of antibiotics are being used for animals as well.  Animals being raised for their meat are often given antibiotics as growth promoters. A 1950 article in Science News announced results from Lederle Laboratories that lacing the hog feed with trace amounts of an antibiotic could increase the yield of meat by a half. Then in 1977 the FDA sent out a notice that it would withdraw approval of non-medical use of penicillin and tetracyclines, but no hearings on the subject followed that non-binding pronouncement.

A Federal District judge finally ordered those FDA hearings in 2012, but an article online less than two weeks ago said only suggestions to the animal-growing industry have resulted. In 2009, more than 3,000,000 kilograms of antibiotics were given to US patients; in 2010, 13,000,000 kilograms were used for animals.

Back to the Wall Street Journal article: it mentions four new approaches to treatment of these deadly bugs. The two I found most intriguing were research to befuddle the bacteria by working against the signaling chemicals they use to become infectious and using silver to increase the ease with which antibiotics enter the microbes.

There's a way to go before these concepts are translated into bedside medicine, but there is more than a glimmer of hope on the horizon.


Noise-Induced Hearing Loss and Acoustic Trauma

Saturday, December 14th, 2013

I was in the gym recently and, after riding a recumbent bike for a little over an hour, went to the mats to do some stretches. There's usually a class in the room on the other side of a wall and I could see young women exercising in a karate-like manner. But what immediately caught my attention was their background "music," vaguely familiar and incredibly loud. That wasn't the first time I'd heard an ear-threatening sound level coming from that room, but it clearly was the worst. It reminded me off a rock concert I went to many years ago.

I wondered how many of the class members had been exposed to that intensity of sound repeatedly and if it had caused them problems. Then I thought about the instructor who must hear the noise many times a week. I couldn't tell if she was wearing any ear protection, but doubted it.

Later in the day I mentioned the episode to my wife Lynnette who wears hearing aids and is at the gym for Pilates at least three times a week. Sometimes her class has music, playing at a much lower decibel level, but when it does she has mentioned difficulty in hearing the leader's voice calling out what move comes next. She said the women's locker room, again a wall away from the class exercise area, almost shakes when that  other group is in session.

When I thought about the noise levels I sometimes hear (noise is defined as "unwanted sound"); one of the loudest forms is often coming from a car next to me at a stop light with a youngster listening to music while leaving the windows of their vehicle open. I guess that's so we can all listen to their choice of music.

I went back to the basics, trying to understand just how loud that studio must be compared to other environments where noise levels can be dangerous to our hearing and our brains.

Noise is measured in decibels (dB), named after Alexander Graham Bell who invented the "electrical speech machine' we now know as the telephone. The subject took me back to the physics of sound and its perception.When you hear a sound, anything from a whisper to a gunshot, your ears and brain are involved in a complex process that begins with an object, let's say a gong, vibrating in something. That something could be solid, liquid or gaseous, but to simplify even a bit, we'll assume it's ordinary air (I've never heard of anyone hitting a gong underwater, so that's a reasonable assumption.)

The anatomy of the middle and inner ear.

The anatomy of the middle and inner ear.

The frequency of the vibrations (in this case how rapidly the metal moves back and forth) is the determining factor in the pitch of the sound, but the energy of the vibration determines its loudness. So if you strike a gong hard, it emits a louder sound than if you barely touch it. The vibrations move tiny particles toward your ear which acts as a funnel to bring the sound energy to your eardrum, through a series of tiny bony connections to your inner ear.

The minuscule bones, technically the malleus, incus and stapes, but usually called the hammer, anvil and stirrup, amplify the pressure the sound exerts on your ear drum, enabling the next step in the hearing process, motion of fluid in a structure called the cochlea. This is a snail-like spiral with three tubes separated by membranes and tiny hair cells that transmit the sound as electrical impulses to your brain.Which hair cells are moved lets your brain know the pitch of the sound; how many hair cells are moved allows the brain to know how loud the sound was.

Here's a link to a loudness comparison chart. The softest sounds we can hear (e.g., rubbing one finger over another next to an ear) are said to be zero dB, but if you whisper to someone a few feet away, the sound is somewhere between 15 and 30 dB. The scale in logarithmic, so 10 dB is 10 times as loud a zero, 20 dB is 100 times as loud and 30 dB is 1,000 times as loud. Talking  at a normal volume to a friend who is three feet away generates a 60 dB sound, a million times as loud as zero dB. Yes, that amazes me too.

Don't sit in the front row.

Don't sit in the front row.

So the next time you (or your kids or grandkids) want to buy front row tickets to a rock concert, remember the sound level will be 115-120 dB. I had recently  seen an article on the subject of noise-induced harm in The New York Times. Its title was "Fighting Hearing Loss from the Crowd's Roar." Fans at several professional football games had broken a Guinness World record for the loudest crowd noise level. The first game's crowd screamed at a measured 136.6 dB; a short time later, another team's fans registered a 137.5 dB roar.

I found a 2001 ENT grand rounds presentation on "Noise-Induced Hearing Loss" from UTMB, the University of Texas Medical Branch. Nearly one-third of Americans with hearing loss, roughly 10 million total, had impaired hearing due to noise. It is the most common preventable cause of permanent hearing loss. Other, more recent comments, mention associated tinnitus (ringing in the ear) and hyperacusis, sensitivity or intolerance to sound, as associated effects from excessive noise.

If your ears are exposed to even less intense sounds over a period of time, the hair cells and their blood vessels, supporting structures and even nerves can be damaged. The loudest recommended exposure with hearing protection is 140 dB and OSHA, The Occupational Safety & Health Administration sets legal limits for sound intensity in workplaces at 90 dB average over an eight-hour day. If the sound is even louder, the permissible time exposure is shorter; it's cut in half for every 5 dB increase in noise level. So if you work in an environment where the sound intensity averages 100 dB, OSHA would say you should have a two-hour shift.

Another federal group, the National Institute for Occupational Safety and Health (NIOSH) sets its eight-hour cutoff at 85 dB and halves that time for every 3 dB increase. So at 100 dB, NIOSH recommends your shift should only last 15 minutes!

This old cannon might explode if it were fired. Don't be nearby!

This old cannon might explode if it were fired. Don't be nearby!

A sudden, exceeding loud noise can also cause a long-term hearing deficit; this form of noise-induced hearing loss is often called acoustic trauma. An explosion or a cannon going off  near to you might be examples, but other noises in the 130-140 dB range can be responsible for this form of damage to your hair cells.

For the past thirty-two years OSHA has mandated a Hearing Conservation Program to protect every worker in general industry who is exposed to 85 dB or more over an eight-hour shift. It includes baseline and yearly free hearing exams, free hearing protectors, training in their use and evaluation of their adequacy.

But a discotheque may have a 110 dB sound level and even using the OSHA limits, much less the NIOSH levels, you shouldn't be exposed to that level of noise for more than a half hour.

So it's wise to stay away from very intense noise levels, especially outside of your work environment, in places where those OSHA rules don't protect you.

I'm afraid that many of our younger generations will lose their hearing as they are exposed to noise levels we once would have thought to be rare.



Medical Marijuana 2: immingrants to Colorado

Sunday, December 8th, 2013
Smokeable pot or marijuana  brownies is what most officials feared.

Smokeable pot or marijuana brownies is what most officials feared.

This morning's edition of The New York Times had an interesting article on marijuana migrants to Colorado. These aren't people looking for recreational pot, they're parents of kids with intractable seizures. In August, Dr. Sanjay Gupta, a neurosurgeon who was President Obama's initial choice as U.S. Surgeon General in 2009 (he's now CNN's chief medical correspondent), published a bombshell article in CNN Health with the title, "Why I changed my mind on weed." Gupta had previously published a 2009 Time magazine article, "Why I would vote No on Pot", but then undertook an extensive review of past efforts pro and con marijuana. He discovered that the 1970 decision to make the drug a Schedule 1 substance was not based on solid evidence of addictive properties and lack of medical efficacy, but rather on the absence of studies and, presumably therefore, was a political choice, not a scientific one.

The problem, of course, is by making pot Schedule 1, those studies could not be easily done, if at all.

Gupta refers back to a 1943 study in New York City under Mayor LaGuardia. The medical arm of that research concluded smoking pot neither led to addiction nor was it a "gateway drug,"

Gupta also reviewed a huge number of relatively recent U.S. studies of the drug; interestingly, 94% of them were designed to show the dangers of marijuana and only 6% looked at its benefits.

I did find a 2009 article in The Journal of Clinical Investigation, a premier research journal, with the arcane title "Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells," Like most JCI articles it was quite complex, but the bottom line was the scientists involved (from Spain and from Harvard) concluded THC, one of the major chemicals in marijuana, may be useful in fighting cancer. They did not suggest cancer patients should smoke pot!!!! Rather, a chemical pathway uncovered in the study could lead eventually to anti-tumor therapies.

A recent review of research studies on the use of cannabinoids (marijuana contains over 500 of these chemicals with THC and CBD being the most significant) for seizure disorders was titled "Slim Evidence for Cannabinoids for Epilepsy." It noted that marijuana appears to have an anti-epileptic effect in animal studies, but we don't know yet if that's true in people. The extensive literature review only found four human studies, none of high quality, and concluded no reliable conclusions could be drawn at the present time. But CBD appeared to be safe for the relatively short time it was given in these projects.

High quality studies clearly need to be done in this arena.

So why did Dr. Gupta change his mind?

In the first place he felt Americans had been misled by the 1970 decision to classify marijuana as a Schedule 1 drug. And then there is Charlotte's Web, an oil said to be low in THC (the chemical which leads to a pot "high') and chock-filled with CBD which has no psychotropic effects, but appears to have a variety of positive medical effects.

In 2006 a Colorado woman gave birth to twins, one of each gender. When they were only 3 months old, the girl started having seizures, first one, then many. The doctors said her scans and blood tests were normal, but eventually, when she was two and a half, a neurologist at Denver Children's Hospital she had found a rare genetic mutation associated with an intractable type of epilepsy. Another specialist put the child, Charlotte, on a special diet sometimes useful in drug-resistant epilepsy.

A plethora of side effects and, two years later, the return of multiple seizures, drove her parents to a relentless hunt for something that could stop her convulsions. Eventually they heard of a California boy being treated with a cannabis product for the same rare syndrome as their child.

Colorado law demanded two doctors approve her application for a medical marijuana card. Charlotte's mom found a Stanford-trained MD, PhD and a Harvard-trained internist who had significant reservations because of Charlotte's age, but felt all other treatment options had been tried. Both signed the card.

An initial dose of a low-THC, high-CBD product in oil form from a Denver dispensary gave incredible results…no seizures for the first week of treatment. But the oil was in short supply and expensive.

And it's not the optimal form for medical use.

This is not the optimal form for medical use; the high CBD oil may be.

Enter the Stanley brothers, six men who owned a large marijuana dispensary and grew their own plants. They had developed another marijuana-derived oil that was low in THC, while containing lots of CBD. They had also started a nonprofit, the Realm of Caring Foundation, to provide cannabis and its derivatives to those who had major diseases (cancer, MS, seizures, Parkinson's), but were unable to pay market prices for the substances.

Fast forward to Charlotte at age six, having seizures in her sleep only two to three times a month (versus up to 300 a week). Her neurologic status has markedly improved and the oil she takes has been named after her. Dr. Gupta visited her and other patients who have had similar results.

Not all find their panacea in Colorado medical marijuana derivatives, but one of the two physicians who signed Charlotte's card, working with Dr. Edward Maa, an assistant professor of neurology at the University of Colorado School of Medicine, has accumulated a series of eleven such children with drug-resistant major seizure disorders and eight had a decline in seizure frequency of 98-100%. The data is about to be presented at an American Epilepsy Society meeting.

There's another side to the Colorado story, a familiar and sordid one. An August, 2013 article in The Denver Post was titled "Oversight of Colorado medical marijuana doctors remains spotty." It detailed a sting operation which led to a conviction of a Loveland physician who prescribed marijuana for an ankle sprain ten years past and for back pain even the patient said wasn't present. The two state governmental agencies who should be providing oversight of those doctors who provide medical marijuana prescriptions have largely been inactive.

The Colorado State Health Department has referred the names to the board of medicine of a very small number of physicians who account for an inordinate percentage of medical marijuana recommendations . They say these are the outliers, implying the vast majority who prescribe the drug are doing in an ethical and appropriate manner. I'm not so sure that is true and a law enforcement officer has been quoted as saying, "Very little has occurred to any of these physicians until now."

To complicate matters, Colorado voters (and those in the state of Washington) in November, 2012, approved the use of recreational marijuana for anyone over 21 years old. The Justice Department response is captured in an online article "Tolerating Pot With a Frown."

I think medical marijuana is here to stay; we'll see how many careful studies get done to determine who should get actually it.