Vol. 173 July 1, 2017 Bugs and Drugs

July 1, 2017

 

“Eat dirt, and thrive”

 

Since Fleming discovered a mold that produced penicillin which killed Streptococcus bacteria, scientists for decades have been mining soil as a source of new antibiotics. There are so many bacteria competing for nutrients in the dirt that some bacteria will produce toxins to kill their neighbors. The current belief is that soil extraction for new antibiotics has been going on for so long that soil is about tapped out as a source for novel ones.

Antibiotics kill bacteria by attacking their cell walls. Bacteria develop “resistance” to antibiotics with changes in their cell walls that resist the medicinal attack. Individual bacteria cells can’t change their cell walls, but the population of pathogen bacteria as a whole, the “microbiome”, can become “resistant” as the bacteria cells replicate again and again. When only the bacteria which have mutated to ones with a different “resistant” wall remain, the bacteria has become “resistant” to the antibiotic. Your body does not become “resistant”, the bacteria community does..

Viruses have no cell walls, and that is why antibiotics don’t work on viruses, like the ones causing the common cold. Anti-viral medicines against the flu and HIV work by attacking the internal functions of the virus. Some anti-viral medicines attack the virus DNA, others attack the virus RNA, and others attack intracellular proteins or enzymes necessary for virus replication.

Scientists at Rutgers have recently described a whole new class of antibiotics extracted from soil (Italian soil to be exact, if you think that’s important) that don’t work by attacking the cell wall. The new compound inhibits an internal protein, a polymerase, in the bacteria which is necessary for the bacteria to survive. The compound is 10 times less likely to trigger a mutation that leads to drug resistance than current antibiotics. Also it can kill dormant, non-replicating bacteria much better than current antibiotics. Similar compounds that attack polymerases has been successful in treating viruses like Hepatitis C and HIV, but this is the first example of a successful antibacterial effect. It will send many scienticists looking for new antibiotics back to the dirt.

Could this just be another reason to eat dirt? Eating dirt, or geophagia, is a recognized way for animals, and some humans in special situations, to obtain minerals. Pica , eating non-food substances, in a child can indicate that the child is iron deficient or anemic. Pregnant women in Africa are known to eat dirt to enrich their stores of calcium for the fetus. Parrots, bats, and some pregnant women have been observed eating soil with a high clay content to help with gastrointestinal distress. Since dirt can contain lead and other toxins, most people are advised to just take a swig of Kaopectate.

Why not just skip the dirt and go right for the pure mixture of bacteria, a probiotic? In fact, the evidence for the benefits of the use of probiotics is mixed. The use of probiotics has not been dramatically positive in treating diarrhea, eczema, and preventing the side effects of antibiotics. True that probiotics have no significant side effects (the FDA has labeled them as “safe”), but some researchers are concerned that overuse may have deleterious effects on our normal gut bacterial flora.

There are approximately 100 Trillion (that is a “T”) bacteria in our gut. They have been officially awarded recognition as the “gut microbiome”. It is a hot research topic focussing on its roles in digestion, metabolism, immunity, dementia, and even autism. Fecal transplant therapy  (infusion of a solution of healthy donor feces through a nasogastric tube) repopulates the intestine with “good” bacteria as treatment for certain diseases caused by “bad” bacteria (Clostridium difficle) (1) More recently, the dscription of a “breast microbiome” in association with some breast cancers is spurring research into using bacteria as biomarkers in screening for breast cancer.

” The Hidden Half of Nature”, published in 2008, tells a positive story of a couple changing their lives by enriching their garden soil with bacteria-heavy materials while enriching the bacteria of their own intestines by “eating healthy”. One of the authors summed up their approach as: “Mulch your soil, inside and out”.

  1. N Engl J Med 2013; 368:407-415, January 31, 2013
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Vol. 171 May 15, 2017 Medical Updates (Real News)

May 15, 2017

 

“The Only Thing That Is Constant Is Change -”― Heraclitus

 

 


Those TV ads work … for the drug companies.
A study of the effectiveness of TV ads (Direct-to-Consumer Advertising or DTCA) for prescribed testosterone supplements (no effectiveness in men without endocrine disease) in 75 regional markets from 2009 to 2013 showed that the addition of ONE TV ad per household per month for 4 years was associated with an increase in new blood tests of testosterone level, new prescriptions with blood level testing, and new prescriptions without any blood level testing. About 2% of the middle-aged men in this study of 17 million men received a testosterone prescription. (JAMA,Mar 21, 2017)

In other news, the British Medical Journal published a study of over 900,000 men which showed that those taking testosterone were 63% more likely to develop potentially fatal blood clots in the legs or lungs during the first six months of taking it. (BMJ, Nov. 13, 2016)

Vitamin D gets an “F”.
Vitamin D supplements became very much in vogue when some studies suggested that people with low blood levels had a higher risk of cardiovascular disease. BUT, in New Zealand 2500 adults were given 1000 units of vitamin D once a month and a matched group of 2500 were given placebo. The vitamin D blood level doubled in the supplemented adults, but at the end of 3 years both groups had identical rates of adverse cardiovascular events (12%). (JAMA Cardiol Apr 5, 2017)

PSA testing -“D” or “C”? It depends.
In 2012 the U.S. Preventative Services Task Force (USPSTF) gave the PSA blood test screening for prostate cancer a “D” – (not recommended) because of false positives leading to unnecessary procedures and treatment, and the fact that PSA screening prevented less than 1 prostate cancer-related death per 1000 men screened.

In 2017 the USPSTF is upgrading that “D” to a “C” (maybe a small benefit) but only for men aged 55-69. (Dare we call it a “gentlemen’s C” ?) The “D” remains for those over 70. This upgrade for the younger men is based mostly on the emergence of the “active surveillance” option to immediate surgery or radiation for positive PSA tests and biopsy. The USPSTF strongly recommends that physicians 1) explain all the risks and benefits of PSA testing to men from 55-69, 2) be aware of the patient’s “values and preferences”, and 3) practice effective “joint decision-making” with the patient. (J Watch General Medicine May 15, 2017)

In other news, a Michigan study of 431 men with localized prostate cancer discovered by PSA testing and confirmed by biopsy who opted for “active surveillance” rather than immediate surgery or radiation showed that only 31% actually followed the complete “active surveillance” protocol. (PSA testing every 6 months and annual repeat biopsy.) Another 31% complied with just the PSA test repeats, but not the biopsy. 22% did neither repeat PSA tests nor biopsy. Outcomes were not measured in this study, (J Urol Mar 2017)

Aspirin may get a third “A”
Aspirin is well-known to relieve pain, reduce inflammation, reduce fever, and reduce blood clotting. It does that by inhibiting the production of prostaglandins, a hormone-like substance in play in all those conditions. In 2000 scientists discovered that aspirin also increases our production of resolvins which also reduce our inflammatory response. We make resolvins from Omega-3 fatty acid precursors (hence the contemporary popularity of fish oil).

Investigators are very interested in a newly defined, third effect of aspirin which is unrelated to its role in anti-inflammation – aspirin’s interference in the ability of cancer cells to metastasize. Cancer cells apparently need to be coated with clumps of platelets in order to survive their trip through the blood stream to distal sites. In mice, aspirin’s anti-platelet action (the “reducing blood clots” function) has been found to interfere with platelet clumping around the cancer cell and successful migration of the cancer cells through blood vessels is inhibited. (Scientific American May 2017)

Trying to avoid sugary beverages? Don’t jump to diet soda.
A 10 year study monitoring 4000 people without diabetes for strokes and cognitive decline found that people who drank diet soda every day were three times more likely to develop strokes and dementia. In a separate study people who drank more juices and more sugar-sweetened soda than others were more likely to have poorer memory and smaller brains on MRI imaging than the other people. The researchers state clearly that this is not a cause and effect situation, just an “association”. (Stroke April 24, 2017)
“More research is needed.” Of course.
“Water is best.”

Bilingual brains remember their first language, even when they can’t speak it!
Korean-born adults who were adopted by Dutch families before the age of six and who did not speak nor understand Korean were better at distinguishing between the sound contrasts of the Korean language and could pronounce the Korean sounds much better than those Dutch adults who had no exposure to the Korean language as children. This better discrimination of sounds is not genetically based because numerous studies have shown that all infants are capable of reproducing all the sounds of all languages. “Remarkably, what we learn before we can even speak stays with us for decades.” (Duh!) (Royal Society Open Science, Mar 2017)

No federal money to study pistols or pot.
According to David Hemenway, Professor of Health Policy, Harvard School of Public Health, an average of 300 people get shot in the U.S. each day. One-third of them die. Twenty years ago the CDC funded about $2.6 million a year (“a small amount”) for firearms research. Now that funding is ZERO. Since 2006 Congress has pprohibited the CDC from gathering any gun-related statistics and developing a gun-related data base, but there is apparently no formal, official prohibition for funding gun-issue research,; just the CDC’s desire to “stay out of congressional crosshairs”.

NIH apparently has the same reticence. In the past 40 years over 486 NIH grants have been awarded in the areas of cholera, diphtheria, polio, and rabies which have caused 2000 deaths in the U.S. Over the same 40 years while 4 million people were shot in the U.S. , NIH has awarded 3 gun-issue research awards. (Note: this period of time is during the relatively scientific-friendly Clinton, Bush, and Obama administrations .)

Marijuana is still classified by the FDA and the DEA as a Schedule I substance which prevents any clinical trial or study of its medicinal benefits. Medicinal marijuana must have FDA required “drug development” studies to get off Schedule I, and those studies are virtually impossible while it is on Schedule I. (Note: current Attorney General Jeff Sessions said in April 2016: “Good people don’t smoke marijuana”) (Scientific American May 2017)


Vol. 148 May 15, 2016 Fun Facts About U.S. Presidents

May 15, 2016

Hub thumbnail 2015Since we are fully immersed in the Presidential primaries, and I just happened to see an illuminating PBS documentary on the death of President James Garfield, I thought that this week’s blog should be about some U.S. Presidents.

President Garfield was not assassinated. He died of medical malpractice.

On September 19, 1881 a disgruntled office seeker who was denied the post of Paris Consulship shot President Garfield twice as he walked through the Washington, D.C. railroad station. This was 16 years after Lincoln’s assassination but secret service protection for the President did not yet exist. A passing policeman wrestled the shooter, Charles Guiteau, to the ground before he could fire a planned third shot. Garfield died 79 days later from overwhelming infection from the one bullet retained in his body.

Though Lister had been writing about anti-sepsis techniques to prevent infection for twenty years, the wound was repeatedly explored by bare hands and unsterilized metal probes in unsuccessful attempts to locate the bullet for removal. Dr. Willard Bliss, an experienced surgeon who had served during the Civil War, took personal charge of the case, refused access to any other physicians, and steadfastly insisted that the bullet was lodged in the President’s right side. He continued to probe the wound looking for it. Alexander Graham Bell designed a metal detector expressly for finding the bullet. Dr. Bliss allowed him to scan the right side only since “that was where the bullet was.” The metal detector scan was ambiguous, perhaps due to the metal bed springs, but Dr. Bliss declared that it showed that he was right, ” the bullet is in the right side of the back”. Dr. Bliss declared the persistent pus as a “sign of healing”, the raging fevers as caused by malaria (which Garfield’s wife did have), and issued several press releases describing Garfield’s “improvement”. Dr. Bliss denied other physicians’ requests to examine the patient in order to help with the treatment. He clearly did not believe in anti-sepsis and the germ theory, both of which were in the medical literature since the 1860’s. Dr. Bliss also rejected the new fangled stethoscope and listened to Garfield’s terminal pneumonia by pressing his ear to the patient’s chest. Emaciated, septic, and covered with carbuncles and abscesses Garfield finally died when his splenic aneurysm burst.

An autopsy revealed that the bullet was lodged in Garfield’s left side of his back, had missed all vital organs, and it was not considered to be a lethal wound. Dr. Bliss was roundly criticized by prominent physicians and the press “for practicing not in accordance with well-defined and acknowledged surgical precepts.” Garfield’s death is considered by some to be a water shed or dividing point in American medicine with subsequently more positive journal articles about anti-sepsis, the development of nurse educational standards (trained nurses were rare and Cabinet wives provided most of his nursing care), and the beginning of the trend toward medical specialization.

Ronald Reagan got his nickname because in those days no one was routinely testing children’s vision before starting school. (1)

President Reagan got his nickname “Dutch” because his parents knew he could not see straight and had his hair cut so that bangs fell over his eyes. The “little Dutchman haircut” gave him his nickname. Reagan was severely near-sighted and developed hobbies involving close-up things like butterfly collecting. He sat in the front row of the classroom to try to see the blackboard. No one picked him for their baseball team because he was a lousy hitter and often got hit by the ball when at bat. When he was thirteen and riding in the country with his family one Sunday he picked up his mother’s eyeglasses which she had left on the car seat. The shout of amazement when he suddenly saw the rest of the world for the first time almost caused his father to crash the car! The next day the eye doctor measured his vision as 20/200 and gave him some thick lenses in ugly frames. His new-found confidence led him to work as a lifeguard for 7 summers, and he saved 77 people, by his count, while wearing his glasses.

Ulysses S. Grant was a horse whisperer long before Nicholas Evans ever wrote a word or Robert Redford ever acted.

When Ulysses was very young a traveling circus came to town and the ringmaster issued a challenge to all the youngsters to try to ride a miniature pony. Ulysses immediately volunteered, but was skipped over for several older boys. When they were all thrown by the pony Ulysses got his chance. Despite the pony’s rearing, kicking, and pawing at the sky Ulysses dug his heels in and held on to the mane until the pony quieted. Ulysses guided him quietly around the ring as the crowd went wild! By the time he was five he could stand up on a trotting horse holding the reins in his hand. By 7 he found a job hauling wood in a horse-drawn wagon. With the money saved from the job he bought his own, first horse. He was not a savvy “horse-trader”, paid a bit too much, and was dubbed by his friends as “Useless Grant.” By age 9 farmers were hiring him to break their unruly colts. His early reputation in the Union Army was based largely on his superb horsemanship. As President he expanded the White House stables and sheltered more horses than any other President. He preferred riding a horse in Washington, D.C. rather than being chauffeured around in a carriage and once got a $5 ticket for speeding while President.

Obama’s early writings predicted the future.

In response to a third grade teacher’s request to write about “What I Want To Be in the Future” Barrack Obama wrote the following:

“My name is Barry Soetoro.
I am a third grade student at SD Asisi.
My mom is my idol.
My teacher is Ibu Fer. I have lots of friends.
I live near the school. I usually walk to the school with my mom, then go home by myself.
Someday I want to be president. I love to visit all the places in Indonesia.
Done.
The eeeeeeeeend.”

Hm-m-m??   I-N-N-teresting.

References:
1. All three of these stories about Presidents as kids are from “Kid Presidents: True Tales of Childhood from America’s Presidents” by David Stabler and Doogie Horner, Quirk Productions Inc., 2014;  www.quirkbooks.com


Vol. 141 February 1, 2016 Newspaper Update from Z to A

February 1, 2016

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All I know is just what I read in the papers.
Will Rogers

You can never get all the facts from just one newspaper,
and unless you have all the facts, you cannot make proper
judgements about what is going on.
Harry S. Truman

I usually start thinking about what to write in my next blog a few days before the 1st and 15th of the month. This Tuesday, January 26 I picked up a newspaper and was immediately struck by the number of medically relevant articles (some of which contained “medical fun facts”, from front page headlines to blurbs in the business section. Here are some of them.

El Salvador Advises Women to Stop having Babies for 2 Years Because of the Zika Virus (front page)
Zika is a mosquito-borne virus that causes minor symptom in an adult but can cause severe microcephaly and even death in a fetus. First reported n Brazil, 5000 adult cases have been identified in El Salvador. The rate of infected fetuses is not known. Turns out that the above recommendation has not caused much of a stir in El Salvador. In comparison to other developing countries its birth rate is low. Salvadorian women list their reasons as:  1. fear of violence, 2. poor economics and widespread poverty, and 3. their acceptance of contraception (despite the church’s stand), and now 4. Zika virus. Some have gone so far as to deride the recommendation as a government conspiracy to reduce the birth rate in “this most densely populated country on the entire continent” (per their Health Minister). Zika has caused more of a stir here, and our CDC has advised pregnant U.S. citizens not to travel to Central and South America.

As someone who is not usually receptive to conspiracy theories, I myself feel a bit concerned about “just who” is controlling information. This story sort of “dribbled out” as a minor note only to explode rapidly on the front page with lots of “known facts.”

Grand Jury Indicts the Accusers of Planned Parenthood (lead story on front page)
The Texas grand jury convened to investigate the criminal activity of Planned Parenthood as alleged by the Center for Medical Progress has instead indicted the Center’s founder Mr.Daleiden and Ms. Merritt, makers of the “selling baby parts” videos. After two months of investigating the evidence the grand jury issued indictments for a federal offense (illegal changes made to fake California driver licenses) and a misdemeanor (offering $1600 per sample to Planned Parenthood for fetal tissue which is against existing law).

That this grand jury was impaneled by a Republic DA in a Republican state with a Republican governor made this unexpected result immediately newsworthy because of the rabid Republican-led Congressional attacks on Planned Parenthood. Planned Parenthood noted that this was the eleventh investigation of them that found no wrongdoing.

Gluten-Free Diet Did Not Benefit Competitive Athletes (first page of Well Section)
A two week double-blind study of 13 seriously training, competitive cyclists eating indistinguishable gluten-free and gluten-laced sports bars revealed no difference in general feeling, performance, or inflammatory markers related to sports bar type. The researcher remarked that, “Unless you are having gastrointestinal problems a gluten-free diet will probably provide no benefit… I hope that people learn to be more objective in terms of what they hear and read about gluten-free diets and nutrition in general.” (1)

EKG Screening For College Basketball Players? (Op Ed page)
When the chief medical officer of the NCAA recommended in March 2015 that all male college basketball players should get a electrocardiogram (EKG) because of the risk of sudden cardiac death, 100 college team physicians reacted very loudly. They strongly pointed out that the inaccuracy of EKG screening causes lots of expensive and unnecessary medical investigation of commonly occurring “false positive” results. Another problem is that rates of sudden death in these students has been calculated to be all the way as low as 1 in 50,000-100,00 to as high as 1 in 1,300 (higher than the risk of dying in an auto accident). The American Heart Association and the American College of Cardiology both oppose EKG screening of 460,000 U.S. college athletes. Some colleges do require it. The newspaper editor suggests “maybe just for high-risk basketball and soccer players”. “More data later” remains the medical mantra.

More Gun Violence,  (multiple pages, no surprise,)
       Dorchester, Boston: A 34 year old male was shot in the abdomen at 2:35 PM because he had taken another male’s parking spot. The shooter sped away in a black BMW.
         East Boston: At 2 PM on the inbound Blue Line of the MBTA a man getting off the train turned around and fired 5 shots at a man he had been arguing with. He hit the 29 year old target and a 43 year old man just standing on the platform.
        Windham, Maine: A 33 year old man arising from bed in his house in the early morning hours opened fire with a shotgun at a figure at the end of the stairs that he thought was an intruder. It was his wife who had gotten up earlier.
        , Mass: An intoxicated 60 year old man was arrested for firing a gun at a snowplow driver in Plymouth Saturday night.
…………(NY Times probably doesn’t even report such common happenings)

Autism Therapies to be Tested on Genetically Engineered Monkeys (bottom of page in Science section)
Mice are not useful research models for studying social cognition and interaction, so scientists in China have turned to genetically engineered monkeys to test drug therapies for autism . The monkeys born from eggs injected with the human MECP2 gene (associated with autism) showed more repetitive behavior, more stress responses, more defensive behavior, more grunting when people gazed at them, and less social interaction than other monkeys. The higher cost of developing such monkeys compared to mice, the difficulty of equating monkey behavior to human autistic behavior, and the fact that the implanted gene is found only in the monkey’s nerves and not throughout their brains means that this “break-through”  may not be all that helpful(2). Though it could be a good science fiction plot. Synopsis: “Lab break-in releases autistic monkeys. Presidential primary candidates attack (or defend) animal rights activists, but most push their campaign ad content up to a higher reading level.”   

References: (other than the January 26, 2016 NY Times and Boston Globe)
1. Medicine & Science in Sports & Exercise, Dec. 2015, Dana Lis
2. Nature, January 2016, Institute of Neuroscience, Chinese Academy of Science,Shanghai


Vol. 139 January 1, 2016 HEROIN: Cape Cod, USA

January 1, 2016

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A HBO documentary shown on December 28, 2015

 As a pediatrician and a parent I found this moving documentary of eight white, middle class heroin addict kids from stable families on Cape Cod to be very disconcerting. It was brutally honest with several scenes of addicts preparing and injecting heroin. The repetitive, “almost-expected”, relapses after detox, and the seemingly casual acceptance of inevitable drug deaths of other addicts set a tone of hopelessness. The onset of addiction in half of these addicts followed standard treatment with opioids for post-accident or post-surgical pain. 30-day detox programs, despite their noble intent, were depicted as mostly fruitless in the long run, like spitting in the ocean. (None of the eight addicts appeared to be enrolled in a heroin-replacement program – Suboxone or methadone) The recognition by the addicts that their craving drove them into behavior they themselves detested confirmed that insight is not enough.

 One addict said that “one dose of heroin was all that was needed to get you addicted”, but NIH statistics suggest that 23% of first heroin users become addicts. Even so, those one-in-four odds are worse than the odds of Russian roulette with a six-shot revolver! One could consider appropriate opioid treatment for post-surgery pain as a “screening test” to find those one-in-four addicts!

For the past decade physicians have been told that the patient should direct pain control. “How bad is your pain on a scale of 1 to 10?” Hospitals and doctors were, and are still, graded on their ability to reduce patient-reported pain quickly. Many of us physicians remember the pain control conferences that basically told us “you are not giving enough”. Perhaps that mind set contributed to the current easy access to opioids.

The Massachusetts Medical Society just promulgated lengthy opioid therapy guidelines consisting of 11 statements for acute care and 16 statements for chronic treatment (over 60 days). The guidelines are sprinkled with words like “function and pain”, “quality of life”, “short-term trial”, “minimum dosage”, “partial-fill prescriptions”, “low-dose sequential prescription”, and “useful consultation with a specialist or a second opinion”. Treatment of cancer. hospice, palliative care, and hospital inpatients is exempt from the guidelines.

The simple patient pain scale of 1 to 10 has been trumped by 11-16 sentences. If you think that is an overstatement then consider these words in the new guidelines,  “The guidelines will provide valuable guidance to physicians [mostly primary care] in their practices and as evidence of best practices and to the Board [of Registration in Medicine] in its responses to patient complaints, accusations of substandard care, or accusation of inappropriate prescribing.” [emphasis added].

The multiple pathways to addiction, its frequent appearance in several members of a family, and on functional MRIs similar active areas of the brain common to all types of addicts suggest a genetic basis of addiction. If that is true, than the cure for heroin addiction in the long run will depend on identification of the responsible genes and the development of drugs that will block or modify those specific genes.

In the short run, maybe we can do more in the U.S. to reduce the harms of addiction; overdose deaths, infectious diseases, and criminal behavior. One mother in the parents’ group eloquently summed up the need to “destigmatize” heroin addiction. ( “No one sent me casseroles when my son died of an overdose.”) To “destigmatize” addiction we will need to “decriminalize” it and treat it as a medical condition. Other countries (Switzerland 1994, Portugal 2000, Vancouver B.C. 2003, Netherlands 2009, Germany 2009, and U.K. 2009) have done that with both “heroin-replacement” and “heroin-assisted” treatment programs. Those programs have resulted in a reduction of overdose deaths and AIDS/Hep C infections WITHOUT increasing drug use.

According to the Boston Globe the “supervised injection site” in Vancouver (called “Insite”) has been shown by 30 peer-reviewed studies to have “saved thousands of lives, saved millions of dollars in both health care and public safety costs, reduced transmission of AIDS and hepatitis C, and promoted entrance into treatment without increasing drug use or drug-related crime”. (1) The Cato Institute studied the results of the successful Portugal program in 2009 and confirmed the same positive results. Critics remarked that such a model would not work in the U.S. because of our size, heterogeneity, and politics.

Isn’t that a shame?

References:
1. Boston Globe, December 27, 2015, K5, “Massachusetts needs safe injection sites”


Vol. 132 September 15, 2015 BUGS: Can’t Live Without Them, Can’t Live With Some of Them

September 16, 2015

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 “Germs make us sick, but everyone focusses on the harm.
And it’s not that simple, because without most of these organisms,
we could not survive.”
– Martin Blaser, MD; Professor of Microbiology, NYU School of Medicine

Bacteria (bugs) on and in our body outnumber our own cells by about 10 to 1. They only comprise 1-3% of our total body mass or up to about 3 pounds. but they essentially make life possible, as well as occasionally cause us great harm. That bacterial crowd, with its companions of fungus, protozoa  other one-celled critters, is called a microbiome (“microbes that share our body space”). We inherit about 23,000 genes from our parents. Our microbiome contains 4 MILLION, and they are always working.

The National Microbiome Project funded by NIH for $115 million and completed in 2012 confirmed many associations between our bacteria and both health and illness. By our bacteria I mean “our” bacteria. Each person develops a unique microbiome starting with maternal bacteria received during birth. By age three years our microbiome is stable, but can be altered by antibiotics, what we eat, and sanitation practices. The “microbiome fingerprint” of an individual’s stool is distinct and can correctly identify a second stool from that same individual a month later 80% of the time.

Most of the bacteria we live with reside in our intestines. Roughly 70-80% of our feces is made up of bacteria living peacefully in our gut helping us to digest food, absorb sugar, protecting us from auto-immune disease, and maybe even to communicate with our brain. Certain groups of gut bacteria in mice have been shown to affect the blood-brain barrier, to make it more open, “to leak”, which has spurred some researchers to study the effect of gut bacteria on mental health. Associations between obesity, diabetes, and auto-immune diseases like Crohn’s and Irritable Bowel Syndrome (IBS) and the gut microbiome in laboratory mice have already been made.

Some gut bacteria in mice have been found to have two different, interchangeable physical shapes which can sense the environment (the kind of food passing by) and change from one shape to the other, just like a silicon chip. Crohn’s disease was long thought to be an infections disease, but is now considered a non-infectious inflammatory disease. In fact, the absence of one particular bacteria in mice reproduces Crohn’s disease symptoms in them. Human clinical researcher of the microbiome is flourishing.

Balance within our microbiome is important. Clostridium difficile, a pathogen when it overgrows in our gut when competing bacteria are knocked out by prolonged use of antibiotics, can cause debilitating diarrhea, dehydration, malnutrition, and even death. “Clostridial clusters”, a group of non-pathogens, on the other hand can detect sugar in the gut, increase insulin sensitivity, and may protect against the development of diabetes. The recently developed treatment of performing fecal transplants from healthy people to patients with C. difficile infections might be more readily accepted if we called them “microbiome transplants”.

What’s New?
Antibacterial soaps containing triclorsan have been found to be no more antibacterial than soap and water after 40 years of study reviewed by the FDA. Because of recent concerns about the effect of triclorsan on hormone levels and the growth of drug-resistant bacteria in lab animals, the FDA will require manufacturers to prove that their anti-bacterial soap or cleanser is better than soap and water or change its claims or cease its sale by 2016. Anti-bacterial solutions (Purell) are effective because they contain alcohol.

A recent study of the treatment of acute appendicitis with antibiotics alone (24 hours of high dose IV and then 10 days of oral antibiotics) has shown that in selected cases that non-operative treatment is as successful as surgical treatment. Long-term follow-up of these patients remains to be done.

The microbiome of the subway was studied in 2013 by Weill Cornell Medical School investigators who collected and analyzed hundreds of DNA samples from the underbelly of New York City. The good news is that very few samples had the DNA of disease-causing bacteria, and only 1% was identifiable as human bacterial DNA. The more striking fact is that “48% of the DNA found did not match any known organism”. Now, the investigators say that’s because our databases of genomes are incomplete, but I think that there is a Stephen King novel waiting to be written there.

References:
1.  Scientific American, June 2012,, The Ultimate Social Network, Jennifer Ackerman
2.  Scientific American, Feb, 2015, Innovations In, The Microbiome
3.  Weill Cornell Medicine, Vol. 14, No. 1
4.  New Yorker, Oct. 22, 2012 p.32, “Germs Are Us” by Michael Specter
5.  Microbes can be used to identify individuals, Boston Globe, May 18,2015, B4


Vol. 131 September 1, 2015 Current, Recurrent Controversies

September 1, 2015

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“Anachron’s Law:
There is no myth which is so irrational that no one will believe it.
Anachron’s Corollary:
There is no truth which is so obvious that everyone will accept it.”
George Hammond

“How Much Is That Pill In The Window?”:
It costs either $2.6 BILLION or $1.4 BILLION to develop a new drug depending on which report you believe… the Tufts Center for the Study of Drug Development (supported in large part by drug companies) or Jeffery Avorn, MD of the Division of Pharmacoepidemiology and Pharmoeconomics of Harvard Medical School. The discrepancy is important since the high price of drugs is becoming a hot topic in this pre-election year. Read this NEJM article to get a glimpse of the smoke and mirrors used in such calculations (how to calculate capital costs?, what is a “self-originated” drug?, how much of R&D costs are covered by public tax money (NIH grants)?, what are R&D and what are marketing costs?, etc.). (1)

  • 80% of new compounds fail to meet expectations and are abandoned during development. This, of course, raises the calculated cost of developing the successful ones.
  • Both reports agree that the time required for new drug approval by the FDA has decreased to the point where it as fast as, or faster than other countries.

“Gadar” is faulty :
Ten years of research has not appreciably advanced our understanding of what makes people gay according to a “state-of-the-art” review of research into sexual orientation held every five years in a remote location. This year’s conference was held at the University of Lethbridge in Western Canada. The sharp dichotomy between nature (genetics) versus nurture (cultural) causes, the focus of numerous “twin studies” in many countries over many years, has been significantly blurred. The search for the “gay gene” has been tempered by the realization that at least 150 genes are involved in determining “something as simple as your height.” (2)

A new concept, the “environment of the womb”, has recently received greater research interest, but data remains inconclusive. The “environment of the womb” swirls with all sorts of different, and changing, levels of hormones and proteins for 9 months, and researchers  continue to look for its effects on the fetus – “epigenetics”. “Genes are the ingredients of grandma’s apple pie. Epigenetics is the recipe of how she actually makes it.” (2)

The scarce support of sexual orientation research is due in large part to societal controversies  (hence the remote locations for conferences to reduce easy access for “Spotlight Investigative Teams” roaming for hot topics). I wonder if such research is even worth it at all. Any research conclusion will likely be ignored by those people with the strongest negative opinions about sexual orientation because many have clearly shown no acceptance of scientific evidence about anything.

“Low-T” is another manufactured diagnosis:
Despite the lack of scientific evidence showing any benefits, 2.2 million men were prescribed testosterone in 2013 for “age-related hypogonadism”, a brand new diagnosis limited to aging men and apparently coined in response to a demand for testosterone prescriptions. Most of the men are 40 to 64 years old, and one-third of them had never had their actual testosterone blood level checked prior to the prescription. The authors of this report suggest that direct-to-consumer marketing for the improvement of “low-T symptoms” is a major reason for this wide-spread, increasing usage. The FDA has identified a “weak signal” that testosterone usage has adverse cardiac effects, and is concerned … so they have… “recommended some drug label revisions”. (3)

“Lingering Lyme”:
The CDC notes that one in five patients treated for Lyme disease may develop a persistent syndrome of fatigue and other symptoms known as “post-treatment Lyme syndrome”, and no one knows what causes it. It is NOT cured by continuous long-term antibiotics. There is new laboratory animal evidence that some of the organisms causing Lyme go into a “dormant state” when under antibiotic attack. They are NOT resistant to the antibiotic. The cell metabolism function that is attacked by the antibiotic just shuts down temporarily when the antibiotic is present, and so the organism survives. The researchers found that reintroducing the same antibiotic in the lab animal after a time off antibiotics subsequently killed these “persister” organisms. This is a new direction of inquiry in Lyme disease, but not everyone believes in “persisters” and “pulsed antibiotics”. They won’t believe, and shouldn’t, until all four of Koch’s postulates  for establishing a link between a disease and an organism are met. (4)

“Water, Water Everywhere…but not needed”:
The persistent myth that 8 glasses of water will keep you healthy was apparently initiated by readers of a 1945 Food and Nutrition Board recommendation that people need 2.5 liters of water a day. BUT, the readers ignored the next sentence that read “most of that quantity is contained in prepared food” … like fruits, vegetables, juice, coffee, tea, and even beer. Prospective studies have failed to find any benefit on skin elasticity, kidney function, “healthy appearance”, disease-free state, or mortality in those healthy people who increase their water intake. A recent study using a urine osmolality of 800 mOsm/kg (a measure of concentration) as the “normal” value in children concluded that more than half of 4,000 symptom-free, healthy children were “dehydrated”! It would seem that we should throw that particular “normal” standard out the window … or at least into the crapper. (5) Water is good for you, but, let’s face it, you really don’t need take a water bottle with you in the car when you go to pick up the mail.

References:
1. “The $2.6 Billion Pill – Methodologic and Policy Considerations”, Jeffery Avorn, MD, NEJM 372;20, May 14, 2015 .
2. “What Makes People Gay?- Revisited” , Neil Swidey, Boston Globe Magazine, August 23, 2015,
3. “Testosterone and ‘Age-Related Hypogonadism’ – FDA Concerns”, NEJM 378;8, Aug 20, 2015
4. “Lingering Lyme”, Scientific American, Sept. 2015, pg.17
5. “The Persistent Health Myth of 8 Glasses of Water A Day”, Aaron J. Carroll, MD, NY Times, Aug. 25, 2015, pg. A3


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