Thursday, November 12, 2020

Best Medicine: Free from Good Friends.

I have stated in the past that the best advice in life is often free, like those from your wise aunt or uncle, if you are lucky enough to have one.

Perhaps I need to modify that now that I have read the following book by Jay Neugeboren.

In life, it is lucky to have school friends that might one day save your life. 

No, it is not about money.
 
Medicine.
 
I suppose without sounding racist, it helps if you are Jewish, went to a Jewish school as you are likely to have school friends who are good doctors.
 
As they say, God works in mysterious ways!
 
I was in the middle of some Scandinavian Fjord on a cruise when I came across a book called Open Heart. Yes, old habits die hard and I still find myself drawn to books about medicine or other people’s medical stories.
 
The Cruise ©2012 Am Ang Zhang


It is peculiar that the commonest diagnosis the average punter, sorry patient is going to hear from their doctor is:
 
Yes: It’s viral.
 
Well, remembering my biology, these creatures are smaller than bacteria and is not really easy to cultivate.
 
Or is it just a way of saying to the punter/patient, go home and do not ask for the antibiotic.
 
Now, it may well be OK if it were a simple cough. But what if you were told it is a viral cardiomyopathy?  
 
 
Now, this is getting serious.
 
Yet this is what happened and it happened to Jay Neugeboren
after some investigations by two doctors, one a cardiologist.
 
About Jay Neugeboren:
Did he smoke?  No!
Was he overweight?  No! 5’7 150lb.
Did he exercise?  Yes, swims a mile every day and plays tennis  full court basketball regularly.
 
He must have a high cholesterol or BP or family history, it just is not right: No, he had no family history of heart disease, and had normal blood pressure, and better-than-normal levels of cholesterol (both 'good' and 'bad').
 
His symptoms:
 
“I had, however, for two months prior to the surgery, been concerned about some shortness of breath I experienced, if intermittently, while swimming, and by an unfamiliar, sporadic pain -- more like a burning sensation -- in my back, between my shoulder blades. When my family doctor suggested I have a check-up with a cardiologist, the cardiologist performed an echo-cardiogram and diagnosed 'a viral cardiomyopathy.' But he saw no urgency in my situation.”
 
Call his friend 3000 miles away:
At the same time, I had been talking regularly with a childhood friend, Richard Helfant, who was a cardiologist in Los Angeles, and had been Chief of Cardiology at Cedars-Sinai Hospital in Los Angeles. When I told him of the viral cardiomyopathy diagnosis, he shouted into the phone, "It's not viral, goddamnit -- I want you in the hospital as soon as possible."

So, to cut the long story short, a healthy New York Times author of some 20 books with no family history of heart disease, a better than normal cholesterol level non smoking 1 mile swimmer that would have been classed as healthy by NICE standards had at the age of 60 --had two of his three major coronary arteries turned out to be 100% shut down, and the third major artery, the LAD (Left Anterior Descending Artery, the so-called 'widow-maker') was more than 95% shut down.

His life was saved by emergency quintuple bypass surgery.
 
What went wrong or what went right?

His childhood friend had made an accurate diagnosis from 3000 miles away because he knew his friend and thus could place his specific symptoms in the context of his full story. What the cardiologist who had misdiagnosed him had done was to pay more attention to tests and numbers and, thus, to forget about the pain between his shoulder blades, which symptom -- referred pain from the heart -- was inconsistent with a diagnosis of viral cardiomyopathy.

His operation took six and half hours at Yale, New Haven Hospital: Medicine at its best and that was over 13 years ago.


It is also not comforting that a study in 1997 of 453 residents in internal medicine and family practice revealed that they failed to identify the distinctive sounds of common heart abnormalities with a stethoscope 80 percent of the time. True, using a stethoscope, listening to the patient and taking a careful history may not be the only ways to accurately diagnose heart disease. But in the words of Dr. Bernard Lown, inventor of the defibrillator, listening to the patient and taking a careful history remains ''the most effective, quickest and least costly way to get to the bottom of most medical problems.''


My old friend the cardiologist has similar concerns. ''The diagnostic acumen of the physician at the bedside, on the phone or in the office, has been severely compromised,'' he told me. ''Because the mind-set has become, 'Well, the tests will tell me anyway, so I don't have to spend a lot of time listening.' ''


…….I worry that our continued focus on medical testing and prescription drugs as the primary ways of preventing heart disease will distract us from a more important element in treating illness: the well-trained doctor who knows his patient.












..….listen to the patient
and
the patient will give you the diagnosis……
 
William Osler 1849 – 1919


Saturday, October 10, 2020

World Mental Health Day: Doctor's Suicides: Maudsley & Lithium!


Atacama where Lithium is extracted  

© Am Ang Zhang 2015

One of my ex-juniors, now retired, called to ask if I have read about another young doctor's suicide. How very sad! If we look back there has been many such suicides and it is sadder that many are very talented people.                   Iris Chang & Nanking: Denial!


Dr. Baldessarini of Harvard:

“Lithium is far from being an ideal medicine, but it’s the best agent we have for reducing the risk of suicide in bipolar disorder,” Dr. Baldessarini says, “and it is our best-established mood-stabilizing treatment.” If patients find they can’t tolerate lithium, the safest option is to reduce the dose as gradually as possible, to give the brain time to adjust. The approach could be lifesaving.

In recent write ups about antidepressants, there is no mention of Lithium. The Cockroach Catcher first worked with one Australian Psychiatrist that worked with Cade and I was, so to speak, very biased towards Lithium. Yes, Lithium has side effects that might be serious. But hang on, you get to live to experience it. Think about it.


"Many psychiatric residents have no or limited experience prescribing lithium, largely a reflection of the enormous focus on the newer drugs in educational programs supported by the pharmaceutical industry."


One might ask why there has been such a shift from Lithium.

Could it be the simplicity of the salt that is causing problems for the younger generation of psychiatrists brought up on various neuro-transmitters?

Could it be the fact that Lithium was discovered in Australia? Look at the time it took for Helicobacter pylori to be accepted.

Some felt it has to do with how little money is to be made from Lithium. After all it is less than one eighth the price of a preferred mood stabilizer that has a serious side effect: liver failure.

 
Perhaps it is in the British History:



First, why a small group from the Maudsley Hospital in the 1960s could, in an almost malicious manner, have sown scholarly confusion about the true effectiveness of lithium. Aubrey Lewis, professor of psychiatry and head of the Maudsley, considered lithium treatment “dangerous nonsense” (). Lewis’s colleague at the Maudsley, Michael Shepherd, one of the pioneers of British psychopharmacology, agreed that lithium was a dubious choice. In his 1968 monograph, Clinical Psychopharmacology, Shepherd said that lithium was toxic in mania and that claims of efficacy for it in preventing depression rested on “dubious scientific methodology” (). Shepherd also scorned “prophylactic lithium” in an article with Barry Blackwell (). Moreover, Shepherd was publicly contemptuous of Schou. He told interviewer David Healy that Schou had put his own brother on it, and that Schou was such a “believer” in lithium that he seemed to think “really there ought to be a national policy in which everybody could get lithium”

Like Covid vaccine now, if developers put brothers or family members on it, we would trust it more.

Quote: In retrospect, “the miracle of lithium was not its treatment of acute mania,” as Dennis Charney at Yale University put it at a 1995 meeting of the Psychopharmacologic Drugs Advisory Committee of the FDA. “Neuroleptics, and even high-dose benzodiazepines, are quite effective for the treatment of acute mania. … The issue is prevention of relapse” (). Indeed, this is the issue, and the mystery is why the FDA has not accepted the prophylaxis of depressive disorder—“bipolar illness,” if one will—as an indication.

With the exception of ECT, lithium is the single most effective treatment in psychiatry. Its side effects are easily manageable, and many patients stay on low-dose lithium for decades. Its benefits, in terms of the relief of mania and the prophylaxis of depression, are incalculable. In assessing the history of lithium, therefore, two questions present themselves:

First, why a small group from the Maudsley Hospital in the 1960s could, in an almost malicious manner, have sown scholarly confusion about the true effectiveness of lithium. Aubrey Lewis, professor of psychiatry and head of the Maudsley, considered lithium treatment “dangerous nonsense” (). Lewis’s colleague at the Maudsley, Michael Shepherd, one of the pioneers of British psychopharmacology, agreed that lithium was a dubious choice. In his 1968 monograph, Clinical Psychopharmacology, Shepherd said that lithium was toxic in mania and that claims of efficacy for it in preventing depression rested on “dubious scientific methodology” (). Shepherd also scorned “prophylactic lithium” in an article with Barry Blackwell (). Moreover, Shepherd was publicly contemptuous of Schou. He told interviewer David Healy that Schou had put his own brother on it, and that Schou was such a “believer” in lithium that he seemed to think “really there ought to be a national policy in which everybody could get lithium” (50, see p. 249). [In a separate interview with Healy, Schou confirmed that the family member was his brother (36, see p. 267)]. Lewis and Shepherd were major figures in the field, and their poorly grounded objections to lithium doubtless steered many practitioners away from a beneficial agent. [Years later, when questioned about this mad campaign against lithium, Shepherd said that English psychiatry did not distinguish between psychogenic and endogenous depression, and if lithium were accepted, “all doctors in England would use it against all types of depression, with the result that many patients not in need of it would only suffer damage from it—therefore lithium must be ravaged with fire and sword” ()].


 Atacama where Lithium is extracted  © Am Ang Zhang 2015

Lithium: The Gift That Keeps on Giving in Psychiatry

Nassir Ghaemi, MD, MPH
June 16, 2017

At the recent American Psychiatric Association annual meeting in San Diego, an update symposium was presented on the topic of "Lithium: Key Issues for Practice." In a session chaired by Dr David Osser, associate professor of psychiatry at Harvard Medical School, presenters reviewed various aspects of the utility of lithium in psychiatry.

Leonardo Tondo, MD, a prominent researcher on lithium and affective illness, who is on the faculty of McLean Hospital/Harvard Medical School and the University of Cagliari, Italy, reviewed studies on lithium's effects for suicide prevention. Ecological studies in this field have found an association between higher amounts of lithium in the drinking water and lower suicide rates.


These "high" amounts of lithium are equivalent to about 1 mg/d of elemental lithium or somewhat more. Conversely, other studies did not find such an association, but tended to look at areas where lithium levels are not high (ie, about 0.5 mg/d of elemental lithium or less). Nonetheless, because these studies are observational, causal relationships cannot be assumed. It is relevant, though, that lithium has been causally associated with lower suicide rates in randomized clinical trials of affective illness, compared with placebo, at standard doses (around 600-1200 mg/d of lithium carbonate).

Many shy away from Lithium not knowing that not prescribing it may actually lead to death by suicide. As such all worries about long term side effects become meaningless. 

Will the new generation of psychiatrists come round to Lithium again? How many talented individuals could have been saved by lithium?

APA Nassir Ghaemi, MD MPH
  • In psychiatry, our most effective drugs are the old drugs: ECT (1930s), lithium (1950s), MAOIs and TCAs (1950s and 1960s) and clozapine (1970s)
    • We haven’t developed a drug that’s more effective than any other drug since the 1970’s
    • All we have developed is safer drugs (less side effects), but not more effective
  • Dose lithium only once a day, at night
  • For patients with bipolar illness, you don’t need a reason to give lithium. You need a reason not to give lithium  (Originally by Dr. Frederick K. Goodwin)



Cade, John Frederick Joseph (1912 - 1980)
Taking lithium himself with no ill effect, John Cade then used it to treat ten patients with chronic or recurrent mania, on whom he found it to have a pronounced calming effect. Cade's remarkably successful results were detailed in his paper, 'Lithium salts in the treatment of psychotic excitement', published in the Medical Journal of Australia (1949). He subsequently found that lithium was also of some value in assisting depressives. His discovery of the efficacy of a cheap, naturally occurring and widely available element in dealing with manic-depressive disorders provided an alternative to the existing therapies of shock treatment or prolonged hospitalization.

In 1985 the American National Institute of Mental Health estimated that Cade's discovery of the efficacy of lithium in the treatment of manic depression had saved the world at least $US 17.5 billion in medical costs.

And many lives too!

I have just received a query from a reader of this blog about Lithium, and I thought it worth me reiterating my views here.      It is no secret that I am a traditionalist who believes that lithium is the drug of choice for Bipolar disorders.
Could Lithium be the Aspirin of Psychiatry? Only time will tell!

Wednesday, October 7, 2020

The Nobel Prize in Chemistry 2020

 


7 October 2020   https://www.nobelprize.org/prizes/chemistry/2020/press-release/

Also: https://www.nobelprize.org/prizes/chemistry/

The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Chemistry 2020 to

Emmanuelle Charpentier  www.pscp.tv/w/ckye6DFETEtCZGtiV1hXRUp8MWxEeEx5cEVxalJLbQ3gvbMuVUdCLtZyl1c88KgK2x3D8Fs2rCueROJLPYY7?t=1m33s
Max Planck Unit for the Science of Pathogens, Berlin, Germany

Jennifer A. Doudna
University of California, Berkeley, USA

“for the development of a method for genome editing”

 

Genetic scissors: a tool for rewriting the code of life

Emmanuelle Charpentier and Jennifer A. Doudna have discovered one of gene technology’s sharpest tools: the CRISPR/Cas9 genetic scissors. Using these, researchers can change the DNA of animals, plants and microorganisms with extremely high precision. This technology has had a revolutionary impact on the life sciences, is contributing to new cancer therapies and may make the dream of curing inherited diseases come true.

Researchers need to modify genes in cells if they are to find out about life’s inner workings. This used to be time-consuming, difficult and sometimes impossible work. Using the CRISPR/Cas9 genetic scissors, it is now possible to change the code of life over the course of a few weeks.

“There is enormous power in this genetic tool, which affects us all. It has not only revolutionised basic science, but also resulted in innovative crops and will lead to ground-breaking new medical treatments,” says Claes Gustafsson, chair of the Nobel Committee for Chemistry.

As so often in science, the discovery of these genetic scissors was unexpected. During Emmanuelle Charpentier’s studies of Streptococcus pyogenes, one of the bacteria that cause the most harm to humanity, she discovered a previously unknown molecule, tracrRNA. Her work showed that tracrRNA is part of bacteria’s ancient immune system, CRISPR/Cas, that disarms viruses by cleaving their DNA.

Charpentier published her discovery in 2011. The same year, she initiated a collaboration with Jennifer Doudna, an experienced biochemist with vast knowledge of RNA. Together, they succeeded in recreating the bacteria’s genetic scissors in a test tube and simplifying the scissors’ molecular components so they were easier to use.

In an epoch-making experiment, they then reprogrammed the genetic scissors. In their natural form, the scissors recognise DNA from viruses, but Charpentier and Doudna proved that they could be controlled so that they can cut any DNA molecule at a predetermined site. Where the DNA is cut it is then easy to rewrite the code of life.

Since Charpentier and Doudna discovered the CRISPR/Cas9 genetic scissors in 2012 their use has exploded. This tool has contributed to many important discoveries in basic research, and plant researchers have been able to develop crops that withstand mould, pests and drought. In medicine, clinical trials of new cancer therapies are underway, and the dream of being able to cure inherited diseases is about to come true. These genetic scissors have taken the life sciences into a new epoch and, in many ways, are bringing the greatest benefit to humankind.

 

Illustrations

The illustrations are free to use for non-commercial purposes. Attribute ”© Johan Jarnestad/The Royal Swedish Academy of Sciences”

Illustration: Using the genetic scissors (pdf)
Illustration: Streptococcus’ natural immune system against viruses:CRISPR/Cas9 pdf)
Illustration: CRISPR/Cas9 genetic scissors (pdf)

Read more about this year’s prize

Popular information: Genetic scissors: a tool for rewriting the code of life (pdf)
Scientific Background: A tool for genome editing (pdf)

 

Emmanuelle Charpentier, born 1968 in Juvisy-sur-Orge, France. Ph.D. 1995 from Institut Pasteur, Paris, France. Director of the Max Planck Unit for the Science of Pathogens, Berlin, Germany.

Jennifer A. Doudna, born 1964 in Washington, D.C, USA. Ph.D. 1989 from Harvard Medical School, Boston, USA. Professor at the University of California, Berkeley, USA and Investigator, Howard Hughes Medical Institute.

 




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