Thursday, September 14, 2017

Eric Kandel: From Memory to Memory!

Eric Kandel, M.D., who was awarded the Nobel Prize in 2000 for discovering molecular mechanisms of memory storage, told the crowd at last week’s Flexner Discovery Lecture that he has recently become interested in memory in the aging brain. “We’ve been studying age-related memory loss, and not a moment too soon,” quipped the 87-year-old Kandel, University Professor and Fred Kavli Professor in the Department of Neuroscience at Columbia University.
“There are many people in the field…who think that the Aplysia rather than the investigator should have won the Nobel Prize,” Kandel said.
In more recent work, Kandel and his colleagues have turned their attention to age-related memory loss. The researchers wondered, Kandel said, if memory loss during normal aging is a distinct process or an early phase of Alzheimer’s disease.
They determined that mice, which do not experience spontaneous Alzheimer’s disease, also experience age-related memory loss, suggesting that the two processes are distinct, he said. Other studies showed that brain regions involved in age-related memory loss and Alzheimer’s disease are different.


©2015 Am Ang Zhang

No I did not do any diving in Patagonia!


We were having dinner at our Ecocamp in Patagonia with a very interesting couple.
The husband is aiming to climb the Matterhorn and somehow in the conversation we talked about their other adventures that included Diving. I show them some of my underwater pictures. Somehow Nudibranch was mentioned and as it turned out we exchange email addresses and became good friends.

Nudibranch reminded me of Aplysia and Kandel:






Nudibranch © 2009 Irene Man


Nudibranch is so named because of its naked gills.
Here is a description in The National Geographic:

Nudibranchs crawl through life as slick and naked as a newborn. Snail kin whose ancestors shrugged off the shell millions of years ago, they are just skin, muscle, and organs sliding on trails of slime across ocean floors and coral heads the world over.

Found from sandy shallows and reefs to the murky seabed nearly a mile down, nudibranchs thrive in waters both warm and cold and even around billowing deep-sea vents. 


So why, in habitats swirling with voracious eaters, aren't nudibranchs picked off like shrimp at a barbecue? The 3,000-plus known nudibranch species, it turns out, are well equipped to defend themselves. Not only can they be tough-skinned, bumpy, and abrasive, but they've also traded the family shell for less burdensome weaponry: toxic secretions and stinging cells. A few make their own poisons, but most pilfer from the foods they eat. Species that dine on toxic sponges, for example, alter and store the irritating compounds in their bodies and secrete them from skin cells or glands when disturbed. Other nudibranchs hoard capsules of tightly coiled stingers, called nematocysts, ingested from fire corals, anemones, and hydroids. Immune to the sting, the slugs deploy the stolen artillery along their own extremities.


Memory & Knowledge: Talmud & Taxi

In 2001 I was fortunate enough to be in New Orleans for the American Psychiatric Association Annual Conference. One of the lectures attracted a long queue and it turned out that the Nobel Laureate Eric Kandel was giving his lecture. I was fortunate enough to be able to secure a seat.

"Different forms of learning result in memories by changing that strength in different ways. Short-term memory results from transient changes that last minutes and does not require any new synthesis of proteins, Kandel said. However, long-term memories are based in more lasting changes of days to weeks that do require new brain protein to be synthesized. And this synthesis requires the input of the neuron’s genes." Eric Kandel.

In his book In Search Of Memory, he remembered his arrival in New York in 1939 after a year under the Nazi in Vienna:

“My grandfather and I liked each other a great deal, and he readily convinced me that he should tutor me in Hebrew during the summer of 1939 so that I might be eligible for a scholarship at the Yeshiva of Flatbush, an excellent Hebrew parochial school that offered both secular and religious studies at a very high level. With his tutelage I entered the Yeshiva in the fall of 1939. By the time I graduated in 1944 I spoke Hebrew almost as well as English, had read through the five books of Moses, the books of Kings, the Prophets and the Judges in Hebrew, and also learned a smattering of the Talmud.”

Eric Kandel/Amazon


“It gave me both pleasure and pride to learn later that Baruch S. Blumberg, who won the Nobel Prize in Physiology or Medicine in 1976, had also benefited from the extraordinary educational experience provided by the Yeshivah of Flatbush.”

In Hebrew and English!!! That did not seem to have done him and Blumberg much harm. Right now some governments seem hell bent in doing away with rote learning and that includes some medical schools.

Lord Brain:
When I was training in London in the 70s, I spent some time at Queen Square. Those in the know will recognize it as the place for neurology this side of the Atlantic. It was drilled into us then that sadly we were given a number of brain cells when we were born and it was all downhill from then on or something to that effect. It was well known that neurologists were great diagnosticians but for most neurological conditions, not much could be done. How depressing indeed. Even as recently as four weeks ago, I heard a young doctor told his father that there was nothing he could do with his brain cells. One is given so many at birth and no more can be expected. Lord Brain (1895-1966) would have been so proud.


Knowledge:

Yet it was also London that shook the world with new discoveries about the brain, and the study was on the most unlikely group of people: Taxi drivers. Their “KNOWLEDGE” was the basis of our knowledge on brain plasticity today. The “KNOWLEDGE” is a term officially used to describe the test the Taxi Drivers had to take to get the license to drive Taxis in London. Streets in London have evolved over time and are not on any grid system at all. Early postmortem examinations led some pathologists to note the small size of the Taxi drivers’ frontal lobes. Yet actual weight measurement showed that size was all relative. It was the enlarged hippocampal region that created that impression. Later work using modern scanning techniques confirmed the early impressions.


Kandel & Doidge: Neuroplasticity & Memory.

Monday, September 11, 2017

Trauma and Human Resilience: II



©2013  Am Ang Zhang  

It seems to be against common sense to suggest that talking may not be good for severe traumatic experiences. This is more so for someone brought up on psychoanalysis; yet, the evidence is clearly against talking especially in severe trauma.
In 
The Cockroach Catcher:
The speaker was a Senior Registrar from the Maudsley.

"......He was a Registrar at the time of the King’s Cross fire. He was just coming out of the station when the accident happened, and so was at the front line so to speak not just as a pedestrian but also as a psychiatrist. He became interested in PTSD (Post Traumatic Stress Disorder) and did a fair bit of research on King’s Cross and other disasters.

He quoted a number of cases, including the Herald of Free Enterprise disaster. There were those who despite help of all kinds would commit suicide. Many were heroes in that they saved many lives. Yet the feeling that they did not deserve to live eventually overtook them and they committed suicide.

What was most surprising was how the group that had counselling generally faired worse, much worse than those without any counselling. The group that did best were the ones that drank, and drank a fair amount.

It was not his intention to promote vodka but he thought we could not be kept from the truth……

His research showed that talking about the incident seemed to make things worse, much worse than anyone ever imagined……”

From To talk or not to talk: Trauma & Human Resilience Part I.


         Then came September 11. I remembered I was on holiday in Spain when it happened. I had just finished golf. I put my clubs away and went to the club house for a drink with my playing partners. As I approached their table, I sensed that something was wrong. There were no drinks.
         Then one of them said, “One of the World Trade Centre Towers is down!”
         I was trying to see if I heard right.
         “In New York?”
         “New York.”
         Then moments later, the Spanish waitress came out and said to us, the second tower was down too.
         I rushed back to our villa and shouted to my wife to turn on CNN and tried to contact our children, one of whom worked in Manhattan.
         Lines were dead.
         Luckily, an Email came through our other daughter who was in England: Sis OK, at a meeting on 55th Street. Now trying to walk home to Brooklyn.
         What a shock.  Unlike my parents’ generation we have had a long period of peace and prosperity but now everything was shattered.
         The following day my office put a call through and I talked to my Associate Specialist.
         The clinic just had an urgent referral. A local girl was referred. Very disturbed by what happened as one of her father’s good friends was one of the pilots whose plane went down. The family spent many holidays with them in their Florida home and she was now most upset.
         “Whatever you do, by all means talk to the parents but not to the girl. No one should see her. They should not turn on the TV and avoid any reminder of what happened.”
         I then nearly said, “Give her Vodka, Gin or similar,” but I did not.
         I gave the next best thing.
         “Put her on a short course of Benzodiazepine to let her sleep for a few days.”
         It shocked my Associate Specialist. It was not a drug I normally used, if at all, and why now?
         Well, whatever happened, all I could say was that the family was in total agreement and months later my Associate Specialist told me that it was brave of me but it seemed to have worked for this girl.
        
        
         In July last year I met a young couple at the swimming pool of our holiday condo. I thought they were Chinese but it turned out they were Vietnamese Chinese.
         We started chatting. He said he left Nam (Vietnam) on the last day.
         Jokingly, I said, you mean you were on the Helicopter?
         “Yeah, how did you know?”
         “You looked too young to be working for the Embassy.”
         “My mum worked there. But my story was nothing, you should hear hers.”
         His wife, an elegant looking petite Chinese swam closer.
         “So, tell me.”
         Well, she came out later. Her mother put her and four sisters on a junk (a Chinese fishing boat), one of those that took refugees out of Nam for an exorbitant fee and generally it had to be gold. Their boat sank outside Hong Kong but they swam ashore. She spent the next three years in one of the Hong Kong camps.
         “Yes, I remember those.”
         “I know - the stench. We got used to it.”
         Those camps were run under the auspices of the United Nations but the UN never really paid Hong Kong a single dollar. However that is beside the point. Conditions were very poor and one could hardly decide if it was Hong Kong’s or UN’s fault. Every time we drove past it was like passing a local authority rubbish tip. We had to wind up the windows. Yet there were politicians who felt they needed to keep it bad to deter people. They continued to flow in right up to the handover. As it was still under British rule, Britain tried its best to keep people from going to Britain. They needed not have worried. Most wanted to go to U.S. An irony really.
         I said something that sounded like an apology, an apology for Hong Kong, and for mankind.
         “No. It’s fine. I am not bitter. We waited and we got to the U.S. There was nothing you could have done anyway.”
         She told me someone suggested that she should have some therapy. She never did.
         “Some things you can never change. If it happened it happened.”
         But she managed to get most of her family out of camps and settled in the US. She was very successful in her business and her only regret was that her parents never made it.
        
         What a story of human resilience and triumph over adversities.
         And I can still remember that lunch time meeting and the learning from King’s Cross.



Now mountains are once again mountains,
and waters once again waters.




The Cockroach Catcher















Latest Views on the book:


5.0 out of 5 stars A Must-read for Students of Psychiatry August 10, 2014
Format:Paperback
We all have stories to tell with regard to our experiences as physicians. Zhang is one of our medical school classmates who took it to a different level by writing and publishing a book. The book details how it all started, from the time his family moved to Hong Kong from China, to his years in medical school, to his experience as a child psychiatrist in the UK. The book is full of interesting case studies of actual patients he saw and the challenges he faced dealing with them.
I was captivated by many of the interesting stories in the book. It’s a must-read for all students of psychiatry. It also makes for good reading material for anyone during their leisure moments.

From another doctor friend:

The Cockroach Catcher has evoked many images, memories, emotions from my own family circumstances and clinical experience.

My 80 year old Mum has a long-standing habit of collecting old newspaper and gossip magazines. Stacks of paper garbage filled every room of her apartment, which became a fire hazard. My siblings tricked her into a prolonged holiday, emptied the flat and refurbished the whole place ten years ago. ……My eldest son was very pretty as a child and experienced severe OCD symptoms, necessitating consultations with a psychiatrist at an age of 7 years. The doctor shocked us by advising an abrupt change of school or we would "lose" him, so he opined. He was described as being aloft and detached as a child. He seldom smiled after arrival of a younger brother. He was good at numbers and got a First in Maths from a top college later on. My wife and I always have the diagnosis of autism in the back of our mind. Fortunately, he developed good social skills and did well at his college. He is a good leader and co-ordinator at the workplace. We feel relieved now and the years of sacrifice (including me giving up private practice and my wife giving up a promising administrative career ) paid off.

Your pragmatic approach to problem solving and treatment plans is commendable in the era of micro-managed NHS and education system. I must admit that I learn a great deal about the running of NHS psychiatric services and the school system.

Objectively, a reader outside of the UK would find some chapters in the book intriguing because a lot of space was devoted to explaining the jargons (statementing, section, grammar schools) and the NHS administrative systems. Of course, your need to clarify the peculiar UK background of your clinical practice is understandable.

Your sensitivity and constant reference to the feelings, background and learning curves of your sub-ordinates and other members of the team are rare attributes of psychiatric bosses, whom I usually found lacking in affect! If more medical students have access to your book, I'm sure many more will choose psychiatry as a career. The Cockroach Catcher promotes the human side of clinical psychiatric practice in simple language that an outsider can appreciate. An extremely outstanding piece of work indeed.

From Australia:

I have finished reading The Cockroach Catcher and thoroughly enjoyed it.

Zhang, I particularly liked the juxtaposition and paralleling of your travel stories and observations with your case studies, Of course, I could appreciate it even more, knowing the author and hearing your voice in the text. Because I’m dealing with anorexia, ADD and ADHD students I was very interested in your experiences with patients and parents and your treatment. Amazing how many parents are the underlying causes of their offspring’s angst. It was an eminently readable text for the medically uninitiated like me. Keep writing, Zhang

The Cockroach Catcher on Amazon Kindle UKAmazon Kindle US

Friday, September 8, 2017

Mysterious 72 Hrs : ?Anti-NMDA Receptor Encephalitis

I had a call from one of my many ex-juniors asking if I have read about the girl that deteriorated within 72 hours. 

Wow as I went through these from mysterious photos!
 ©2015 Am Ang Zhang
"She cannot read, she cannot write, she cannot walk or go to the toilet. She is back in pads. She cannot do anything on her own. And there is a waiting list of 6 months to see a specialist at GOSH. Sounds like one of those NMDA cases!"


 ©2015 Am Ang Zhang

Well, what can I say. Time will tell and let me reprint my post:


The Power of Prayers & Teratoma: Brain & NMDA!

As the BBC reported on the work on NMDA, this blog post was from Sep 1, 2013 and it was an answer to my case of Teratoma induced coma/psychosis.

In medicine, truly new discoveries are uncommon and with the emergence of guidelines and protocols it has become even more difficult to make new discoveries. It has taken over 30 years before I could understand what happened to my Teratoma patient. Luckily for her, the treatment she received would have been in line with what we know now of the condition.


Hospital Medicine indeed has its important place and most important of all in the discovery of new conditions and establishing diagnostic and treatment programmes.

It is perhaps timely to remind the next generation of Bright Young Things that become doctors to remember that psychiatric symptoms presented by a patient may indeed be the presentation of a neurological condition.

This is more so for bizarre combinations of psychiatric and other symptoms. It was in the last five years or so that much progress has been made on what is now called Anti-NMDA Receptor Encephalitis.

Who knows, one day medical scientists might be able to decipher the most difficult of psychiatric conditions: Schizophrenia. Bright Young Psychiatrist might have noticed that Clozapine, one of the most effective drugs for schizophrenia has a marked effect on the immune system. 

In the mean time Pennsylvania might have something they could be proud of: the discovery of this new neurological condition.

For now, my patient’s parents’ prayer has been answered. 

Chapter 29  The Power of Prayers


Anti-NMDA Receptor Encephalitis

NEW ORLEANS — A mysterious, difficult-to-diagnose, and potentially deadly disease that was only recently discovered can be controlled most effectively if treatment is started within the first month that symptoms occur, according to a new report by researchers from the Perelman School of Medicine at the University of Pennsylvania. The researchers analyzed 565 cases of this recently discovered paraneoplastic condition, called Anti-NMDA Receptor Encephalitis, and determined that if initial treatments fail, second-line therapy significantly improves outcomes compared with repeating treatments or no additional treatments (76 percent versus 55 percent). The research is being presented at the American Academy of Neurology's 64th Annual Meeting in New Orleans.

565 cases! Not so rare!

The condition occurs most frequently in women (81 percent of cases), and predominately in younger people (36 percent of cases occurring in people under 18 years of age, the average age is 19). Symptoms range from psychiatric symptoms, memory issues, speech disorders, seizures, involuntary movements, to decreased levels of consciousness and breathing. Within the first month, movement disorders were more frequent in children, while memory problems and decreased breathing predominated in adults.

My patient was under 18 and presented with catatonia symptoms. She later lose consciousness and was ventilated.

"Our study establishes the first treatment guidelines for NMDA-receptor encephalitis, based on data from a large group of patients, experience using different types of treatment, and extensive long-term follow-up," said lead author Maarten TitulaerMD, PhD, clinical research fellow in Neuro-oncology and Immunology in the Perelman School of Medicine at the University of Pennsylvania. "In addition, the study provides an important update on the spectrum of symptoms, frequency of tumor association, and the need of prolonged rehabilitation in which multidisciplinary teams including neurologists, pediatricians, psychiatrists, behavioral rehabilitation, and others, should be involved."

The disease was first characterized by Penn's Josep Dalmau, MD, PhD, adjunct professor of Neurology, and David R. Lynch, MD, PhD, associate professor of Neurology and Pediatrics, in Annals of Neurology in 2007. One year later, the same investigators in collaboration with Rita Balice-Gordon, PhD, professor of Neuroscience, characterized the main syndrome and provided preliminary evidence that the antibodies have a pathogenic effect on the NR1 subunit of the NMDA receptor in the Lancet Neurology in December 2008. The disease can be diagnosed using a test developed at the University of Pennsylvania and currently available worldwide. With appropriate treatment, almost 80 percent of patients improve well and, with a recovery process that may take many months and years, can fully recover.

Teratoma: finally!

In earlier reports, 59 percent of patients had tumors, most commonly ovarian teratoma, but in the latest update, 54 percent of women over 12 years had tumors, and only six percent of girls under 12 years old had ovarian teratomas. In addition, relapses were noted in 13 percent of patients, 78 percent of the relapses occurred in patients without teratomas.
As Anti-NMDA Receptor Encephalitis, the most common and best characterized antibody-mediated encephalitis, becomes better understood, quicker diagnosis and early treatment can improve outcomes for this severe disease.
The study was presented in a plenary session on Wednesday, April 25, 2012 ET at 9:35 AM at the American Academy of Neurology's annual meeting.
[PL01.001] Clinical Features, Treatment, and Outcome of 500 Patients with Anti-NMDA Receptor Encephalitis

Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies

Of 100 patients with anti-NMDA-receptor encephalitis, a disorder that associates with antibodies against the NR1 subunit of the receptor, many were initially seen by psychiatrists or admitted to psychiatric centres but subsequently developed seizures, decline of consciousness, and complex symptoms requiring multidisciplinary care. While poorly responsive or in a catatonic-like state, 93 patients developed hypoventilation, autonomic imbalance, or abnormal movements, all overlapping in 52 patients. 59% of patients had a tumour, most commonly ovarian teratoma. Despite the severity of the disorder, 75 patients recovered and 25 had severe deficits or died.

Related paper:

Chapter 29  The Power of Prayers             

Friday, September 1, 2017

From Tampopo to Sideways: Wine, Media and The Mind



Napa Valley© 2015 Am Ang Zhang

It is amazing how easy it is to influence modern day consumers with nothing other than a well made film. As far as wine is concerned the film Sideways has more or less changed the wine landscape of California if not elsewhere. This is because of two simple lines from the film. The wine snob character Miles tells friend Jack before a double-date dinner:

“If anyone orders Merlot, I'm leaving. I am not drinking any……Merlot.”

All of a sudden, it is no longer cool to order Merlot, and Pinot Noir becomes the new Merlot.
The fact that the same snob Miles’ most treasured wine Cheval Blanc is 45% Merlot is lost to the vast majority. In fact if Petrus had not refused permission, Miles would have drunk Petrus in the film, and that, one of the most expensive wines in the world, is 95% Merlot.

In the animated hit Ratatouille, feared critic Anton Ego visits Gusteau's, the restaurant in which the movie is set, and orders a bottle of 1947 Ch√Ęteau Cheval Blanc to go with his meal. The '47 Cheval is probably the most celebrated wine of the 20th century. However, there has been no rush to buy cases of this as you are unlikely to find them except in top merchants and private cellars.

I have my own suspicion about some lesser known films that may have influenced wine drinking habits in the Far East.

In 1985 the film Tampopo came out of Japan. This comedy features a truck driver who helps a young widow named Tampopo improve her noodle restaurant, and draws attention to the power of food.
There is a beautiful wine tasting scene, by a group of hobos following the lead of a professor. The professor realises that life as a hobo is much freer, with no one above him telling him what he should do, no targets to meet, and no paperwork.

The wine tasting is not at a winery or a restaurant. It is in a park by the back door of a restaurant. The wine is that little bit left at the bottom of a bottle. There is not enough to go round; so the hobos allow the professor to do the tasting and are content to just listen to his analysis. (In the Cockroach Catcher, I wrote that a blind case presentation at Queen Square was a bit like wine tasting.)

It is one of the most enjoyable scenes for wine lovers and if you are not a wine lover you will become one.

The wine?

Chateau Pichon Longueville Comtesse de Lalande,” announced the professor in perfect French.
This wine has since become a favourite of the Far East.

Chateau Pichon Lalande is not as expensive as the First Growths but is fast catching up. Fortnum and Mason of London used to have a house Pauillac made by Chateau Pichon Lalande. I was tipped off to get the last few bottles some years ago. Now the supplier of their house Pauillac is Chateau Haut Bages Averous, a vineyard next to the new rising star of Bordeaux: Chateaux Lynch-Bages.

The best year in recent vintages has to be 1989, a great year for most of Bordeaux and rumour has it that it will become drinkable in 2009. Hurrah. The 2000 is superb too but recent vintages have all been great and if you can store them buy them now.

The biggest wine influence worldwide came from a documentary. In 1991, after the airing of 60 Minutes on CBS, wine sales went up 44% in the next four weeks in the U.S. It was about the French Paradox: the incidence of coronary heart disease in France being 40% percent lower than in the U.S.
Health sells.

Once upon a time in Hong Kong, when people made money they drank the most expensive Cognac and Scotch, with Hennesy XO and Dimple being the “Gold Standards”, partly because of their highly recognisable bottles. To have such a bottle on your dining table was a sure sign that you had arrived. Now, the status symbol is the most expensive red wine, and it is often taken with just about any dish that is served.
But then the French perhaps always knew; including its own most famous psychoanalyst Jean Laplanche (born 1924). His book The Language of Psychoanalysis was first published in 1967 and translated into English in 1973. All of us training at the Tavistock had a copy and it is to this day one of the best reference books on the subject. He has co-authored a number of other books in psychoanalysis.

What is not so widely known is that Laplanche was for many years the owner of Chateau de Pommard, a Burgundy vineyard, and actively involved with the wine-making processes. He sold the vineyard in 2003 but continues to live on the estate with his wife and to act in the capacity of a consultant to the new owners on wine making matters.

Wine Posts: