Wednesday, August 15, 2018
Sepsis & Quorum Sensing!
For the past three hundred years……we’ve been completely wrong……we don’t know anything about bacteria until about a decade ago….”
Bonnie Bassler
Bassler group finds an alternative mode of bacterial quorum sensing
Whether they are growing in a puddle of dirty water or inside the human body, large groups of bacteria have to interact with each other and coordinate their behavior in order to perform essential tasks that they would not be able to carry out on their own. Bacteria achieve this coordination through a process called quorum sensing, in which the microorganisms produce and secrete small molecules, called autoinducers, that can be detected by neighboring bacterial cells. Only when a large number of bacteria are present can the levels of secreted autoinducer build up to the point where the community can detect it and, in response, alter their behavior as a coordinated group.
In a paper published last month in PLoS Pathogens, a team of researchers led by Sampriti Mukherjee and Bonnie Bassler from the Department of Molecular Biology revealed the existence of a new quorum sensing molecule that increases the virulence of the pathogenic bacterium Pseudomonas aeruginosa. The finding could help researchers develop new antimicrobial drugs to treat the serious infections caused by this bacterium.
P. aeruginosa is an incredibly adaptable organism that can grow in diverse environments, from soil and freshwater to the tissues of plants and animals. It thrives on the surfaces of medical equipment and is therefore a major cause of hospital-acquired infections, causing life-threatening conditions, such as pneumonia and sepsis, in vulnerable patients. The bacterium has become resistant to most commonly used antibiotics, making the development of new antimicrobial treatments a priority for both the Centers for Disease Control and Prevention and the World Health Organization.
Hospital Infection: Quorum Sensing
This is the story of a much respected retired professor. As he celebrated his 82nd birthday, we have to be thankful that he must have some strong genes to have survived the last eight months. An unfortunate slip at home fractured one of his ankles, and as a pin was needed a surgical procedure was performed in a local hospital by the Orthopaedic surgeon. For the following eight months an otherwise independent and healthy eighty one year old had to suffer the indignity of many more hospital procedures because of a lingering infection.
“I don’t know” was his answer when we visited him and asked if it was the dreaded MRSA.
He was never tested!
Nearly 15 years since the discovery of Quorum Sensing by Nottingham University the topic seemed to be shrouded in some mystery. The Cockroach Catcher read about it by chance in an airline magazine and his own survey of some recent medical school graduates from Cambridge and Southampton indicated that this was not in their curriculum and they had never heard of it.
There is of course a Nottingham Quorum Sensing website and certainly Cambridge produced some research papers.
Why?
Bonnie Bassler said that all we knew about bacteriology in the last 300 years is all wrong. Strong words indeed. So are we still teaching medical students all the wrong stuff?
Is professional jealousy at work here? Surely not. But Quorum Sensing will itself lead to other exciting findings about the world of the microbe that has so far got the upper hand on the ever so clever Homo sapiens.
Think MRSA and C.difficile and I am sure you will agree.
I know that it is a new field and much of it theoretical and conjectural but I was a medical student once and the greatest buzz for me then was Heart Transplant, and VAMP treatment for some kind of leukaemia. So could we not let the future doctors have some excitement other than the 3G iPhone?
Surely we need to inspire some great brains to go where no men have gone before.
It is now well established that in France and Holland where hospitals do not run to capacity, they do not have the level of MRSA and C. difficile problem that we have here.
I do not think that is the result of them using some of the methods we have been known to use here, i.e. not testing the patients. Their standard of care is probably different and their wards are not as crowded.
We do seem to have lots of “good” lateral thinkers working in the NHS. In the meantime, our well loved professor has decided to move to sheltered housing. Months of struggling with his immobility and inability to go walking, swimming, shopping and getting on with his daily chores robbed him of his desire to be independent. But at least he survived.
What about his hospital manager? Did he or she get the bonus? 
SARS and Quorum Sensing
There is a chapter in The Cockroach Catcher called “SARS, Freedom and Knowledge”. I wrote about the SARS virus:
“For the first time, doctors and nurses who were normally in the forefront of the fight against diseases were fighting for survival from SARS (Severe Acute Respiratory Syndrome), a new and dangerously contagious disease. ……
Our knowledge base was in total chaos. What we knew was obviously not good enough. Nor were the most up to date antiviral drugs……”
I am not a bacteriologist nor virologist but that did not stop me writing about these little creatures.
When I picked up the in-flight magazine on a recent flight, an article titled “Genius at Work” caught my eye. Bonnie Bassler is the bacteriologist at Princeton who discovered and pioneered the work on what she now called quorum sensing in microbes. To be more precise her initial work was with Vibrio harveyi. Vibrio is in the family of bacteria that causes Cholera. Vibrio vulnificus is carried by oysters and was most likely responsible for the serious illness of Michael Winner, film producer and now food writer of the London Sunday Times.
On following this up back home, I found an article on the website of Howard Hughes Medical Institute – she is one of the HHMI Investigators. From this article, I learned that:
“Virulent bacteria do not want to begin secreting toxins too soon, or the host's immune system will quickly eliminate the nascent infection. Instead, Bassler explained, using quorum sensing, the bacteria count themselves and when they reach a sufficiently high number, they all launch their attack simultaneously. This way, the bacteria are more likely to overpower the immune system….
For the past three hundred years……we’ve been completely wrong……we don’t know anything about bacteria until about a decade ago….”
Wow! Just as we thought we knew everything there is to know about microbes.
Bonnie Bassler will one day get the Nobel prize for medicine. You read it here first.
Fascinated, I wanted to find out more about this genius. I would like to share with you her answers to some of questions that children were invited to ask about her life and work:
“You all asked me essentially the same question: how and when did I get interested in science. As a kid, I loved doing puzzles, solving riddles, and reading mystery books. I also loved animals and always had pets. Around high school, those interests (puzzle solving and animals) convinced me that I should be a veterinarian so I could work on mysterious illnesses in animals and cure them. In college, I realized I did not like big-bloody stuff. It became clear to me that I probably wouldn't enjoy being a vet, but I did not know what I'd do instead.
Fortunately, the vet curriculum required me to take biochemistry, genetics, and lab courses. Once I got into those classes, I fell in love with doing puzzles about little things (DNA and RNA and proteins and how they all fit together in cells). I also adored doing lab experiments and puzzling over my results. I realized that lab research was the perfect path for me. It allowed me to spend every day figuring out mysteries/puzzles that have to do with what make us alive. What could be a bigger mystery or puzzle? I changed my major in my junior year, and I have not left the lab since. (I still love animals and have a pet—Spark my cat—and I often go hiking hoping to see animals in the wild.)
I think being open-minded about what Nature is trying to tell you is the key to being creative and successful.”
Now in England , only a couple of Medical Schools require biology. In my book, I puzzled over this fact:
“The ability to dissect out a full set of cockroach salivary glands was a prerequisite requirement for medical school entrance in Hong Kong in our days. It is almost a 180 degree turn around nowadays when many young doctors have no idea about the biological world we live in. Nearly all Medical Schools in England no longer specify biology as a prerequisite subject for anybody who wishes to embark on the study of the human body. As we are so intertwined with the rest of the living biological world I find this policy quite extraordinary.”
Book I am reading:
As the Nazi regime slaughtered millions across Europe during WWII, it sorted people according to race, religion, behavior, and physical condition for either treatment or elimination. Nazi psychiatrists targeted children with different kinds of minds―especially those thought to lack social skills―claiming the Reich had no place for them. Asperger and his colleagues endeavored to mold certain “autistic” children into productive citizens, while transferring others they deemed untreatable to Spiegelgrund, one of the Reich’s deadliest child-killing centers.
SARS ACCOUNTS: Dr Yannie Soo, Tom Buckley.
Other Posts:
Learning From History: 1918 Flu Pandemic, Hong Kong SARS, Swine Flu & Influenza A(H1N1)
Swine Flu: WHO Level 5 & The 1976 Vaccine Disaster.
Swine Flu: WHO Level 5 & The 1976 Vaccine Disaster.
Monday, August 13, 2018
NHS & Gawande: Morbidity and Mortality Conference M+M
It seem timely to bring back an old Blog!
We need to look at the way medical liability is covered in Hospitals where indeed all juniors must be covered by a consultant in one way or another. The responsibility would indeed be that of the hospital management and not on the poor Junior Doctor. The difficulty is the choice between NO doctor or a less experienced one. Should the patient be told or should the A&E just be closed? Will management do that or just continue to abuse the poor juniors and blame them when things go wrong. No wonder my friends' children prefer to become lawyers.
I read Gawande when I was touring Peggy's Cove and posted about his book Complications! Honestly, I did not know Gawande was giving the Reith Lectures.
Latest Gawande Book:
In one of the most moving passages in the book, Gawande’s father, in hospice, rises from his wheelchair to hear his son lecture at their hometown university. “I was almost overcome just witnessing it,” Gawande writes.
........Gawande offers no manifesto, no checklist, for a better end of life. Rather, he profiles professionals who have challenged the status quo, including Bill Thomas and other geriatricians, palliative-care specialists, and hospice workers. Particularly inspiring are the stories of patients who made hard decisions about balancing their desire to live longer with their desire to live better. These include Gawande’s daughter’s piano teacher, who gave lessons until the last month of her life, and Gawande’s father, also a surgeon, who continued work on a school he founded in India
He’s awed not only by his father’s strength, but by the hospice care that helped the dying man articulate what mattered most to him, and to do it. Gawande thinks, as he watches his proud father climb the bleachers, “Here is what a different kind of care — a different kind of medicine — makes possible.”
What would lawyers say about M + M:
- ‘There is one place, however, where doctors can talk candidly about their mistakes, if not with patients, then at least with one another. It is called the Morbidity and Mortality Conference – or, more simply, M+M – and it takes place, usually once a week, at nearly every academic hospital in the country. This institution survives because laws protecting its proceedings from legal discovery have stayed on the books in most states, despite frequent challenges.’
>>>See also Dr No: We Have No Black Boxes
>>>See also Dr No: We Have No Black Boxes
Abetternhs's Blog What are we afraid of?
August 27 2014:
What a charming place: Peggy's Cove of Halifax.
The Cockroach Catcher was finishing reading the book Complications and such charming old landscape reminds him of the old traditional medical training he received and how some doctors still do. Like the author of this book.
The book reads more like a collection of blog posts and in fact it was. Yet it was real and touching. Sometimes it was brunt and brutal. and after all doctors are as human as anyone. Complications includes those doctors themselves may suffer: mental illness and alcoholism as well as the serious cardiac condition of the author's young son.
We, doctors make mistakes and please we must be allowed to sort them out without affecting career or worst, future medical behaviour.
A great book for doctors in particular and when on holiday in a charming place.
All photos©2014 Am Ang Zhang
(Metropolitan Books, 288 pages, $24), a collection of 14 pieces, some of which were originally published in The New Yorker and Slate magazines, Gawande uses real-life scenarios – a burned-out doctor who refuses to quit; a terminal patient who opts for risky surgery, with fatal results – to explore the larger ethical issues that underlie medicine. He asks: How much input should a patient have? How can young doctors gain hands-on experience without endangering lives? And how responsible are these doctors for their mistakes?
While “Complications” is full of tragic errors and near misses, the book is not intended to be an expose. Rather, Gawande asserts, it is meant to deepen our understanding of the intricacies of medicine. “In most medical writing, the doctor is either a hero or a villain,” he says, with an edge in his voice. “What I am trying to do is push beyond that and show how ordinary doctors are – and at the same time show that what they can do is extraordinary.”
John Freeman, Copyright (c) 2002 The Denver
Quotes
- ‘There have now been many studies of elite performers – international violinists, chess grand masters, professional ice-skaters, mathematicians, and so forth – and the biggest difference… is the cumulative amount of deliberate practice they’ve had.’
- ‘We have long faced a conflict between the imperative to give patients the best possible care and the need to provide novices with experience. Residencies attempt to mitigate potential harm through supervision and graduated responsibility. And there is reason to think patients actually benefit from teaching. Studies generally find teaching hospitals have better outcomes than non-teaching hospitals. Residents may be amateurs, but having them around checking on patients, asking questions, and keeping faculty on their toes seem to help. But there is still getting around those first few unsteady times a young physician tries to put in a central line, remove a breast cancer, or sew together two segments of a colon… the ward services and clinics where residents have the most responsibility are populated by the poor, the uninsured, the drunk, and the demented… By traditional ethics and public insistence (not to mention court rulings), a patient’s right to the best care possible must trump the objective of training novices. We want perfection without practice. Yet everyone is harmed if no one is trained for the future. So learning is hidden behind drapes and anesthesia and the elisions of language.’
- ‘There is one place, however, where doctors can talk candidly about their mistakes, if not with patients, then at least with one another. It is called the Morbidity and Mortality Conference – or, more simply, M+M – and it takes place, usually once a week, at nearly every academic hospital in the country. This institution survives because laws protecting its proceedings from legal discovery have stayed on the books in most states, despite frequent challenges.’
Quotes
- ‘There have now been many studies of elite performers – international violinists, chess grand masters, professional ice-skaters, mathematicians, and so forth – and the biggest difference… is the cumulative amount of deliberate practice they’ve had.’
- ‘We have long faced a conflict between the imperative to give patients the best possible care and the need to provide novices with experience. Residencies attempt to mitigate potential harm through supervision and graduated responsibility. And there is reason to think patients actually benefit from teaching. Studies generally find teaching hospitals have better outcomes than non-teaching hospitals. Residents may be amateurs, but having them around checking on patients, asking questions, and keeping faculty on their toes seem to help. But there is still getting around those first few unsteady times a young physician tries to put in a central line, remove a breast cancer, or sew together two segments of a colon… the ward services and clinics where residents have the most responsibility are populated by the poor, the uninsured, the drunk, and the demented… By traditional ethics and public insistence (not to mention court rulings), a patient’s right to the best care possible must trump the objective of training novices. We want perfection without practice. Yet everyone is harmed if no one is trained for the future. So learning is hidden behind drapes and anesthesia and the elisions of language.’
- ‘There is one place, however, where doctors can talk candidly about their mistakes, if not with patients, then at least with one another. It is called the Morbidity and Mortality Conference – or, more simply, M+M – and it takes place, usually once a week, at nearly every academic hospital in the country. This institution survives because laws protecting its proceedings from legal discovery have stayed on the books in most states, despite frequent challenges.’
Read more:
NHS: The Way We Were! Free!
FREE eBook: Just drop me a line with your email.
FREE eBook: Just drop me a line with your email.
Email: cockroachcatcher (at) gmail (dot) com.
Wednesday, August 1, 2018
Junior Doctors & Sunset: 1st day & Tears?
No, it was not the sunset that brought tears:
From Avatar Land© 2015 Am Ang Zhang
This is extracted from another post that is about not just the strange medical condition that I have to wait 30 plus years for an answer but to the Junior Doctor that I fondly remembered. This brought tears to my eyes as it was NHS at its best.
Now are we seeing the end game. Well only 54,000 pawns left on the Chess Board.
.........Perhaps we should catheterise her. She had not been seen to use the toilet for hours although she was not drinking much. She was still going round in her room – we gave her the side room and a nurse – and we put on an input output chart so we knew. The new junior doctor’s car broke down so she was late in examining her.
Bother, I forgot it was changeover time, when new doctors came in for their new six-month rotation. This is one of the days of the year not to be ill.
“Good work Sister. What do we do without you?”
Sister did the catheterisation but only got about 150ml. The mass was still there.
I phoned Ob-Gyn. The consultant had left for home, but I got her Senior Registrar.
He came over. Yes, it was possible that she was pregnant but unlikely as there were no breast changes. He would hate to do an X-ray but that seemed justified in the case of an undiagnosed abdominal mass.
My mind was racing now. Sometimes you do have to believe what you see. Sometimes you have to believe the parents. She was not one of those girls. She could not be pregnant. So now we had to go through the differential diagnosis for abdominal mass in a young girl of thirteen.
Ovarian cyst was the obvious one.
This big?
Possible.
No. It cannot be.
The x-ray came back. The tell tale tooth was there and yes – a Teratoma, the distinctive type of tumour that can include teeth, hair, sometimes, even a jaw and tongue. I guessed just a split second before the results came back. How annoying.
Working diagnosis: Teratoma with possible toxic psychosis.
Emergency operation was arranged. Yes, she would be fine a little while after the operation, I reassured the parents.
Junior Doctor arrived:
Junior Doctor arrived:
The junior arrived and took some history and did a quick physical before she was prepared for the theatre. This petite doctor with a very babyish face told me that on her first day in her last job she had to do an emergency tracheotomy. This time she had been on call for the last three nights and the battery in her old Mini could not cope with the heavy frost so she had to wait for AA before coming. She was most apologetic for not having got in earlier.
She asked if I had seen many toxic psychosis cases and I asked if she had come across any in her psychiatric placement. As with all good psychiatrists answering a question with another is in our blood and here it worked well.
Neither of us knew what was to hit us next.
At 2 A.M. I had a call from her.
“Your patient – I mean our patient could not be aroused after the operation. Yes they removed the teratoma, complete and intact. It is bigger than any specimen I have seen but she could not be aroused. Any ideas?”
“Call the paediatrician on call in the regional paediatric unit and I will be in.”
What happened? I asked myself as I drove to the hospital.
What had we done? This was fast becoming a nightmare situation.
What was I going to say to the parents?
Something else was going on here, and I was not happy because I did not know what it was. I was supposed to know and I generally did. After all I was the consultant now.
Thank goodness she could breathe without assistance. That was the first thing I noticed. I saw mother in the corner obviously in tears. She asked if her daughter would be all right. I cannot remember what I said but knowing myself I could not have said anything too discouraging. But then I knew I was in tricky territory and it was unlikely to be the territory of a child psychiatrist.
A good doctor is one who is not afraid to ask for help but he must also know where to ask.
“Get me Great Ormond Street
“I already did.”
She is going to be a good doctor.
“Well, the Regional unit said that they had no beds so I thought I should ring up my classmate at GOS and she talked to her SR who said “send her in”.”
Who needs consultants when juniors have that kind of network? This girl will do well.
“Everything has been set up. The ambulance will be here in about half an hour and if it is all right I would like to go with her.”
“Yes, you do and thanks a lot.”
I told mother that we were transferring her daughter to the best children’s hospital in England
.........She was impressed with mother’s faith and trust in God.
She said mother was near to tears. It was bad enough to have such a large Teratoma and then to have the patient unconscious with no one knowing what was going on was very frightening.
“I have seen some deaths as a medical student but never since I was registered. I do not want this to be my first.”
I knew the feeling well but what could I say? A doctor has to face it some time.
“Do you believe there is God?” She asked
“Do you really think I can answer that one?”
“Well, you have more experience.”
“To me it is like reading a good book. You would not know until the end.”
“So you mean I am not going to know until then.”
“Interpret whichever way you like. I remember Jung in his Memoir gave quite an account on the Holy Trinity. There were seventeen bishops in Jung’s family including his own father. Jung had always been puzzled by deity and the bible and most of all by the concept of the Holy Trinity. I know many religious philosophers struggle with that too. By some accident he had access to his father’s inner library. He saw this folder clearly marked Holy Trinity. The relief was phenomenal. He could now have the answer. He hesitated before opening the folder.”
“What did the folder contain?”
“See, you want the last chapter. I wanted to know as well. The folder contained pieces of blank paper.”
“That was it?”
“That was it.”
NHS & Ham: World Class Medicine without trying!
Those doctors that grew up here may not know but those of us from overseas looked forward to coming for our specialist training in this country. A number of us went to the US Hong Kong or the rest of the commonwealth.
Why?
We provided World Class Medicine without trying. A quote from a fellow blogger, Dr. No.
Dr No said...
Excellent post - and yes, that is exactly how it used to be. World class medicine without even trying - we just did it, because that is what we did, just as the dolphin swims, and the eagle soars. A key, even vital feature was that the doctors looking after their patients did not need to worry about money or managers. They just got on with it. There was no market to get in the way of truly integrated care. Some may point out that 13 year olds with teratomas are rare, and that is true, but what this case shows us, precisely because of its complexity, is just how capable the system was. And most of the time (of course not always), it dealt just as capably with more routine cases. "How is (sic) the new Consortia going to work out the funding and how are the three Foundation Trust Hospitals going to work out the costs." Exactly. And then: who is going to pay for the staff and their time to work out out all those costs and conduct the transactions?
What many politicians may not know is that pride in what we do is often more important than money or anything else. Our pride is one sure way to ensure quality of practice.
Do we really want to take that away now? Years of heartless re-organisation has left many of us dedicated doctors disillusioned. Many young ones have left. Poorly trained doctors that have no right to be practising medicine now even have jobs in some of these well known hospitals.
Can we continue to practise World Class Medicine even if we wanted to?
Back to the patient:
Would my patient be dealt with in the same way in 2015?
GP to Paediatrician: 13 year old with one stiff arm. Seen the same day.
Paediatrician to me: ? Psychosis or even Catatonia.
Seen same day and admitted to Paediatric Ward, DGH.
Child Psychiatrist to Gynaecologist: ? Pregnancy or tumour. Still the same day.
Gynaecologist to Radiologist: Unlikely to be pregnant, ? Ovarian cyst.
Radiologist (Hospital & no India
Gynaecologist: Operation on emergency basis with Paediatric Anaethetics Consultant. Still Day 1.
Patient unconscious and transferred to GOS on same day. Seen by various Professors.
Patient later transferred to Queen’s Square (National Hospital
Seen by more Professors.
Regained consciousness after 23 days.
Eventually transferred back to local Hospital.
None of the Doctor to Doctor decisions need to be referred to managers.
We did not have Admission Avoidance then.
How is the new Consortia going to work out the funding and how are the three Foundation Trust Hospitals going to work out the costs.
The danger is that the patient may not even get to see the first Specialist: Paediatrician not to say the second one: me.
Not to mention the operation etc. and the transfer to the Centres of excellence.
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:
Post Script:
“Ten years later mother came to see my secretary and left a photo. It was a photo of her daughter and her new baby. She had been working at the local bank since she left school, met a very nice man and now she had a baby. Mother thought I might remember them and perhaps I would be pleased with the outcome.
“Ten years later mother came to see my secretary and left a photo. It was a photo of her daughter and her new baby. She had been working at the local bank since she left school, met a very nice man and now she had a baby. Mother thought I might remember them and perhaps I would be pleased with the outcome.
I was very pleased for them too but I would hate for anyone to put faith or god to such a test too often.”
King’s Fund: Million £ GP.
See also:
NHS Reform: Dr House & Integrated Service.
Can it be that it was all so simple then
Or has time rewritten every line
If we had the chance to do it all again
Tell me - Would we? Could we?
The Way We Were
The Cockroach Catcher on Amazon Kindle UK, Amazon Kindle US