Blog posts

Encephalitis: the rare disease with a million implications

 

22 February is World Encephalitis Day. Founded by The Encephalitis Society four years ago, it aims to help raise awareness of the disease on an international scale.

In a nutshell, encephalitis refers to the inflammation of the brain. Up until recently, it was thought that encephalitis was simply either a viral or bacterial infection. However, in 2005, research described a new version of the disease: auto-immune or ‘anti-NMDAR encephalitis’, which is caused by antibodies that attack the brain tissue. In all its forms, encephalitis is incredibly rare: herpes simplex encephalitis (HSE), for instance, affects approximately one in 1,000,000 children. Although there are clear treatment routes available, viral encephalitis is incredibly destructive. The virus can cause irreversible damage in the brain, which will continue to impact upon a patient’s quality of life well after their short-term recovery from the disease itself.

Despite its often devastating consequences, the rarity of encephalitis might raise some important questions for those hearing about the disease for the first time, namely: why should we spend our time researching something that affects so few people?

It’s crucial to acknowledge that just because something is rare, it doesn’t mean that it’s not important. I started working on herpes simplex encephalitis during my time as a postdoc, because it’s an incredibly useful paradigm for studying genetic disorders, and human genetics in general. Looking at cases of encephalitis can also tell us so much about human immune responses to infection. By investigating what has gone wrong in the body in these rare cases of encephalitis, we also learn more about which immune responses are essential to fighting diseases in the average person. Not only does our research into encephalitis allow us to better combat the disease itself, it also give us insights into the mechanisms at work in our body that help to protect the brain from infection and inflammation. We’re beginning to see that our findings have far-reaching implications for other neurological disorders that may be linked to encephalitis via a crossover of immune mechanisms.

With the relatively recent discovery of anti-NMDAR encephalitis, the field of autoimmune encephalitis has blossomed. Although my primary research is rooted in the viral, infectious type of the disease, we’re beginning to investigate its relationship to this newer form. I’m now working with Dr Ming Lim at the Evelina’s Children Hospital at King’s College London, and Dr Yael Hacohen at the Great Ormond Street Institute of Child Health at UCL, to try and pinpoint whether there is a link between the two. More specifically, I’m interested in finding out if suffering from HSE means that a patient is more predisposed to developing autoimmune encephalitis further down the line. (more…)

Cracking the genetic code of cardiomyopathy in Egyptians

 

Over the past decade, several institutions in Egypt have been making huge scientific progress that is steadily reaching worldwide recognition. It is under these circumstances that I have been fortunate to join the Magdi Yacoub Foundation (MYF), which is recognised as one of Egypt’s most prominent charity organisations. The Aswan Heart Centre – located along the banks of the Nile in Aswan – is an integral part of MYF, offering state-of-the-art medical services for the underprivileged. It focuses on expanding the research on heart disease across the Middle East and beyond to contribute to the world’s scientific knowledge.

With the rise of precision medicine, an approach that uses clinical, molecular, cellular and genetic information to offer effective personalised treatment to patients, Imperial’s Professor Sir Magdi Yacoub emphasised the need to investigate the genetic architecture of the Egyptian population. Understanding the genetics of the disease in the local population will allow for a more accurate diagnosis, a better understanding of the disease mechanism and could potentially facilitate the development of better treatment.

The focus of my PhD project is to identify the genetic determinants of cardiomyopathy – a term which encompasses different heart diseases that often progress to heart failure. Ultimately, I will try to correlate this genetic information with the clinical phenotype of these patients. This project is a collaboration with Imperial College London under joint supervision by Dr Yasmine Aguib and Professor Sir Magdi Yacoub from MYF-Egypt and Dr Paul Barton and Dr James Ware from Imperial. (more…)

“You don’t defibrillate asystole…” and other arguments with creatives

It is a favourite pastime of anyone who works in healthcare to scoff at the mistakes we see when medicine is portrayed on film. From the back-to-front chest X-ray on Scrubs to the miraculous success rates of chest compressions in soaps we love to mock. However, for the last four years I have been working with various TV programmes to try to inject a degree of realism without dampening the drama.

This started with Holby City when I helped out on set, making sure that operating scenes looked realistic and that the actors could pass off as surgeons. This was my introduction to the tension between realism and plot. Being a medical drama, Holby had the budget and resources to try and get things right, but even they couldn’t keep viewers interested if they showed a lovely routine list of day cases where nothing goes wrong!

Holby led to me being approached by Eastenders,  which was a different type of work. With 6–8 million viewers every week, this is a show with massive reach. They have a surprising number of storylines involving medicine, ranging from characters with chronic health problems, through to the massive set piece car crashes and explosions. Even with the minor stuff, when they get it wrong they face a slew of complaints from the public and charities. Often Eastenders will want me to come up with injuries or illnesses that fit a story arc. For example, they will want someone stabbed, look like they are going to die, but then get better and be out of the hospital in seven days. This is normally straightforward, apart from making sure they aren’t reusing stuff from previous years!

Working on longer running storylines is more interesting, the most exciting of which was Phil Mitchell’s liver transplant story on Eastenders. They came to me wanting a way to rejuvenate Phil, who had become a belligerent drunk who had lost his sparkle. I suggested a storyline that took him into liver failure and then showed a long climb back to health, with a liver transplant as the final redemption. However, this was a story fraught with public health issues. It was well established that when the famous liver transplant recipient and footballer George Best started drinking again organ donation rates fell. (more…)

Autumn term – gone in a flash!

My name is James Moss and this is my second blog post (the first is here). I’m a Senior Teaching Fellow in the Faculty of Medicine and I focus on teaching physiology – the body and how it works – to our medical and science students. These posts will be my own thoughts and reflections, and will hopefully give you a (non-invasive) look inside my head at different times of the year.

Students’ arrival

After a long summer of tumbleweeds rolling through the foyer of the Sir Alexander Fleming Building, our Freshers arrived and second years returned, and the building regained its usual hustle and bustle. There were downsides, however: much longer queues for lunch and much more difficult to book a room at short notice! That said, the buzz is totally worth it.

Commemoration Day and my President’s Medal

October 2017 was the first year I attended the Commemoration Day, where our graduating students celebrate their enormous achievements in the Royal Albert Hall, alongside their friends and family. Seeing students that I’ve taught hear their name, smile widely and walk across the stage to shake hands with senior academic staff generated many proud moments.

This was a particularly humbling day for me because I was the recipient of a prestigious internal award (a President’s medal*) for my contribution to teaching. As such, my family and I were treated as VIPs for the day and even had a chaperone. For someone like me who is independent to a fault, this was a very weird situation)! My parents, wife and brother watched the ceremony from the Queen’s Box and were treated to great wine and food. Fortunately, when the time came to receive the award, I made it safely to my prearranged spot without tripping – the Events Team plan the day with military precision. Later, a student in the audience did send me a photo accusing me of sleeping during the kind words the Vice-Provost said about me. That definitely wasn’t the case! (more…)

The Asbestos Story: a tale of public health and politics

The Asbestos Story: a tale of public health and politics
Public awareness of the hazards of asbestos can be dated to the period immediately following the death of Nellie Kershaw aged 33 in 1924.  She had worked during the previous seven years in a textile factory spinning asbestos fibre into yarn. She died of severe fibrosis of the lungs. The pathologist, William Cooke, who found retained asbestos fibres in the lungs, called the cause of death asbestosis.  Nellie Kershaw was not the first case to be reported of lung fibrosis caused by asbestos. Montague Murray in 1899 had reported the case of a 33-year-old man who had worked for 14 years in an asbestos textile factory. He had died of fibrosis of the lungs which Montague Murray, also finding asbestos in the lungs, had attributed to inhaled asbestos fibres.  The patient had told Murray he was the only survivor from ten others who had worked in his workshop.

However, unlike the Montague Murray case, which had aroused little interest, the death of Nellie Kershaw and its cause was widely reported. It led to the government commissioning the Chief Inspector of Factories, Edward Merewether, with an engineer, Charles Price, to report on workers’ health in the asbestos industry. They found, among those still at work who had been employed for more than five years, one third had asbestosis and of those still working in the factory after 20 years, four-fifths had the disease.

The government introduced regulations in 1931 to control exposure to asbestos, together with arrangements for regular medical surveillance of the workforce and eligibility for compensation for factory workers with asbestosis. A benefit commented on by the workers in one factory was a clock on the wall becoming visible to them for the first time. (more…)

Leprosy in 2018: an ancient disease that remains a public health problem today

World Leprosy Day. Image courtest of Wellcome Collection.

28 January 2018 is World Leprosy Day

I have always found leprosy a fascinating disease. It is an incredible example of how microbiology, immunology, and social sciences can collide and impact significantly on human health.

Leprosy has been affecting humans for at least 4000 years. It has played a huge part in teaching us about disease caused by bacteria. In 1873 when Hansen discovered Mycobacterium leprae in tissue samples from patients with leprosy, this became the first bacteria to be directly linked to causing disease in humans. Since then we have developed an understanding of the complex range of types of leprosy that occur depending on how an individual’s immune system responds to the challenge of infection with Mycobacterium leprae. We have also observed the consequences of the deformities and disability caused by the body responding to Mycobacterium leprae, which favours human nerves and skin. In turn, we have seen how the appearance of individuals with disability and disfigurement from leprosy has driven stigma, misinformation, and the discrimination of those affected by the disease.

For many people in the UK and around the world, leprosy, or Hansen’s disease, is an ancient condition of our ancestors. It is something that we hear about in religious scripture or watching films like Ben-Hur or the Life of Brian.  Associated with exile from communities, deformity, and poverty. Something that no longer affects the modern world that we now live in.

Leprosy is often referred to in Sanskrit from around 1400 BC, with the term “kushtha” used to describe it. This translates to “eating away”. Courtesy of Wellcome Collection.

In 2000, the World Health Organisation (WHO) made an announcement that leprosy had been eliminated as a public health issue, with the global prevalence finally falling below one case per 10,000 people. This was the culmination of many years of identifying and treating patients with leprosy. This included the development of multi-drug therapy – a real game-changer in the treatment of Hansen’s disease. In total, over 16 million people affected by leprosy were treated, often free of charge. This was a great success.

And so for the elephant in the room. If we have eliminated leprosy as a public health problem, why do we still need to worry about World Leprosy Day?

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Could gut hormones help make Dry January last all year?

After the excesses of Christmas and New Year, it has become fashionable for January to be promoted as a time for reassessment and resolutions. There are promises and attempts at living a healthier lifestyle, including stopping drinking alcohol (‘Dry January’), joining that gym, stopping smoking, and eating better. However, we know how difficult it is to maintain behaviour change over the longer term. People start drinking excessively again, put back on the weight they lose, start smoking again, and their attendance at the gym wanes. For people who have hazardous levels of drinking, and those who are dependent on alcohol, this is particularly problematic.

If people manage to stop drinking alcohol, we know that there are high relapse rates. In some studies, 60% of people with alcohol dependence have started drinking alcohol again after 6 months of abstinence. This is often precipitated by exposure to social events and situations where there is drinking, and stresses with family, job, and social circumstances. What is needed are strategies to help prevent relapse into drinking. While psychological and group support can be of benefit, there is also a potential role for medications to help reduce the craving for alcohol and the response to stress.

The Division of Brain Sciences in the Department of Medicine at Imperial College London are currently running a research study in this area. We are investigating the potential benefit of a completely novel therapeutic strategy to prevent relapse in alcohol dependence. This is the ‘Gut Hormone in Addiction’ (GHADD) Study, funded by the Medical Research Council. This is targeting hormones from our guts, which can act on our brain to influence eating and addictive behaviours. (more…)

How machine learning will transform the way we look at medical images

Medical imaging is key in today’s delivery of modern healthcare, with an immense 41 million imaging tests taking place in England in every year. Thousands upon thousands of patients safely undergo imaging procedures such as X-ray, ultrasound, and MRI every day, and the product of these tests – the images – play an essential role in informing the decisions of medical professionals and patients in nearly every area of disease.

At its core, medical imaging is the application of physics, and sometimes biochemistry, to visually represent the biology and anatomy of living humans. We have progressed from the first, blurry, x-ray in 1895, to being able to measure minute changes in oxygenation within the brain; whilst major technological advancements continue to be made every year.  In the field of medical imaging, these techniques are applied to expand our understanding of the human body and disease in research settings, but much of this technology does not actually make it into every day clinical practice. For me, this has been the drive to move from a career in sonography into clinical research: to implement novel technology and investigate how it can be used to improve patient care.

One of these advancements is the use of image analysis technology to obtain more information from medical images. There has always been an interest in the use of computers to analyse medical images as computers are not biased by optical illusions or experience like human readers are. In image analysis, an image is no longer considered as visual, but rather as digital information. Each pixel contains a value representing biophysical properties, and you can write a program that finds a specific pattern or feature across the image that can represent disease. However, this process is time-consuming, and a single feature probably doesn’t represent a disease very accurately. (more…)

Death of a cell: the vital process of tidying up cell debris to prevent blood clots

Your cells die every day. Don’t worry, your body is protecting itself. In a process known as apoptosis or programmed cell death, cells that are no longer needed commit suicide. Some cells are only required for a short time, they may be infected by a virus or develop harmful cancerous mutations. Cell death is also an essential part of development from an embryo. For example, mouse paws begin as spade-like structures and only form the individual digits as the cells in between die. During apoptosis the cells fragment into smaller apoptotic bodies, and their cell surface is flipped open to display lipid molecules called phosphatidylserines, which act as an ‘eat me’ signal to recruit cells called macrophages to engulf them, before their contents spill out and damage the surrounding tissue. This is a process known as efferocytosis.

However cell death is not always so orderly. Some cells suffer premature death known as necrosis, where they burst open for various reasons such as infection, physical trauma or extreme temperatures. As the cell’s contents are released into the open, an inflammatory response is triggered. Studies are ongoing to establish the many mechanisms by which this process occurs. For example, it is known that proteins on the surface of immune cells, called pattern recognition receptors or PRRs, detect the material released by dying cells, and trigger the expression of genes leading to the release of inflammatory substances. When an infection occurs, the immune response is usually short-lived as it rapidly kills the infection. However, when cell necrosis and subsequent inflammation occurs over a longer period, the substances released by macrophages – that have migrated in to engulf the dying cells – can damage the surrounding tissue, resulting in a build-up of dead cells.

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Big hearts and giant genes: What lies at the end of the yellow brick road?

Upasana Tayal was shortlisted for the MRC Max Perutz Science Writing Competition 2017 for the following article:

“Hearts will never be practical until they can be made unbreakable”, said the Wizard of Oz. “But I still want one”, replied the Tin Woodsman.

Your heart makes you human, makes you love, and keeps you alive. In just one year, it will beat 40 million times, without rest or time off for good behaviour. A pretty impressive piece of machinery you might agree, no wonder the Tin Man wanted one so much.

And like many things in life, he may have wished for a big heart at the end of the yellow brick road.

He would be forgiven for imagining a big heart to be a good thing, extra caring and compassionate, and if the Tin Man was scientifically inclined, more effective at doing its job of pumping blood around the body.

Unfortunately for the 1 in 250 people in the world living life with a big heart, the reality is very different. (more…)