Institute Chairman Shaughn O’Brien Bows Out

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After three long years as chairman, Professor Shaughn O’Brien is leaving the North Staffordshire Medical Institute. The obstetrician and gynaecologist takes a moment to reflect on his time at the helm.

“It’s a lovely building for meeting and conferences,” he says. “It’s a good focus for research, a good focus for postgraduate education, it’s a good focus for the community and it’s a good focus for people people putting on meetings an conferences of a high standard.”

During two separate tenures as chairman, Prof. O’Brien has seen the Institute through some challenging times. His first, from 2002 to 2005, included the biggest shake-up in the charity’s history when the hospital trust’s Clinical Education Centre, part of Keele University’s Medical School, was built at the University Hospital of the North Midlands.

The Institute, which had been the area’s main teaching centre for postgraduate medicine, was suddenly left with less purpose and little funding.

“The medical library was moved and all the funding went with it,” says Prof. O’Brien. “In the process of that we had to really set up the Institute as a conference centre. One of the key things we achieved was to make sure we took ownership of the land rather than leasing it from the NHS – and more importantly for conferences, the whole of the parking facilities.

“We also made a lot of changes to the structure of our grants, making them pump-priming for new researchers.”

Appointed vice chairman of the Royal College of Gynaecologists (RCOG) in 2004, Prof. O’Brien stepped back from the Institute to concentrate on the role and his own research. He found himself taking the reins again in 2015, admitting: “It seemed like a good idea at the time.”

The chairman went on to face another period of change with his trademark creativity and vision. His legacy at the Institute includes their support for the annual Firelighter Awards, organised by Keele University’s Dr Adam Farmer, which give NHS staff the chance to pitch for medical research grants in a Dragon’s Den-style competition.

He also arranged Institute funding for the ASPIRE programme at Keele University, designed to help medical students engage with academic research. The scheme is led by Professor Divya Chari and Dr Samantha Hider.

Prof. O’Brien is now behind plans to rebrand the Institute as part of a major refurbishment project. The facility will even be given a new name – as yet being kept under wraps.

He says: “We’ve had a significant donation to allow us to redevelop the Institute as North Staffordshire’s  high-profile, named conference centre. It should highlight our ability to hold conferences which are not only medical, while retaining the loyalty we’ve built up with our existing customers.”

While he hopes to remain involved with the building work, the father-of-two already knows how he will fill his semi-retirement. It will begin with his valedictory meeting at the RCOG in September.

As well as his continuing research and private practice, he plans to devote the extra hours to his artistic side.

He says: “I’ve already begun to go to sculpture school in London, I’ve got some pieces in the Medical Art Society’s Annual Exhibition at the Royal Society of Medicine in July. I also want to get back to playing the clarinet and saxophone some more.”

Prof. O’Brien has been replaced as chairman by Mr John Muir, the UK’s longest-serving NHS consultant.

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North Staffs Scientists Seek Cure for ‘Silent Killer’ Heart Defect Affecting 620,000 Brits

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North Staffordshire researchers have been awarded £20,000 to help cure a heart defect that causes thousands of sudden deaths each year.

The experts hope to understand and control arrhythmogenic right ventricular cardiomyopathy (ARVC) – a condition that affects around 620,000 people in the UK and causes up to five per cent of young adult deaths.

Sufferers often fail to notice any symptoms, which can mean they do not know they have the genetic disease until it is too late.

While ARVC cannot be prevented, group leader Dr Vinoj George believes it could be controlled in the early stages through genetic engineering to stop it becoming lethal.

His pioneering study will receive the funds from local charity the North Staffordshire Medical Institute.

Dr George said: “This disease manifests with different severity. In some patients even a little bit of stress can trigger it, often resulting in sudden cardiac death.

“There are other people who live perfectly well with it and it can be controlled by drugs or devices that can be put in to maintain heart rate.”

He explained that ARVC is caused by a genetic mutation affecting the cell protein that ‘glues’ the heart muscles together. This leads to the death of cardiac cells, stopping the heart from pumping properly and causing an irregular heartbeat.

The same problem gene can manifest with different severities.

Genetic Engineering

Dr George’s team, based at Keele University’s Institute for Science and Technology in Medicine (ISTM), will create the ARVC mutation in human stem cells in the laboratory, before converting them into cardiac muscle cells.

They will then use optogenetic technology – which uses light to change the behaviour of mutated cells – to look for the genetic triggers that make the disease more severe.

He said: “We’re taking stem cells, we’re creating the protein mutation in the cell and then we’re making the cell behave like it would in the heart. Then what we’re doing is trying to use genetics to control how the disease can be reproduced and modified at the cellular level.

“Once we identify the genes that are responsible, then it will help us to find drugs or strategies to control that mechanism.”

Patients are usually diagnosed with ARVC on the basis of their symptoms, but the underlying genetic cause can only be confirmed by a test in a specialist clinic. This is often reserved for severe cases and the relatives of known sufferers, who have a 50 per cent chance of passing the disease on to their children.

Dr George’s study will use genetic data provided by St George’s Hospital in London, which treats a range of ARVC patients with various mutations and severities.

He added: “We hope to translate our work to benefit clinicians at the Royal Stoke Hospital in devising treatment strategies to control ARVC severities, potentially at a younger age.”

NSMI Funding

The grant was allocated as part of the NSMI’s annual awards, which are funded by a combination of public donations, bequests and the income from conferences and room hire facilities at the charity’s base on Hartshill Road, Stoke.

Once Britain’s first postgraduate centre, the iconic building is now used as a conference facility.

While the annual funding has now all been allocated, researchers will soon be able to apply for the Institute and UHNM’s Firelighter Awards of up to £10,000.

For more information, visit www.nsmedicalinstitute.co.uk, like us on Facebook or follow us on Twitter. Anyone interested in making a bequest is asked to email manager Jacqui Robinson at jacqui@nsmedicalinstitute.co.uk.

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NSMI-funded scientists seek genetic treatments to fight frailty in older people

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North Staffs researchers have won a £19,985 grant to investigate whether gene therapy can stop older people becoming frail.

The group, led by Dr Adam Sharples, hopes to pave the way for new treatments that will reduce falls and weakness in the elderly by switching off the genes that cause muscle wasting.

They will study tissue samples donated by hip and knee replacement patients to find which genes cause unused muscles to break down – with the help of the funding from local charity the North Staffordshire Medical Institute.

Dr Sharples said they expect to find these genes are ‘marked’ by special chemical ‘tags’ that tell them to be active or inactive, known as epigenetic modifications.

The discovery could eventually allow doctors to give patients medication that will replace the effects of exercise.

He said: “It’s very difficult to persuade an older person who’s never exercised in their life to take up a fitness regime. If we identify genes that we already know there are drugs for we can give them to people who don’t want to or can’t exercise due to frailty.”

Discovery

The team, based at Keele University’s Institute of Science and Technology in Medicine, has previously found muscles can remember periods of growth, so they can grow larger later in life.

They will investigate whether the opposite applies after wasting – meaning muscles may break down more quickly if an injury is repeated.

If so, the muscle memory could potentially be ‘switched off’ in older people hurt in a fall, slowing down the wasting process that makes them more likely to fall again.

He added: “Can we intervene if a patient has had a fall and lost muscle to prevent that from happening again and make people less frail? The cost of frailty to the NHS is on the increase, especially with an aging population.

“The thing it impacts on is quality of life, so people can’t do simple tasks like walking upstairs or opening a can of beans. So our aim is not necessarily to extend life but to improve quality of life as people get older.”

Using the latest genome wide techniques, the team will study more than 850,000 sites on the DNA of patients with muscle wasting after an operation. They will then compare them to a control group of normal muscle samples.

Dr Sharples said: “What we’re going to do is take a chunk of muscle about the size of a broad bean, usually from the quadricep, and look at the difference between someone who’s had a trauma or an injury and had to have an operation and someone who hasn’t.

“Normally those people have some kind of muscle wasting in a very short period, even in two or three weeks where the limb is suspended.”

Grant

The grant was allocated as part of the NSMI’s annual awards, which are funded by a combination of public donations, bequests and the income from room hire at the charity’s base on Hartshill Road, Stoke.

Once Britain’s first postgraduate centre, the iconic building is now used as a conference facility.

While the annual funding has now all been allocated, researchers will soon be able to apply for the Institute and UHNM’s Firelighter Awards of up to £10,000.

For more information, visit www.nsmedicalinstitute.co.uk, like us on Facebook or follow us on Twitter.

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NSMI Charity’s £58,000 cash boost for local medical research

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Charity the North Staffordshire Medical Institute has announced a £58,000 cash injection for three “outstanding” local research projects.

The money will support new studies based at Keele University and the University Hospital of the North Midlands (UHNM), designed to improve treatments for cancer, heart disease and muscle wasting in the elderly.

A panel of experts led by Institute chairman Professor Shaughn O’Brien allocated the funds after reviewing applications for their annual grants.

Prof. O’Brien said: “We were very impressed by the research proposals we received on a wide range of topics, all of which could have been funded.

“The reasons for our choices were the outstanding quality of the applications, the importance of the disease areas and the strong track records of the departments involved in delivering research.”

The professor, a leading obstetrician and gynaecologist, oversaw the award process alongside colleagues from a range of medical disciplines.

They included gastroenterologist Dr Adam Farmer, clinical biochemist Professor Richard Strange and Professor of Biomedical Imaging Melissa Mather.

He added: “We are confident these projects will be of great value to the community of Staffordshire and to medicine as a whole.”

Award recipients

The panel awarded £18,450 towards a study into treatment-resistant cancers, led by Dr Alan Richardson at Keele’s Institute of Science and Technology in Medicine (ISTM). His team aim to restore the sensitivity of cancer cells to chemotherapy drug paclitaxel.

A second group based at the ISTM, led by Dr Vinoj George, were awarded £20,000 to investigate heart condition Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC). They hope to identify those at most risk from the disease, which can cause sudden death.

Cell and tissue engineer Dr Adam Sharples and his colleagues, also from the ISTM, were given £19,985 to research muscle wasting in the elderly.

The awards were funded by a combination of public donations, bequests and the income from room hire at the Institute’s base on Hartshill Road, Stoke. Once Britain’s first postgraduate centre, the iconic building is now used as a conference facility.

While the annual grants have now all been allocated, researchers will soon be able to apply for the Institute and UHNM’s Firelighter Awards of up to £10,000.

For more information, visit www.nsmedicalinstitute.co.uk, like us on Facebook or follow us on Twitter.

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In their own words: NSMI-funded scientists on their groundbreaking work

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North Staffordshire Researchers undertake innovative brain injury study involving surgeons and scientists

In a new study started in 2017, a North Staffordshire research team has succeeded in keeping adult human brain tissue alive in a dish outside of the body, using samples of tissue donated by living patients undergoing surgery for a brain condition called ‘Chiari malformation’.

Clinical lead for the study, consultant neurosurgeon Mr Nikolaos Tzerakis explained: “The Chiari malformation is a fairly common problem in Neurosurgical practice. Simply put, the part of the brain at the back of the head which is called the cerebellum, lies lower than the normal level.

“This creates crowding in a tight bony space called foramen magnum, which then causes some difficulty in the circulation of the brain fluid. Patients with Chiari malformation present with headaches mostly during coughing, laughing and straining.

“When surgical treatment is required the usual operation is called Foramen Magnum Decompression, during which we remove a small part of the bone at the back of the head and the spine. On a few occasions, some cerebellar tissue has to be removed to allow adequate decompression and circulation of the brain fluid.

“This sample would have been of no use until now because according to the classical surgical protocol it is removed and disposed. However, this tissue has living nerve cells and they can be grown in the laboratory without any additional risk to the patient.”

Patients with Chiari malformation are widely believed to have essentially healthy (viable) tissue because the brain tissue is misplaced rather than diseased. In the past, scientists studying the human brain have been limited by the difficulty in obtaining tissue for such studies.

Their options have been limited to samples removed post mortem – which can quickly die – or tissue from cancerous or diseased brains.

Proving the successful use of Chiari tissue in a dish has the potential to be a very useful new scientific development, which could help in the study and discovery of new treatments for brain injuries and diseases which could be investigated using such a model.

Before they could start their research, the scientists went through a three-year planning process including an exhaustive review within the NHS to make sure their methods were ethical.

They sought consent from a number of patients, some of whom agreed for their cerebellar tissue to be kept for the research study, rather than be incinerated, as would be the normal practice.

Clinical Lecturer Mr Jon Sen, a neurosurgeon, said: “It made me think ‘why has no one thought of doing this before?’ The simplest ideas are often some of the best ones, but it still took a lot of banging our heads together in the neurosurgery department to reach the idea of trying to obtain tissue from our Chiari patients.

“A key issue is that Chiari is the only surgery we ever do where we take out brain tissue that we could consider within a ‘normal’ enough limit that we could develop a meaningful tissue injury model from.”

The study – supported by a grant from the North Staffordshire Medical Institute – is being led by Professor of Neural Tissue Engineering at Keele’s medical school, Divya Chari.

This new scientific advance also has the potential to reduce the need for animal testing, and could allow the Keele University scientists to simulate the effects of injuries on brain tissue in a laboratory environment.

Prof. Chari said: “I feel passionate about the need for models to reduce animal experimentation. In my early training, I learned to reproduce brain and spinal cord injuries in rodents so I know first-hand the major ethical and technical difficulties these have.

“In animal models there’s potential for substantial suffering – they can lose movement and bladder control, become quadriplegic.

“Our aim is to develop a successful dish model for use in laboratories, that’s relevant to human injuries. We’ve previously proven we can develop models in a dish using tissue derived from rodents, but this is the first time we’ve done it using human tissue.

“Make no mistake, this is a huge undertaking and the success of the work relies on collaboration of a big team working across the hospital and laboratory units. This includes neurosurgeons Mr Nikolaos Tzerakis and Mr Rupert Price, research nurse Holly McGuire and scientists Dr Jacqueline Tickle and Dr Christopher Adams at Keele University.”

The study was a long time in the planning, however, the process accelerated rapidly when the team finally received their first tissue sample this summer.

Researcher Dr Jacqueline Tickle said: “The time for collection from the patient and processing in the laboratory was less than an hour. It has to happen very quickly so there’s less time for the tissue to die and it remains viable.”

The tissue samples were cut into slices of varying thickness to examine the tissue survival and observe major brain cell types.

At first the researchers had no idea what to expect.

Prof. Chari said: “The fact that we have seen tissue survival for well over two weeks made us excited because we had no idea whether we could get it to remain viable for even 24 hours. The fact that we can detect the major cell types present in the brain is very positive”

When an incision was made in one of the samples to replicate an injury, the researchers believe they can see some changes that are typical of genuine brain injuries.

Prof. Chari and Mr Sen added: “This is still very, very early. We’ve only got the tissue from two patients so far. Getting the tissue depends on many factors- whether the patient consents to donating the sample, whether the surgery goes ahead as planned, and ultimately whether the surgeon makes the decision to remove the tissue.”

“So we are in it for the long haul, but we all believe it is worth the effort, because the first results are pretty exciting. The main outcome at this stage is that we’re confident that the tissue can remain viable for a relatively long time, if the conditions are kept right.  It suggests that we could make an injury model in these tissue samples and then look at responses to therapeutic manoeuvres.”

Professor Shaughn O’Brien, chairman of the North Staffordshire Medical Institute, said: “This is an outstanding research project and a unique and clever approach to the study of neural/brain tissue which will attempt to replicate the real life situation in human tissue but without being in any way additionally invasive for any patients.”

The North Staffordshire Medical Institute is a charity funded by public donations that provides grants for vital medical research in the Staffordshire area.

To find out more about their work, visit nsmedicalinstitute.co.uk.

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