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

Research , Wade Conference Centre

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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North Staffordshire scientists invent new home test for diabetics

Research , Wade Conference Centre

A North Staffordshire research team hopes to save patients time and the NHS millions with a new home testing kit for diabetics.

The scientists, led by Clinical Biochemist Dr Chris Duff, want to end the need for Britain’s four million patients with diabetes to visit a clinic for routine haemoglobin testing every four months.

Their DIY version of the HbA1c test will be similar to the finger prick kit some diabetic patients currently use to monitor their own blood sugar.

Patients will be shown how to collect tiny samples of blood using the kits, which will be delivered to their homes at regular intervals then returned by post for laboratory testing.

The project, based at Keele University and University Hospital of North Midlands, has been funded in part with a £7,515 grant from the North Staffordshire Medical Institute.

Time-saving innovation

Researcher Kathryn Ford explained: “We’re trying to help patients do their diabetes monitoring at home rather than coming into hospital because it’s inconvenient.

“At the moment they have to take time off work, then they have to go to the hospital, they have to park.

“We want them to be able to do a finger prick at home and send it in on a card rather than coming in to have their blood taken.”

The team have already developed the test and shown that the dried blood can survive the postal system until it is reconstituted in the laboratory.

Their next step will be to create the kit itself and recruit patients to take part in a pilot scheme.

She added: “I need to get a focus group of about 20 patients with diabetes and ask them if they would like to take part in the trial.

“We can then get patient feedback and hopefully roll it out.”

Preventing Complications

The HbA1c test measures the levels of glycated haemoglobin in a patient’s blood to see how well they have been controlling their diabetes over the previous months.

A healthy level for non-diabetics is below 42 mmol/mol, whereas diabetics are told to aim for around 48mmol/mol.

Higher levels of the substance show a patient’s diabetes is badly-controlled, putting them at risk of serious complications like blindness, heart disease and limb amputations.

Kate said: “You can end up with kidney disease, heart disease, eye problems, numbness in your hands. It’s all very unpleasant.

“We want them to test every three to four months but to get patients to test every three to four months is very difficult.

“By sending the kits out at the right time we can better control the frequency of the testing and by doing that we can optimise monitoring.”

Professor Shaughn O’Brien, chairman of the North Staffordshire Medical Institute, said: “I expect this to be a very real advance in diabetic care.

“As well as the convenience for the patients improved blood sugar control is likely to be very much improved.

“I look forward to seeing the data on the cohort being presented at next year’s annual research awards event.”

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 our work, visit nsmedicalinstitute.co.uk.

By Meg Jorsh

 

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Keele student showcase highlights the future of medical research

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Student doctors had the chance to present their research to leading academics in a showcase event at Keele University.

The ASPIRE Research Showcase – supported by the North Staffordshire Medical Institute and led by Professor Divya Chari – is designed to give the medical researchers of the future the chance to show off their ideas and develop their presentation skills.

This year’s event on Wednesday, November 22nd featured talks and poster displays from 37 medical school undergraduates.

Institute chairman Shaughn O’Brien said: “I was so impressed with the professionalism, eloquence and obvious intelligence of the ASPIRE students and the content of their presentations and posters.

“These are obviously the medical academics of the future and the sooner they can aim their careers in that direction the better.”

The event has taken place annually since 2013 and was recently awarded Institute funding of £15,000 a year, guaranteed for at least five years.

Guest Speakers

This year’s programme included talks by Obstetrics and Gynaecology lecturer Dr Pensee Wu and infectious diseases expert Dr Andrew Ustianowski.

Professor O’Brien added: “The collaboration between the Institute and the Medical School is proving to be very fruitful.

“This is very good use of the charitable donations that the Institute receives and awards.”

Students presented their research on a wide range of subjects including concussion education in elite rugby, the effect of marital status on the risk of cardiovascular disease and the role of genetics in mental illness.

The prize for the best oral presentation was awarded to Jessica Green for her research into preventing intestinal blockages in cystic fibrosis patients.

Meanwhile Will Woods won the best poster award for his work on using chick embryos as models for spinal cord injury research.

Partnerships

The initiative is one of several organised by the NSMI in partnership with Keele University and the University Hospital of the North Midlands NHS Trust.

It has also collaborated with the trust to organise their annual Firelighter awards, taking place for the second time  in spring 2018.

Staff from all over the UHNM will be invited to submit their ideas for new research projects, with the winners to be chosen in a Dragon’s Den-style event.

The Institute is currently considering applications for its next round of pump-priming grants to kickstart new research projects, with the winners due to be announced in February.

ASPIRE is an Academy of Medical Sciences and Wellcome Trust-funded programme that helps medical students to engage with medical research.

It also supports a student-led research network and provides holiday bursaries for students to undertake summer research projects at Keele.

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Sunshine vitamin D holds the key to beat childhood asthma, North Staffs scientists claim

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A North Staffordshire research team hopes to prove spending time in the sunshine is the key to improving childhood asthma.

The experts, led by consultant paediatrician Dr Will Carroll, believe many asthma attacks in children can be linked to a deficiency in vitamin D – a substance produced by the body when it is exposed to sunlight.

Their preliminary research has found asthmatic youngsters are hospitalised more often in less sunny parts of the country.

Controlled trials

Dr Carroll now hopes to prove that giving children vitamin D supplements will cause asthma complications to fall, in a study part-funded with a £19,884 grant from the North Staffordshire Medical Institute.

He said: “We know from the analysis that in regions of the UK that are more sunny they have lower rates of childhood asthma.

“But between October and February each year, the sun doesn’t get high enough in the sky in the UK to produce vitamin D anyway, so we have to rely on supplementation in those months.

“Previous studies have shown that small doses of vitamin D can reduce asthma exacerbations in children.”

The team, based at Keele University, plans to start with a small study in which asthmatic children will be given either vitamin D or a placebo and the progress of their asthma will be monitored.

They will use this to help them design a much larger controlled trial to take place in several locations around the country.

Dr Carroll, an expert in paediatric lung disease, added: “The purpose of the programme is to show that it’s more effective to give vitamin D to children than a placebo.

“The vitamin D available now is colourless and odourless, so that helps us to do our research. What we’re hoping to find is that it reduces asthma exacerbations in children.”

Health advice

If the programme proves a success, it could mean dramatic changes to the official health advice around taking children out in the sun.

At the moment, parents are advised to cover kids up as much as possible and use high-factor sunscreen to prevent the risk of burns, heatstroke and ultimately skin cancer.

But if vitamin D is important for respiratory health doctors may start advising that children spend short periods outdoors without sun protection.

He said: “If you cover yourself in sun cream you don’t get vitamin D because you need to have exposure to UVB rays.

“Nearly all children in the UK have insufficient levels of vitamin D. We’re designed as human beings to be semi-clothed and to live outside, we’re not meant to be indoor creatures.”

There are currently 5.4million people living with asthma in the UK – one of the highest rates in Europe – including 1.1million children.

The lung condition killed 1,468 people in 2015 and costs the NHS an average of £1billion a year.

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

By Meg Jorsh

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Heart surgery safer thanks to £250,000 North Staffs research project

Research , Wade Conference Centre

By Meg Jorsh

North Staffordshire scientists are making heart surgery safer with a groundbreaking £250,000 study.

The research team, led by Professor Mamas Mamas, hopes to revolutionise the way patient health records are used by the NHS to prevent complications after coronary stent procedures.

Patients often have a stent – a short wire-mesh tube – inserted to treat angina or following a heart attack. It works by stretching open a narrowed or blocked artery.

Although a common procedure, it carries a small risk of complications ranging from bruising to heart attacks, strokes and even death.

Prof. Mamas and his team hope to cut this risk even further by analysing millions of records to identify the patients who experience the best outcomes and those with greatest chance of their operation going wrong.

He explained: “It’s a programme of work and my ultimate aim is that we use this data to more efficiently in a way that provides insight for the whole patient journey rather than just the short time they’re in hospital.

“Ultimately it’s about getting the right outcomes, getting the right procedures to the patient in the safest manner.”

Using ‘big data’

The massive study, which started in 2011, was funded in part with a £249,983 grant from the North Staffordshire Medical Institute.

It involves millions of local, national and international records, which makes the data exceptionally accurate compared to an average-sized medical trial.

Prof Mamas said: “We’ve looked at the procedure to see if there is an optimal way of doing it, which may be related to drugs or how you actually perform the operation.

“The other thing that it’s told us is how commonly complications occur. If you’re looking at a rare outcome it’s very difficult to study that in a randomised trial – getting three complications in a thousand cases wouldn’t tell you very much.

“If you have half a million patients you can get a lot more information.”

The Professor of Cardiology, based at Keele University, has already used the data to give each UK doctor performing the procedure a safety rating, which is available for patients to view online.

His team now hopes to provide a longer-term picture of surgery outcomes by combining the separate records held by hospitals and community-based services.

Their research has already shown that post-operative bleeding is far more common than previously recognised – affecting around one in five patients compared to the previous statistic of one in 20.

He added: “In the past this information wasn’t collected electronically. You wouldn’t have the whole of the UK’s collected data on a particular procedure, the computers simply weren’t there.

“The challenge that still remains is comingling the data. I can tell you what are the outcomes of these procedures in hospitals, but I can’t tell you what happens after patients are discharged, because it isn’t shared across the data sets.”

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 about our world-class conference facilities, visit http://www.nsconferencecentre.co.uk

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Understanding Grief – an Interview with Linda Machin

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Meg Jorsh speaks to bereavement theory pioneer Linda Machin about her groundbreaking research

Grief affects all of us at some point in our lives. When a loved one dies we may feel crushed, overwhelmed. Then it fades to a quiet pain that hides behind everything we do until we finally learn to live with it.

But for some of us, relief never comes. The waves of sadness continue to mount, so that everyday life seems tiny by comparison. For these people bereavement holds risks of its own – depression, anxiety disorders, substance misuse, sudden cardiac events and potentially suicide. They need professional help to adjust to their new way of living.

Unfortunately it can be hard to tell the difference between those treading water and those not waving, but drowning. It has been the life’s work of bereavement expert Dr Linda Machin to better understand the landscape of loss and the ways individuals grieve. Her pioneering research has helped countless professionals to understand grief and bereaved people to feel better understood.

“I think a lack of understanding can make grief longer-lasting than it needs to be,” says Dr Machin. “It can bubble along even worse for some people if they feel misunderstood and their care isn’t addressed appropriately.

“People who begin to grieve chronically can also become depressed and anxious, the ultimate potential risk is suicide. You only have to look at the media attention to Princes William and Harry and their comments about losing their mother to appreciate the long-lasting and persistent nature of grief. They were young people then but it can apply to people at any stage of their lives.”

Models of Bereavement

Dr Machin is best-known in her field as the creator of the Range of Response to Loss model and Adult Attitude to Grief scale. These psychological tools allow professionals to categorise a bereaved person’s  grief according to their levels of overwhelmed, controlled and resilient reactions. A more overwhelmed person may be so distressed they feel they can never be happy again, whereas a more controlled person may refuse to accept the reality of their loss. On the other hand, a resilient mourner may feel they are able to cope with their pain.

“The AAG scale is a kind of a triage system,” Dr Machin explains. “The interventions that are deemed appropriate are based on the scale. Some people who are very overwhelmed by their grief will need a very different intervention to someone who’s closed down on their grief but is still not coping.”

“NICE have produced guidance for bereavement intervention – the first group is one where people simply need signposting to practical advice and support from family and friends. The second is one where people do need some opportunity to talk about things that are troubling to them. Then the third are the group who are most vulnerable and are likely to need longer-term intervention by therapists.”

Further Research

The more recent development of the AAG scale to identify  vulnerability was funded by the North Staffordshire Medical Institute for research with two Marie Curie hospices (Hampstead and Belfast), the Dove Service bereavement support team in Stoke-on-Trent and the bereavement service of St Giles’ Hospital in Lichfield. It is now being used by a range of UK organisations including Marie Curie and Cruse Bereavement Care, as well as internationally by groups in Canada, Iceland, Portugal, Australia, Pakistan and the USA. Dr Machin is also working on a modified version for people affected by terminal illness.

“It’s  looking at the whole question of mental health and loneliness,” she says. “The ultimate aim is that this is a method that allows the practitioner to enhance their work with people as  they progress from end of life care  to bereavement.”

Dr Machin and her team, based at Keele University, received a £4,500 grant from the North Staffordshire Medical Institute in 2011.

For more information on the medical research charity or to make a donation, visit our website at https://nsmedicalinstitute.co.uk/. You can also like us on Facebook at @nsmedicalinstitute or follow us on Twitter at @nsccentre.

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Safer cannabis use a myth, North Staffordshire research reveals

Research , Wade Conference Centre

The North Staffordshire Medical Institute supports research in a wide range of fields – including substance misuse. We spoke to expert Dr Roger Bloor about his study of cannabis vaporisers.


If you believed the manufacturers, you might think that vaporisers were a safe way of using cannabis.

The smoke-free inhalers are sold as a harmless way of getting high without lighting up. They do allow users to avoid some of the cancer-causing chemicals in cannabis smoke – but it comes at a price, according to research funded by the NSMI. The vaporiser fumes do not contain as much tar, hydrogen cyanide and nitrous oxide as would be produced by a cannabis ‘joint’. But they do contain toxic levels of ammonia, putting users at risk of serious lung disorders.

Lead researcher Roger Bloor, a former psychiatrist and addiction specialist, explains: “Cannabis, which is illegal in this country, is very widely used but carries risks from things like tar, which clogs up your lungs and can cause all sorts of health problems.

“Some people devised a way of using cannabis without smoking it by heating it up on an electronic plate and that reduces the risk. We investigated and we found that it does reduce the tar, but there’s a massive spike in the production of ammonia when you use these devices. The type of level whereby if you were running a factory, it would be shut down as a public health risk.”

Ammonia, which is commonly used in agriculture as fertiliser, is a poisonous chemical that can cause blindness, lung damage or death when inhaled at high concentration. Large quantities were detected in cannabis vapour produced in the labs at Keele University and analysed with cutting edge SIFT-MS
technology. The study looked at popular vaporiser brands available online, including the notorious Blue Meanie and Volcano models.

“We used standardised cannabis, where we knew what was in it, and we also had a license to have any seized drugs sent to us so we had street cannabis as well,” says Dr Bloor. “Street cannabis contains far more ammonia than the farmed cannabis usually used for research. This is because ammonia is found in the buds of the plant, which street cannabis is full of, rather than the leaves.”

The original research, funded by a grant of just £4,869 in 2004, went on to inspire several follow-up studies and an article in world-renowned journal Addiction. It is regularly cited as a warning to those considering buying a vaporiser as a ‘safe’ alternative to cannabis cigarettes. The devices, which cost from £35 to £350, are still widely available from specialist shops.

Dr Bloor said: “People recommend them, and they recommend things like water pipes, to take out the high tars. There’s a whole industry producing things to technically reduce the risk from cannabis which people are keen to use, but the research into them is not complete.”

Even if the devices could make smoking cannabis physically safe, they would not prevent the risk of psychiatric side effects. “The major risk of cannabis is that it can trigger schizophrenia,” he adds. “The strong stuff can be highly dangerous, but with the lower-powered stuff most people use the main risks are physical.”

To find out more about the research funded by the North Staffordshire Medical Institute, like us on Facebook and follow us on Twitter. Please help us to support pioneering research projects by making a donation through the link to the right of this page.

 

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