BIRMINGHAM CHILDREN'S HOSPITAL RESEARCH FOUNDATION
Current Projects (as at October 2013)
BCHRF Awards 2006 (June & October)
Applicant(s) / Project Title & Lay Summary / Amount Requested / *Type of Award / Ref No. /1. Dr H Duncan, Dr H Rowlands, Dr O Bagshaw / Project Title: Use of trans-oesophageal Doppler to monitor cardiac output in Paediatric Intensive Care
Lay Summary: Children in Intensive Care often have poor heart function needing fluid or drugs into a vein to support the heart. Sometimes it is difficult to know how much drug or fluid is needed. The trans-oesophageal Doppler uses ultrasound to measure how well blood is pumped from the heart. This information enables us to estimate heart function and decide on the amount of drugs or fluid needed.
It has been used for several years in adult and children but little is known about normal measurements for children and how well the measurements match what estimates from examination of children. We will assess if there is a difference between doctor’s estimates of heart function and measurements taken from the probe. / £14,214.00 / RP / BCHRF133
2. Dr M S Murphy, Dr M Cooper, Dr N Shaw, Dr C Cummins / Project Title: Adverse Effects of Glucocorticoid Therapy on Bone in Childhood Crohn’s Disease (CD)
Lay Summary: Crohn’s disease is a life-long condition of recurrent intestinal inflammation. If not effectively treated it causes severe symptoms and children become malnourished and fail to grow. It can also cause thinning of the bones (osteoporosis) with a risk of fractures. When active it is either treated with steroid tablets or a special nutrition treatment in which for 6 weeks the child must live on an exclusively liquid diet (LDT). Steroids are very effective but may have side-effects, unfortunately including (like Crohn’s itself) a risk of osteoporosis. LDT is a challenging and difficult treatment for children and their families. It is not yet agreed which of these treatments is best, and so we are planning a national study to answer this question. The present one-year study will be the first-phase of that study. It will focus particularly on the effects of Crohn’s disease and of its treatment on bone. Using bone scans we will examine the effects on bone density. Using specialized urine and blood tests we will explore the underlying biochemical mechanisms. / £48,696.00 / RP / BCHRF136
BCHRF Awards 2007
Applicant(s) / Project Title & Lay Summary / Amount Awarded / *Type of Award / Ref No. /1. Dr NJ Shaw, Dr H Roper, Miss N Crabtree / Project Title: A longitudinal study of bone density and geometry in boys with Duchenne Muscular Dystrophy (DMD) and the impact of corticosteroids.
Lay Summary: Duchenne muscular dystrophy is a disorder which mainly affects boys and causes progressive muscle weakness such that they are unable to walk by their mid-teens. Currently corticosteroids are used to improve muscle strength to enable the boys to remain mobile for longer. There are concerns however, about possible side effects of steroids, particularly the fact that they can cause thinning of bones which may lead to a risk of fracture.
This longitudinal study will examine bone density and bone geometry in boys with DMD before and after they commence treatment with steroids. This will provide important information that will separately identify the effect of the underlying condition on bone density and the potential detrimental effect of corticosteroids on the skeleton. / £35,974.00 / RP / BCHRF161
2. Mr T Jones, Mr D Barron, Mr R Willetts, Mr W Brawn / Project Title: Techniques to Reduce Gaseous Microemboli during Cardiopulmonary Bypass.
Lay Summary: Over the last 20 years significant advances in the care of children undergoing heart surgery have resulted in a mortality rate of less than 5% but despite these advances brain damage during surgery continues to occur with 25% or 1 in 4 children having long-term developmental or neurobehavioral problems. Emboli such as small gas bubbles have been demonstrated in the blood stream during surgery and are known to cause brain damage. The aim of this laboratory research is to look at the heart lung machine used during heart surgery and to study different techniques to see if we can reduce the number of gaseous microemboli in the patient’s circulation. The results of this research will be of immediate patient benefit. / £40,981.99 / RP / BCHRF164
BCHRF Awards 2008
Applicant(s) / Project Title & Lay Summary / Amount Requested / *Type of Award / Ref No. /1. Prof T Barrett, Drs J Kirk, M Taylor, M Desai, C Hendriksz, U Baumann, R Moy, A MacDonald, C Cummins / Project Title: Developing a research clinic for the study of obesity in children
Lay Summary: Childhood obesity is increasing in the UK, with up to a third of Birmingham children now affected; we know this is a risk factor for heart disease in adulthood, and fat children tend to become fat adults. We do not however understand the complications of fatness in childhood, or its relationship with diet and exercise. We plan to set up a research clinic to study obesity in childhood; its associated complications; and what are the predictors for future development of heart disease. We hope to use this as a platform for designing intervention studies to treat obesity in the future. We also plan to offer children participation in an exercise study based on dancing, to improve their cardiorespiratory fitness. / £52,793.00 / RP / BCHRF169
2. Dr LM Notghi , Mr P Bill, Professor S Seri, Dr S Philip, Dr R Gupta / Project Title: A new treatment of children with refractory epilepsy using repetitive transcranial magnetic stimulation (rTMS): pilot study to assess feasibility, acceptability and anti-epileptic effects.
Lay Summary: Some children with severe epilepsy have frequent fits which cannot be controlled by anti-epileptic drugs, or by surgical treatment. Adult patients with epilepsy have been shown to suffer fewer fits after treatment with repetitive transcranial magnetic stimulation (rTMS). TMS uses a high intensity magnetic field above the scalp to induce tiny electrical currents in underlying brain, which may block the electrical discharges responsible for epileptic seizures. The technique is safe and painless. We aim to assess whether this treatment can be used for children, and whether it is likely to be effective as an additional treatment for children with poorly controlled fits. / £48,238.00 / ER / BCHRF191
3. Dr K Morris, Prof S Gough, Dr D Macrae, Prof D Elborune, Prof F Gao, Mr P Narendran / Project Title: Towards a better understanding of hyperglycaemia in critically ill children.
Lay Summary: Every year more around 800 children die in intensive care units across the UK. We know that children who develop a high blood sugar whilst in ICU are more likely to die. We are about to embark on a large trial of 1500 critically ill children to find out whether aggressively controlling blood sugar with insulin will reduce mortality, as has been suggested in adults. We propose to use this unique opportunity to improve our understanding of factors associated with the development of high blood sugar and the response to insulin therapy. Specifically we aim to investigate, for the first time, the importance of increased body weight and whether hyperglycaemia is related to a lack of insulin or a resistance to the action of insulin. / £29,204.00 / RP / BCHRF200
4. Dr M S Murphy, Dr N Crabtree, Dr N Shaw / Project Title: Bone metabolism, bone mineral density and bone strength in childhood IBD - The impact of the biological agent infliximab versus the immune-modulator Azathioprine.
Lay Summary: IBD is a serious and incurable disorder of the digestive system and occurs in children. It can cause severe symptoms including stomach pain, diarrhoea, weight loss and lethargy. It can also lead to thinning of the bones (osteoporosis) resulting in fractures. There are two treatments in common use – azathioprine and infliximab. Both can be very effective in settling active IBD so that symptoms go away. We want to know if they prevent osteoporosis.
We plan to study children taking these drugs over a one year period. We can study bone chemical processes using blood and urine tests. We intend to use two types of x-ray scanner (DXA & pQCT) to study the density of bone in the spine and the arm. pQCT is a very new technique and may be especially useful.
If these techniques prove effective we will also be able to use them in future clinical studies. / £45,499.00 / RP / BCHRF207
BCHRF Awards – 2009
Applicant(s) / Project Title & Lay Summary / Amount Requested / *Type of Award / Ref No. /1. Dr C Patel, Prof E Maher, Dr H Cox / Project Title: High Resolution Microarray Analysis in Congenital Heart Disease (CHD).
Lay Summary: We wish to identify genes that cause inherited congenital heart disease. This will enhance the diagnosis and management of children with congenital heart disease. This will also enable clinicians to counsel families appropriately on the risks to other relatives. Identification of novel conditions associated with congenital heart disease will enable the development of new tests to facilitate early diagnosis, provide information into the cause of the condition, and help guide the development of novel treatment strategies. We are requesting funding for a “Springboard Fellowship” for Dr Chirag Patel so that he can gain research training prior to applying for a national research fellowship. / £65,090.00 / SPRF / BCHRF215
2. Drs W Högler, AL McDermott, M Velangi, N Krone, Prof W Arlt / Project Title: Comparison of adrenal recovery after short- and long-term glucocorticoid therapy.
Lay Summary: Many diseases in children require treatment with steroids (glucocorticoids, GC). However, GC treatment suppresses the function of the organs that naturally produce GC, the adrenal glands. Once GC treatment ends, the adrenals need to recover from long-term suppression. This study investigates how long this period of adrenal recovery lasts. This is important as the adrenals are urgently needed to fight off infections and react to stress.
This study compares adrenal recovery after short-term (5 weeks) GC use in children treated for acute leukaemia and long-term (>2 months) GC use in children treated for airway disorders, in particular haemangiomas (benign condition affecting blood vessels). Blood tests and short adrenal stimulation tests will assess adrenal function at various time points after the last GC dose. In addition, the study explores the comparison of two GC weaning strategies in the long-term GC group. / £29,000.00 / RP / BCHRF226
3. Drs A Peet, P Gissen, C Hendriksz, A Olson, Prof Z Kourtzi / Project Title: Non-invasive investigation of brain metabolism and function in children with neurodegenerative diseases.
Lay Summary: Our research will measure activity in the brains of children with neurodegenerative diseases so we can detect early signs of the disease and understand changes that occur as the disease progresses. At the moment, most of these devastating diseases cannot be cured. Understanding the early signs is critical for diagnosis and for measuring the success of promising new treatments. Treatments that replace genes, for example, are now starting to become a real possibility. We will measure brain chemistry and brain connections. We will also measure brain activity during tasks that exercise vulnerable areas. We want learn to detect reliable changes in chemistry or activity that signal problems before the changes in brain structure become clear and advanced. / £62,224.00 / RP / BCHRF230
BCHRF Awards 2010
Applicant(s) / Project Title & Lay Summary / Amount Requested / *Type of Award / Ref No.1. Dr Wolfgang Högler, Dr Nick Shaw, Dr Nicola Crabtree, Ms Lindsay Rae, Dr Paul Davis / Project Title: Whole body vibration as an osteogenic treatment for mild osteogenesis imperfecta.
Lay Summary: Children with osteogenesis imperfecta (OI, brittle bone disease) have weak bones, weak muscles, fractures and immobility. Milder forms of OI (type 1,4) may not require drug therapy but would benefit from bone-forming treatment. Whole body vibration with side-alternating platforms uses the body’s neuromotor reflex system to train muscles. Recent studies in children with cerebral palsy but also OI suggest that this muscle strengthening therapy also improves bone strength. No study in OI children has compared vibration training effects to a control group.
Our randomized controlled study assesses the effect of 6 months whole body vibration training (2x10min/day) on muscle strength, mobility, bone structure and density. 20 children older than 5 years with mild OI will be randomized into a vibration group and a control group. Patients will be equipped with vibration platforms for home use. / £68,044.94 / RP / BCHRF252
2. Professor Jane McKeating, Professor Deirdre Kelly / Project Title: Molecular studies of hepatitis C virus mother-child transmission.
Lay Summary: Hepatitis C virus (HCV) is the main cause for liver transplantation in adults. HCV is transmitted via infected blood and most children with HCV are born to infected mothers. They have a lifelong risk of developing serious liver disease and liver cancer. We do not understand why some mothers infect their children during pregnancy and why children have a milder illness despite being infected with the same viral strain. We plan to study the genetic structure of the virus in mothers and their children using molecular and biological methods to discriminate between transmitting and non-transmitting virus strains. These studies will help us understand the molecular events that control vertical HCV transmission and will allow us to direct future treatment. / £69,633.00 / PhD / BCHRF253
3. Dr Welch, Dr Shaw, Dr Hackett, Dr Lammas, Dr Akula / Project Title: Vitamin D and innate immunity in children screened for tuberculosis.
Lay Summary: Vitamin D is made by the action of sunlight on skin, with a small amount being obtained from diet. Lack of vitamin D is known to cause the skeletal disease rickets, but it also has many other actions, including an effect on the immune system. Both vitamin D deficiency and tuberculosis are more common in non-white populations in the UK. This may be because of sociological association or a direct biological effect. We plan to measure firstly whether vitamin D levels differ between groups of children with different outcomes after household exposure to TB. In those children with active TB disease, we will investigate whether supplementation with vitamin D has a measurable effect on activation of their immune system. / £9,004.00 / SP / BCHRF255
4. Dr Paul Gissen, Dr James Davison, Dr Phillip Newsome, Professor Jon Frampton / Project Title: Generation of Induced Pluripotent Stem Cells from Fibroblastic Cells obtained from Patients with Inherited Disorders of Protein Metabolism.
Lay Summary: In this project we aim to study severe genetic disorders in which patients cannot normally degrade proteins in the liver. Liver transplantation can prevent brain damage in these disorders but is a high-risk procedure. Recent developments allow patient skin cells to be converted in the laboratory into normal liver cells. The converted cells can be used for designing treatments in PA and OTC. Potential drugs can be tested on the patient-derived cells for their efficacy. Novel technologies allow correction of the genetic defect in the patient cells, which can then be given back to the patient to provide a life-long cure. As the cells come originally from the same patient, they will not require immunity lowering drugs to combat rejection. / £67,228.00 / RP / BCHRF258
5. Andrew Peet, Pam Kearns, Lesley MacPherson, Nigel Davies, Theo Arvanitis / Project Title: 31P Magnetic Resonance Spectroscopy as an early biomarker of tumour response in childhood tumours.
Lay Summary: How quickly tumours respond to treatment is a very good indicator of long term outcome. Improving methods for determining tumour response earlier in treatment is an important research goal allowing effective treatments to be continued and ineffective ones to be stopped in a timely manner. In this project we will assess a new method 31P Magnetic Resonance Spectroscopy (31P MRS) for determining treatment response in children with cancer. The method is closely related to the MRI scans which are a routine part of the children’s care ensuring that the method could be incorporated into current practice quickly and easily. 31P MRS shows particular promise for assessing new drugs which are being developed for combating cancer. / £69,737.00 / RP / BCHRF261
BCHRF Awards 2011