BJA/RCoA PhD Studentship
The successful applicants for the BJA / RCoA PhD Studentship were:
Principal Applicants
Dr Claire Gibson & Prof Dave Lambert
University of Leicester
Title
Investigating the pharmacology of Nociceptin/OrphaninFQ receptors during cerebral ischaemia
Amount
£72,310
Scientific Abstract
Nociceptin/OrphaninFQ (N/OFQ), and its receptor (NOP), is classified as a non-classical member of the opioid family. NOP plays many diverse roles and drugs targeting this system are involved in modulating pain processing, cardiovascular control and immunomodulation. Previous work from our labs has shown that activation of central NOP inhibits K+ and ischaemia-evoked glutamate release. Excess glutamate release is excitotoxic and a significant contributor to the cell death observed following cerebral stroke. Thus, mechanisms which may reduce excessive glutamate release, for example NOP activation, would be predicted to be neuroprotective following cerebral stroke. This project will use in vitro and in vivo models of ischaemia in order to determine the contribution of these receptors to the damage produced as a consequence of ischaemia. The contribution of receptors will be determined by the application of drugs (i.e. agonists and antagonists) that modulate receptor activity and the use of NOP-deficient mice. Likely techniques to be used during the PhD project include: cell culture, immunocytochemistry, in vivo surgical techniques, RT-PCR and other molecular biology techniques.
Please see the NIAA's position statement on the use of animals in medical research.
Principal Applicant
Dr Graeme McLeod
University of Dundee
Title
Improved patient safety with microultrasound: Development of anatomical models for evaluating clinical potential of microultrasound imaging during epidural and regional anaesthesia
Amount
£72,363
Scientific Abstract
Epidural analgesia and peripheral nerve block are an integral component of NHS accelerated recovery programmes. However, block success requires precise and safe placement of needles, and circumferential local anaesthetic spread. For labour, 28% of our epidural insertions need multiple attempts, and 1 in 60 patients have major side effects; a third of our thoracic epidural patients have pain in the recovery room, and 1 in 7 have technical problems; our meta-analysis of 47 studies has shown better anaesthesia using ultrasound guidance but no difference in the incidence of temporary nerve damage (1 in 14 patients) compared to nerve stimulation techniques. Our recent RAUK funded study, validated high resolution microultrasound nerve imaging - the number, dimensions, pattern and distribution of fascicles were similar when compared to histology sections. We visualised the tip of the needle as it displaced and traumatically split fascicles.
We now wish to: (1) validate epidural and peripheral nerve models encompassing adipose tissue, muscle, ligaments and fascia; (2) to establish the ultrasound characteristics needed to image anatomy within these models; and (3) to propose engineering and design criteria for a microultrasound needle with an ultrasound array at the tip to visualise anatomy real-time during epidural and regional anaesthesia.
Please see the NIAA's position statement on the use of animals in medical research.
Principal Applicant
Dr Marie-Anne Shaw & Prof Phil Hopkins
University of Leeds
Title
Identification of genes contributing to malignant hyperthermia and related phenotypes from differential gene expression
Amount
£72,186
Malignant hyperthermia (MH) is a potentially lethal disorder triggered by inhalation anaesthetics, which can be explained by disrupted calcium homeostasis in skeletal muscle. Two genes have been identified, though no major gene has been found in many families, and there is evidence suggesting the genetics of MH is complex. Exertional heat illness (EHI) has phenotypic and likely genetic similarities to MH. MH and EHI patients, and their relatives, are tested by the in vitro contracture test (IVCT), where biopsy muscle is exposed to caffeine and halothane. Using microarrays, the student will identify differences in gene expression in muscle, taken for IVCT, before and after exposure to caffeine and halothane. Parallel studies will test effects of triggering agents on myoblasts derived from IVCT muscle. Employing bioinformatics approaches, expression quantitative trait loci (eQTLs) will be identified, with eQTLs local to the loci showing differential expression, or distant. Such eQTLs provide candidate loci for control of MH and related phenotypes, which will be tested using high throughput microfluidics, the largest collection of MH-related DNA samples worldwide, and analysed by genetic association methods. Better genetic understanding will pave the way to pre-operative genetic testing for MH and genetic screening of military personnel for EHI.
