Abstracts of the Warwick Undergraduate Medical Research Conference 2010
On 27 November 2010 the Warwick Medical School, University of Warwick, hosted the Warwick Undergraduate Medical Research Conference to showcase undergraduate medical research. Some papers were presented orally, others as posters; selected abstracts may be found below.
CONTENTS
Oral presentations: Research
Tissue miRNA expression profiles as biomarkers for staging melanomas
A. Sasegbon, Dr G. Saldanha and Dr H. Pringle
University of Leicester Medical School
Genetic variation in the FADS gene cluster in relation to hyperlipidaemic phenotypes
S. Wedderburn and A. Cumming
Institute of Medical Science, University of Aberdeen
Preventing chronic diseases in people with mental health problems: the HEALTH Passport approach
N. Anderson1, S. Sridharan2, M. Megson1 and V. Patel1 3 4
1Warwick Medical School, 2The Caludon Centre, Coventry, 3Diabetes Centre, George Eliot Hospital NHS Trust, Nuneaton, 4Clinical lead for long-term conditions, NHS West Midlands Strategic Health Authority
Oral presentations: Audits
Care of the Dying – Are we getting it right?
Amy Ritchie1, Libby Holland2, Svitlana Austin1 and Dr Julia Grant2
1Warwick Medical School, 2George Eliot Hospital NHS Trust
Peripheral Arterial Disease in Primary Care – pigeon-holed plumbing?
N. Boxall1 and P. Jackson2
1University of Manchester, 2Trafford Primary Care Trust
Risk assessment of pressure ulcers at a London teaching hospital
L. Gao1, S. Mahalingam1, S. Nageshwaran1 and P. Grewal 2
1 University College London Medical School, 2The Royal Free Hospital, London
A study of excision margins in squamous cell carcinoma of the tongue
M. Jaspal, Y. P. Tan, Mr A. Kalantzis and Mr P. Ameerally
University of Leicester
Oral presentations: Case Reports
A rare association of recurrent pericardial effusion in the background of polymyositis
J. Apps and Dr M. Bean
Warwick Medical School
Methadone-induced syncope secondary to long QT interval
J. Farikullah, O. Mirza and M. Thomas
Salford Royal Infirmary
Posters
Reliability of self-reported breast cancer risk data
R. Prajapati1, J. Diffey1, C. Finegan1, Dr A. Hufton,2 Dr J. Morris3 and Dr S. Astley1
1University of Manchester, 2University Hospital of South Manchester, 3The Nightingale Breast Centre
How is Aberrant Notch Signalling Activated in Human Breast Cancer?
E. Maile and Dr K. Brennan
University of Manchester
Potential autologous graft donor sites for proximal interphalangeal fracture-dislocations
T. Berrington, Mr T. Sillitoe, Dr W. Bhatti and Professor D. A. McGrouther
University of Manchester
Peer-Assisted Learning: the future of medical education?
L. Magee, E. Maile and J. Farikullah
University of Manchester
Characterisation of the net effect of multiple endogenous modulators on calcium-sensing receptor activity
M. Barrett
University of Manchester
Analysis of differential gene expression induced by invasion-promoting Tenascin-C isoforms in breast cancer cells
J. S. Smith1, D. S. Guttery1, J. A. Shaw1and R. Kilpatrick2
1Department of Cancer Studies and Molecular Medicine, University of Leicester, 2Leicester Royal Infirmary
Evolution of the pharmacological management of rheumatoid arthritis: a historical review
M. Shumbusho
Warwick Medical School
Lenalidomide treatment in myeloma patients
M. Jaspal, D. Jollychen and Dr S. Mittal
University of Leicester
Promising findings for additional mediators of human melanocyte senescence
C. Asher
Department of Basic Medical Sciences, St. George's University of London
Is short-term mortality risk higher among patients admitted on the weekends?
M. Megson and C. Marshall
Warwick Medical School
Traumas of medical training in Zimbabwe: an educational research project
S. Austin
Warwick Medical School
Evaluation of the experiences and impact of UNTRAP involvement in teaching and research
M. Mylne and Professor G. Hundt
Warwick Medical School
ABSTRACTS
Oral presentations: Research
Tissue miRNA expression profiles as biomarkers for staging melanomas
A. Sasegbon, Dr G. Saldanha and Dr H. Pringle
University of Leicester Medical School
Background
Malignant melanoma is a common highly aggressive cancer with a poor prognosis. The current clinical AJCC staging system can be improved with the use of molecular techniques such as miRNA expression profiling.
Aim
To compare the miRNA expression profiles of primary melanomas with no metastasis at 5 years (Controls) and primary melanoma with metastasis at 5 years (Cases) looking for differences between the two groups.
Methods
20 Controls and 20 Cases were identified from the Histopathology archives of UHL NHS Trust. Total RNA was extracted from FFPE melanoma tissue sections and converted to cDNA. The cDNA was then amplified and pooled into 4 Control groups and 4 Case groups before being run on Taqman microRNA microarrays. Four miRNAs found to be significantly differentially expressed were then selected and validated using qPCR.
Results
64 miRNAs were found to be significantly differentially expressed between Controls and Cases on the microarray with the majority being down-regulated (54/64). 12 miRNAs were selected as candidates for use in a literature search. 10 of the 12 selected miRNAs were found to be new to melanoma research. miR-329, miR-148b*, miR-612 and miR-221 were selected for validation using qPCR. Of these miR-221 and miR-329 were successfully validated and shown to separate Controls and Cases reflecting the changes seen in the microarray.
Conclusion
The findings of this study confirm that tissue miRNAs can act as biomarkers to separate primary melanomas with no metastasis at 5 years from primary melanomas with metastasis at 5 years. This suggests that tissue based miRNAs are markers of primary melanoma metastatic potential.
Genetic variation in the FADS gene cluster in relation to hyperlipidaemic phenotypes
S. Wedderburn and A. Cumming
Institute of Medical Science, University of Aberdeen
Genome-wide association studies have recently associated the FADS gene cluster with hyperlipidaemia. The FADS gene cluster consists of FADS1, 2 and 3. FADS1 and 2 are on chromosome 11q12-13.1 and encode for Δ-5 and Δ-6 desaturase, the key enzymes in long chain ω-6 and ω-3 fatty acid metabolism. Plasma fatty acid levels are measurable and studies have shown that there are strong associations between polymorphisms in the FADS gene cluster and fatty acid levels. Alterations in fatty acid components could indicate variation in the desaturase pathway potentially influencing lipid metabolism and hence hyperlipidaemia.
The aim of this study was to determine the influence of these polymorphisms in relation to hyperlipidaemia as fatty acids contribute to regulation of gene transcription in lipid metabolism. The study investigated the association of two polymorphisms (rs174537 and rs3834458) in the FADS gene cluster with hyperlipidaemic phenotypes by conducting a case-control study involving two Scottish populations consisting of 500 individuals in total.
Results showed an increase in the number of rare homozygotes in the case population, and that male rare homozygotes had a decrease in BMI but an increase in triglyceride levels. This relationship was interesting as it deviated from the norm by its inverse nature. As phenotypic associations tended only to occur in the male rare homozygote individuals for both polymorphisms, a likelihood ratio test (G-test) was performed and for rs174537 a recessive model of inheritance has been indicated with statistical significance.
This supports rs174537 as being influential in determining certain hyperlipidaemia phenotypes.
Preventing chronic diseases in people with mental health problems: the HEALTH Passport approach
N. Anderson1, S. Sridharan2, M. Megson1 and V. Patel1 3 4
1Warwick Medical School, 2The Caludon Centre, Coventry, 3Diabetes Centre, George Eliot Hospital NHS Trust, Nuneaton, 4Clinical lead for long-term conditions, NHS West Midlands Strategic Health Authority
Background
People with mental health problems can lose over 20 years of potential life compared with the general population. Lifestyle choices that increase the risk of chronic diseases contribute to this mortality. The HEALTH Passport (Helping Everyone Achieve Long Term Health) is a tool that helps patients make lifestyle choices that will reduce the burden of chronic disease in the future.
Objective
Assess the HEALTH Passport's potential to reduce the modifiable risk of chronic disease in psychiatric inpatients.
Method
50 psychiatric inpatients were introduced to the HEALTH Passport and asked to complete a semi-qualitative questionnaire. Results were compared with a study of 100 general medical patients.
Results
Currently, 4.2 times as many psychiatric participants as general medical participants smoke, and 2.1 times as many are at high risk of developing chronic diseases as a result of lifestyle choices. The HEALTH Passport has the potential to reduce the number of modifiable risk factors that participants are exposed to by an average of 1.7, sufficient to halve the number of participants at high risk of developing chronic disease and to reduce the prevalence of smoking by 37%.
Conclusions
The HEALTH Passport is likely to be a cost effective method of reducing the future burden of chronic disease in both general medical and mental health patients. However, objective assessment of the correlation between intent and actual lifestyle change is required to fully quantify its future potential.
Oral presentations: Audits
Care of the Dying – Are we getting it right?
Amy Ritchie1, Libby Holland2, Svitlana Austin1 and Dr Julia Grant2
1Warwick Medical School, 2George Eliot Hospital NHS Trust
For doctors, treating patients with irreversible illness will be an inevitable part of the job. However, recognizing the dying patient, stopping active medical treatment and initiating comfort care only will be difficult. Care of such patients presents unique challenges and the recently published General Medical Council guidance on end-of-life care highlights the importance of a framework for treatment provision.
The Liverpool Care Pathway (LCP) is a tool to promote best practice for care of the dying. The LCP enables professionals to focus on providing physical comfort measures and encompasses the psychological, spiritual and social care needs of the patient. By instigating this pathway at the earliest possible moment, patient needs can be effectively addressed and the family is supported throughout.
An audit was carried out to determine LCP uptake at the George Eliot Hospital NHS Trust (GEH) in May 2010. The standard was that all patients identified as dying were cared for on the LCP. Of the fifty-three deaths, eighteen were not identified as dying. Of the thirty-five that were, only fifteen were on the LCP.
Greater awareness of the LCP is needed in order to instigate its use in all predictable deaths. To do this, the GEH have formed an End of Life Action Team and are funding an LCP facilitator to educate and empower multidisciplinary teams to drive LCP use. Understanding the LCP is invaluable preparation for providing the best possible care, in a patient's final hours and days, as a junior doctor, and beyond.
Peripheral Arterial Disease in Primary Care – pigeon-holed plumbing?
N. Boxall1 and P. Jackson2
1University of Manchester, 2Trafford Primary Care Trust
Peripheral Arterial Disease (PAD) is highly asymptomatic with a significant hazard ratio for mortality. While there are known effective interventions in treating PAD, there are currently no guidelines or set targets for managing PAD in primary care in England or Wales. This audit aims to investigate whether or not PAD is under-diagnosed and/or undertreated in primary care.
A retrospective tracer audit was conducted by reviewing patients' notes at a primary care health centre. The treatment of patients with PAD who were not on a chronic disease register for either stroke or coronary heart disease (CHD) (n=48) was compared with those who were on such a register and also had PAD (n=54). A prospective study was set up which measured the ankle brachial pressure index (ABPI) of patients who were at high-risk of having PAD (n=64) to investigate if it was under-diagnosed.
The percentage of patients with PAD who were not on the selected chronic disease registers who were on antithrombotic prophylaxis was 85.4% compared with 92.6% of those who were on the registers. 81.3% of patients with PAD who were not on the selected chronic disease registers were on lipid-lowering therapies compared to 96.3% of those who were on the registers. From the prospective side of the audit, six patients out of 64 had an ABPI diagnostic of PAD.
This audit indicates that even in a well-run primary care health centre, PAD is under-diagnosed and undertreated. Patients could potentially benefit if a cost-effective screening process were introduced.
Risk assessment of pressure ulcers at a London teaching hospital
L. Gao1, S. Mahalingam1, S. Nageshwaran1 and P. Grewal 2
1 University College London Medical School, 2The Royal Free Hospital, London
Introduction
Pressure ulcers remain a significant burden costing the NHS £1.2-£1.4 billion annually (2004). Inadequate risk assessment has been cited as one of the principal drawbacks in their prevention. This audit examines how consistently and accurately patients are risk stratified with the widely used Waterlow score.
Methods
We assessed the Waterlow score for 100 in-patients during a six-month period, and compared this with the corresponding nursing team's score using the Student t-test. The incidence of pressure ulcers, the type of mattress used and relevant documentation was also documented.
Results
The average nursing score was 20% lower than that from the audit (13.7 vs. 17.1, p<0.01). Risk groups were No Risk (0-9), At Risk (10+), High Risk (15+) and Very High Risk (20+). The audit identified twice as many patients as 'Very High Risk' than documented (20 vs. 9).
Discussion
While the Waterlow score is a tool forming only part of the overall assessment, these discrepancies can impact directly upon judgement of a patient's risk. We discuss the factors leading to the discrepancies, and suggest proposals to improve risk stratification and hence, prevention of pressure ulcers.
A study of excision margins in squamous cell carcinoma of the tongue
M. Jaspal, Y. P. Tan, Mr A. Kalantzis and Mr P. Ameerally
University of Leicester
Introduction
This study aims to identify close excision margins (<5mm) in surgically resected squamous cell carcinoma of the tongue in two different maxillofacial units in England. As close margins, especially the deep, are associated with increased incidence of local recurrence and reduced survival, identifying them could change the glossectomy surgical approach.
Methods
Retrospective review of excision margins from histopathological reports of 63 patients who underwent partial glossectomies, in two different hospitals, from January 2006 to July 2010. Superior/medial, inferior/lateral, anterior, posterior and deep margins were recorded. Histological reporting of margins was not always complete, resulting in different total number of cases for each margin.
Results
The deep margin was the most frequently close/involved (35%) followed by the inferior/lateral margin (23%). The results were very similar between the two hospitals. Hospital A had proportionally equal deep and inferior/lateral close margins whereas Hospital B had a higher involvement of the deep margin and a lower involvement of the inferior/lateral margin. Superior/medial margins were the least close/involved.
Conclusion
High incidence of close/involved deep and inferior margins could be a result of muscle shrinkage post-resection and physical limitation arising from neighbouring periosteum respectively. The use of diathermy for tumour resection may also increase the incidence of ‘apparent’ close margins. Solutions to reduce the involvement of the deep margins: improved surgical access by splitting the lip and mandible more frequently and using newer equipment for resection, such as a harmonic scalpel.
Oral presentations: Case Reports
A rare association of recurrent pericardial effusion in the background of polymyositis
J. Apps and Dr M. Bean
Warwick Medical School
A 74-year-old lady with diagnosed polymyositis presented with recurrent pericardial effusions. Pericardiocentesis was performed and analysis of the fluid on both occasions showed a clear yellow fluid with no organisms. A pericardial biopsy obtained on the second presentation showed that the pericardial tissue was lined by foamy mesothelial-like cells. There was underlying fibrosis and chronic inflammation but no evidence of malignancy. The aetiology of the effusion remains unknown. We propose that there may be a link between the pericardial effusions developing and the history of polymyositis.
Methadone-induced syncope secondary to long QT interval
J. Farikullah, O. Mirza and M. Thomas
Salford Royal Infirmary
Introduction
Methadone is a synthetic opioid used both for the treatment of heroin addiction and for chronic pain.
Case Presentation
A 43-year-old male presented to the emergency department with a syncopal episode. He had previously suffered recurrent syncopal episodes over the last year. He was a former heroin user and has been taking methadone for the past 20 years. An Electrocardiogram reported a long QT interval (526 milliseconds). Potassium levels were low (3.1 mmol/L), and ALT levels were raised (136). Potassium supplements were given which then restored these levels. Methadone was discontinued. Within a few days the QT interval returned to normal. Methadone was re-integrated at lower doses under Cardiology supervision.
Discussion
Given the benefits for methadone substitution for illicit opioids and its use in chronic pain, the finding of an association between methadone and prolonged QT interval is of a great concern. Progression can lead to the life threatening torsade de pointes.
Lessons Learned
Clinicians should obtain a careful medical history and full examination, while screening for risk factors associated with a prolonged QT interval. Clinicians should also be made aware that occurrence of QT prolongation is more frequent with high doses of methadone, concomitant administration of CYP3A4 inhibitors, hypokalaemia, hepatic failure, administration of other QT prolonging drugs and also pre-existing heart disease. We believe patients maintained on methadone who are at a high risk for developing QT interval prolongation should be investigated with an Electrocardiogram during outpatient appointments.
Posters
Reliability of self-reported breast cancer risk data
R. Prajapati1, J. Diffey1, C. Finegan1, Dr A. Hufton,2 Dr J. Morris3 and Dr S. Astley1
1University of Manchester, 2University Hospital of South Manchester, 3The Nightingale Breast Centre
Background
Development of breast cancer models may rely on self-reported data obtained from questionnaire-based studies - however the reliability and accuracy of these data is often questioned.
Objectives
In an attempt to assess reliability, questionnaires asking for breast cancer risk data were sent to women of screening age approximately two years apart. Responses were analysed to see how consistently and with how much confidence women replied.
Methods
Questionnaire data were entered onto a database; women responding to both questionnaires were identified. Responses for the breast cancer risk factors: height, weight, age at menarche, age at natural menopause and age at first child were analysed. A paired T-test was used to compare the change in response for each variable; changes in confidence were analysed using a Wilcoxson's signed rank test.
Results
527 women responded to both questionnaires. The changes in response for self-reported height (p=0.087), weight (0.399) and age at menarche (p=0.432) were not statistically significant. However, reporting of age of natural menopause (p<0.056) and age at first child (p<0.001) were found to be statistically significant. Confidence in reporting of answers increased in the second questionnaire for all of the variables investigated (p<0.001).
Conclusions
Even though women responded consistently to questions relating to breast cancer risk, the accuracy of the information provided cannot be ascertained as objective measurements were not taken. Cross-checking questionnaire responses with independent records where objective measurements have been taken may provide a way of determining the accuracy of responses.
How is Aberrant Notch Signalling Activated in Human Breast Cancer?
E. Maile and Dr K. Brennan
University of Manchester
Background
Notch is a short-range cell signalling mechanism that functions in a diverse array of developmental processes throughout the animal kingdom. However, deregulated signalling is implicated in a variety of cancers including breast carcinoma. This is because aberrant Notch signalling confers cancer cells with resistance to apoptosis. The exact cause of inappropriate Notch activation in cancer remains elusive, although previous work suggests it may be ligand-dependent. Therefore, I aimed to elucidate the point at which aberrant Notch activation occurs in breast cancer, paying particular attention to possible ligand-dependent mechanisms.
Methods
MCF-7 and DCIS.com breast cancer cell lines were used as a model. I inhibited points in the Notch pathway which are crucial for ligand-dependent activation of signalling and treated the cells with the chemotherapeutic doxorubicin. This allowed me to see if inhibition of a particular pathway component silenced Notch signalling and therefore sensitised the cells to apoptosis. In this way it was possible to determine the point at which aberrant pathway activation occurs and whether activation is ligand-dependent.
Results
This paper shows, for the first time, that treatment with doxorubicin causes apoptosis in the breast cancer derived cell line DCIS.com. The results were inconclusive as to whether the mechanism of Notch pathway hyperactivation is ligand-dependent.
Conclusion and Implications
A clear understanding of the exact mechanism of aberrant Notch activation would be highly beneficial for the development of novel therapies aimed at reducing the mortality of breast cancer. Further work that may go some way to achieving this goal is also discussed.
Potential autologous graft donor sites for proximal interphalangeal fracture-dislocations
T. Berrington, Mr T. Sillitoe, Dr W. Bhatti and Professor D. A. McGrouther
University of Manchester
Purpose
Hemi-hamate resurfacing arthroplasty is one of the treatment options for the management of proximal interphalangeal (PIP) fracture-dislocations. This study aims to evaluate the remaining carpal bones for supplementary suitable autograft sites.
Methods
Plaster moulds of the carpal bones of a model skeleton were systematically examined for sites with similar contours to the volar base of the middle phalanx. When a potential donor site was found it was harvested and transplanted onto an artificially fractured middle phalanx.
Results
A potential donor site was located on the most medial point of the dorsal aspect of the trapezium, between the articular surfaces with the scaphoid and trapezoid.A further site on the most superior point of the volar aspect of the capitate that articulates with the base of the third metacarpal was also found.
Conclusions
Hemi-hamate resurfacing arthroplasty repair is suitable for the treatment of both extensive and chronic presentations of PIP fracture-dislocations. Access difficulty, disease, or injury may preclude the use of the hamate, necessitating the availability of further donor sites, such as those evaluated in this study.
Peer-Assisted Learning: the future of medical education?
L. Magee, E. Maile and J. Farikullah
University of Manchester
Background
The Peer-Assisted Learning (PAL) scheme is facilitated by medical students at Salford Royal University Hospital and delivers clinical skills teaching to peers. We facilitated PAL sessions covering examination of the neck and thyroid. This study examined the efficacy of PAL and students' perceptions of PAL versus consultant-led teaching.
Methods
We surveyed third-year students (n=16) attending small-group PAL sessions, led by fourth-year students. The students rated their confidence at tackling an OSCE station before and after PAL, using a scale from 1 (no confidence) to 10 (most confident). We compared PAL and consultant-led teaching by asking which they found: a) most enjoyable and b) most useful for OSCE preparation.
Results
Students' confidence at a head and neck OSCE station demonstrated a significant improvement from a mean of 5.1/10 before the teaching session to a mean of 8/10 after (p<0.001). When comparing PAL and consultant-led teaching, 69% of students thought that PAL was most enjoyable and 63% found it most useful for their learning. None of the students picked consultant-led teaching alone as the most enjoyable or useful form of teaching. 12% of students found both forms of teaching equally enjoyable and 12% found them equally useful.
Conclusions
Students were significantly more confident in performing the clinical skill after the PAL session; they enjoyed and found PAL more useful than consultant-led teaching.
We conclude that enjoyment of learning via PAL may contribute to enhanced confidence of medical students and belief in their OSCE abilities.
Proposals
We propose that PAL should be widely employed in synergy with consultant-led teaching. The GMC requires all medical students to be involved in teaching; PAL can be used effectively to achieve this.
Characterisation of the net effect of multiple endogenous modulators on calcium-sensing receptor activity
M. Barrett
University of Manchester
The calcium-sensing receptor (CaR) controls blood calcium (Ca2+o) concentration by regulating parathyroid hormone secretion. The Ca2+o sensitivity of CaR in vitro appears lower than in vivo and one possible explanation for this is the routine exclusion of endogenous CaR modulators from in vitro studies.
Thus, human embryonic kidney-293 cells expressing CaR stably (CaR-HEK) were exposed to various concentrations of Ca2+o.To this experimental buffer were added physiological concentrations of a) albumin and phosphate, which lower free Ca2+o concentration by binding to blood calcium and, b) spermine and aromatic amino acids - known positive CaR allosteric modulators. Their effects on Ca2+o–induced intracellular calcium (Ca2+i) mobilisation, measured to indicate CaR activity, were determined by epifluorescence microscopy. Sensitivity of CaR to Ca2+o was increased by cotreatment with 30 M spermine (EC50, 2.8±0.3 mM vs 3.3±0.1 control, P<0.05). In contrast, addition of 1mM phosphate or 5% (w/v) albumin to the Ca2+o- containing buffer appeared to decrease Ca2+o sensitivity (EC50, 4.4±0.2 mM phosphate, 4.2±0.2 albumin vs 3.3±0.1 control, P<0.05), most likely due to buffering of the free Ca2+o.
Finally, cotreatment with physiologically-relevant concentrations of all 4 positive and negative CaR modulators had a significant net increase in Ca2+o sensitivity of the CaR overall (EC50, 1.6±0.1 mM vs 3.1±0.2 control, P<0.001). In conclusion, these data suggest that modelling CaR activity in vitro requires inclusion of all endogenous CaR modulators in the experimental buffer, or, at least more serious consideration of the likely consequence of their exclusion.
Analysis of differential gene expression induced by invasion-promoting Tenascin-C isoforms in breast cancer cells
J. S. Smith1, D. S. Guttery1, J. A. Shaw1and R. Kilpatrick2
1Department of Cancer Studies and Molecular Medicine, University of Leicester, 2Leicester Royal Infirmary
Tenascin-C (TNC) is an ECM glycoprotein which is up-regulated in the stroma surrounding breast cancers. Specific isoforms of TNC (TNC-9/16, TNC-9/14/16 and TNC-14/AD1/16) have been shown to increase breast cancer cell proliferation and invasion. Previous studies using a cDNA microarray has compared gene expression profiles of MCF-7 cells transfected with these TNC isoforms. The aim of this study was to validate expression of selected targets identified by the microarray.
TNC plasmids (TNC-Short, TNC-9/16, TNC-9/14/16, TNC-14/AD1/16) and an empty vector control were transfected into MCF-7, T-47D, MDA-MB-231 and Hs578T breast cancer cells. Expression of candidate genes DSP, CTBP1, IGFBP5, CDC42, RAB25 and CCND1 was analysed by RT-qPCR, and CTBP and CCND1 protein expression by western blotting (WB).
RT-qPCR and WB confirmed the transfected TNC isoforms were expressed in each cell background, but at lower levels than for the microarray. In MDA-MB-231 cells, DSP was significantly down-regulated by TNC-14/AD1/16 (p<0.009), and CDC42 was significantly down-regulated by both TNC-9/16 (p<0.039) and TNC-14/AD1/16 (p<0.003). Other candidate genes showed no statistically significant changes in expression. RT-qPCR of candidate genes was replicated on cDNA from transfected cells used in previous invasion studies, where transfected TNC isoform expression was higher. However, no significant differences in gene expression were found. In MCF-7s, WB showed CTBP was up-regulated by TNC-9/16 and CCND1 down-regulated by TNC-14/AD1/16, but up-regulated by TNC-9/14/16 and TNC-14/AD1/16 in T-47Ds.
Conclusion
Candidate gene mRNA expression was not altered significantly by TNC isoforms in the cell backgrounds, although preliminary data showed changes in CTBP and CCND1 proteins.
Evolution of the pharmacological management of rheumatoid arthritis: a historical review
M. Shumbusho
Warwick Medical School
Rheumatoid arthritis (RA) is a systemic disease characterised by chronic inflammatory polyarthritis, with frequent progression to joint destruction and disability. Symptoms of what we now call RA were first discovered in the remains of Native American skeletons as early as 4500 BC. The first recognised description of RA was in 1800 by French physician Dr Augustin Jacob Landré-Beauvais.
The clinical picture seen in RA is the result of a cascade involving T cells, B cells, antigen-presenting cells, and pro-inflammatory cytokines, including tumour necrosis factor (TNF)-α and interleukins. With the knowledge that RA is initiated by immune mechanisms, therapy has evolved from an eminently immunosuppressive approach to a more targeted approach.
During the last 25 years we have seen major developments in the management of RA, most notably since the introduction of anti-TNFα agents. There has been a shift from simply controlling symptoms to modifying the disease course. As such patients need to be treated with aggressive therapy in order to limit subsequent damage and delay progression. Apart from anti-TNFα, several other biological treatments are now available, including those that target cytokines such as IL1 (Anakinra), IL6 (Tocilizumab), and molecules that cause interaction between antigen presenting cells and T cells (Abatacept).
Lenalidomide treatment in myeloma patients
M. Jaspal, D. Jollychen and Dr S. Mittal
University of Leicester
Introduction
This study aims to ensure that the newly licensed lenalidomide treatment in myeloma patients is in accordance with June 2009 NICE guidelines. This drug is a derivative of thalidomide that caused worldwide controversy for its teratogenic properties. Therefore, monitoring patients closely and hospital adherence to guidelines is crucial.
Method
The data were collected, using a combined proforma of NICE and East Midlands Myeloma Treatment Guidelines, from hospital notes of eleven myeloma patients at Northampton General Hospital.
Results
This audit shows that the use of lenalidomide in myeloma patients in the NGH meets all the criteria set out by NICE and the East Midlands Myeloma Treatment guidelines. Median age of patients was 69 years with a median time from diagnosis to lenalidomide initiation of three years. IgG was the most common paraprotein (eight patients). All except two experienced one or more side effects, the commonest being anaemia and thrombocytopenia with the mean number of side effects being three.
Conclusion
Four patients stopped treatment, one due to reaching plateau phase and three due to side effects. Lenalidomide had a mixed response; 27.3% of patients had no response and 72.7% showed a response which was only either minor (45.5%) or partial (27.3%). But as it has only been a year since it was licensed, we appreciate that these figures could significantly change with time. We hope to complete the audit circle by re-auditing in a few years’ time.
Promising findings for additional mediators of human melanocyte senescence
C. Asher
Department of Basic Medical Sciences, St. George's University of London
Background
The best-established familial melanoma locus CDKN2A encodes two mediators of cell senescence, p16 and ARF. p16 at least is involved in the proliferative arrest of naevi (moles). Both p16 and the cell senescence barrier are lost in advanced melanoma. However this senescence appears not to be mediated solely by p16, because although all naevi express p16, not all cells within a given naevus seem to express it. Accordingly it seems likely there are other growth inhibitors involved.
Aims
-
Determine whether expression of likely growth inhibitors (ARF, p27, p21, p15) rose as normal human melanocytes became senescent.
-
Determine whether similar tests on p16 deficient human melanocytes (which also senesce although after many extra divisions) reveal even higher expression of potential mediators.
Methods
Growth inhibitors were selected based on demonstration of growth arrest typical of senescence in murine studies and human fibroblasts. The expression of potential growth inhibitors was investigated using immunostaining which was used to check the location of any inhibitor that was expressed
Results and Conclusions
This is the first association of ARF and p15 increase with cell senescence in normal human melanocytes. ARF was further elevated in senescent p16-deficient melanocytes, suggesting a secondary/backup role in senescence in the absence of p16.The results for p27 and p21 were relatively consistent with current evidence that suggests neither may be involved in human melanocyte senescence. This suggests novel candidates for additional mediators of human melanocyte senescence. Further research will help with the understanding of melanoma and perhaps diagnostic testing.
Is short-term mortality risk higher among patients admitted on the weekends?
M. Megson and C. Marshall
Warwick Medical School
Background
Several studies have indicated that short-term mortality risk is higher among patients who are admitted on the weekends. This “weekend effect” has been observed among patients admitted with a variety of diagnoses, including myocardial infarction, pulmonary embolism, ruptured abdominal aortic aneurysm, and stroke. Ananthakrishnan et al. found that patients admitted on a weekend had a 22% higher adjusted in-hospital mortality. Our audit was influenced by this apparent weekend effect. As this phenomenon is mostly blamed on staff shortages, this audit is looking at how many surgical in-patients are reviewed over the weekend.
Audit Criteria
In-patients who were admitted by handover on the day before the study period, under a surgical team, and outliers are included.
Method
This was a retrospective study, examining whether entries had been made in the patient’s notes over three weekends. The standard was that 100% of surgical patients should be reviewed.
Results
Although on two out of three of the weekends up to 79% of the patients were seen on each day, one of the weekends showed that as few as 28% of patients were seen in any one day.
Conclusion
Fewer patients appear to be reviewed on some weekends; at least 10% of patients are not reviewed at all. This should be re-audited after the introduction of the computerised handover system
Traumas of medical training in Zimbabwe: an educational research project
S. Austin
Warwick Medical School
Extreme poverty and political turmoil in Zimbabwe left its only medical school in a desperate situation. Despite rapidly increasing demand for doctors in the country, students face many challenges. This ultimately results in an overwhelming efflux of newly qualified doctors to other countries, worsening the crisis of practically non-functional healthcare system.
The Wolstecroft fund has sponsored a research project carried out at the College of Health Sciences in Harare. The aim was to identify the most appropriate and cost-effective interventions that could be undertaken by Warwick medical students in order to assist their Zimbabwean colleagues in their training. Questionnaires and interviews were used to gather the information, while group discussions and attendance of lectures helped to gain an objective perspective on students' educational experience.
The data collected revealed extreme shortage of resources in many areas. The most prominent issues were high tuition fees, lack of books, teaching equipment or internet access and shortage of qualified lecturers, resulting in some lectures being conducted by senior students or cancelled altogether. The proposed list of interventions includes activities to be completed by Warwick students in the UK and during their subsequent trips to Zimbabwe. The initial step of creating a dedicated student society at Warwick is currently under way with the first consignment of donated books being delivered to Zimbabwe.
This exciting and rewarding project gives Warwick students a unique opportunity to improve the educational experience of their Zimbabwean colleagues and to establish long-term, mutually beneficial links between the universities.
Evaluation of the experiences and impact of UNTRAP involvement in teaching and research
M. Mylne and Professor G. Hundt
Warwick Medical School
Universities/User Teaching and Research Action Partnership (UNTRAP) is an organisation that promotes the engagement and involvement of service users and carers from the local community in research and teaching in health and social care at the University of Warwick. The aim of this project is to capture the views, experiences and impact of UNTRAP involvement by academic stakeholders in teaching and research at the University of Warwick. The methodology was qualitative. A questionnaire of six open-ended questions was designed to obtain feedback and opinions about UNTRAP member participation in teaching and research.
The sample was selected for representativeness of stakeholders of UNTRAP, with assistance from Professor Gillian Hunt; 9 stakeholders in research and 8 stakeholders in teaching were identified. There were a total of nine respondents and questionnaire responses were analysed using qualitative computer software to identify themes for manual analysis.
Overall, the feedback from respondents suggested that UNTRAP was beneficial for both teaching and research purposes. Stakeholders recruited UNTRAP members for a variety of educational purposes, from MBChB admissions to lay opinion on a committee. Furthermore, lack of guidance from UNTRAP organisation was mentioned by 7 out of 9 stakeholders. To maximise the impact of UNTRAP there need to be publicity campaigns in order to increase awareness, recruit more service users or carers, and improve current understanding of UNTRAP participation by stakeholders in teaching and research.