Leeds Institute of Genetics

Medicine and, United Kingdom

Leeds Institute of Genetics

Medicine and, United Kingdom
Time filter
Source Type

Chang K.-V.,National Taiwan University Hospital | Chang K.-V.,National Taiwan University | Chen S.-Y.,National Taiwan University Hospital | Chen S.-Y.,National Taiwan University | And 6 more authors.
Archives of Physical Medicine and Rehabilitation | Year: 2012

Objectives: To compare the effectiveness of focused shock wave (FSW) therapy of different intensity levels and a new alternative, radial shock wave (RSW) for managing plantar fasciitis. Data Sources: Electronic databases including MEDLINE and PubMed were searched from January 1996 to June 2011. Study Selection: Randomized controlled trials comparing shock wave and placebo therapy were included. Two reviewers independently scrutinized eligible articles, and disagreement was resolved by discussion. Literature searching identified 93 nonduplicate citations, of which 12 trials comprising 1431 participants were included. Data Extraction: Information, such as patient characteristics, shock wave intensity, and outcome measures, was extracted by 1 reviewer and checked by another. Both reviewers assessed the trials' quality by using the Jadad scale. Data Synthesis: FSW therapy of different intensity ranges was treated as 3 subgroups, whereas studies using RSW therapy were regarded as a separate group. The success rates of treatment and pain reduction magnitudes were used as the outcomes. The traditional meta-analysis showed that medium and high-intensity FSW therapy had reliably higher success rates and pain reduction than the placebo, while the effectiveness of low-intensity FSW therapy and RSW therapy appeared less convincing because of very large confidence intervals. After employing network meta-analysis, the probability of being the best therapy was the highest in RSW therapy, followed by low-, medium-, or high-intensity FSW therapy. The meta-regression indicated that the success rate of FSW therapy was not related to its intensity, whereas elevated energy efflux densities tended to relieve pain more. Conclusions: Setting the highest and mostly tolerable energy output within medium intensity ranges is the ideal option when applying FSW therapy on plantar fasciitis. RSW therapy is considered an appropriate alternative because of its lower price and probably better effectiveness. © 2012 American Congress of Rehabilitation Medicine.

Morton G.,King's College London | Jogiya R.,King's College London | Plein S.,King's College London | Plein S.,Leeds Institute of Genetics | And 3 more authors.
European Heart Journal Cardiovascular Imaging | Year: 2012

Aims: To evaluate the inter-study reproducibility of quantitative cardiovascular magnetic resonance (CMR) myocardial perfusion imaging and the influence of diurnal variation on perfusion. Data on these are limited, despite being crucially important for performing serial examinations both in clinical practice and in trials. Methods and results: Sixteen healthy volunteers underwent high-resolution 3 T perfusion imaging three times during a single day to evaluate inter-study reproducibility and the effects of diurnal variation. Absolute perfusion was determined in each coronary artery territory and globally by Fermi constrained deconvolution of myocardial signal intensity curves. Left ventricular (LV) volumes and function were also calculated. Eleven full data sets were suitable for quantitative perfusion analysis. Global rest and stress perfusion and myocardial perfusion reserve (MPR) were 0.6 ± 0.1 and 2.5 ± 0.5 mL/min/g and 4.3 ± 0.9, respectively, for the first scan and were 0.5 ± 0.2 and 2.1 ± 0.5 mL/min/g and 4.2 ± 1.2 for the second (P 0.1, 0.19, and 0.37, respectively). Inter-study reproducibility was moderate. The coefficient of variation (CV) was 16.0, 26.8, and 23.9 for global rest and stress perfusion and MPR, respectively. The corresponding territorial CVs were 27.5, 35.2, and 33.5. The reproducibility of LV volumes and function was excellent (CV 4, 7.7, and 4.6 for end-diastolic volume, end-systolic volume, and ejection fraction, respectively). There were no significant detectable diurnal variations in perfusion or LV volumes and function (P< 0.05 for all). Conclusion: The inter-study reproducibility of quantitative myocardial perfusion is reasonable and best for global rest perfusion. No significant diurnal variation in perfusion was observed. © The Author 2012.

Horng Y.-S.,Buddhist Tzu Chi General Hospital | Horng Y.-S.,Tzu Chi University | Hsieh S.-F.,Buddhist Tzu Chi General Hospital | Tu Y.-K.,Leeds Institute of Genetics | And 4 more authors.
American Journal of Physical Medicine and Rehabilitation | Year: 2011

Objective: The aim of this study was to investigate the effectiveness of tendon and nerve gliding exercises as a part of combined treatments for carpal tunnel syndrome. Design: Patients with carpal tunnel syndrome were randomized into three groups. All patients received conventional treatments (splint and paraffin therapy, as in group 3), but group 1 underwent additional tendon gliding exercises and group 2 underwent additional nerve gliding exercises. Each patient received a package of questionnaires and underwent physical examinations and nerve conduction study of the upper limbs before and after treatment for 2 mos. Results: Sixty patients were recruited, and 53 completed the study. There were significant improvements in symptom severity and pain scale scores in all groups. However, only group 1 showed significant improvements in their scores on functional status; the Disabilities of the Arm, Shoulder, and Hand questionnaire; and the physical domain of the World Health Organization Quality of Life Questionnaire Brief Version. After adjusting for baseline data, we found significant differences in the functional status scores among the groups. Post hoc analyses detected a significant difference in functional status scores between groups 1 and 2. Conclusions: The combination of tendon gliding exercises with conventional treatments may be more effective than that of nerve gliding exercises with conventional treatments. Copyright © 2011 by Lippincott Williams & Wilkins.

Ramnarayan P.,Transport for London | Thiru K.,City University London | Thiru K.,Care Network | Parslow R.C.,Care Network | And 5 more authors.
The Lancet | Year: 2010

Background Intensive care services for children have undergone substantial centralisation in the UK. Along with the establishment of regional paediatric intensive care units (PICUs), specialist retrieval teams were set up to transport critically ill children from other hospitals. We studied the outcome of children transferred from local hospitals to PICUs. Methods We analysed data that were gathered for a cohort of children (≤16 years) admitted consecutively to 29 PICUs in England and Wales during 4 years (Jan 1, 2005, to Dec 31, 2008). We compared unplanned admissions from wards within the same hospital as the PICU and from other hospitals; interhospital transfers by non-specialist and specialist retrieval teams; and patients transferred to their nearest PICU and those who were not. Primary outcome measures were mortality rate in PICU and length of stay in PICU. We analysed data by use of logistic regression analysis. Findings There were 57 997 admissions to PICUs during the study. Nearly half of unplanned admissions (17 649 [53] of 33 492) were from other hospitals. Although children admitted from other hospitals were younger (median 10 months [IQR 1-55] vs 18 months [3-85]), sicker at admission (median predicted risk of mortality 6 [4-10] vs 4 [2-7]), stayed longer in PICUs (75 h [33-153] vs 43 h [18-116]), and had higher crude mortality rates (1384 [8] of 17 649 vs 996 [6] of 15 843; odds ratio 1·27, 95 CI 1·16- 1·38), the risk-adjusted mortality rate in PICUs was lower than among children admitted from within the same hospital (0·65, 0·53-0·80). In a multivariable analysis, use of a specialist retrieval team for transfer was associated with improved survival (0·58, 0·39-0·87). Interpretation These findings support the policy of combining centralisation of intensive care services for children with transfer by specialist retrieval teams. Funding National Clinical Audit and Patient Outcomes Programme through Healthcare Quality Improvement Partnership, Health Commission Wales Specialised Services, National Health Service (NHS) Lothian and National Service Division NHS Scotland, the Royal Belfast Hospital for Sick Children, and the Pan Thames PICU Commissioning Consortium. © 2010 Elsevier Ltd.

Maqbool A.,Leeds Institute of Genetics | West R.M.,Center for Epidemiology and Biostatistics | Galloway S.L.,Leeds Institute of Genetics | Drinkhill M.J.,Leeds Institute of Genetics | And 3 more authors.
Journal of Hypertension | Year: 2010

Objective: Sympathetic nerve hyperactivity has been associated with hypertension and heart failure and their cardiovascular complications. The α2-adrenergic receptors have been proposed to play a prominent role in the control of sympathetic neural output, and their malfunction to constitute a potential central mechanism for sympathetic hyperactivity of essential hypertension. Reports on the relationship between variant alleles of α2-adrenergic receptor subtypes and sympathetic drive or its effects, however, have not been consistent. Therefore, this study was planned to test the hypothesis that variant alleles of subtypes of α2-adrenergic receptors are associated with raised muscle sympathetic nerve activity (MSNA) in man. Methods: One hundred and seventy-two individuals, with a wide range of arterial pressure, were prospectively examined. Resting MSNA was quantified from multiunit bursts and from single units, and α2-adrenergic receptor subtypes were genotyped from DNA extracted from leucocytes and quantified by spectrophotometry. RESULTS: No significant relationships between variant alleles of any of the α2A, α2B or α2C subtypes and raised muscle sympathetic activity were found. In contrast, MSNA showed a marked significant curvilinear relationship with age and systolic pressure; sex had a small but statistically significant effect. The α2-adrenergic receptor variants had a similar frequency when hypertensive and normotensive individuals were compared. Conclusion: Variant alleles of three α2-adrenergic receptor subtypes were not related to resting muscle sympathetic nerve hyperactivity, indicating that their functional differences shown in vitro are not reflected in sympathetic activity in man. Age had a marked effect likely influencing arterial pressure through sympathetic activity. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Gore M.O.,University of Texas Southwestern Medical Center | Luneburg N.,University of Hamburg | Schwedhelm E.,University of Hamburg | Schwedhelm E.,University of Lübeck | And 10 more authors.
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2013

OBJECTIVE-: Increased asymmetrical dimethylarginine (ADMA), a NO synthase inhibitor, and its congener symmetrical dimethylarginine (SDMA), predict cardiovascular and all-cause mortality in at-risk populations. Their prognostic value in the general population remains uncertain. We investigated the correlations of SDMA and ADMA with atherosclerosis and cardiovascular/all-cause mortality in the Dallas Heart Study, a multiethnic probability-based cohort aged 30 to 65 years. APPROACH AND RESULTS-: SDMA and ADMA were measured by liquid chromatography-tandem mass-spectrometry (n=3523), coronary artery calcium by electron-beam computed tomography, and abdominal aortic wall thickness by MRI. In unadjusted analyses, categories of increasing SDMA and ADMA were associated with higher prevalence of cardiovascular risk factors, increased risk markers, and all-cause and cardiovascular mortality (median follow-up, 7.4 years). After adjustment for age, sex, and race, traditional cardiovascular risk factors, and renal function, SDMA and ADMA analyzed as continuous variables were associated with coronary artery calcium >10, but only SDMA was associated with abdominal aortic wall thickness. SDMA, but not ADMA, was associated with cardiovascular mortality (hazard ratio per log unit change, 3.36 [95% confidence interval, 1.49-7.59]; P=0.004). SDMA and ADMA were both associated with all-cause mortality, but after further adjustment for N-terminal pro-brain-type natriuretic peptide, high-sensitivity C-reactive protein, and high-sensitivity cardiac troponin T, only SDMA was associated with all-cause mortality (hazard ratio per log unit change, 1.86 [95% confidence interval, 1.04-3.30]; P=0.01). CONCLUSIONS-: SDMA, but not ADMA, was an independent predictor of all-cause and cardiovascular mortality in a large multiethnic population-based cohort. © 2013 American Heart Association, Inc.

Gierula J.,Leeds Institute of Genetics | Jamil H.A.,Leeds Institute of Genetics | Byrom R.,Leeds Institute of Genetics | Joy E.R.,Leeds Institute of Genetics | And 3 more authors.
Heart | Year: 2014

Objective: Heart failure and left ventricular systolic dysfunction (LVSD) are common in patients with permanent pacemakers, but whether right ventricular (RV) pacing is contribut ory or merely a bystander in patients with more severe cardiac disease is controversial. The aim of the present study was to determine whether reprogramming of existing pacemakers to reduce RV pacing is safe and leads to improvements in cardiac function. Methods: This was a prospective service evaluation of the effects of optimising pacemaker programming to avoid RV pacing in 66 consecutive attendees of a teaching hospital pacemaker clinic without complete heart block. The main outcome measures were left ventricular ejection fraction (LVEF), N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) levels, quality of life and cardiopulmonary exercise testing at baseline and after 6 months. Results: At 6 months, the protocol reduced absolute RV pacing by a mean of 49% (95% CI 41% to 57%) (p<0.0001 from baseline) and resulted in a mean absolute improvement in LVEF of 6% (4% to 8%) (p<0.0001 from baseline) but no reduction in exercise capacity, NT-pro-BNP or quality of life. There was a relationship between the magnitude of change in EF and the reduction in RV pacing (p=0.04) and changes in NTpro- BNP seemed to relate to change in RV pacing ( p=0.07). Conclusions: Programming standard pacemakers to avoid RV pacing is safe, does not adversely affect patients' symptoms or quality of life and is associated with improved LV function, related to the reductions in RV pacing percentage.

Boycott H.E.,Leeds Institute of Genetics | Dallas M.L.,Leeds Institute of Genetics | Elies J.,Leeds Institute of Genetics | Pettinger L.,University of Leeds | And 4 more authors.
FASEB Journal | Year: 2013

T-type Ca2 channels play diverse roles in tissues such as sensory neurons, vascular smooth muscle, and cancers, where increased expression of the cytoprotective enzyme, heme oxygenase-1 (HO-1) is often found. Here, we report regulation of T-type Ca2 channels by carbon monoxide (CO) a HO-1 by-product. CO (applied as CORM-2) caused a concentrationdependent, poorly reversible inhibition of all T-type channel isoforms (Cav3.1-3.3, IC50 ∼3 μM) expressed in HEK293 cells, and native T-type channels in NG108-15 cells and primary rat sensory neurons. No recognized CO-sensitive signaling pathway could account for the CO inhibition of Cav3.2. Instead, CO sensitivity was mediated by an extracellular redoxsensitive site, which was also highly sensitive to thioredoxin (Trx). Trx depletion (using auranofin, 2-5 μM) reduced Cav3.2 currents and their CO sensitivity by >50% but increased sensitivity to dithiothreitol ∼3-fold. By contrast, Cav3.1 and Cav3.3 channels, and their sensitivity to CO, were unaffected in identical experiments. Our data propose a novel signaling pathway in which Trx acts as a tonic, endogenous regulator of Cav3.2 channels, while HO-1-derived CO disrupts this regulation, causing channel inhibition. CO modulation of T-type channels has widespread implications for diverse physiological and pathophysiological mechanisms, such as excitability, contractility, and proliferation. © FASEB.

Abdelrahman M.A.,University of Leeds | Marston G.,University of Leeds | Hull M.A.,University of Leeds | Markham A.F.,University of Leeds | And 3 more authors.
Ultrasound in Medicine and Biology | Year: 2012

Mouse models are becoming increasingly important in the study of molecular mechanisms of colorectal disease and in the development of novel therapeutics. To enhance this phase of preclinical research, cost-effective, easy to use noninvasive imaging is required to detect and monitor changes in the colon wall associated with disease pathology. This study investigated the feasibility of using 40-MHz (high frequency) B-mode ultrasound (HF-US) to image the normal mouse colon and measure its thickness invivo by establishing a robust imaging protocol and conducting a blinded comparison of colon wall thickness (CWT) measurement between and within operators. The invivo and exvivo appearance of mouse colon under HF-US revealed distinct patterns. Colon wall thickness was reproducibly and accurately measured using HF-US compared with histology measurement. The technique was more sensitive in detecting changes in CWT in distal than proximal colon as it showed the highest level of inter- and intraoperator reproducibility. Using the protocol described, it is possible to detect changes in thickness of0.09mm and 0.25 mm in distal and proximal colon, respectively. In conclusion, HF-US provides an easy to use and noninvasive method to perform anatomical investigations of mouse colon and to monitor changes in CWT. © 2012 World Federation for Ultrasound in Medicine & Biology.

Shantikumar S.,Leeds Institute of Genetics | Ajjan R.,Leeds Institute of Genetics | Porter K.E.,Leeds Institute of Genetics | Scott D.J.A.,Leeds Institute of Genetics
European Journal of Vascular and Endovascular Surgery | Year: 2010

Objective: The aim of this review is to delineate the association between abdominal aortic aneurysms (AAAs) and diabetes mellitus. Mechanisms for the underlying association are then discussed. Methods: A systematic review of the English-language literature using PubMed, EMBASE and Cochrane databases was undertaken up to September 2009. Studies reporting appropriate prevalence data were identified and a meta-analysis performed. Results: Eleven studies were identified. The prevalence of diabetes mellitus in studied patients with AAA ranged from 6% to 14%. The prevalence of diabetes in control patients without AAA ranged from 17% to 36%. Pooled analysis suggested a reduced rate of diabetes amongst people with AAA compared to those without (OR 0.65, 0.60-0.70, p < 0.001). Conclusions: Studies so far suggest a protective role for diabetes on the development of AAA. Further research is required to demarcate the underlying mechanisms for this possible association. © 2009 European Society for Vascular Surgery.

Loading Leeds Institute of Genetics collaborators
Loading Leeds Institute of Genetics collaborators