1,720,971 research outputs found

    An observational study of natural history of cardiovascular diseases

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    Atherosclerosis is a chronic, progressive, inflammatory disease with a long asymptomatic phase that can be identified by several methods when the disease is still in a subclinical stage. Lifestyle modifications and medical managements such as statin therapy can slow, halt or even reverse the progression of atherosclerotic disease. Whether to screen and treat patients for subclinical atherosclerosis remains controversial. Demographic data and risk factors were collected retrospectively from 300,000 asymptomatic individuals who attended for self-funding, private cardiovascular screening in the UK and Ireland. Invitations were sent to men and women aged over 50 years in all UK and Ireland postcodes and regions for a cardiovascular health check. Detailed health questionnaire were self-reported by attendees and investigations were completed by trained technicians. Tests included ultrasound screening for AAA, ankle:brachial pressure index (ABPI), carotid duplex imaging for carotid atherosclerosis, electrocardiography for atrial fibrillation and rapid blood test for cholesterol, blood sugar and creatinine levels. The association between risk factors and prevalence of subclinical atherosclerosis and atrial fibrillation in different subgroups were determined using univariable analysis and odds ratios. After recoding continuous variables that were not normally distributed, significant risk factors were included in a multivariable linear logistic regression analysis in different models establishing two models to identify women at high risk of developing Abdominal Aortic Aneurysm. In addition, Analysis of newly diagnosed cases of Atrial Fibrillation showed a noticeable detection rate of new cases with high 3 CHA2DS2-VASc score, indicating initiation of anticoagulation for stroke prevention. Moreover, data related to kidney function and cardiovascular risk factors showed significantly higher prevalence of subclinical atherosclerosis among those with stage 3 or worse Chronic Kidney Disease. A small cohort of participants were prospectively followed up to assess the correlation between asymptomatic Carotid Artery disease and cardiovascular events which established that smoking history and the presence of asymptomatic Carotid artery disease as well as peripheral arterial disease were statistically significant and predictors of cardiovascular event. These findings highlights the value of ultrasound as a non-invasive and inexpensive tool to identify common and important conditions and sub-clinical atherosclerosis early in order to manage the atherosclerotic process at early stages where individual and healthcare system has the most benefit to achieve.Open Acces

    Histological morphology related to angiogenesis and hypoxia in congenital vascular malformations : exploring aetio-pathology and future target therapy

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    Background Musculoskeletal arteriovenous malformations (AVMs) result from abnormal angiogenesis and belong to congenital vascular malformations (CVMs) group. AVMs persist and have associated morbidity and even mortality. The aetio-pathogenesis of AVMs is unknown. This study analyses histological morphology and the immunohistological expression of specific angiogenesis and hypoxia markers in comparison with control tissues in patients with CVMs. CVM pO2 was further assessed. This work was performed to gain insight into possible mechanisms involved in aetio-pathogenesis of CVMs. Methods Thirty three consecutive CVMs and 10 control specimens were analysed morphologically using routine techniques, histochemical (H&E, Masson Trichrome, Elasic Von Gieson, Toluidine blue) and immunohistochemical (CD68, CD3, CD20, Factor VIII, actin 1-α, ki67 and S100). Further immunohistochemical studies analysed VEGF A, VEGFR-1, Tie-2, αV3 and αV5 integrins, HIF-1α and HIF-2α, CAIX. The neutral endopeptidase (NEP) was studied by immunostaining for CD10 on 38 CVMs. Intraoperative blood samples from CVMs were analysed for pO2. Results Macrophages (p<0.0001), mast cells (p<0.0001), vessel number (p=0.0004) and diameters (p=0.0005) were significantly higher in the CVMs compared to controls. The expression of all angiogenesis markers were significantly higher in CVMs comparing to controls. HIF-1α, HIF-2α and CD10 (p=0.0002) were over-expressed in CVMs. There was a positive correlation between HIF-2α expression and VEGF A (p=0.0001), VEGFR-1 (p=0.0043), Tie-2 (p=0.03), αVβ3 (p=0.029), αVβ5 (0.045), CD10 (p=0.0002) and inflammatory cells in CVMs. Comparisons of CVM and arterial blood pO2 were not significant (p=1). Discussion Inflammation and imbalance of angiogenic and hypoxia markers are implicated in CVM pathogenesis. HIF-2α may play a more important role in CVM pathgogenesis than HIF-1α. CVM blood has an arterial pattern in spite of expressing HIF. CD10 may be a potential marker for CVMs in biopsies. Molecular patterns and potential signalling pathways involved in CVM pathogenesis are implicated in this work. This enhanced clinico-pathological correlation should improve therapeutic options and efficacy

    Endothelial function/ dysfunction and oxidative stress during ischaemia reperfusion injury as a consequence of intermittent claudication. Is good endothelial function a prognostic indicator for poor cardiovascular outcome in intermittent claudication?

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    Peripheral Vascular Disease (PVD) has a major morbidity and mortality in the general population. The spectrum of PVD ranges from intermittent claudication to critical limb ischaemia. There is a high prevalence of intermittent claudication in the general population, however only five to ten percent will progress to more severe disease. The progression of disease is at present unpredictable. There is a growing awareness that patients with intermittent claudication may have differing propensities for developing cardiovascular morbidity and mortality. This study aims to investigate the relationship between the endothelial response to exercise in the macro and microcirculation and correlate this with plasma inflammatory cytokine levels, plasma oxidative state and a marker of acute kidney injury in patients with peripheral vascular disease and healthy controls. This information may lead to a new screening test for patients with an increased risk of disease progression who once identified could be better managed to reduce their risk. Furthermore potential new cytokine targets for halting disease progression and potential treatment will be investigated.Open Acces

    Development and assessment of vascular phantoms for research and education

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    Ultrasound practices encompass a wide variety of diagnostic and interventional procedures that increasingly fall under a wide variety of medical specialities. The major drawback of ultrasound use, is that considerable experience is required to gain the most from procedures. The skill of Ultrasound (U/S) operator is known to positively correlate with the number of scans performed. The practice of U/S is expanding in clinical medicine, and as a consequence, there is an increasing demand for education and training. Medical phantoms and simulators are rapidly expanding and are credited with improving safety and reducing medical errors. One of the most attractive areas where the medical phantoms and simulation systems could effectively help to achieve training goals and to improve practitioner skills in detection and diagnosis of variable disease is the vascular ultrasound applications. Duplex ultrasound is now recognised as a gold standard for many cardiovascular and peripheral vessel investigations. To establish our experience to deal with medical phantoms and build up knowledge to help us to use theoretical physics principles, an existing medical phantom was used. The Circle of Willis (CoW) replica was used to investigate the effects of occlusions on the cerebral blood flow in an anatomical replica of the circle of Willis. We succeeded to match the theoretical prediction of the peripheral resistance by adjusting the inlet pressure. The total cerebral flow was 444 mL/min in our model which is close to mathematical predicted value of 454 mL/min. The values and distribution of the anterior, middle, and posterior cerebral arteries were similar to mathematical measurements predicted by Alastruey. Our results suggest that the internal carotid artery (ICA) occlusion is more critical than the basilar artery occlusion and that the greatest reduction in the mean cerebral outflows occurred when the right ICA and contralateral anterior cerebral artery (A1) were occluded. As it has been known that ultrasound transducer of a single crystal with a frequency of around 2 MHz used for embolus detection in the Middle Cerebral Artery (MCA), but no specific transducer have been validated for embolus detection in Common Carotid Artery (CCA) yet. We used ultrasound as a diagnostic tool and carotid phantom in a novel study to investigate the sensitivity and specificity of embolus detection of Pulsed Waved probes in continuous monitoring of the common carotid artery. This was to establish validity and sensitivity of these Doppler transducers to detect solid embolic particles up to the size of 200 μm in a phantom of the common carotid artery. All the particles of 1000, 500, 200 μm diameter were detected and recorded by the fast speed camera. It was found that the particles of 1000μm and 500μm were detected with 100% sensitivity by 2MHz and 4MHz transducers. The 200 μm particles were detected with 94% sensitivity by 2MHz and 92% sensitivity and high specificity by 4 MHz transducers. The information from these studies could be used for the simultaneous monitoring of MCA and CCA with the use of 2 MHz probe to identify the active embolic signal source in patients with acute stroke. We successfully established the reliability of simultaneously monitoring of embolic signal from two sources. This monitoring technique could be used for monitoring patients with suspicion of Transient Ischemic Attack and all those who have had a stroke in acute stroke unit. The information and experience gained from the above investigations were used to develop a life size lower limb phantom. The phantom was subsequently used with a vascular simulator for the lower limb blood flow studies. Additionally, this setup was used to assess the scanning competency of novice vascular surgeon. Tissue mimicking materials were used to create life-size lower limb phantom that contains multilayers, skin-fat-muscle-bone and blood vessels. An extracorporeal circuit incorporating lower limb phantom and complex vascular simulator was set up to assess how effectively participants achieved training goals to improve their scanning skills in detection and diagnosis of peripheral vascular diseases in a life size leg phantom.Open Acces

    The creation and validation of an immersive virtual reality simulator to teach and assess clinical reasoning

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    Introduction Emerging technologies such as virtual reality(VR) and 360-degree cameras have been presented as a technological solution that, through increased realism and presence, could lead to improved learning gains versus existing teaching modalities. Aims The main aim of the thesis is to create an immersive VR simulator using 360-degree camera technology to teach and assess clinical reasoning skills. Methods A multi-method approach across a series of studies were used to achieve the thesis aims. The first study aimed to develop a VR clinical scenario and scoring system using validated virtual patient guidelines, VR usability guidelines and scoring rubrics. A 360-degree camera and VR editing software were used for scenario construction. Three experimental studies were performed. Study 1: randomised controlled trial(RCT) comparing the simulator across two delivery modes - 2D screen(n=19) versus immersive head-set(n=20); assessing system usability and level of presence. Study 2: cohort study assessing the contrast validity of the simulator (medical students; n=16), foundation year doctors (n=21), and core surgical doctors (n=19). Study 3: RCT assessing learning gains (using Script Concordance test) with the simulator versus traditional methods(n=53). Results Four scenarios were created with scoring systems. The system was equally usable in both delivery forms(80.3 control vs 80 in treatment; p>0.05) with significantly higher levels of presence in the immersive group(0.81 vs 0.67; p<0.05). The simulator was able to differentiate between the most and least experienced group(57.3% vs 46.4%; p<0.05). Finally, the simulator learning gains were significantly higher compared to the traditional learning group(2.35 vs 1.64, p<0.05). Discussion This thesis demonstrates the feasibility of construction of a series of immersive VR clinical scenarios using 360-degree video. Taken together the results present a robust methodology for the creation and assessment of simulations using this technology and demonstrate the educational benefit for the teaching and assessment of clinical reasoning.Open Acces

    The laser Doppler assessment of sternal wound microcirculation in patients undergoing  cardiac surgery

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    Background: Cardiac surgical procedures such as a coronary artery bypass graft (CABG) and aortic valve replacement (AVR) surgeries with a cardiopulmonary bypass (CPB) which can lead to a spectrum of post-operative complications mainly as a result of delayed sternal wound healing and activation of systemic inflammatory responses. Delayed wound healing is secondary to a reduced regional blood flow, systemic diseases, poor surgical techniques and many other reasons can lead to sternal wound dehiscence and infection. Diabetic mellitus (DM) is a major metabolic disease, involving most of the systems of the body. One of the long-term consequences of DM is pathological changes of macro and microcirculation that causes narrowing of vasculature and reduced response to hormonal and neurological stimulation to control the rate of regional perfusion. Aim: This study is to establish the role and significance of the laser Doppler scanner in the sternal wound healing in patients undergoing cardiac surgery such as CABG and AVR. Reduced sternal perfusion follows cardiac surgery secondary to progression of DM uses of left internal mammary artery as a bypass graft. The laser Doppler can be used as a diagnostic and prognostic tool to forecast and predict the disease process of delayed wound healing and sequalae of consequences. Method: 60 patients of CABG and AVR were selected fulfilling the inclusion and exclusion criteria equally divided into diabetic and non-diabetic. The sternal area of interest was scanned using the laser Doppler scanner at 5 time point readings such as preoperatively, 24 hours postoperatively, 48 hours postoperatively and 72 hours postoperatively.Results: Patients undergoing CABG with use of left internal mammary artery, the perfusion on the left lateral aspect of sternal incision mirroring the left internal mammary artery harvests sites in diabetic and non-diabetic patients. There was a statistically significant difference (P <0.05) in skin perfusion in mean area studied on both sides and in both diabetic and non-diabetic patients. Importantly both groups showed lower perfusion on the left side. Diabetic patients had a more pronounced drop in perfusion on the left side compared to the right side, however by 72 hours skin perfusion was near normal in both diabetic and non-diabetic patients. The difference in skin perfusion between diabetic and non-diabetic patients was present throughout all the time points studied and pre-operative measurements returned to near normal at last time point studied. (T1 – pre-operative, T5 – 72 hours post-operative and P = 0.30). One of the non-diabetic patients showed delayed perfusion and treated with surgical debridement, VAC pump and antibiotics. Patients undergoing aortic valve replacement surgery showed similar perfusion bilaterally due to absence of left internal mammary artery harvest sites in diabetic and non-diabetic patients. There was a statistically significant difference (P <0.05) in skin perfusion in mean area studied on both sides and in both diabetic and non-diabetic patients and this difference was present throughout all the time points studied. There was no difference as expected between left and right side in diabetic and non-diabetic patients undergoing valvular heart surgery due to absence of left internal mammary artery harvest. The difference in skin perfusion between diabetic and non-diabetic patients was present throughout all the time points studied and pre-operative measurements returned to near normal at last time point studied. (T1 – pre-operative, T5 – 72 hours post-operative and P = 1.0). There was a delayed sternal perfusion on the left side of the sternum in one of the diabetic patient. He suffered from wound infection and treated responded to antibiotics. Conclusion: LDF of sternal wound can be used as a diagnostic and prognostic tool in patients undergoing open cardiac surgery to predict the outcome and management.Open Acces

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    The influence of exercise on ulcer healing in patients with chronic venous insufficiency

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    Venous leg ulcer (VLU) is a common chronic clinical problem and it is the most serious complication of chronic venous insufficiency. Although venous ulcer has a huge burden on individuals and states, the standard type of treatment for this debilitating condition, compression therapy, has not changed in the last 2000 years. There is growing evidence that exercise could help in venous ulcer management. This study investigated the effect of exercise on 80 VLU patients. These patients were randomised into four groups; a control group, a compression therapy only group, an exercise only group and a compression and exercise group. Non-invasive measurements were performed at the beginning of the 3 month period of regular exercise, and again at the end of the exercise period. This was necessary in order to evaluate the effect of exercise on VLU healing parameters, which include; tcPO2 level, laser Doppler measurements, resting skin flux (RF), range of ankle joint movement (ROM) and ulcer size. The exercise composed of 10 dorsiflexions each hour, while the participant was awake over a period of 3 months. Findings included, an increase in the tcPO2 level and range of ankle joint movement in individuals who had performed the exercise compared to those who did not (p < 0.001). Moreover tcPO2 measurements were higher in the exercise and compression group than those seen in the exercise only group. Ulcer size and RF measurements decreased in patients who had performed exercise compared to those who did not, groups 3 and 4 showed a significant decrease in ulcer size with p values = 0.001 and < 0.001 respectively. With RF measurements, only groups 3 and 4 showed significant decrease, p < 0.001. The findings indicated that there were changes in the VLU parameters in response to the 3 months period of regular exercise. Regular unsupervised exercise may be included as an integral part of the leg ulcer management.Open Acces
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