tbuckley/cabot-search huggingface dataset:
Abstract 3114: The Ageing Process of the Heart: the Effect of Smoking on Arterial Stiffness and Left Ventricular Diastolic Function - The MONICA/KORA-Study
Authors: Jan Stritzke, Marcello R Markus, Stefanie Duderstadt, Wolfgang Lieb, Andreas Luchner, Angela Döring, Helmholtz Zentrum München, Ulrich Keil, Hans-Werner Hense, Heribert Schunkert
Journal: Circulation (2008)

Smoking is an important cardiovascular risk factor and thereby strongly related to cerebral ischemia and myocardial infarction. Here we evaluated subclinical effects of smoking behaviors on arterial stiffness and left ventricular diastolic function in middle-aged individuals without known cardiovascular disease. Within a gender and age stratified random sample diastolic function was assessed by standardized echocardiography at baseline and again after ten years. Furthermore pulse wave analysis was performed at the follow-up investigation. Within a healthy subgroup aged 25 to 44 years at baseline (n=400) associations between smoking behaviors and LV diastolic function as well as arterial stiffness were assessed by comparison of non-smokers (nonS, consisted of never smokers and individuals who stopped active smoking at least 10 years before follow-up investigation), ex-smokers (exS, individuals who stopped smoking within 10 years of follow-up), and current smokers (curS). Adjusted mean values were calculated by linear regression models. As compared to non-smokers, current smokers as well as ex-smokers presented with worse diastolic function at follow-up. Specifically, they displayed lower e/a-ratios (curS 1.23 95%-CI [1.19, 1.28]; exS 1.23 [1.15, 1.32]) as compared to nonS (1.33 [1.29, 1.36], p-values 0.001 and 0.041, respectively). Additionally, declines of e/a-ratios associated with ageing by 10 years were also significantly different (curS −0.35 [−0.39, −0.31]; exS −0.39 [−0.46, −0.31]; vs. nonS −0.27 [−0.30, −0.24]; each p=0.006). Furthermore, curS presented with increased arterial stiffness as displayed by higher augmentation index (curS 20.1 [18.5, 21.6]; exS 16.7 [13.9, 19.6]; vs. nonS 16.7 [15.5, 17.9], p&lt;0.001 and p=0.995) and shorter time to reflection (curS 141ms [139, 143]; exS 147ms [143, 151]; vs. nonS 145ms [143, 146], p=0.005 and p=0.265). In middle-aged healthy individuals smoking is strongly related to subclinical changes in arterial stiffness and diastolic function. But even after termination of active smoking these changes partly persist. Consequently, interventional programs addressing younger adults are essential to prevent premature cardiovascular ageing.
Genetic Algorithms Applied to Multi-Class Clustering for Gene Expression Data
Authors: Haiyan Pan, Jun Zhu, Danfu Han
Journal: Genomics Proteomics & Bioinformatics (2003)

A hybrid GA (genetic algorithm)-based clustering (HGACLUS) schema, combining merits of the Simulated Annealing, was described for finding an optimal or near-optimal set of medoids. This schema maximized the clustering success by achieving internal cluster cohesion and external cluster isolation. The performance of HGACLUS and other methods was compared by using simulated data and open microarray gene-expression datasets. HGACLUS was generally found to be more accurate and robust than other methods discussed in this paper by the exact validation strategy and the explicit cluster number.
Abstract 237: The Apolipoprotein A-I Mimetic Peptide D-4F Acts As A Scavenger For Myeloperoxidase-Derived Hypochlorous Acid
Authors: Amanda Wake, Geeta Datta, Harry Mahtani, Mayakonda Palgunachari, Dale Parks, Vinod Mishra, Gm Anantharamaiah, C. Roger White
Journal: Circulation (2007)

Background: Myeloperoxidase (MPO) and its product hypochlorous acid (HOCl) are proatherogenic molecules that functionally modify lipoproteins and impair endothelial cell function. MPO- and HOCl-induced changes in HDL function are thought to occur via modifications at the level of apolipoprotein (apo) A-I. Objective : We tested the hypothesis that the apo A-I mimetic peptide D-4F, which possesses HDL-like properties, prevents endothelial dysfunction by acting as a reactive substrate for HOCl. Methods and Results: Rat aortic ring segments were isolated and suspended in an isolated tissue bath and exposed to HOCl (10μM, 30min, n=7). Acetylcholine (Ach)-induced relaxation was inhibited by 51% compared to saline-treated controls (n=8). Concurrent exposure to HOCl and D-4F (10μM, n=9) significantly improved the response to Ach (15% inhibition vs control). Incubation of tissues with D-4F alone (n=9) did not impair endothelial function. Since increased superoxide formation has been implicated in HOCl-induced endothelial dysfunction, we tested whether D-4F influences formation of this oxidant. Electroparamagnetic resonance spectroscopy, in conjunction with BMPO (25mM) spin trapping, was used to determine whether D-4F reduces superoxide generated by xanthine (1mM)/xanthine oxidase (15mU). There was no difference in BMPO resonance spectra in the presence and absence of D-4F at concentrations up to 300 μM. In subsequent studies, effects of HOCl on structural properties of D-4F were assessed. Fluorescence spectroscopy revealed a significant reduction in tryptophan fluorescence of D-4F (20μM) in the presence of HOCl (10μM). Time of flight mass spectrometry was used to characterize reaction products formed by HOCl and D-4F. MS analysis of D-4F (20μM) alone yielded a product with the expected m/z ratio of 2,310. Addition of 10μM HOCl to D-4F yielded a new product with a net gain of 16 mass units. MS/MS analysis confirmed the addition of this mass to the tryptophan residue, reflecting oxidation of this residue. Conclusion: While D-4F was previously shown to inhibit lesion formation and inflammation in experimental models of atherosclerosis, results of the current studies suggest that D-4F may also serve as a scavenger of MPO-derived HOCl.
Abstract 2057: Over-expression of p27 Inhibits Vascular Smooth Muscle Cells Proliferation and Neointima Formation in Rabbit Vein Graft Model
Authors: Paula F Vassallo, Giovana A Gonçalves, Leandro Cardoso, Jose Krieger
Journal: Circulation (2007)

Neointima formation caused by vascular smooth muscle cells (VSMC) proliferation is an early event in vascular remodeling associated with arterialization of vein graft and the magnitude of this process may contribute for late failure. Cell cycle is tightly regulated and cyclin-dependent kinase inhibitor p27 kip1 plays a critical role in this process. We investigated whether overexpression of p27 can modulate this early cell proliferative response in rabbit vein grafts. First generation bicistronic adenovirus AdCMVp27hEGFP, (AV1) harbouring the human p27 sequence, and AdCMVLacz (AV2) were engineered. Overexpression of p27 was analyzed by immunofluorescence and the antiproliferative effect of AV1 was assessed in primary culture of VSMC followed by 1, 3, 5, and 9 days after AV1 transduction vs. AV2. A segment of jugular vein vas exposed to AV1 and AV2 (10 9 –10 11 pfu/mL) or placebo for 30 min and then interposed, end to end, to the carotid artery of adult male New Zealand rabbits. After 28 days the vein grafts were harvested and stained with Miller for neointima analyses. Imunofluorescence of VSMC showed positive cells 72 hs following AV1 transduction. Significant inhibition of cell proliferation was observed 7 and 9 days after the cells were exposed to AV1 compared to AV2 or control cells (7 days: 0.34 ± 0.15 × 10 5 vs. 1.5 ± 0.22 × 10 5 , 2.04 ± 0.29 × 10 5 cell/ml, p&lt;0.01; 9 days: 0.23 ± 0.1 × 10 5 vs. 1.49 ± 0.31 × 10 5 , 2.31 ± 0.41 × 10 5 cell/ml, p&lt;0.01). In vivo , transduction efficiency was evaluated by the expression of B-galactosidase 48 hs. after surgery in vein grafts exposed to AV2. Vein grafts transduced with AV1 showed significant reduction in neointima hyperplasia compared with AV2 or to control animals not exposed to any viral treatment (47.33 ± 5.36 vs. 112.83 ± 24.2 and 80.08 ± 10.51μm, p&lt;0.05). These results show that adenovirus mediated over expression of human protein p27 can inhibit VMSC proliferation in vitro and significantly impair the neointima formation associated with arterialization of vein graft after 28 days. It will important to establish the long term effects of this intervention specially when associated with other environment stimuli such as high fat that can clearly influence the outcome of this therapeutic intervention.
Abstract 5553: Hypercholesterolemia Induced Overexpression of Caveolin-1 and LOX-1 Downregulates HO-1/HSP-90 Mediated e-NOS Activation: A Novel Therapeutic Strategy for the Improvement of Left Ventricular Function
Authors: Suresh Varma Penumathsa, Srikanth Koneru, Gautam Maulik, Nilanjana Maulik
Journal: Circulation (2008)

Hypercholesterolemia (HC) related decrease in eNOS phosphorylation &amp; endothelial dysfunction may account for impaired angiogenesis and subsequent increased ventricular remodeling. Over expression of Caveolin-1 (Cav-1) and Lectin-like oxidized LDL receptor (LOX-1) has been demonstrated during HC but the mechanism needs to be elucidated. To investigate this we randomized the rats into control (normal diet) and HC (5% high cholesterol diet for 8 weeks). The cholesterol, triglycerides &amp; LDL levels were increased &amp; the HDL levels decreased in HC compared to control. After the experimental diet period the rats were subjected to Left Anterior Descending Artery (LAD) ligation. We evaluated the expression of Cav-1, LOX-1, Heme Oxygenase (HO-1), HSP-90, phospho(p)-Akt &amp; p-eNOS in HC and control. Significant increase in Cav-1, LOX-1 (2, 1.8 fold) &amp; decrease in HO-1, HSP-90, p-Akt, p-eNOS &amp; VEGF (0.5, 0.6, 0.4, 0.5 &amp; 0.6 fold) was observed in HC compared to control. The LV functional reserve was evaluated by measuring the ejection fraction (EF), fractional shortening (FS) &amp; LV internal diameter (LVID) after 30 days of LAD ligation. Significant increase in LVID ( 8.6 vs 7) and decrease in EF (39 vs 53%), FS (20 vs 28%), LVID (2 vs 2.7mm) as well as capillary (1888 vs 2424) &amp; arteriolar density (1.5 vs 2.5) counts/mm2 was observed in HC compared to control. Earlier we have reported that over expression of HO-1 mediates eNOS activation &amp; cardioprotection in MI model. To investigate the mechanism involved in HO-1 mediated cardioprotection we generated cardiac specific HO-1 over expressed transgenic (Tg) mice. Immunohistochemical analysis of HO-1 Tg mice has clearly demonstrated decreased Cav-1-eNOS interaction. Immunoblot analysis has shown to decrease Cav-1 (0.6 fold) &amp; increased HSP-90, p-Akt, p-eNOS &amp; VEGF expression (1.5, 1.6, 1.4 &amp; 1.5 fold) as compared to control. These findings demonstrated that HO-1 over expression regulates HSP-90 &amp; Cav-1 for eNOS activation. In conclusion, we demonstrate a novel mechanism of HO-1/HSP-90 mediated Cav-1-eNOS regulation leading to increased neovascularization &amp; reduced ventricular remodeling during HC for the regression of clinical complications which would be crucial for cardiovascular drug therapy.
Abstract 2: Sodium-Hydrogen Exchanger Inhibition Attenuates Traumatic Hemorrhage Induced Acute Lung Injury in Pigs
Authors: Dongmei Wu, Jiansong Qi, William Abraham
Journal: Circulation (2008)

Background: Acute lung injury is a complication of traumatic hemorrhagic shock, and contributes to the high mortality rate. This study examined the effects of Na+/H+ exchanger inhibition on traumatic hemorrhage induced acute lung injury in pigs. Methods: Tibia fractures with soft tissue injury were induced in 12 anesthetized instrumented male pigs. The animals underwent hemorrhage of 25ml/kg for 20min, followed by a 4mm abdominal aortic tear with surgical repair after 30minutes. Animals then underwent initial fluid resuscitation with either 15ml/kg Hextend (n=6) or 3mg/kg BIIB513 +15ml/kg Hextend (n=6). Resuscitation occurred over 40 minutes. A second resuscitation was given 4 hours later. Hemodynamics, arterial and mix-venous blood gases were measured throughout the experiment, which was terminated 6 hours after initial resuscitation. Results: Hemorrhage and resuscitation with Hextend alone resulted in a significant increase in pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR). These changes were accompanied by a significant decrease in mix-venous oxygen saturation, decreased oxygen delivery and an increased oxygen extraction ratio. BIIB513 + Hextend treatment significantly attenuated the increase in PAP by 26% and PVR by 50%, as well as significantly improving blood oxygen delivery by 30%. BIIB513+ Hextend treatment group had a 70% higher blood oxygen content and mixed venous blood oxygen saturation than did the control group (61% vs. 42%). NHE-1 inhibition with BIIB513 reduced lung tissue levels of IL-6 by 80%, TNF-á by 37%, and myeloperoxidase activity by 38%. Nuclear factor (NF)-ê B DNA binding activity in the lung was slightly attenuated in BIIB513 treated animals), compared to those treated with hextend alone. Conclusion : The present study shows that the response to fluid resuscitation after controlled hemorrhage is improved by the addition of the NHE-1 inhibitor BIIB513. NHE-1 inhibition resulted in attenuation of traumatic hemorrhage and resuscitation induced acute lung injury by improving pulmonary vascular function, possibly by reducing NF-κB activation and neutrophil infiltration, thereby limiting the tissue inflammatory injury.
Electronic patient records in general practice
Authors: P. J B. Brown, R. G Newcombe, D. G Altman, T. N Bryant, A. Hassey, D. Gerrett, A. Wilson
Journal: BMJ (2001)

Editor—Hassey et al have highlighted the importance of ensuring that electronic records are accurate.1 In their study they explored a method of measuring the validity and utility of electronic records in general practice, including whether the coding of 15 marker diagnoses was a true reflection of the actual prevalence.

They are, however, wrong in their assertion that no published accounts of measuring the validity of electronic record contents exist. Hogan and Wagner performed a literature review and compared 20 articles that met certain quality criteria.2 They recommended (as did Hassey et al) that measures of completeness (sensitivity or detection rate) and correctness (positive predictive value) were valuable. These measures have also been shown to be valuable in measuring the quality of data retrieval.3

Other measures derived from 2×2 contingency tables are less likely to be helpful because of the combination of a large total number of records and true negatives. To compensate for this, Hassey et al propose two new descriptive statistics. Previous reports have used Cohen's κ,4 a measure of the strength of agreement between the observed retrieval and the gold standard, against a result that might be expected by chance. Cohen's κ has the advantage of being a well validated single index and has been shown to be a useful index of measuring data retrieval from electronic records where performances of >0.9 can be achieved.3

When Cohen's κ is applied to the data by Hassey et al, it highlights similar priority areas of data concern where the value is <0.9 (obesity 0.04, hypothyroidism 0.89, iron deficiency anaemia 0.86, asthma 0.86). Prescriptions generated were also compared with those dispensed by a local pharmacy. As they were computer generated, 99.7% were reported to be valid, but of the 10 handwritten prescriptions only 80% were accurately recorded. Perhaps a more suitable design would have been to check in a sample how many of the prescriptions reflected the correct dose and frequency. Hassey et al claim that the principal innovation of the study was the use of Read codes as the test for the true presence of a diagnosis, despite Gray et al's earlier account of identifying patients with ischaemic heart disease by using a similar technique and reporting exactly the same sensitivity rate (96%).5 The approach used by Hassey et al in triangulating disease codes with treatments and other findings has merit, but due consideration should have been given to existing literature.
Abstract 2453: Exercise Capacity is Inversely Associated with Mortality Risk in Pre-Hypertensive Men
Authors: Andreas E Pittaras, Jonathan Myers, Puneet Narayan, Athanasios Manolis, Charles Faselis, Steven Singh, Peter Kokkinos
Journal: Circulation (2008)

Introduction: Epidemiologic evidence supports an inverse and strong association between fitness status, and mortality in healthy individuals. Pre-hypertensive individuals are at increased risk for cardiovascular events compared to those with normal blood pressure. However, there is no information on the association between exercise capacity and mortality in pre-hypertensive individuals. Methods: We assessed the association between peak exercise capacity (METs) and all-cause mortality in pre-hypertensive men (n=4,735; age=56±12). We established four fitness categories based on the MET level achieved. Those who achieved &lt;5 METs (n=674); 5–7 METs (n=1,170); 7.1 to 10 METs (1,784); and &gt; 10 METs (n= n=1,107). There were 943 deaths over 22 years of follow-up (mean=8.0±5.5). Results : After adjusting for age, BMI, diabetes and dyslipidemia, exercise capacity was the strongest predictor of risk for mortality. The adjusted risk was reduced by 14% for every 1-MET increase in exercise capacity (Hazard Ratio= 0.86; CI: 0.84 – 0.88; p&lt;0.001). When compared to those who achieved ≥5 METs, the mortality risk in those who achieved 5.1–7 METs was 25% lower (hazard ratio= 0.75; CI: 0.64 – 0.87; p&lt;0.001); 60% lower for those who achieved 7.1–10 METs (hazard ratio= 0.40; CI: 0.33– 0.48; p&lt;0.001), and 75% lower for those achieving &gt;10 METs (Hazard Ratio= 0.25; CI: 0.19 – 0.33; p&lt;0.001). Conclusions: The association between exercise capacity and mortality in pre-hypertensive individuals was strong, inverse and graded. The mortality risk was lowered by 14% for each 1-MET increase in exercise capacity. The overall reduction in mortality was 25% to 75% for those with an exercise capacity of &gt;7 METs compared to those who achieved &lt;5 METs.
Abstract 752: HOXA9 and FLK1 Expression in CD34+ Peripheral Cells of Hypertensive Patients Correlates with the Number of Circulating Endothelial Progenitor Cells
Authors: Matteo Pirro, Cinzia Menecali, Francesco Bagaglia, Massimo R Mannarino, Donatella Siepi, Giuseppe Schillaci, Elmo Mannarino
Journal: Circulation (2006)

Objective. HoxA9, a critical regulator of postnatal neovascularization and endothelial commitment during progenitor cell maturation, is essential for the expression of the endothelial-committed gen...
Abstract 718: Local Lentiviral ShRNA Mediated Silencing of CCR2 Inhibits Intimal Hyperplasia in ApoE3Leiden Mice
Authors: Ilze Bot, Daniel Eefting, Margreet R de Vries, Hajo van Bockel, Theo J Van Berkel, Erik A Biessen, Paul H Quax
Journal: Circulation (2006)

Intimal hyperplasia and accelerated atherosclerosis in venous bypass grafts are major causes of graft failure, in which inflammatory responses to vascular injury and smooth muscle cell (SMC) migrat...
Relationship of expression level of CD133 with tumor angiogenesis and prognosis of hepatocellular carcinoma after liver transplantation.
Authors: Y. Xu, J. Fan
Journal: Journal of Clinical Oncology (2010)

10568 Background: CD133 has been reported as a cancer stem cell marker in hepatocellular carcinoma (HCC). CD133-positive cells are related to tumor angiogenesis, growth and metastasis, therefore may influence clinical outcome. Local recurrence and metastasis remains to be the largest obstacle for survival after liver transplantation for HCC. The goal of the current study was to elucidate the prognostic significance of CD133 and VEGF in HCC patients after liver transplantation. Methods: Tumor tissue microarrays were used to detect the expressions of CD133 and VEGF in 190 HCC patients underwent liver transplantation between 2001 and 2006 in our Institute. Clinicopathologic data for these patients were investigated. Prognostic effects of CD133 and VEGF were evaluated by Kaplan-Meier method and compared by the log rank test. The Spearman rank test and Fisher's exact test were applied to demonstrate correlations. Results: Both CD133 and VEGF were independent predictors for relapse-free survival (RFS, p < 0.05) according to multivariate survival analysis. Compared with the CD133-negative patients, CD133-positive patients had significantly lower RFS (p < 0.05), expressed higher VEGF levels (p < 0.05) and microvessel density (MVD, determined by CD34 immunostaining). The patients with positive expressions of both CD133 and VEGF had the worst RFS (p < 0.05). Conclusions: High expression level of CD133 is related to tumor angiogenesis and poor prognosis of HCC patients after liver transplantation. CD133 combined with VEGF can be used to classify HCC patients with high risk of tumor recurrence after liver transplantation. No significant financial relationships to disclose.
Grand Rounds - Hammersmith Hospital: Clinicopathological conference Dizziness and confusion after bone marrow transplantation
Authors: D O'Shaughnessy, J M Goldman, M Roddie, J B Schofield
Journal: BMJ (1994)

A 44 year old woman presented to the Hammersmith Hospital with dizziness and cognitive impairment five months after receiving a bone marrow transplant. Despite intensive treatment her condition deteriorated and she died two months later. A stereotactic biopsy of the brain and postmortem findings were diagnostic. We presented a summary of her case, minus the final diagnosis, to Professor Christopher Kennard, professor of clinical neurology at Charing Cross and Westminster Medical School, and asked him to reach a diagnosis.

DOS: A 44 year old woman, who had received a bone marrow transplant, presented in October 1991 with a two week history of cognitive impairment noted by her husband. Eight years previously she had had Philadelphia positive chronic myeloid leukaemia diagnosed while she was pregnant. After delivery she was treated with hydroxyurea and busulphan, and in May 1991 she received bone marrow from a volunteer unrelated donor after conditioning with cyclophosphamide and total body irradiation. Her prophylaxis against graft versus host disease comprised T cell antibodies (Campath 1G), cyclosporin A, and methotrexate. The transplant was complicated by grade II graft versus host disease of the skin and upper gastrointestinal tract and candidiasis, which responded to high dose steroids and fluconazole.

Five months later, she presented with dizziness and severe oral herpes simplex ulcers. Despite treatment with acyclovir the dizziness persisted, and she was also found to have behavioural changes, poor concentration, and reading and writing difficulties and she was unable to count money in the shops. On examination she had no fever impaired short term memory, severe dyscalculia, mild constructional apraxia, and left visual inattention. She scored 25 out of 30 on the Folstein mini-mental state questionnaire.

CK: Before considering any investigations we should try to localise the lesions that are giving rise to the symptoms and signs. This patient presented …