tbuckley/cabot-search huggingface dataset:
Percutaneous Pulmonary Valve Implantation in Humans
Authors: Sachin Khambadkone, Louise Coats, Andrew Taylor, Younes Boudjemline, Graham Derrick, Victor Tsang, Jeffrey Cooper, Vivek Muthurangu, Sanjeet R. Hegde, Reza S. Razavi, Denis Pellerin, John Deanfield, Philipp Bonhoeffer
Journal: Circulation (2005)

Right ventricular outflow tract (RVOT) reconstruction with valved conduits in infancy and childhood leads to reintervention for pulmonary regurgitation and stenosis in later life.Patients with pulmonary regurgitation with or without stenosis after repair of congenital heart disease had percutaneous pulmonary valve implantation (PPVI). Mortality, hemodynamic improvement, freedom from explantation, and subjective and objective changes in exercise tolerance were end points. PPVI was performed successfully in 58 patients, 32 male, with a median age of 16 years and median weight of 56 kg. The majority had a variant of tetralogy of Fallot (n=36), or transposition of the great arteries, ventricular septal defect with pulmonary stenosis (n=8). The right ventricular (RV) pressure (64.4+/-17.2 to 50.4+/-14 mm Hg, P<0.001), RVOT gradient (33+/-24.6 to 19.5+/-15.3, P<0.001), and pulmonary regurgitation (PR) (grade 2 of greater before, none greater than grade 2 after, P<0.001) decreased significantly after PPVI. MRI showed significant reduction in PR fraction (21+/-13% versus 3+/-4%, P<0.001) and in RV end-diastolic volume (EDV) (94+/-28 versus 82+/-24 mL.beat(-1).m(-2), P<0.001) and a significant increase in left ventricular EDV (64+/-12 versus 71+/-13 mL.beat(-1).m(-2), P=0.005) and effective RV stroke volume (37+/-7 versus 42+/-9 mL.beat(-1).m(-2), P=0.006) in 28 patients (age 19+/-8 years). A further 16 subjects, on metabolic exercise testing, showed significant improvement in VO2max (26+/-7 versus 29+/-6 mL.kg(-1).min(-1), P<0.001). There was no mortality.PPVI is feasible at low risk, with quantifiable improvement in MRI-defined ventricular parameters and pulmonary regurgitation, and results in subjective and objective improvement in exercise capacity.
Assessment of outcome in ankylosing spondylitis: an extended radiographic scoring system
Authors: M C W Creemers, M J A M Franssen, M A van 't Hof, F W J Gribnau, L B A van de Putte, P L C M van Riel
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objective:</b> To develop and validate an extensive radiographic scoring system for ankylosing spondylitis (AS). <b>Methods:</b> The Stoke Ankylosing Spondylitis Spinal Score (SASSS) was modified by adding a score for the cervical spine and defining squaring. This modified SASSS (mSASSS) is the sum of the lumbar and cervical spine score (range 0–72). 370 lateral views of the lumbar and cervical spine were used for development of the mSASSS, standardisation of observers, and for studying reliability. In a 48 week NSAID study of 57 patients, change over time and construct validity were studied. <b>Results:</b> Interobserver correlations of the lumbar and cervical spine scores were good (<i>r</i>&gt;0.95). The interobserver duplicate error was 0.55 in a range from 0 to 36. The mean change in the cervical and lumbar spine scores between weeks 0 and 48 of all patients was 1.45 (range 0–6.0) and 1.06 (0–5.0), respectively (paired <i>t</i> testing, p&lt;0.001). Change in radiological score was seen in 36/57 (63%) patients (lumbar and cervical spine 11, cervical spine 12, lumbar spine 13 patients). <b>Conclusion:</b> The mSASSS is useful for assessing extensive radiographic damage in AS. It is reliable, detects changes over 48 weeks, and shows a satisfactory face and construct validity.
Antisense Oligonucleotide Targeting of Raf-1
Authors: Peter Mullen, Fiona McPhillips, Kenneth MacLeod, Brett Monia, John F. Smyth, Simon P. Langdon
Journal: Clinical Cancer Research (2004)

We sought to identify determinants of growth response to the Raf-1-targeted antisense oligonucleotide (ASO; ISIS 5132) using a large panel of ovarian cancer cell lines.First-(ISIS 5132) and second-generation (ISIS 13650) anti-Raf 1 ASOs were compared with control oligonucleotides. Growth was assessed by cell counts; apoptosis was assessed by poly(ADP-ribose) polymerase cleavage; and cell cycle analysis was assessed by flow cytometry. Protein expression was detected by Western blot analysis, and mRNA expression was detected by quantitative reverse transcription-PCR. Raf-1 kinase activity was detected by anti-Raf-1 immunoprecipitation, followed by myelin basic protein phosphorylation.A panel of 15 ovarian cancer cell lines was used to model a range of growth responses to ASOs targeting Raf-1 mRNA. Growth inhibition varied from 10% to >90% inhibition. Growth inhibition was associated with increased apoptosis and accumulation of cells in the G(2)-M and S phases of the cell cycle. Growth response was not related to level of Raf-1 protein expression, Raf-1 kinase activity, intracellular ASO uptake, or degree of Raf-1 protein inhibition. However, ASO growth response was associated with a high proportion of Raf-1 mRNA [relative to total (i.e., Raf-1 + A-Raf + B-Raf) Raf mRNA] and significantly higher Raf-1 kinase activity induction following growth factor (transforming growth factor alpha) stimulation in the cell lines consistent with dependency of these cell lines on Raf-1.These data indicate that ovarian cancers demonstrate differential sensitivity to ASOs targeted against Raf-1, and target expression levels and degree of utilization of Raf-1 signaling are implicated. Clinically sensitive tumors could feasibly be identified.
Altered Arterial Expression Patterns of Inducible and Endothelial Nitric Oxide Synthase in Pulmonary Plexogenic Arteriopathy Caused by Congenital Heart Disease
Authors: ROLF M. F. BERGER, RALF GEIGER, JOHN HESS, AD J. J. C. BOGERS, WOLTER J. MOOI
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Flow-associated pulmonary hypertension leads to pulmonary plexogenic arteriopathy (PPA), a specific pulmonary vascular disease that includes vascular lesions characterized by abnormal vasodilatation and endothelial cell proliferation. Increased local production of NO has been suggested in this condition. Because reported data on the expression of endothelial NO-synthase (ecNOS) have been contradictory, we speculated that the expression of the inducible isoform of NOS (iNOS) is enhanced in this form of pulmonary hypertension. We investigated immunohistochemically the expression of ecNOS and iNOS in lung tissue of patients with flow-associated pulmonary hypertension (n = 18) and compared the findings with those in patients with increased pulmonary blood flow but normal pulmonary artery pressure (n = 10), with congestive vasculopathy (n = 6) and control subjects (n = 4). Immunoreactivity for ecNOS and iNOS was present both in normal and diseased pulmonary arteries. Marked immunoreactivity to both isoforms was present within the advanced lesions of PPA, including plexiform lesions. Semiquantitative analysis of immunoreactivity, both for ecNOS and iNOS, showed no correlation with the severity of morphologic vascular lesions (p = 0.29 and p = 0.23, respectively). In contrast to ecNOS, immunoreactivity for iNOS was increased in patients with flow-associated pulmonary hypertension compared with other patients (p = 0.02). The present study has demonstrated enhanced expression of iNOS in patients at risk for advanced PPA, but not in patients with other forms of pulmonary arteriopathy. Moreover, high expression of both ecNOS and iNOS were present in advanced lesions of PPA. These data suggest differentiated roles for different isoforms of NOS in the pathogenesis of this specific pulmonary arteriopathy.
Variations in codons 84-101 in the core nucleotide sequence correlate with hepatocellular injury in chronic hepatitis B virus infection.
Authors: T Ehata, M Omata, O Yokosuka, K Hosoda, M Ohto
Journal: Journal of Clinical Investigation (1992)

Individuals with chronic hepatitis B virus (HBV) infection are generally divided into asymptomatic healthy carriers and patients with chronic liver disease. Several studies have suggested that the hepatitis B core antigen could be an immunological target of cytotoxic T lymphocytes (CTL). To investigate the possible pressure site from CTL, the entire core region of HBV DNA was sequenced in 30 subjects (10 asymptomatic healthy carriers and 20 patients with chronic liver disease). No significant changes in the nucleotide sequence and deduced amino acid residue were noted in the 10 healthy carriers. In contrast, a cluster of changes in a small segment of 18 amino acids (codons 84-101 from the start of the core gene) was found in 15 of the 20 chronic liver disease patients. All these 15 patients had advanced liver diseases (chronic active hepatitis and cirrhosis), whereas only mild liver disease (chronic persistent hepatitis) was found in the five patients without mutations. These data suggest that the region with mutation clustering is the major target of CTL, and that the mutations evolve under the pressure of immune selection.
The Quality of Pharmacologic Care for Vulnerable Older Patients
Authors: Takahiro Higashi, Paul G. Shekelle, David H. Solomon, Eric L. Knight, Carol Roth, John T. Chang, Caren J. Kamberg, Catherine H. MacLean, Roy T. Young, John Adams, David B. Reuben, Jerry Avorn, Neil S. Wenger
Journal: Annals of Internal Medicine (2004)

Background: Although pharmacotherapy is critical to the medical care of older patients, medications can have considerable toxicity in this age group. To date, research has focused on inappropriate prescribing and policy efforts have aimed at access, but no comprehensive measurement of the quality of pharmacologic management using explicit criteria has been performed. Objective: To evaluate the broad range of pharmacologic care processes for vulnerable older patients. Design: Observational cohort study. Setting: 2 managed care organizations enrolling older persons. Patients: Community-dwelling high-risk patients 65 years of age or older continuously enrolled in the managed care organizations from 1 July 1998 to 31 July 1999. Measurements: Patients' receipt of care as specified in 43 quality indicators covering 4 domains of pharmacologic care: 1) prescribing indicated medications; 2) avoiding inappropriate medications; 3) education, continuity, and documentation; and 4) medication monitoring. Results: Of 475 vulnerable older patients, 372 (78%) consented to participate and had medical records that could be abstracted. The percentage of appropriate pharmacologic management ranged from 10% for documentation of risks of nonsteroidal anti-inflammatory drugs to 100% for avoiding short-acting calcium-channel blockers in patients with heart failure and avoiding β-blockers in patients with asthma. Pass rates for quality indicators in the "avoiding inappropriate medications" domain (97% [95% CI, 96% to 98%]) were significantly higher than pass rates for "prescribing indicated medications" (50% [CI, 45% to 55%]); "education, continuity, and documentation" (81% [CI, 79% to 84%]); and "medication monitoring" (64% [CI, 60% to 68%]). Limitations: Fewer than 10 patients were eligible for many of the quality indicators measured, and the generalizability of these findings in 2 managed care organizations to the general geriatric population is uncertain. Conclusions: Failures to prescribe indicated medications, monitor medications appropriately, document necessary information, educate patients, and maintain continuity are more common prescribing problems than use of inappropriate drugs in older patients.
TCS: A New Multiple Sequence Alignment Reliability Measure to Estimate Alignment Accuracy and Improve Phylogenetic Tree Reconstruction
Authors: Jia-Ming Chang, Paolo Di Tommaso, Cedric Notredame
Journal: Molecular Biology and Evolution (2014)

Multiple sequence alignment (MSA) is a key modeling procedure when analyzing biological sequences. Homology and evolutionary modeling are the most common applications of MSAs. Both are known to be sensitive to the underlying MSA accuracy. In this work, we show how this problem can be partly overcome using the transitive consistency score (TCS), an extended version of the T-Coffee scoring scheme. Using this local evaluation function, we show that one can identify the most reliable portions of an MSA, as judged from BAliBASE and PREFAB structure-based reference alignments. We also show how this measure can be used to improve phylogenetic tree reconstruction using both an established simulated data set and a novel empirical yeast data set. For this purpose, we describe a novel lossless alternative to site filtering that involves overweighting the trustworthy columns. Our approach relies on the T-Coffee framework; it uses libraries of pairwise alignments to evaluate any third party MSA. Pairwise projections can be produced using fast or slow methods, thus allowing a trade-off between speed and accuracy. We compared TCS with Heads-or-Tails, GUIDANCE, Gblocks, and trimAl and found it to lead to significantly better estimates of structural accuracy and more accurate phylogenetic trees. The software is available from www.tcoffee.org/Projects/tcs.
The cutaneous corticosteroid vasoconstriction assay: a reflectance spectroscopic and laser-Doppler flowmetric study
Authors: P. ANDERSEN, K. MILIONI, H. MAIBACH
Journal: British Journal of Dermatology (1993)

Cutaneous vasoconstriction induced by topical corticosteroids was investigated using non‐invasive bioengineering techniques. Corticosteroids of different potency in alcoholic solution were applied topically, under occlusion, and cutaneous blanching was investigated using visual scoring, reflectance spectroscopy (RS) and laser‐DoppIer flowmetry (LDF), The RS technique allowed separation of cutaneous haemoglobin content into arterial oxygenated (OH) and venous deoxygen‐ated haemoglobin (DOH) components. Application of alcohol decreased total haemoglobin by 10%, with a corresponding 8% increase in blood flow (BF). Clobetasol propionate was the most potent vasoconstrictor, inducing signiflcant visible blanching and decreasing DOH (30%), OH (33%) and BF (18%) (P<0.01). Fluocinolone acetonide, betamethasone‐17‐valerate and dexamethasone also caused visible blanching (P<0.01). There was no signiflcant decrease in BF, but reflectance spectroscopy showed a decrease in DOH (P<0.01). Tixocortol, CMJ and hydrocortisone acetate did not produce signiflcant blanching, although DOH was decreased compared with the alcohol control. Measured by reflectance spectroscopy, corticosteroid‐induced blanching was predominantly venoconstriction and only the most potent corticosteroid caused a significant decrease in OH and blood flow. This may explain why previous attempts to improve cutaneous vasoconstriction assays using laser‐Doppler flowmetry have been unsuccessful.
A randomised phase III study on capecitabine, oxaliplatin and bevacizumab with or without cetuximab in first-line advanced colorectal cancer, the CAIRO2 study of the Dutch Colorectal Cancer Group (DCCG). An interim analysis of toxicity
Authors: J. Tol, M. Koopman, C.J. Rodenburg, A. Cats, G.J. Creemers, J.G. Schrama, F.L.G. Erdkamp, A.H. Vos, L. Mol, N.F. Antonini, C.J.A. Punt
Journal: Annals of Oncology (2008)
Left ventricular dysfunction among elderly patients in general practice
Authors: S Talwar, P F Downie, S. Zaman, P. A Poole-Wilson
Journal: BMJ (1999)

Editor—Morgan et al have shown that left ventricular systolic dysfunction is common in elderly patients in a general practice setting.1 They mention that an optimal method of screening for the condition in general practice is not known and go on to conclude that “targeting individuals for more detailed assessment ... would help detect a substantial proportion of the currently unrecognised left ventricular systolic dysfunction.”

Davie et al have shown that left ventricular systolic dysfunction is unlikely to be present if an electrocardiogram is normal or shows only minor abnormalities.2 The electrocardiogram has a sensitivity of 94% and a negative predictive value of 98%, making it invaluable in any general practice screening programme for left ventricular systolic dysfunction.2 Conversely, a major electrocardiographic abnormality usually exists in the presence of left ventricular systolic dysfunction.2

In our opinion, electrocardiography, which is cheap and easily performed, should be incorporated into any general practice screening programme for left ventricular systolic dysfunction. Furthermore, electrocardiographic abnormalities such as left bundle branch block can give rise to paradoxical motion of the interventricular septum and subsequent underestimation of left ventricular systolic function.3,4 This could then lead to an overestimation of the prevalence of heart failure. The presence of an electrocardiogram at the time of echocardiographic reporting would therefore be useful.

Plasma measurement of the natriuretic peptides offers an additional tool for the assessment of left ventricular systolic dysfunction.5 The exact role of these peptides in screening programmes for heart failure remains to be more precisely determined.
Clinical assessment of diaphragm strength by cervical magnetic stimulation of the phrenic nerves.
Authors: C. H. Hamnegard, S. D. Wragg, G. H. Mills, D. Kyroussis, M. I. Polkey, B. Bake, J. Moxham, M. Green
Journal: Thorax (1996)

BACKGROUND: Accurate assessment of diaphragm strength can be difficult. Transdiaphragmatic pressure (PDI) measurements during volitional manoeuvres are useful but it may be difficult to ensure maximum patient effort. Magnetic stimulation of the phrenic nerves is easy to perform and the results are reproducible in normal subjects. The purpose of the present study was to evaluate the usefulness of magnetic stimulation of the phrenic nerves in the assessment of diaphragm weakness in patients. METHODS: Sixty-six patients referred for assessment of respiratory muscle strength and 23 normal subjects were studied. Twitch PDI (TwPDI) following magnetic stimulation of the phrenic nerves and sniffPDI were obtained in all individuals. TWPDI following bilateral electrical stimulation of the phrenic nerves was also obtained in eight patients. RESULTS: Mean (SD) TwPdi for the normal subjects was 31 (6) cm H2O and 18 (11) cm H2O for the patients. TwPDI and sniffPDI were correlated (r = 0.77). Seven of the 37 patients (19%) with a reduced sniffPDI had a TwPDI within the normal range whereas two of the 32 patients (6%) with a reduced TwPDI had a normal sniffPDI. TwPDI was similar with magnetic and electrical stimulation. CONCLUSIONS: TwPDI following magnetic stimulation of the phrenic nerves is a clinically useful measurement when assessing diaphragm weakness.
Mortality in Patients Hospitalized for Asthma Exacerbations in the United States
Authors: Vidya Krishnan, Gregory B. Diette, Cynthia S. Rand, Andrew L. Bilderback, Barry Merriman, Nadia N. Hansel, Jerry A. Krishnan
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Hospitalizations for asthma exacerbations are common in the United States, but there are no national estimates of outcomes in this population. It is also not known if race disparities in asthma deaths exist among hospitalized patients.
Protein-Bound Uremic Toxins Stimulate Crosstalk between Leukocytes and Vessel Wall
Authors: Anneleen Pletinck, Griet Glorieux, Eva Schepers, Gerald Cohen, Bertrand Gondouin, Maria Van Landschoot, Sunny Eloot, Angelique Rops, Johan Van de Voorde, An De Vriese, Johan van der Vlag, Philippe Brunet, Wim Van Biesen, Raymond Vanholder
Journal: Journal of the American Society of Nephrology (2013)

Leukocyte activation and endothelial damage both contribute to cardiovascular disease, a major cause of morbidity and mortality in CKD. Experimental in vitro data link several protein-bound uremic retention solutes to the modulation of inflammatory stimuli, including endothelium and leukocyte responses and cardiovascular damage, corroborating observational in vivo data. However, the impact of these uremic toxins on the crosstalk between endothelium and leukocytes has not been assessed. This study evaluated the effects of acute and continuous exposure to uremic levels of indoxylsulfate (IS), p-cresylsulfate (pCS), and p-cresylglucuronide (pCG) on the recruitment of circulating leukocytes in the rat peritoneal vascular bed using intravital microscopy. Superfusion with IS induced strong leukocyte adhesion, enhanced extravasation, and interrupted blood flow, whereas pCS caused a rapid increase in leukocyte rolling. Superfusion with pCS and pCG combined caused impaired blood flow and vascular leakage but did not further enhance leukocyte rolling over pCS alone. Intravenous infusion with IS confirmed the superfusion results and caused shedding of heparan sulfate, pointing to disruption of the glycocalyx as the mechanism likely mediating IS-induced flow stagnation. These results provide the first clear in vivo evidence that IS, pCS, and pCG exert proinflammatory effects that contribute to vascular damage by stimulating crosstalk between leukocytes and vessels.
Periostin is required for maximal airways inflammation and hyperresponsiveness in mice
Authors: J. Kelley Bentley, Qiang Chen, Jun Young Hong, Antonia P. Popova, Jing Lei, Bethany B. Moore, Marc B. Hershenson
Journal: Journal of Allergy and Clinical Immunology (2014)

BackgroundPeriostin, a secreted extracellular matrix protein, has been localized to deposits of subepithelial fibrosis in asthmatic patients, and periostin levels have been linked to increases in IL-13.ObjectiveWe hypothesized that periostin is required for airway inflammatory responses to a physiologic aeroallergen, house dust mite (HDM).MethodsWe studied F4-F6 B6;129-Postntm1Jmol/J wild-type (Postn+/+) and null (Postn−/−) mice, as well as C57BL/6 mice treated with either IgM or OC-20 periostin neutralizing antibody. Mice were exposed to 5 doses of HDM intranasally over a 16-day period.ResultsHDM increased airways responsiveness in Postn+/+ but not Postn−/− mice. In addition, HDM-treated C57BL/6 mice injected with OC-20 had lower airways responsiveness than HDM-treated mice injected with IgM. Compared with Postn+/+ mice, Postn−/− mice showed decreases in HDM-induced inflammation and mucous metaplasia, as well as reduced IL-4, IL-25, CD68, Gob5, and periostin mRNA expression. OC-20 antibody produced similar results. HDM exposure increased periostin expression in the airway epithelium, subepithelium, smooth muscle and inflammatory cells. OC-20 blocked the HDM-induced IgE response, and T cells incubated with dendritic cells (DCs) from Postn−/− mice or treated with OC-20 showed deficient DNA synthesis and IL-13 responses compared with T cells incubated with wild-type DCs. Finally, adoptive transfer of bone marrow–derived DCs from Postn+/+ mice was sufficient to promote allergic responses in F6 Postn−/− littermates.ConclusionsIn mice, periostin is required for maximal airways hyperresponsiveness and inflammation after HDM sensitization and challenge. Periostin is required for maximal HDM-induced T-cell responses.