tbuckley/cabot-search huggingface dataset:
Early results of cardiac transplantation at the Texas Heart Institute.
Authors: I J Reece, O H Frazier, A Painvin, O J Okereke, L B Chandler, T W Krudewig, D A Cooley
Journal: Thorax (1984)

From July 1982 to November 1983 18 patients (one female) underwent orthotopic cardiac transplantation at the Texas Heart Institute. Prednisone and cyclosporin were used for maintenance immunosuppression in all patients. Cumulative follow up has now been for 90 patient months (0.75-20 months). Rejection occurred in 10 recipients (56%) and was fatal in three, giving an incidence of rejection of 0.6 episodes per recipient and a mortality rate of 30% per episode. At one year 39% of recipients were free of infection and 73% free of fatal rejection. Infection episodes occurred on 32 occasions in 14 patients and 24 episodes required treatment. There were no infection related deaths, although the first year actuarial freedom from infection rate was only 24%. With 14 of the 18 patients surviving (78%), an actuarial one year survival of 74%, and freedom from major complications in the short term, the efficacy of cyclosporin immunosuppression for cardiac transplantation is confirmed.
Eya4-deficient mice are a model for heritable otitis media
Authors: Frederic F.S. Depreux, Keith Darrow, David A. Conner, Roland D. Eavey, M. Charles Liberman, Christine E. Seidman, J.G. Seidman
Journal: Journal of Clinical Investigation (2008)

Otitis media is an extremely common pediatric inflammation of the middle ear that often causes pain and diminishes hearing. Vulnerability to otitis media is due to eustachian tube dysfunction as well as other poorly understood factors, including genetic susceptibility. As EYA4 mutations cause sensorineural hearing loss in humans, we produced and characterized Eya4-deficient (Eya4(-/-)) mice, which had severe hearing deficits. In addition, all Eya4(-/-) mice developed otitis media with effusion. Anatomic studies revealed abnormal middle ear cavity and eustachian tube dysmorphology; thus, Eya4 regulation is critical for the development and function of these structures. We suggest that some human otitis media susceptibility reflects underlying genetic predisposition in genes like EYA4 that regulate middle ear and eustachian tube anatomy.
Incidence, Location, Magnitude, and Clinical Correlates of Saphenous Vein Graft Calcification
Authors: Marco T. Castagna, Gary S. Mintz, Patrick Ohlmann, Jun-Ichi Kotani, Akiko Maehara, Natalie Gevorkian, Edouard Cheneau, Eugenio Stabile, Andrew E. Ajani, William O. Suddath, Kenneth M. Kent, Lowell F. Satler, Augusto D. Pichard, Neil J. Weissman
Journal: Circulation (2005)

The pattern of saphenous vein graft (SVG) calcification before percutaneous intervention has not been studied.We used diagnostic and preintervention intravascular ultrasound (IVUS) to determine the incidence and magnitude of SVG calcification in 334 SVG lesions in 274 consecutive patients. Calcium was found in 133 SVGs (40%). Calcium was uniformly distributed among 48 lesion sites (14%), 43 proximal references (13%), and 42 distal references (13%). Calcium was superficial in 20 (40%) and deep in 28 (60%). Over the entire length of the SVGs, the maximum arc and length of calcium (in calcium-containing SVGs) averaged 174+/-107 degrees and 6.8+/-4.8 mm, respectively. In calcium-containing SVGs, lesion site arc and length of calcium measured 151+/-107 degrees and 4.1+/-3.7 mm, similar to the proximal and distal references (175+/-121 degrees and 4.0+/-2.3 mm and 177+/-121 degrees and 4.1+/-2.5 mm, respectively). Graft age (7.5+/-4.7 versus 10.5+/-4.7 years, P<0.0001), insulin-treated diabetes mellitus (40% versus 60%, P=0.02), and tobacco use (44% versus 55%, P=0.06) were clinical independent predictors of SVG calcification.Sixty-five percent of calcium-containing SVGs had reference calcium in the absence of lesion calcium. Calcium was located primarily in SVG wall and not at the plaque. These data suggest that SVG calcium is not just part of lesion formation and maturation. SVG calcium occurred more commonly in older grafts, in insulin-treated diabetic patients, and in smokers.
Allosteric enhancer PD 81,723 acts by novel mechanism to potentiate cardiac actions of adenosine.
Authors: C Kollias-Baker, J Ruble, D Dennis, R F Bruns, J Linden, L Belardinelli
Journal: Circulation Research (1994)

The 2-amino-3-benzoylthiophene derivative PD 81,723 is an allosteric enhancer of agonist binding to brain A1 adenosine receptors. One aim of this study was to characterize and contrast the effects of PD 81,723 on the A1 receptor-mediated negative dromotropic and A2a receptor-mediated vasodilatory actions of adenosine and of a nonmetabolizable and unselective N6-(3-pentyl)adenosine derivative. A second aim was to determine the mechanism of action of PD 81,723. In guinea pig isolated hearts, PD 81,723 potentiated the adenosine and the N6-(3-pentyl)adenosine derivative-induced prolongations of the stimulus-to-His bundle (S-H) interval in a concentration-dependent manner. PD 81,723 (30 mumol/L) decreased the EC50 value for adenosine to prolong the S-H interval by ninefold from 7.4 +/- 1.2 to 0.8 +/- 0.1 mumol/L but did not increase the content of adenosine in cardiac effluent. PD 81,723 (30 mumol/L) increased the specific binding of the A1 agonist [3H]cyclohexyladenosine ([3H]CHA) to human atrial and guinea pig atrial and brain membranes by 38%, 78%, and 300%, respectively. PD 81,723 also increased the fraction of A1 receptors in the high-affinity binding state by an average of 56 +/- 13%. The dissociation rate of [3H]CHA from guinea pig brain membranes was decreased in the presence of PD 81,723 (10 mumol/L) from 0.55 +/- 0.01/min to 0.35 +/- 0.01/min. PD 81,723 did not alter the binding of the A1 antagonist [3H]cyclopentyldipropylxanthine to guinea pig brain membranes. The IC50 values for 5'-guanylylimidodiphosphate to reduce specific binding of [3H]CHA to guinea pig cardiac and brain membranes were increased from 1.5 +/- 0.2 and 2.0 +/- 0.2 mumol/L in the absence of PD 81,723 to 10 +/- 3.3 and 18 +/- 0.5 mumol/L, respectively, in the presence of PD 81,723 (30 mumol/L). PD 81,723 did not potentiate the coronary vasodilatory actions of the N6-(3-pentyl)adenosine derivative. Specific binding of the A2a agonist [3H]CGS 21680 to brain membranes and the nucleoside transporter ligand [3H]nitrobenzylthioinosine to cardiac membranes was unchanged in the presence of PD 81,723. The results suggest that PD 81,723 specifically potentiates the action of adenosine on A1 receptors by stabilizing receptor-G protein interactions in the presence of agonists.
A pathobiologic pathway linking thrombopoietin, GATA-1, and TGF-β1 in the development of myelofibrosis
Authors: Alessandro M. Vannucchi, Lucia Bianchi, Francesco Paoletti, Alessandro Pancrazzi, Eugenio Torre, Mitsuo Nishikawa, Maria Zingariello, Angela Di Baldassarre, Rosa Alba Rana, Rodolfo Lorenzini, Elena Alfani, Giovanni Migliaccio, Anna Rita Migliaccio
Journal: Blood (2005)
Role of a 48-week pegylated interferon therapy in hepatitis B e antigen positive HIV-co-infected patients on cART including tenofovir: EMVIPEG study
Authors: Patrick Miailhes, Marianne Maynard-Muet, Fanny Lebossé, Fabrice Carrat, Cécile Bouix, Caroline Lascoux-Combe, Philippe Sogni, David Rey, Yoann Barthe, Stanislas Pol, Patrice Cacoub, Fabien Zoulim, Lionel Piroth
Journal: Journal of Hepatology (2014)
A gastrointestinal cause for heart failure
Authors: A. Aravinthan, Y. Al-naeeb, Z. Abubacker, P. Richardson
Journal: Gut (2009)

A 67-year-old man presented with worsening shortness of breath on exertion and peripheral oedema of 3 months duration. He had evidence of heart failure including raised jugular venous pressure, gallop rhythm and bilateral pedal oedema. …
Measuring "goodness" in individuals and healthcare systems
Authors: M. Pringle
Journal: BMJ (2002)

All agree that we need to measure the quality of health care, including the care given by individual doctors. Measuring "goodness" requires accurate data used appropriately, and it must be done without demoralising and demotivating staff. Do current measures fulfil these requirements, and if not, what measures should be used? In the recent Reith lectures (broadcast annually by BBC radio on issues of contemporary interest), Onora O'Neill explored the new age of accountability. She concluded that increasing reliance on measurement reduced trust in health (and other public) services and that professionals and public servants should be free to serve the public.'1 This will ring true with many. However, patients, funders, commissioners, provider organisations, and health professionals legitimately want to know just how "good" are individual doctors, teams, and healthcare providing organisations. The traditionally qualitative, anecdotal approach, supplemented by trust, is being increasingly replaced by data on effectiveness, safety, acceptability, and efficiency. Measurement is crucial for a range of purposes—learning, quality improvement, accountability, and regulation—but must be used appropriately. We contend that measurement can be used to reinforce the natural desire of healthcare staff to improve care at the same time as understanding the quality of the service delivered. However, creating meaningful information from accurate data to facilitate rational choices is a real challenge. It must be done without distorting staff behaviour or demoralising and demotivating health professionals (including managers), and it must offer true comparisons. #### Summary points
Bovine endometrial epithelial cells as a model system to study oxytocin receptor regulation
Authors: S Horn, R Bathgate, C Lioutas, K Bracken, R Ivell
Journal: Human Reproduction Update (1998)

Endometrial epithelial cell cultures were established from bovine uterine tissue collected during the oestrous cycle from commercially slaughtered animals. These cells were shown to express moderately high levels of oxytocin receptors (OTR) (up to 30 000 per cell) after about one week in culture. These receptors have been characterized at the molecular, pharmacological and functional level and shown to be identical to those expressed in the bovine endometrium in vivo. Preliminary experiments to investigate the regulation of the OTR and its gene using this system, have shown that expression is to a large degree constitutive, the receptors being spontaneously upregulated during culture. Sex steroids at concentrations close to or above the serum limits observed in vivo appeared to have no effect, although the cells were shown to express mRNA for the specific steroid receptors throughout culture. Only the blastocyst procedure, interferon-τ, showed a significant effect, downregulating both OTR and their gene transcripts in the cultured endometrial epithelial cells. Although more extensive studies are necessary, these results support the view that the OTR gene is controlled in part at least by a combination of constitutive and inhibitory elements.
Electrical Remodeling of the Atria Associated With Paroxysmal and Chronic Atrial Flutter
Authors: Paul B. Sparks, Shenthar Jayaprakash, Jitendra K. Vohra, Jonathan M. Kalman
Journal: Circulation (2000)

Background —Atrial electrical remodeling may be important for the initiation and perpetuation of atrial arrhythmias. Whether paroxysmal atrial flutter (AFL) and chronic AFL cause electrical remodeling of the atria has not been conclusively determined. Methods and Results —Before radiofrequency ablation of paroxysmal AFL, 15 patients in sinus rhythm were evaluated under autonomic blockade. Lateral right atrial (LRA) effective refractory periods (ERPs) at 600 and 450 ms were measured before and at 1-minute intervals for 10 minutes after spontaneous or pace termination of a 5- to 10-minute period of induced AFL. In 10 patients with chronic AFL, LRA, septal, and coronary sinus (CS) ERPs and corrected sinus node recovery times (cSNRTs) at 600 and 450 ms were measured under autonomic blockade 15 minutes, 30 minutes, and 3 weeks after termination of chronic AFL by ablation. In the paroxysmal AFL group, LRA ERPs decreased by 18% at 600 ms and 12% at 450 ms ( P &lt;0.01) after induced AFL and recovered to baseline over ≈5 minutes. Atrial fibrillation developed during AFL in 3 patients and during ERP testing in 3 patients when refractoriness was at its nadir. In the chronic AFL group, LRA, septal, and CS ERPs at 3 weeks were significantly greater than at 15 and 30 minutes after termination of chronic AFL at both cycle lengths ( P &lt;0.01). Three weeks after ablation, cSNRT decreased 35% at 600 ms ( P &lt;0.05) and decreased 44% at 450 ms ( P &lt;0.05). Both ERPs and cSNRTs measured 15 and 30 minutes after ablation of chronic AFL were not significantly different. Conclusions —Both paroxysmal AFL and chronic AFL cause reversible electrical remodeling of the atria but demonstrate different time courses of recovery.
Autoantibodies in coeliac disease: tissue transglutaminase—guilt by association?
Authors: L M SOLLID, Ø MOLBERG, S McADAM, K E A LUNDIN
Journal: Gut (1997)

Endomysial antibodies are a hallmark of coeliac disease. The existence of autoantibodies whose titres fluctuate with ingestion of gliadin is enigmatic. Gliadin seems to drive this antibody secretion as endomysial antibodies are produced in biopsy samples cultured with a peptic/tryptic digest of gliadin.1 The phenomenon of endomysial antibodies has been explained by molecular mimicry between gliadin and the endomysial antigen, or unmasking of cryptic epitopes in the endomysial antigen upon exposure to gliadin.1 2Recently, Dieterich and colleagues identified tissue transglutaminase (tTG) as the antigen for endomysial antibodies.3 Their data indicate that tTG forms complexes with gliadin, and they hypothesise that neoepitopes in the complex between gliadin and tTG initiate an immune response that is finally directed against gliadin and tTG.3 4 Based on the observation that tTG and gliadin form complexes, we would like to propose an alternative mechanism for the production of antibodies to tTG.

The prevailing view of B cell tolerance states that tolerance to soluble self-antigens, in contrast …
Ventilatory responses to hypercapnia and hypoxia in relatives of patients with the obesity hypoventilation syndrome
Authors: R Jokic
Journal: Thorax (2000)

<h3>BACKGROUND</h3> It is unclear why some morbidly obese individuals have waking alveolar hypoventilation while others with similar obesity do not. Some evidence suggests that patients with the obesity hypoventilation syndrome (OHS) may have a measurable premorbid impairment of ventilatory chemoresponsiveness. Such an impairment of ventilatory chemoresponsiveness in OHS, however, may be an acquired and reversible consequence of severe obstructive sleep apnoea (OSA). We hypothesised that, in patients with OHS who do not have coincident severe OSA, there may be a familial impairment in ventilatory responses to hypoxia and hypercapnia. <h3>METHODS</h3> Sixteen first degree relatives of seven patients with OHS without severe OSA (mean (SD) age 40 (16) years, body mass index (BMI) 30 (6) kg/m<sup>2</sup>) and 16 subjects matched for age and BMI without OHS or OSA were studied. Selection criteria included normal arterial blood gas tensions and lung function tests and absence of sleep apnoea on overnight polysomnography. Ventilatory responses to isocapnic hypoxia and to hyperoxic hypercapnia were compared between the two groups. <h3>RESULTS</h3> The slope of the ventilatory response to hypercapnia was similar in the relatives (mean 2.33 l/min/mm Hg) and in the control subjects (2.12 l/min/mm Hg), mean difference 0.2 l/min/mm Hg, 95% confidence interval (CI) for the difference –0.5 to 0.9 l/min/mm Hg, p=0.5. The hypoxic ventilatory response was also similar between the two groups (slope factor A: 379.1 l/min • mm Hg for relatives and 373.4 l/min • mm Hg for controls; mean difference 5.7 l/min • mm Hg; 95% CI –282 to 293 l/min • mm Hg, p=0.7; slope of the linear regression line of the fall in oxygen saturation and increase in minute ventilation: 2.01 l/min/% desaturation in relatives, 1.15 l/min/% desaturation in controls; mean difference 0.5 l/min/% desaturation; 95% CI –1.7 to 0.7 l/min/% desaturation, p=0.8). <h3>CONCLUSION</h3> There is no evidence of impaired ventilatory chemoresponsiveness in first degree relatives of patients with OHS compared with age and BMI matched control subjects.
Response to Letter Regarding Article, “Long-Term Adherence to Evidence-Based Secondary Prevention Therapies in Coronary Artery Disease”
Authors: L. Kristin Newby, Nancy M. Allen-LaPointe, Anita Y. Chen, Judith M. Kramer, Bradley G. Hammill, Elizabeth R. DeLong, Lawrence H. Muhlbaier, Robert M. Califf
Journal: Circulation (2006)
Association between randomised trial evidence and global burden of disease: cross sectional study (Epidemiological Study of Randomized Trials--ESORT)
Authors: C. A. Emdin, A. Odutayo, A. J. Hsiao, M. Shakir, S. Hopewell, K. Rahimi, D. G. Altman
Journal: BMJ (2015)

<b>Objectives</b> To determine whether an association exists between the number of published randomised controlled trials and the global burden of disease, whether certain diseases are under-investigated relative to their burden, and whether the relation between the output of randomised trials and global burden of disease can be explained by the relative disease burden in high and low income regions. <b>Design</b> Cross sectional investigation. <b>Study sample</b> All primary reports of randomised trials published in December 2012 and indexed in PubMed by 17 November 2013. <b>Main outcome measures</b> Number of trials conducted and number of participants randomised for each of 239 different diseases or injuries; variation in each outcome explainable by total disability adjusted life years (a measure of the overall burden of each disease) and the ratio of disability adjusted life years in low income to high income regions (a measure of whether a disease is more likely to affect people living in high income regions) quantified using multivariable regression. <b>Results</b> 4190 abstracts were reviewed and 1351 primary randomised trials identified, of which 1097 could be classified using the global burden of disease taxonomy. Total disability adjusted life years was poorly associated with number of randomised trials and number of participants randomised in univariable analysis (Spearman's <i>r</i>=0.35 and 0.33, respectively), although it was a significant predictor in the univariable and multivariable models (P&lt;0.001). Diseases for which the burden was predominantly located in low income regions had sevenfold fewer trials per million disability adjusted life years than diseases predominantly located in high income regions. However, only 26% of the variation in number of trials among diseases could be explained by total disability adjusted life years and the ratio of disability adjusted life years in low income regions to high income regions. Many high income type diseases (for example, neck pain, glomerulonephritis) have proportionally fewer randomised trials compared with low income type diseases (for example, vitamin A deficiency). <b>Conclusions</b> Overall, a weak association existed between global burden of disease and number of published randomised trials. A global observatory for research is needed to monitor and reduce the discordance between the output of randomised trials and global burden of disease.
Sputum T lymphocytes in asthma, COPD and healthy subjects have the phenotype of activated intraepithelial T cells (CD69+ CD103+)
Authors: M J Leckie
Journal: Thorax (2003)

T cells of intraepithelial phenotype have previously been detected in bronchoalveolar lavage (BAL) fluid in a range of lung diseases; these cells express the adhesion molecule alpha(E)beta(7) integrin, CD103, the ligand for epithelial cell E-cadherin. In subjects with asthma CD4+ lymphocytes are the predominant T cell subtype found in bronchial biopsy specimens and in BAL fluid, whereas CD8+ lymphocytes have been shown to predominate in subjects with chronic obstructive pulmonary disease (COPD). The aim of this study was to analyse the expression of CD103, activation markers (CD25 and CD69), and chemokine receptors (CXCR3, CCR5 and CCR3) on CD4+ and CD8+ lymphocytes from sputum and peripheral blood of subjects with asthma, COPD, and healthy controls.T cell surface markers were assessed by immunofluorescence labelling and flow cytometry of gated lymphocytes among CD45+ leucocytes in sputum cell suspensions.Sputum lymphocytes expressed higher levels of CD103 and CD69 than blood lymphocytes in all subject groups, with CD103 expressed at higher levels on CD8+ than on CD4+ cells. There were no detectable differences in numbers of CD4+ and CD8+ T cells between subjects with asthma, COPD and controls. The percentage of sputum lymphocytes expressing CXCR3 was lower in subjects with asthma or COPD than in healthy controls; CCR3 was not detectable on sputum or blood lymphocytes.Sputum T lymphocytes are predominantly of activated intraepithelial phenotype (CD103+ CD69+), and normal numbers of CD4+ and CD8+ T cell populations are found in the sputum of patients with asthma and COPD.
Short segments of Barrett’s epithelium and intestinal metaplasia in normal appearing oesophagogastric junctions: the same or two different entities?
Authors: A Dias Pereira, A Suspiro, P Chaves, A Saraiva, L Glória, J C Mendes de Almeida, C N Leitão, J Soares, F C Mira
Journal: Gut (1998)

Endoscopic diagnosis of short segments of Barrett's epithelium (SSBE)' is difficult and its meaning in terms of the presence of specialised columnar epithelium (SCE) has not been prospectively evaluated.To evaluate the prevalence of SCE in patients with an endoscopic diagnosis of SSBE and in individuals with normal appearing oesophagogastric junctions, and to compare the clinical characteristics of these two groups.Thirty one patients with an endoscopic diagnosis of short Barrett's oesophagus, less than 3 cm in length (group A), and 44 consecutive patients with normal appearing oesophagogastric junctions (group B).Multiple biopsies were performed in suspicious epithelium and at the oesophagogastric junction in groups A and B, respectively.Age and sex distribution were similar in both groups. Reflux symptoms were more frequent in group A (p < 0.001), as were endoscopic and histological signs of oesophagitis (p < 0.001 and p = 0.001, respectively). SCE was found in 61.3% of group A patients compared with 25% in group B (p < 0.002), with men predominating in group A while women were more frequent in group B (p = 0.02). The differences in reflux symptoms and endoscopic/histological oesophagitis remained significant.These results show that endoscopic diagnosis of SSBE is associated with a high prevalence of SCE, significantly higher than that found in normal appearing oesophagogastric junctions. Differences between patients with SCE in the two groups suggest they may represent two different entities.