tbuckley/cabot-search huggingface dataset:
Outcomes and Predictors of Perinatal Mortality in Fetuses With Ebstein Anomaly or Tricuspid Valve Dysplasia in the Current Era
Authors: Lindsay R. Freud, Maria C. Escobar-Diaz, Brian T. Kalish, Rukmini Komarlu, Michael D. Puchalski, Edgar T. Jaeggi, Anita L. Szwast, Grace Freire, Stéphanie M. Levasseur, Ann Kavanaugh-McHugh, Erik C. Michelfelder, Anita J. Moon-Grady, Mary T. Donofrio, Lisa W. Howley, Elif Seda Selamet Tierney, Bettina F. Cuneo, Shaine A. Morris, Jay D. Pruetz, Mary E. van der Velde, John P. Kovalchin, Catherine M. Ikemba, Margaret M. Vernon, Cyrus Samai, Gary M. Satou, Nina L. Gotteiner, Colin K. Phoon, Norman H. Silverman, Doff B. McElhinney, Wayne Tworetzky
Journal: Circulation (2015)

Ebstein anomaly and tricuspid valve dysplasia are rare congenital tricuspid valve malformations associated with high perinatal mortality. The literature consists of small, single-center case series spanning several decades. We performed a multicenter study to assess the outcomes and factors associated with mortality after fetal diagnosis in the current era.Fetuses diagnosed with Ebstein anomaly and tricuspid valve dysplasia from 2005 to 2011 were included from 23 centers. The primary outcome was perinatal mortality, defined as fetal demise or death before neonatal discharge. Of 243 fetuses diagnosed at a mean gestational age of 27±6 weeks, there were 11 lost to follow-up (5%), 15 terminations (6%), and 41 demises (17%). In the live-born cohort of 176 live-born patients, 56 (32%) died before discharge, yielding an overall perinatal mortality of 45%. Independent predictors of mortality at the time of diagnosis were gestational age <32 weeks (odds ratio, 8.6; 95% confidence interval, 3.5-21.0; P<0.001), tricuspid valve annulus diameter z-score (odds ratio, 1.3; 95% confidence interval, 1.1-1.5; P<0.001), pulmonary regurgitation (odds ratio, 2.9; 95% confidence interval, 1.4-6.2; P<0.001), and a pericardial effusion (odds ratio, 2.5; 95% confidence interval, 1.1-6.0; P=0.04). Nonsurvivors were more likely to have pulmonary regurgitation at any gestational age (61% versus 34%; P<0.001), and lower gestational age and weight at birth (35 versus 37 weeks; 2.5 versus 3.0 kg; both P<0.001).In this large, contemporary series of fetuses with Ebstein anomaly and tricuspid valve dysplasia, perinatal mortality remained high. Fetuses with pulmonary regurgitation, indicating circular shunt physiology, are a high-risk cohort and may benefit from more innovative therapeutic approaches to improve survival.
The Rate of Establishment of Complex Adaptations
Authors: M. Lynch, A. Abegg
Journal: Molecular Biology and Evolution (2010)

A central problem in evolutionary theory concerns the mechanisms by which adaptations requiring multiple mutations emerge in natural populations. We develop a series of expressions that clarify the scaling of the time to establishment of complex adaptations with population size, mutation rate, magnitude of the selective disadvantage of intermediate-state alleles, and the complexity of the adaptation. In general, even in the face of deleterious intermediate steps, the time to establishment is minimized in populations with very large size. Under a broad range of conditions, the time to establishment also scales by no more than the square of the mutation rate, regardless of the number of sites contributing to the adaptive change, demonstrating that the emergence of complex adaptations is only weakly constrained by the independent acquisition of mutations at the underlying sites. Mutator alleles with deleterious side effects have only moderate effects on the rate of adaptation in large populations but can cause a quantum decrease in the time to establishment of some adaptive alleles in small populations, although probably not at a high enough rate to offset the increased deleterious mutation load. Transient hypermutability, whereby a subset of gamete-producing cells mutate at an elevated rate in a nonheritable manner, may also elevate the rate of adaptation, although the effect is modest and appears to result from a simple increase in the rate of transitions between intermediate states rather than from the saltational production of doublet mutations. Taken together, these results illustrate the plausibility of the relatively rapid emergence of specific complex adaptations by conventional population genetic mechanisms and provide insight into the relative incidences of various paths of allelic adaptation in organisms with different population genetic features.
Blood pressure-lowering treatment based on cardiovascular risk: a meta-analysis of individual patient data
Authors: Johan Sundström, Hisatomi Arima, Mark Woodward, Rod Jackson, Kunal Karmali, Donald Lloyd-Jones, Colin Baigent, Jonathan Emberson, Kazem Rahimi, Stephen MacMahon, Anushka Patel, Vlado Perkovic, Fiona Turnbull, Bruce Neal
Journal: The Lancet (2014)
P214 Improving Outcomes–the Work of a Specialist Mesothelioma MDT: Abstract P214 Table 1.
Authors: M Murthy, D Komrower, G Jones, N Hunt, M Walshaw, M Ledson
Journal: Thorax (2013)

<h3>Introduction</h3> Mesothelioma is an uncommon malignancy with a poor prognosis, and in order to improve its management all cases within each cancer network should be discussed at a specialist MDT, which advises individual cancer units on the best treatment approach for their patients. We have reviewed the work of the specialist mesothelioma MDT for the Mersey and Cheshire Network (MCCN) since its inception in 2009. <h3>Aim and Methods</h3> We assessed all patients referred from the 6 contributing lung cancer units (A to F) over 4 years, looking at histology, performance status (PS), investigations undertaken, treatments offered, and mortality rate. <h3>Results</h3> Of 182 patients (mean age 76 years [SD 8], median PS 1, 157 male), 11 (6%) had a clinical diagnosis only. One hundred and seventy one patients had a tissue diagnosis (45% epitheliod, 7% sarcomatoid, 13% mixed, 29% unspecified). This was obtained by VATS in 79/171 (46%) and CT-guided biopsy in 43/171 (25%). 21 (12%) had a cytological diagnosis only. MDT advice on treatment options was offered in all cases; 88 (48%) received radiotherapy and 51 (28%) chemotherapy. 142 (78%) patients have died (median survival of 378 days). 1-year and 2-year survival rates were 51.3% and 16.9% respectively. However, in those who received chemotherapy, survival improved significantly (1-year 91.7% and 2-year 63.5% respectively; both p &lt; 0.0001). Data for individual cancer units is given in the table (table 1). <h3>Conclusions</h3> We have shown that those patients offered active treatment have a distinct survival advantage compared to the remainder. The cooperation of 6 cancer units in the MCCN to form a specialist mesothelioma network with a regular MDT has shown that this approach can improve the outcome for this unfortunate group of patients.
Multidrug-resistant tuberculosis in Eastern Europe: still on the increase?
Authors: Giovanni Battista Migliori, Masoud Dara, Pierpaolo de Colombani, Hans Kluge, Mario C. Raviglione
Journal: European Respiratory Journal (2012)

The recently published World Health Organization (WHO) 2011 Global Report [1] provides important new information on the status of the tuberculosis (TB) epidemic and better estimates are now available on different indicators of TB control. These were possible thanks to new methodologies used to measure the disease, producing more precise figures on mortality, number of children orphaned by TB, budget needs and financial gaps. Overall, a clearer picture of TB in general, and multidrug-resistant (MDR)- and extensively drug-resistant (XDR)-TB in particular, is now available to guide the necessary national and international public health response [1–4].

A major response to this is that of the WHO Regional Office for Europe (Copenhagen, Denmark), which has recently prioritised MDR-TB prevention and control by developing a consolidated 5-yr action plan. The action plan and its resolution were endorsed at the 61st Regional Committee in Baku, Azerbaijan in September 2011. The plan envisages identifying and addressing the causes leading to emergence of drug-resistant TB in the region [5]. A complex interplay of factors, such as irrational drug policies, and social and clinical determinants ( e.g. HIV infection, imprisonment, migration and socioeconomic factors), are driving the emergence and the spread of MDR-TB and XDR-TB [6, 7].

Surveillance of drug resistance is a major tool to document the situation at the national level, and the trends in performance of TB care and control efforts, as long as three simple …
Successful Catheter Ablation of Electrical Storm After Myocardial Infarction
Authors: Dietmar Bänsch, Feifan Oyang, Matthias Antz, Thomas Arentz, Reinhold Weber, Jesus E. Val-Mejias, Sabine Ernst, Karl-Heinz Kuck
Journal: Circulation (2003)

Background— We report on 4 patients (aged 57 to 77 years; 3 men) who developed drug-refractory, repetitive ventricular tachyarrhythmias after acute myocardial infarction (MI). All episodes of ventricular arrhythmias were triggered by monomorphic ventricular premature beats (VPBs) with a right bundle-branch block morphology (RBBB). Methods and Results— Left ventricular (LV) mapping was performed to attempt radiofrequency (RF) ablation of the triggering VPBs. Activation mapping of the clinical VPBs demonstrated the earliest activation in the anteromedial LV in 1 patient and in the inferomedial LV in 2 patients. Short, high-frequency, low-amplitude potentials were recorded that preceded the onset of each extrasystole by a maximum of 126 to 160 ms. At the same site, a Purkinje potential was documented that preceded the onset of the QRS complex by 23 to 26 ms during sinus rhythm. In 1 patient, only pace mapping was attempted to identify areas of interest in the LV. Six to 30 RF applications abolished all local Purkinje potentials at the site of earliest activation and/or perfect pace mapping and suppressed VPBs in all patients. No episode of ventricular tachycardia or fibrillation has recurred for 33, 14, 6, and 5 months in patients 1, 2, 3, and 4, respectively. Conclusions— Incessant ventricular tachyarrhythmias after MI may be triggered by VPBs. RF ablation of the triggering VPBs is feasible and can prevent drug-resistant electrical storm, even after acute MI. Catheter ablation of the triggering VPBs may be used as a bailout therapy in these patients.
Molecular characterization of a repeat element causing large-scale size variation in the mitochondrial DNA of the sea scallop Placopecten magellanicus.
Authors: J La Roche, M Snyder, D I Cook, K Fuller, E Zouros
Journal: Molecular Biology and Evolution (1990)

The scallop Placopecten magellanicus has the largest reported animal mitochondrial DNA (average 35 kb) and exhibits large inter- and intraindividual length variation owing to the varying copy number of a repeated element. We have characterized the repeat array by using restriction mapping and sequence analysis. The repeated element consists of 1,442 bp flanked on either side by the sequence ACTTTCC in a direct orientation. The array contains two to eight copies of the repeated element arranged in a direct orientation and in tandem. Only complete copies of the element are present in the array. The repeat element contains three regions with characteristic nucleotide sequences: a 10-bp inverted repeat shown to extrude into a cruciform in a supercoiled DNA plasmid, a 120-bp tract rich in G/C (70%) and adjacent to the inverted repeat, and periodically interspersed homopolymer runs of A and T occurring near the middle of the element which induce DNA curvature in dimeric constructs of the element. The element appears to be unique to P. magellanicus. The structural properties of the repeat element and its organization in an array of repeats may be important in explaining the generation and maintenance of large-scale mitochondrial DNA size variation observed in many animal species.
Identification of the target antigen in chronic bullous disease of childhood and linear IgA disease of adults
Authors: FENELLA WOJNAROWSKA, P. WHITEHEAD, I. M. LEIGH, B. S. BHOGAL, M. M. BLACK
Journal: British Journal of Dermatology (1991)

Disease-associated autoantibodies to basement membrane proteins have been used to characterize structural components of the epidermal basement membrane such as bullous pemphigoid (BP) antigen and epidermolysis bullosa acquisita (EBA) antigen (type VII collagen). The autoimmune bullous diseases characterized by IgA autoantibodies to the basement membrane zone (BMZ), i.e. linear IgA disease of adults (LAD) and chronic bullous disease of childhood (CBDC) may have circulating antibodies. Previous studies of tissue distribution and ultrastructural binding have suggested that the LAD and CBDC antigens are similar, if not identical, and differ from the target antigens of the other bullous diseases. We present the molecular characterization of the LAD/CBDC antigens by Western blotting of a large series of antisera. Seven of 33 sera (21%) were positive on immunoblotting and bound to the same antigen which has a molecular weight (MW) of 285 kDa. Using both defined polyclonal antisera to BP and LH 7.2 monoclonal antibody to type VII collagen (carboxy terminal) we have shown that the LAD and CBDC antisera both bind to an identical molecular weight protein which clearly differs from both the BP and EBA (type VII collagen) antigens. Although detectable in dermal tissue extracts like EBA, the MW of 285 kDa is heavier than type VII collagen (250 kDa, in our system, using non-collagenous standards). This study confirms the identity of LAD and CBDC antigens to be the same and to differ from previously described basement membrane proteins.
Elevated IL-8 Levels in Allergic Airways Inflammation is Downregulated Following Aerosolized Red Tide Toxin (Brevetoxin) Exposure
Authors: M.J. Dorsey, C.J. Walsh, B. Kirkpatrick, S. Leggett, J. Romeo, J.W. Sleasman
Journal: Journal of Allergy and Clinical Immunology (2010)
Infliximab, Azathioprine, or Combination Therapy for Crohn's Disease
Authors: Jean Frédéric Colombel, William J. Sandborn, Walter Reinisch, Gerassimos J. Mantzaris, Asher Kornbluth, Daniel Rachmilewitz, Simon Lichtiger, Geert D'Haens, Robert H. Diamond, Delma L. Broussard, Kezhen L. Tang, C. Janneke van der Woude, Paul Rutgeerts
Journal: New England Journal of Medicine (2010)

The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for Crohn's disease are unknown.
Expression of Tissue Inhibitor of Metalloproteinases-3 in Human Atheroma and Regulation in Lesion-Associated Cells
Authors: Rosalind P. Fabunmi, Galina K. Sukhova, Seigo Sugiyama, Peter Libby
Journal: Circulation Research (1998)

Abstract —Atherosclerotic plaque stability depends on the structural integrity of its extracellular matrix skeleton. The balance between degradation by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) may regulate plaque stability. Although MMP expression in atheroma is well documented, localization and control of expression of TIMPs in these lesions is incomplete. Extracts of atheroma (n=14) had 5-fold higher levels of TIMP-3 than nonatherosclerotic tissue (n=10). Plaques (n=24) contained abundant TIMP-1, -2, and -3 in macrophages in plaque shoulders, intimal-medial borders, and areas overlying the lipid core, as well as in medial smooth muscle cells, albeit in lesser amounts. These observations suggested that macrophages, a cell type not heretofore known to express TIMP-3, did so in atheroma in vivo. Further studies in vitro established the human macrophage as a novel source of TIMP-3 mRNA and protein. Human smooth muscle cells constitutively expressed TIMP-1, -2 and -3 proteins; platelet-derived growth factor and transforming growth factor-β augmented levels of TIMP-1 and TIMP-3 but not TIMP-2. These findings suggest that regulated expression of TIMP-3, in addition to the presence of TIMP-1 and TIMP-2, counteracts MMP activity in atheroma and hence influences plaque stability.
Clinicopathological differences between colonic and rectal carcinomas: are they based on the same mechanism of carcinogenesis?
Authors: K Konishi, T Fujii, N Boku, S Kato, I Koba, A Ohtsu, H Tajiri, A Ochiai, S Yoshida
Journal: Gut (1999)

<h3>BACKGROUND</h3> There is a difference in the location of colorectal mucosal lesions and invasive cancers. <h3>AIMS</h3> To ascertain whether the location of colorectal neoplasms reflects the carcinogenesis pathway. <h3>METHODS</h3> The subject material consisted of 4147 neoplastic lesions that had been resected endoscopically or surgically from 5025 patients. Mucosal lesions and submucosal cancers were classified into depressed and non-depressed types endoscopically or histologically. The relations between macroscopic type, size, histology, and location were investigated. <h3>RESULTS</h3> (<i>a</i>) Non-depressed type. A total of 1774 of 3454 (51%) mucosal lesions were located in the right colon, 1212 (35%) in the left colon, and 468 (14%) in the rectum. The incidence of mucosal lesions larger than 10 mm was 10% (185/1774) in the right colon, 21% (254/1212) in the left colon, and 27% (127/468) in the rectum. The incidence of mucosal lesions with villous components was 2% (32/1774) in the right colon, 5% (63/1212) in the left colon, and 13% (62/468) in the rectum. The ratio of submucosal cancers to mucosal lesions was significantly higher in the rectum (0.064, 30/469) than in the left (0.034, 43/1279) or right (0.010, 18/1857) colon. (<i>b</i>) Depressed type. The incidences of depressed type mucosal lesions and submucosal cancers were 5% (83/1857) and 17% (3/18) in the right colon, 5% (67/1279) and 5% (2/43) in the left colon, and 0.2% (1/469) and 0% (0/30) in the rectum, respectively. <h3>CONCLUSION</h3> There may be some mechanisms that promote the progression of mucosal lesions to invasive cancers in the left colon and rectum, whereas a de novo pathway from depressed type lesions may be implicated in some cancers of the right colon.
Gross total but not incomplete resection of glioblastoma prolongs survival in the era of radiochemotherapy
Authors: F. -W. Kreth, N. Thon, M. Simon, M. Westphal, G. Schackert, G. Nikkhah, B. Hentschel, G. Reifenberger, T. Pietsch, M. Weller, J. -C. Tonn
Journal: Annals of Oncology (2013)
Therapeutic application of RNAi: is mRNA targeting finally ready for prime time?
Authors: Dirk Grimm, Mark A. Kay
Journal: Journal of Clinical Investigation (2007)

With unprecedented speed, RNA interference (RNAi) has advanced from its basic discovery in lower organisms to becoming a powerful genetic tool and perhaps our single most promising biotherapeutic for a wide array of diseases. Numerous studies document RNAi efficacy in laboratory animals, and the first clinical trials are underway and thus far suggest that RNAi is safe to use in humans. Yet substantial hurdles have also surfaced and must be surmounted before therapeutic RNAi applications can become a standard therapy. Here we review the most critical roadblocks and concerns for clinical RNAi transition, delivery, and safety. We highlight emerging solutions and concurrently discuss novel therapeutic RNAi-based concepts. The current rapid advances create realistic optimism that the establishment of RNAi as a new and potent clinical modality in humans is near.
Randomised, placebo controlled trial of effect of a leukotriene receptor antagonist, montelukast, on tapering inhaled corticosteroids in asthmatic patients
Authors: C.-G. Lofdahl, T. F Reiss, J. A Leff, E. Israel, M. J Noonan, A. F Finn, B. C Seidenberg, T. Capizzi, S. Kundu, P. Godard
Journal: BMJ (1999)

<h3>Abstract</h3> <b>Objective:</b> To determine the ability of montelukast, a leukotriene receptor antagonist, to allow tapering of inhaled corticosteroids in clinically stable asthmatic patients. <b>Design:</b> Double blind, randomised, placebo controlled, parallel group study. After a single blind placebo run in period, during which (at most) two inhaled corticosteroids dose decreases occurred, qualifying, clinically stable patients were allocated randomly to receive montelukast (10 mg tablet) or matching placebo once daily at bedtime for up to 12 weeks. <b>Setting:</b> 23 academic asthma centres in United States, Canada, and Europe. <b>Participants:</b> 226 clinically stable patients with chronic asthma receiving high doses of inhaled corticosteroids (113 randomised to montelukast and 113 to placebo). <b>Interventions:</b> Every 2 weeks, the inhaled corticosteroids dose was tapered, maintained, or increased (rescue) based on a standardised clinical score. <b>Main outcome measures:</b> Last tolerated dose of inhaled corticosteroids. <b>Results:</b> Compared with placebo, montelukast allowed significant (P=0.046) reduction in the inhaled corticosteroid dose (montelukast 47% <i>v</i> placebo 30%; least square mean difference 17.6%, 95% confidence interval 0.3 to 34.8). Fewer patients on montelukast (18 (16%) <i>v</i> 34 (30%) placebo, P=0.01) required discontinuation because of failed rescue. <b>Conclusions:</b> Montelukast reduces the need for inhaled corticosteroids among patients requiring moderate to high doses of corticosteroid to maintain asthma control. <h3>Key messages</h3> Leukotriene receptor antagonists have complementary action to inhaled corticosteroids in asthma Many patients receive higher doses of inhaled corticosteroids than clinically required In this placebo controlled trial, montelukast allowed significant reduction of inhaled corticosteroid doses Fewer patients receiving montelukast had failed rescue than patients receiving placebo
Chemokine involvement in tetracycline-induced pleuritis
Authors: EJ Miller, O Kajikawa, S Pueblitz, RW Light, KK Koenig, S Idell
Journal: European Respiratory Journal (1999)

Sclerosants such as tetracycline (TCN) have often been used in the control of malignant pleural effusions. Although the resultant inflammatory response is probably important in the ensuing pleural fibrosis, the signals responsible for the cellular influx into the pleural space following TCN instillation are not well understood. This study, therefore, sought to determine whether the chemokines interleukin-8 (IL-8), growth-related protein (Gro), and monocyte chemotactic protein-1 (MCP-1) were locally elaborated within the first 72 h following intrapleural TCN administration. TCN induced an exudative effusion with high lactate dehydrogenase activity. Although there was no significant change in the pleural fluid total leukocyte content, the median polymorphonuclear neutrophil concentration decreased from 1.067x10(6) to 2.03x10(5) cells x mL(-1) between 24 and 72 h, whereas the median macrophage concentration increased from 1.44x10(5) to 5.98x10(5) cells x mL(-1) over the same period. Furthermore, IL-8, Gro and MCP-1 concentrations decreased between 24 and 72 h. Immunocytochemistry indicated expression of IL-8 by pleural mesothelial cells 24 h, but not 72 h, following TCN administration. The data suggest that local elaboration of interleukin-8 and growth-related protein, in part of mesothelial origin, may influence neutrophil recruitment in tetracycline-induced pleuritis.
Primary extranodal non-Hodgkin’s lymphoma (NHL): the impact of alternative definitions tested in the Comprehensive Cancer Centre West population-based NHL registry
Authors: A.D.G. Krol, S. le Cessie, S. Snijder, J.C. Kluin-Nelemans, P.M. Kluin, E.M. Noordijk
Journal: Annals of Oncology (2002)