tbuckley/cabot-search huggingface dataset:
Risk factors for COPD spirometrically defined from the lower limit of normal in the BOLD project
Authors: Richard Hooper, Peter Burney, William M. Vollmer, Mary Ann McBurnie, Thorarinn Gislason, Wan C. Tan, Anamika Jithoo, Ali Kocabas, Tobias Welte, A. Sonia Buist
Journal: European Respiratory Journal (2011)

Chronic obstructive pulmonary disease (COPD) is predicted to become the third most common cause of death and disability worldwide by 2020. The prevalence of COPD defined by the lower limit of normal was estimated using high-quality spirometry in surveys of 14 populations aged ≥40 yrs. The strength and consistency of associations were assessed using random effects meta-analysis. Pack-years of smoking were associated with risk of COPD at each site. After adjusting for this effect, we still observed significant associations of COPD risk with age (OR 1.52 for a 10 yr age difference, 95% CI 1.35–1.71), body mass index in obese compared with normal weight (OR 0.50, 95% CI 0.37–0.67), level of education completed (OR 0.76, 95% CI 0.67–0.87), hospitalisation with a respiratory problem before age 10 yrs (OR 2.35, 95% CI 1.42–3.91), passive cigarette smoke exposure (OR 1.24, 95% CI 1.05–1.47), tuberculosis (OR 1.78, 95%CI 1.17–2.72) and a family history of COPD (OR 1.50, 95% CI 1.19–1.90). Although smoking is the most important risk factor for COPD, other risk factors are also important. More research is required to elucidate relevant risk factors in low- and middle-income countries where the greatest impact of COPD will occur.
Clinical health education for patients with asthma-like symptoms but negative asthma tests
Authors: K. C. Ringsberg, T. Timpka
Journal: Allergy (2001)

Patients with asthma-like symptoms but negative asthma tests often state that they lack strategies to cope with their symptoms. The aim of the study was to determine whether a problem-based health education program had a beneficial effect on the participants' experience of symptoms and subjective health.Thirty-eight patients, consecutively drawn from an outpatient clinic for asthma and allergy, were randomly allocated to an intervention group (I group, n=18) and a control group (C group, n=20). The I group, divided into three subgroups, met on seven occasions over 5 months. The program had a multidisciplinary approach, used exercises inspired by cognitive behavioral therapy, and was performed according to the principles of problem-based learning. All patients answered the Nijmegen Symptom Questionnaire (NQ) and the SF-36 health survey before and 2 months after the training was terminated.Before the program, there were no significant differences between the groups in their earlier experience of symptoms. After it, the I group scored significantly lower on shortness of breath (P=0.001) and central tetany (P=0.05) than the C group. On both test occasions, the asthma-like patients scored lower on all variables of the SF-36 than the reference groups of asthmatics and healthy subjects. No significant differences were seen between the I group and the C group except for vitality, in which the C group scored lower before the intervention.Patients with asthma-like symptoms but negative asthma tests benefit from taking part in a problem-based health education program. It mainly reduces the frequency of symptoms.
A selective COX-2 inhibitor suppresses chronic pancreatitis in an animal model (WBN/Kob rats): significant reduction of macrophage infiltration and fibrosis
Authors: T Reding
Journal: Gut (2005)

Therapeutic strategies to treat chronic pancreatitis (CP) are very limited. Other chronic inflammatory diseases can be successfully suppressed by selective cyclooxygenase 2 (COX-2) inhibitors. As COX-2 is elevated in CP, we attempted to inhibit COX-2 activity in an animal model of CP (WBN/Kob rat). We then analysed the effect of COX-2 inhibition on macrophages, important mediators of chronic inflammation.Male WBN/Kob rats were continuously fed the COX-2 inhibitor rofecoxib, starting at the age of seven weeks. Animals were sacrificed 2, 5, 9, 17, 29, 41, and 47 weeks later. In some animals, treatment was discontinued after 17 weeks, and animals were observed for another 24 weeks.Compared with the spontaneous development of inflammatory injury and fibrosis in WBN/Kob control rats, animals treated with rofecoxib exhibited a significant reduction and delay (p<0.0001) in inflammation. Collagen and transforming growth factor beta synthesis were significantly reduced. Similarly, prostaglandin E(2) levels were markedly lower, indicating strong inhibition of COX-2 activity (p<0.003). If treatment was discontinued at 24 weeks of age, all parameters of inflammation strongly increased comparable with that in untreated rats. The correlation of initial infiltration with subsequent fibrosis led us to determine the effect of rofecoxib on macrophage migration. In chemotaxis experiments, macrophages became insensitive to the chemoattractant fMLP in the presence of rofecoxib.In the WBN/Kob rat, chronic inflammatory changes and subsequent fibrosis can be inhibited by rofecoxib. Initial events include infiltration of macrophages. Cell culture experiments indicate that migration of macrophages is COX-2 dependent.
Venous thrombotic events are not increased in patients with rheumatoid arthritis treated with anti‑TNF therapy: results from the British Society for Rheumatology Biologics Register
Authors: Rebecca Davies, James B Galloway, Kath D Watson, Mark Lunt, Deborah P M Symmons, Kimme L Hyrich
Journal: Annals of the Rheumatic Diseases (2011)

Past studies have reported conflicting rates of venous thrombotic events (VTEs) in rheumatoid arthritis (RA). The current study aimed to compare (1) the rates of VTEs in patients with RA treated with anti-tumour necrosis factor (anti-TNF) therapy versus those treated with non-biological disease-modifying antirheumatic drugs (nbDMARDs) alone and (2) the rates between each individual anti-TNF agent and nbDMARDs.Using data from the British Society for Rheumatology Biologics Register, a national prospective observational cohort study of biological safety in patients with RA, the authors compared the incidence of VTEs between 11 881 anti-TNF- and 3673 nbDMARD-treated patients. Analysis was limited to the first VTE per person. HRs were calculated using Cox modelling. Adjustment was made for potential confounders including surgery performed during follow-up.A total of 196 first VTEs were reported (151 anti-TNF, 45 nbDMARD). Overall there was no difference in the rates of VTEs between anti-TNF- and nbDMARD-treated patients (adjusted HR 0.8 (95% CI 0.5 to 1.5)). The risk was similar across all anti-TNF agents. Rates of postoperative VTEs did not significantly differ between groups.These data suggest that anti-TNF therapy is not associated with an increased risk of VTEs in RA patients.
Diagnosis of pulmonary arteriovenous malformations by colour Doppler ultrasound and amplitude ultrasound angiography
Authors: H.-C. Wang, P.-H. Kuo, Y.-S. Liaw, C.-J. Yu, S.-H. Kuo, K.-T. Luh, P.-C. Yang
Journal: Thorax (1998)

<h3>BACKGROUND</h3> The clinical value of colour Doppler ultrasound and amplitude ultrasound angiography in the diagnosis and follow up of pulmonary arteriovenous malformations (PAVM) was investigated. <h3>METHODS</h3> Six consecutive patients suspected by clinical appearance and abnormal chest radiographic findings of having PAVM were included in the study. Ultrasonography was performed first by real time grey scale imaging then by colour Doppler imaging and amplitude ultrasound angiography in a random order. All were later proved by angiography to have PAVM. <h3>RESULTS</h3> The ultrasound study was successfully performed in all six patients. A total of eight lesions was detected. The real time grey scale image of PAVM revealed well defined hypoechoic subpleural nodules with strong posterior acoustic enhancement. Colour Doppler ultrasound of PAVM showed turbulent flow, manifest as an area of intense colour with high and mixed velocities (reticulated or mosaic-like pattern). Anatomical continuity was demonstrated in some PAVM. Amplitude ultrasound angiography can delineate a tangled vascular structure with a clear vessel wall and anatomical continuity as well as conventional angiography. Spectral wave analysis showed a relatively low impedance flow presenting with high peak systolic velocity (mean 44.4 cm/s) and relatively high diastolic velocity (mean 19.3 cm/s). The mean pulsatility index (PI) and resistive index (RI) were 1.80 and 0.49, respectively. In two patients who received embolotherapy the colour Doppler ultrasound scan obtained after the procedure showed that the previous focal areas of colour flow signals disappeared or diminished in size. This was compatible with the decrease in, or absence of, blood flow demonstrated by angiography after embolotherapy. <h3>CONCLUSIONS</h3> Combined colour Doppler ultrasound and amplitude ultrasound angiography are useful non-invasive techniques for diagnosing PAVM and provide an alternative approach to angiography in evaluating the efficacy of embolotherapy.
Computerised clinical decision support for suspected PE: Table 1
Authors: David Jiménez, Santiago Resano, Remedios Otero, Carolina Jurkojc, Ana Karina Portillo, Pedro Ruiz-Artacho, Jesús Corres, Agustina Vicente, Paul L den Exter, Menno V Huisman, Lisa Moores, Roger D Yusen
Journal: Thorax (2015)

This study aimed to determine the effect of an evidence-based clinical decision support (CDS) algorithm on the use and yield of CT pulmonary angiography (CTPA) and on outcomes of patients evaluated in the emergency department (ED) for suspected PE. The study included 1363 consecutive patients evaluated for suspected PE in an ED during 12 months before and 12 months after initiation of CDS use. Introduction of CDS was associated with decreased CTPA use (55% vs 49%; absolute difference (AD), 6.3%; 95% CI 1.0% to 11.6%; p=0.02). The use of CDS was associated with fewer symptomatic venous thromboembolic events during follow-up in patients with an initial negative diagnostic evaluation for PE (0.7% vs 3.2%; AD 2.5%; 95% CI 0.9% to 4.6%; p&lt;0.01).
Sequential measurements of procalcitonin levels in diagnosing ventilator-associated pneumonia
Authors: P. Ramirez, M. A. Garcia, M. Ferrer, J. Aznar, M. Valencia, J. M. Sahuquillo, R. Menéndez, M. A. Asenjo, A. Torres
Journal: European Respiratory Journal (2007)

The utility of procalcitonin levels to improve the accuracy of clinical and microbiological parameters in diagnosing ventilator-associated pneumonia (VAP) was evaluated. Sequential measurement of procalcitonin and C-reactive protein levels and the calculation of the simplified Clinical Pulmonary Infection Scores (CPIS) were performed in 44 patients mechanically-ventilated for &gt;48 h with neither active infection for the duration or suspicion of VAP. Patients who developed extrapulmonary infection were excluded. In total, 20 cases were suspected of having VAP and diagnosis was microbiologically confirmed in nine. In patients with confirmed VAP, procalcitonin levels were higher than in those without VAP. C-reactive protein levels and CPIS were lower in patients without suspected VAP, but could not discriminate confirmed and nonconfirmed suspicion of VAP. The best sensitivity and specificity (78 and 97%, respectively) corresponded to procalcitonin. The CPIS resulted in the same sensitivity, but had a lower specificity (80%). C-reactive protein had the worst sensitivity (56%), but a good specificity (91%). A CPIS ≥6 combined with serum levels of procalcitonin ≥2.99 ng·mL −1 did not improve the sensitivity (67%), but resulted in 100% specificity. Procalcitonin might be useful in the diagnosis of ventilator-associated pneumonia. Combined values of Clinical Pulmonary Infection Scores and procalcitonin below the cut-off points excluded false-positive diagnoses of ventilator-associated pneumonia.
Itraconazole, a Commonly Used Antifungal that Inhibits Hedgehog Pathway Activity and Cancer Growth
Authors: James Kim, Jean Y. Tang, Ruoyu Gong, Jynho Kim, John J. Lee, Karl V. Clemons, Curtis R. Chong, Kris S. Chang, Mark Fereshteh, Dale Gardner, Tannishtha Reya, Jun O. Liu, Ervin H. Epstein, David A. Stevens, Philip A. Beachy
Journal: Cancer Cell (2010)
Individual exome analysis in diagnosis and management of paediatric liver failure of indeterminate aetiology
Authors: Sílvia Vilarinho, Murim Choi, Dhanpat Jain, Ajay Malhotra, Sanjay Kulkarni, Dinesh Pashankar, Uma Phatak, Mohini Patel, Allen Bale, Shrikant Mane, Richard P. Lifton, Pramod K. Mistry
Journal: Journal of Hepatology (2014)
The Fanconi anemia core complex associates with chromatin during S phase
Authors: Jun Mi, Gary M. Kupfer
Journal: Blood (2004)

Abstract Fanconi anemia (FA) is an autosomal recessive disease marked by bone marrow failure, birth defects, and cancer. The FA proteins FANCA, FANCC, FANCE, FANCF, FANCG, and FANCL participate in a core complex. We previously have shown that several members of this complex bind to chromatin until mitosis and that this binding increases after DNA damage. The purpose of the present study was to determine the dynamics of complex movement between cytoplasm and nuclear compartments. Fluorescent-tagged versions of FANCA, FANCC, and FANCG colocalize in cytoplasm and nucleus, chiefly in chromatin. At the G1-S border, the FA core complex exists as foci on chromatin, progressively diffusing and migrating to the nuclear periphery and becoming completely excluded from condensed chromosomes by mitosis. Chromatin fiber analysis shows FA proteins diffusely staining along chromatin fibers during G1-S and S phase. Treatment with the DNA cross-linker mitomycin C results in a diffusion of foci and increased binding of complex proteins to chromatin, as well as diffuse and increased complex binding to chromatin fibers. These data are consistent with the idea that the FA proteins function at the level of chromatin during S phase to regulate and maintain genomic stability.
Underestimation of Risk of a <i>BRCA1</i> or <i>BRCA2</i> Mutation in Women With High-Grade Serous Ovarian Cancer by BRCAPRO: A Multi-Institution Study
Authors: Molly S. Daniels, Sheri A. Babb, Robin H. King, Diana L. Urbauer, Brittany A.L. Batte, Amanda C. Brandt, Christopher I. Amos, Adam H. Buchanan, David G. Mutch, Karen H. Lu
Journal: Journal of Clinical Oncology (2014)

Identification of the 10% to 15% of patients with ovarian cancer who have germline BRCA1 or BRCA2 mutations is important for management of both patients and relatives. The BRCAPRO model, which estimates mutation likelihood based on personal and family cancer history, can inform genetic testing decisions. This study's purpose was to assess the accuracy of BRCAPRO in women with ovarian cancer.BRCAPRO scores were calculated for 589 patients with ovarian cancer referred for genetic counseling at three institutions. Observed mutations were compared with those predicted by BRCAPRO. Analysis of variance was used to assess factors impacting BRCAPRO accuracy.One hundred eighty (31%) of 589 patients with ovarian cancer tested positive. At BRCAPRO scores less than 40%, more mutations were observed than expected (93 mutations observed v 34.1 mutations expected; P < .001). If patients with BRCAPRO scores less than 10% had not been tested, 51 (28%) of 180 mutations would have been missed. BRCAPRO underestimated the risk for high-grade serous ovarian cancers but overestimated the risk for other histologies (P < .001), underestimation increased as age at diagnosis decreased (P = .02), and model performance varied by institution (P = .02).Patients with ovarian cancer classified as low risk by BRCAPRO are more likely to test positive than predicted. The risk of a mutation in patients with low BRCAPRO scores is high enough to warrant genetic testing. This study demonstrates that assessment of family history by a validated model cannot effectively target testing to a high-risk ovarian cancer patient population, which strongly supports the recommendation to offer BRCA1/BRCA2 genetic testing to all patients with high-grade serous ovarian cancer regardless of family history.
Rapid Sequence and Expression Divergence Suggest Selection for Novel Function in Primate-Specific KRAB-ZNF Genes
Authors: K. Nowick, A. T. Hamilton, H. Zhang, L. Stubbs
Journal: Molecular Biology and Evolution (2010)

Recent segmental duplications (SDs), arising from duplication events that occurred within the past 35–40 My, have provided a major resource for the evolution of proteins with primate-specific functions. KRAB zinc finger (KRAB-ZNF) transcription factor genes are overrepresented among genes contained within these recent human SDs. Here, we examine the structural and functional diversity of the 70 human KRAB-ZNF genes involved in the most recent primate SD events including genes that arose in the hominid lineage. Despite their recent advent, many parent–daughter KRAB-ZNF gene pairs display significant differences in zinc finger structure and sequence, expression, and splicing patterns, each of which could significantly alter the regulatory functions of the paralogous genes. Paralogs that emerged on the lineage to humans and chimpanzees have undergone more evolutionary changes per unit of time than genes already present in the common ancestor of rhesus macaques and great apes. Taken together, these data indicate that a substantial fraction of the recently evolved primate-specific KRAB-ZNF gene duplicates have acquired novel functions that may possibly define novel regulatory pathways and suggest an active ongoing selection for regulatory diversity in primates.
The influence of parents' level of general education on the efficiency of childhood asthma educational program
Authors: Snezana Radic, Zorica Zivkovic, Sofija Cerovic, Olivera Calovic, Tamara Krivokapic, Milka Micic-Stanojevic, Spomenka Smiljanic
Journal: European Respiratory Journal (2012)

Aim: To investigate how important parent9s level of general education was for the success of organized Asthma Educational Intervention (AEI) program. Methodology: We assessed parents9 knowledge of asthma by questionnaire before, immediately after and 12 months after AEI in hospital settings. The Intervention I group of parents (N 231) received full AEI (audiovisual education about all the aspects of asthma and proper use of asthma medications, and workshop/panel discussions with the hand-on book “Meet your asthma”). The Control C group of parents (N 171) received instructions for proper medications inhalation technique and the hand-on book. Results: There was no difference in the knowledge of asthma between I and C groups at the beginning of the study. The knowledge of asthma in I group significantly increased immediately after the AEI (χ2=144.14, p 0.05) during 12 months period after the AEI. The knowledge of asthma in C group did not improve during the study (Z=0.73, p=0.17). According to their level of general education, we had four groups in I group of parents: with low ( 15 years of education). The final knowledge of asthma was significantly higher in I group (t=7.79, p=0.01) compared to C group, and did not differ between parents according to the parent9s level of general education (p>0.05). Conclusion: Parent9s level of general education was not relevant for the AEI. The C group of parents did not read hand-on book and did not improve asthma knowledge. Audiovisual education/workshop/discussion was successful way to transfer knowledge of asthma to I group of parents.
Pericardial actinomycosis with cardiac tamponade from a contiguous thoracic lesion.
Authors: A D Slutzker, W D Claypool
Journal: Thorax (1989)

A case of acute pericardial tamponade due to actinomycotic infection is reported, in which computed tomography showed a mass adjacent to the heart and a pericardial effusion. The patient had aggressive medical treatment with penicillin and survived.
Nocturnal Oxygenation and Prognosis in Duchenne Muscular Dystrophy
Authors: MARGARET F. PHILLIPS, PHILIP E. M. SMITH, NADINE CARROLL, RICHARD H. T. EDWARDS, PETER M. A. CALVERLEY
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

REM-related oxygen desaturation occurs in advanced Duchenne muscular dystrophy (DMD) and might be an independent predictor of disease progression. We have followed 18 patients for 10 yr after an initial respiratory sleep study or until death or onset of nasal ventilation. We measured baseline spirometry, blood gas tensions, maximal respiratory pressures, and body mass index. In 11 cases, VC was recorded serially. Median survival was 50 (range, 13 to 89) mo from initial study and unrelated to age at time of study, BMI, or mouth pressures but correlated with PaCO2 (r = − 0.72, p < 0.005, n = 17), minimal nocturnal SaO2 (r = 0.62, p < 0.007, n = 18) and VC (r = 0.65, p < 0.005, n = 17). Cox regression analysis showed a VC of less than 1 L at the time of study to be the best single predictor of subsequent survival. The only measure associated with age of death was the age at which the VC fell below 1 L (r = 0.79, p < 0.004). These data suggest measurement of PaCO2 or serial assessment of VC should be studied further as valid methods of assessing prognosis in DMD.
Contribution of ADAM33 polymorphisms to the population risk of asthma
Authors: J Blakey
Journal: Thorax (2005)

<b>Background:</b><i>ADAM 33</i> is the first gene identified as a candidate for asthma by positional cloning techniques, with association studies reaching impressive statistical significance. It has a postulated role in myogenesis, airway modelling, and signalling via protein shedding. Concerns over the methodology of the initial study have led to several attempts at replication, with inconsistent results. <b>Method:</b> To clarify the role of <i>ADAM33</i> in determining the risk of asthma in the general population, new transmission disequilibrium and case-control studies were undertaken followed by a meta-analysis of all existing data. <b>Results:</b> Studies in Icelandic and UK populations revealed no association when taken in isolation. The meta-analysis, however, showed that the F+1 and ST+7 variants were significantly associated with asthma in both types of study. <b>Conclusions:</b> The additional risk imparted by this variation would account for 50 000 excess asthma cases in the UK alone. This study also demonstrates the size of study required to investigate such hypotheses adequately.
Copy-number variation in sporadic amyotrophic lateral sclerosis: a genome-wide screen
Authors: Hylke M Blauw, Jan H Veldink, Michael A van Es, Paul W van Vught, Christiaan GJ Saris, Bert van der Zwaag, Lude Franke, J Peter H Burbach, John H Wokke, Roel A Ophoff, Leonard H van den Berg
Journal: The Lancet Neurology (2008)
Fatty acid levels and risk of asthma in young adults
Authors: R K Woods
Journal: Thorax (2004)

<b>Background:</b> There is current interest in the possible protective effect of long chain (n-3) fatty acids from fish in chronic lung diseases such as asthma. The aim of this community based cross sectional study was to determine whether plasma long chain (n-3) fatty acids, as a measure of dietary intake, differed between 1601 young adults with and without asthma. <b>Methods:</b> Subjects of mean (SD) age 34.6 (7.1) years completed a detailed respiratory questionnaire, food frequency questionnaire, skin prick testing, and lung function tests including methacholine challenge test for bronchial hyperreactivity (BHR) and had venous blood taken for analysis of plasma fatty acids. Plasma fatty acid levels (%) were analysed using multiple logistic regression with alternative definitions of asthma and atopy as the outcomes. <b>Results:</b> Atopy was not associated with any plasma fatty acid. The n-3 polyunsaturated fatty acids and n-6:n-3 ratio were not consistently associated with asthma or atopy. The n-6 polyunsaturated fatty acid dihomo γ-linolenic acid (DHGLA) was positively associated with current asthma (OR = 1.30, 95% CI 1.06 to 1.60), asthma (OR = 1.34, 95% CI 1.13 to 1.60), and doctor diagnosed asthma (OR = 1.25, 95% CI 1.06 to 1.48). <b>Conclusion:</b> Plasma n-3 fatty acids are not associated with a reduced risk of asthma or atopy among young adults. The association of DHGLA with asthma warrants further research to determine a cause-effect relationship.