tbuckley/cabot-search huggingface dataset:
Azithromycin for the Secondary Prevention of Coronary Heart Disease Events
Authors: Christopher M. O'Connor, Michael W. Dunne, Marc A. Pfeffer, Joseph B. Muhlestein, Louis Yao, Sandeep Gupta, Rebecca J. Benner, Marian R. Fisher, Thomas D. Cook, None for the Investigators in the WIZARD Study
Journal: JAMA (2003)

Several lines of evidence have implied an association between Chlamydia pneumoniae infection and atherogenesis.To determine the effect of 12 weeks of antibiotic therapy on coronary heart disease events in patients with stable coronary artery disease and known C pneumoniae exposure.Randomized, placebo-controlled trial of 7747 adults with previous myocardial infarction that had occurred at least 6 weeks previously (median, 2.6 years) and a C pneumoniae IgG titer of 1:16 or more. Patients were recruited from 271 clinical practices in North America, Europe, Argentina, and India, from October 10, 1997, to July 22, 2001.The patients received either azithromycin (600 mg/d for 3 days during week 1, then 600 mg/wk during weeks 2-12; n = 3879) or placebo (n = 3868).The primary event was the first occurrence of death from any cause, nonfatal reinfarction, coronary revascularization, or hospitalization for angina. Patients were followed up until 1038 events accrued.After a median of 14 months of follow-up, there was no significant risk reduction in the likelihood of a primary event with azithromycin vs placebo (7% [95% confidence interval, -5% to 17%], P =.23). Analysis of hazard ratios suggested early benefits of azithromycin on the primary event and on death or reinfarction, but these decreased over time. There were no significant risk reductions for any of the components of the primary end point including death (8%), recurrent myocardial infarction (7%), revascularization procedures (5%), or hospitalizations for angina (-1%). Adverse events related to study drug were reported by 13.2% of those randomized to receive azithromycin, predominantly a result of diarrhea, compared with 4.6% randomized to receive placebo, and resulted in discontinuation of drug in 1.6% of those taking azithromycin and 0.4% taking placebo.Among stable patients with previous myocardial infarction and with evidence of C pneumoniae exposure, a 3-month course of azithromycin did not significantly reduce the clinical sequelae of coronary heart disease.
Hypersensitivity pneumonitis in a technician using Pauli's reagent.
Authors: W V Evans, A Seaton
Journal: Thorax (1979)

A technician working in a medical laboratory used a spray of sodium diazobenzenesulphate (Pauli9s reagent) in chromatography. She developed a respiratory illness with both airways obstruction and radiographic and physiological evidence of interstitial pneumonitis. An occupational type of challenge test was followed by both immediate and late bronchial obstructive responses, by a fall in arterial oxygen tension, and by increased radiographic shadowing. Histology of a lung biopsy specimen, a low serum C3, and a postive skin prick test to the reagent suggested that the illness was a hypersensitivity reaction to Pauli9s reagent.
An Official American Thoracic Society Clinical Practice Guideline: The Clinical Utility of Bronchoalveolar Lavage Cellular Analysis in Interstitial Lung Disease
Authors: Keith C. Meyer, Ganesh Raghu, Robert P. Baughman, Kevin K. Brown, Ulrich Costabel, Roland M. du Bois, Marjolein Drent, Patricia L. Haslam, Dong Soon Kim, Sonoko Nagai, Paola Rottoli, Cesare Saltini, Moisés Selman, Charlie Strange, Brent Wood
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Section:ChooseTop of pageAbstract <<ContentsExecutive SummaryIntroductionMethodsBal Cellular Analyses as ...Performing, Handling, and...Bal Cellular Analysis In ...Conclusions and Future Di...Note From ATS Documents E...ReferencesCITING ARTICLES
A new system for grading recommendations in evidence based guidelines
Authors: R. Harbour, J. Miller
Journal: BMJ (2001)

The Scottish Intercollegiate Guidelines Network (SIGN) develops evidence based clinical guidelines for the NHS in Scotland. The key elements of the methodology are (a) that guidelines are developed by multidisciplinary groups; (b) they are based on a systematic review of the scientific evidence; and (c) recommendations are explicitly linked to the supporting evidence and graded according to the strength of that evidence.

Until recently, the system for grading guideline recommendations was based on the work of the US Agency for Healthcare Research and Quality (formerly the Agency for Health Care Policy and Research). 1 2 However, experience over more than five years of guideline development led to a growing awareness of this system's weaknesses. Firstly, the grading system was designed largely for application to questions of effectiveness, where randomised controlled trials are accepted as the most robust study design with the least risk of bias in the results. However, in many areas of medical practice randomised trials may not be practical or ethical to undertake; and for many questions other types of study design may provide the best evidence. Secondly, guideline development groups often fail to take adequate account of the methodological quality of individual studies and the overall picture presented by a body of evidence rather than individual studies or they fail to apply sufficient judgment to the overall strength of the evidence base and its applicability to the target population of the guideline. Thirdly, guideline users are often not clear about the implications of the grading system. They misinterpret the grade of recommendation as relating to its importance, rather than to the strength of the supporting evidence, and may therefore fail to give due weight to low grade recommendations.

#### Summary points

A revised system of determining levels of evidence and grades …
Hepatic arterial infusion chemotherapy with cisplatin before radical local treatment of early hepatocellular carcinoma (JIS score 0/1) improves survival
Authors: T. Ishikawa, T. Kubota, S. Abe, Y. Watanabe, T. Sugano, R. Inoue, A. Iwanaga, K. Seki, T. Honma, T. Yoshida
Journal: Annals of Oncology (2014)
Role of the Adrenal Glands in the Development of Severe Hypertension
Authors: OSCAR A. CARRETERO, GARY ENZMANN, CARL POLOMSKI, ALEXSANDRA PIWONSKA, NARENDRA B. OZA, ANTHONY SCHORK
Journal: Circulation Research (1973)

It has been previously shown that angiotensin II is involved in the pathogenesis of severe hypertension resulting from ligation of the aorta between the origins of the renal arteries. To see if part of the effect of the angiotensin II was due to the stimulation of mineralocorticoid secretion, blood pressure and plasma renin activity were studied after ligation of the aorta in adrenalectomized rats receiving maintenance doses of steroids. Rats subjected to adrenalectomy and aortic coarctation developed hypertension as severe as that in rats with intact adrenal glands. Thus, an increase in the secretory rate of adrenal hormones is not a pathogenetic factor in the development of severe hypertension after aortic coarctation.
Muscle Pumping in the Dependent Leg
Authors: H. FRED STEGALL
Journal: Circulation Research (1966)

Since the exercising dependent leg displaces blood toward the heart, against a potential gradient, it must perform useful circulatory work. We studied the peripheral circulation in healthy, sedentary males by measuring calf circumference (using mercury-in-Silastic strain gages), muscle pump ejection velocity (using a transcutaneous Doppler flowmeter), intrathoracic and intra-abdominal pressures (through catheters in the esophagus and rectum) and power of the leg muscle pump (product of blood flow and the upstream-downstream venous pressure difference). Measurements of pressure, flow velocity, and volume changes in the dependent venous beds of healthy young men demonstrated that during running in place, (1) the abdominal contraction necessary to fix the pelvis raised inferior caval pressure and impeded venous outflow from the legs, but that, (2) the leg muscles themselves were capable of effectively pumping blood past this functional obstruction. By doing so, these peripheral pumps contributed more than 30% of the energy required to circulate blood during running.
An uncommonly serious case of an uncommon sport injury * Commentary
Authors: A Abedin, H-C Chen
Journal: British Journal of Sports Medicine (2005)

Background: A 55 year old man sustained a severe ocular injury when hit by a cricket ball even though he was wearing a helmet. Methods: A suprachoroidal haemorrhage was drained and dense intravitreal blood was removed. An inferior buckle was applied with the use of intraocular gas. A macular haemorrhage resolved slowly. Results: Despite several surgical procedures over 1.5 years, the final visual acuity of the patient was only 6/60 because of a dense macular scar. Conclusions: Helmets worn as protection when playing cricket need to be designed better and be of better material. Eye protection should be worn at all levels of play.
Upregulation of COX-1 and COX-2 in nasal polyps in cystic fibrosis
Authors: J Roca-Ferrer
Journal: Thorax (2006)

Early Warning Scores (EWS) have become increasingly used by hospitals throughout the world to prevent unexpected admission to intensive care or even death in their inpatient population. It is well known that signs of deterioration are present well before collapse and by a combination of systems, EWS enable healthcare professionals to intervene at an appropriate time. A number of national bodies and regulators in the UK have required the use of Early Warning Scores in locations where children are inpatients. This article attempts to describe the background to their development, identify common problems and provide information for units interested in introducing an EWS into their department.
Effects of inhaled fluticasone on angiogenesis and vascular endothelial growth factor in asthma
Authors: B N Feltis, D Wignarajah, D W Reid, C Ward, R Harding, E H Walters
Journal: Thorax (2006)

<b>Background:</b> Subepithelial hypervascularity and angiogenesis in the airways are part of structural remodelling of the airway wall in asthma, but the effects of inhaled corticosteroids (ICS) on these have not been explored. Increased vascularity in asthma may contribute to a number of functional abnormalities. A study was undertaken to explore angiogenic modulation by ICS and its likely regulation via vascular endothelial growth factor (VEGF), its receptors and the angiopoietins. <b>Methods:</b> A placebo-controlled intervention study with ICS in asthma was performed, examining vascularity, VEGF, its receptors (VEGFR1 and VEGFR2), and angiopoietin-1 (Ang1) to assess which of these factors were changed in the asthmatic airways after ICS treatment. Airway wall biopsy specimens, lavage fluid and cells were obtained from 35 patients with mild asthma randomised to receive ICS or placebo for 3 months, after which bronchoscopic examination and sample collection were repeated. Immunohistochemistry and image analysis were used to obtain quantitative measures of vessels, angiogenic sprouts, VEGF, VEGFR1, VEGFR2 and Ang1 staining in airway biopsy specimens. ELISA was used to assess VEGF concentrations in the lavage fluid. <b>Results:</b> Vessel, VEGF and sprout staining were decreased after 3 months of ICS treatment. VEGF levels remained unchanged. VEGF receptors and Ang1 staining were not reduced after treatment. <b>Conclusions:</b> The findings of this study support an effect of ICS in downregulating angiogenic remodelling in the airways in asthma, associated with decreasing VEGF activity within the airway wall. The environment of the airways after treatment with ICS, with changes in the balance between VEGF, its receptors, Ang1 and sprouts, appears to be less angiogenic than in untreated asthma.
Interaction of hemopexin, albumin and liver fatty acid-binding protein with protoporphyrin
Authors: Elizabeth Knobler, Maureen B. Poh-Fitzpatrick, Donna Kravetz, William R. Vincent, Ursula Muller-Eberhard, Styliani H. Vicent
Journal: Hepatology (1989)

Equilibrium constants for the binding of protoporphyrin to serum albumin and hemopexin and liver cytosolic fatty acid–binding protein of the rat were determined fluorometrically. The experimental equilibrium constant [10 6 M -1 (mean ± S. D.)] values were 8.4 ± 1.3, 10.0 ± 2.4 and 34.0 ± 3.0 for albumin, hemopexin and liver fatty acid–binding protein, respectively. Statistical analysis showed the equilibrium constant of binding of protoporphyrin to liver fatty acid–binding protein to be significantly (p &lt; 0.01) higher than that to albumin and hemopexin. The data suggest that in patients with erythropoietic protoporphyria an equilibrium gradient may exist which favors the uptake by hepatocytes of plasma protoporphyrin as a result of its greater affinity for intracellular liver fatty acid–binding protein.
Imperfect centered miRNA binding sites are common and can mediate repression of target mRNAs
Authors: Hilary C Martin, Shivangi Wani, Anita L Steptoe, Keerthana Krishnan, Katia Nones, Ehsan Nourbakhsh, Alexander Vlassov, Sean M Grimmond, Nicole Cloonan
Journal: Genome biology (2014)

Abstract Background MicroRNAs (miRNAs) bind to mRNAs and target them for translational inhibition or transcriptional degradation. It is thought that most miRNA-mRNA interactions involve the seed region at the 5′ end of the miRNA. The importance of seed sites is supported by experimental evidence, although there is growing interest in interactions mediated by the central region of the miRNA, termed centered sites. To investigate the prevalence of these interactions, we apply a biotin pull-down method to determine the direct targets of ten human miRNAs, including four isomiRs that share centered sites, but not seeds, with their canonical partner miRNAs. Results We confirm that miRNAs and their isomiRs can interact with hundreds of mRNAs, and that imperfect centered sites are common mediators of miRNA-mRNA interactions. We experimentally demonstrate that these sites can repress mRNA activity, typically through translational repression, and are enriched in regions of the transcriptome bound by AGO. Finally, we show that the identification of imperfect centered sites is unlikely to be an artifact of our protocol caused by the biotinylation of the miRNA. However, the fact that there was a slight bias against seed sites in our protocol may have inflated the apparent prevalence of centered site-mediated interactions. Conclusions Our results suggest that centered site-mediated interactions are much more frequent than previously thought. This may explain the evolutionary conservation of the central region of miRNAs, and has significant implications for decoding miRNA-regulated genetic networks, and for predicting the functional effect of variants that do not alter protein sequence.
Aging-associated changes in cardiac gene expression
Authors: M VOLKOVA, R GARG, S DICK, K BOHELER
Journal: Cardiovascular Research (2004)

Cardiovascular diseases (e.g., vascular diseases, strokes, heart failure) reach epidemic proportions in the elderly and are the primary limits to survival in man. Age-associated changes in heart structure and function represent the major risk factors in heart failure (HF) syndromes and are associated with altered patterns of gene expression that can generally be seen as relative changes in the abundance of gene transcripts. An understanding of the molecular mechanisms underlying these changes should be tantamount to defining a genetic basis for aging; however, the analysis of processes as complicated as aging requires an accounting of biological diversity. Until recently, most of the changes in transcript abundance were identified one at a time, but the advent of gene expression arrays has permitted rapid, large-scale expression profiling. This has provided information about the dynamics of total gene expression, which can be used to identify pathways and elucidate regulatory events that may be affected during senescence or in response to disease. Importantly, very large sample sizes or meta-analyses of studies of smaller sample sizes should be sufficient to account for the diversity of altered gene expression that directs alterations in specific molecular pathways, which underlie changes in cardiac structure and function in senescence and disease.
Phase I/randomized phase II study of afatinib, an irreversible ErbB family blocker, with or without protracted temozolomide in adults with recurrent glioblastoma
Authors: D. A. Reardon, L. B. Nabors, W. P. Mason, J. R. Perry, W. Shapiro, P. Kavan, D. Mathieu, S. Phuphanich, A. Cseh, Y. Fu, J. Cong, S. Wind, D. D. Eisenstat
Journal: Neuro-Oncology (2014)

This phase I/II trial evaluated the maximum tolerated dose (MTD) and pharmacokinetics of afatinib plus temozolomide as well as the efficacy and safety of afatinib as monotherapy (A) or with temozolomide (AT) vs temozolomide monotherapy (T) in patients with recurrent glioblastoma (GBM). Phase I followed a traditional 3 + 3 dose-escalation design to determine MTD. Treatment cohorts were: afatinib 20, 40, and 50 mg/day (plus temozolomide 75 mg/m2/day for 21 days per 28-day cycle). In phase II, participants were randomized (stratified by age and KPS) to receive A, T or AT; A was dosed at 40 mg/day and T at 75 mg/m2 for 21 of 28 days. Primary endpoint was progression-free survival rate at 6 months (PFS-6). Participants were treated until intolerable adverse events (AEs) or disease progression. Recommended phase II dose was 40 mg/day (A) + T based on safety data from phase I (n = 32). Most frequent AEs in phase II (n = 119) were diarrhea (71% [A], 82% [AT]) and rash (71% [A] and 69% [AT]). Afatinib and temozolomide pharmacokinetics were unaffected by coadministration. Independently assessed PFS-6 rate was 3% (A), 10% (AT), and 23% (T). Median PFS was longer in afatinib-treated participants with epidermal growth factor receptor (EFGR) vIII-positive tumors versus EGFRvIII-negative tumors. Best overall response included partial response in 1 (A), 2 (AT), and 4 (T) participants and stable disease in 14 (A), 14 (AT), and 21 (T) participants. Afatinib has a manageable safety profile but limited single-agent activity in unselected recurrent GBM patients.
Maturation of Marginal Zone and Follicular B Cells Requires B Cell Activating Factor of the Tumor Necrosis Factor Family and Is Independent of B Cell Maturation Antigen
Authors: Pascal Schneider, Hisakazu Takatsuka, Anne Wilson, Fabienne Mackay, Aubry Tardivel, Susanne Lens, Teresa G. Cachero, Daniela Finke, Friedrich Beermann, Jürg Tschopp
Journal: The Journal of Experimental Medicine (2001)

B cells undergo a complex series of maturation and selection steps in the bone marrow and spleen during differentiation into mature immune effector cells. The tumor necrosis factor (TNF) family member B cell activating factor of the TNF family (BAFF) (BLyS/TALL-1) plays an important role in B cell homeostasis. BAFF and its close homologue a proliferation-inducing ligand (APRIL) have both been shown to interact with at least two receptors, B cell maturation antigen (BCMA) and transmembrane activator and cyclophilin ligand interactor (TACI), however their relative contribution in transducing BAFF signals in vivo remains unclear. To functionally inactivate both BAFF and APRIL, mice transgenic for a soluble form of TACI were generated. They display a developmental block of B cell maturation in the periphery, leading to a severe depletion of marginal zone and follicular B2 B cells, but not of peritoneal B1 B cells. In contrast, mice transgenic for a soluble form of BCMA, which binds APRIL, have no detectable B cell phenotype. This demonstrates a crucial role for BAFF in B cell maturation and strongly suggests that it signals via a BCMA-independent pathway and in an APRIL-dispensable way.
Comparison of the effects of a gastrin extract and a synthetic pentapeptide on gastrointestinal motility in the cat.
Authors: J Neely
Journal: Gut (1967)

OBJECTIVE: To estimate the prevalence of short term and longterm musculoskeletal activity limitation among the general adult population of the province of Quebec, and to identify which factors are associated with these limitations. METHODS: We analyzed cross-sectional data from the 1998 Quebec Health Survey. Logarithmic binomial regression models were used to estimate prevalence ratios of (1) short term activity limitation related to musculoskeletal disorders (MSD); and (2) longterm activity limitation related to MSD in relation to demographic and behavioral variables and comorbidity factors. RESULTS: About one-fifth of participants reporting short term activity limitation and one-third of participants reporting longterm activity limitation mentioned MSD as a cause. Multivariate analyses showed that higher age, lower income, being overweight, ill defined nervousness, and the number of traumatic events that occurred before age 18 years were significantly associated with short term and longterm activity limitation related to MSD, whereas being in the minority ethnic group was protective for both outcomes. Female sex, physical inactivity, being a former alcohol drinker, and mental disorders were also associated with longterm activity limitation. CONCLUSION: MSD are a major cause of activity limitation among adults from Quebec. With the aging population and the increasing prevalence of obesity, increasing prevalence of activity limitation related to MSD is to be expected.
Off-Pump Bilateral Versus Single Skeletonized Internal Thoracic Artery Grafting in High-Risk Patients
Authors: Takeshi Kinoshita, Tohru Asai, Tomoaki Suzuki, Atsushi Kambara, Keiji Matsubayashi
Journal: Circulation (2011)

We compared the outcomes in propensity score-matched high-risk patients (European System for Cardiac Operative Risk Evaluation [EuroSCORE] ≥ 5) undergoing off-pump coronary artery bypass graft surgery using bilateral or single skeletonized internal thoracic artery (ITA).Of 794 consecutive patients undergoing isolated coronary artery bypass graft surgery (788 by the off-pump technique without emergent conversion to cardiopulmonary bypass), the 536 who had a EuroSCORE ≥ 5 and underwent off-pump skeletonized single (n=236) or bilateral (n=300) ITA were retrospectively analyzed after excluding the 6 who were transferred to our hospital after receiving percutaneous cardiopulmonary support, the 45 who had only 1 target in the left-side coronary area, and the 207 with EuroSCORE <5. A total of 235 pairs were matched using propensity scores calculated from 7 preoperative factors (C statistic, 0.65). The rate of postoperative complications was similar between the groups. The mean observation period was 3.2 years. The 5-year estimated survival rate free from overall death and cardiac event in patients receiving bilateral versus single ITA grafting was 85.8 ± 5.5% versus 74.8 ± 4.9% (P=0.002) and 87.4 ± 4.6% versus 66.1 ± 5.7% (P=0.001), respectively. In multivariate Cox proportional hazard models, bilateral ITA grafting was significantly associated with a lower risk of overall death (hazard ratio, 0.56; 95% CI, 0.32 to 0.87; P=0.009) and cardiac event (hazard ratio, 0.40; 95% CI, 0.24 to 0.69; P=0.001).In high-risk patients, off-pump skeletonized left-sided bilateral in situ ITA grafting is associated with lower risk of overall death and cardiac event than single ITA grafting without increased operative risk.