tbuckley/cabot-search huggingface dataset:
The 2011 update of the World Health Organization guidelines for the programmatic management of drug-resistant tuberculosis
Authors: Dennis Falzon, Ernesto Jaramillo, Holger Schünemann
Journal: European Respiratory Journal (2011)

Introduction:  The production of guidelines for the programmatic management of drug-resistant tuberculosis fit into the mandate of the World Health Organization (WHO) to provide technical support to countries to reinforce care of drug resistant tuberculosis patients.   Methods:  WHO commissioned systematic reviews of evidence, including meta-analysis and modeling studies, to summarize evidence on priority questions regarding case finding, treatment regimens for multidrug-resistant TB (MDR-TB), monitoring of response to MDR-TB treatment and models of care. The quality of evidence assembled varied from low to very low. A multidisciplinary expert panel used the GRADE approach to develop recommendations based on best available evidence.   Findings:  The recommendations encourage the wider use of rapid drug-susceptibility testing with molecular techniques to detect rifampicin resistance and treat patients adequately. The use of culture remains important for the early detection of failure during MDR-TB treatment. The guidelines provide recommendations about the early use of anti-retroviral agents for TB patients with HIV who are on second-line TB drug regimens. Systems that primarily employ ambulatory models of care to manage MDR-TB patients are recommended over others based mainly on hospitalization.   Conclusion:  Practitioners and decision makers involved in MDR-TB care should be guided in their work by these updated recommendations. Additional research is necessary to improve the quality of existent evidence, particularly on regimen composition and duration of treatment.
Noninvasive Prenatal Testing
Authors: Amy E. Thompson
Journal: JAMA (2015)

Diana W. Bianchi, MD; Darya Chudova, PhD; Amy J. Sehnert, MD; Sucheta Bhatt, MD; Kathryn Murray, MS; Tracy L. Prosen, MD; Judy E. Garber, MD; Louise Wilkins-Haug, MD, PhD; Neeta L. Vora, MD; Stephen Warsof, MD; James Goldberg, MD; Tina Ziainia, MD; Meredith Halks-Miller, MD
Abstract 12351: Exercise Training May Reduce Intrinsic Heart Rate
Authors: Samira Bahrainy, Wayne C Levy, Janet May, James Caldwell, John R Stratton
Journal: Circulation (2010)

Background:  Resting heart rate (RHR) declines with exercise training. Possible mechanisms include: 1) increased parasympathetic tone, 2) decreased responsiveness to beta-adrenergic stimulation, 3) decreased intrinsic heart rate, which is the heart rate independent of any nervous or hormonal influences, and 4) a combination of these factors.   Objectives:  To determine whether an increase in resting parasympathetic tone or a decrease in response to beta-adrenergic stimulation contribute to the decrease in RHR with exercise training.   Methods:  51 rigorously screened sedentary healthy subjects aged 18–32 (n= 20, mean age 26, 11 female) or 65–80 (n= 31, mean age 69, 16 female) were tested before and after 6 months of supervised endurance exercise training. Heart rate response to parasympathetic withdrawal was assessed using atropine (0.02mg/kg up to 2mg). During continued parasympathetic blockade, beta-adrenergic responsiveness was assessed using isoproterenol (14ng/kg/min x 14min).   Results:  Training increased VO2 max by 17% (28.7 to 33.6 ml/kg/min, p   Conclusions:  In healthy subjects, this study did not find evidence that an increase in parasympathetic tone or a decrease in responsiveness to beta-adrenergic stimulation accounts for the reduction in resting heart rate with exercise training, and suggests that a decline in heart rate with training is most likely due to a decrease in the intrinsic heart rate.
Abstract 1876: Beta-blocker Therapy alters Myofilament Function in Patients with Congestive Heart Failure
Authors: Nazha Hamdani, Loek van Heerebeek, Attila Borbely, Nicky M Boontje, Hans W Niessen, Ger J Stienen, Walter J Paulus, Jolanda van der Velden
Journal: Circulation (2006)
Increased alveolar soluble annexin V promotes lung inflammation and fibrosis
Authors: Susan Buckley, Wei Shi, Wei Xu, Mark R. Frey, Rex Moats, Annie Pardo, Moises Selman, David Warburton
Journal: European Respiratory Journal (2015)

The causes underlying the self-perpetuating nature of idiopathic pulmonary fibrosis (IPF), a progressive and usually lethal disease, remain unknown. We hypothesised that alveolar soluble annexin V contributes to lung fibrosis, based on the observation that human IPF bronchoalveolar lavage fluid (BALF) containing high annexin V levels promoted fibroblast involvement in alveolar epithelial wound healing that was reduced when annexin V was depleted from the BALF. Conditioned medium from annexin V-treated alveolar epithelial type 2 cells (AEC2), but not annexin V per se , induced proliferation of human fibroblasts and contained pro-fibrotic, IPF-associated proteins, as well as pro-inflammatory cytokines that were found to correlate tightly (r&gt;0.95) with annexin V levels in human BALF. ErbB2 receptor tyrosine kinase in AECs was activated by annexin V, and blockade reduced the fibrotic potential of annexin V-treated AEC-conditioned medium. In vivo , aerosol delivery of annexin V to mouse lung induced inflammation, fibrosis and increased hydroxyproline, with activation of Wnt, transforming growth factor-β, mitogen-activated protein kinase and nuclear factor-κB signalling pathways, as seen in IPF. Chronically increased alveolar annexin V levels, as reflected in increased IPF BALF levels, may contribute to the progression of IPF by inducing the release of pro-fibrotic mediators.
Early Inflammation and Risk of Long-Term Development of Heart Failure and Mortality in Survivors of Acute Myocardial Infarction
Authors: Mahmoud Suleiman, Rania Khatib, Yoram Agmon, Riad Mahamid, Monther Boulos, Michael Kapeliovich, Yishai Levy, Rafael Beyar, Walter Markiewicz, Haim Hammerman, Doron Aronson
Journal: Journal of the American College of Cardiology (2006)
Understanding the ecological fallacy
Authors: Philip Sedgwick
Journal: BMJ (2015)

Researchers investigated whether an association existed between antibiotic prescribing by general practices and antibiotic resistance. A cross sectional study design was used. The setting was 28 general practices in Scotland. The participants were patients registered with a general practitioner between January 1995 and December 1996 who provided a urine sample for analysis during this period. In total, 8833 patients were included in the sample. For each patient in each of the practices the number of dispensed prescriptions for trimethoprim was obtained from databases of health records.1

Data were aggregated at the general practice level. For each general practice, antibiotic prescribing was measured as the number of dispensed trimethoprim prescriptions per 100 practice patients. Antibiotic resistance was defined as the proportion of patients in the practice with a urine sample that contained trimethoprim resistant Gram negative bacteria. Rates of trimethoprim prescription varied from 67 to 357 prescriptions per 100 patients between practices. The prevalence of trimethoprim resistance in Gram negative bacteria isolated from urine specimens varied between 26% and 50%. A weak negative association was seen between trimethoprim prescription and antibiotic resistance across the 28 general practices (Spearman rank …
Drug points: Erythromelalgia induced by possible calcium channel blockade by ciclosporin
Authors: G. P Thami
Journal: BMJ (2003)

large cities in industrialised nations. 5This might be because tuberculosis may be suspected and investigated more readily among men or black or Asian people.Our study was limited by the amount of missing surveillance data.It was also impossible to determine the relative contribution of patient and healthcare provider to the total delay.Potential confounders-for example, coinfection with HIV or the accuracy of the data among patients whose first language was not English-were not taken account of.Recent campaigns have tried to raise awareness of tuberculosis, particularly among ethnic minority groups.Our data suggest that campaigns also need to be targeted at white people, who comprise a third of cases.We thank John Watson for access to the anonymised data from the national tuberculosis survey 1998.
Congenital annular multiple fibrofolliculomas occurring with deformity of the ear and ventricular septal defect
Authors: None Park, None Ham, None Cho, None Kim, None Cho
Journal: British Journal of Dermatology (1999)

We describe a 5‐year‐old girl who had multiple fibrofolliculomas with an unusual annular configuration, present since birth, localized to the mid‐back. She had no family history of similar skin lesions. Examination showed a depigmented patch on her left buttock and other congenital anomalies, i.e. deformity of the auricle of the ear and ventricular septal defect. There has been no previous report of congenital multiple fibrofolliculomas occurring with congenital malformations such as deformity of the auricle of the ear and ventricular septal defect. The congenital occurrence and unusual configuration of the lesions in our patient may suggest a naevoid origin for these tumours.
Abstract 9575: Myocyte-Specific Catalase Overexpression Prevents Age-Related Left Ventricular Diastolic Dysfunction: Association with Reduction of Oxidation of SERCA at Cysteine 674
Authors: Fuzhong Qin, Luptak Ivan, Deborah Siwik, Lei Wang, James Kang, Richard Cohen, Wilson Colucci
Journal: Circulation (2011)

Background: Age-related myocardial diastolic dysfunction is associated with impaired calcium handling and reduced sarcoplasmic reticulum calcium ATPase (SERCA) activity. Oxidative sulfonylation of SERCA at cysteine 674 inhibits SERCA activity. We tested the hypothesis that a) aging is associated with sulfonylation of SRECA at cysteine 674, and b) cardiac myocyte-specific over-expression of catalase would decrease SERCA sulfonylation, restore SERCA activity, improve myocyte function and correct diastolic dysfunction. Methods and Results: Young (Y, 5-month) and senescent (S, 21-month) wild-type (WT) or CAT mice were compared (n=8-13). In S-WT there was markedly impaired diastolic function as reflected by a) decreased peak early-to-late diastolic transmitral velocity ratio (E/A, 1.36±0.06 vs. 1.96±0.10 in Y-WT or 1.89±0.06 in Y-CAT, P&lt;0.01), b) decreased early myocardial tissue velocity (E m , mm/s, 20.1±0.6 vs. 26.6±0.1 in Y-WT or 24.9±0.7 in Y-CAT, P&lt;0.01), and c) leftward/upward shift in the end-diastolic pressure volume relationship by Langendorff perfusion. Diastolic dysfunction in S-WT was associated with decreased SERCA activity (nmol/mg protein/min, 3.37±0.45 vs. 5.50±0.55 in Y-WT, P&lt;0.01) and increased oxidation of SERCA at cysteine 674 (Scores, 2.4±0.3 vs. 1.1±0.2 in Y-WT or 1.1±0.1 in Y-CAT, P&lt;0.02). Likewise, in isolated myocytes from S-WT there was slowed relaxation (+dL/dt, μ m/s, 1.35±0.07 vs. 2.68±0.17 in Y-WT, P&lt;0.01) and prolongation of Ca 2+ reuptake (Tau, ms, 46.7±0.15 vs. 35.7±0.16 in Y-WT, P&lt;0.01). In senescent mice with CAT overexpression (S-CAT) there was complete normalization of LV diastolic function (E/A, 1.97±0.12; E m , 24.9±1.4), SERCA activity (6.10±0.36 nmol/mg/min), SERCA oxidation (Score, 1.23±0.08), myocyte relaxation (+dL/dt, 2.34±0.14 μ m/s) and myocyte calcium handling (Tau, 38.3±0.08 ms). Conclusion: Age-related impairment of SERCA activity is associated with sulfonylation of cysteine 674. Myocyte-specific overexpression of CAT, which prevents aging-induced LV diastolic dysfunction and myocyte calcium dysregulation, prevents SERCA sulfonylation at cysteine 674 and restores SERCA activity, suggesting that SERCA sulfonylation plays a central role in the age-related myocyte dysfunction.
Abstract 5920: Usefulness of Late Gadolinium Enhancement as Non-invasive Arrhythmic Risk Marker in Patients with Heart Failure and Systolic Dysfunction
Authors: Alfonso Valle, Mercedes Nadal, Jordi Estornell, Nieves Martinez, Miguel Corbi, Aurelio Quesada, Victor Palanca, Rafael Romaguera, Ana Laynez, Candela Rodriguez, Rafael Paya, Francisco Ridocci-Soriano
Journal: Circulation (2008)

The identification of prognostic markers in patients with heart failure of both ischemic and non ischemic etiology is an increasing need in the era of devices therapy. Risk stratification for sudden cardiac death (SCD) remains problematic with reliance on left ventricular function which predicts total mortality rather than arrhythmic events (AE). Recently cardiac magnetic resonance was employed to predict susceptibility for malignant arrhythmias. This study sought to determine the utility of late gadolinium enhancement (LGE) to predict AE. Three hundred consecutive patients with symptomatic heart failure and systolic dysfunction of both ischemic and non ischemic cause undergoing CMR, were classified into two groups attending to the presence (n 160) or absence of LGE (n 140), and were followed prospectively during 842 days. The primary endpoint was the combined of SCD or Ventricular tachycardia (VT). 23 patients had AE (8 SCD/15 VT) during the follow-up, 19 of them presenting LGE (83%). The presence of LGE was associated to a significantly higher AE rate (11.8.% vs 2.8% p&lt; 0.001)(figure ). Compared to patients without LGE, midwall fibrosis and an ischemic pattern of LGE predicted AE. (3% vs 5% vs 14%, p= 0.001) LGE is a new non-invasive predictor of AE in patients with heart failure and systolic dysfunction. This suggest a potential role for risk stratification and better selection of patients who needs device therapy
Abstract 15284: Von Hippel Lindau Mutant Zebrafish Display Pathological Angiogenesis That is Blood Flow Dependent
Authors: Oliver Watson, Fredericus van Eeden, Timothy J Chico
Journal: Circulation (2011)

Introduction: Hypoxia drives pathological angiogenesis but the contribution of hemodynamic force in these processes is unknown. Mutations in von hippel lindau protein (vhl) upregulate hypoxic signa...
Microbiota and Host Nutrition across Plant and Animal Kingdoms
Authors: Stéphane Hacquard, Ruben Garrido-Oter, Antonio González, Stijn Spaepen, Gail Ackermann, Sarah Lebeis, Alice C. McHardy, Jeffrey L. Dangl, Rob Knight, Ruth Ley, Paul Schulze-Lefert
Journal: Cell Host & Microbe (2015)
Frequent deletion of p16INK4a/MTS1 and p15INK4b/MTS2 in pediatric acute lymphoblastic leukemia
Authors: T Okuda, SA Shurtleff, MB Valentine, SC Raimondi, DR Head, F Behm, AM Curcio- Brint, Q Liu, CH Pui, CJ Sherr
Journal: Blood (1995)
Abstract 2097: Acute Ventricular Unloading in Dogs with Chronic Heart Failure: Comparison Between Intra-Aortic Balloon Counterpulsation and Continuous Aortic Flow Augmentation
Authors: Mengjun Wang, Robert Brewer, Itamar Ilsar, Alice Jiang, Tony Viole, Marvin A Konstam, Hani N Sabbah
Journal: Circulation (2007)

Background: Continuous aortic flow augmentation (CAFA) therapy provided by the Cancion ® system (Orqis Medical, Inc.) for decompensated heart failure (HF)has been shown to effectively unload the left ventricle (LV) in dogs with chronic HF. In the present study, we compared the extent of acute LV unloading elicited by CAFA to that elicited by intra-aortic balloon counterpulsation (IABP) in normotensive dogs with HF produced by multiple sequential intracoronary microembolizations. Methods: Studies were performed in 6 dogs with HF. Each dog was studied with CAFA and with IABP. Studies were performed one week apart. For each study, therapy with CAFA or IABP was maintained for 4 hours. The Cancion system was positioned using a dual femoral approach configuration with constant pump flow of 250 ml/min thus superimposing an element of continuous flow on existing pulsatile aortic flow. In all dogs and with both devices, LV end-diastolic pressure (LVEDP), LV end-diastolic volume (EDV), LV end-systolic volume (ESV) and LV ejection fraction (EF) were measured at baseline prior to initiating therapy and were repeated at 2 hours and 4 hours after insituting CAFA or IABP. Results: Data (mean SEM) are shown in the table . Up to 4 hours of IABP had no significant effects on LVEDP, EDV, ESV or EF. In contrast, institution of CAFA for 4 hours significantly decreased LVEDP, EDV and ESV and significantly increased EF. Conclusions: In normotensive dogs with chronic HF and no epicardial coronary artery disease, acute therapy with IABP for up to 4 hours had no effect on LV unloading defined as a reduction in LV filling pressure and LV size. In the same cohort of dogs, CAFA therapy elicited marked LV unloading. These data indicate that CAFA is superior to IABP in achieving acute LV unloading in the setting of chronic HF not complicated by ongoing myocardial ischemia and/or cardiogenic shock.
Differential effects of budesonide and fluticasone propionate on bronchial epithelial barrier function
Authors: Irene Heijink, Marnix Jonker, Nick Ten Hacken, Eef Telenga, Dirkje Postma, Maarten Van den Berge
Journal: European Respiratory Journal (2014)

Rationale:  COPD patients treated with inhaled corticosteroid fluticasone propionate(FP) have an increased risk of pneumonia as compared to non-ICS treatment and budesonide (BUD). The mechanisms underlying this difference are not yet understood. We hypothesized that FP and BUD differentially affect the airway epithelial barrier in response to viral infection and/or cigarette smoke.  Methods:  We assessed the protective effect of equivalent concentrations of FP and BUD on pro-inflammatory cytokine production (IL-8, ELISA) and barrier function (electrical resistance measurements, ECIS) in the human bronchial epithelial cell line 16HBE and primary bronchial epithelial cells (PBECs) from smoking individuals upon exposure to the viral mimetic poly-(I:C) and/or cigarette smoke extract (CSE).  Results:  BUD and FP were equally effective in suppression of poly-(I:C) and/or CSE-induced IL-8 secretion in 16HBE and PBECs. Poly-(I:C) substantially decreased electrical resistance in 16HBE cells and both BUD and FP fully counteracted this effect. However, FP hardly affected 16HBE barrier dysfunction induced by CSE with/without poly-(I:C), while BUD (16 nM) provided full protection, an effect likely mediated by affecting EGFR-downstream target GSK-3β. Similarly, BUD, but not FP, significantly improved CSE-induced barrier dysfunction in PBECs.   Conclusions:  While BUD and FP both efficiently control epithelial pro-inflammatory responses and barrier function upon mimicry of viral infection  in vitro , BUD is more effective in counteracting cigarette smoke-induced barrier dysfunction, thereby reinforcing the epithelial barrier and potentially limiting access of pathogens upon cigarette smoking .
Predictors of an Inadequate Defibrillation Safety Margin at ICD Implantation
Authors: Jonathan C. Hsu, Gregory M. Marcus, Sana M. Al-Khatib, Yongfei Wang, Jeptha P. Curtis, Nitesh Sood, Matthew W. Parker, Jeffrey Kluger, Rachel Lampert, Andrea M. Russo
Journal: Journal of the American College of Cardiology (2014)
PcrV antibody prophylaxis in combination with antibiotic therapy reduces lung injury and improves survival in Pseudomonas aeruginosa infected mice
Authors: Yuanlin Song, Mark Baer, Ramya Srinivasan, Juliana Lima, Geoffrey Yarranton, Christopher Bebbington, Susan Lynch
Journal: European Respiratory Journal (2011)

The type III secretion system (TTSS) of Pseudomonas aeruginosa facilitates direct injection of cytotoxins into host cell cytoplasm. PcrV, located at the tip of the needle-like injectosome, is an essential component of this virulence system. Mab166, a murine monoclonal antibody against PcrV has demonstrated efficacy against P. aeruginosa infection resulting in increased survival and reduced lung injury in a variety of mouse models of infection. We hypothesized that administration of Mab166 prophylactically in combination with conventional antibiotics (administered subsequent to infection) could further improve survival of P. aeruginosa infected mice. Three antibiotics (ciprofloxacin, tobramycin and ceftazidime), commonly prescribed for P. aeruginosa infections were used for this study. Consistently, compared to other treatment groups, the combination of Mab166 administered with an antibiotic significantly improved survival of mice infected with three times the lethal dose (LD90) of the highly cytotoxic ExoU-secreting strain, PA103. The underlying mechanism of the anti-PcrV-tobramycin combination appears to involve a synergistic protection against lung injury and bactericidal effect in the airways, ultimately preventing bacterial dissemination to other organs.  We conclude that a combination of prophylactic Mab166 with subsequent antibiotic administration provides a new strategy against P. aeruginosa airway infection, even heavy burden of highly virulent strains are present and may represent a viable prophylactic approach for patients at high risk for P. aeruginosa infection.
Prevalance of pulmonary hypertension in chronic myeloproliferative diseases
Authors: Esen Kiyan, Gulfer Okumus, Goksen Kuran, Burak Pamukcu, Hasan Göksoy, Aysu Kiyan, Selim Yavuz, Zehra Bugra, Orhan Arseven
Journal: European Respiratory Journal (2011)

To evaluate the incidence of pulmonary hypertension (PH) in essential thrombocythemia (ET) and polycythemia Vera (PV), which are chronic myeloproliferative disorders, 70 patients (55PV+15ET), who have no co-morbidity causing PH, were prospectivelly evaluated. All patients had echocardiography done by the same cardiologist, spirometry and DLCO. Two parameters were used for PH: mean pulmonary artery pressure (PAP) calculated by Mahan formula>25 mmHg and right ventricular systolic pressure (RVSP)>35 mmHg. For the first parameter, 3 (4,3%) patients (1ET, 2PV) and for the second parameter, 4 (5.7%) patients (2ET, 2PV) had PH. Patients9 characteristics are reported in the table.   Conclusion:  When compared with the previous few studies done by small populations, PH incidence in our study was found very low. This result may be related to effective treatment (cytoreductive treatment) of myeloproliferative diseases in the majority of the patients.
The Utility of Preoperative Six-Minute-Walk Distance in Lung Transplantation
Authors: Anthony W. Castleberry, Brian R. Englum, Laurie D. Snyder, Mathias Worni, Asishana A. Osho, Brian C. Gulack, Scott M. Palmer, R. Duane Davis, Matthew G. Hartwig
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: The use of 6-minute-walk distance (6MWD) as an indicator of exercise capacity to predict postoperative survival in lung transplantation has not previously been well studied.Objectives: To evaluate the association between 6MWD and postoperative survival following lung transplantation.Methods: Adult, first time, lung-only transplantations per the United Network for Organ Sharing database from May 2005 to December 2011 were analyzed. Kaplan-Meier methods and Cox proportional hazards modeling were used to determine the association between preoperative 6MWD and post-transplant survival after adjusting for potential confounders. A receiver operating characteristic curve was used to determine the 6MWD value that provided maximal separation in 1-year mortality. A subanalysis was performed to assess the association between 6MWD and post-transplant survival by disease category.Measurements and Main Results: A total of 9,526 patients were included for analysis. The median 6MWD was 787 ft (25th–75th percentiles = 450–1,082 ft). Increasing 6MWD was associated with significantly lower overall hazard of death (P < 0.001). Continuous increase in walk distance through 1,200–1,400 ft conferred an incremental survival advantage. Although 6MWD strongly correlated with survival, the impact of a single dichotomous value to predict outcomes was limited. All disease categories demonstrated significantly longer survival with increasing 6MWD (P ≤ 0.009) except pulmonary vascular disease (P = 0.74); however, the low volume in this category (n = 312; 3.3%) may limit the ability to detect an association.Conclusions: 6MWD is significantly associated with post-transplant survival and is best incorporated into transplant evaluations on a continuous basis given limited ability of a single, dichotomous value to predict outcomes.