tbuckley/cabot-search huggingface dataset:
When should we use inhaled steroids in 'asthmatic' infants?
Authors: C Church
Journal: Thorax (2006)

▴ Bisgaard H, Hermansen MN, Loland L, et al. Intermittent inhaled corticosteroids in infants with episodic wheezing. N Engl J Med2006;354:1998–2005[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] It is unclear when to treat wheezy infants with inhaled corticosteroids. In this single centre, prospective, double blind, randomised, placebo controlled trial, the authors hypothesised that the development of asthma in infants is predated by episodes of wheezing … [1]: {openurl}?query=rft.jtitle%253DNew%2BEngland%2BJournal%2Bof%2BMedicine%26rft.stitle%253DNEJM%26rft.aulast%253DBisgaard%26rft.auinit1%253DH.%26rft.volume%253D354%26rft.issue%253D19%26rft.spage%253D1998%26rft.epage%253D2005%26rft.atitle%253DIntermittent%2Binhaled%2Bcorticosteroids%2Bin%2Binfants%2Bwith%2Bepisodic%2Bwheezing.%26rft_id%253Dinfo%253Adoi%252F10.1056%252FNEJMoa054692%26rft_id%253Dinfo%253Apmid%252F16687712%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1056/NEJMoa054692&link_type=DOI [3]: /lookup/external-ref?access_num=16687712&link_type=MED&atom=%2Fthoraxjnl%2F61%2F8%2F677.atom [4]: /lookup/external-ref?access_num=000237413100004&link_type=ISI
1151 GENETIC VARIANTS AT ITPA THE LOCUS PROTECTS AGAINST RIBAVIRIN-INDUCED HEMOLYTIC ANEMIA – A REPLICATION STUDY IN A SCANDINAVIAN HCV G2/G3 COHORT
Authors: A. Eskesen, E. Melum, A. Moghaddam, K. Bjøro, H. Verbaan, H. Ring-Larsen, O. Dalgard
Journal: Journal of Hepatology (2011)
Study of the Hurler syndrome using cell culture: definition of the biochemical phenotype and the effect of ascorbic acid on the mutant cell
Authors: Irwin A. Schafer, Julia C. Sullivan, Jiri Svejcar, Jorge Kofoed, William Van B. Robertson
Journal: Journal of Clinical Investigation (1968)

Fibroblasts from patients with Hurler syndrome retain a distinctive biochemical phenotype when grown in culture which is characterized by increased synthesis of both nonsulfated and sulfated glycosaminoglycans. Ascorbic acid reinforces the phenotypic expression of the biochemical abnormality, producing not only increased synthesis of sulfated glycosaminoglycans, but selective retention of sulfated glycosaminoglycans within the cell. Although the synthesis of nonsulfated glycosaminoglycans is also increased, these compounds, particularly hyaluronic acid are not retained by the cell but are secreted into the medium. Analyses of urine from patients with Hurler syndrome show increased absolute concentrations of nonsulfated glycosaminoglycans in addition to the expected increase in sulfated glycosaminoglycans. This indicates that the biochemical phenotype as defined in cell culture is not an artifact of the experimental model but reflects the biochemical defect in the patient. Redefinition of the biochemical defect to include nonsulfated as well as sulfated glycosaminoglycans contradicts explanations of this disease which are based on a single structural gene mutation.
Approaches to Uremia
Authors: Timothy W. Meyer, Thomas H. Hostetter
Journal: Journal of the American Society of Nephrology (2014)

The development of dialysis was a dramatic step forward in medicine, allowing people who would soon have died because of lack of kidney function to remain alive for years. We have since found, however, that the “artificial kidney” does not live up fully to its name. Dialysis keeps patients alive but not well. Part of the residual illness that dialysis patients experience is caused by retained waste solutes that dialysis does not remove as well as native kidney function does. New means are available to identify these toxic solutes, about which we currently know remarkably little, and knowledge of these solutes would help us to improve therapy. This review summarizes our current knowledge of toxic solutes and highlights methods being explored to identify additional toxic solutes and to enhance the clearance of these solutes to improve patient outcomes.
Trimetazidine inhibits pressure overload-induced cardiac fibrosis through NADPH oxidase–ROS–CTGF pathway
Authors: Xuehui Liu, Yingli Gai, Fei Liu, Wei Gao, Youyi Zhang, Ming Xu, Zhaoping Li
Journal: Cardiovascular Research (2010)

Cardiac fibrosis contributes to the transition from compensated ventricular hypertrophy to heart failure, which can be promoted by connective tissue growth factor (CTGF). Trimetazidine (TMZ), an anti-angina drug, also has benefits in non-ischaemic heart disease. We wondered whether TMZ has an effect on cardiac fibrosis from pressure overload by downregulating CTGF.Male Sprague-Dawley rats underwent transverse aortic constriction (TAC) or sham operation and then after 20 weeks were assigned to receive TMZ or saline for another 5 weeks. TMZ significantly inhibited collagen accumulation, CTGF expression, and reactive oxygen species (ROS) production induced by TAC. Furthermore, the effects of TMZ on ROS, the upstream signal of CTGF synthesis signal transduction, were evaluated in cardiac fibroblasts. The result showed that the ROS level was reduced by TMZ on stimulation with angiotensin II. Additionally, the NADPH oxidase activity was ameliorated with TMZ by the regulation of translocation of its subunit Rac1.TMZ effectively inhibits myocardial fibrosis, perhaps through the NADPH oxidase-ROS-CTGF signalling pathway. Our findings may be used to provide new clues for the potential function of TMZ in pressure overload-induced myocardial fibrosis.
Results of the Fludarabine and Cyclophosphamide Combination Regimen in Chronic Lymphocytic Leukemia
Authors: Susan M. O’Brien, Hagop M. Kantarjian, Jorge Cortes, Miloslav Beran, Charles A. Koller, Francis J. Giles, Susan Lerner, Michael Keating
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To assess the efficacy of combination therapy with fludarabine and cyclophosphamide in patients with chronic lymphocytic leukemia (CLL) based on data suggesting in vitro synergistic activity of the two agents. PATIENTS AND METHODS: A total of 128 patients with CLL were treated with fludarabine 30 mg/m 2 intravenously daily for 3 days and cyclophosphamide at either 500 mg/m 2 daily for 3 days (n = 11), 350 mg/m 2 /d for 3 days (n = 26), or 300 mg/m 2 daily for 3 days (n = 91). The cyclophosphamide dose was decreased because of myelosuppression in the early part of the study. Patients were divided into four groups based on the expectation for response to single-agent fludarabine, including previously untreated patients, patients previously treated with alkylating agents, patients successfully treated with alkylating agents and fludarabine but relapsing, and patients refractory to fludarabine with or without alkylating agents. RESULTS: Fludarabine and cyclophosphamide produced ≥ 80% response rates in all patients not refractory to fludarabine at the start of therapy as well as a 38% response rate in patients who were refractory to fludarabine. The complete remission (CR) rate was 35% in previously untreated patients, which was not significantly different from the CR rate in historical control patients treated with single-agent fludarabine. However, residual disease assessed by flow cytometry occurred in only 8% of previously untreated patients achieving CR, and median time to progression has not been reached after a median follow-up of 41 months. The main complication of therapy was related to myelosuppression and infection. Neutropenia to less than 500 × 10 9 /L was noted in 48% of patients who received cyclophosphamide 300 mg/m 2 . Pneumonia or sepsis occurred in 25% of patients, and fever of unknown origin occurred in another 25%. Pneumonia or sepsis were significantly more frequent in patients who were refractory to fludarabine at the start of combination chemotherapy. CONCLUSION: Fludarabine and cyclophosphamide seem to have a significant advantage over single-agent fludarabine in the salvage setting. Although the CR rate was not increased in previously untreated patients, residual disease detected by flow cytometry was rare and remission durations seemed to be prolonged in this subset. Myelosuppression and infection remain the most significant complications of therapy in CLL.
Change in respiratory symptoms in young adults as they age: European community respiratory health survey 3 (ECRHS 3)
Authors: Deborah Jarvis, Roger Newson, Peter Burney
Journal: European Respiratory Journal (2013)

Aim:  To describe change in prevalence of asthma/asthma-like symptoms in European adults over 20 years.  Method:  In 1991/2, research centres sent a questionnaire to community based samples of adults (20-44yrs) asking about asthma symptoms (ECRHS1). A random sample of responders had clinic-based assessment. In 27 centres (12 countries) these intensively studied adults completed the same postal survey in 2000/2 & 2010/2 (ECRHS 2 & 3). Absolute change in symptoms from ECRHS 1 to 3 was estimated from logistic generalized estimating equations. Inverse propensity weights (for sex, age, smoking & symptoms at ECRHS1) were used to adjust for non-response.  Results:  Overall, 60.9% (8373/13747) of eligible adults took part in ECRHS3. Response was higher in women, older adults, non-smokers & those without wheeze in ECRHS1. Over the 20 yr period, the prevalence of symptoms fell or changed little but use of treatment for asthma increased.  This broad pattern was seen in a) most centres b) the first, and the second, 10yrs of follow-up c) men and women d) younger and older participants.  Conclusion:  In young adults followed from 1992-2012 there was a marked increase in the use of asthma treatment, with a smaller reduction in wheeze and less marked changes in other symptoms.
Inhibition of Mitochondrial Permeability Transition Pore Opening by Ischemic Preconditioning Is Probably Mediated by Reduction of Oxidative Stress Rather Than Mitochondrial Protein Phosphorylation
Authors: Samantha J. Clarke, Igor Khaliulin, Manika Das, Joanne E. Parker, Kate J. Heesom, Andrew P. Halestrap
Journal: Circulation Research (2008)

Inhibition of mitochondrial permeability transition pore (MPTP) opening at reperfusion is critical for cardioprotection by ischemic preconditioning (IP). Some studies have implicated mitochondrial protein phosphorylation in this effect. Here we confirm that mitochondria rapidly isolated from preischemic control and IP hearts show no significant difference in calcium-mediated MPTP opening, whereas IP inhibits MPTP opening in mitochondria isolated from IP hearts following 30 minutes of global normothermic ischemia or 3 minutes of reperfusion. Analysis of protein phosphorylation in density-gradient purified mitochondria was performed using both 2D and 1D electrophoresis, with detection of phosphoproteins using Pro-Q Diamond or phospho-amino-specific antibodies. Several phosphoproteins were detected, including voltage-dependent anion channels isoforms 1 and 2, but none showed significant IP-mediated changes either before ischemia or during ischemia and reperfusion, and neither Western blotting nor 2D fluorescence difference gel electrophoresis detected translocation of protein kinase C (α, ε, or δ isoforms), glycogen synthase kinase 3β, or Akt to the mitochondria following IP. In freeze-clamped hearts, changes in phosphorylation of GSK3β, Akt, and AMP-activated protein kinase were detected following ischemia and reperfusion but no IP-mediated changes correlated with MPTP inhibition or cardioprotection. However, measurement of mitochondrial protein carbonylation, a surrogate marker for oxidative stress, suggested that a reduction in mitochondrial oxidative stress at the end of ischemia and during reperfusion may account for IP-mediated inhibition of MPTP. The signaling pathways mediating this effect and maintaining it during reperfusion are discussed.
Role of Xanthine Oxidase in Passive Heymann Nephritis in Rats
Authors: WILFRIED GWINNER, JENS PLASGER, RALF P. BRANDES, BIRGIT KUBAT, MATTHIAS SCHULZE, HEINZ REGELE, DONTSCHO KERJASCHKI, CHRISTOPH J. OLBRICHT, KARL-MARTIN KOCH
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Passive Heymann nephritis (PHN) in rats is a model of human membranous nephropathy characterized by formation of subepithelial immune deposits in the glomerular capillary wall and complement activation. Oxygen radicals have been implicated in the subsequent glomerular damage which leads to proteinuria. This study examines the involvement of xanthine oxidase in this process. Xanthine oxidase activity was increased nearly twofold in glomeruli isolated 1 and 12 d after induction of PHN, and this was associated with increased glomerular superoxide anion generation. Analysis of glomerular samples by Northern and Western blotting revealed no quantitative changes in xanthine oxidoreductase expression in PHN, suggesting conversion of xanthine dehydrogenase to the oxidase form as the cause of increased activity. Treatment of rats with tungsten, an inhibitor of xanthine oxidase, before induction of PHN resulted in a marked decrease in glomerular xanthine oxidase activity and superoxide anion generation, and decreased proteinuria by 80% (day 12: 423 ± 245 mg/d in PHN versus 78 ± 53 mg/d in tungsten-treated PHN animals, P &lt; 0.01). These findings point to a pivotal role of xanthine oxidase in the pathophysiology of PHN and could be of importance in the therapy of human membranous nephropathy.
Hemodynamic correlates of right ventricular afterload and pulmonary artery pulsatility under treatment with prostacyclin: Retrospective analysis of changes from baseline in pulmonary arterial hypertension
Authors: Christian Gerges, Mario Gerges, Yi Zhou, Diana Lam, Marie Lang, Irene Lang
Journal: European Respiratory Journal (2013)

PURPOSE: Survival in pulmonary arterial hypertension (PAH) is significantly dependent on right ventricular (RV) function. We characterized the change from baseline in hemodynamic correlates of RV afterload that reflects the arterial load to steady flow (pulmonary vascular resistance [PVR]) and parameters of oscillatory load, including pulmonary arterial compliance (PAC) and pulmonary valve resistance (ZVA).  METHODS: Parameters of RV afterload were analyzed in a prospective data base of 933 PAH patients receiving treprostinil or placebo.  RESULTS: Within 12 weeks of treatment parameters of oscillatory load did not change, while PVR was significantly reduced in patients on treprostinil compared to placebo (Mean, [95%C.I.]: -2.6WU [-4.2, -1.0]). ROC analysis revealed that PVR has to be reduced by at least 3WU to achieve an improvement in ZVA, (area under the curve [AUC]: 0.84), whereas an increase in PAC is already reached after a reduction of 1WU (AUC: 0.90). However, only baseline PVR (p  CONCLUSION: PVR is the key steady flow parameter that is changed under treatment with treprostinil, while parameters of pulsatility did not change significantly over 12 weeks. Baseline PVR (p
A NEW METHOD OF STAINING SKIN AND HAIRS FOR THE DETECTION OF FUNGI.
Authors: H. LEIGHTON KESTEVEN
Journal: British Journal of Dermatology (1937)

Journal Article A NEW METHOD OF STAINING SKIN AND HAIRS FOR THE DETECTION OF FUNGI. Get access H. LEIGHTON KESTEVEN, M.D., D.Sc H. LEIGHTON KESTEVEN, M.D., D.Sc Sydney, N.S.W., Australia Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 49, Issue 11, 1 November 1937, Pages 500–501, https://doi.org/10.1111/j.1365-2133.1937.tb11666.x Published: 01 November 1937
Sleep Disturbances in the Vietnam Generation: Findings From a Nationally Representative Sample of Male Vietnam Veterans
Authors: Thomas C. Neylan, Charles R. Marmar, Thomas J. Metzler, Daniel S. Weiss, Douglas F. Zatzick, Kevin L. Delucchi, Roger M. Wu, Frank B. Schoenfeld
Journal: American Journal of Psychiatry (1998)

OBJECTIVE: This study analyzed questionnaire items that address complaints about sleep from the National Vietnam Veterans Readjustment Study, a nationally representative sample of the 3.1 million men and women who served in Vietnam. This study compared the frequency of nightmares and difficulties with sleep onset and sleep maintenance in male Vietnam theater veterans with male Vietnam era veteran and male civilian comparison subjects. It focused on the role of combat exposure, nonsleep posttraumatic stress disorder (PTSD) symptoms, comorbid psychiatric and medical disorder, and substance abuse in accounting for different domains of sleep disturbance. METHOD: The authors undertook an archival analysis of the National Vietnam Veterans Readjustment Study database using correlations and linear statistical models. RESULTS: Frequent nightmares were found exclusively in subjects diagnosed with current PTSD at the time of the survey (15.0%). In the sample of veterans who served in Vietnam (N=1,167), combat exposure was strongly correlated with frequency of nightmares, moderately correlated with sleep onset insomnia, and weakly correlated with disrupted sleep maintenance. A hierarchical multiple regression analysis showed that in Vietnam theater veterans, 57% of the variance in the frequency of nightmares was accounted for by war zone exposure and non-sleep-related PTSD symptoms. Alcohol abuse, chronic medical illnesses, panic disorder, major depression, and mania did not predict the frequency of nightmares after control for nonsleep PTSD symptoms. CONCLUSIONS: Frequent nightmares appear to be virtually specific for PTSD. The nightmare is the domain of sleep disturbance most related to exposure to war zone traumatic stress. (Am J Psychiatry 1998; 155:929–933)
An 87-Year-Old Woman Taking a Benzodiazepine
Authors: Carl Salzman
Journal: JAMA (1999)

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Salbutamol infusion worsens outcomes in ARDS
Authors: Osita Okafor
Journal: Thorax (2012)

Salbutamol infusion worsens outcomes in ARDSSalbutamol infusion has previously been shown to significantly reduce extravascular lung water in mechanically ventilated patients with acute respiratory distress syndrome (ARDS).This double-blind randomised placebo-controlled study investigated the effects of early salbutamol infusion on the clinical outcome of patients with ARDS.The authors recruited a total of 326 patients from 46 UK intensive care units and randomly assigned them to receive either intravenous salbutamol or placebo for 7 days.Exclusion criteria included patients requiring continuous or regular aerosolized b 2 agonists and those receiving b-adrenergic antagonists.All other treatment measures were carried out according to local practice.The trial was terminated early due to safety concerns.When compared with those in the placebo arm, patients receiving continuous salbutamol infusion demonstrated significantly higher mortality rates at 28 days (34% vs 23%, RR 1.47, 95% CI 1.03 to 2.08).There was also a trend towards increased adverse rates necessitating drug withdrawal, including tachycardia (14% vs 1%), arrhythmias (9% vs 2%) and lactic acidosis (6% vs <1%).This effect maintained statistical significance even after adjustment for age, cause, PaO 2 /FiO 2 ratio and sex.Secondary outcome measures, including organ failure-free days and ventilator-free days, were also adversely affected by salbutamol infusion.In conclusion, the results suggest that salbutamol infusion in patients with ARDS leads to detrimental outcomes.The drug was poorly tolerated by patients, resulting in an increased incidence of drug side effects, serious adverse effects or death.Routine use of b 2 agonist therapy in ARDS cannot be recommended.
Comparative Effectiveness of Diagnostic Testing Strategies in Emergency Department Patients With Chest Pain
Authors: Andrew J. Foy, Guodong Liu, William R. Davidson, Christopher Sciamanna, Douglas L. Leslie
Journal: JAMA Internal Medicine (2015)

Patients presenting to the emergency department (ED) with chest pain whose evaluation for ischemia demonstrates no abnormalities receive further functional or anatomical studies for coronary artery disease; however, comparative evidence for the various strategies is lacking and multiple testing options exist.To compare chest pain evaluation pathways based on their association with downstream testing, interventions, and outcomes for patients in EDs.Retrospective analysis of health insurance claims data for a national sample of privately insured patients from January 1 to December 31, 2011. Individuals with a primary or secondary diagnosis of chest pain in the ED were selected and classified into 1 of 5 testing strategies: no noninvasive testing, exercise electrocardiography, stress echocardiography, myocardial perfusion scintigraphy, or coronary computed tomography angiography.The proportion of patients in each group who received a cardiac catheterization, coronary revascularization procedure, or future noninvasive test as well as those who were hospitalized for an acute myocardial infarction (MI) during 7 and 190 days of follow-up.In 2011, there were 693 212 ED visits with a primary or secondary diagnosis of chest pain, accounting for 9.2% of all ED encounters. After application of the inclusion and exclusion criteria, 421 774 patients were included in the final analysis; 293 788 individuals did not receive an initial noninvasive test and 127 986 did, representing 1.7% of all ED encounters. Overall, the percentage of patients hospitalized with an MI was very low during both 7 and 190 days of follow-up (0.11% and 0.33%, respectively). Patients who did not undergo initial noninvasive testing were no more likely to experience an MI than were those who did receive testing. Compared with no testing, exercise electrocardiography, myocardial perfusion scintigraphy, and coronary computed tomography angiography were associated with significantly higher odds of cardiac catheterization and revascularization procedures without a concomitant improvement in the odds of experiencing an MI.Patients with chest pain evaluated in the ED who do not have an MI are at very low risk of experiencing an MI during short- and longer-term follow-up in a cohort of privately insured patients. This low risk does not appear to be affected by the initial testing strategy. Deferral of early noninvasive testing appears to be reasonable.
Group support psychotherapy for depression treatment in people with HIV/AIDS in northern Uganda: a single-centre randomised controlled trial
Authors: Etheldreda Nakimuli-Mpungu, Kizito Wamala, James Okello, Stephen Alderman, Raymond Odokonyero, Ramin Mojtabai, Edward J Mills, Steve Kanters, Jean B Nachega, Seggane Musisi
Journal: The Lancet HIV (2015)