tbuckley/cabot-search huggingface dataset:
P191 QVA149 once daily improves exercise tolerance and lung function in patients with moderate to severe COPD: the BRIGHT study: Abstract P191 Table 1
Authors: KM Beeh, S Korn, J Beier, D Jadayel, M Henley, J Tylek, I Berhane, P D’Andrea, D Donald Banerji
Journal: Thorax (2012)

<h3>Introduction</h3> QVA149 is a novel once-daily fixed-dose combination of the long-acting β<sub>2</sub>-agonist indacaterol and the long-acting muscarinic antagonist glycopyrronium (NVA237) in development for the treatment of chronic obstructive pulmonary disease (COPD). The BRIGHT study evaluated the effects of QVA149 versus placebo and tiotropium on exercise tolerance and lung function in patients with moderate-to-severe COPD. <h3>Methods</h3> In a double-blind, double-dummy, 3-period crossover study, patients with moderate-to-severe COPD were randomised to QVA149 110/50 µg, placebo or tiotropium 18 µg once daily for 3 weeks. The primary endpoint was exercise endurance time for QVA149 versus placebo during a submaximal exercise tolerance test (SMETT) via cycle ergometry at Day 21. Dynamic inspiratory capacity (IC) at isotime during exercise, trough IC, trough FEV1 and trough forced vital capacity (FVC) were also measured. <h3>Results</h3> Eighty five patients were randomised; mean age was 62 years, mean post-bronchodilator FEV1 56% predicted. 86% patients completed the study. At Day 21, QVA149 significantly improved exercise endurance time by 59.5 seconds versus placebo (p=0.006), which was of a similar magnitude to the improvement seen with tiotropium versus placebo (66.3 seconds; p=0.002). More patients stopped exercise due to dyspnoea with placebo (43% versus 36% with both QVA149 and tiotropium) and due to muscle fatigue with QVA149 and tiotropium (44–46% versus 38% with placebo). QVA149 also produced significant and clinically meaningful improvements in trough FEV1, dynamic IC at exercise isotime, trough IC and trough FVC versus placebo and tiotropium (table). <h3>Conclusion</h3> QVA149 once daily provided significant and clinically meaningful improvements in exercise tolerance and lung function in patients with moderate-to-severe COPD. Despite superior bronchodilation demonstrated by QVA149 versus tiotropium, improvements seen in exercise endurance were similar, perhaps due to extra-pulmonary factors (muscle fatigue, ceiling effect). There were no safety concerns.
Oxidative stress is more important than acid in the pathogenesis of reflux oesophagitis in rats
Authors: T Y Oh
Journal: Gut (2001)

<h3>BACKGROUND</h3> Although antisecretory medications such as histamine type II receptor antagonists or proton pump inhibitors have been used to treat reflux oesophagitis, a considerable number of patients do not achieve complete mucosal healing or suffer from either sustained symptoms or ensuing complications, suggesting other damaging factors or impaired mucosal resistance are also involved in the pathogenesis of reflux oesophagitis. <h3>AIMS</h3> The present study was designed to evaluate oxidative stress as the major pathogenic factor of reflux oesophagitis and to determine the usefulness of antioxidants in the treatment of reflux oesophagitis. <h3>MATERIALS AND METHODS</h3> Reflux oesophagitis was induced by insertion of a 3 mm calibre ring into the duodenum, 1 cm distal to the ligament of Treitz, in Sprague-Dawley rats. <h3>RESULTS</h3> DA-9601, a novel antioxidant substance, significantly attenuated the gross and histopathological scores of reflux oesophagitis compared with those treated with ranitidine alone or reflux oesophagitis controls in a dose dependent manner. Only scattered erosions were observed in the antioxidant pretreated group but acid suppression by ranitidine was not effective in decreasing the severity of reflux oesophagitis. Significantly increased amounts of malondialdehyde (MDA), increased nuclear factor κB (NFκB) activation, and depletion of reduced glutathione (GSH) were observed in experimentally induced reflux oesophagitis. DA-9601 pretreatment attenuated the decrement in mucosal GSH levels and decreased MDA formation significantly. DA-9601 treatment caused significant reductions in activation of NFκB transcription factor, especially the p50 subunit, in accordance with the significantly higher levels of inhibitory protein of NFκB expression. <h3>CONCLUSION</h3> Reflux oesophagitis caused considerable levels of oxidative stress in the oesophageal mucosa and antioxidant treatment should be considered as supplementary therapy in the prevention or treatment of reflux oesophagitis with acid suppression.
Comparative trial of two non-sedative H1 antihistamines, terfenadine and astemizole, for hay fever.
Authors: S Shuster
Journal: Thorax (1986)

A new single breath test has been developed that measures pulmonary blood flow (Qc) and pulmonary tissue volume by using the fact that Qc is proportional to the relationship between the absorption rate of acetylene (C2H2) from the alveolar gas and the rate of change of lung volume during constant expiratory flow. To make these measurements a bag in bottle system with a rolling seal spirometer, a mass spectrometer, and a minicomputer with analogue to digital conversion have been used. Qc was compared with cardiac output measured by the thermodilution technique in 20 patients with cardiac disease; some also had mild chronic obstructive pulmonary disease. The mean (SD) resting Qc for the group was 5.27 (1.22) l/min and the cardiac output measured by thermodilution was 5.30 (1.31) l/min. The mean difference between the two estimations of cardiac output was 0.03 l and the standard deviation of this difference was 0.76 l. The Qc technique was not successful in patients with an FEV1/FVC less than 60%, but seemed to be accurate in those with higher FEV1/FVC values. Correction of Qc for the effect of venous admixture in 14 patients resulted in an average 19% overestimation of cardiac output (6.01 (2.52) l/min v 5.05 (1.64) l/min). It is concluded that cardiac output can be accurately measured in patients with cardiac or mild pulmonary disease. No correction for venous admixture due to ventilation-perfusion mismatch was necessary in these patients, presumably because the large breath used by the technique overcomes most mild ventilation-perfusion maldistribution. These findings, in addition to the non-invasive nature of the technique, suggest potential value for the measurement of cardiac output in various clinical conditions.
Autoantibodies in Heart Failure and Cardiac Dysfunction
Authors: Ziya Kaya, Christoph Leib, Hugo A. Katus
Journal: Circulation Research (2012)

Human heart failure is a disease with multifactorial causes, considerable morbidity, and high mortality. Several circulating autoantibodies, some of them being heart-specific, play a crucial role in the progression and induction of heart failure. However the precise mechanisms on how these autoantibodies perpetuate or even induce an organ specific autoimmune response are not yet fully understood. Also it is being a matter of current research to elucidate a potential pathophysiological role of the innate immune system in generating auto-reactive antibodies. In this review we will summarize the current available literature on circulating autoantibodies which are related to human heart failure. We will present clinical and animal studies that demonstrate the occurrence and pathophysiological relevance of several autoantibodies in heart failure, as well as point out biological mechanisms on molecular and cellular level. Finally the beneficial therapeutic effects of numerous clinical studies that target the humoral arm of the immune system by using either intravenous immunoglobulins and/or immunoadsorption will be critically discussed.
SIGNIFICANCE OF THE HYDROXYL GROUPS OF STEROIDS IN PROMOTING GROWTH
Authors: Charles Huggins, Elwood V. Jensen
Journal: The Journal of Experimental Medicine (1954)

The presence of a 17beta-hydroxyl group endows the simple androstane molecule with the ability to produce growth of the uterus, vagina, and prostate of the female hypophysectomized albino rat. It appears that hydrogen atoms at position 17 are of critical importance since related compounds with a ketone group at this site are inactive. Monofunctional steroids with a hydroxyl or a ketone group at position 3 likewise are devoid of activity. If a phenolic A-ring is present in monofunctional steroids the 17beta-hydroxyl group is not obligatory for growth. Proliferation of the uterus and vagina were found to follow the administration of 17-desoxyestradiol.
The Pastor and the Party of the Century
Authors: Ted Louie
Journal: JAMA (2005)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Biochemotherapy with thymosin α1, interleukin-2 and dacarbazine in patients with metastatic melanoma: Clinical and immunological effects
Authors: M Lopez, S Carpano, R Cavaliere, L Di Lauro, F Ameglio, G Vitelli, A M Frasca, P Vici, F Pignatti, M Rosselli
Journal: Annals of Oncology (1994)

DTIC and interleukin-2 (IL-2), as single agents, have a limited anti-tumor activity in patients with metastatic melanoma. Experimentally, thymosin alpha 1 (TA1) may modulate the action of IL-2. We investigated the clinical and immunological effects of a combination with these three agents.Forty-six patients with measurable metastatic melanoma were treated with DTIC 850 mg IV on day 1, TA1 2 mg s.c. on days 4 to 7, and IL-2 18 MU/m2/d by continuous intravenous infusion on days 8 to 12. Cycles were repeated every 3 weeks.Objective responses were obtained in 15 (36%) of 42 evaluable patients (CI at 95%: 22%-50%). Two patients experienced complete responses, and stable disease was observed in five. The median time to progression was 5.5 months and median survival was 11 months. Side effects were predominantly caused by IL-2. Treatment was tolerated reasonably well, and there was no overlapping toxicity or interference between chemotherapy and biotherapy. Baseline sCD4 levels seem to correlate to tumor burden. Patients benefiting from treatment had lower sCD4 and higher sCD8 than did progressing patients.The combination of DTIC + TA1 + IL-2 is active in the treatment of advanced melanoma, with acceptable toxicity. However, even more active regimens are needed, and the interactions between thymic hormones and cytokines should be further explored.
Consensus exercise on domains in psoriatic arthritis
Authors: D D Gladman
Journal: Annals of the Rheumatic Diseases (2005)

Recent studies with biological therapy in psoriatic arthritis (PsA) have highlighted the need for validated and widely accepted assessment tools and outcome measures for this disease. A Delphi process was established through the CASPAR group where domains for assessment of PsA in clinical trials, longitudinal studies, and rehabilitation were identified. Although the process reduced the list of possible domains to approximately 12, it was not able to detect those that would be most important. Moreover, skin assessment was left out. A further study through the GRAPPA group subsequently identified the following domains: inflammation (peripheral joints, axial skeleton, physician global assessment), other features (dactylitis, enthesitis), skin and nails, imaging, biomarkers, and patient derived indices (pain, quality of life, itch, function), as important in the assessment of patients with PsA. These domains require further refining, and instruments to measure the items need to be developed.
Shorter treatment duration for selected patients with multidrug-resistant tuberculosis
Authors: E.C.C. Leung, W.W. Yew, C.C. Leung, W.M. Leung, C.M. Tam
Journal: European Respiratory Journal (2011)

To the Editors:

Tuberculosis (TB) is still an infectious disease of public health importance today [1]. Of particular concern is the occurrence of multidrug-resistant (MDR)-TB with resistance to at least isoniazid and rifampicin, and extensively drug-resistant (XDR)-TB with additional resistance to any fluoroquinolone and at least one of the second-line injectable drugs, including kanamycin, amikacin and capreomycin. MDR- and XDR-TB need prolonged treatment duration, from 18 to 24 months after sputum culture conversion, as recommended by the World Health Organization (WHO) [2]. A prolonged duration of treatment may lead to poor adherence, higher cost and undue toxicity. In our previous studies, we found that the use of ofloxacin/levofloxacin-containing regimens had a favourable effect on MDR-TB outcome [3, 4]. Our studies also suggested that shorter treatment duration (mean duration 14 months) might be feasible in selected MDR-TB patients. Based on this finding, the treatment duration of selected MDR-TB patients under programmatic management in Hong Kong was changed from the rigid enforcement of ≥18 months after sputum conversion to an individualised duration tailored by the physician's judgement. The determinants favouring longer treatment included extensive drug resistance, delayed sputum culture conversion, greater extent of radiographic disease (including cavities), presence of diabetes or silicosis, and extrapulmonary disease. Out of these factors, the extent of drug resistance was the most important. Ofloxacin-resistant MDR-TB was arbitrarily given a prolonged treatment based on our previous studies [3, 4]. Despite a relatively high TB incidence (76 cases per 100,000 population in 2009), both TB and MDR-TB rates are actually decreasing under the local TB control programme [5]. Therefore, we conducted a retrospective evaluation of the long-term outcomes of our MDR-TB patients, focusing on the factors affecting the efficacy and relapse rate of a shorter treatment duration. …
IDH1 mutant malignant astrocytomas are more amenable to surgical resection and have a survival benefit associated with maximal surgical resection
Authors: Jason Beiko, Dima Suki, Kenneth R. Hess, Benjamin D. Fox, Vincent Cheung, Matthew Cabral, Nicole Shonka, Mark R. Gilbert, Raymond Sawaya, Sujit S. Prabhu, Jeffrey Weinberg, Frederick F. Lang, Kenneth D. Aldape, Erik P. Sulman, Ganesh Rao, Ian E. McCutcheon, Daniel P. Cahill
Journal: Neuro-Oncology (2013)

IDH1 gene mutations identify gliomas with a distinct molecular evolutionary origin. We sought to determine the impact of surgical resection on survival after controlling for IDH1 status in malignant astrocytomas—World Health Organization grade III anaplastic astrocytomas and grade IV glioblastoma. Clinical parameters including volumetric assessment of preoperative and postoperative MRI were recorded prospectively on 335 malignant astrocytoma patients: n = 128 anaplastic astrocytomas and n = 207 glioblastoma. IDH1 status was assessed by sequencing and immunohistochemistry. IDH1 mutation was independently associated with complete resection of enhancing disease (93% complete resections among mutants vs 67% among wild-type, P < .001), indicating IDH1 mutant gliomas were more amenable to resection. The impact of residual tumor on survival differed between IDH1 wild-type and mutant tumors. Complete resection of enhancing disease among IDH1 wild-type tumors was associated with a median survival of 19.6 months versus 10.7 months for incomplete resection; however, no survival benefit was observed in association with further resection of nonenhancing disease (minimization of total tumor volume). In contrast, IDH1 mutants displayed an additional survival benefit associated with maximal resection of total tumor volume (median survival 9.75 y for >5 cc residual vs not reached for <5 cc, P = .025). The survival benefit associated with surgical resection differs based on IDH1 genotype in malignant astrocytic gliomas. Therapeutic benefit from maximal surgical resection, including both enhancing and nonenhancing tumor, may contribute to the better prognosis observed in the IDH1 mutant subgroup. Thus, individualized surgical strategies for malignant astrocytoma may be considered based on IDH1 status.
Notch signaling inhibits hepatocellular carcinoma following inactivation of the RB pathway
Authors: Patrick Viatour, Ursula Ehmer, Louis A. Saddic, Craig Dorrell, Jesper B. Andersen, Chenwei Lin, Anne-Flore Zmoos, Pawel K. Mazur, Bethany E. Schaffer, Austin Ostermeier, Hannes Vogel, Karl G. Sylvester, Snorri S. Thorgeirsson, Markus Grompe, Julien Sage
Journal: The Journal of Experimental Medicine (2011)

Hepatocellular carcinoma (HCC) is the third cancer killer worldwide with &amp;gt;600,000 deaths every year. Although the major risk factors are known, therapeutic options in patients remain limited in part because of our incomplete understanding of the cellular and molecular mechanisms influencing HCC development. Evidence indicates that the retinoblastoma (RB) pathway is functionally inactivated in most cases of HCC by genetic, epigenetic, and/or viral mechanisms. To investigate the functional relevance of this observation, we inactivated the RB pathway in the liver of adult mice by deleting the three members of the Rb (Rb1) gene family: Rb, p107, and p130. Rb family triple knockout mice develop liver tumors with histopathological features and gene expression profiles similar to human HCC. In this mouse model, cancer initiation is associated with the specific expansion of populations of liver stem/progenitor cells, indicating that the RB pathway may prevent HCC development by maintaining the quiescence of adult liver progenitor cells. In addition, we show that during tumor progression, activation of the Notch pathway via E2F transcription factors serves as a negative feedback mechanism to slow HCC growth. The level of Notch activity is also able to predict survival of HCC patients, suggesting novel means to diagnose and treat HCC.
Patients' Global Ratings of Their Health Care Are Not Associated with the Technical Quality of Their Care
Authors: John T. Chang, Ron D. Hays, Paul G. Shekelle, Catherine H. MacLean, David H. Solomon, David B. Reuben, Carol P. Roth, Caren J. Kamberg, John Adams, Roy T. Young, Neil S. Wenger
Journal: Annals of Internal Medicine (2006)

Background: Patient global ratings of care are commonly used to assess health care. However, the extent to which these assessments of care are related to the technical quality of care received is not well understood. Objective: To investigate the relationship between patient-reported global ratings of health care and the quality of providers' communication and technical quality of care. Design: Observational cohort study. Setting: 2 managed care organizations. Patients: Vulnerable older patients identified by brief interviews of a random sample of community-dwelling adults 65 years of age or older who received care in 2 managed care organizations during a 13-month period. Measurements: Survey questions from the second stage of the Consumer Assessment of Healthcare Providers and Systems program were used to determine patients' global rating of health care and provider communication. A set of 236 quality indicators, defined by the Assessing Care of Vulnerable Elders project, were used to measure technical quality of care given for 22 clinical conditions; 207 quality indicators were evaluated by using data from chart abstraction or patient interview. Results: Data on the global rating item, communication scale, and technical quality of care score were available for 236 vulnerable older patients. In a multivariate logistic regression model that included patient and clinical factors, better communication was associated with higher global ratings of health care. Technical quality of care was not significantly associated with the global rating of care. Limitations: Findings were limited to vulnerable elders who were enrolled in managed care organizations and may not be generalizable to other age groups or types of insurance coverage. Conclusions: Vulnerable elders' global ratings of care should not be used as a marker of technical quality of care. Assessments of quality of care should include both patient evaluations and independent assessments of technical quality.
IL-4, IFN-gamma and TNF-alpha levels in serum of patients with COPD, bronchial asthma and GERD
Authors: Kirill Sysoev
Journal: European Respiratory Journal (2012)

Gastroesophageal reflux disease (GERD) is tightly linked to bronchial asthma and COPD. In our study we evaluated serum of 54 patients. Diagnoses was as follows: asthma (n=14), COPD (n=12), GERD (n=20), asthma and GERD (n=8). Serum of 19 volunteers was studied as a control group. IL-4, IFN-gamma and TNF-alpha levels were detected by ELISA. All patients underwent upper gastrointestinal endoscopy and spirometry. For statistics nonparametric method of Kruskal-Wallis and Spearman9s correlation were used. Results. The IL-4 and IFN-gamma levels in all groups of patients were significantly higher than control (p=2.5E-09 and 1.76E-09 respectively). Meanwhile TNF-alpha values in patients cohorts was lower than in control group (p=0.007). Patients were divided into three groups according to endoscopy: (i) no symptoms (n=6), (ii) chronic gastritis (n=27), and (iii) reflux esophagitis (n=21). The level of IFN-gamma was lowest in no symptoms group (91.6±41.9 pg/mL), intermediate in gastritis patients (204.2±255.8 pg/mL), and highest in reflux eosophagitis group (404.8±455.7 pg/mL) — p=0.01. IFN-gamma/IL-4 ratio had similar dynamics (p=0.01). TNF-alpha value was maximal in reflux esophagitis group (p=0.0004). We investigated cytokines values depending on severity of respiratory failure. In patients with no respiratory failure level of IL-4 was minimal, stage 1 patients had medium elevation of IL-4 value, and in patients with stage 2 of RF level of cytokine was maximal (p=0.001). Conclusion. In our study IL-4 exhibited a significant role in the severity of respiratory disorders, whereas IFN-gamma and TNF-alpha were determined degree of damage to the gastrointestinal tract.