tbuckley/cabot-search huggingface dataset:
Nebulized Budesonide for Children with Mild-to-Moderate Croup
Authors: Terry P. Klassen, Mark E. Feldman, Lise K. Watters, Teresa Sutcliffe, Peter C. Rowe
Journal: New England Journal of Medicine (1994)

Although recent evidence has strongly supported the use of glucocorticoid therapy in children hospitalized with croup, the benefit of this therapy in children with less severe croup has not been documented. This randomized, double-blind trial compared a nebulized glucocorticoid, budesonide, with placebo in outpatients with mild-to-moderate croup.
Effect of Aminophylline on Respiratory-Center Sensitivity in Cheyne-Stokes Respiration and in Pulmonary Emphysema
Authors: A. R. Dowell, A. Heyman, H. O. Sieker, K. Tripathy
Journal: New England Journal of Medicine (1965)

ALTHOUGH aminophylline has been known for many years to abolish Cheyne-Stokes respiration and restore a normal breathing pattern, the mechanism of this phenomenon is poorly understood. This agent acts either by stimulating the respiratory center directly or by increasing its sensitivity to carbon dioxide.1 , 2 Recent studies of aminophylline in patients with Cheyne-Stokes respiration associated with congestive heart failure have shown that the agent reduces blood flow and oxygen consumption of the brain.3 The elimination of periodic breathing in these subjects was thought to be due to the decrease of cerebral circulation, with subsequent elevation of carbon dioxide tension in the . . .
ET-19 * A PHASE 1 STUDY EVALUATING ABT-414 WITH TEMOZOLOMIDE (TMZ) OR CONCURRENT RADIOTHERAPY (RT) AND TMZ IN GLIOBLASTOMA (GBM)
Authors: H. K. Gan, L. Fichtel, A. B. Lassman, R. Merrell, M. van den Bent, P. Kumthekar, A. M. Scott, M. Pedersen, E. Gomez, J. Fischer, W. Ames, H. Xiong, M. Dudley, W. Munasinghe, L. Roberts-Rapp, P. Ansell, K. Holen, D. A. Reardon
Journal: Neuro-Oncology (2014)

BACKGROUND: Standard therapies have little effect on the poor survival rates of GBM. Abnormal epidermal growth factor receptor (EGFR) expression and signaling are common in GBM. ABT-414 is a unique antibody-drug conjugate, with a toxic payload (MMAF) targeted to active EGFR or mutant EGFRvIII, that has demonstrated high antitumor activity in preclinical GBM tumor models. METHODS: Objectives were to evaluate the safety, pharmacokinetics (PK), and the maximum tolerated dose (MTD) of ABT-414 when administered with TMZ (recurrent or unresectable GBM, Arm B) or concurrent RT and TMZ (newly diagnosed GBM, Arm A). Adverse events (AEs), PK parameters, objective response (RANO), and tumor tissue EGFR biomarkers were assessed. Dose escalation was determined by the continual reassessment method (CRM). RESULTS: As of April, 2014, 22/21 pts were treated in Arm A/B. Common treatment-emergent AEs included fatigue(n= 11/ 6, Arm A/B); blurred vision(n = 10/9); AST increase(n = 9, Arm A); and nausea(n = 7/7) Grade 3/4 AEs (≥ 2 pts) included lymphopenia(n = 3); eye toxicity(n = 3); brain edema, ALT, AST(n = 2 each) in Arm A and keratitis(n = 2) in Arm B. Doses from 0.5-3.2mg/kg have been explored. Dose limiting toxicities primarily affecting the eye (keratitis) and liver occurred at multiple doses. The CRM has predicted 2.4mg/kg as the MTD in Arm A and 1.25mg/kg in Arm B. Patient samples are being evaluated for EGFR expression, amplification and EGFRvIII status. Efficacy endpoints are not yet mature in Arm A, but 4 patients in Arm B have best responses of 3 PRs and 1 CR. CONCLUSIONS: PK and safety data support doses of 2.4 and 1.25mg/kg as the predicted MTD in Arms A and B. Preliminary safety data demonstrate liver and eye toxicities in Arm A and primarily eye toxicities in Arm B. Updated biomarker results as they correlate with efficacy will be reported. Phase 2 studies assessing ABT-414 in GBM are planned.
Abstract 34: Inhibitory effects of betulinic acid isolated from <i>Nelumbo nucifera</i> (Lotus) on breast cancer-mediated bone destruction
Authors: Se-Young Park, Kwang-Kyun Park, Won-Yoon Chung
Journal: Cancer Research (2012)

Abstract Most of cancer patients die, not because of the tumor in the primary site, but because of spreading to other site. In particular, bone metastasis is relatively common in patients with breast, prostate, and lung cancer. Many breast cancer patients suffer from bone metastasis with bone pain and pathological fractures. These metastases are predominantly osteolytic and develop when tumor cells interact with bone. Tumor and bone interact in a vicious cycle, where tumor-secreted factors stimulate bone cells, which in turn release growth factors and cytokines that act back on the tumor cells. Within the vicious cycle are many potential therapeutic targets for treatment of bone metastatic disease. Nelumbo nucifera (Lotus) has been known as a medicinal herb for treatment of cough, fever and hyperdipsia. Betulinic acid (BA) is a naturally occurring triterpenoid present in lotus. In this study, we found that BA reduced mRNA expressions of osteolytic factors in MDA-MB-231 human metastatic breast cancer cells. In particular, mRNA level of parathyroid hormone-related protein (PTHrP), the major component of vicious cycle within bone, was significantly inhibited by BA. Treatment with BA decreased receptor activator of nuclear factor kappa-B ligand (RANKL) /osteoprotegerin (OPG) ratio in PTHrP-treated human osteoblasts. In addition, BA dose-dependently inhibited the RANKL-induced osteoclast differentiation and bone resorption by reducing the secretion of matrix metalloproteinases (MMPs) and cathepsin K derived from osteoclasts, without any evidence of cytotoxicity. We further examined the effect of BA on ovariectomy-induced osteoporosis in mice. Serum levels of tartrate-resistant acid phosphatase isoform 5b, alkaline phosphate, calcium, osteocalcin and C-terminal telopeptide of type I collagen were significantly increased in ovariectomized (OVX) mice than in sham mice. BA inhibited increases in the serum levels of these osteoporotic markers in OVX mice. We analyzed bone volume, trabecular bone thickness, trabecular number and trabecular separation by micro-computer tomography (μ-CT) scanning. Taken together, BA may reduce the expression of PTHrP in MDA-MB-231 human metastatic breast cancer cells, RANKL/OPG ratio in PTHrP-stimulated human osteoblasts, and RANKL-induced osteoclastogenesis in bone marrow macrophages. BA may also prevent osteoporotic bone loss in OVX mice. Thus, BA can be beneficial agents for patients with secondary bone lesions associated with breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 34. doi:1538-7445.AM2012-34
P586Modeling hypertrophic cardiomyopathy with human induced pluripotent stem cells
Authors: M Ojala, K Rajala, R-P Polonen, K Larsson, K Aalto-Setala
Journal: Cardiovascular Research (2014)

Purpose: The two most predominant Finnish founder mutations for hypertrophic cardiomyopathy (HCM) are located in cardiac myosin binging protein C (cMYBPC, Q1061X) and in α-tropomyosin (TPM1, D175N). The functional consequences and the mechanisms by which mutations cause diverse phenotypes in HCM are still only partly understood. Here we have developed cell models for studying pathophysiological mechanisms of the Finnish HCM founder mutations by using human induced pluripotent stem cells (hiPSCs).
SAT0366 Effect of First-Line Anti-TNF Therapy on Fatigue in Patients with Ankylosing Spondylitis – Results from the Czech BIOLOGICS Registry Attra
Authors: S. Forejtova, K. Jarosova, M. Votavova, M. Uher, K. Hejduk, K. Pavelka
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> The aim of this study was to describe the influence of anti-TNF therapy on the fatigue in patients with ankylosing spondylitis (AS) and compare the results with the influence of the therapy on the disease activity <h3>Methods</h3> We used Vitality score (subscale from SF-36) for the assessment of fatigue and BASDAI for the evaluation of the disease activity. Values of Vitality score, BASDAI and their improvements were described using median and interquartile range (IQR). Statistical significance of differences between 3-month visit and treatment initiation and between one-year visit and 3-month visit were assessed using Wilcoxon Signed Ranks Test. Kruskal-Wallis H test was used to assess differences between gender and age categories (while level of significance α =0.05). <h3>Results</h3> 588 AS patients [mean age of 37,6 years (standard deviation 10,5) and mean disease duration of 8 years (standard deviation 7,4) at the start of anti-TNF treatment]were included in the analyses. Men assessed Vitality at the start of treatment better than women (p=0.003), but there was no difference in improvement in Vitality after therapy between the sexes. Compare to patients aged &gt;50 years, there was more improvement in BASDAI assessment in patients aged &lt;30 years (p=0.002) and also in group aged 30-39 (p=0.020) after 3 months of therapy, but there were no statistical differences between various age groups in the improvement of Vitality score after 3 and 12 months of therapy. <h3>Conclusions</h3> Based on subanalysis of age groups there were significant improvements in fatigue and disease activity after 3 months and also significant improvement in disease activity between 12 and 3 months within all age groups, but interestingly there was no significant improvement in fatigue between 12 and 3 months within all age groups besides group of patients aged 30-39 years. <h3>Acknowledgements</h3> Supported by project 00023728 from Ministry of Health in the Czech Republic. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3184
Abstract SY26-03: Innate immune sensing of tumors via the host STING pathway as a bridge to a spontaneous adaptive T cell response.
Authors: Thomas Frank Gajewski
Journal: Cancer Research (2013)

Abstract Recent evidence has suggested that clinical responses to immunotherapeutic interventions occur predominantly in patients having a pre-existing anti-tumor immune response and a T cell-inflamed tumor microenvironment. It has therefore become critical to understand the mechanism by which a subset of patients generates this phenotype, which should instruct on how to deliberately facilitate generation of appropriate tumor-based inflammation and thereby expand the fraction of patients deriving clinical benefit from immunotherapy. However, the mechanisms by which innate immune responses become activated in response to cancer, and how they can bridge to spontaneous T cell priming against tumor antigens, have remained poorly defined. We recently reported that host type I IFN signals are required for a spontaneous T cell response against tumors. In the current work, we have mapped the sensing mechanism to one involving STING/TBK1/IRF3 which drives IFN-β transcription by host APCs. Spontaneous T cell responses against tumors were eliminated in mice deficient in STING or IRF3, and rejection of immunogenic tumors was abrogated. The tumor-derived ligand that triggers this pathway appears to be DNA. Using the DNA-specific dye DRAQ5 or EDU labeling and single cell ImageStream analysis, we demonstrated that in vivo transfer of tumor DNA to host APCs occurs in vivo; this was confirmed using PCR specific for tumor DNA. APC uptake of tumor DNA was associated with IFN-β mRNA induction and nuclear translocation of IRF-3, which were dependent upon host STING. We hypothesized that autophagosome provide a mechanism for delivery of protected tumor DNA into APCs. Inhibition of tumor cell autophagy using the chemical 3-MA, or shRNA silencing of Becn or ATG5, led to a marked reduction in the induction of host IFN-β production and spontaneous T cell responses in vivo. Our data suggest that tumor cell autophagy is required for optimal T cell priming against tumor antigens in vivo, that occurs through DNA-mediated activation of host IFN-β production through a STING-dependent pathway. Analysis of these biologic steps in human melanoma metastases is ongoing. Strategies to mimic activation of the STING pathway should be considered as a mechanism to create an inflamed tumor microenvironment with the hope of expanding the clinical efficacy of T cell-based immunotherapies. Citation Format: Thomas Frank Gajewski. Innate immune sensing of tumors via the host STING pathway as a bridge to a spontaneous adaptive T cell response. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr SY26-03. doi:10.1158/1538-7445.AM2013-SY26-03
The flat polyp: does too much flattening occur with full air insufflation on colonoscopy?
Authors: S. Adler, Y. Metzger, T. Roesch
Journal: Endoscopy (2010)

Flat polyps have been described by our Japanese colleagues. Recently flat polyps have also been recognized in the West and have been noticed to have a higher incidence of significant neoplastic histology [1]. We describe two cases of a flat polyp missed or almost missed at colonoscopy, perhaps due to the effects of full insufflation.
Colonoscopy in a patient with a giant Morgagni hernia
Authors: J. Sebastián
Journal: Endoscopy (2011)

Morgagni hernia is an uncommon type of diaphragmatic hernia, which usually appears in adulthood. The diagnosis is mainly made by chest radiograph and multidetector computed tomography (CT) [1]. As in this case, colonoscopy with fluoroscopic control is very helpful too. Repair can be performed either by using a transthoracic or transabdominal approach, and good results with laparoscopic transabdominal repair have been reported [2].
THU0369 The Effect of Anti-TNF Treatment in Axial Spondyloarthritis Patients Treated in Ordinary Clinical Practice – Results from Two Biorheuma Clinics in Norway
Authors: G. Haugeberg, S. Kalstad, D. M. Soldal, I. J. W. Hansen, G. Bakland
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The BIORHEUMA (BIOlogic treatment of patients suffering from inflammatory RHEUMAtic disorders in Norway) project encourage participating departments to use outcome measures in daily clinical practice (ref.1). Further to obtain unselected real life data on clinical status and treatment practices in patient with inflammatory rheumatic joint disorders. <h3>Objectives</h3> To explore in ordinary rheumatology practice the efficacy of anti-TNF treatment in axial spondyloarthritis (ax-SpA). <h3>Methods</h3> Ax-SpA patients were recruited from two BIORHEUMA departments, one located in the southernmost part and one in the northernmost part of Norway. Both departments are monitoring their ax-SpA patients using validated outcome measures and data is primary registered for benchmarking in a clinical computer database. Data collected for structured follow up and monitoring includes demographics, disease measures (e.g. BASDAI, ASDAS, BASFI, ESR, CRP and MHAQ) and treatment registration. Anonymized data were analyzed in SPSS. <h3>Results</h3> Among the 393 (men 271, women 122) identified patients exposed for anti-TNF treatment mean (SD) age was 46.1 (12.5) yrs, and 87% were HLAB-27+. A total of 265 had tried only one, 81 had tried 1 and 2 and 47 patients had tried 1, 2, 3 or more anti-TNF drugs. First anti-TNF treatment, sequence 1 (seq.1) was in median used for 29, seq.2 for 11 and seq.3 for 17 months. In the table mean baseline and last visit data for anti-TNF treatment is shown for seq.1, 2, and 3. <h3>Conclusions</h3> Our real life data shows that when anti-TNF treatment is used for the first time in ax-SpA the efficacy is far better than when an anti-TNF drug is used for the second or third time. <h3>References</h3> Erik Rødevand et al. The Norwegian BIORHEUMA project – Achieving patient benchmarking and patient register in one work flow using the GoTreatIt computer software system. EULAR 2012-1882 <h3>Disclosure of Interest</h3> G. Haugeberg Shareholder of: Founder and shareholder in DiaGraphIT manufacturing GoTreatIT computer system, S. Kalstad: None Declared, D. Soldal: None Declared, I. J. Hansen: None Declared, G. Bakland: None Declared
AB1162-HPR Relationship between Optimism and Quality of Life in Patients with Chronic Rheumatic Diseases: A Systematic Literature Review
Authors: S. Kreis, F. Zenasni, B. Fautrel, L. Gossec
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Dispositional optimism is defined as a stable, trait-like personality characteristic consisting of a general positive mood or attitude about the future with a tendency to expect favorable outcomes in life situations. It has been shown in some chronic disease groups (e.g. cancer) that dispositional optimism is related to both physical and psychological outcomes and seems to lead to better quality of life (QoL). <h3>Objectives</h3> To review data concerning the relationship between optimism and QoL in rheumatic diseases. <h3>Methods</h3> A Systematic literature review search was performed in December 2013 in PUBMED for studies involving the construct of optimism in various medical contexts. Only studies concerning rheumatic diseases were included. Keywords used were: optimism, quality of life, spondyloarthritis, rheumatic diseases, musculoskeletal, low back pain. <i>Data extraction:</i> (a) description of patient populations, (b) level of optimism. Only studies using the Life Orientation Test- Revised (LOT-R) to assess optimism were included. The LOT-R has a scale ranging from 0-24 where higher levels indicate higher optimism. Of note, in the general population, the mean LOT-R results are reported around 14 points [1]. (c) All available information about links between optimism, QoL and other disease aspects were collected. <i>Data analysis:</i> descriptive analysis. <h3>Results</h3> Of 50 articles, 4 were analyzed: total 2327 patients, of whom 971 had a rheumatic complaint (49% knee osteoarthritis, 23% rheumatoid arthritis, and the rest other rheumatic complaints); 47% females, mean age 59 yrs. The LOT-R mean scores ranged between 15-16.7, which is equivalent to moderate optimism, slightly higher than scores usually reported in the general population. Optimism seemed to be an independent factor affecting QoL and appeared positively correlated with QoL. It was negatively correlated with disease activity in rheumatoid arthritis only. Optimism seemed to be in one study a stronger predictor of mental than physical health; all p values were highly significant. <h3>Conclusions</h3> Although optimism has been repeatedly reported as related to QoL in chronic diseases, its importance in rheumatic diseases has been little explored. Existing studies indicate that optimism levels appear similar to the general population or higher. It seems that optimistic patients have higher QoL than less optimistic patients even after adjusting on confounding factors. The links between optimism and coping strategies should be further explored. <h3>References</h3> Scheier MF, Carver CS, Bridges MW. J Pers Soc Psychol 1994. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3538
P169 Subclinical ocular manifestations of pulmonary and extrapulmonary tuberculosis in a Hampshire population
Authors: S. Beeson, N. Wetherill, S. Mansour, A. K. Banerjee, D. Rowen, N. Hall, B. G. Marshall
Journal: Thorax (2010)

<h3>Background</h3> Intraocular tuberculosisis capable of imitating numerous uveitis entities; the ability of TB to causeuveitis is multi-factorial including virulence of the infecting organism, anindividual9s immune response, and the location of the disease. The non-specificnature of uveitis makes diagnosis difficult, and allowed to progressunchallenged, intraocular tuberculosis can be sight-threatening. We postulate that subclinical ocular signs of TB might coexist with TB activeat other sites. <h3>Methods</h3> 14 TB latent, 14 TB active, and 3 TB-HIV co-infected patients were recruited for this pilot study, between October 2009 and April 2010, from the TB service at the Royal South Hants Hospital. At Southampton General Hospital9s Eye Unit patients provided detailed ocular and tuberculosis histories; all patients then underwent a series of extensive ocular examinations, including best corrected visual acuity and colour vision, intraocular pressure, pupillary response, ocular motility, slit lamp and dilated fundus examinations; finally each patient9s ocular findings were correlated against their TB and TB-HIV co-infection clinical profiles. <h3>Results</h3> 14 patients were classified “latent TB” (IGRA positive, asymptomatic) and 14 patients were classified “active TB” (symptoms, culture positive) of whom three were “TB-HIV co-infected”. Patients with active TB were identified as having significantly more symptoms associated with anterior uveitis, such as pain, photophobia, redness and blurred vision/floaters, compared to those patients with latent TB. We demonstrated objective evidence of anterior chamber inflammation inpatients with active disease, but not latent disease. The patients with HIV coinfection exhibited combined anterior and posterior segment abnormalities consistent with an active uveitis. <h3>Conclusions</h3> The results of this pilot study suggest that patients with active TB have symptoms suggestive of uveitis, but these are unrecognised by the patient unless specifically sought. These patients have anterior chamber findings of uveitis. TB-HIV co-infected patients appear to present asymptomatically with anterior segment and potentially posterior segment signs. These findings suggest that units treating TB should actively screen all patients newly presenting with TB for occult ocular disease.
Nitric oxide and its congeners in mitochondria: implications for apoptosis.
Authors: C Richter
Journal: Environmental Health Perspectives (1998)

Apoptosis is an evolutionarily conserved form of physiologic cell death important for tissue development and homeostasis. The causes and execution mechanisms of apoptosis are not completely understood. Nitric oxide (NO) and its congeners, oxidative stress, Ca2+, proteases, nucleases, and mitochondria are considered mediators of apoptosis. Recent findings strongly suggest that mitochondria contain a factor or factors that upon release from the destabilized organelles, induce apoptosis. We have found that oxidative stress-induced release of Ca2+ from mitochondria followed by Ca2+ reuptake (Ca2+ cycling) causes destabilization of mitochondria and apoptosis. The protein product of the protooncogene bcl-2 protects mitochondria and thereby prevents apoptosis. We have also found that NO and its congeners can induce Ca2+ release from mitochondria. Thus, nitrogen monoxide (.NO) binds to cytochrome oxidase, blocks respiration, and thereby causes mitochondrial deenergization and Ca2+ release. Peroxynitrite (ONOO-), on the other hand, causes Ca2+ release from mitochondria by stimulating a specific Ca2+ release pathway. This pathway requires oxidized nicotinamide adenine dinucleotide (NAD+) hydrolysis to adenosine diphosphate ribose and nicotinamide. NAD+ hydrolysis is only possible when some vicinal thiols are cross-linked. ONOO- is able to oxidize them. Our findings suggest that NO and its congeners can induce apoptosis by destabilizing mitochondria via deenergization and/or by inducing a specific Ca2+ release followed by Ca2+ cycling.
Functional Hearing Loss in Children
Authors: Robert L. Berk, Alan S. Feldman
Journal: New England Journal of Medicine (1958)

IN the normal course of events persons who exhibit a hearing loss by virtue of a screening test are routinely referred to an otologist for further evaluation. As in all screening devices, there is a greater chance for error to occur than with individual testing, and the hearing screening tests are not an exception to this statistical fact. Hence, the subsequent individual testing in some cases reveals that no hearing loss, or at least no significant loss, is present, and the patient is sent back to school or plant with a diagnosis of normal hearing.On the other hand, some . . .