tbuckley/cabot-search huggingface dataset:
More on DSMBs
Authors: Michael Rosenblatt, Peter S. Kim
Journal: New England Journal of Medicine (2011)

To the Editor: Merck, sponsor or financial supporter of Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) (ClinicalTrials.gov number, NCT00092677), Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) (NCT00202878), and Study of Heart and Renal Protection (SHARP) (NCT00125593), agrees with the importance of an independent data and safety monitoring board (DSMB), a point made by Drs. Drazen and Wood (July 29, 2010, issue).1 We disagree, however, with their suggestion that Merck failed to give the DSMBs full independence, for the following three reasons: In January 2008, the SEAS DSMB informed the steering committee of an imbalance in cancers. They contacted . . .
NUEVO MÉTODO DE LESION SUBMUCOSA ARTIFICIAL PARA DISECCIÓN SUBMUCOSA ENDOSCÓPICA EN MODELO ANIMAL
Authors: A Herreros De Tejada, S Méndez, M Santos, M Hernández, J De La Revilla, E Blázquez, J Santiago, F Pons, F Tendillo, JL Calleja, L Abreu
Journal: Endoscopy (2014)

Introducción: La disección submucosa endoscópica (DSE) se ha utilizado con éxito en el tratamiento de lesiones submucosas (LSM) como tumores neuroendocrinos o GIST.
Suppression of Lymphocyte Transformation after Aspirin Ingestion
Authors: James E. Crout, Bonnie Hepburn, Roy E. Ritts
Journal: New England Journal of Medicine (1975)

To learn whether in vitro blastogenesis of lymphocytes is affected by in vivo salicylate ingestion, blood samples were obtained from 19 normal volunteers before and after therapeutic doses of aspirin. Lymphocyte transformation studies performed on these blood samples showed marked and statistically significant suppression of blastogenesis. Maximum suppression was observed in blood samples obtained 12 hours after the last aspirin ingestion. As compared to controls, samples obtained at this time showed mean blastogenic responses to phytohemagglutinin and pokeweed mitogens of 49 and 56 per cent respectively. No correlation could be demonstrated between the plasma salicylic acid level and the degree of suppression of blastogenesis. Aspirin ingestion altered neither the proportions of circulating T and B cells nor the viability of lymphocytes in culture. (N Engl J Med 292:221–223,1975)
SAT0456 Outcome of a national immunization campaign indicated that children and adult rubella vaccination does not induce the development of chronic arthritis
Authors: G.S. Pileggi, M. Mansur David, C.C. de Paula, F.A. de Rosis, G.D. Saquy, M.F.L. Giuberti, L.C. de Souza, C.M. Côrtes, E.J. Alvim Junior, F.E.G.V. de Lima, G.V. Ferreira, L.B. Calheiros
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Vaccinations have long been considered to be possible triggering agents for chronic arthritis, but no sufficiently definitive epidemiological study has been published on this issue. There are case reports of chronic arthropathy presumably induced by rubella, meales and mumps vaccination (MMR), but controlled studies have failed to establish this association <h3>Objectives</h3> The aim of the present prospective cohort study was to investigate the association of MMR vaccination and the onset of acute or chronic articular symptom in healthy subjects <h3>Methods</h3> In Brazil, two prospective cohorts studies taken place during two National immunization campaign: first in 2008 against rubella to reach subjects aged 20-40 years and another in 2011 against measles to reach children aged 1-7 years. In both the vaccine used was MMR. In our city the target was the coverage of 9,000 people to be vaccinated in these age groups, including both males and females. Among those, near 2,000 subjects were randomly selected. Follow-up telephone calls were conducted 2 weeks post vaccination and subsequently monthly after the vaccination over a 6 month period, in order to inquire about occurrence and duration of articular symptoms. In cases where the subjects circumstances were unclear a medical visit was scheduled. Subjects with a preexisting autoimmune disease were excluded from the study <h3>Results</h3> Of the 2,000 selected vaccinated subjects, 972 adults and 827 children have completed the follow up period of 6 months. The vaccine was the first dose for 543 subjects (55%) in the adult group and for 672 children (81%). At the time of the first phone call 17/972 (1.7%) adults subjects and 14/827 (1,7%) childhood age group reported acute articular symptoms: twelve reported arthralgia and five arthritis with all of them being fleeting, lasting no longer than 7 days; eleven were female and six male (p=0.5); twelve had received their first dose of RV and the remaining five following a booster (p=1,0). For the childhood group the rate of acute articular symptoms in the first evaluation was the same 1,7% (14/827), among of them 4 had arthritis and only in two lasting one month; in 13/14 had received their first dose of RV and in only one was a booster (p=0,71). None in the both groups had a chronic outcome. <h3>Conclusions</h3> In our study, which comprised a large number of healthy subjects in different age groups, rubella vaccination was safe and was not associated with the development of chronic arthritis. These findings should be spread among public healthcare providers in order to encourage vaccinations in accordance with recommended national vaccination schedules. <h3>Disclosure of Interest</h3> None Declared
Abstract 4739: Interactions between variants of angiogenesis pathway genes and reflux symptom, BMI, and smoking in esophageal adenocarcinoma susceptibility
Authors: Rihong Zhai, Feng Chen, Geoffrey Liu, Monica Ter-Minassian, Li Su, Kofi Asomaning, Zhaoxi Wang, Matthew H. Kulke, Xihong Lin, Rebecca S. Heist, Chau-Chyun Sheu, John C. Wain, Susanne H. Hooshmand, Norman S. Nishioka, David C. Christiani
Journal: Cancer Research (2010)

Abstract Esophageal adenocarcinoma (EA) is a complex malignancy that involves multiple genetic and environmental risk factors. Genetic polymorphisms in angiogenesis pathway, gastroesophageal reflux symptoms (reflux), higher body mass index (BMI), and tobacco smoking have been individually associated with EA development. However, interactions among multiple factors in EA risk have not been well characterized. We conducted a case-only study to investigate gene-environment interactions among 145 functional/tagging SNPs of angiogenesis pathway genes, reflux, smoking, and BMI in 335 patients with EA. We used a two-stage approach to detect interactions: first, we applied random forest (RF) approach to select important interacting markers based on mean decrease in accuracy and mean decrease in GINI index; then we estimated the interaction odds ratios (ORinter) of RF selected interaction markers by case-only logistic regression, adjusting for covariates and false discovery rate (FDR). We identified twelve interaction markers that were significantly associated with EA risk (all FDR_Ps&amp;lt;0.05). Among them, six interaction markers, including reflux*rs2295778 (HIF1AN) (ORinter=2.27; 95% CI, 1.44-3.57), reflux*rs996999 (MMP1) (ORinter=1.80; 95%CI, 1.12-2.89), reflux*rs13337626 (TSC2) (ORinter=2.18; 95%CI, 1.15-4.12), BMI*rs2114039 (PDGFRA) (ORinter=2.06; 95%CI, 1.29-3.30), BMI*rs6554164 (PDGFRA) (ORinter=1.92; 95% CI, 1.20-3.08), and BMI*rs17708574 (PDGFRB) (ORinter=1.89; 95%CI, 1.12-3.18) were significantly associated with increased risk of EA. On the other hand, six interaction markers, including reflux*rs2519757 (TSC1) (ORinter=0.43; 95% CI, 0.21-0.83), smoking*rs2295778 (HIF1AN) (ORinter=0.45; 95%CI, 0.26-0.79), smoking*rs2296188 (FLT1) (ORinter=0.50; 95%CI, 0.28-0.87), BMI*rs2296188 (FLT1) (ORinter=0.41; 95%CI, 0.24-0.73), BMI*rs11941492 (KDR) (ORinter=0.52; 95%CI, 0.32-0.85), and BMI*rs17619601 (FLT1) (ORinter=0.26; 95%CI, 0.09-0.75) were significantly associated with decreased risk of EA. These findings suggest that variants in angiogenesis pathway genes, reflux, smoking, and BMI jointly contribute to EA development through gene-environment interactions. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4739.
Spirituality and religion in terminally ill patients with cancer
Authors: P. Heras, K. Kritikos, A. Georgopoulou, A. Hatzopoulos, N. Kritikos
Journal: Journal of Clinical Oncology (2007)

19587 Background: The importance of spirituality and religion in coping with a terminal illness is becoming increasingly recognised. We aimed to assess the relation between spiritual well-being, religiosity, depression, and end-of-life despair in terminally-ill cancer patients. Methods: One hundred forty three terminally ill cancer patients with a life expectancy of less than 6 months were interviewed with a series of standardised instruments, including the FACIT Spiritual Well-Being Scale, a religiosity index similar to those used in previous research, the Hamilton depression rating scale, the Memorial Symptom Assessment Scale and the Duke-UNC Functional Social Support Questionnaire. Results: A strong negative association was observed between the FACIT Spiritual Well-Being scale and the HDRS, but no such relationship was found for religiosity. Similar patterns were observed for the FACIT subscales, finding a strong negative association between the meaning and peace subscale (which corresponds to the more existential aspects of spirituality) and HDRS scores, whereas a positive, albeit nonsignificant, association was observed for the faith subscale (which corresponds more closely to religiosity). Conclusions: These results suggest that the beneficial aspects of religion may be primarily those that relate to spiritual well-being rather than to religious practices per se. Spiritual well-being offers some protection against end-of-life despair in those for whom death is imminent. The area of spiritual work is fertile ground for further investigation, especially interventions aimed at improving spiritual health and general quality of life among terminally ill patients with cancer. No significant financial relationships to disclose.
Abstract 1975: Discovery of a potent and selective Jak2 inhibitor that suppresses GM-CSF-induced STAT5 phosphorylation and Erythropoietin-induced reticulocytosis <i>in vivo</i>
Authors: Liqin Liu, Gordon Moody, Jeanne Pistillo, Renee Emkey, Violeta Yu, Elizabeth M. Doherty, Xin Huang, Joseph L. Kim, Angus M. Sinclair
Journal: Cancer Research (2011)

Abstract Essential thrombocythemia (ET), polythemia vera (PV) and myelofibrosis (MF) are myeloproliferative disorders (MPDs) characterized by a chronic excessive production of cells from one or more myeloid lineages and/or bone marrow fibrosis, and have the potential to progress to AML. Recently, gain-of-function mutations in intracellular tyrosine kinase Janus kinase 2 (Jak2) were identified to be associated with MPDs. Jak2 is a member of the Jak family of kinases including Jak1, Jak3, and Tyk2 and is the most proximal signaling component for a number of cytokine receptors. The most common Jak2 mutation identified in MPDs is a substitution of valine to phenylalanine at codon 617 (V617F) located in the pseudokinase domain, which results in the loss of its repressive function, and subsequently leads to the constitutive activation of Jak2 and downstream signaling pathways (STAT, MAP kinase, and PI3 kinase) which affect the survival, differentiation and proliferation of hematopoietic progenitors. Highly selective Jak2 inhibitors may provide a better therapeutic window in chronic dosing settings (ET and PV patients) than non-selective Jak inhibitors. Here we report the discovery of a potent and highly selective Jak2 inhibitor, AMG-Jak2-01. In enzyme assays, AMG-Jak2-01 was potent (3 nM) and selective over other Jak family kinases (&amp;gt; 2000-fold over Jak1, 10-fold over Jak3 and &amp;gt; 400-fold over Tyk2). In isogenic BaF3 cell lines expressing constitutively active Jak kinases (Tel-Jak fusion), AMG-Jak2-01 showed over 40-fold Jak2 selectivity against Jak1 or Tyk2 and 10-fold selectivity against Jak3 based on the inhibition of STAT5 phosphorylation (pSTAT5 – detected with AlphaScreen®). In cytokine-stimulated primary PBMC or whole blood assays, AMG-Jak2-01 demonstrated more than 25-fold Jak2 selectivity over Jak1and Jak3 based on inhibition of pSTAT5 (detected by flow cytometry). In vivo, oral administration of AMG-Jak2-01 at 100 mg/kg for 1 hr inhibited GM-CSF-induced pSTAT5 by approximately 70% (p&amp;lt;0.01) in a mouse peripheral blood pharmacodynamic assay. Finally, two doses of AMG-Jak2-01(100 mg/kg) given 4 hrs apart were able to suppress Epo-induced reticulocytosis in the mouse by 70% (p&amp;lt;0.02). In summary, we have discovered a potent Jak2 inhibitor, AMG-Jak2-01, which is selective over other Jak family members in both enzyme and cell-based assays and demonstrates inhibitory activity in GM-CSF-induced STAT5 phosphorylation and erythropoietin-induced reticulocytosis in vivo. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1975. doi:10.1158/1538-7445.AM2011-1975
Traffic-related air pollution and alveolar nitric oxide in southern California children
Authors: Sandrah P. Eckel, Zilu Zhang, Rima Habre, Edward B. Rappaport, William S. Linn, Kiros Berhane, Yue Zhang, Theresa M. Bastain, Frank D. Gilliland
Journal: European Respiratory Journal (2016)

Mechanisms for the adverse respiratory effects of traffic-related air pollution (TRAP) have yet to be established. We evaluated the acute effects of TRAP exposure on proximal and distal airway inflammation by relating indoor nitric oxide (NO), a marker of TRAP exposure in the indoor microenvironment, to airway and alveolar sources of exhaled nitric oxide ( F eNO ). F eNO was collected online at four flow rates in 1635 schoolchildren (aged 12–15 years) in southern California (USA) breathing NO-free air. Indoor NO was sampled hourly and linearly interpolated to the time of the F eNO test. Estimated parameters quantifying airway wall diffusivity ( D awNO ) and flux ( J′ awNO ) and alveolar concentration ( C ANO ) sources of F eNO were related to exposure using linear regression to adjust for potential confounders. We found that TRAP exposure indoors was associated with elevated alveolar NO. A 10 ppb higher indoor NO concentration at the time of the F eNO test was associated with 0.10 ppb higher average C ANO (95% CI 0.04–0.16) (equivalent to a 7.1% increase from the mean), 4.0% higher J′ awNO (95% CI −2.8–11.3) and 0.2% lower D awNO (95% CI −4.8–4.6). These findings are consistent with an airway response to TRAP exposure that was most marked in the distal airways.
FRI0340 Inhibition of Collagen-Induced Arthritis in Rats by Intra-Articular Injection with an Inhibitor of the Tyrosine Kinase Epidermal Growth Factor Receptor
Authors: C.-R. Wang, S.-Y. Chen, A.-L. Shiau, Y.-T. Li, C.-T. Weng, I.-M. Jou, M.-F. Liu, C.-L. Wu
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Epidermal growth factor receptors (EGFR) can trigger intracellular signal cascades such as PI3K-Akt pathway, and participate in the regulation of cell proliferation. Synovium of rheumatoid arthritis (RA) has high expressions of EGF and EGFR. Therapeutic effects of systemically targeting EGFR have been demonstrated in experimental models, and tyrosine kinase inhibitors (TKI) of EGFR are potential therapeutics in RA. Intra-articular (i.a.) injection, a method bypassing inherited adverse effects associated with the systemic administration, can offer better bioavailability with fewer extra-articular side effects in rheumatoid joint. Indeed, an i.a. injection of biologics such as etanercept can achieve a long-term efficacy in RA monoarthritis without significant adverse events. <h3>Objectives</h3> This study explored the possibility of i.a. administration of a small-molecule EGFR TKI (AstraZeneca Pharmaceutics) as a therapeutic strategy in rheumatoid joint by examining its effect on collagen-induced arthritis (CIA) in rats. <h3>Methods</h3> The 8 w/o male Sprague-Dawley rats were immunized by intradermal injection of bovine type II collagen with complete Freund9s adjuvant. Their ankle joints received an injection of the compound with different concentration after the onset of arthritis. Articular indexes were evaluated following the induction of arthritis, and histological scores were analyzed upon sacrifice of rats. Synovial fibroblasts (SF) were prepared from CIA and RA, and examined for Akt expression and cell proliferation with the EGF stimulation under various concentration of the compound. <h3>Results</h3> Injection of the EGFR TKI into CIA joints significantly reduced articular indexes and histological scores. <i>In vitro</i> results of phospho- to total Akt expression ratios and proliferation responses in SF were reduced in the presence of EGFR TKI. <h3>Conclusions</h3> These data demonstrate firstly the therapeutic effect of i.a. injection of an EGFR TKI in inhibition of an experimental model of arthritis in rats through the mechanism of reduced Akt activation in SF. <h3>References</h3> Wang CR, et al. Inhibition of experimental collagen-induced arthritis in rats by adenovirus-mediated human kallistatin gene therapy. Ann Rheum Dis 2004;63:S270. Hennequin LF, et al. Novel 4-anilinoquinazolines with C-6 carbon-linked side chains: synthesis and structure-activity relationship of a series of potent, orally active, EGF receptor tyrosine kinase inhibitors. Bioorg Med Chem Lett 2006;16:2672-6. Evans CH, et al. Progress in intra-articular therapy. Nat Rev Rheumatol 2014;10:11-22. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1358
T cell derived IL-6 and IL-13 drive fibroblast fibrosis: implications for systemic sclerosis
Authors: S O'Reilly, T Hugle, B Griffiths, A Krippner, J M van Laar
Journal: Annals of the Rheumatic Diseases (2012)

Systemic Sclerosis (SS) is an autoimmune disease of unknown aetiology that is characterised by inflammation, vasculopathy and excessive extracellular matrix deposition. The extracellular matrix deposition is primarily in the skin and organs. The immune abnormalities in the disease include T and B cell activation and a host of proinflammatory cytokines that may mediate the fibrotic response characteristic of the disease. Tumour necrosis factor α (TNFα) is a pro-inflammatory cytokine that may be involved in disease pathogenesis and has been demonstrated to be upregulated in SS. TNFα signals through two receptors causing a variety of downstream effects that depends on cell type and context. The aim was to investigate the role of TNFα in T cells and the role of cytokines in scleroderma and matrix deposition. The authors used T cells from scleroderma and controls and analysed these for the TNFα receptor using flow Cytometry to examine expression, both in skin and PBMCs. Specific mutant ligands that are recombinant for TNFα receptor subtypes or soluble TNF was used to examine downstream effects. T cell conditioned medium was added to normal dermal fibroblasts and markers of fibrosis were examined including collagen type I by real time PCR (RT-PCR). T cell-derived cytokines were measured using ELISA and subsequent cytokines neutralised with antibodies or isotype controls and collagen I measured. <h3>Results</h3> T cells were present in high numbers in the skin of patients. Also TNFαR II was elevated in T cells from both the skin of affected patients and also T cells from peripheral blood compared to healthy controls. Mutant ligands to receptor subtypes leads to elevated interleukin-6 and also IL-13 expression from healthy and scleroderma donors. However scleroderma donors have a much higher constitutive level of both cytokines without the addition of TNFα ligands suggesting activation of T cells. Conditioned medium leads to upregulated α-smooth muscle actin content in dermal fibroblast and also upregulated collagen I expression by 20-fold after incubation with TNFR subtypes both R1 and R2. A differential response was seen between 'activated' and non 'activated' T cells in collagen expression. Suppression of T cell derived cytokines IL-6 and IL-13 in combination by neutralising antibodies leads to an attenuated increase in collagen I mRNA expression as compared to the relevant matched isotype controls, indicating a pivotal role of these cytokines in fibrogenesis. There is also a differential response between patients and controls. <h3>Conclusion</h3> Scleroderma T cells expressed elevated TNFR 2 expression, this maybe an activation marker in scleroderma. T cells are activated 'in vivo' and secrete the cytokines IL-6 and IL-13. IL-6 and IL-13 work in a synergistic fashion leading to enhanced extracellular matrix deposition.
Rhabdomyolysis of Bilateral Teres Major Muscles
Authors: UMESH D. OZA, ELIZABETH OATES
Journal: Clinical Nuclear Medicine (2003)

From the Departments of Radiology, New England Medical Center, Tufts University School of Medicine,* and Boston Medical Center, Boston University School of Medicine,† Boston, Massachusetts Received for publication April 22, 2002. Revision accepted August 5, 2002. Reprint requests: Umesh D. Oza, NEMC #299, 750 Washington Street, Boston, Massachusetts 02111. E-mail: [email protected]
Liver Regeneration After Partial Hepatectomy in a Patient with Hepatoblastoma
Authors: RAKESH KUMAR, BHARATHI DASAN J, SAIKAT CHOUDHURY, GURUPAD BANDOPADHAYAYA, ARUN MALHOTRA
Journal: Clinical Nuclear Medicine (2001)

KUMAR, RAKESH D.R.M., D.N.B.; DASAN J, BHARATHI M.B.B.S.; CHOUDHURY, SAIKAT M.B.B.S.; BANDOPADHAYAYA, GURUPAD Ph.D.; MALHOTRA, ARUN D.R.M., Ph.D. Author Information
Exclusion of Chronic Osteomyelitis With F-18 Fluorodeoxyglucose Positron Emission Tomographic Imaging
Authors: HONGMING ZHUANG, PAULO S. DUARTE, MICHAEL POURDEHAND, DARRYL SHNIER, ABASS ALAVI
Journal: Clinical Nuclear Medicine (2000)

Excluding the diagnosis of chronic osteomyelitis is often difficult with noninvasive techniques, especially when bone anatomy and structure have been altered by trauma, surgery, or soft-tissue infection. It has been reported that fluorodeoxyglucose (FDG) positron emission tomography (PET) has excellent potential to diagnose osteomyelitis. In this study, the accuracy of FDG PET in the diagnosis of chronic osteomyelitis was determined.Twenty-two patients with possible osteomyelitis (5 in the tibia, 5 in the spine, 4 in the proximal femur, 4 in the pelvis, 2 in the maxilla, and 2 in the feet) who underwent FDG PET imaging and on whom operative or clinical follow-up data were available were included in this analysis. The final diagnosis was made by surgical exploration or clinical follow-up during a 1-year period.FDG PET correctly diagnosed the presence or absence of chronic osteomyelitis in 20 of 22 patients. Six had chronic osteomyelitis and 16 proved to be free of osteomyelitis. FDG PET correctly identified all six patients with chronic osteomyelitis but produced two false-positive results. This study had a sensitivity rate of 100%, a specificity rate of 87.5%, and an accuracy rate of 90.9%.FDG PET is a highly effective imaging method to exclude osteomyelitis when a negative scan result is obtained. However, positive results can be caused not only by true osteomyelitis but also by inflammation in the bone or surrounding soft tissues as a result of other causes. Overall, FDG PET may prove to be the preferred study in the management of patients with possible chronic osteomyelitis.