tbuckley/cabot-search huggingface dataset:
AB0814-PC The patients with osteoarthritis and the primary care of general practitioners
Authors: N. Nikolov, M. Panchovska, Z. Kolarov
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Osteoarthritis (OA) is the most common rheumatic disease, which appears after the age of 40 years. Patients with osteoarthritis comprise up to 43% of the general practitioners’ patients (GP)<sup>1</sup>. The treatment of this disease engage other specialists also – rheumatologists and orthopaedists. The OA prognosis concerning life longevity is good, but it is one of the most essential reasons for disability. This defines the social importance of OA<sup>2,3</sup>. <h3>Objectives</h3> The aim of this study is to evaluate the competence of GPs in Bulgaria for the treatment of OA patients and the collaboration with the specialists – rheumatologists and orthopaedists. <h3>Methods</h3> A questionnaire was filled in by 27 GPs, who have 29 465 patients (aged above 18) in their registers. Patients with OA present 54,11% of all registered patients. The questionnaire includes questions about pharmacological and non-pharmacological agents for OA treatment; intraarticular injection of corticosteroids and synthetic hyaluronic acid; referrals of patients to a specialists; prevalence of visits of OA patients in GP’s practices. <h3>Results</h3> Data of the questionnaires indicates : 74,07% of GPs use most often nonsteroid anti-inflammatory drugs (NSAIDs) for control of pain in OA patients; 77,77% of GPs require body weight reduction as a basic non-pharmacological agent; 14,81% of GPs inject intraarticular corticosteroids; 3,70% of GPs inject intraarticular synthetic hyaluronic acid; 55,55% of GPs refer the OA patients to a rheumatologist and 44,45 refer them to an orthopaedist; <h3>Conclusions</h3> GPs control the pain of OA patients most often with non-steroid antiinflamatory drugs. GPs refer the OA patients to specialists for intraarticular injection of drugs. In Bulgaria OA patients are dyspancerized by specialists rheumatologists. Guidelines for management of OA patients from general practitioners need to be introduced and applied. <h3>References</h3> Rasker J.J.Rheumatology in general practice. Br J Rheumatol 1995, 34:494-7 Lopez-Olivo MA, Suarez -Almazor ME.Developing guidlines in musculoskeletal disorders. Clin Exp Rheumatol.2007 Nov-Dec:25 Dziedzic KS, Hill JC, Porcheret M, Croft PR: New models for primary care are needed for osteoarthritis. <i>Phys Ther</i> 2009, 89(12):1371-1378. 6 Suppl 47):28-36 <h3>Disclosure of Interest</h3> None Declared
Early-Onset Asthma Is Associated with a Specific Polymorphisms of TLR-4 (Asp299Gly) in Ukrainian Adults
Authors: Yuri Bisyuk, A.I. Kurchenko, V.a. Beloglazov, A.I. Dubovyi, L.K. Znamenska, Lawrence M. DuBuske
Journal: Journal of Allergy and Clinical Immunology (2015)
Abstract 1875: A novel series of metabolic activators of PKM2 alter oncogene-meditated changes in tumor cell metabolism.
Authors: Brigham L. Bahr, Jenny Stevens, Spencer Squire, Christopher Moreno, Lee T. Call, Bret J. Stephens, Alexis Mollard, Steven L. Warner, David J. Bearss
Journal: Cancer Research (2013)

Abstract Rather than relying on oxidative phosphorylation for the generation of ATP, human tumor cells primarily utilize aerobic glycolysis to metabolize glucose (the Warburg effect). Pyruvate kinase is a metabolic enzyme that converts phosphoenolpyruvate (PEP) to pyruvate, catalyzing the rate-limiting step of glycolysis. The M1 isoform of pyruvate kinase (PKM1) that is the principal isoform in most adult differentiated tissues, while the PKM2 splice variant is the main isoform in embryonic tissues and in all cancer cells. Unlike the M1 splice form (PKM1), which is found in its tetrameric active form in cells, PKM2 is found in cells as an inactive dimer under normal physiological conditions. Tetramerization of PKM2 requires binding of the allosteric activator fructose-1,6-bisphosphate (FBP), an upstream glycolytic intermediate, resulting in a fully active enzyme. Regulation of PKM2 activity in cancer cells may allow glycolytic intermediates to be diverted into other biosynthetic pathways necessary for biomass production. PKM2 expression enhances tumorigenicity of cells while PKM1 expression represses it. This suggests that activators of PKM2 may have anti-tumor properties by forcing PKM2 to act more like PKM1. We have a series of small molecule PKM2 activators that exhibit low nM activation activity in biochemical and cell-based assays. These compounds increase pyruvate kinase activity in cancer cells and lead to an increase in pyruvate and ATP production. Our studies show that PKM2 activators inhibit the growth of lung cancer cell lines in vitro and in vivo and can reverse the metabolic changes induced by oncogenes such as k-Ras and c-Myc in lung cancer cells. The current lead compound was tested in established subcutaneously implanted A549 lung adenocarcinoma xenografts, where we observed a statistically significant 54% decrease in tumor growth, with no observable toxicity. These data suggest that this class of PKM2 activators is effective as tumor cell metabolic regulators with anti-tumor activity for lung cancer and potentially other malignancies. Citation Format: Brigham L. Bahr, Jenny Stevens, Spencer Squire, Christopher Moreno, Lee T. Call, Bret J. Stephens, Alexis Mollard, Steven L. Warner, David J. Bearss. A novel series of metabolic activators of PKM2 alter oncogene-meditated changes in tumor cell metabolism. [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 1875. doi:10.1158/1538-7445.AM2013-1875
Prognosis of adult acute myeloid leukemia in Southern Switzerland: A population-based analysis
Authors: E. Lerch, V. Espeli, E. Zucca, M. Ghielmini, L. Leoncini, G. Scali, O. Mora, A. Bordoni, F. Cavalli
Journal: Journal of Clinical Oncology (2005)

6689 Background: This study was aimed to evaluate the treatment outcome of adult patients with acute myeloid leukaemia (AML) diagnosed in the Italian-speaking part of Switzerland from 1983 to 2003. Methods: Data were collected retrospectively for all adult patients diagnosed with AML in public hospitals and compared to tumour registry data to assess completeness. Univariate and multivariate analysis was performed to determine prognostic factors for progression-free survival (PFS) and overall survival (OS). Results: 132 AML patients were identified with an incidence of 2.1/100,000 per year. Complete clinicopathological data and follow-up information were available for 128 cases. Median age was 67 years. At a median follow-up time of 97 months the median OS was 6 months and the median PFS was 3 months. 35 patients were treated with supportive care only or palliative chemotherapy. The median OS for this group was 2 months. 93 patients were treated with myelosuppressive chemotherapy with curative intent. The CR-rate was 74% for patients younger than 60 years and 29% for those older than 60 years (p< 0.001) with a median OS of 16 and 6 months, respectively (p< 0.0005) and a median PFS of 8 and 2 months, respectively (p< 0.0005). Not surprisingly, survival was significantly longer (p< 0.0005) for the patients with less than 40 years (median OS, 55 months and median PFS, 54 months). 48 patients were treated in a controlled clinical trial: they were significantly younger than the others (median age 57 vs. 73 years, p<0.0005) and had a significantly better prognosis (median OS 13 vs. 4 months, p=0.0019). High dose Ara-C was given to 25 of 93 patients treated with curative intent and resulted in a OS advantage compared to standard dose (p<0.0005). Finally, patients treated after 1993 had a better OS (p= 0.026) compared to the previous cohort. A multivariate analysis performed excluding cytogenetic data (available only for 51 cases) found age (p= 0.005), PS (p= 0.001) and treatment before 1994 (p= 0.044) to be the independent prognostic factors for both OS and PFS. Conclusions: Young adults can be cured in appproximately half of the cases but the outcome for the general population of adult AML, which is mainly an elderly disease, remains disappointing. No significant financial relationships to disclose.
Abstract 5730: Dosimetric properties of a new thermobrachytherapy seed with ferromagnetic core for treatment of solid tumors
Authors: R Subramanian, Ishmael E. Parsai, Gautam R. Bhoj, Diana Shvydka, Feldmeier J. John
Journal: Cancer Research (2012)

Abstract Studies of the curative effects of hyperthermia and radiation therapy on treatment of cancer show a strong evidence of a synergistic enhancement when both radiation and hyperthermia modalities are applied simultaneously. Varieties of tissue heating approaches developed up to date still fail to overcome such essential limitations as an inadequate temperature control, temperature non-uniformity, and prolonged time delay between hyperthermia and radiation treatments. We propose a new self-regulating Thermobrachytherapy seed, which serves as a source of both radiation and heat for concurrent administration of brachytherapy and hyperthermia. The proposed seed is based on the BEST Seed Model 2301-I125, where tungsten marker core and the air gap are replaced with a ferromagnetic material. The ferromagnetic core produces heat when subjected to alternating electro-magnetic (EM) field and effectively shuts off after reaching the Curie temperature (TC) of the ferromagnetic material thus realizing the temperature self-regulation. We present the Monte Carlo study of dose rate constant and the other TG-43 radiation characteristic factors for the proposed seed. For the thermal characteristics, we studied a model consisting of 16 seeds placed in the central region of a cylindrical water phantom using a finite-element partial differential equation solver package “COMSOL Multiphysics”. The modeling result shows that temperature of the thermoseed surface rises rapidly and stays constant around TC of the ferromagnetic material. The amount of heat produced by the ferromagnetic core is sufficient to raise the temperature of the surrounding volume to the therapeutic range. The volume of the therapeutic temperature range increases with increase of frequency or magnetic field strength. These studies demonstrate that an optimal isothermal distribution can be achieved on a target volume to match with the radiation isodose distribution for the seed configuration by tuning frequency and intensity of the alternating magnetic field. The proposed combination seed model has a high potential for implementation of concurrent brachytherapy and hyperthermia. 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 5730. doi:1538-7445.AM2012-5730
Glutamine in the Phenylketonuric Central Nervous System
Authors: Charles M. McKean, Neal A. Peterson
Journal: New England Journal of Medicine (1970)

Concentrations of glutamine in 31 untreated phenylketonuric adults were decreased in the serum but increased in cerebrospinal fluid (131 per cent of nonphenylketonuric values) and in cerebral white matter (in three patients, 155 per cent of control values). Tyrosine, serine and histidine concentrations in the cerebrospinal fluid were also increased, whereas threonine was significantly lower in untreated phenylketonuria. Of the amino acids reported, only tyrosine was consistently lower in brain tissue. These findings do not support the hypothesis that Central-nervous-system glutamine depletion is responsible for the cerebral abnormalities in phenylketonuria. Alterations in amino acid concentration of the central nervous system may be the result of competitive impairment of active transport mechanisms that control influx to brain and efflux from the cerebrospinal-fluid compartment. In a phenylketonuric subject with relatively normal intellect, amino acid efflux from this compartment appeared less impaired than in patients with severe cerebral maldevelopment.
Sun-Less Tans May Be Possible With New Synthetic Hormone
Authors: C. Vanchieri
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Sun-Less Tans May Be Possible With New Synthetic Hormone Get access Cori Vanchieri Cori Vanchieri Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 16, 19 August 1992, Pages 1234–1235, https://doi.org/10.1093/jnci/84.16.1234 Published: 19 August 1992
Nephrotoxic Potential of Bence Jones Proteins
Authors: A Solomon, D T Weiss, A A Kattine
Journal: New England Journal of Medicine (1991)

The renal manifestations of diseases associated with the production of monoclonal light chains—myeloma (cast) nephropathy, light-chain deposition disease, and amyloidosis AL—result from the deposition of certain Bence Jones proteins as tubular casts, basement-membrane precipitates, or fibrils, respectively. For unknown reasons, the severity of the renal manifestations of these diseases varies greatly from patient to patient. We employed an experimental in vivo model to determine the pathologic importance of various Bence Jones proteins.
Thermocoagulation for the Early Treatment of Pregnancy with an Acardiac Twin
Authors: Charles Rodeck, Anne Deans, Eric Jauniaux
Journal: New England Journal of Medicine (1998)

In twin pregnancy with acardia, which occurs in about 1 in 35,000 deliveries, the heart and usually other organs fail to develop in one twin.1 The acardiac (“recipient”) twin receives blood from the normal (“pump”) twin, and the blood is then returned to the normal twin.2 The natural history is variable, and some pregnancies proceed to term. Commonly, the acardiac twin becomes grossly edematous, and its size may exceed that of the pump twin. Hydramnios may occur in either sac. The perinatal mortality rate for pump twins is around 55 percent, with death due mainly to congestive cardiac failure or . . .
Conventional vs. waterjet-assisted endoscopic submucosal dissection in early gastric cancer: a randomized controlled trial
Authors: Ping-Hong Zhou, Brigitte Schumacher, Li-Qing Yao, Mei-Dong Xu, Thomas Nordmann, Ming-Yan Cai, Jean-Pierre Charton, Michael Vieth, Horst Neuhaus
Journal: Endoscopy (2014)

<b>Background and study aims: </b>A hybrid knife was recently developed to allow waterjet-assisted endoscopic submucosal dissection, which aims to speed up and simplify the procedure. This technique has been shown to be effective and safe for the treatment of early gastric cancer (EGC) but it has not yet been compared with conventional ESD. <b>Patients and methods:</b> In this two-center study, patients with an endoscopic and histopathological diagnosis of gastric adenoma or early gastric adenocarcinoma (meeting the extended Japanese criteria for local resection) were randomized to either conventional or waterjet-assisted ESD. The choice of knife was left to the endoscopist in the conventional group whereas the hybrid knife was used in the waterjet group. The primary end point was procedure time, and secondary outcomes included rates of en bloc resection, R0 resection, and complications. <b>Results: </b>A total of 117 patients (mean age 63.0 ± 10.6 years, 76 men) were randomized to either conventional ESD (n = 59; control group) or waterjet-assisted ESD (n = 58). There were no significant differences in patient demographics or lesion features between the groups. The mean procedure time was significantly shorter in the waterjet group compared with the conventional group (27.5 ± 30.6 vs. 35.0 ± 22.5 minutes; <i>P</i> = 0.0008), and a change of accessories was less frequently required (mean number of changes 1.4 ± 2.0 vs. 23.0 ± 15.4; <i>P</i> < 0.0001). There was no significant difference between the groups in the size of resected specimen, R0 resection rates, number of perforations, major delayed bleedings, or rates of complete remission of neoplasia after 3 months. <b>Conclusions: </b>Waterjet-assisted ESD and conventional ESD are comparably effective and safe techniques for the local treatment of EGC. The waterjet-assisted technique is a faster and simpler procedure and requires fewer accessory changes compared with conventional ESD. ClinicalTrial.gov registration: NCT01943253
Acute Cardiac Events Temporally Related to Cocaine Abuse
Authors: Jeffrey M. Isner, N.A. Mark Estes, Paul D. Thompson, Maria Rosa Costanzo-Nordin, Ramiah Subramanian, Gary Miller, George Katsas, Kristin Sweeney, William Q. Sturner
Journal: New England Journal of Medicine (1986)

The increasingly widespread use of cocaine in the United States has been accompanied and perhaps exacerbated by the misconception that the drug is not associated with serious medical complications. In particular, the potential for cocaine to precipitate life-threatening cardiac events needs to be reemphasized. We report the clinical and pathological findings in seven people in whom nonintravenous "recreational" use of cocaine was temporally related to acute myocardial infarction, ventricular tachycardia and fibrillation, myocarditis, sudden death, or a combination of these events. We also review data on 19 previously reported cases of cocainerelated cardiovascular disorders. Analysis of all 26 patients indicated the following findings: (1) the cardiac consequences of cocaine abuse are not unique to parenteral use of the drug, since nearly all the patients took the drug intranasally; (2) underlying heart disease is not a prerequisite for cocaine-related cardiac disorders; (3) seizure activity, a well-documented noncardiac complication of cocaine abuse, is neither a prerequisite for, nor an accompanying feature of, cardiac toxicity of cocaine; and (4) the cardiac consequences of cocaine are not limited to massive doses of the drug. Although the pathogenesis of cardiac toxicity of cocaine remains incompletely defined, available circumstantial evidence suggests that cocaine has medical consequences that are equal in importance to its well-documented psychosocial consequences. (N Engl J Med 1986; 315:1438–43.)
EPIGENETICALLY DISTURBED NEURAL STEM/PROGENITOR CELLS IN THE PRE-NEOPLASTIC STAGE OF PDGF-INDUCED MOUSE GLIOMA
Authors: M. Nister, X. He, M. Karimi, A. Hedren, T. J. Ekstrom
Journal: Neuro-Oncology (2014)

BACKGROUND: Platelet-derived growth factors (PDGFs) are produced and secreted by human glioblastoma cells, and the PDGFR-α gene is amplified in a fraction of both low- and high-grade gliomas. Glioma involves interactions between the malignant cells and their microenvironment. We have therefore studied glioma formation in two PDGF-dependent brain tumor models where PDGF is expressed in vivo in astrocytic cells under control of the GFAP-promoter (Hede et al. 2009; Nazarenko et al 2011). PDGF-AL transgenic mice develop a characteristic, lethal phenotype due to highly proliferating oligodendrocyte progenitor cells that spread diffusely throughout the brain. A few of the PDGF-AL mice present with advanced lesions similar to human anaplastic oligoastrocytoma. PDGF-B transgenic mice do not develop brain tumors and are phenotypically normal, but when crossed with p53 null mice, they develop brain tumors at a high rate. The tumors occur between 2-6 months, are similar to human glioblastoma, and consistent with previous findings from human brain tumors Pdgfr-α is localized on glial tumor cells, while Pdgfr-β is on the vasculature. Thus, PDGF-AL and –B differ in their capacity to induce brain tumors. METHODS: Efforts to target the PDGF pathway for treatment of glioma have not been successful. In search for new therapies, we need more knowledge on the early stage of glioma development. Therefore we have used the PDGF-B transgenic mice in crossings with p53null to study the pre-neoplastic stage. Immuno-histochemical stainings and immuno-blot analyses were used to detect changes in histone methylation and the Luminometric Methylation Assay (LUMA) to monitor global DNA methylation in the brain. RESULTS: The hGFAPpPDGFB/Trp53 null (B + p53-/-) mice develop glioblastoma-like brain tumors at a high frequency in adulthood. The present work reveals epigenetic changes in the mouse brain tumors as well as in neural stem/progenitor cells during the histologically normal pre-neoplastic stage of the brain. DNA hypomethylation and elevated Histone3 Lysine9 di-methylation (H3K9Me2) were detected in the tumors. During the pre-neoplastic stage, global DNA hypomethylation was also observed in samples of the adult frontal brain lateral ventricular wall, but could not be observed in whole brain samples. Elevated H3K9Me2 levels were observed in neurosphere cultures from the B + p53-/- pre-neoplastic brain but not in wild type (WT) neurospheres using immuno-blot analysis. The H3K9Me2 level was also higher in brain tumor spheres compared to neurospheres derived from the same mouse. CONCLUSIONS: We propose that epigenetically disturbed neural stem/progenitor cells are the early targets of neoplastic transformation in the brain. SECONDARY CATEGORY: n/a.
THOR METHYLATION PROVIDES INSIGHT INTO THE TELOMERE MAINTENANCE LANDSCAPE OF MALIGNANT GLIOMAS
Authors: U. Tabori, P. Castelo-Branco, D. Lee, M. Gallo, T. Limpan, J. Mangerel, A. Price, M. Remke, C. Zhang, A. Heidari, K. Wani, R. Vanner, G. Zadeh, J. Karamchandani, S. Das, m. Taylor, C. Hawkins, H. Yan, K. Aldape, P. B. Dirks
Journal: Neuro-Oncology (2014)

BACKGROUND: Gliomas are a deadly group of childhood and adult cancers associated with high relapse rate following current therapies. Limitless self-renewal is a hallmark of cancer recurrence and is controlled by telomerase activation and telomere maintenance. We have recently uncovered THOR (TERT Hypermethylated Oncological Region) which is paradoxically hypermethylated in gliomas with telomerase activation. In order to further explore the biological impact of THOR hypermethylation on self renewal and telomere maintenance of gliomas we undertook a stepwise approach. METHODS: RESULTS: Mapping of the human TERT promoter reveals that THOR spans 432 BP and comprises 52 CG sites. In contrast, the area where mutations in TERT promoter were uncovered is permanently hypomethylated. Promoter driven expression was analysed through luciferase assays and unveiled a repressive effect of THOR on the TERT promoter. Moreover, TERT mutations promoted hyperactivation of the reporter gene providing explanations for the methylation pattern observed in malignant gliomas. THOR methylation increases in gliomas as they transform from low to high grade and from primary tumor to established cell lines (p < 0.001). Analysis of allelic Tert expression reveals that THOR is initally methylated in the mutant allele and throughout tumor progression, the other allele eventually becomes methylated. This correlates with higher TERT expression. In contrast, tumors utilizing alternative lengthening of telomeres (ALT) lack THOR methylation and TERT mutations. Glioma stem cells (n = 32) are addicted to telomerase and have higher THOR methylation than the bulk tumor. Strikingly, glioblastomas which activate ALT lack this phenotype in their stem cells compartment. Whole exome sequencing reveals multiple ALT related mutations (TP53 and ATRX) which are present in the mature tumor cells subpopulation and absent in the TERT expressing stem cell subpopulation. THOR demethylation with Decitabine results in loss of telomerase activation only in tumor cells and not in normal and embryonic stem cells which lack THOR methylation. Combining telomerase inhibition with decitabine result in permanent loss of self renewal capacity of patient derived cell lines in vitro and lack of tumor formation in vivo. CONCLUSIONS: We offer a model and a novel classification of gliomas based on THOR hypermethylation and alterations in the telomere maintenance pathway. We also suggest that intratumoral heterogeneity in telomere maintenance might be the result of secondary hits in the non-stem cell compartment Finally, we propose that THOR demethylation can be a safe and viable option for exhausting the self renewal capacity of gliomas. SECONDARY CATEGORY: Pediatrics.