tbuckley/cabot-search huggingface dataset:
Improvement in the Diagnosis of Abscesses Associated with Endocarditis by Transesophageal Echocardiography
Authors: Werner G. Daniel, Andreas Mügge, Randolph P. Martin, Oliver Lindert, Dirk Hausmann, Barbara Nonnast-Daniel, Joachim Laas, Paul R. Lichtlen
Journal: New England Journal of Medicine (1991)

Echocardiography is recognized as the method of choice for the noninvasive detection of valvular vegetations in patients with infective endocarditis, with transesophageal echocardiography being more accurate than transthoracic echocardiography. The diagnosis of associated abscesses by transthoracic echocardiography is difficult or even impossible in many cases, however, and it is not known whether transesophageal echocardiography is any better.To determine the value of transesophageal echocardiography in the detection of abscesses associated with endocarditis, we studied prospectively by two-dimensional transthoracic and transesophageal echocardiography 118 consecutive patients with infective endocarditis of 137 native or prosthetic valves that was documented during surgery or at autopsy.During surgery or at autopsy, 44 patients (37.3 percent) had a total of 46 definite regions of abscess. Abscesses were more frequent in aortic-valve endocarditis than in infections of other valves, and the infecting organism was more often staphylococcus (52.3 percent of cases) in patients with abscesses than in those without abscesses (16.2 percent). The hospital mortality rate was 22.7 percent in patients with abscesses, as compared with 13.5 percent in patients without abscesses. Whereas transthoracic echocardiography identified only 13 of the 46 areas of abscess, the transesophageal approach allowed the detection of 40 regions (P less than 0.001). Sensitivity and specificity for the detection of abscesses associated with endocarditis were 28.3 and 98.6 percent, respectively, for transthoracic echocardiography and 87.0 and 94.6 percent for transesophageal echocardiography; positive and negative predictive values were 92.9 and 68.9 percent, respectively, for the transthoracic approach and 90.9 and 92.1 percent for the transesophageal approach. Variation between observers was 3.4 percent for transthoracic and 4.2 percent for transesophageal echocardiography.The data indicate that transesophageal echocardiography leads to a significant improvement in the diagnosis of abscesses associated with endocarditis. The technique facilitates the identification of patients with endocarditis who have an increased risk of death and permits earlier treatment.
AB0731 Risk factors and prevalence of osteoporosis in patients with systemic lupus erythematosus
Authors: V. Rodríguez-García, C.M. Romero-Barco, S. Manrique-Arija, F.G. Jimenez-Nuñez, B. Panero, M.C. Ordoñez, L. Nieves-Martín, M.A. Belmonte, V. Coret, L. Cano, M.V. Irigoyen, M. Rodríguez-Perez, A. Fernandez-Nebro
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To determine the prevalence and risk factors of osteoporosis in patients with Systemic Lupus Erythematosus (SLE) in our hospital. <h3>Methods</h3> Design: Retrospective study. 101 SLE-patients were studied in the Rheumatology Department in Carlos Haya Hospital in Malaga. Patients' disease and demographic data (including SLEDAI) were collected. Bone mineral density (BMD) was measured at the lumbar spine (LS) and femoral neck (FN) with a DEXA-LUNAR- PRODIGY. The results were classified according to WHO criteria. Thoracic and lumbar spine radiographies were assessed using the Genant method. <h3>Results</h3> Data from 98 SLE-patients were available for analysis (94% women, mean age 42±14 years). Only 61 patients (62%) had a DEXA. Patients with DEXA were similar to others in terms of gender, race, history of fracture, alcohol, tobacco, sedentary, photosensitivity or use of corticosteroids. However, patients with DEXA were older (42.3±14 years vs. 40.6±13.5 years, T-test p=0.002), had a longer duration of lupus (120.7±103.3 months vs. 89.6±68.4, U of MW p no significant differences were found in the prolonged steroids taking (&gt;6 months) [4 (44.4%) vs. 30 (66.7%), Fisher's exact test p=0.266] and SLICC (0.9±0.9 VS. 0.9±1.5, T-test p=0.937). <h3>Conclusions</h3> The prevalence of osteopenia and osteoporosis in our SLE-patients is greater than in general population and it is more frequent in older age, menopausal status and history of fracture. The profile of patients with DEXA reflects that this test is not request systematically in clinical practice but only to those patients with more osteoporosis risk, this is a considerable bias in our study. The small sample size and the systematic use of prophylactic treatmentin patients treated with corticosteroids may be also explained why it was not found relationship between glucocorticoids and low mineral bone density <h3>Disclosure of Interest</h3> None Declared
PTU-019 Methadone use is associated with the development of common bile duct dilatation among patients with hepatitis C: results of a retrospective cohort study
Authors: A Ahmed, A Stanley, E Forrest, R Gillespie, M Neilson, S Barclay
Journal: Gut (2012)

<h3>Introduction</h3> The synthetic opioid Methadone is widely used in the treatment of opioid dependence. Opioids are known to induce spasm of the sphincter of Oddi, increase common bile duct (CBD) pressures and induce bile duct dilatation. A prior study has shown methadone use to be associated with asymptomatic CBD dilatation among patients with viral hepatitis. We aimed to examine the prevalence of CBD dilatation among methadone users with hepatitis C (HCV) at first attendance and subsequent liver clinic follow-up, in comparison with a control group. <h3>Methods</h3> Patients with chronic HCV attending our institution between 2003 and 2010 were identified from the Scottish HCV Database. Age, gender, methadone use, and CBD dilatation (≥8 mm) identified on initial and follow-up abdominal ultrasound scan (AUS) were recorded. Statistical analysis was performed using SPSS to compare methadone users, vs a control group not on methadone. <h3>Results</h3> 618 patients were identified, 316 (51.1%) on methadone and 302 (48.9%) not. Mean age (42.3 vs 48.5, p=0.99) and gender (71.5% male vs 69.2%, p=0.53) were similar in the methadone group vs controls. CBD dilatation on initial AUS was significantly higher among the methadone group (47/316 (14.9%) vs 18/302 (6%), p=0.0003). Post cholecystectomy CBD dilatation was uncommon (4/47 (8.5%) vs 3/18 (16.6%), p=0.38). Of those with a normal initial CBD, 111/269 (41.3%) methadone patients and 115/284 (40.5%) controls had an interval scan. Over similar durations of follow-up (38.1 months vs 45 months controls, p=0.53), methadone use was associated with increased de-novo CBD dilatation (15/111 (13.5%) vs 6/115 (5.2%), p=0.03). Rates of subsequent biliary investigation (MRCP/ERCP) were low (12/62 (19.3%) and 7/24 (29.2%). An obstructive cause of biliary dilatation was infrequently found among methadone receiving patients and controls (1/12 (8.3%) vs 1/7 (14.3%), p=0.49). No obstructive biliary pathology was found among patients with normal alkaline phosphatase (ALP) in either group. <h3>Conclusion</h3> Our study confirms the association between methadone use and CBD dilatation among patients referred for assessment of HCV. For the first time we have demonstrated an increased rate of new CBD dilatation among methadone users on longitudinal follow-up. Given that one in five patients on methadone demonstrated CBD dilatation during initial assessment or follow-up, with no alternate cause identified among those with a normal ALP, further investigation of these patients may not be necessary. Further work is required to establish and validate algorithms identifying those patients receiving methadone with CBD dilatation in whom further investigation can be safely omitted. <h3>Competing interests</h3> None declared.
THU0369 The Medical Burden of Rare Autoinflammatory Diseases: Exemple of Mevalonate Kinase Deficiency in France
Authors: C. Galeotti, S. Bérody, I. Koné-Paut, M. Piram
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Mevalonate kinase deficiency (MKD) is a very rare autosomic recessive autoinflammatory disease caused by mutations of the <i>MVK</i> gene. Two phenotypes of MKD are delineated according to the level of enzymatic deficiency, complete (MA) or partial (HIDS), however a wide spectrum of intermediate phenotypes has been reported. First symptoms of MKD appear very early in life, occasionally with severe neonatal hepatitis, but most patients will undergo an extensive workup before coming to the diagnosis sometimes many years later. The fact that MKD deficiency is rare means that a quantity of mistaken diagnoses and medical referrals will precede the right diagnosis, amplifying the burden of the disease. <h3>Objectives</h3> A retrospective survey and chart review to evaluate the patient9s medical referrals between the first symptom and the diagnosis of MKD. <h3>Methods</h3> A questionnaire was sent to French paediatric and adult rheumatologists to collect information from genetically confirmed MKD patients, regarding the first symptoms of the disease, the different diagnoses previously made with the treatment received, and the disease burden evaluated by the hospitalizations. <h3>Results</h3> Thirteen patients were analyzed (11 HIDS and 2 MA). The median age at onset was 9.5 months (from birth to 36 months) in twelve cases. The average diagnosis delay was 7.1 years. A wide variety of diseases had been suspected: systemic JIA, PFAPA syndrome, other hereditary recurrent fever (FMF, TRAPS, CINCA), vasculitis (Kawasaki, Henoch Scholein purpura), connective tissue disease, lupus, digestive inflammatory bowel disease, gastritis, infections (recurrent viral infection, recurrent UTI, maternal to foetal infection), and immunodeficiency. Before the right diagnosis, 9 patients received corticosteroids and 6 patients received NSAIDS. Half patients had received repeated antibiotics, one third had received IV Immunoglobulin, and others were treated with immunosuppressive drugs (ciclosporine and methotrexate), and hydroxychloroquine. Eleven on 13 patients were hospitalized at least 5 times before the establishment of the diagnosis. <h3>Conclusions</h3> MKD is a serious disease still difficult to treat, however earlier accurate medical referral and care, by increasing physicians9 awareness, is critical to improve both the disease course and the quality of life. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5636
Abstract 3009: Genetic and epigenetic variations resulting from Alu retrotransposition
Authors: Alexandre de Andrade, Hehuang Xie, Min Wang, Maria F. Bonaldo, Marcelo B. Soares
Journal: Cancer Research (2011)

Abstract Alu repeats are the most prevalent retrotransposons, comprising approximately 10% of the human genome. Alu retrotransposons have amplified during primate evolution by an RNA-mediated copy and paste mechanism. Among the Alu subfamilies, AluY elements and its variants exhibit the highest rates of retrotransposition. De novo retrotransposition of active Alu elements have given rise to insertion polymorphisms in human populations. While generating methylation maps of Alu elements in human normal cerebellum and in ependymoma tumors, Xie and colleagues (2009, 2010) also identified putative new Alu element insertions. In this study, we explored these Alu libraries to identify recent Alu element insertions and to understand the (epi)genetic variations that result from such events. This study may also enable identification of DNA structural variation that may occur at the onset of tumorigenesis and/or during tumor progression. A total of 327 putative recent Alu element insertions represented by 1,762 sequence reads were identified, including 316 events that have not yet been documented in either dbSNP or dbRIP. Forty-seven out of a total of forty-nine randomly selected events representing nineteen genomic loci were sequence-verified. Alu element insertions remained heterozygous for sixteen out of nineteen genomic loci in one or more individuals. The polymorphic Alu elements are enriched for young Alu families and they present some characteristic sequence features, such as longer poly(A) tails. In addition, they also present the TT/AAAA consensus sequence at their 3’-flanking regions, and AT-rich target site duplications. Despite being homozygous or heterozygous insertions, these Alu elements are heavily methylated. Further methylation analysis on two genomic loci revealed no methylation difference in two heterozygous alleles and also no methylation difference at CpG dinucleotides flanking the Alu insertion sites. These results indicate that the recently integrated Alu elements have not influenced the methylation status of their neighboring CpG dinucleotides. 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 3009. doi:10.1158/1538-7445.AM2011-3009
Tamoxifen inhibits cytochrome P450 2C9 activity: A possible mechanism for tamoxifen-warfarin interaction
Authors: M. C. Boruban, M. O. Babaoglu, O. Sencan, A. Bozkurt, U. Yasar
Journal: Journal of Clinical Oncology (2004)

2133 Background: Cytochrome P450 2C9 (CYP2C9) is a clinically important drug metabolizing enzyme, responsible for degradation of warfarin and some other drugs such as acenocoumarol, phenytoin, losartan, oral antidiabetics, non-steroidal anti-inflammatory drugs, etc. Tamoxifen has been reported to potentiate the anticoagulant effect of warfarin, and this interaction can be life-threatening. The mechanism of this interaction has not been identified, yet. Recently, urinary losartan/E-3174 (carboxy metabolite of losartan) ratio has been suggested as a marker for CYP2C9 metabolic activity. The aim of this study was to determine the influence of tamoxifen on CYP2C9 activity. Patients & Method: Six breast cancer patients that would start tamoxifen after adjuvant chemotherapy were included. A single oral dose of 25 mg losartan was given to the patients two days before and two weeks after starting tamoxifen therapy. Losartan and E-3174 in 8-hour urine were assayed by HPLC. The ratios of losartan/E-3174 before the tamoxifen treatment were compared to those during the treatment for each patient. Results: Tamoxifen increased the urinary losartan/E-3174 ratio in five of the patients, up to 6-fold (2.8-fold ± 0.8; mean ± SEM, p=0.03). Conclusion: Tamoxifen inhibits CYP2C9 activity in breast cancer patients as assessed with losartan as a probe drug. The inhibition of CYP2C9 activity may be the possible explanation for tamoxifen-warfarin interaction. CYP2C9 inhibition by tamoxifen may also be important for other CYP2C9 substrates with low therapeutic index like acenocoumarol, phenytoin and oral antidiabetics. (Supported by a grant from the Scientific and Technical Research Council of Turkey, SBAG-COST B15 –2356) No significant financial relationships to disclose.
Abstract 1831: Functional analysis of a novel long ncRNA involved in the tumorigenicity of colorectal cancer.
Authors: Kenzui Taniue, Akiko Kurimoto, Hironobu Sugimasa, Emiko Nasu, Takeshi Nagashima, Mariko Okada-Hatakeyama, Tetsu Akiyama
Journal: Cancer Research (2013)

Abstract In recent years, the advent of high-throughput sequencing technologies has revealed that in addition to protein-coding genes, there are an even larger number of RNA transcripts that do not encode proteins and are instead defined as noncoding RNAs (ncRNAs). Numerous ncRNAs are misregulated in various diseases, especially cancer. We therefore attempted to identify and characterize novel long ncRNAs that regulate the tumorigenicity of colorectal cancer. Here we show that a novel long ncRNA, termed NR-X, is required for proliferation and tumorigenicity of colorectal cancer cells. We further show that NR-X is upregulated under hypoxic conditions and induces expression of hypoxia-responsive genes. Moreover, we succeeded to identify a chromatin-related protein that is associated with NR-X. In this presentation, we would like to present our data on the molecular functions of NR-X and discuss its significance in tumorigenesis. Citation Format: Kenzui Taniue, Akiko Kurimoto, Hironobu Sugimasa, Emiko Nasu, Takeshi Nagashima, Mariko Okada-Hatakeyama, Tetsu Akiyama. Functional analysis of a novel long ncRNA involved in the tumorigenicity of colorectal cancer. [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 1831. doi:10.1158/1538-7445.AM2013-1831
DETERMINANTS OF DIASTOLIC FUNCTION IN ATHLETES AND ROLE OF LEFT VENTRICULAR RELAXATION IN DIFFERENTIATING PHYSIOLOGICAL ADAPTATION FROM HYPERTROPHIC CARDIOMYOPATHY
Authors: Gherardo Finocchiaro, Harshil Dhutia, Michael Papadakis, Alexandros Steriotis, Keerthi Prakash, Elijah Behr, Nabeel Sheikh, Sanjay Sharma
Journal: Journal of the American College of Cardiology (2016)
Prognostic quality of activating TERT promoter mutations in glioblastoma: interaction with the rs2853669 polymorphism and patient age at diagnosis
Authors: Sabine Spiegl-Kreinecker, Daniela Lötsch, Bahil Ghanim, Christine Pirker, Thomas Mohr, Magdalena Laaber, Serge Weis, Alfred Olschowski, Gerald Webersinke, Josef Pichler, Walter Berger
Journal: Neuro-Oncology (2015)

Expression of the telomerase reverse transcriptase (TERT) might be altered by activating mutations of the rs2853669 polymorphism within the promoter region. Here we investigate the impact of these genomic alterations on telomerase activation and dissect their prognostic potential in glioblastoma (GBM).The respective TERT promoter region was sequenced in 126 GBM tissues and compared with clinical parameters and glioma biomarkers MGMT promoter methylation and IDH1 mutation. TERT mRNA expression, telomerase activity, and telomere lengths were determined by reverse transcriptase PCR, TRAP assay, and real-time PCR, respectively.Seventy-three percent of GBM patients harbored TERT promoter mutations associated with enhanced telomerase activity and TERT mRNA expression but reduced telomere lengths (P < .001 for all). Patients with mutated tumors exhibited significantly shorter overall survival in the entire cohort (11.5 vs 23.1 months; P < .0001) and in the primary GBM patient subgroup lacking IDH1 mutations (n = 120; P = .0084). This prognostic impact was confined to younger patients (aged <65 years), while the negative prognostic power of enhanced age at diagnosis was limited to those patients lacking TERT promoter mutations. Presence of the common single nucleotide polymorphism rs2853669, disrupting an endogenous Ets2 transcription factor-binding site, was associated with improved survival exclusively in patients with a wild-type TERT promoter. On the contrary, the shortest mean overall survival was detected in those patients harboring both an activating TERT promoter mutation and homozygous rs2853669 alleles.In summary, TERT promoter mutations are powerful prognosticators for worse course of disease in human GBM patients but their prognostic value is influenced by the rs2853669 polymorphism and age at diagnosis.
Maternal Autoimmunization to Thyroid as a Probable Cause of Athyrotic Cretinism
Authors: Robert M. Blizzard, Robert W. Chandler, Benjamin H. Landing, Mary D. Pettit, Clark D. West
Journal: New England Journal of Medicine (1960)

IMMUNIZATION of animals with extracts of homologous thyroid glands produces circulating antithyroid antibodies. Frequently, lymphocytic infiltration and destruction of the animal's thyroid gland subsequently occurs.1 2 3 4 It is probable that the same phenomena — that is, autoimmunization and autodestruction — similarly contribute to the pathologic physiology of the thyroid gland in patients with Hashimoto's thyroiditis and spontaneous myxedema, and possibly to that in patients with other types of thyroid disease.5 6 7 The current data and present concepts pertaining to the role of autoimmunization and autodestruction in thyroid disease have recently been reviewed by Blizzard and Chandler.8 These accumulated data support the thesis . . .
SP0076 Emerging genetics and molecular aspects of autoinflammatory bone disease
Authors: P. Ferguson
Journal: Annals of the Rheumatic Diseases (2013)

Autoinflammatory disorders of the bone are innate immune system disorders that result in chronic sterile inflammation in the bone. Chronic recurrent multifocal osteomyelitis (CRMO) is the most common autoinflammatory bone disorder in children and synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome is the most common autoinflammatory bone disease in adults. These disorders are often seen in conjunction with chronic inflammatory disorders of the skin (palmar plantar pustulosis and psoriasis vulgaris) and intestine (Crohn disease) suggesting shared pathophysiology. The genetic basis of several autoinflammatory bone diseases have been discovered by studying single gene disorders that have CRMO as a subphenotype. Mutations in <i>LPIN2</i> cause Majeed syndrome, an autosomal recessive disorder which presents with CRMO, congenital dyserythropoietic anemia and neutrophilic dermatosis. Mutations in <i>pstpip2</i> cause chronic multifocal osteomyelitis in an autosomal recessive murine model of the disease that is results in a phenotype and histology that is very similar to human CRMO, however, to date no <i>PSTPIP2</i> mutations have been identified in humans with CRMO. Mutations in <i>IL1RN</i> which encodes the interleukin 1 receptor antagonist have been identified in infants with neonatal onset chronic sterile osteitis, sterile generalized pustulosis associated with systemic inflammation. This syndrome named DIRA (Deficiency of the Interleukin-1 Receptor Antagonist) unequivocally implicates the IL-1 pathway in the pathogenesis of sterile osteomyelitis. An update of the genetics and pathogenesis of the autoinflammatory syndromes will be presented. <h3>Disclosure of Interest</h3> None Declared