tbuckley/cabot-search huggingface dataset:
Evaluation of Chest Pain in the Emergency Department
Authors: Jeffrey M. Bloom
Journal: Annals of Internal Medicine (1995)

Letters15 August 1995Evaluation of Chest Pain in the Emergency DepartmentJeffrey M. BloomJeffrey M. BloomSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-123-4-199508150-00018 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:In an otherwise excellent summary of the problems of cost-effective emergency department evaluation of chest pain, Drs. Kaul and Abbott [1] provided two “cost-effective and efficient approaches” that I believe do not realistically apply to the managed care era. For example, they recommend for chest pain of uncertain origin, a cardiology consultation and possible nuclear perfusion imaging, echocardiography, coronary angiography, and percutaneous transluminal angioplasty—procedures that may be unnecessary and are costly. What must first be evaluated is the relative risk for myocardial infarction based on the history, physical examination, electrocardiogram, chest radiograph, and so forth before a ...REFERENCE1. Kaul S, Abbott RD. Evaluation of chest pain in the emergency department (Editorial). Ann Intern Med. 1994; 121:976-8. Google Scholar Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 August 1995Volume 123, Issue 4Page: 314-318KeywordsCardiac care unitElectrocardiographyEmergency departmentIschemiaLower back painMyocardial infarctionPatientsRelative riskThoraxTroponin T Issue Published: 15 August 1995 Copyright & PermissionsCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Loss of CD55 in Eculizumab-Responsive Protein-Losing Enteropathy
Authors: Alina Kurolap, Orly Eshach-Adiv, Tova Hershkovitz, Tamar Paperna, Adi Mory, Danit Oz-Levi, Yaniv Zohar, Hanna Mandel, Judith Chezar, David Azoulay, Sarit Peleg, Elizabeth E Half, Vered Yahalom, Lilach Finkel, Omer Weissbrod, Dan Geiger, Adi Tabib, Ron Shaoul, Daniella Magen, Lilach Bonstein, Dror Mevorach, Hagit N Baris
Journal: New England Journal of Medicine (2017)

Loss of CD55 in Eculizumab-Responsive Protein-Losing EnteropathyTo the Editor: Protein-losing enteropathy usually manifests as peripheral and visceral edema due to hypoalbuminemia. 1 We followed a large consanguineous Muslim-Arab family that included six patients who had protein-losing enteropathy associated with hypercoagulability (Fig. S1A in the Supplementary Appendix, available with the full text of this letter at NEJM.org).Disease onset was between 10 months and 3 years of age, and the patients presented with generalized edema, severe hypoalbuminemia (reaching 0.5 g per deciliter), diarrhea, and abdominal complications, with repeated thrombotic events occurring in three of them.Supportive management of the disorder with a low-fat diet and supplementation with medium-chain triglycerides only partially improved the nutritional status of the patients who adhered to the dietary regimen.Two patients died from disease complications.Additional clinical data are available in the Supplementary Appendix.Whole-exome sequencing analysis revealed a homozygous frameshift variant in CD55 (GenBank number, NM_001114752 .1), c.43del (p.Leu15Serfs*46) (ClinVar accession number, SCV000579315).The variant segregated with the disease phenotype in the extended family; that is, only patients were homozygotic for the variant, whereas healthy family members either were heterozygotic for the variant or had the wildtype gene.Flow cytometric and hemagglutination studies revealed markedly decreased binding of CD55 antigens on patients' red cells and granulocytes, as compared with those of unaffected persons.Abnormal complement activation was observed in patients with CD55 deficiency; that is, membrane attack complex (MAC) deposition
Abstract 049: Functional Characterization of KCNQ1 Channel Subunit With an A590T Mutation
Authors: Koshi Kinoshita, Katsuya Kimoto, Takuto Komatsu, Kohki Nishide, Toshihide Tabata, Fukiko Ichida, Yoshiaki Yamaguchi, Kunihiro Nishida, Hiroshi Inoue, Yukiko Hata, Naoki Nishida
Journal: Circulation Research (2013)

Background: KCNQ1 encodes the alpha subunit of the voltage-gated K + channel that mediates the cardiac slow delayed rectifier K + current (I Ks ). A mutation, A590T, in KCNQ1 was incidentally identified in a 40 years old female. She had a mild QTc prolongation in electrocardiogram but has never experienced any cardiac events. A590 is located in the C-terminal domain forming a coiled-coil structure, which has been suggested as a pivotal component for subunit tetramerization and channel trafficking to the cell surface. The previously reported mutations around A590 result in markedly reduced cell surface expression and loss of functional channel. We, for the first time, examined whether and how the A590T mutation affects the I Ks channel function. Methods: To assess the trafficking and channel function of KCNQ1(A590T) mutant subunit, we performed immunostaining, immunoblotting, and voltage-clamp measurements in HEK-293T cells transfected with wild-type or the A590T mutant KCNQ1 or their mixture (WT, A590T, and A590T/WT cells, respectively). Results: The density of a depolarization-activated current in the A590T cells was smaller than that in the WT cells. The threshold, half-maximal activation, and saturating voltages of the depolarization-activated current in the A590T cells were more positive than those in the WT cells. The immunoreactivity against KCNQ1 subunit on the cell surface in the A590T cells is lower than in WT cells. The A590T/WT cells had a similar density of the depolarization-activated current and a similar level of immunoreactivity against the channel subunit to the WT cells. Furthermore, the immunoblotting detected subunit oligomers in the membrane fraction of the A590T cells while their densities were lower than those of the WT cells. Conclusion: Although the A590T mutant subunit can form oligomers for itself, this subunit is not efficiently trafficked to the cell surface without the aid of the WT subunit. Thus, homozygous inheritance of the mutant KCNQ1 might be pathogenic. By contrast, the cells expressing both the mutant and wild-type KCNQ1 subunit had normal I Ks and cell surface expression, indicating that the heterozygous inheritance of the mutant KCNQ1 might not cause severe cardiac diseases.
Regulation of C-terminal and N-terminal fragments of HER2 by mRNA.
Authors: Daishu Miura, Masami Kadowaki, Nobuko Tamura, Hidetaka Kawabata, Takeshi Fujii
Journal: Journal of Clinical Oncology (2014)

e11593 Background: A subgroup of HER2-positive breast cancers express a series of C-terminal fragments of HER2 (H2CT) collectively known as HER2 CTFs or p95HER2. H2CT cancers have worse prognosis and are resistant to the treatment with trastuzumab. While the existence of a novel N-terminal fragment of HER2 (H2NTF), characterized to be devoid of the tyrosine kinase domain but it readily interacts with full-length HER2 (H2FL) and other HER families was recently described. H2NT is frequently expressed in breast cancer samples and acts as a dominant negative, attenuating the signaling triggered by full-length HER receptors. We wish to determine whether H2FL, H2CT, and H2NT are regulated by the transcription of mRNA using clinical samples and also determine the clinical characterizations of these cancers. Methods: Among early breast cancers with HER2 over-expressed who received neo-adjuvant chemotherapy (FEC/EC followed by weekly paclitaxel and trastuzumab), 20 samples of pre-treatment biopsy specimen available were selected (10 ER+ve. and 10 ER–ve. samples). We performed in situ hybridization of mRNA using the QuantiGene viewRNA (Affymetrix) that has unique probe designing and branched DNA to amplify the signal to detect mRNA in FFPE tissue samples. We used 2 kinds of probes for human erbb2 (NM_004448). Targeted sequence of one probe is from 1nt to 2068nt (NTF, red) and another is from 2069nt to the end (CTF, blue). We used these probes to identify the truncated region of HER2 and defined H2NT as having red dominant, H2CT as having blue dominant, and H2FL as almost similar number of red and blue signals. Results: Among 20 cases, pathological CR (pCR) was found in 6 and distant recurrence in 3 cases. Both red (N-terminal) and blue (C-terminal) were found in all 20 samples. Twelve samples were in H2FL, 4 in H2NT, and 4 in H2CT. All 4 in H2CT were ER negative and 3 out of 4 had pCR. Two out of 3 who had distant recurrence were in H2NT. Conclusions: We found the short fragments of HER2 mRNA in HER2 over-expressed breast cancer samples by in situ hybridization and also one of the possibilities that different subtype of H2CT and H2NT from H2FL were generated by mRNA transcription. As similar results of previous description, none of the H2CT was ER positive.
Statistical Approaches for Estimating Sex-Specific Effects in Endocrine Disruptors Research
Authors: Jessie P. Buckley, Brett T. Doherty, Alexander P. Keil, Stephanie M. Engel
Journal: Environmental Health Perspectives (2017)

Background: When a biologic mechanism of interest is anticipated to operate differentially according to sex, as is often the case in endocrine disruptors research, investigators routinely estimate sex-specific associations. Less attention has been given to potential sexual heterogeneity of confounder associations with outcomes. When relationships of covariates with outcomes differ according to sex, commonly applied statistical approaches for estimating sex-specific endocrine disruptor effects may produce divergent estimates. Objectives: We discuss underlying assumptions and evaluate the performance of two traditional approaches for estimating sex-specific effects, stratification and product terms, and introduce a simple modeling alternative: an augmented product term approach. Methods: We describe the impact of assumptions regarding sexual heterogeneity of confounder relationships on estimates of sex-specific effects of the exposure of interest for three approaches: stratification, traditional product terms, and augmented product terms. Using simulated and applied examples, we demonstrate properties of each approach under a range of scenarios. Results: In simulations, sex-specific exposure effects estimated using the traditional product term approach were biased when confounders had sex-dependent associations with the outcome. Sex-specific estimates from stratification and the augmented product term approach were unbiased but less precise. In the applied example, the three approaches yielded similar estimates, but resulted in some meaningful differences in conclusions based on statistical significance. Conclusions: Investigators should consider sexual heterogeneity of confounder associations when choosing an analytic approach to estimate sex-specific effects of endocrine disruptors on health. In the presence of sex-dependent confounding, our augmented product term approach may be advantageous over stratification when there is prior knowledge available to fit reduced models or when investigators seek an automated test for effect measure modification. https://doi.org/10.1289/EHP334
INJURIES AND ILLNESS DURING MASS-PARTICIPATION TRIATHLON RACES: OPTIMISING COMPETITOR SAFETY
Authors: Courtney Kipps, Ralph Smith, Nick Knight, James Parkin
Journal: British Journal of Sports Medicine (2017)

Background Triathlon is an increasingly popular mass-participation endurance sport which incorporates swimming, cycling and running stages over a variety of distances. Overuse injuries during triathlon training are common (Zwingenberger et al . 2014; Korkia et al . 1994) however the incidence of illness and injury during triathlon races is less well described. A clear understanding of this data is valuable in planning medical care for mass-participation triathlon races. Objective To describe the epidemiology of illness and injuries during triathlon races in the UK. Design Retrospective analysis of competitors' medical records (CMRs). Setting Two large summer triathlons over 5 years. Participants All triathlon competitors requiring treatment by the triathlon medical team (TMT) for illness or injury (excluding first aid). Assessment of Risk Factors Age, gender, race distance, race experience, mechanism of injury, co-morbidities, and medical management was recorded. Main Outcome Measurements Number of cases of medical illness, musculoskeletal (MSK) injury, and topical injury (e.g. abrasions) treated by the TMT. Results There were 68557 starters and 67270 finishers across Supersprint, Sprint, Olympic and OlympicPlus distances (2.3% did not finish) from 11 consecutive events. The TMT treated 429 competitors (0.62%, 1/161 starters) for complaints including falls, fractures, breathlessness and collapse. Medical illness was the most common complaint (44.1%), followed by MSK injury (27.1%) and topical injury (24.8%). There were three cardiorespiratory arrests during the swim leg including two successful resuscitations (1/34279 starters) and one fatality (1/68557). The run leg was responsible for most MSK injuries (41.4% of all injuries) and nearly a third (11/38) of all hospital transfers. Conclusions Triathlons have a high incidence of both illness and injury. The swim leg had the most serious medical conditions whilst the run accounted for most injuries. Triathlon organisers should be aware of these findings to ensure optimal medical care and competitor safety at mass-participation triathlon races.
Abstract 273: Levels Of Vcam-1 Are Associated With Flow-mediated Dilation In Healthy African American Adults
Authors: CHENYI LING, Sheara Williamson, Keith Diaz, Jan Kretzschmar, Deborah Feairheller, Kathleen Sturgeon, Praveen Veerabhadrappa, Amanda Perkins, Hojun Lee, Heather Grimm, Abul Kashem, Dianne Babbitt, Michael Brown
Journal: Circulation Research (2013)

Background: Vascular cell adhesion molecule-1 (VCAM-1) mediates the adhesion of monocytes to vascular endothelium, which play a role in the development of endothelial dysfunction and atherosclerosis. Flow-mediation dilation (FMD) is an endothelium-dependent response, which is mediated by nitric oxide and closely related to endothelial function. The purpose of the study was to test whether levels of VCAM-1 were associated the endothelial-dependent (FMD) in normotensive African Americans. Normotensives were studied in order to eliminate the influence of hypertension. Methods and Results: Blood was collected in 22 subjects aged 41-62 yrs with normal blood pressure (125.0 ± 9.1 mmHg) after 12 hr fast. Plasma was obtained by centrifugation within 15 min after collection in 4 degree. A commercially available solid phase sandwich enzyme linked immuno-sorbent assay kit was used to detect VCAM-1 levels in plasma. FMD was measured after 5-min cuff occlusion using Doppler ultrasound. The maximum FMD diameters were calculated. In the entire study population, levels of VCAM-1 (556.92 ± 154.20 ng/mL) were negatively correlated with the true peak FMD (FMD: 7.81 ± 2.22 %, r=-0.484, P=0.023). Conclusion: Levels of VCAM-1 were associated with endothelial responsiveness in healthy African Americans with normal blood pressure. These results suggest that the level of VCAM-1 may be a predictive of endothelial dysfunction in the unique healthy populations.
Identification of a PVL-negative SCC mec -IVa sublineage of the methicillin-resistant Staphylococcus aureus CC80 lineage: understanding the clonal origin of CA-MRSA
Authors: S.M. Edslev, H. Westh, P.S. Andersen, R. Skov, N. Kobayashi, M.D. Bartels, F. Vandenesch, A. Petersen, P. Worning, A.R. Larsen, M. Stegger
Journal: Clinical Microbiology and Infection (2017)

ObjectivesCommunity-acquired (CA) methicillin-resistant Staphylococcus aureus (MRSA) isolates belonging to clonal complex 80 (CC80) are recognized as the European CA-MRSA. The prevailing European CA-MRSA clone carries a type IVc staphylococcal cassette chromosome mec (SCCmec) and expresses Panton-Valentine leukocidin (PVL). Recently, a significant increase of PVL-negative CC80 MRSA has been observed in Denmark. The aim of this study was to examine their genetics and epidemiology, and to compare them to the European CA-MRSA clone in order to understand the emergence of PVL-negative CC80 MRSA.MethodsPhylogenetic analysis of the CC80 S. aureus lineage was conducted from whole-genome sequences of 217 isolates (23 methicillin-susceptible S. aureus and 194 MRSA) from 22 countries. All isolates were further genetically characterized in regard to resistance determinants and PVL carriage, and epidemiologic data were obtained for selected isolates.ResultsPhylogenetic analysis revealed the existence of three distinct clades of the CC80 lineage: (a) an methicillin-susceptible S. aureus clade encompassing Sub-Saharan African isolates (n = 13); (b) a derived clade encompassing the European CA-MRSA SCCmec-IVc clone (n = 185); and (c) a novel and genetically distinct clade encompassing MRSA SCCmec-IVa isolates (n = 19). All isolates in the novel clade were PVL negative, but carried remnant parts (8–12 kb) of the PVL-encoding prophage ΦSa2 and were susceptible to fusidic acid and kanamycin/amikacin. Geospatial mapping could link these isolates to regions in the Middle East, Asia and South Pacific.ConclusionsThis study reports the emergence of a novel CC80 CA-MRSA sublineage, showing that the CC80 lineage is more diverse than previously assumed.
RANK/EGFR interplay in breast cancer.
Authors: Anastasios D Papanastasiou, Chaido Sirinian, Eva Plakoula, Thomas Makatsoris, Vassiliki Zolota, Maria Repanti, Haralabos Kalofonos
Journal: Journal of Clinical Oncology (2016)

e13011 Background: Breast cancer is the most common malignancy, affecting one in eight women in North America and Europe. The human epidermal growth factor receptor (EGFR) protein is a type I transmembrane receptor that comprise a major determinant of normal development but also cancer. RANK receptor (Receptor Activator of Nuclear factor-kB) is a tumor necrosis superfamily member and binding partner for RANKL, which was recently implicated in breast cancer initiation, progression and metastasis. Here we provide preliminary evidence of a possible interplay between RANK and EGFR signaling in breast cancer. Methods: TCGA (cancergenome.nih.gov) publicly available mRNA and protein expression data (RNA Seq V2 RSEM) for EGFR and TNFSRF11A (RANK) genes from an unselected cohort of 1036 breast cancer patients and 58 breast cancer cell lines were retrieved and analyzed. EGFR and TNFSRF11A mRNA expression were also evaluated through real-time RT-PCR in a panel of 7 human breast cancer cell lines and 22 FFPE breast cancer samples. Plasmid transfections and western blots were performed to evaluate EGFR and RANK downstream signaling after EGF stimulation. Results: Between the four family members of ErbB (EGFR, ERBB2/3/4) receptors, RANK mRNA showed a statistically significant positive correlation (p< 0.001) with the mRNA and protein expression of EGFR, but not with ERBB2/3/4. The same positive mRNA correlation was observed in between the 58 CCLE breast cancer cell lines, seven in house breast cancer cell lines and 22 FFPE cases. RANK plasmid transfection and western blotting revealed a significant upregulation of ERK (pp44/42) signaling after EGF stimulation in cell lines. Finally, further analyses of survival data of a group of breast cancer patients (n = 248) from TCGA, revealed an EGFRhi RANKhi subpopulation that showed a statistically significant (p= 0.001) reduced overall survival when compared to EGFRlowRANKlowgroup of patients. Conclusions: In this study we provide preliminary evidence that RANK is co-expressed with EGFR in a subset of breast cancer patients, with worse clinical outcome. RANK and EGFR co-expression in cell lines seems to augment EGF-induced ERK signaling, giving raise to the possibility of simultaneous therapeutic targeting of RANK/EGFR in breast cancer.
Chief medical officer wants genomic services to be centralised within five years
Authors: Ingrid Torjesen
Journal: BMJ (2017)

Genomics medicine needs to evolve from a “cottage industry” to become a centralised service if its full potential to improve the diagnosis and management of patients with rare diseases and cancer is to be realised, England’s chief medical officer (CMO) says.

Sally Davies set out a series of recommendations on genomics medicine in her annual report.1

“We have got patients across the NHS accessing the latest genomic diagnoses and treatments. But not everyone is, and I want us to democratise genomics,” she told a press conference in London on Monday.

Currently genomic services are delivered by 25 regional laboratories plus a …
Historical demography and longevity genetics: Back to the future
Authors: Niels van den Berg, Marian Beekman, Ken Robert Smith, Angelique Janssens, Pieternella Eline Slagboom
Journal: Ageing Research Reviews (2017)

Research into the genetic component of human longevity can provide important insights in mechanisms that may protect against age-related diseases and multi-morbidity. Thus far only a limited number of robust longevity loci have been detected in either candidate or genome wide association studies. One of the issues in these genetic studies is the definition of the trait being either lifespan, including any age at death or longevity, i.e. survival above a diverse series of thresholds. Likewise heritability and segregation research have conflated lifespan with longevity. The heritability of lifespan estimated across most studies has been rather low. Environmental factors have not been sufficiently investigated and the total amount of genetic variance contributing to longevity has not been estimated in sufficiently well-defined and powered studies. Up to now, genetic longevity studies lack the required insights into the nature and size of the genetic component and the optimal strategies for meta-analysis and subject selection for Next Generation Sequencing efforts. Historical demographic data containing deep genealogical information may help in estimating the best definition and heritability for longevity, its transmission patterns in multi-generational datasets and may allow relevant additive and modifying environmental factors such as socio-economic status, geographical background, exposure to environmental effects, birth order, and number of children to be included. In this light historical demographic data may be very useful for identifying lineages in human populations that are worth investigating further by geneticists.
Comparison of ERCP procedures performed in a tertiary referral centre in 1996 and 2002
Authors: R Cooney, J Groarke, N Mahmud, PWN Keeling, S McKiernan
Journal: Endoscopy (2006)

The number of procedures performed decreased from 768 in 1996 to 541 in 2002 (29.6% decrease). The average age in 1996 was 66 years (median 69 years and range 17–94 years) and 52 years in 2002 (median 65 years and range 24–93 years). The redo rate was similar 19.34% (148) in 1996 and 19.96% (108) in 2002. In 1996 there were 321 repeat procedures recommended and this decreased to 120 in 2002.
Efficacy and Safety of Melphalan 140mg/m2 Conditioned Autologous Stem Cell Transplantation in Elderly Pre-Dialysis and Dialysis Patients with Multiple Myeloma
Authors: Hatem Ali, Baharani Jyoti, Shankaranarayana Paneesha, Richard Lovell, Alex George Kanellopoulos, Evgenia Xenou, Iman Qureshi, Lorna Cain, Maria Kaparou, David John Sutton, Rebecca Pryor, Emmanouil Nikolousis, Bhuvan Kishore
Journal: Blood (2016)