tbuckley/cabot-search huggingface dataset:
Tranfusion independence assessed using three alternative dosing schedules of azacitidine in patients with myelodysplastic syndromes
Authors: S. Anthony, R. Lyons, T. Cosgriff, S. Modi
Journal: Journal of Clinical Oncology (2006)

6574 Background: The dosing schedule of azacitidine (75 mg/m 2 /day subcutaneous [SC] × 7 days, every 28 days) decreased transfusion requirements in myelodysplastic syndrome (MDS) patients in a CALGB trial by Silverman et al (JCO 2002;20:2429). Our study assessed effects on transfusion requirements in MDS patients receiving 3 alternative azacitidine dosing regimens not requiring weekend injections. Methods: This phase II, multicenter study enrolled MDS patients with any FAB subtype, life expectancy ≥7 months, and ECOG performance grade of 0–3. RA/RARS patients had to have ≥1 of the following: hemoglobin &lt;110 g/L with transfusion need, platelet counts &lt;100 × 10 9 /L, or ANC &lt;1.5 × 10 9 /L. Patients were randomized to 1 of 3 SC regimens: AZA 5–2-2 (75 mg/m 2 /day × 5 days, followed by 2 days no treatment, followed by 75 mg/m 2 /day × 2 days), AZA 5–2-5 (50 mg/m 2 /day × 5 days, followed by 2 days no treatment, followed by 50 mg/m 2 /day × 5 days), or a 3rd regimen added later by protocol amendment: AZA 5 (75 mg/m 2 /day × 5 days). After 6 cycles, patients meeting International Working Group MDS response/improvement criteria (Blood 2000;96: 3671) of ≥ stable disease could continue in study for 12 more cycles. Results: In all, 75 patients (median age, 74.5 years; 61% male) are currently enrolled with 49 evaluable (completed ≥ 2 treatment cycles). To date, 12, 9, and 1 patient(s) have received ≥6 cycles of AZA 5–2-2, AZA 5–2-5, or AZA 5, respectively. RA + RARS, defined by FAB (60%) or WHO (47%), are the most common MDS subtypes. Of 24 patients, RBC transfusion dependent at baseline, 13 (54%) became independent ( Table ). Only 2 patients were platelet transfusion dependent at baseline; both became independent. After a median followup of 24 weeks, median duration of transfusion independence has not been reached. Conclusions: Treatment with azacitidine yields transfusion independence rates of 40%-60%. These preliminary results are similar across the 3 alternative doses and consistent with previous azacitidine data. [Table: see text] No significant financial relationships to disclose.
Assessment of the impact of the chemotherapeutic regimen on the Cockroft-Gault formulae in estimating renal function in elderly cancer patients.
Authors: J. Spano, N. Magné, P. Chaïbi, C. Hochart, L. Hannoun, C. Tresallet, F. Ménégaux, j. Lefranc, A. Bellanger, D. Khayat
Journal: Journal of Clinical Oncology (2010)

e19662 Background: More and more elderly cancer patients are treated with cytotoxic agents. Elderly patients represent an heterogeneous population in which anticancer therapeutic decision is often difficult and consequences of chemotherapy regimens not clearly established notably in term of renal aspects. Physiological changes such as declining renal function are particularly associated with aging. The present study was conducted in order to evaluate the impact on renal function in a series of elderly cancer patients treated by common chemotherapies regimens. Methods: From May 2005 to October 2009, 375 patients aged over 70 years with solid malignancies were systematically treated by common chemotherapies regimens and registered in a prospective databank at the salpetriere hospital, in Paris, France. Glomerular filtration rate (GFR) was estimated at baseline and before every chemotherapeutic cycle by creatinine clearance (CrCl) measurements. CrCl was calculated by the Cockcroft-Gault formula and values were in ml/min. CrCl under 30 (IV) was defined as severe renal impairment, between 30–60 (III) moderated renal impairment, 60–80 (II) low renal impairment and over 80 (I) normal function. Results: One hundred sixty five male and 210 female with a mean age of 76.3 years (range 70-101.3) were evaluated. Each patient received between 1 to 16 lines of chemotherapy (median of 2) for a total of 1135 lines. More than 75 % of patients had a colorectal, breast, lung, ovary and prostate cancer treated regarding common chemotherapies guidelines. At baseline out of 375 elderly patients, 68 patients (18.1 %) presented a CrCl noted I, 119 (31.7 %) presented a CrCl noted II, 188 (50.1 %) presented a CrCl noted III. At the last evaluation, did not significantly change during the course although a certain decrease of CrCL was found in most of the patients comparing to baseline values. Conclusions: In this representative cohort of elderly cancer patients treated by standard chemotherapeutic regimens, there is no significant impact on the renal functions. However, regarding the degree of the decrease of the glomerular function, physicians must be aware in order to give adapted dose regimen. No significant financial relationships to disclose.
Medicine and multimedia: The RCSE SELECT Programme
Authors: John G Temple
Journal: BMJ (1998)

Royal College of Surgeons of Edinburgh


Available from RCSE (free introductory sample of 3 modules, £400 for all 43 modules) 




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Rating: ★★★

Set at a level sufficient for the basic examinations of the UK Royal Colleges of Surgeons, The RCSE SELECT Programme is a new and innovative distance learning package that comprises 43 modules. It is suggested that this programme will also be of use to higher surgical trainees in all surgical specialties and, as a reference tool, to those at more advanced levels, including those in consultant practice.

The three introductory modules cover the initial stages of this comprehensive package and comprise “Setting the scene”; the first module of critical care, which covers “altered consciousness and confusion”; and the first module of surgery in general, which reviews “rectal bleeding and altered bowel habits.” Each module has the same basic format and covers only one topic. They are clearly set out, easy to read, and well organised. The format is somewhat unusual, but it presents facts, discussion, and management in a way that is easy to assimilate. It concentrates on task based learning, and encourages a rapid assimilation of physiology and pathology, but also indicates up to date sources for further reading. The annotations and line diagrams are generally very clear, although some are rather small and the occasional x rays used are not as distinct as a full page format would have allowed.

These first modules have been well written and fulfil their aims completely. If the remaining 40 modules can maintain this standard, particularly in terms of the clarity of information and explanation, then this will truly be a useful addition to the learning tools available for young surgeons. This is the audience who will derive the most direct benefit from such a modular system, although those at a more senior level who are called on to examine across the broad scope of surgery in general will also find this system a most useful method of revision. The RCSE SELECT Programme deserves to succeed, providing the initial high quality is maintained throughout the remaining modules.
Late-breaking abstract: Respiratory symptoms and inflammatory biomarkers among individuals with nocturnal gastroesophageal reflux
Authors: Össur Ingi Emilsson, Einar Stefán Björnsson, Sunna Gudlaugsdóttir, Anna Soffía Gudmundsdóttir, Bryndís Benediktsdóttir, Ísleifur Ólafsson, Elizabeth Cook, Anna-Carin Olin, Christer Janson, Thórarinn Gíslason
Journal: European Respiratory Journal (2014)

Introduction  Nocturnal gastroesophageal reflux (nGER) has been associated with various respiratory symptoms, but the pathogenesis is still unclear. Our aim was to investigate the association between nGER and exacerbations of respiratory symptoms, with assessment of inflammatory biomarkers both in plasma and exhaled air.  Methods  Participants in the European Community Respiratory Health Survey III (ECRHS III) in Iceland who reported any symptoms of nGER (n=53) as well as age and gender paired controls (n=67) were studied further by using questionnaires, blood tests, laryngeal fiberscopy, exhaled breath condensate (EBC), particles in exhaled air (PEx) measurements and 24 hours esophageal pH impedance measurements. Exacerbations were defined as having at least one episode of marked worsening of respiratory symptoms in the previous 12 months.  Results  Exacerbations were more common in the nGER group compared to controls (19% vs 6%, p=0.03). In EBC, 8-isoprostane was increased in subjects with nGER compared with controls (median (IQR): 2.9 pg/ml (2.7-3.8) vs. 2.8 pg/ml (2.4-3.3), p=0.05). Interleukin 8 (IL-8) in plasma was significantly increased only among those with both exacerbations and nGER compared with controls (median (IQR): 1.8 pg/ml (1.2-5.0) vs. 0.2 pg/ml (0.2-2.5), p=0.01). A positive association was also found between exacerbation frequency and IL-8 level in plasma (p=0.01). Neurokinin A, substance P, surfactant protein A and NO in exhaled air were not related to nGER or exacerbations.  Conclusion  In a general population sample, nGER is associated with more frequent exacerbations of respiratory symptoms and their inflammatory profile seems to differ from those without nGER.
Hybridization of a Myeloid Leukemia-Derived Human Cell Line (K562) With a Human Burkitt's Lymphoma Line (P3HR-1)&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Klein, George, Zeuthen, Jesper, Eriksson, Ingrid, Terasaki, Paul, Bernoco, Marietta, Rosén, Anders, Masucci, Giuseppe, Povey, Susan, Ber, Rosalie
Journal: JNCI Journal of the National Cancer Institute (1980)

The myeloid leukemia-derived Epstein-Barr virus (EBV)-negative human lymphoid cell line K562 was successfully hybridized with the EBV-carrying Burkitt's lymphoma line P3HR-1. Authenticity of the hybrid PUTKO-1 was established by chromosome and isoenzyme studies. A virtually complete hybrid PUTKO-1 carried the EBV genome derived from the lymphoma parent. It averaged 26 EBV DNA copies per cell and was 100% positive for Epstein-Barr virus-associated nuclear antigen (EBNA). In most respects, the hybrid resembled the K562 parent: It had a high Fc receptor concentration, high sensitivity to natural killer cells, absence of EBV C3 receptors, and deficiency of membrane-associated beta 2-microglobulin (beta 2M) and HLA, in parallel with intracellular synthesis and secretion of beta 2M to the medium. Unlike the P3HR-1 parent, the hybrid was completely nonpermissive for antigens of the EBV cycle, early antigen, and viral capsid antigen. None of the 3 inducing agents, 5-lodo-2'-deoxyuridine, 12-O-tetradecanoyl-phorbol 13-acetate, or sodium butyrate, caused any viral antigen synthesis in PUTKO-1 in contrast to the good inducibility of the parental P3HR-1 subline. Thus the myeloid parent restricted expression of EBV antigens except EBNA. This exception further supports the concept that EBNA is an autonomous function of the viral genome, independent of host cell control that regulates expression of antigens related to the viral cycle. On the contrary, extinction of viral antigens in this hybrid between 2 cell lineages supports our previous concept that the ability to produce viral antigens is similar to a differentiated B-cell property.
mtDNA diversity in rhesus monkeys reveals overestimates of divergence time and paraphyly with neighboring species.
Authors: D J Melnick, G A Hoelzer, R Absher, M V Ashley
Journal: Molecular Biology and Evolution (1993)

Reconstructions of the human-African great ape phylogeny by using mitochondrial DNA (mtDNA) have been subject to considerable debate. One confounding factor may be the lack of data on intraspecific variation. To test this hypothesis, we examined the effect of intraspecific mtDNA diversity on the phylogenetic reconstruction of another Plio-Pleistocene radiation of higher primates, the fascicularis group of macaque (Macaca) monkey species. Fifteen endonucleases were used to identify 10 haplotypes of 40-47 restriction sites in M. mulatta, which were compared with similar data for the other members of this species group. Interpopulational, intraspecific mtDNA diversity was large (0.5%-4.5%), and estimates of divergence time and branching order incorporating this variation were substantially different from those based on single representatives of each species. We conclude that intraspecific mtDNA diversity is substantial in at least some primate species. Consequently, without prior information on the extent of genetic diversity within a particular species, intraspecific variation must be assessed and accounted for when reconstructing primate phylogenies. Further, we question the reliability of hominoid mtDNA phylogenies, based as they are on one or a few representatives of each species, in an already depauperate superfamily of primates.
Abstract 16640: Association of Cardiovascular Health in Young Adulthood with Left Ventricular Structure and Function Later in Life: The Coronary Artery Risk Development in Young Adults (Cardia) Study
Authors: Chintan S Desai, Hongyan Ning, Kiang Liu, Jared Reis, Samuel S Gidding, Joao C Lima, Donald M Lloyd-Jones
Journal: Circulation (2012)

BACKGROUND: The American Heart Association defines cardiovascular health (CVH) based on seven metrics. We sought to determine the association between CVH in young adulthood and left ventricular (LV...
Bullous pemphigoid suggestive of complement‐independent blister formation with anti‐ <scp>BP</scp> 180 IgG4 autoantibodies
Authors: T. Dainichi, W. Nishie, Y. Yamagami, H. Sonobe, H. Ujiie, Y. Kaku, K. Kabashima
Journal: British Journal of Dermatology (2016)

Journal Article Bullous pemphigoid suggestive of complement‐independent blister formation with anti‐BP180 IgG4 autoantibodies Get access T. Dainichi, T. Dainichi Department of Dermatology Kyoto University Graduate School of Medicine Kyoto Japan E‐mail: dainichi@kuhp.kyoto-u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar W. Nishie, W. Nishie Department of Dermatology Hokkaido University Graduate School of Medicine Sapporo Japan Search for other works by this author on: Oxford Academic Google Scholar Y. Yamagami, Y. Yamagami Department of Dermatology Nagahama Red Cross Hospital Nagahama Japan Search for other works by this author on: Oxford Academic Google Scholar H. Sonobe, H. Sonobe Department of Dermatology Yamatotakada Municipal Hospital Yamatotakada Japan Search for other works by this author on: Oxford Academic Google Scholar H. Ujiie, H. Ujiie Department of Dermatology Hokkaido University Graduate School of Medicine Sapporo Japan Search for other works by this author on: Oxford Academic Google Scholar Y. Kaku, Y. Kaku Department of Dermatology Kyoto University Graduate School of Medicine Kyoto JapanDepartment of Dermatology Nagahama Red Cross Hospital Nagahama Japan Search for other works by this author on: Oxford Academic Google Scholar K. Kabashima K. Kabashima Department of Dermatology Kyoto University Graduate School of Medicine Kyoto JapanSingapore Immunology Network (SIgN) and Institute of Medical Biology Agency for Science Technology and Research (A*STAR) Biopolis SingaporePRESTO Japan Science and Technology Agency Kawaguchi Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 175, Issue 1, 1 July 2016, Pages 187–190, https://doi.org/10.1111/bjd.14411 Published: 01 July 2016
Array comparative genomic hybridization and expression analyses for the identification of candidate oncogenes co-amplified on chromosomes 8p and 11q in breast cancer
Authors: Serena S. Kwek, Antoine M. Snijders, Bauke Ylstra, Jane Fridlyand, Ritu Roydasgupta, Daniel Pinkel, Donna G. Albertson
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4190 

Co-amplification of chromosomes 11q12-11q14 and 8p12-8p11 occurs frequently together in breast cancer. Preliminary analyses of 60 ductal invasive breast tumors with whole genome array Comparative Genomic Hybridization (array CGH) show that 7% contain both of these amplifications, another 7% contain amplification on chromosome 11q but not on 8p, and 3% contain amplification on 8p but not on 11q. To identify the minimal amplified regions on chromosomes 8p and 11q, array CGH was carried out on a high-resolution array containing a contig of overlapping DNA sequences in these regions. Eight cell lines from breast tumors, three with amplifications on both chromosomes 8p and 11q, three with amplifications on chromosome 11q but not on 8p, and two with amplifications on chromosome 8p but not on 11q, and five ductal invasive breast tumors with amplifications on both chromosomes previously analyzed with the whole genome array were analyzed with the high-resolution array. Real-time PCR was used to determine the expression of RNA of candidate genes in these regions in the cell lines with amplifications in comparison with cell lines without amplification on chromosome 8p and 11q. Affymetrix expression and array CGH data from a further set of 90 breast tumors and 54 cell lines with all forms of aberrations were used to narrow down the candidate genes in these regions. Where antibodies are available, the protein levels of some of these genes in the cell lines correlate with the RNA expression levels. Functional assays are underway to determine which genes are the driving oncogenes and if there are cooperating oncogenes on chromosomes 8p and 11q in breast tumors with these aberrations.
The Role of Tumor-Infiltrating Lymphocytes in Development, Progression, and Prognosis of Non–Small Cell Lung Cancer
Authors: Roy M. Bremnes, Lill-Tove Busund, Thomas L. Kilvær, Sigve Andersen, Elin Richardsen, Erna Elise Paulsen, Sigurd Hald, Mehrdad Rakaee Khanehkenari, Wendy A. Cooper, Steven C. Kao, Tom Dønnem
Journal: Journal of Thoracic Oncology (2016)
Abstract 208: Defining the functions of mitochondrial Telomerase Reverse Transcriptase
Authors: Nicole Buechner, Christine Goy, Lothar Ludwig Rabanter, Sascha Jakob, Joachim Altschmied, Judith Haendeler
Journal: Circulation Research (2013)

Over the last few years it has become clear that mitochondria are not only the powerhouses of the cells, having their sole function in producing ATP. Proteome-analyses of mitochondria from different organisms and organs revealed that more than 1000 proteins are localized in and or on the mitochondria. This by far exceeds the number of proteins required for classical mitochondrial functions, e.g. the respiratory chain, the tricarboxylic acid cycle, fatty acid oxidation and apoptosis. This suggests that many of these proteins have other, as yet unknown functions. We identified Telomerase Reverse Transcriptase (TERT), an enzyme that, in the nucleus, protects telomeres, the ends of the chromosomes, against shortening, also in the mitochondria. However, up to now only (TERT) deficient cells and mice or TERT overexpressing cells were used to study nuclear and mitochondrial functions of TERT. In this context, we demonstrated that reduction of endogenous TERT leads to increased reactive oxygen species (ROS) production in the cytosol as well as in the mitochondria. To analyze now specifically the functions of mitochondrial TERT, we isolated TERT deficient fibroblasts and transduced them with lentiviruses containing mitochondrially targeted TERT. We first validated these newly generated cells for transgene insertion and expression. Next, we analyzed compartment specific ROS production and apoptosis in the cells. We observed a reduction specifically in the levels of mitochondrial, but not cytosolic ROS. Moreover, apoptosis induction was significantly reduced in these cells compared to TERT deficient cells as well as cells containing endogenous TERT. Thus, mitochondrial TERT specifically reduces mitochondrially produced ROS and protects cells against apoptosis. In comparison to nuclear TERT, which has the main function to prolong telomeres, mitochondrial TERT specifically protects mitochondria from damage. Currently, we are creating mice that carry mitochondrially targeted TERT on an otherwise TERT deficient background for in vivo experiments.
THE EFFECT OF FREE FATTY ACID AND REACTIVE OXYGEN SPECIES ON CIDEB EXPRESSION IN IN VITRO MODEL OF STEATOSIS
Authors: Khalida A. Lockman, Nikolas Plevris-Papaioannou, James P. Baren, Pauline Cowan, Patricia Lee, Anne Pryde, Peter C. Hayes, Alan J. Jaap, Celine Filippi, John N. Plevris
Journal: Hepatology (2010)
Abstract 16875: Clinical and Echocardiographic Predictors of Deterioration in Left Ventricular Ejection Fraction in Patients With Low-Flow Significant Aortic Stenosis
Authors: Glenn K Lee, Valencia Lim, Ivandito Kuntjoro, Edgar L Tay, Tiong Cheng Yeo, Kian Keong Poh
Journal: Circulation (2013)
Cherry-flavoured electronic cigarettes expose users to the inhalation irritant, benzaldehyde
Authors: Leon Kosmider, Andrzej Sobczak, Adam Prokopowicz, Jolanta Kurek, Marzena Zaciera, Jakub Knysak, Danielle Smith, Maciej L Goniewicz
Journal: Thorax (2016)

Many non-cigarette tobacco products, including e-cigarettes, contain various flavourings, such as fruit flavours. Although many flavourings used in e-cigarettes are generally recognised as safe when used in food products, concerns have been raised about the potential inhalation toxicity of these chemicals. Benzaldehyde, which is a key ingredient in natural fruit flavours, has been shown to cause irritation of respiratory airways in animal and occupational exposure studies. Given the potential inhalation toxicity of this compound, we measured benzaldehyde in aerosol generated in a laboratory setting from flavoured e-cigarettes purchased online and detected benzaldehyde in 108 out of 145 products. The highest levels of benzaldehyde were detected in cherry-flavoured products. The benzaldehyde doses inhaled with 30 puffs from flavoured e-cigarettes were often higher than doses inhaled from a conventional cigarette. Levels in cherry-flavoured products were &gt;1000 times lower than doses inhaled in the workplace. While e-cigarettes seem to be a promising harm reduction tool for smokers, findings indicate that using these products could result in repeated inhalation of benzaldehyde, with long-term users risking regular exposure to the substance. Given the uncertainty surrounding adverse health effects stemming from long-term inhalation of flavouring ingredients such as benzaldehyde, clinicians need to be aware of this emerging risk and ask their patients about use of flavoured e-cigarettes.