tbuckley/cabot-search huggingface dataset:
Effect of aclidinium bromide/formoterol fumarate fixed-dose combination (FDC) on exacerbations in moderate-to-severe COPD: Pooled analysis of two studies
Authors: Eric Bateman, Stephen Rennard, Paul Jones, Eduard Molins, Man Jin, Anne Leselbaum
Journal: European Respiratory Journal (2014)

Background 

Twice-daily (BID) aclidinium/formoterol 400/12 µg FDC is in development for treatment of COPD.

Methods 

Data were pooled for two 24-week, randomised, double-blind Phase 3 studies of aclidinium/formoterol FDC in patients with moderate-to-severe COPD (ACLIFORM and AUGMENT). Patients received FDC (400/6 µg or 400/12 µg), aclidinium 400 µg, formoterol 12 µg or placebo (all BID via Genuair® inhaler). Prior exacerbation was not an inclusion criterion. Exacerbations (reported and unreported) were assessed by healthcare resource utilisation (HCRU; symptom increase on ≥2 consecutive days requiring treatment change) and the EXAcerbations of Chronic pulmonary disease Tool (EXACT; increase ≥9 points for ≥3 days or ≥12 points for ≥2 days).

Results 

Data were analysed for 3398 patients (safety population; means: age 63.5 years, 60.5% male, GOLD stage II, 58.6%; III, 40.8%). Treatment with FDC 400/12 µg significantly reduced moderate-severe HCRU (29%; p<0.05) and EXACT (22%; p<0.01) exacerbation rates vs placebo. Time to first exacerbation was significantly delayed for FDC 400/12 µg vs placebo (hazard ratio 0.70 [moderate-severe HCRU] and 0.79 [EXACT]; both p<0.05).

Conclusion 

In a study population where prior exacerbation was not an inclusion criterion, aclidinium/formoterol 400/12 µg FDC reduced the rate of COPD exacerbations defined by HCRU or EXACT.

![Figure][1]  [1]: pending:yes
Septicaemia due to Colonization of Spitz-Holter Valves by Staphylococci
Authors: R. P. Callaghan, S. J. Cohen, G. T. Stewart
Journal: BMJ (1961)

In progressive hydrocephalus treated by a ventriculo- caval shunt using a Spitz-Holter valve, infection at the site of operation is apt to cause septicaemia.We are describing here five cases in which the problems of chemotherapy were closely studied, because (1) the valves were controlling the hydrocephalus perfectly, (2) the removal of the valve renders that internal jugular vein unsuitable for use later should a further shunt be required, and (3) the infants were not uncontrollably ill with the septicaemia.The clinical and the bacteriological approach to this study are described in separate publications (Cohen and Callaghan, 1961 Stewart, 1961).
Use of the Rat Gene Index to examine gene expression patterns from Src-transformed rat fibroblasts that exhibit broad differences in metastatic potential
Authors: Renae L. Malek, Qingbin Guo, Mauro Ruffy, Edison T. Liu, Ingeborg Holt, Ishwar Chandra, Feng Liang, Jonathan Upton, John Quackenbush, Richard Jove, Timothy J. Yeatman, Norman H. Lee
Journal: Nature Genetics (1999)
The RyR2 central domain peptide DPc10 lowers the threshold for spontaneous Ca2+ release in permeabilized cardiomyocytes
Authors: Z YANG, N IKEMOTO, G LAMB, D STEELE
Journal: Cardiovascular Research (2006)

In vitro experiments have shown that the ryanodine receptor-2 (RyR2) central domain peptide DPc10 (Gly(2460)-Pro(2495)) mimics channel dysfunction associated with catecholaminergic polymorphic ventricular tachycardia (CPVT) by acting competitively to reduce stabilizing interactions between the N-terminal and central domains. In the present study, DPc10 was used as a tool to establish an adult cell model of the disease and to analyse the underlying mechanisms.Rat ventricular myocytes were permeabilized with saponin and perfused with solutions approximating the intracellular milieu containing fluo-3. Sarcoplasmic reticulum (SR) Ca(2+) release was detected using confocal microscopy. DPc10 (10 or 50 microM) was compared with 0.2 mM caffeine, which is known to activate RyR2 and to facilitate Ca(2+)-induced Ca(2+) release (CICR).Introduction of DPc10 induced a transient increase in spark frequency and a sustained rise in resting [Ca(2+)]. Under conditions causing initial Ca(2+) overload of the SR, DPc10 reduced the frequency and amplitude of spontaneous, propagated Ca(2+) release (SPCR). Following equilibration with 10microM DPc10, the cytosolic [Ca(2+)] threshold for SPCR was markedly reduced and the proportion of spontaneously active cells increased. Caffeine induced a similar, transient increase in spark frequency and a reduction in the [Ca(2+)] threshold for SPCR. However, unlike DPc10, caffeine increased SPCR frequency and had no sustained effect on resting [Ca(2+)]. These results suggest that the net effect of DPc10 (and CPVT mutations) on RyR2 function in situ is not only to increase the sensitivity to CICR as caffeine does, but also to potentiate Ca(2+) leakage from the SR. As SPCR can trigger delayed after-depolarisations, the decrease in [Ca(2+)] threshold may contribute to arrhythmias in CPVT patients during exercise or stress.
Factors affecting the response to insulin in the normal subhuman pregnant primate
Authors: Ronald A. Chez, Daniel H. Mintz, Edgar O. Horger, Donald L. Hutchinson
Journal: Journal of Clinical Investigation (1970)

The concentrations of plasma glucose, free fatty acids, insulin, growth hormone, and placental prolactin in subhuman primate fetal and maternal plasma were examined following intravascular administration of insulin and glucagon to the fetus and mother. The neonatal plasma responses to these same stimuli were also examined.
A LAST PLEA FOR A USEFUL PHARMACOPEIA.
Authors: OLIVER T. OSBORNE
Journal: JAMA (1913)

Shall we have the United States Pharmacopeia up to date and of scientific and therapeutic value, or shall it be a book of ancient drug lore intermixed with drugs of real value? It is now nearly three years since the Pharmacopeial Convention of 1910, and what has been accomplished? Many of the drugs which have been approved have already been announced, and, as it has wisely been determined that a subject of such wide, almost universal, interest as the United States Pharmacopeia should not be made a secret affair—in other words, that its decisions should be public, what follows is not a breach of confidence. The subject, in every detail, is one of public interest, and, therefore, should be of public knowledge. In this age of exposure of "patent-medicine" frauds, and the age of education as to the danger of some drugs, the uselessness of others, and the limitations of
Multiple and recurrent inflammatory fibroid polyps in a Devon family ('Devon polyposis syndrome'): an update.
Authors: R O Allibone, J K Nanson, P P Anthony
Journal: Gut (1992)

Inflammatory fibroid polyps are uncommon but well documented as solitary polyps occurring typically in the stomach or ileum. A Devon family has previously been reported in which a female in three successive generations has presented with multiple polyps requiring repeated surgery over a number of years. A further two female family members, both siblings from the 3rd generation, who required surgery for the same condition are now reported.
Interferon-γ inhibits liver regeneration by stimulating major histocompatibility complex class II antigen expression by regenerating liver
Authors: Yoshinobu Sato, Kazuhiro Tsukada, Yoh Matsumot, Toru Ab
Journal: Hepatology (1993)

The effects of interferon-γ and interleukin-2 on liver regeneration after 70% hepatectomy in rats was studied immunohistologically, with special attention paid to major histocompatibility complex class II antigen expression. Liver regeneration 2 days after partial hepatectomy as assessed on the basis of bromodeoxyuridine labeling index revealed that regeneration was inhibited significantly in rats given a single dose of interleukin-2 or interferon-γ compared with rats that underwent only partial hepatectomy. Simultaneous administration of interleukin-2 and interferon-γ inhibited liver regeneration more markedly than administration of either drug. In rats subjected to partial hepatectomy, Kupffer cells around the portal vein expressed slightly more major histocompatibility complex class II antigen than did sham-operated controls. In the group given interferon-γ, major histocompatibility complex class II antigen expression was markedly increased. Major histocompatibility complex class II antigen expression was greatest in most Kupffer cells of rats given both interleukin-2 and interferon-γ. These results suggest that interferon-γ activates (proliferating) Kupffer cells, in turn leading to suppression of liver regeneration. These major histocompatibility complex class II antigen-positive Kupffer cells act as antigen-presenting cells and present hepatocyte as antigen, the so-called abnormal self, to helper and cytotoxic T cells. Both types of T cells, in turn, may suppress hepatocyte proliferation. The various cytokines induced by the activated Kupffer cells and helper T cells seem to form a network with interferon-γ to regulate liver regeneration. (Hepatology 1993;18:340-346).
Blink Yes; Crane No: More on Video Display Terminals
Authors: Frank J. Weinstock
Journal: JAMA (1987)

To the Editor.—  It was refreshing to see the fresh approach taken in the COUNCIL REPORT 1 to video display terminals (VDTs) and the emphasis on ergonomics.  Over the years, there has never been any evidence that would even hint of any adverse effects of VDTs on the visual system. However, it is not unusual to hear complaints from patients concerning their eyes and associated discomfort.  My experience as an ophthalmologist indicates two prime reasons for ocular fatigue that might be associated with VDT use. The main factor appears to be lack of blinking. While scrolling on a VDT, the user has a tendency to stare and decrease blinking to avoid missing anything on the screen. As with contact lens wearers, it is necessary to remind VDT users to blink sufficiently often to lubricate the cornea. This simple act will decrease ocular fatigue significantly.  Ergonomics come into play with the
Harold Gordon Mather
Authors: Robert Mather
Journal: BMJ (2007)

Gordon Mather was born in Sheffield; his father, as well as continuing to run the family cutlery firm, trained as an osteopath in midlife and was a pioneer of vegetarianism. Gordon's medical career was more mainstream: a first in natural sciences at Cambridge then clinical studies at King's. From there he was awarded a Rockefeller Foundation studentship to Western Reserve University, Cleveland, Ohio, where he qualified MD. As this was wartime, during the crossing in a convoy he was the acting medical officer on the ship, and was also made part of the crew of a gun. On return after Cambridge finals and house jobs he did his national service with the Royal Army …
Response to Comment on: Ekinci et al. Dietary Salt Intake and Mortality in Patients With Type 2 Diabetes. Diabetes Care 2011;34:703–709
Authors: Elif I. Ekinci, Richard J. MacIsaac, Merlin C. Thomas, George Jerums
Journal: Diabetes Care (2011)

We thank Lambers Heerspink et al. (1) for their comments and agree that observational studies are prone to confounding. We also agree that our study population represents high-risk patients with advanced type 2 diabetes and does not represent the general population. Importantly, after adjusting for factors independently associated with all-cause mortality including age, sex, duration of diabetes, atrial fibrillation, the presence and severity of chronic kidney disease (estimated glomerular filtration rate and log albumin excretion rate), and parameters associated with 24-h urinary sodium excretion (24hUNa) including BMI, all-cause mortality remained inversely associated …
Papillary Thyroid Carcinoma with Fibromatosis-like Stroma: A Report of Two Cases
Authors: Michiko Inaba, Shinobu Umemura, Haruhiro Satoh, Yasuko Ichikawah, Yoshifumi Abe, Kiyoshi Kurokawa, Hideto Sakai, R. Yoshiyuki Osamura
Journal: Endocrine Pathology (2002)
Abstract 2334: Identification of differentially expressed genes and somatic mutations in esophageal adenocarinoma cancer patients
Authors: Bodil Oster, Anika Joecker, Anne-Mette K. Hein, Patrick Dekker, Robert O'Neill, Adam Krejci, Anne Arens, Naomi Thomson, Cecilie Boysen, Søren Mønsted, Roald Forsberg, Bjarne Knudsen, Thomas Knudsen, Richard Lussier, Ted R. Hupp
Journal: Cancer Research (2014)

Abstract High throughput sequencing technologies are currently revolutionizing the cancer research area with rapid improvements in sequencing capacity and time consumption. As a result the most time consuming step has moved from being the sequencing process itself to being the bioinformatic data analysis. RNA sequencing (RNA-Seq) is used in an increasing number of transcriptomic studies. The great advantage of using RNA-Seq is its ability to precisely quantify transcript levels and identify novel transcripts, isoforms, and splice junctions, while further providing information of the mutational landscape down to single base resolution. To ease the hurdles associated with RNA-Seq data analysis there is an increasing demand for tools that are specifically tailored to RNA-Seq data. Here we describe how the newly developed CLC Cancer Research Workbench can be used to analyze and visualize RNA-Seq data with ready-to-use workflows that automatically map, quantify, and annotate transcriptomes. We identify differentially expressed genes and transcripts in Illumina HiSeq transcriptomic data from matched tumor and normal samples from four esophageal adenocarinoma cancer patients, and compare the mutational patterns in the samples with the expression values of the corresponding genes. Results are visualized in a track based genome browser view, which provides the means for quick and easy navigation as well as allowing the user to simultaneously view and annotate multiple samples and different data types (e.g. genes, transcript expression levels, and detected variants). Citation Format: Bodil Oster, Anika Joecker, Anne-Mette K. Hein, Patrick Dekker, Robert O'Neill, Adam Krejci, Anne Arens, Naomi Thomson, Cecilie Boysen, Søren Mønsted, Roald Forsberg, Bjarne Knudsen, Thomas Knudsen, Richard Lussier, Ted R. Hupp. Identification of differentially expressed genes and somatic mutations in esophageal adenocarinoma cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2334. doi:10.1158/1538-7445.AM2014-2334
No effect of intramuscular gold therapy on serological parameters of Helicobacter pylori infection in patients with rheumatoid arthritis: a 12 month prospective study.
Authors: S ten Wolde, M Janssen, W van Duijn, C B Lamers, J Hermans, B A Dijkmans
Journal: Annals of the Rheumatic Diseases (1994)

To assess prospectively the influence of intramuscular gold therapy on Helicobacter pylori serology in patients with rheumatoid arthritis (RA).Fifty patients with RA were started on intramuscular gold or chloroquine, as the control group and were followed serologically for H pylori infection for 12 months.Twelve patients treated with gold and eight control patients treated with chloroquine, all with serological evidence for H pylori infection, showed no significant decline of IgA and IgG anti-H pylori antibody levels or serum pepsinogen A and C levels. Total serum IgA and IgG levels declined significantly during gold therapy, while they remained unchanged during chloroquine therapy.Intramuscular gold therapy in patients with RA does not influence the serological parameters of H pylori infection.
The course of eczema in children aged 5-7 years and its relation to atopy: differences between boys and girls
Authors: M. Möhrenschlager, T. Schäfer, J. Huss-Marp, B. Eberlein-König, S. Weidinger, J. Ring, H. Behrendt, U. Krämer
Journal: British Journal of Dermatology (2005)

Background The role of atopy in the pathophysiology of eczema is still under debate. The concept and analyses of the nonatopic and atopic subtypes of eczema have gained increasing interest in recent studies. The course of these subtypes and differences between boys and girls have not been investigated so far. Objectives To examine the course of nonatopic and atopic eczema in preschool children from Germany with regard to sex. Methods Repeated cross-sectional studies were performed in 5–7-year-old preschool children from Germany between 1994 and 2000. Individuals with eczema were identified by a dermatological examination. In addition to a questionnaire, skin prick tests and analyses of serum IgE antibodies against seven and five environmental allergens, respectively, were performed. Atopy was defined by sensitization to at least one of five common aeroallergens (birch, grass and mugwort pollen, house dust mites, cat dander). In part of the study population investigations of spare time behaviour and skin function were carried out (including stratum corneum hydration and skin surface pH). Results A total of 2693 girls and 2783 boys underwent a full dermatological examination of the skin and determination of sensitization. Among the girls, 8·7% demonstrated eczema clinically at the day of investigation in contrast to 6·1% of the boys. In girls, early onset eczema (< 2 years of age) was strongly related to atopy at age 5–7 years [odds ratio (OR) 3·7; 95% confidence interval (CI) 2·7–5·1], whereas late-onset eczema (≥ 2 years of age) was not (OR 1·0; 95% CI 0·7–1·5). Boys were more often atopic at the age of 5–7 years than girls (28·3% vs. 20·6%), and early and late-onset eczema were related to atopy without such a difference (OR 2·8, 95% CI 2·0–4·0; OR 1·9, 95% CI 1·3–2·8, respectively). The excess of current eczema in 5–7-year-old girls compared with boys was related to the nonatopic type. The higher susceptibility of girls in that age group to develop eczema was reflected by the skin physiological examination: even girls without eczema had significantly higher skin surface pH and lower stratum corneum hydration than boys. Additionally, questionnaire data revealed that girls more often than boys predominantly played indoors, which was associated with more eczema. Conclusions Atopy and eczema develop differently in boys and girls. Boys are more often atopic, whereas girls suffer significantly more often from eczema without relation to atopy. The nonatopic type of eczema in preschool girls is noticed predominantly after their second birthday. Genetic and lifestyle factors may contribute to this difference.
Imprime PGG, a yeast β-glucan immunomodulator, has the potential to repolarize human monocyte-derived M2 macrophages to M1 phenotype
Authors: Anissa SH Chan, Xiaohong Qiu, Adria Jonas, Myra L Patchen, Nandita Bose
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Imprime PGG (IPGG) has shown promising clinical efficacy in combination with monoclonal antibody treatment of cancer [[1][1]]. In mice, complement receptor 3 (CR3) on innate immune cells (neutrophils and macrophages) is required for IPGG's anti-tumor activity [[2][2], [3][3]]. In
Is Reform Coverage Really Universal?
Authors: Rebecca Voelker
Journal: JAMA (1993)

IF THE Clinton administration's health care destination is universal coverage, the nation's public health community says the president and his wife have set out on the wrong path.  Thousands of public health practitioners and administrators have called Clinton's reform proposal a discriminatory plan that will leave millions without coverage. Their call for a more equitable alternative—a single-payer plan—was loud and clear during the annual meeting of the American Public Health Association (APHA), held in San Francisco, Calif.  At the same time, however, APHA and other public health groups are walking a politically fine line. After months of lobbying the administration, they came away with respectable victories. Clinton's plan supports core public health functions such as surveillance, data collection, environmental protection, disease and injury control, and quality assurance.  See also p 2670.  In addition, Clinton's health care legislation, released during APHA's meeting, includes a provision to fund those core functions with
Announcing “New Methods in Cardiovascular Biology”
Authors: Roberto Bolli
Journal: Circulation Research (2010)

The purpose is to publish articles that describe enabling technologies-new tools and techniques that have the potential to facilitate advances in cardiovascular research and be useful to a broad spectrum of investigators.We realize that this initiative represents a departure from the praxis of the journal, which has traditionally shunned purely methodological articles.Although we recognize that articles describing methods are (obviously) not mechanistic and not hypothesis driven, we believe that they can have a significant impact on cardiovascular science.As pointed out in the manifesto of the new Circulation Research, 2 history teaches us that advances in science are driven by new techniques at least as much as they are driven by new ideas.The microscope was certainly not a mechanistic advance, but it had an incalculable impact on medicine.Over and over again, we see that new concepts emerge as a result of new techniques, probably more often than the other way around.And countless studies are done because a new tool or method becomes available to answer a question that could not be answered with the old technology.In view of the impact that enabling technologies can have on scientific progress, we
Atopic and non‐atopic individuals react to nickel challenge in a similar way. A study of the cytokine profile in nickel‐induced contact dermatitis
Authors: J.C. SZEPIETOWSKI, R.C. MCKENZIE, S.G. KEOHANE, R.D. ALDRIDGE, J.A.A. HUNTER
Journal: British Journal of Dermatology (1997)

Journal Article Atopic and non‐atopic individuals react to nickel challenge in a similar way. A study of the cytokine profile in nickel‐induced contact dermatitis Get access J.C. SZEPIETOWSKI, J.C. SZEPIETOWSKI Department of Dermatology, University of Edinburgh, Royal Infirmary, Lauriston Building (floor 4), Lauriston Place, Edinburgh EH3 9YW, Scotland, U.K. Search for other works by this author on: Oxford Academic Google Scholar R.C. MCKENZIE, R.C. MCKENZIE Department of Dermatology, University of Edinburgh, Royal Infirmary, Lauriston Building (floor 4), Lauriston Place, Edinburgh EH3 9YW, Scotland, U.K. Search for other works by this author on: Oxford Academic Google Scholar S.G. KEOHANE, S.G. KEOHANE Department of Dermatology, University of Edinburgh, Royal Infirmary, Lauriston Building (floor 4), Lauriston Place, Edinburgh EH3 9YW, Scotland, U.K. Search for other works by this author on: Oxford Academic Google Scholar R.D. ALDRIDGE, R.D. ALDRIDGE Department of Dermatology, University of Edinburgh, Royal Infirmary, Lauriston Building (floor 4), Lauriston Place, Edinburgh EH3 9YW, Scotland, U.K. Search for other works by this author on: Oxford Academic Google Scholar J.A.A. HUNTER J.A.A. HUNTER Department of Dermatology, University of Edinburgh, Royal Infirmary, Lauriston Building (floor 4), Lauriston Place, Edinburgh EH3 9YW, Scotland, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 137, Issue 2, 1 August 1997, Pages 195–200, https://doi.org/10.1046/j.1365-2133.1997.18051888.x Published: 01 August 1997