tbuckley/cabot-search huggingface dataset:
S91 A randomised, double-blind, placebo-controlled crossover study to assess the efficacy of a single dose of 100 mg of VRP700 by inhalation in reducing the frequency and severity of cough in adult patients with Idiopathic Pulmonary Fibrosis
Authors: I Satia, H Badri, R Dockry, N Chaudhuri, G Brown, K Abbott-Banner, JA Smith
Journal: Thorax (2015)

<h3>Background</h3> Cough is a common, troublesome symptom in idiopathic pulmonary fibrosis (IPF), but the underlying mechanisms are poorly understood and effective therapies are lacking. VRP700 is thought to inhibit ion-channels found on sensory afferents innervating the airways. We aimed to investigate the efficacy of VRP700 in reducing cough frequency in patients with IPF. <h3>Method</h3> A single centre double-blind randomised, placebo controlled crossover study in patients with IPF with chronic cough. Patients were randomised to receive a single inhaled dose of VRP700 (100 mg) or placebo and then crossed-over after a 7 day washout period. The primary endpoint was the number of coughs in the 4 h following the end of nebulisation for VRP700 compared with placebo, measured using an objective cough monitoring system (VitaloJAK, Vitalograph Ltd). Secondary endpoints included urge to cough visual analogue scale (VAS), cough severity VAS, and dyspnoea VAS, recorded at 1,2 and 4 h post-dose, at the end of the day and 24 hrs post-dose. <h3>Results</h3> Twenty five patients were screened, 5 were ineligible and therefore 20 were randomised [mean age 69.8(±6.9) yrs, 12 female, mean FEV<sub>1</sub> 1.97 ± 0.39 L, mean FVC 1.86 ± 0.42 L]. The geometric mean number of coughs in the 4 h following VRP700 treatment was significantly higher compared with placebo [136.8 (95% CI 80.3- 233.1) vs. 64.9 (95% CI 38.1–110.6), p &lt; 0.001). There was no evidence of an order or period effect. The difference in cough counts was greatest during the first hour after VRP700 nebulization [63.3 (95% CI 36.4–109.8) vs. 24.1 (95% CI 13.9–41.9), p &lt; 0.001). For reported cough severity, urge to cough, and dyspnoea severity scores there were no differences between VRP700 and placebo at almost all time-points, apart from the dyspnoea severity VAS at 24 h post-dose, where VRP700 was significantly better than placebo (p = 0.012). <h3>Conclusion</h3> VRP700, administered by nebuliser as a single inhaled dose of 100 mg, did not reduced the frequency and severity of cough in IPF patients with troublesome cough. Instead the inhalation of VRP700 seemed to evoke coughing.
Erythropoiesis in Patients with Renal Failure Undergoing Chronic Dialysis
Authors: J. W. Eschbach, D. Funk, J. Adamson, I. Kuhn, B. H. Scribner, C. A. Finch
Journal: New England Journal of Medicine (1967)

THE anemia of renal insufficiency is associated with both increased red-cell destruction and impaired erythropoietic response to anemia. Variations in the relative importance of these 2 mechanisms and in the degree of the anemia observed may be due, at least in part, to the severity of renal disease in the patients studied. The purpose of the present report is to characterize red-cell production and destruction in a special group of patients with severe renal failure who have been stabilized at a similar degree of azotemia by repeated dialysis. An additional finding emerging from this study is the improvement in erythroid . . .
Aspirin may reduce risk of metastases and death in patients with cancer, study finds
Authors: Susan Mayor
Journal: BMJ (2016)

Taking low dose aspirin in addition to treatment for cancer is associated with a 15-20% reduction in mortality and reduced metastatic spread in people with a range of different cancers, a review in PLoS One has shown.1

Researchers looked for published studies involving patients with cancer who took aspirin after diagnosis. They found five randomised trials and 42 observational studies that met their criteria, including 16 of patients with colorectal cancer, 10 of breast cancer, and 10 of prostate cancer mortality. Patients in most of the studies were …
Pathophysiology and Treatment of Adrenal Crisis
Authors: Mortimer B. Lipsett, Olof H. Pearson
Journal: New England Journal of Medicine (1956)

THE treatment of adrenal crisis has become an increasingly important topic for surgeons and internists. This derives from the ever-widening use of adrenalectomy as a therapeutic procedure in a variety of conditions. The consequent availability of bilaterally adrenalectomized patients has permitted a study of adrenal crisis and an analysis of its pathophysiology. It is the purpose of this paper to analyze the separate aspects of this syndrome and, on the basis of theoretical considerations and our own experience, to suggest a rational plan of therapy.For some years the term adrenal crisis has implied a specific clinical situation — namely, . . .
The Intensity of Physicians' Work in Patient Visits — Implications for the Coding of Patient Evaluation and Management Services
Authors: Roz D. Lasker, M. Susan Marquis
Journal: New England Journal of Medicine (1999)

Clinicians use visit codes to bill for services involving the evaluation of patients and the management of their care. The existing guidelines for coding and documenting these services, as well as proposed revisions, have been criticized as complex, clinically irrelevant, and costly. We investigated whether easily measured characteristics of physician–patient visits accurately reflect differences in the amount of work performed. Such characteristics might provide the basis for a simple and equitable physician-payment scheme.
Association between a Deletion Polymorphism of the Angiotensin-Converting-Enzyme Gene and Left Ventricular Hypertrophy
Authors: Heribert Schunkert, Hans-Werner Hense, Stephan R. Holmer, Monica Stender, Siegfried Perz, Ulrich Keil, Beverly H. Lorell, Gunter Riegger
Journal: New England Journal of Medicine (1994)

Epidemiologic studies have shown that left ventricular hypertrophy is often found in the absence of an elevated cardiac workload. To investigate whether such hypertrophy is determined in part by genetic factors, we studied the association between this condition, as assessed by electrocardiographic criteria, and a deletion (D)-insertion (I) polymorphism of the angiotensin-converting-enzyme (ACE) gene.
Loss of SPINK7 in Esophageal Epithelial Cells Unleashes a Pro-Inflammatory Response Characterized By Excessive Cytokine Production and Loss of Barrier Function
Authors: Nurit Pereg Azouz, Demetria Michael, Laetitia Furio, Alain Hovnanian, Marc E. Rothenberg
Journal: Journal of Allergy and Clinical Immunology (2016)
Asymptomatic Structural Liver Disease in Hemophilia
Authors: Joel A. Spero, Jessica H. Lewis, David H. Van Thiel, Ute Hasiba, Bruce S. Rabin
Journal: New England Journal of Medicine (1978)

In a study of persistent abnormalities of liver-function tests in hemophilic patients deficient in factor VIII or IX and treated with factor VIII or IX concentrates, we examined 14 liver biopsies from 13 anti-HBs-positive patients. None had any symptoms of liver disease. All had chronically abnormal levels of alanine aminotransferase. Histologic studies showed chronic persistent hepatitis in eight patients, chronic active hepatitis in four and fatty infiltration with portal fibrosis in one. Indirect immunofluorescence of anti-serums containing anti-HBs or anti-HBc (or both) revealed nuclear and cytoplasmic fluorescence in the hepatocytes of eight of 12 patients. Specificity testing of these antiserums confirmed that hepatitis B viral markers are present in the hepatocytes of these anti-HBs-positive patients. These histologic derangements are probably related to frequent treatment with blood products obtained from multiple donors and to the persistence of hepatitis B virus in hepatocytes despite the presence of circulating anti-HBs. (N Engl J Med 298:1373–1378, 1978)
Mammographic Parenchymal Pattern and the Risk of Breast Cancer 2
Authors: E. Wilkinson, C. Clopton, J. Gordonson, R. Green, A. Hill, M. C. Pike
Journal: JNCI Journal of the National Cancer Institute (1977)

Xeromammograms of women with breast cancer detected at the National Cancer Institute's Breast Cancer Detection Demonstration Project at the Los Angeles County/University of Southern California School of Medicine were compared with those of control women, chosen from the Project's files, who showed no evidence of breast cancer. The mammograms were categorized according to the classification scheme of J. N. Wolfe into four groups (N1, P1, P2, and DY).ln group N1, the parenchyma was composed primarily of fat with, at most, small amounts of “dysplasia,” and no ducts were visible. In group P1, the parenchyma was chiefly fat with prominent ducts in the anterior portion up to one-fourth the volume of the breast, but it also could be a thin band of ducts extending into a quadrant. In group P2, prominent ducts occupied more than one-fourth the volume of the breast. In group DY, severe "dysplasia" was found. To avoid bias, only mammograms from the breast opposite the breast with cancer were used for the breast cancer patients, and those from the corresponding breasts in the patient's 2 matched controls were utilized. In comparison to N1, the breast cancer risk ratios were 2.1 for both P1 and P2 and 5.8 for DY (P<0.01). The scheme appeared particularly useful in women under 55 years of age. Mammographic pattern was a risk factor over and above the known risk factors of age at birth of first child, age at menopause, and family history of breast cancer. In control women, these known risk factors were correlated with the parenchymal pattern but the results were not statistically significant.
Sildenafil and Ocular Perfusion
Authors: William E. Sponsel, Gianmarco Paris, Sal S. Sandoval, Donald K. Sanford, Joseph M. Harrison, W. Rowe Elliott, Yolanda Trigo
Journal: New England Journal of Medicine (2000)

To the Editor: Mild, transient visual changes such as increased sensitivity to light and color-tinge alterations occur in 3 percent of men who take sildenafil.1–3 We therefore assessed whether sild...
TriLoNet: Piecing Together Small Networks to Reconstruct Reticulate Evolutionary Histories
Authors: James Oldman, Taoyang Wu, Leo van Iersel, Vincent Moulton
Journal: Molecular Biology and Evolution (2016)

Phylogenetic networks are a generalization of evolutionary trees that can be used to represent reticulate processes such as hybridization and recombination. Here, we introduce a new approach called TriLoNet (Trinet Level- one Network algorithm) to construct such networks directly from sequence alignments which works by piecing together smaller phylogenetic networks. More specifically, using a bottom up approach similar to Neighbor-Joining, TriLoNet constructs level-1 networks (networks that are somewhat more general than trees) from smaller level-1 networks on three taxa. In simulations, we show that TriLoNet compares well with Lev1athan, a method for reconstructing level-1 networks from three-leaved trees. In particular, in simulations we find that Lev1athan tends to generate networks that overestimate the number of reticulate events as compared with those generated by TriLoNet. We also illustrate TriLoNet's applicability using simulated and real sequence data involving recombination, demonstrating that it has the potential to reconstruct informative reticulate evolutionary histories. TriLoNet has been implemented in JAVA and is freely available at https://www.uea.ac.uk/computing/TriLoNet.
Infantile Progressive Spinal Muscular Atrophy in Identical Negro Twins
Authors: J. E. Marquardt, James MacLowry, Ralph E. Perry
Journal: New England Journal of Medicine (1962)

INFANTILE progressive spinal muscular atrophy (Werdnig–Hoffmann syndrome) has been reported as occurring in 7 pairs of twins.1 2 3 4 5 6 In only 4 of these cases were the twins thought to be monozygotic in type.1 2 3 4 The purpose of this paper is to report the first example of this disease in identical male Negro twins.Case ReportF.H., a 9-month-old Negro male, was admitted to the Los Angeles County Hospital shortly after experiencing an apneic spell, which had occurred during feeding. On examination it was noted that he was markedly hypotonic and had absent deep tendon reflexes. Further questioning of the mother revealed that . . .
Feline Oncovlrus-Assoclated Cell Leukemia Virus Group-Specific Antigen Marrow and Serum&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: Jacqueline B. Rice, Richard G. Ollen
Journal: JNCI Journal of the National Cancer Institute (1981)

Feline retrovirus-induced possible preneoplastic lesions were identified by detection of feline oncovirus-associated cell membrane antigen (FOCMA) in bone marrow (BM) and mesenteric lymph nodes of noninbred, domestic short- or long-hair kittens. Cell-bound FOCMA was detected 1-3 weeks after feline leukemia virus (FeLV) infection and at least 6 months before a tumor was evident. BM FOCMA was detected earlier and reached higher levels at early periods in cats that became persistently viremic. Serum FeLV group-specific antigen (gsa) increased more rapidly and reached a higher level in cats that became persistently viremic, but nonviremic cats still had detectable gsa as late as 7-9 months after FeLV infection, even in the presence of high levels of viral antibody. The presence in nonviremic cats of FeLV gsa in sera and FOCMA in BM and sera suggests that these cats may have a persistent, low-level FeLV infection.
Phagocytic Capacity of Normal and Malignant Rat Glial Cells in Culture&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: R Bjerknes, R Bjerkvig, O D Laerum
Journal: JNCI Journal of the National Cancer Institute (1987)

The phagocytic capacity of 4 continuous rat glioma cell lines (BT2C, BT4Cn, BT5c, and 9L) and normal BD IX fetal rat glial cells in culture has been studied. This was done by flow cytometric measurements of single cells from monolayer cultures having ingested fluorescent bacteria, zymosan particles, red blood cells, or fragments of normal glial cells. In addition, phagocytosis was studied in a three-dimensional culture system. The BT4Cn, BT5C, and 9L cell lines were tumorigenic and invasive both in vivo and in organ culture in vitro. In contrast, BT2C has shown variable tumorigenicity and does not seem to be invasive. The phagocytic capacity of the cell lines was compared to their destructive properties during invasion. Depending on the particle type, 30-40% of the normal glial cells were phagocytic. The fractions of phagocytic glioma cells were dependent on the particle type and the prey load. Of the invasive cell lines, BT5C showed high phagocytic activity both in monolayer and three-dimensional cultures. Two of the invasive cell lines (BT5C and 9L) had about the same fraction of phagocytic cells as normal glial cells. These 2 cell lines showed highly destructive growth during invasion. In contrast, the third invasive cell line (BT4Cn) had almost no phagocytic cells. The BT4Cn cells showed single-cell invasion with little destruction of target tissue. The noninvasive cell line (BT2C) showed low phagocytic activity, and almost no destruction was observed in the border zone between tumor cells and normal tissue. Phagocytosis seems to be an inherent property of both normal and malignant glial cells, although the fraction of phagocytic cells varies from one cell line to another. In organ culture high phagocytic capacity of invasive glioma cells seems to be related to destructive activity on the normal brain tissue during invasion.
Differentiation between the EGFR antibodies necitumumab, cetuximab, and panitumumab: Antibody internalization and EGFR degradation.
Authors: M. B. Topper, J. R. Tonra, B. Pytowski, S. W. Eastman
Journal: Journal of Clinical Oncology (2011)

e13022 Background: Targeting the epidermal growth factor receptor (EGFR) with monoclonal antibodies has proven to be an effective therapy for the treatment of cancer. In addition to blocking activation, antibodies directed to the ligand-binding domain also induce EGFR degradation. A number of EGFR antibodies are approved for use in patients and/or in clinical development, including cetuximab (chimeric IgG1), necitumumab (human IgG1), and panitumumab (human IgG2). It is important to understand the similarities and differences between these antibodies to guide future drug development strategies. Methods: We used confocal live cell microscopy to measure EGFR antibody internalization and EGFR degradation. To obtain kinetic data on antibody induced receptor degradation, a HELA reporter cell line expressing EGFR fused to the green fluorescent protein (GFP) was utilized to quantify the decrease in sum pixel intensity of EGFR-GFP over a 24-hour time course in live cells. EGFR antibody trafficking to the lysosome was also monitored with a pH-activated dye (pHrodo) conjugated to an anti-human IgG FAB antibody. The fluorescence intensity signal from pHrodo increases upon decrease in pH, allowing the use of this dye as a surrogate for delivery of EGFR to a low-pH degradative compartment. We used these novel assays to directly compare cetuximab, necitumumab, and panitumumab. Results: Necitumumab and cetuximab were internalized at a faster rate, and resulted in more rapid degradation of EGFR, compared to panitumumab. Experiments performed in reporter cells revealed a 2-3 fold increase in the rate of antibody-mediated degradation of EGFR-GFP induced by necitumumab and cetuximab as compared to panitumumab. Similar studies using three NSCLC cell lines (HCC827, NCI-H1650, and EKVX) uncovered a 1.5-2 fold increase in the rate of EGFR-antibody delivery to lysosomes with necitumumab and cetuximab, as compared to panitumumab. Conclusions: Necitumumab and cetuximab are internalized to a low-pH compartment more quickly than panitumumab in NSCLC cells. This difference correlated with a more rapid degradation of EGFR induced by necitumumab and cetuximab, compared to that induced by panitumumab.
Regional variation in patterns of inpatient psychiatric care
Authors: R Rosenheck, B Astrachan
Journal: American Journal of Psychiatry (1990)

Regional variation in both average length of stay and number of beds per 100,000 population is described for inpatient psychiatric care in the United States during 1983. The greatest differences were between the Northeast and Mid-Atlantic regions, on the one hand, and the Pacific and Southwest regions, on the other. Medical centers of the U.S. Department of Veterans Affairs (VA), whose policies are largely centrally determined, followed the same regional trends. Regional average length of stay, particularly in public sector mental health care organizations, was higher in regions with more occupied beds per 100,000 population.
Unfavourable effects of medically indicated oral anticoagulants on survival in idiopathic pulmonary fibrosis
Authors: Michael Kreuter, Marlies S. Wijsenbeek, Martina Vasakova, Paolo Spagnolo, Martin Kolb, Ulrich Costabel, Derek Weycker, Klaus-Uwe Kirchgaessler, Toby M. Maher
Journal: European Respiratory Journal (2016)

Procoagulant and antifibrinolytic activity has been associated with idiopathic pulmonary fibrosis (IPF); however, investigation of anticoagulant therapy in IPF has suggested deleterious effects. This post hoc analysis evaluated the effect of medically indicated anticoagulation on mortality and other clinical outcomes in IPF. Patients randomised to placebo (n=624) from three controlled trials in IPF were analysed by oral anticoagulant use. End-points included all-cause and IPF-related mortality, disease progression, hospitalisation, and adverse events, over 1 year. At baseline, 32 (5.1%) patients randomised to placebo were prescribed anticoagulants for non-IPF indications, 29 (90.6%) of whom received warfarin. Unadjusted analyses demonstrated significantly higher all-cause and IPF-related mortality at 1 year in baseline anticoagulant users versus nonusers (15.6% versus 6.3%, p=0.039 and 15.6% versus 3.9%, p=0.002, respectively). In multivariate analyses, baseline use of anticoagulants was an independent predictor of IPF-related mortality (hazard ratio 4.7, p=0.034), but not other end-points. Rates of bleeding and cardiac events did not differ significantly between groups. In an exploratory analysis, anticoagulant use at any time during the study was an independent predictor of all end-points. This post hoc analysis suggests that anticoagulants used for non-IPF indications may have unfavourable effects in IPF patients. Future studies are needed to explore this relationship further.
Getting the Story Right
Authors: Thomas P. Duffy
Journal: New England Journal of Medicine (1993)

A 47-year-old executive experienced several episodes of brief, exertion-related precordial chest pain in the six weeks before his initial evaluation. A single episode of midsternal vise-like pain that began after he lifted his child lasted 20 minutes. He had a remote history of cigarette smoking and a strong family history of atherosclerotic cardiovascular disease, but no history of diabetes, hypertension, or obesity.Coronary artery disease needs primary consideration, although the lifting episode suggests that musculoskeletal strain or costochondritis may be contributing to his problems. I don't give much credence to the notion of gastrointestinal disease as a cause . . .
Gain of Toxicity from ALS/FTD-Linked Repeat Expansions in C9ORF72 Is Alleviated by Antisense Oligonucleotides Targeting GGGGCC-Containing RNAs
Authors: Jie Jiang, Qiang Zhu, Tania F. Gendron, Shahram Saberi, Melissa McAlonis-Downes, Amanda Seelman, Jennifer E. Stauffer, Paymaan Jafar-nejad, Kevin Drenner, Derek Schulte, Seung Chun, Shuying Sun, Shuo-Chien Ling, Brian Myers, Jeffery Engelhardt, Melanie Katz, Michael Baughn, Oleksandr Platoshyn, Martin Marsala, Andy Watt, Charles J. Heyser, M. Colin Ard, Louis De Muynck, Lillian M. Daughrity, Deborah A. Swing, Lino Tessarollo, Chris J. Jung, Arnaud Delpoux, Daniel T. Utzschneider, Stephen M. Hedrick, Pieter J. de Jong, Dieter Edbauer, Philip Van Damme, Leonard Petrucelli, Christopher E. Shaw, C. Frank Bennett, Sandrine Da Cruz, John Ravits, Frank Rigo, Don W. Cleveland, Clotilde Lagier-Tourenne
Journal: Neuron (2016)
Cytokine Profiles and Eosinophil Activation in Sensitized and Nonsensitized Cases of Virus-Induced Acute Exacerbations of Childhood Wheezing/Asthma.
Authors: Masahiko Kato, Kazuo Suzuki, Yoshiyuki Yamada, Kenichi Maruyama, Hiroyuki Mochizuki
Journal: Journal of Allergy and Clinical Immunology (2016)
Doctors’ worry about NHS “privatisation” is growing, says BMA
Authors: Adrian O’Dowd
Journal: BMJ (2016)

Two thirds of doctors are uncomfortable with “privatisation” of the NHS in England and the growing role of independent sector organisations in providing NHS services, a BMA survey has found.

In a report published on 18 April the BMA examined how much NHS money was being spent on independent providers, the effects of independent providers taking over NHS services, and the opinions of around 500 doctors on these issues.1

The BMA said that official government data showed that the amount of money that NHS England spent on healthcare provided by the independent sector had risen every year for the past five years. The total for 2014-15 was …
Combination Treatment with Zidovudine, Didanosine, and Nevirapine in Infants with Human Immunodeficiency Virus Type 1 Infection
Authors: Katherine Luzuriaga, Yvonne Bryson, Paul Krogstad, James Robinson, Barbara Stechenberg, Michael Lamson, Susannah Cort, John L. Sullivan
Journal: New England Journal of Medicine (1997)

In infants and children with maternally acquired human immunodeficiency virus type 1 (HIV-1) infection, treatment with a single antiretroviral agent has limited efficacy. We evaluated the safety and efficacy of a three-drug regimen in a small group of maternally infected infants.