tbuckley/cabot-search huggingface dataset:
Genomic analysis identifies targets of convergent positive selection in drug-resistant Mycobacterium tuberculosis
Authors: Maha R Farhat, B Jesse Shapiro, Karen J Kieser, Razvan Sultana, Karen R Jacobson, Thomas C Victor, Robin M Warren, Elizabeth M Streicher, Alistair Calver, Alex Sloutsky, Devinder Kaur, Jamie E Posey, Bonnie Plikaytis, Marco R Oggioni, Jennifer L Gardy, James C Johnston, Mabel Rodrigues, Patrick K C Tang, Midori Kato-Maeda, Mark L Borowsky, Bhavana Muddukrishna, Barry N Kreiswirth, Natalia Kurepina, James Galagan, Sebastien Gagneux, Bruce Birren, Eric J Rubin, Eric S Lander, Pardis C Sabeti, Megan Murray
Journal: Nature Genetics (2013)
Prophylaxis of Pneumocystis carinii pneumonia: too much of a good thing?
Authors: R. Miller
Journal: Thorax (2000)

Background.Azithromycin in combination with sulphonamides is active against Pneumocystis carinii (PCP) in animals.We assessed the clinical efficacy of azithromycin for PCP prophylaxis in human beings.Methods.We identified HIV-1-infected patients with PCP during a prospective randomised trial comparing azithromycin, rifabutin, and the two drugs in combination for prevention of disseminated Mycobacterium avium infection.Patients had CD4-cell counts less than 100⁄ L at entry and received PCP prophylaxis according to the standard practice of their clinician.Analysis was by intention to treat.Findings.Patients receiving azithromycin, either alone (n=233) or in combination with rifabutin (n= 224), had a 45% lower risk of developing PCP than those receiving rifabutin alone (n=236; p= 0.008).Compared with rifabutin alone, hazard ratio for azithromycin was 0.54 (95% CI 0.32-0.94),for azithromycin plus rifabutin was 0.55 (0.32-0.94), and for regimens containing azithromycin was 0.55 (0.35-0.86).The most common side-effects involved the gastrointestinal tract with dose-limiting toxicities, and were mainly seen in patients receiving combination therapy.Interpretation.Azithromycin as prophylaxis for M avium complex disease provides additional protection against P carinii over and above that of standard PCP prophylaxis.Use of azithromycin is beneficial only as primary prophylaxis.
Recombinant Alpha-2 Interferon Therapy for Kaposi's Sarcoma Associated with the Acquired Immunodeficiency Syndrome
Authors: JEROME E. GROOPMAN
Journal: Annals of Internal Medicine (1984)

In a randomized prospective study we tested the toxicity and efficacy of recombinant alpha-2 interferon in the treatment of Kaposi's sarcoma associated with the acquired immunodeficiency syndrome. High doses (50 X 106 U/m2 body surface area, intravenously) or low doses (1 X 106 U/m2, subcutaneously) of recombinant alpha-2 interferon were administered to 20 patients for 5 days/ wk, every other week, for four treatment cycles. Therapy was well tolerated subjectively and caused only mild hematologic and hepatic toxicity at both dose levels. No consistent or sustained changes were seen in immunologic variables during or after treatment. Six patients with Kaposi's sarcoma, four at high dose and two at low dose, had objective responses (complete or partial) to treatment. However, therapy did not appear to eradicate cytomegalovirus carriage or prevent opportunistic infections related to cytomegalovirus.
Ca <sup>2+</sup> Waves During Triggered Propagated Contractions in Intact Trabeculae
Authors: Masahito Miura, Penelope A. Boyden, Henk E. D. J. ter Keurs
Journal: Circulation Research (1999)

Abstract —During triggered propagated contractions, Ca 2+ waves travel along cardiac trabeculae with a constant velocity (V prop ) ranging from 0.34 to 5.47 mm/s. To explore the determinants of V prop , we studied (1) the relationship between [Ca 2+ ] i and V prop and (2) the effect of low concentrations of caffeine on V prop . Trabeculae were dissected from the right ventricle of rat hearts. [Ca 2+ ] i was measured using electrophoretically injected fura-2 and an image-intensified CCD camera. Force was measured using a silicon strain gauge, and sarcomere length was measured using laser diffraction techniques. After induction of reproducible Ca 2+ waves by trains of electrical stimuli (2.5 Hz) at 21.9±0.2°C, the number of stimuli or [Ca 2+ ] o was varied in 9 trabeculae. In 5 trabeculae, the effects of caffeine (0.1 to 1.0 mmol/L) at [Ca 2+ ] o of 2.2±0.3 mmol/L were determined. All images were recorded under stable conditions of wave propagation. The increment in [Ca 2+ ] i during the last electrically stimulated transient (ΔCa T ) and [Ca 2+ ] i just before onset of the Ca 2+ waves (Ca D ) were used to estimate the Ca 2+ loading of the sarcoplasmic reticulum (SR) and the myoplasm, respectively. The ratio (ΔCa W /ΔCa T ) of the [Ca 2+ ] i increment during the waves (ΔCa W ) to ΔCa T was used to estimate the probability of opening of the SR-Ca 2+ release channel during wave propagation. As a result of an increase of the number of stimuli or [Ca 2+ ] o , V prop increased in proportion to (1) ΔCa T ( r =0.82); (2) Ca D ( r =0.88); (3) ΔCa W ( r =0.85); and (4) ΔCa W /ΔCa T ( r =0.74). The addition of caffeine (≤0.3 mmol/L) increased V prop for any ΔCa T and any ΔCa W , revealing an increased sensitivity of V prop to ΔCa T and ΔCa W . In contrast, caffeine had little effect on the relationship between V prop and Ca D and no effect on that between V prop and ΔCa W /ΔCa T . These results suggest that both the cellular Ca 2+ loading and open probability of the SR-Ca 2+ release channels determine the velocity of propagation of Ca 2+ waves.
Report of Tuberculin Survey in the Rhondda Fach
Authors: T. F. Jarman
Journal: BMJ (1953)

HEALTH OF PREMATURE CHILDRENduring the first two years.This greater susceptibility to infection is found among premature children even when they are reared in an apparently favourable home environment.In general, premature children-after they have reached the age of 2-appear to be as healthy as those born at term.We wish to thank the chairman and members of the Joint Committee for their help and advice, especially Professor Aubrey Lewis, Professor I. G. Davies, and Professor R. M. Titmuss; the medical officers of health and the health visitors whose generous co-operation made this survey possible; and the mothers in all parts of the country who willingly answered numerous and detailed questions on their children's health.
Mucosal Tear in Collagenous Colitis
Authors: Thomas Dunzendorfer, Sarah Wilkins, Rebecca Johnson
Journal: Clinical Gastroenterology and Hepatology (2008)

The patient is a 60-year-old woman with a long history of constipation. One year before presentation she started to experience rectal pain and watery, nonbloody diarrhea. She had a 6-pound weight loss, and empiric treatment elsewhere with antimotility agents was unsuccessful. Physical examination and stool and blood test results were unremarkable. She did not use nonsteroidal anti-inflammatory drugs, enemas, or other rectal manipulations. Colonoscopy showed a 3-cm-long linear, raised mucosal tear in the sigmoid on insertion of the endoscope (Figure A).
PSYCHIATRIC USES OF INTRAVENOUS SODIUM AMYTAL
Authors: DANIEL J. SULLIVAN
Journal: American Journal of Psychiatry (1942)

Sodium amytal intravenously is a valuable diagnostic and therapeutic agent in psychiatry meriting more usage than given. Many patients in whom shock therapy or hypnosis cannot be utilized can be helped therapeutically or palliatively by suitable administration of this drug. It is convenient, safe and inexpensive, and can be used in stimulating doses, in narcosis regimen or as a powerful sedative.
Cyclin-dependent kinase inhibitor 2B regulates efferocytosis and atherosclerosis
Authors: Yoko Kojima, Kelly Downing, Ramendra Kundu, Clint Miller, Frederick Dewey, Hope Lancero, Uwe Raaz, Ljubica Perisic, Ulf Hedin, Eric Schadt, Lars Maegdefessel, Tom Quertermous, Nicholas J. Leeper
Journal: Journal of Clinical Investigation (2014)

Genetic variation at the chromosome 9p21 risk locus promotes cardiovascular disease; however, it is unclear how or which proteins encoded at this locus contribute to disease. We have previously demonstrated that loss of one candidate gene at this locus, cyclin-dependent kinase inhibitor 2B (Cdkn2b), in mice promotes vascular SMC apoptosis and aneurysm progression. Here, we investigated the role of Cdnk2b in atherogenesis and found that in a mouse model of atherosclerosis, deletion of Cdnk2b promoted advanced development of atherosclerotic plaques composed of large necrotic cores. Furthermore, human carriers of the 9p21 risk allele had reduced expression of CDKN2B in atherosclerotic plaques, which was associated with impaired expression of calreticulin, a ligand required for activation of engulfment receptors on phagocytic cells. As a result of decreased calreticulin, CDKN2B-deficient apoptotic bodies were resistant to efferocytosis and not efficiently cleared by neighboring macrophages. These uncleared SMCs elicited a series of proatherogenic juxtacrine responses associated with increased foam cell formation and inflammatory cytokine elaboration. The addition of exogenous calreticulin reversed defects associated with loss of Cdkn2b and normalized engulfment of Cdkn2b-deficient cells. Together, these data suggest that loss of CDKN2B promotes atherosclerosis by increasing the size and complexity of the lipid-laden necrotic core through impaired efferocytosis.
Patient-Derived Xenografts from Non–Small Cell Lung Cancer Brain Metastases Are Valuable Translational Platforms for the Development of Personalized Targeted Therapy
Authors: Hye Won Lee, Jung-il Lee, Se Jeong Lee, Hyun Jung Cho, Hye Jin Song, Da Eun Jeong, Yun Jee Seo, Sang Shin, Je-Gun Joung, Yong-Jun Kwon, Yoon-La Choi, Woong-Yang Park, Hyun Moo Lee, Ho Jun Seol, Young Mog Shim, Kyeung Min Joo, Do-Hyun Nam
Journal: Clinical Cancer Research (2014)

Abstract Purpose: The increasing prevalence of distant metastases from non–small cell lung cancer (NSCLC) indicates an urgent need for novel therapeutic modalities. Brain metastasis is particularly common in NSCLC, with severe adverse effects on clinical prognosis. Although the molecular heterogeneity of NSCLC and availability of various targeted agents suggest personalized therapeutic approaches for such brain metastases, further development of appropriate preclinical models is needed to validate the strategies. Experimental Design: We established patient-derived xenografts (PDX) using NSCLC brain metastasis surgical samples and elucidated their possible preclinical and clinical implications for personalized treatment. Results: NSCLC brain metastases (n = 34) showed a significantly higher successful PDX establishment rate than primary specimens (n = 64; 74% vs. 23%). PDXs derived from NSCLC brain metastases recapitulated the pathologic, genetic, and functional properties of corresponding parental tumors. Furthermore, tumor spheres established in vitro from the xenografts under serum-free conditions maintained their in vivo brain metastatic potential. Differential phenotypic and molecular responses to 20 targeted agents could subsequently be screened in vitro using these NSCLC PDXs derived from brain metastases. Although PDX establishment from primary NSCLCs was significantly influenced by histologic subtype, clinical aggressiveness, and genetic alteration status, the brain metastases exhibited consistently adequate in vivo tumor take rate and in vitro tumor sphere formation capacity, regardless of clinical and molecular conditions. Conclusions: Therefore, PDXs from NSCLC brain metastases may better represent the heterogeneous advanced NSCLC population and could be utilized as preclinical models to meet unmet clinical needs such as drug screening for personalized treatments. Clin Cancer Res; 21(5); 1172–82. ©2014 AACR.
Association of circulating retroviral gp70-anti-gp70 immune complexes with murine systemic lupus erythematosus.
Authors: S Izui, P J McConahey, A N Theofilopoulos, F J Dixon
Journal: The Journal of Experimental Medicine (1979)

Endogenous retroviral gp70 was investigated as a participant in the pathogenesis of a lupus-like disease that spontaneously develops in four kinds of mice (NZB, NZB x W MRL/1, and male BXSB). Sera from these strains contain a heavy form of gp 70 that varies in sedimentation rates from 9S to 19S in sucrose density gradient analysis and appears with the onset of disease and persists throughout its course. Immunologically normal strains of mice do not develop rapidly sedimenting gp70 by 8-10 mo of life. The fact that the heavy gp70 is selectively absorbed with anti-IgG antibodies or with Staphylococcus aureus protein A suggests that it is complexed with antibodies. The incidence and quantities of these gp70 ICs rise with the progression of disease in all strains with lupus. These findings suggest that Ig-complexed heavy gp70 may be involved in the pathogenesis of glomerulonephritis of mice with SLE.
Short course chemotherapy followed by concomitant chemoradiotherapy and surgery in locally advanced rectal cancer: a randomized multicentric phase II study
Authors: R. Maréchal, B. Vos, M. Polus, T. Delaunoit, M. Peeters, P. Demetter, A. Hendlisz, A. Demols, D. Franchimont, G. Verset, P. Van Houtte, J. Van de Stadt, J.L. Van Laethem
Journal: Annals of Oncology (2011)
Increase in gamma/delta T cell receptor bearing lymphocytes in normal small bowel mucosa in latent coeliac disease.
Authors: M Maki, K Holm, P Collin, E Savilahti
Journal: Gut (1991)

A jejunal biopsy specimen from an asymptomatic 35 year old man was studied because of a low serum titre of reticulin antibody and the finding of coeliac disease in his son. In this specimen villous structure was quite normal as was the total number of intraepithelial lymphocytes, but the number of gamma/delta T cell receptor bearing lymphocytes was 10 times higher than the mean in control subjects. Two years later a further biopsy specimen was obtained because of clinical symptoms and an increased titre of reticulin antibody. This specimen showed villous atrophy with crypt hyperplasia and increased infiltration of intraepithelial lymphocytes compatible with coeliac disease. A control biopsy specimen taken during gluten free diet showed normalisation of the villous architecture. Latent coeliac disease may be characterised by an increase in gamma/delta positive cells similar to that seen in established coeliac disease.
Vocal Cord Paralysis After Tracheal Intubation
Authors: H. Steele Holley
Journal: JAMA (1971)

In skilled hands, tracheal intubation during anesthesia is a relatively safe procedure. Nonetheless, laryngeal complications may occur after intubation, although they are usually transient and minor. Sore throat occurs about 40% of the time and usually lasts 48 to 72 hours.<sup>1</sup>Laryngitis has been reported after 3% of intubations and may last several days. Postintubation laryngeal edema occurs rarely in adults, but can be a distressing complication in infants and young children. Occasionally, membrane formation and laryngeal ulceration have been reported. Lesions on the vocal cords seem to be rare, but granulomas or ulcerations have been reported, particularly after prolonged tracheal intubation. A few cases of vocal cord paralysis following endotracheal anesthesia have been reported.<sup>2-4</sup>The following four case reports illustrate this complication. <h3>Report of Cases</h3><h3>Case 1.—</h3> A 64-year-old man entered the hospital with a history of worsening intermittent claudication of the left leg. He was admitted
Role of Hematotoxicity and Sex in Patients With Hodgkin's Lymphoma: An Analysis From the German Hodgkin Study Group
Authors: Beate Klimm, Thorsten Reineke, Heinz Haverkamp, Karolin Behringer, Hans T. Eich, Andreas Josting, Beate Pfistner, Volker Diehl, Andreas Engert
Journal: Journal of Clinical Oncology (2005)

Purpose Several scores have described sex as a prognostic factor in patients with Hodgkin's lymphoma (HL). However, little is known how sex-specific factors influence treatment outcome. We systematically investigated sex differences with regard to pretreatment characteristics and therapy-related variables, and examined their influence on the outcome of HL patients. Patients and Methods This analysis comprises 4,626 HL patients of all prognostic risk groups who were enrolled onto the multicenter studies HD4 to HD9 of the German Hodgkin Study Group. At 5.5 years, 2,050 female and 2,576 male patients were analyzed. Results Male and female patients had similar prognostic factors. There was more acute chemotherapy-related hematotoxicity in women, especially more severe leucopenia (WHO grade 3/4, 69.9% female and 55.2% male; P &lt; .0001). Importantly, this did not translate into more infections. Female patients had similar response rates but fewer relapses and deaths, leading to a significantly better freedom from treatment failure (FFTF; at 66 months, 81% female [95% CI, 79% to 82%] and 74% male [95% CI, 72% to 76%]). Severe leucopenia during chemotherapy was strongly associated with better FFTF, both for males and females. In addition, when only those patients who developed severe leucopenia within the first two cycles of chemotherapy were included, the factor maintained its protective role. Conclusion The protective role of severe leucopenia suggests the testing of a more individualized therapy. In future trials, this therapy may be tailored in a response-adapted manner depending on the individual toxicity profile within the first cycles.
Evaluating the Expression and Prognostic Value of TRAIL-R1 and TRAIL-R2 in Breast Cancer
Authors: Mary M. McCarthy, Mario Sznol, Kyle A. DiVito, Robert L. Camp, David L. Rimm, Harriet M. Kluger
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The cell surface receptors tumor necrosis factor–related apoptosis-inducing ligand receptor 1 (TRAIL-R1) and TRAIL-R2 transmit apoptotic signals, and agents that activate these receptors are in clinical development. We sought to determine the expression and prognostic value of TRAIL-R1 and TRAIL-R2 in early-stage breast cancer. Experimental Design: Tissue microarrays containing specimens from 655 breast cancer patients with 20-year follow-up were employed and evaluated with our automated quantitative analysis (AQUA) system. The system uses cytokeratin to define pixels as breast cancer (tumor mask) within the array spot, and measures intensity of TRAIL receptor expression using Cy5 conjugated antibodies within the mask. AQUA scores were correlated with clinical and pathologic variables. TRAIL-R1 and TRAIL-R2 expression were similarly studied on 95 unmatched normal breast specimens. Results: TRAIL-R1 expression was not associated with survival. High TRAIL-R2 expression strongly correlated with decreased survival (P = 0.0005). On multivariate analysis, high TRAIL-R2 expression remained an independent prognostic marker, as did nodal status and tumor size. High TRAIL-R2 expression correlated strongly with lymph node involvement (P = 0.0003). TRAIL-R2 expression was stronger in malignant specimens than in normal breast epithelium (P &amp;lt; 0.0001). Conclusions: High TRAIL-R2 expression was independently associated with decreased survival in breast cancer. The biological basis and the sensitivity of high TRAIL-R2 expressing cells to TRAIL agonists and/or chemotherapy are subject to further investigation. Evaluation of TRAIL-R2 expression in early-stage breast cancer may identify a subset of patients requiring more aggressive or pathway-targeted adjuvant treatment. Clinical trials involving TRAIL-R2 agonists should stratify patients based on TRAIL-R2 expression.
Depth of remission may not predict outcome of UC over 2 years
Authors: D. C. Burger, S. J. Thomas, A. J. Walsh, A. Von Herbay, O. C. Buchell, O. A. Brain, S. Keshav, S. P. Travis
Journal: Gut (2011)

<h3>Introduction</h3> Remission is the goal of therapy in ulcerative colitis (UC) and a primary endpoint of clinical trials. Disparity between clinical, endoscopic and histological assessments of activity has long been recognised, but since the definition of remission affects clinical and regulatory decisions, the disparity and impact on outcome needs re-evaluation. <h3>Methods</h3> Consecutive patients requesting an early appointment were assessed by 4 gastroenterologists, before videosigmoidoscopy and mucosal biopsy. Each scored clinical and endoscopic activity independently. Histological activity was scored by two pathologists. Clinical activity was defined by the Simple Clinical Colitis Activity Index, endoscopic activity by the Baron score and microscopic activity by the Truelove &amp; Richards9 score (remission scores ≤2, ≤1 and ‘no significant inflammation’ respectively). Outcome measures included treatment escalation, hospitalisation and colectomy. Fleiss9 κ was used to evaluate interobserver variation and two-tailed Fisher9s exact test to compare outcomes. <h3>Results</h3> 91 patients were recruited, median age at diagnosis 31 year (11–66); 60 were in remission by at least one definition: 37 (41%) were in clinical, 30/37 (81%) were also in histological remission, 30/37 (81%) were in endoscopic remission and 20/37 (76%) (20/91 = 22%) were in remission by all three measures. Of 56 in endoscopic remission: 26/56 (46%) had clinical activity and 10/26 (38%) had moderate clinical activity (SCCAI 6–8). Of 47 in histological remission only 42 (81%) were in endoscopic remission and 30 (64%) were in clinical remission. Agreement between histological and endoscopic assessment (k=0.58, moderate agreement) was better than between clinical and endoscopic (k=0.27), or clinical and histological (k=0.47), or between all three methods (k=0.44). follow-up data was available in 54/60 (90%), with 29 month (5–35 month) median follow-up; median age at review 48 year (19–74), 57% female, 30% proctitis, 48% distal, 22% extensive. Most (83%) took maintenance therapy: 5ASA (31/54), immunomodulators (13/54), or infliximab (1/54). 43 (80%) maintained steroid-free remission at 12 month and 34 (63%) during follow-up; of those needing steroids, 9 (45%) had &gt;1 course during follow up and 3 (15%) infliximab. 4 (7%) needed hospitalisation and 1 (2%) colectomy. 12 month steroid-free remission did not differ according to the depth of remission (80% all 3 criteria, 75% on 2 criteria, 83% on 1 criterion, p=0.7). <h3>Conclusion</h3> Modest agreement between clinical, endoscopic or histological activity emphasises the differences between the measures, all of which may have prognostic value. Clinical assessment systematically over-estimates disease activity, but the outcome over 2 years was not affected by the definition of remission.
Teaching Human Relations in Legal Negotiation
Authors: E. MANSELL PATTISON
Journal: American Journal of Psychiatry (1969)

This paper describes the method and content of an experimental course aimed at teaching human relations in legal role performance. In both the lawyer-client relationship and the lawyer-lawyer relationship, human factors often play a determining role in the success or failure of the lawyer's task. For such teaching to be effective, the author believes it must involve the student experientially and must also be tied in with his expected professional role performance.
Is Tremelimumab Beneficial in Advanced Melanoma?
Authors: Kenneth S. Wilson, Rami Kotb
Journal: Journal of Clinical Oncology (2013)

necessary to unravel the potentially complex etiology of elevated tricuspid regurgitant jet velocity among adult survivors of childhood cancer.Right heart catheterization augmented by exercise testing will be the next step in validating these findings, determining etiology, and most importantly, directing appropriate medical therapy.More comprehensive evaluation and continued follow-up of the St Jude Lifetime Cohort will allow us to clarify these issues and determine the impact of elevated tricuspid regurgitant velocity on subsequent morbidity and mortality.