tbuckley/cabot-search huggingface dataset:
P18 Liver fibrosis assessed by transient elastography predicts response in chronic hepatitis C infected patients treated with PEG-Interferon and Ribavirin
Authors: A. N. S. Nkhoma, D. A. Sheridan, D. A. Price, M. L. Schmid, C. Miller, K. Baxter, M. F. Bassendine, S. McPherson
Journal: Gut (2011)

Introduction Chronic hepatitis C virus infection (HCV) is a common cause of cirrhosis and end stage liver disease. Treatment with Pegylated interferon (PEG-IFN) and ribavirin (RBV) results in sustained virological response (SVR) in approximately 60% of infected individuals. Increasing stage of fibrosis is known to be a key factor associated with non-response to treatment with PEG-IFN+RBV. Traditionally, fibrosis stage has been determined by liver biopsy, but this is invasive. Newer non-invasive methods of assessing fibrosis such as transient elastography (TE) are now available. Aim To assess baseline liver stiffness measurement (LSM) assessed by TE as a predictor of SVR in HCV-infected subjects treated with PEG-IFN+RBV. Method Retrospective review of outcomes of treatment in naïve patients treated with PEG-IFN+RBV for HCV between 7 January and 9 June. Post-transplant and co-infected patients were excluded. Patients who had valid LSM within 6 months of treatment were included in the TE analysis. Results 168 patients (mean age 39±10, 70% male, 14% cirrhotic, 53% high viral load) received PEG-IFN+RBV for HCV in the study period. The overall SVR rate was 59% (50% for genotype [G] 1/4 and 70% for G2/3, p<0.001). The SVR rate was only 28% in cirrhotics (10% for G1/4 and 43% for G2/3). 87 patients had a pre-treatment TE (median LSM 6.6 KPa [3.3–73]). LSM was significantly associated with treatment response to PEG-IFN (p=0.01), with the effect more pronounced in HCV G2/3 infection (p=0.001). The optimum cut-off to predict non-response to treatment was 11 KPa. 30 patients (16%) stopped treatment due to side-effects or non-compliance, including 1 death from pneumonitis. Conclusion (1) LSM determined by transient elastography may be used as a non-invasive tool to predict treatment response in subjects infected with HCV. (2) LSM >11 KPa could be used to identify patients who may have lower response rates and may benefit from longer treatment.
Traditional Versus Up-Front [<sup>18</sup>F] Fluorodeoxyglucose–Positron Emission Tomography Staging of Non–Small-Cell Lung Cancer: A Dutch Cooperative Randomized Study
Authors: Gerarda J.M. Herder, Henk Kramer, Otto S. Hoekstra, Egbert F. Smit, Jan Pruim, Harm van Tinteren, Emile F. Comans, Paul Verboom, Carin A. Uyl-de Groot, Alle Welling, Marinus A. Paul, Maarten Boers, Pieter E. Postmus, Gerrit J. Teule, Harry J.M. Groen
Journal: Journal of Clinical Oncology (2006)

We investigated whether application of positron emission tomography (PET) immediately after first presentation might simplify staging while maintaining accuracy, as compared with traditional strategy in routine clinical setting.At first presentation, patients with a provisional diagnosis of lung cancer without overt dissemination were randomly assigned to traditional work-up (TWU) according to international guidelines or early PET followed by histologic/cytologic verification of lesions, or imaging and follow-up. Patients with [18F] fluorodeoxyglucose (18FDG) -avid, noncentral tumors without suspicion of mediastinal or distant metastases on PET proceeded directly to thoracotomy. Follow-up in presumed benign lesions was at least 12 months. In patients treated with surgery or neoadjuvant therapy, the quality of staging was measured by comparing the clinical stage to the final stage (combination of peroperative staging and 6 months of follow-up). To investigate test substitution, we analyzed the number of (non)invasive tests to achieve clinical TNM staging, and its associated costs.Between 1999 and 2001, 465 patients (233 TWU, 232 PET) were enrolled at 22 hospitals. The mean (standard deviation) number of procedures to finalize staging was equal in the TWU arm and the PET arm: 7.9 (2.0) v 7.9 (1.9), P = .90, respectively. Mediastinoscopies occurred significantly less often in the PET arm. Agreement between clinical and final stage was good in both arms (kappa = .85 v .78; P = .07). Costs did not differ significantly.Up-front 18FDG-PET in patients with (suspected) lung cancer does not reduce the overall number of diagnostic test, but it maintains quality of TNM staging with the use of less invasive surgery.
Partial Purification of Plasma Thromboplastin Antecedent (Factor XI) and its Activation by Trypsin
Authors: Hidehiko Saito, Oscar D. Ratnoff, James S. Marshall, Jack Pensky
Journal: Journal of Clinical Investigation (1973)

A persistent puzzle in our understanding of hemostasis has been the absence of hemorrhagic symptoms in the majority of patients with Hageman trait, the hereditary deficiency of Hageman factor (factor XII). One proposed hypothesis is that alternative mechanisms exist in blood through which plasma thromboplastin antecedent (PTA, factor XI) can become active in the absence of Hageman factor. In order to test this hypothesis, the effect of several proteolytic enzymes, among them thrombin, plasma kallikrein, and trypsin, was tested upon unactivated PTA. PTA was prepared from normal human plasma by Ca3(PO4)2 adsorption, ammonium sulfate fractionation, and successive chromatography on QAE-Sephadex (twice). Sephadex-G150, and SP-Sephadex. The partially purified PTA was almost all in its native form, with a specific activity of 45-70 U/mg protein; the yield was about 10%. It contained no measurable amounts of other known clotting factors, plasmin, plasminogen, nor IgG. Incubation of PTA with trypsin generated potent clot-promoting activity that corrected the abnormally long clotting time of plasma deficient in Hageman factor or PTA but not in Christmas factor. This clot-promoting agent behaved like activated PTA on gel filtration (apparent molecular weight: 185,000) and was specifically inhibited by an antiserum directed against activated PTA. These data suggested that PTA can be converted into its active form by trypsin. PTA was not activated by thrombin, chymotrypsin, papain, ficin, plasmin, plasma kallikrein, tissue thromboplastin, or C̄. Trypsin converted PTA to its active form enzymatically. Whether trypsin serves to activate PTA in vivo is not yet clear.
THE CELLULAR REACTIONS TO LIPOID FRACTIONS FROM ACID-FAST BACILLI
Authors: Kenneth C. Smithburn, Florence R. Sabin
Journal: The Journal of Experimental Medicine (1932)

1. A comparative study has been made of the cellular reactions induced by phosphatides from five strains of acid-fast bacilli. Each of these reactions is characterized principally by epithelioid cells and giant cells. 2. The phosphatides are first phagocytized by young connective tissue cells or monocytes. The lipoid is then dispersed into fine particles with the formation of classical epithelioid cells. 3. A comparison has been made of the reactions induced by heat-killed and defatted tubercle bacilli with those induced by tuberculophosphatide. 4. Further studies have been made to determine whether or not the phosphatide causes sensitization to tuberculin. It does not do so. 5. The life cycle of the epithelioid cell has been observed in all its stages.
How to Survive Medical School
Authors: Michael Kastan
Journal: JAMA (1984)

This book is the story of one physician's experiences throughout her medical training. The title may seem to be a bit of a misnomer because the book does not concentrate on instructions in how to survive the modern educational system. However, in sharing her anecdotes Dr Martin may be helping the reader to survive the process by showing that others have experienced similar feelings of anxiety and inadequacy at each level of training. She has found ways (often humorous) to verbalize thoughts and emotions that most of us experience through the years of premedical education, medical school, and postgraduate training. There is a certain bluntness and honesty in her approach and she pulls no punches. She doesn't try to paint a rosy picture of the process of medical training ("my years of medical training were not the happiest ones of my life"). At times, she is even quite cynical ("All
Broncholithiasis and lithoptysis associated with silicosis
Authors: V.C.S. Antão, G.A. Pinheiro, J.M. Jansen
Journal: European Respiratory Journal (2002)

A case of broncholithiasis associated with massive silicosis is reported, showing a rare aspect of parenchymal lesions generating broncholiths as well as the presence of recurrent lithoptysis, with subsequent regression of radiological lesions. Aetiological, clinical, physiopathological, and radiological aspects of the disease are discussed, demonstrating the importance of the use of computed tomography in diagnosis. The mineralogical analysis of expectorated fragments is also shown.
Acute Myocardial Infarction in Doncaster. II--Delays in Admission and Survival
Authors: H. C. Smyllie, M. P. Taylor, R. A. Cuninghame-Green
Journal: BMJ (1972)

The speed of admission of patients with suspected acute myocardial infarction was observed over a period of 12 months during which a "no refusal" coronary care scheme was functioning, with emphasis on minimizing delay. During the same period the duration of survival of cases diagnosed as coronary thrombosis by the coroner9s pathologist was measured. Comparison of the two series shows that 75% to 80% of the coroner9s cases had died before the median time of notification of the general practitioner by those patients referred to hospital. We argue that the provision of mobile coronary care on request from general practitioners is unlikely to have an appreciable effect in preventing deaths from acute myocardial infarction outside hospital.
Transition of Extremely Low-Birth-Weight Infants From Adolescence to Young Adulthood
Authors: Saroj Saigal, Barbara Stoskopf, David Streiner, Michael Boyle, Janet Pinelli, Nigel Paneth, John Goddeeris
Journal: JAMA (2006)

Traditionally, educational attainment, getting a job, living independently, getting married, and parenthood have been considered as markers of successful transition to adulthood.To describe and compare the achievement and the age at attainment of the above markers between extremely low-birth-weight (ELBW) and normal birth-weight (NBW) young adults.A prospective, longitudinal, population-based study in central-west Ontario, Canada, of 166 ELBW participants who weighed 501 to 1000 g at birth (1977-1982) and 145 sociodemographically comparable NBW participants assessed at young adulthood (22-25 years). Interviewers masked to participant status administered validated questionnaires via face-to-face interviews between January 1, 2002, and April 30, 2004.Markers of successful transition to adulthood, including educational attainment, student and/or worker role, independent living, getting married, and parenthood.At young adulthood, 149 (90%) of 166 ELBW participants and 133 (92%) of 145 NBW participants completed the assessments at mean (SD) age of 23.3 (1.2) years and 23.6 (1.1) years, respectively. We included participants with neurosensory impairments (ELBW vs NBW: 40 [27%] vs 3 [2%]) and 7 proxy respondents. The proportion who graduated from high school was similar (82% vs 87%, P = .21). Overall, no statistically significant differences were observed in the education achieved to date. A substantial proportion of both groups were still pursuing postsecondary education (47 [32%] vs 44 [33%]). No significant differences were observed in employment/school status; 71 (48%) ELBW vs 76 (57%) NBW young adults were permanently employed (P = .09). In a subanalysis, a higher proportion of ELBW young adults were neither employed nor in school (39 [26%] vs 20 [15%], P = .02 by Holm's correction); these differences did not persist when participants with disabilities were excluded. No significant differences were found in the proportion living independently (63 [42%] vs 70 [53%], P = .19), married/cohabitating (34 [23%] vs 33 [25%], P = .69), or who were parents (16 [11%] vs 19 [14%], P = .36). The age at attainment of the above markers was similar for both cohorts.Our study results indicate that a significant majority of former ELBW infants have overcome their earlier difficulties to become functional young adults.
The dynamical hypothesis in cognitive science
Authors: Tim van Gelder
Journal: Behavioral and Brain Sciences (1998)

According to the dominant computational approach in cognitive science, cognitive agents are digital computers; according to the alternative approach, they are dynamical systems. This target article attempts to articulate and support the dynamical hypothesis. The dynamical hypothesis has two major components: the nature hypothesis (cognitive agents are dynamical systems) and the knowledge hypothesis (cognitive agents can be understood dynamically). A wide range of objections to this hypothesis can be rebutted. The conclusion is that cognitive systems may well be dynamical systems, and only sustained empirical research in cognitive science will determine the extent to which that is true.
Arterial Carbon Dioxide and Oxygen Tensions During Spinal Block
Authors: Rudolph H. de Jong
Journal: JAMA (1965)

Subarachnoid or peridural anesthesia (spinal block) was administered to 32 patients undergoing major surgery. Cutaneous sensory levels ranged from the tenth thoracic to the fifth cervical dermatomes. Supplemental sedation was given to 19 patients during surgery. The arterial Pco2and Po2prior to induction of block, but after premedication, were compared with values obtained during spinal block. There was no significant change in the arterial Pco2and Po2before and after spinal block. Thus, normal ventilation appeared to be unaffected by block of the intercostal nerves. Although the mean arterial Po2remained unchanged, the administration of supplemental oxygen to patients with cardiopulmonary disease might be a wise precaution. A disposable plastic face mask performed this function satisfactorily, raising the Po2above 100 mm Hg.
Rodent cell transformation and immediate early gene expression following 60-Hz magnetic field exposure.
Authors: E K Balcer-Kubiczek, X F Zhang, G H Harrison, W A McCready, Z M Shi, L H Han, J M Abraham, L L Ampey, S J Meltzer, M C Jacobs, C C Davis
Journal: Environmental Health Perspectives (1996)

Some epidemiological studies suggest that exposure to power frequency magnetic fields (MFs) may be associated with an elevated risk of human cancer, but the experimental database remains limited and controversial. We investigated the hypothesis that 60-Hz MF action at the cellular level produces changes in gene expression that can result in neoplastic transformation. Twenty-four hour 200 microT continuous MF exposure produced negative results in two standard transformation systems (Syrian hamster embryo cells and C3H/10T1/2 murine fibroblasts) with or without postexposure to a chemical promoter. This prompted a reexamination of previously reported MF-induced changes in gene expression in human HL60 cells. Extensive testing using both coded and uncoded analyses was negative for an MF effect. Using the same exposure conditions as in the transformation studies, no MF-induced changes in ornithine decarboxylase expression were observed in C3H/10T1/2 cells, casting doubt on a promotional role of MF for the tested cells and experimental conditions.
Extraosseous Ewing's Sarcoma
Authors: Mark E. Miller, Lyska Emerson, Frederic Clayton, Brandon G. Bentz, Richard E. Data, Karen L. Salzman, Lynn M. Smith, Margaret K. Yu
Journal: Journal of Clinical Oncology (2007)

or subcutaneous injection sites.Cutaneous zygomycosis usually appears as a single, painful, indurated skin lesion characterized by rapid infarction and necrosis of host tissues that result from invasion of the vasculature by hyphae. 5Dissemination or deep tissue involvement are unusual complications of cutaneous zygomycosis.Zygomycosis is diagnosed on biopsy or resection of the involved area followed by histopathological tissue examination and microbiological culture.Furthermore, species identification can be confirmed by molecular methods, such as polymerase chain reaction-based restriction fragment length polymorphism or amplification and direct sequencing of fungal ribosomal RNA genes and their intergenic spacer. 2,4,8arly diagnosis is critical for successful treatment of zygomycosis that requires immediate surgical intervention.For adjunctive antifungal therapy, amphotericin B or its lipid derivatives remain first-line agents, as several antifungal agents, such as voriconazole and caspofungin, are not effective against zygomycetes.However, in vitro data with posaconazole, a novel extended-spectrum triazole, suggested that it may be also effective against these pathogens. 9,10Moreover, posaconazole has been used for successful in vivo salvage therapy in patients who experienced treatment failure or could not tolerate standard therapy. 11,12Antimycotic therapy is often required for long-term periods.][15][16] Often, both diagnostic and therapeutic measures are performed too late and are inadequate.Death rates in infected transplantation recipients with zygomycosis are approximately 50%. 15Despite early diagnosis and aggressive combined surgical and antifungal therapy, the prognosis of zygomycosis is not favorable.In the case of zygomycosis, localized disease, absence of pulmonary involvement, neutrophil recovery, and stabilization, or improvement of the patients' underlying diseases, early surgical resection of affected tissues, and therapy with highdose amphotericin B are assumedly associated with the best chance for survival of cancer patients. 15,17
Abstract 5371: Synergistic antitumor effect of HDAC inhibitor PXD101 in combination with irinotecan in colon cancer
Authors: Young-Soon Na, Kyung-A Jung, Seung-Mi Kim, Min-Hee Ryu, Yong Sang Hong, Jin Cheon Kim, Jung Shin Lee, Tae Won Kim
Journal: Cancer Research (2010)

Abstract The histone deacetylase inhibitors (HDACi), such as PXD101 or SAHA, inhibit the proliferation and stimulate the apoptosis in tumors. The enhanced effect of HDACi combined with chemotherapy or radiotherapy has been reported in several cancers. In this study, we investigated the antitumor effect of HDACi PXD101 combined with irinotecan in colon cancer. PXD101 and SN38, active form of irinotecan, had a dose-dependent anti-proliferative activity in HCT116 and HT29 colon cancer cells. PXD101 combined with SN38 had a synergistic effect in colon cancer cell lines, as shown by combination index. The combination of PXD101 with SN38 had an effect on XIAP and p21 protein expressions with time- and dose-dependent manner, more prominently in HCT116 than HT29 cells. These effects were further enhanced by the addition of PXD101 than irinotecan alone in both cell lines. In xenograft mice, PXD101 in combination with irinotecan dramatically inhibited tumor growth without additive toxicity. In addition, antiumor effect was more prominent in HCT116 than HT29 xenografts. Apoptotic effects of tumor in xenografts treated with these combinations were better than irinotecan alone. Combination of PXD101 and irinotecan resulted in 63 % of relative SUV mean in [18F]FLT-PET in mice with established HCT116 xenograft. Early response to these agents can be detected with [18F]FLT-PET. These data suggest that PXD101 increases the cytotoxic activity of iriontecan in colon cancer and these drug combinations should be explored in the treatment of colon cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5371.
The Pathophysiology of Human Immunologic Disorders
Authors: Carlos R. Abramowsky
Journal: JAMA (1983)

This volume is not a textbook of clinical immunology in the usual sense. It deals with immunologic mechanisms and is meant for readers with a good foundation in immunobiology who wish to gain some clinical perspective or update their information in areas of human immunology other than their own. The book is divided into 12 chapters written by 17 authors, a sign of the times and the explosion in the field. Some of the topics include "Disorders of B Lymphocytes," "Macrophages and Immune Regulation," "Immunodeficiencies," "Immune Complexes," "T-Cell Differentiation," "Immunology of Aging," and "Immunobiology of Cancer and Lymphoid Neoplasms." The most objectionable aspects of the book are those that could have been very easily corrected. All chapters are variably plagued by typographic errors and misspellings of words and sometimes of names of authors. In addition, literature references are frequently wrong or discrepant with the text as to the year of
Transstenotic coronary pressure gradient measurement in humans: In vitro and in vivo evaluation of a new pressure monitoring angioplasty guide wire
Authors: Bernard De Bruyne, Walter J. Paulus, Pascal J. Vantrimpont, Stanislas U. Sys, Guy R. Heyndrickx, Nico H.J. Pijls
Journal: Journal of the American College of Cardiology (1993)
COMBINATION SURGICAL INSTRUMENT.
Authors: HENRY EMERSON WETHERILL
Journal: JAMA (1902)

<h3>THE OBJECTS OF THE INSTRUMENT.</h3> The purpose of this instrument is to combine such surgical instruments together that are ordinarily used by the physician, nurse, medical student and others that may from time to time need a few surgical tools. So far as possible the great danger of a combination instrument, that is to say one instrument interfering with the effectiveness of another, has been overcome. The instrument is not intended to supplant ordinary instruments as in the surgeon's pocket case, but it is intended to be used where one instrument at a time is desired. It is meant particularly for emergencies, as it is an instrument that one is likely to have with him at all times and in this respect not like the pocket case which sooner or later is apt to be at home when the emergency occurs. By the use of a small and a large
The role of VHL in clear-cell renal cell carcinoma and its relation to targeted therapy
Authors: Peter E. Clark
Journal: Kidney International (2009)

The basic biology underlying the development of clear-cell renal cell carcinoma (ccRCC) is critically dependent on the von Hippel-Lindau gene (VHL), whose protein product is important in the cell's normal response to hypoxia. Aberrations in VHL's function, either through mutation or promoter hypermethylation, lead to accumulation of the transcriptional regulatory molecule, hypoxia-inducible factor alpha (HIFalpha). HIFalpha can then dimerize with HIFbeta and translocate to the nucleus, where it will transcriptionally upregulate a series of hypoxia-responsive genes, including vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and others. Binding of these ligands to their cognate receptors activates a series of kinase- dependent signaling pathways, including the RAF-MEK-ERK and phosphatidylinositol-3 kinase-AKT-mTOR pathways. Targeted agents developed and now approved for use in advanced ccRCC include humanized monoclonal antibodies against VEGF, small-molecule tyrosine kinase inhibitors, and inhibitors of mTOR. Understanding the biology of ccRCC is critical in understanding the current therapy for the disease and in developing novel therapeutics in the future. This review will provide an overview of the genetics of ccRCC, with an emphasis on how this has informed the development of the targeted therapeutics for this disease.