tbuckley/cabot-search huggingface dataset:
Relationship between pretreatment specific IgE and the response to omalizumab therapy
Authors: U. Wahn, C. Martin, P. Freeman, M. Blogg, P. Jimenez
Journal: Allergy (2009)

Omalizumab, an anti-IgE antibody, has proven efficacy in patients with moderate-to-severe and severe persistent allergic (IgE-mediated) asthma. While previous analyses have had some limited success in predicting which patients will gain greatest benefit based on pretreatment baseline characteristics, it remains important to try to improve this predictability.Following a run-in phase, patients (12-75 years) inadequately controlled despite current therapy were randomized to receive omalizumab or placebo for 28 weeks in a double-blind, parallel-group, multicenter study (INNOVATE). Univariate analyses were performed to assess whether pretreatment specific IgE serum levels and related variables could be identified that were predictive of a response to omalizumab patients (n = 337) enrolled in INNOVATE. Response was measured via variables including exacerbations, QoL, FEV(1) and physicians' overall assessment.A total of 305 patients (90.5%) were sensitive to more than one allergen and the majority of patients were positive to D1 Dermatophagoides pteronyssinus and D2 Dermatophagoides farinae. Patients with relatively high values of D1 or D2, but with these making a relatively low contribution to total specific IgE load, appeared to attain most benefit from omalizumab. However, no consistent predictive effect for omalizumab response was observed either for total specific IgE or levels of IgEs specific for individual allergens.Based on these data, pretreatment allergen-specific IgE levels do not provide any better prediction of response to treatment as compared with pretreatment total IgE. At present, the most reliable method of identifying patients who respond to omalizumab treatment remains a physician's assessment.
Gene Expression in Fixed Tissues and Outcome in Hepatocellular Carcinoma
Authors: Yujin Hoshida, Augusto Villanueva, Masahiro Kobayashi, Judit Peix, Derek Y. Chiang, Amy Camargo, Supriya Gupta, Jamie Moore, Matthew J. Wrobel, Jim Lerner, Michael Reich, Jennifer A. Chan, Jonathan N. Glickman, Kenji Ikeda, Masaji Hashimoto, Goro Watanabe, Maria G. Daidone, Sasan Roayaie, Myron Schwartz, Swan Thung, Helga B. Salvesen, Stacey Gabriel, Vincenzo Mazzaferro, Jordi Bruix, Scott L. Friedman, Hiromitsu Kumada, Josep M. Llovet, Todd R. Golub
Journal: New England Journal of Medicine (2008)

It is a challenge to identify patients who, after undergoing potentially curative treatment for hepatocellular carcinoma, are at greatest risk for recurrence. Such high-risk patients could receive novel interventional measures. An obstacle to the development of genome-based predictors of outcome in patients with hepatocellular carcinoma has been the lack of a means to carry out genomewide expression profiling of fixed, as opposed to frozen, tissue.We aimed to demonstrate the feasibility of gene-expression profiling of more than 6000 human genes in formalin-fixed, paraffin-embedded tissues. We applied the method to tissues from 307 patients with hepatocellular carcinoma, from four series of patients, to discover and validate a gene-expression signature associated with survival.The expression-profiling method for formalin-fixed, paraffin-embedded tissue was highly effective: samples from 90% of the patients yielded data of high quality, including samples that had been archived for more than 24 years. Gene-expression profiles of tumor tissue failed to yield a significant association with survival. In contrast, profiles of the surrounding nontumoral liver tissue were highly correlated with survival in a training set of tissue samples from 82 Japanese patients, and the signature was validated in tissues from an independent group of 225 patients from the United States and Europe (P=0.04).We have demonstrated the feasibility of genomewide expression profiling of formalin-fixed, paraffin-embedded tissues and have shown that a reproducible gene-expression signature correlated with survival is present in liver tissue adjacent to the tumor in patients with hepatocellular carcinoma.
Therapeutic Pancreatic Endoscopy
Authors: M. J. Schmalz, J. E. Geenen
Journal: Endoscopy (1999)

Therapeutic endoscopic retrograde cholangiopancreatography (ERCP) has established itself as a valuable tool for the treatment of a variety of biliary tract disorders. Fueled by an ever-increasing demand for minimally invasive therapy, pancreatic endoscopy was the logical frontier for expansion of therapeutic ERCP. Endoscopic treatment of benign pancreatic disorders can be a cost-effective alternative to more invasive radiological or surgical methods. Conditions such as acute and chronic pancreatitis, pancreatic calculi, and pseudocysts can in many cases be managed endoscopically. This review summarizes the current state of the art in therapeutic pancreatic endoscopy.
The Immorality of New York's Doctors' Strike
Authors: Fred Rosner
Journal: JAMA (1975)

<h3>To the Editor.—</h3> The recent doctors' strike in New York City reemphasizes serious questions surrounding the morality and ethics of a physician "abandoning" his patients. Is there ever an issue greater in importance to a physician than the care of his patients? Can financial considerations or working conditions ever be of such a nature that they override the doctor's primary responsibility of caring for his patients? I think not. The League of Voluntary Hospitals and the Committee of Interns and Residents (CIR) were unable to resolve their differences, so that a strike ensued. Most issues had been satisfactorily resolved prior to the strike. The major stumbling block was the demand by the CIR that the workweek for house staff not exceed 80 hours. The League had proposed that house staff not work more than every third night, a schedule that would average out to approximately 80 hours a week. Yet
Lack of trained personnel thwarts Sudan's plans to rebuild health services
Authors: P. Moszynski
Journal: BMJ (2008)

Four years after a comprehensive peace agreement was signed, and despite a massive international drive to improve the situation, Southern Sudan still has the worst health statistics in the world. Fewer than one in four of the population has access to any medical facility.

A strategy to improve outreach was launched last month at Southern Sudan’s health assembly, which saw donors, international agencies, and service providers come together with the nascent Ministry of Health to try to redress the problems created by more than four decades of conflict in one of Africa’s most impoverished areas.

The assembly …
Are leukocytes in asthmatic patients aging faster? A study of telomere length and disease severity
Authors: Shigenori Kyoh, Narayanan Venkatesan, Audrey H. Poon, Michiyoshi Nishioka, Ting-Yu Lin, Carolyn J. Baglole, David H. Eidelman, Qutayba Hamid
Journal: Journal of Allergy and Clinical Immunology (2013)
Helper T cells are required for the polyclonal stimulation of cytotoxic T cells by concanavalin A.
Authors: L M Pilarski, P A Bretscher, L L Baum
Journal: The Journal of Experimental Medicine (1977)

Concanavalin A stimulation of T-cell cytotoxicity has been shown to be absolutely dependent on helper T-cell collaboration. Thymocytes stimulated with ConA do not differentiate to yield cytotoxic effector cells. However, thymocytes cocultured with irradiated spleen cells as helpers and ConA yield high levels of cytotoxicity. The helper cell bears theta antigens on its surface, is not an adherent cell, and does not require any adherent cell functions in our culture conditions. The ConA-dependent helper cells appear to be polyclonal in specificity. Thus, polyclonal stimulation of cytotoxicity by ConA requires T helper-T precursor collaboration in analogy to antigen-specific T helper-T precursor interactions. Unlike the antigen-specific interacitons, the ConA-driven cytotoxicity does not appear to require linked associative recognition for induction of cytotoxicity.
Ferroportin disease: A systematic meta-analysis of clinical and molecular findings
Authors: Roman Mayr, Andreas R. Janecke, Melanie Schranz, William J.H. Griffiths, Wolfgang Vogel, Antonello Pietrangelo, Heinz Zoller
Journal: Journal of Hepatology (2010)

Classical ferroportin disease is characterized by hyperferritinemia, normal transferrin saturation, and iron overload in macrophages. A non-classical form is characterized by additional hepatocellular iron deposits and a high transferrin saturation. Both forms demonstrate autosomal dominant transmission and are associated with ferroportin gene (SLC40A1) mutations. SLC40A1 encodes a cellular iron exporter expressed in macrophages, enterocytes, and hepatocytes. The aim of the analysis is to determine the penetrance of SLC40A1 mutations and to evaluate in silico tools to predict the functional impairment of ferroportin mutations as an alternative to in vitro studies.We conducted a systematic review of the literature and meta-analysis of the biochemical presentation, genetics, and pathology of ferroportin disease.Of the 176 individuals reported with SLC40A1 mutations, 80 were classified as classical phenotype with hyperferritinemia and normal transferrin saturation. The non-classical phenotype with hyperferritinemia and elevated transferrin saturation was present in 53 patients. The remaining patients had normal serum ferritin or the data were reported incompletely. Despite an increased hepatic iron concentration in all biopsied patients, significant fibrosis or cirrhosis was present in only 11%. Hyperferritinemia was present in 86% of individuals with ferroportin mutations. Bio-informatic analysis of ferroportin mutations showed that the PolyPhen score has a sensitivity of 99% and a specificity of 67% for the discrimination between ferroportin mutations and polymorphisms.In contrast to HFE hemochromatosis, ferroportin disease has a high penetrance, is genetically heterogeneous and is rarely associated with fibrosis. Non-classical ferroportin disease is associated with a higher risk of fibrosis and a more severe overload of hepatic iron.
The Risk of Hepatitis B Among Select Employee Groups in an Urban Hospital
Authors: John F. Jovanovich
Journal: JAMA (1983)

Hospital employees are at various degrees of risk for development of hepatitis B infections. A retrospective review of surveillance records in five clinical areas at high risk for hepatitis B exposure was carried out to determine its prevalence and incidence in each area. The area surveyed with the highest risk was the emergency department. It was followed, in descending order, by the operating room, the medical and surgical intensive care units, and the dentistry—oral surgery clinic. The surveyed area at the lowest risk was the hemodialysis unit. Strict infection-control guidelines probably minimize the employees' risk to hepatitis in the hemodialysis unit. In the emergency department, however, employees may be increasingly exposed to hepatitis B by dealing with life-threatening problems in an uncontrolled setting. (<i>JAMA</i>1983;250:1893-1894)
Use of 3 mm percutaneous instruments with 5 mm end effectors during different laparoscopic procedures
Authors: Giulia David, Luigi Boni, Stefano Rausei, Elisa Cassinotti, Gianlorenzo Dionigi, Francesca Rovera, Sebastiano Spampatti, Elisabetta Marta Colombo, Renzo Dionigi
Journal: International Journal of Surgery (2013)
Portacaval Transposition in the Rat: Definition of a Valuable Model for Hepatic Research
Authors: Irving S. Benjamin, Calvin J. Ryan, Gert H. C. Engelbrecht, John A. H. Campbell, Rosemaryvan Hoorn-Hickman, Leslie H. Blumgart
Journal: Hepatology (1984)

Portacaval transposition (PCT) in rats results in a smaller loss of body mass and liver mass than end-to-side portacaval shunt (PCS). Detailed studies of liver function, mass and histology were not previously available and have been undertaken in two different strains of growing rat in order to define the value of this model. PCT rats gained weight normally, while only 50% of PCS rats regained their preoperative weight by the tenth week. Wet and dry weights of liver fell relative to control values after both operations, but the fall was significantly greater after PCS than after PCT: there were parallel changes in hepatocyte size. There was a marked rise in liver-associated enzymes in the first 2 days after PCS only, and minimal enzyme elevations persisted in this group. The extent of cellular damage seen histologically closely parallelled the rise in SGOT in individual rats. At 72 hr, PCS rats showed focal necrotic changes, and by 10 weeks there was marked fatty infiltration: PCT rats had normal histology or showed minimal changes. PCT therefore provides a model in which there is total portal diversion without the more severe effects of the conventional PCS on hepatic structure and function. This has particular value in studies of experimental hepatic encephalopathy, of hormonal and amino acid changes after portal diversion, and of factors initiating or controlling liver regeneration.
Time dependent changes in the concentration and type of bacterial sequences found in cholesterol gallstones
Authors: Alexander Swidsinski, Michael Khilkin, Hartmut Pahlig, Sonja Swidsinski, Friedrich Priem
Journal: Hepatology (1998)

The role of bacteria in gallstone formation could not be conclusively evaluated until bacterial presence or absence in a stone was consistently shown. Cultural bacteriologic investigations at the time of cholecystectomy, however, led to the assumption that cholesterol gallstones were free of bacteria. In this study, we used a culture independent, molecular genetic approach to detect, quantify, and identify bacteria in cholesterol gallstones from 100 patients at the time of cholecystectomy and 6 months following. Bacterial growth was recorded in the culture in 9 of 100 gallstones; bacterial DNA, however, was detected in 82 of 91 sterile gallstones. High concentrations corresponding to between 10 6 to 10 7 bacteria/g were detected in 11 stones and low concentrations of 10 5 bacteria/g were detected in 71 sterile stones. The infection in stones with a positive bacterial culture was characterized by the predominance of single bacterial sequence(s) of the bacteria cultured. A similar predominance, indicating a recent infection, was found in sterile gallstones with low DNA concentrations. A high diversity of non-repeating bacterial sequences, possibly arising from previous overlapping infections, was found in sterile gallstones with high concentrations of bacterial DNA. After 6 months concentrations of bacterial DNA fell significantly in all groups of gallstones. As bacterial DNA is quickly destroyed upon storage, but is nevertheless readily found in most gallstones at the time of cholecystectomy, there must be a mechanism by which it is replenished. One such mechanism is the frequently reoccurring, possibly self-terminating infection and another one is the permanent colonization of the gallstone with bacteria at low concentrations. Both can promote cholecystolithiasis.
Ischemic Inactivation of G Protein–Coupled Receptor Kinase and Altered Desensitization of Canine Cardiac β-Adrenergic Receptors
Authors: Xichun Yu, Min Zhang, Kimberly Kyker, Eugene Patterson, Jeffrey L. Benovic, David C. Kem
Journal: Circulation (2000)

G protein-coupled receptor kinases (GRKs) modulate myocardial beta-adrenergic receptor (betaAR) signaling. We examined whether GRK activity was altered 6, 24, and 96 hours after left anterior descending coronary artery ligation (LAD CAL) in the dog.GRK activity was measured in arrhythmogenic subepicardial border zone (EBZ) tissue overlying the infarct and from nonischemic remote-site (RS) subepicardial tissue from the same animal. GRK activity in the ischemic EBZ was 15% of RS (P:=0.03, n=6) 24 hours after CAL and appeared to start as early as 6 hours through 96 hours. GRK activity and immunoblot data demonstrated a marked decrease of GRK2 but not GRK5 at 24 hours. EBZ tissue exhibited high-affinity binding for (-)-isoproterenol (K:(i) of 0. 076+/-0.026 nmol/L [SEM]) at 24 hours, which was not significantly different from control tissue from nonoperated animals (1.2+/-0.8 nmol/L, P:>0.05, n=6). A significantly lower K:(i) of 13.8+/-2.8 nmol/L (P:<0.001, n=6) was observed for RS taken from the ischemic animals. This was reflected by a 4-fold increase in the EC(50) of isoproterenol-stimulated adenylyl cyclase activity from 18 nmol/L in EBZ tissue to 73 nmol/L in RS (P:<0.05, n=4).There is a selective decrease in GRK2 activity and a loss of the ability of the arrhythmia-prone EBZ tissue to desensitize to beta-adrenergic stimulation 24 hours after CAL. This correlates temporally with a second (late) peak in sudden cardiac death previously observed between 6 and 24 hours in dog and rat models of myocardial infarction.
LEFT VENTRICULAR CARDIAC OUTPUT FROM EQUILIBRIUM GATED BLOOD POOL SCANS
Authors: R. D. Burow, P. Heath, A. Amil, U. Thadani, M. F. Wilson
Journal: Clinical Nuclear Medicine (1982)

Department of Electrical Engineering, Rice University, and Department of Radiology, Baylor College of Medicine, and Nuclear Medicine Service, St. Luke's Episcopal – Texas Children's Hospitals and The Texas Heart Institute, Houston, TX
Bacterial Colonization and Infection of Electrophysiological Cardiac Devices Detected With Sonication and Swab Culture
Authors: Martin Rohacek, Maja Weisser, Richard Kobza, Andreas W. Schoenenberger, Gaby E. Pfyffer, Reno Frei, Paul Erne, Andrej Trampuz
Journal: Circulation (2010)

Electrophysiological cardiac devices are increasingly used. The frequency of subclinical infection is unknown. We investigated all explanted devices using sonication, a method for detection of microbial biofilms on foreign bodies.Consecutive patients in whom cardiac pacemakers and implantable cardioverter/defibrillators were removed at our institution between October 2007 and December 2008 were prospectively included. Devices (generator and/or leads) were aseptically removed and sonicated, and the resulting sonication fluid was cultured. In parallel, conventional swabs of the generator pouch were performed. A total of 121 removed devices (68 pacemakers, 53 implantable cardioverter/defibrillators) were included. The reasons for removal were insufficient battery charge (n=102), device upgrading (n=9), device dysfunction (n=4), or infection (n=6). In 115 episodes (95%) without clinical evidence of infection, 44 (38%) grew bacteria in sonication fluid, including Propionibacterium acnes (n=27), coagulase-negative staphylococci (n=11), Gram-positive anaerobe cocci (n=3), Gram-positive anaerobe rods (n=1), Gram-negative rods (n=1), and mixed bacteria (n=1). In 21 of 44 sonication-positive episodes, bacterial counts were significant (>or=10 colony-forming units/mL of sonication fluid). In 26 sterilized controls, sonication cultures remained negative in 25 cases (96%). In 112 cases without clinical infection, conventional swab cultures were performed: 30 cultures (27%) were positive, and 18 (60%) were concordant with sonication fluid cultures. Six devices and leads were removed because of infection, growing Staphylococcus aureus, Streptococcus mitis, and coagulase-negative staphylococci in 6 sonication fluid cultures and 4 conventional swab cultures.Bacteria can colonize cardiac electrophysiological devices without clinical signs of infection.
Folic Acid and Prevention of Spina Bifida
Authors: Norman W. Klein
Journal: JAMA (1996)

<h3>To the Editor.</h3> —In their Editorial, Dr Oakley and colleagues<sup>1</sup>failed to address the mechanisms by which folic acid acts to close neural tubes. Oakley and colleagues note that folic acid supplements may reduce the levels of circulating homocysteine, a substance that may be involved in vascular disease, but they failed to mention that with the methyl group from folic acid, homocysteine becomes methionine. This essential amino acid has been recognized not only as a normal constituent of proteins, but also as one that plays a key role in cellular methylation reactions as the most immediate precursor of<i>S</i>-adenoylmethionine. A considerable amount of experimental evidence now exists showing that methionine supplements allowed neural tube closure to be completed under conditions of nutritional deficiencies,<i>2,3</i>the presence of the human teratogen valproic acid,<i>4</i>and in the presence of a genetic mutation that caused neural tube defects (NTDs).<sup>5</sup>
Book: Twice Dead: Organ Transplants and the Reinvention of Death
Authors: C. Gray
Journal: BMJ (2002)

Margaret Lock University of California Press, $24.95/£17.95, pp 429 ISBN 0 529 22814 6 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img>![Graphic][4]</img> Perhaps most British doctors feel that the subject of brain death is complete. Surely Christopher Pallis and his colleagues did a good job 15 years ago in defining the clinical criteria for diagnosing brain stem death ( Medico-Legal Journal 1987;2:84-104). These have proved well defined and robust in practice. British procedures for obtaining organs and tissues from donors are careful and dignified. Transplantation is necessarily a good thing. We sympathise with relatives of the tragically dead and their predicament in contemplating organ harvesting from the loved one. … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif
Induction and molecular signature of pathogenic TH17 cells
Authors: Youjin Lee, Amit Awasthi, Nir Yosef, Francisco J Quintana, Sheng Xiao, Anneli Peters, Chuan Wu, Markus Kleinewietfeld, Sharon Kunder, David A Hafler, Raymond A Sobel, Aviv Regev, Vijay K Kuchroo
Journal: Nature Immunology (2012)
From Efficacy to Effectiveness in the Face of Uncertainty
Authors: Benjamin Djulbegovic, Ash Paul
Journal: JAMA (2011)

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Bone marrow embolism in sickle cell disease: A review
Authors: Nghia C. Dang, Cage Johnson, Mahmoud Eslami-Farsani, L. Julian Haywood
Journal: American Journal of Hematology (2005)

The fat embolism syndrome is an important complication of patients with sickle cell hemoglobinopathies because of severe morbidity and mortality. Our recent experience with three cases that survived with intensive supportive care and prompt use of transfusion stimulates this review. A high index of suspicion, prompt use of diagnostic tools, and aggressive clinical management are the keys to a successful outcome. Am. J. Hematol. 79:61–67, 2005. © 2005 Wiley-Liss, Inc.