tbuckley/cabot-search huggingface dataset:
LEUKOPENIA WITH GRANULOCYTOPENIA IN EXPERIMENTAL MUCORMYCOSIS (RHIZOPUS ORYZAE INFECTION
Authors: Heinz Bauer, Walter H. Sheldon
Journal: The Journal of Experimental Medicine (1957)

Mucormycosis was produced in rabbits with sustained, severe leukopenia and granulocytopenia induced by repeated injections of nitrogen mustard. Initially, these animals developed extensive fungus lesions at the site of inoculation which later became granulomatous and tended to heal. Only the early phases of host resistance appeared impaired by the virtual elimination of the polymorphonuclear leukocyte as a factor in the host response. Despite the persistent leukopenia and granulocytopenia, the later phases of host resistance resembled those of the normal animal. Thus, the behavior of the infection in this experiment differs greatly from the unchecked progression of mucormycosis in the metabolically abnormal animal with acute alloxan diabetes. The differences in the course of the disease and in the morphologic appearance of the lesions indicate that metabolic alterations in the host affect all phases of host resistance and not only the polymorphonuclear leukocytic response.
Acceleration of Cardiovascular Disease by a Dysfunctional Prostacyclin Receptor Mutation
Authors: Eric Arehart, Jeremiah Stitham, Folkert W. Asselbergs, Karen Douville, Todd MacKenzie, Kristina M. Fetalvero, Scott Gleim, Zsolt Kasza, Yamini Rao, Laurie Martel, Sharon Segel, John Robb, Aaron Kaplan, Michael Simons, Richard J. Powell, Jason H. Moore, Eric B. Rimm, Kathleen A. Martin, John Hwa
Journal: Circulation Research (2008)

Recent increased adverse cardiovascular events observed with selective cyclooxygenase-2 inhibition led to the withdrawal of rofecoxib (Vioxx) and valdecoxib (Bextra), but the mechanisms underlying these atherothrombotic events remain unclear. Prostacyclin is the major end product of cyclooxygenase-2 in vascular endothelium. Using a naturally occurring mutation in the prostacyclin receptor, we report for the first time that a deficiency in prostacyclin signaling through its G protein-coupled receptor contributes to atherothrombosis in human patients. We report that a prostacyclin receptor variant (R212C) is defective in adenylyl cyclase activation in both patient blood and in an in vitro COS-1 overexpression system. This promotes increased platelet aggregation, a hallmark of atherothrombosis. Our analysis of patients in 3 separate white cohorts reveals that this dysfunctional receptor is not likely an initiating factor in cardiovascular disease but that it accelerates the course of disease in those patients with the greatest risk factors. R212C was associated with cardiovascular disease only in the high cardiovascular risk cohort (n=980), with no association in the low-risk cohort (n=2293). In those at highest cardiovascular risk, both disease severity and adverse cardiovascular events were significantly increased with R212C when compared with age- and risk factor-matched normal allele patients. We conclude that for haploinsufficient mutants, such as the R212C, the enhanced atherothrombotic phenotype is likely dependent on the presence of existing atherosclerosis or injury (high risk factors), analogous to what has been observed in the cyclooxygenase-2 inhibition studies or prostacyclin receptor knockout mice studies. Combining both biochemical and clinical approaches, we conclude that diminished prostacyclin receptor signaling may contribute, in part, to the underlying adverse cardiovascular outcomes observed with cyclooxygenase-2 inhibition.
Phosphoinositide-Dependent Kinase 1 and p21-Activated Protein Kinase Mediate Reactive Oxygen Species–Dependent Regulation of Platelet-Derived Growth Factor–Induced Smooth Muscle Cell Migration
Authors: David S. Weber, Yoshihiro Taniyama, Petra Rocic, Puvi N. Seshiah, Melissa A. Dechert, William T. Gerthoffer, Kathy K. Griendling
Journal: Circulation Research (2004)

Smooth muscle cell migration in response to platelet-derived growth factor (PDGF) is a key event in several vascular pathologies, including atherosclerosis and restenosis. PDGF increases intracellular levels of reactive oxygen species (ROS) in vascular smooth muscle cells (VSMCs), but the ROS sensitivity of migration and of the signaling pathways leading to migration are largely unknown. In VSMCs, PDGF dose-dependently increased migration compared with nonstimulated cells, with a maximum increase at 10 ng/mL. Pretreatment with the antioxidant N -acetyl-cysteine, the flavin-containing enzyme inhibitor diphenylene iodonium, or the glutathione peroxidase mimetic ebselen significantly attenuated migration (PDGF alone, 5.0±1.1-fold; NAC, 1.8±0.2-fold; diphenylene iodonium, 1.4±0.3-fold migration; and ebselen, 2.0±0.5-fold migration), as did overexpression of catalase. Pretreatment of VSMCs with the Src inhibitor PP1 or dominant-negative Rac adenovirus significantly inhibited migration, but only Src activation was attenuated by ROS inhibitors. Phosphorylation of the Src- and Rac-effector p21-activated protein kinase (PAK) 1 on Thr423 (the phosphoinositide-dependent kinase-1 [PDK1] site) was attenuated by ROS inhibition, and infection of VSMCs with dominant-negative PAK1 adenovirus attenuated migration. Moreover, kinase-inactive K111N-PDK1 inhibited PAK1 phosphorylation on Thr423, and both K111N-PDK1 and Y9F-PDK1 significantly inhibited VSMC migration. PDK1 tyrosine phosphorylation was also ROS dependent. These data indicate that PDGF-induced VSMC migration is ROS dependent and identify the Src/PDK1/PAK1 signaling pathway as an important ROS-sensitive mediator of migration. Such information is critical to understanding the role of ROS in vascular diseases in which migration of VSMCs is an important component.
Randomized Study of Intensified Anthracycline Doses for Induction and Recombinant Interleukin-2 for Maintenance in Patients With Acute Myeloid Leukemia Age 50 to 70 Years: Results of the ALFA-9801 Study
Authors: Cecile Pautas, Fatiha Merabet, Xavier Thomas, Emmanuel Raffoux, Claude Gardin, Selim Corm, Jean-Henri Bourhis, Oumedaly Reman, Pascal Turlure, Nathalie Contentin, Thierry de Revel, Philippe Rousselot, Claude Preudhomme, Dominique Bordessoule, Pierre Fenaux, Christine Terré, Mauricette Michallet, Hervé Dombret, Sylvie Chevret, Sylvie Castaigne
Journal: Journal of Clinical Oncology (2010)

PURPOSE In patients with acute myeloid leukemia (AML), induction chemotherapy is based on standard doses of anthracyclines and cytarabine. High doses of cytarabine have been reported as being too toxic for patients older than age 50 years, but few studies have evaluated intensified doses of anthracyclines. PATIENTS AND METHODS In this randomized Acute Leukemia French Association 9801 (ALFA-9801) study, high doses of daunorubicin (DNR; 80 mg/m(2)/d x 3 days) or idarubicin (IDA4; 12 mg/m(2)/d x 4 days) were compared with standard doses of idarubicin (IDA3; 12 mg/m(2)/d x 3 days) for remission induction in patients age 50 to 70 years, with an event-free survival (EFS) end point. After two consolidation courses based on intermediate doses of cytarabine, patients in continuous remission were randomly assigned to receive or not receive maintenance therapy with recombinant interleukin-2 (rIL-2; 5 x 10(6) U/m(2) x 5 days each month) for a total duration of 12 months. A total of 468 patients entered the study (median age, 60 years). Results Overall complete remission rate was 77% with significant differences among the three randomization arms (83%, 78%, and 70% in the IDA3, IDA4, and DNR arms, respectively; P = .04). However, no significant differences were observed in relapse incidence, EFS, or overall survival among the three arms. In the 161 patients randomly assigned for maintenance therapy, no difference in outcome was observed between the rIL-2 and the no further treatment arms. CONCLUSION Neither intensification of anthracycline doses nor maintenance with rIL-2 showed a significant impact on AML course, at least as scheduled in this trial.
Euthanasia and suicide in antiquity: viewpoint of the dramatists and philosophers
Authors: John D Papadimitriou, Panayiotis Skiadas, Constantinos S Mavrantonis, Vassilis Polimeropoulos, Dimitris J Papadimitriou, Kyriaki J Papacostas
Journal: Journal of the Royal Society of Medicine (2007)

‘It is not the death I fear to face but dying.’
Evidence-based and complementary medicine
Authors: S. Butterworth
Journal: Journal of the Royal Society of Medicine (2004)

The two articles on evidence-based medicine versus complementary medicine, published in the January 2004 JRSM1,2, would perhaps be more convincing if they did not ignore the numerous drugs which we are happy to peddle and the benefits of which, while `evidence-based', are all too obviously either doubtful or negative. As I survive into retirement I have to listen more and more to the experiences of friends and relations who are on various tablets. Many are on six or more different compounds, often given to counteract the side-effects of the others. Some are more or less disabled by their pills. As a purely social acquaintance one cannot be too inquisitive about the exact identities of the substances involved, but ordinary conversation often raises doubts about what has been prescribed and what for.

An example might be provided by a close relation, aged 74, who was found at a routine examination to have a marginally raised blood pressure. He was given medication for this, and as a consequence suffered from dizziness, which prevented him from driving a car. He went back to the surgery, where he saw another doctor, who put him on another medicine for the dizziness. This gave him a dry mouth and indigestion, so he went back to the surgery again, where yet another doctor diagnosed depression and put him on an SSRI. Following this he became confused and inarticulate and even more depressed. His wife and daughters began to think about funeral arrangements. Fortunately he went back to the surgery again, where he saw the practice principal, a woman on the verge of retirement and still applying a measure of commonsense, who decided that there never had been any hypertension and took him off all medication. He is now symptom-free and alert and drives his car all over the county where he lives.

This is an anecdote. Does that mean we must ignore it? How many such anecdotes constitute evidence? How can there be a controlled trial of old folk who are on too many pills? Which drug company will subsidize such a trial?

My first experience as a house physician was in 1955 with Donald Hunter, then senior physician to the London Hospital. He used to say that we were leaving the period of dangerous surgery and entering that of dangerous medicine. He seems to have been right.
Viral and metabolic factors influencing alanine aminotransferase activity in patients with chronic hepatitis C
Authors: Daniele Prati, Mitchell L. Shiffman, Moisés Diago, Edward Gane, K. Rajender Reddy, Paul Pockros, Patrizia Farci, Christopher B. O'Brien, Pilar Lardelli, Steven Blotner, Stefan Zeuzem
Journal: Journal of Hepatology (2006)
Transbronchial fine needle aspiration.
Authors: J Lemer, E Malberger, R Konig-Nativ
Journal: Thorax (1982)

In a pilot study, 21 patients underwent transbronchial fine needle aspiration (TBFNA) using a 45 cm-22 gauge needle guided by means of a semi-rigid metal sleeve, which was introduced through a standard rigid bronchoscope. A total of 33 aspirations were performed from main carina (15), paratracheal (five), and lobar carinal (13) foci. Six aspirations yielded malignant cellular samples, 22 aspirations presented only normal cells, and in five no adequate cellular sample was obtained. Fifteen patients underwent surgical exploration (mediastinoscopy with or without thoracotomy). Four of the cytologically malignant cases were explored and in three the aspiration site was confirmed histologically. In the remaining patients where the site of aspiration was explored, no tumour was demonstrated in the cytologically negative or cytologically inadequate cases. There were no complications from TBFNA. We suggest that TBFNA is useful in determining mediastinal malignant involvement rapidly and with lesser invasion than with current techniques.
Analysis of the influence of OCTN1/2 variants within the IBD5 locus on disease susceptibility and growth indices in early onset inflammatory bowel disease
Authors: R K Russell
Journal: Gut (2005)

<b>Background and aims:</b> The OCTN1 (SLC22A4 1672C→T) and OCTN2 (SLC22A5 −207G→C) variants within the IBD5 locus have been associated with susceptibility to adult onset Crohn's disease (CD), but their contribution in children has not been examined. <b>Methods:</b> These OCTN1/2 variants and IBD5 marker single nucleotide polymorphisms (SNPs) (IGR2096a_1, IGR2198a_1, and IGR2230a_1) were examined in 299 Scottish children (200 with CD, 74 with ulcerative colitis (UC), and 25 with indeterminate colitis (IC)), together with 502 parents (for transmission disequilibrium testing) and 256 controls. <b>Results:</b> All SNPs were in strong linkage disequilibrium (D′ &gt;0.94). TDT analysis showed association of the OCTN1 variant with inflammatory bowel disease (IBD) (p = 0.01) and CD (p = 0.04). Allele frequencies of the OCTN1/2 variants were significantly higher in IBD/CD cases (p&lt;0.04). The homozygous mutant OCTN1/2 haplotype was increased in IBD (24.3% <i>v</i> 16.1%, p = 0.02) and UC (28.2% <i>v</i> 16.1%, p = 0.02) compared with controls. The OCTN1/2 variants were not independent of the background IBD5 risk haplotype in conferring disease susceptibility. Unifactorial analysis in CD patients showed that carriage of the TC haplotype was associated with lower weight, height, and BMI centile (&lt;9<sup>th</sup> centile) at diagnosis (weight: 87.9% <i>v</i> 67.3% (p = 0.002), odds ratio (OR) = 3.52 (95% confidence interval, 1.51 to 8.22); height: 84.1% <i>v</i> 68.4% (p&lt;0.05), OR = 2.44 (1.00 to 5.99); BMI: 79.6% <i>v</i> 61.1% (p = 0.02), OR = 2.49 (1.14 to 5.44)), and lower weight centile at follow up (87.5% <i>v</i> 64.6% (p = 0.03), OR = 3.83 (1.03 to 14.24)). Multifactorial binary logistic regression analysis confirmed association of the TC haplotype with lower weight centile at diagnosis (p = 0.02, OR = 3.41 (1.20 to 9.66)). <b>Conclusions:</b> These data implicate variants within the IBD5 haplotype, as determinants of disease susceptibility and growth indices in early onset IBD. The OCTN1/2 variants remain potential positional candidate genes, but require further analysis.
B Cells Directly Tolerize CD8+ T Cells
Authors: Sally R.M. Bennett, Francis R. Carbone, Tracey Toy, Jacques F.A.P. Miller, William R. Heath
Journal: The Journal of Experimental Medicine (1998)

This report investigates the response of CD8+ T cells to antigens presented by B cells. When C57BL/6 mice were injected with syngeneic B cells coated with the Kb-restricted ovalbumin (OVA) determinant OVA257–264, OVA-specific cytotoxic T lymphocyte (CTL) tolerance was observed. To investigate the mechanism of tolerance induction, in vitro–activated CD8+ T cells from the Kb-restricted, OVA-specific T cell receptor transgenic line OT-I (OT-I cells) were cultured for 15 h with antigen-bearing B cells, and their survival was determined. Antigen recognition led to the killing of the B cells and, surprisingly, to the death of a large proportion of the OT-I CTLs. T cell death involved Fas (CD95), since OT-I cells deficient in CD95 molecules showed preferential survival after recognition of antigen on B cells. To investigate the tolerance mechanism in vivo, naive OT-I T cells were adoptively transferred into normal mice, and these mice were coinjected with antigen-bearing B cells. In this case, OT-I cells proliferated transiently and were then lost from the secondary lymphoid compartment. These data provide the first demonstration that B cells can directly tolerize CD8+ T cells, and suggest that this occurs via CD95-mediated, activation-induced deletion.
Dose duration of nebulized nedocromil sodium in exercise-induced asthma
Authors: MK Albazzaz, MG Neale, KR Patel
Journal: European Respiratory Journal (1992)

The dose-duration effect of nebulized nedocromil sodium was studied in ten patients with exercise-induced asthma (7 males mean (SEM) age 30.1 (3.5) yrs and predicted forced expiratory volume in one second (FEV1) 102%). All of these patients showed > 40% protection of their exercise asthma with 4 mg of nedocromil sodium delivered via metered dose inhaler. Three concentrations of nedocromil sodium (0.5, 2.5 and 10 mg.ml-1) and placebo were administered in double-blind, randomized manner. One ml of each solution was nebulized via a Wright nebulizer. Effects were assessed from the mean maximal percentage fall in FEV1 after 6-8 min treadmill exercise at 15, 135 and 255 min following each treatment and expressed as percentage protection. The mean baseline FEV1 values before and after treatments were comparable on four days of testing. Nedocromil sodium inhibited exercise-induced fall in FEV1 at all concentrations (p < 0.001) and the inhibitory effect was still present at 255 min. No differences were observed between active treatments.
Influence of splenectomy on first set rejection reactions of C57BL/6 females to male skin isografts.
Authors: J W Streilein, J Wiesner
Journal: The Journal of Experimental Medicine (1977)

The tempo with which C57BL/6 females reject male skin isografts is determined in part by the immunogenicity of the H-Y antigen and in part by the capacity of the host to respond immunologically. Our studies indicate that the spleen plays an important role in determining the briskness of the rejection process in that splenectomy 7-30 days before grafting with male skin significantly shortens the survival time. The results of reconstitution experiments suggests that a population of cells is present in spleens of normal, but not specifically sensitized, females which can restore the conventional first set reaction in splenectomized females. It is inferred that this resident population normally operates in spleen-intact females to delay the development of specific effector responses. Lymphoid cells from H-Y antigen-sensitized, splenectomized females failed to evoke graft-vs.-host responses in males whereas similar cells from females with spleens intact did possess graft-vs.-host potential.
Toward Optimal Central Nervous System–Directed Treatment in Childhood Acute Lymphoblastic Leukemia
Authors: Ching-Hon Pui
Journal: Journal of Clinical Oncology (2003)

Article Tools EDITORIAL Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.10.032 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12525506 Toward Optimal Central Nervous System–Directed Treatment in Childhood Acute Lymphoblastic Leukemia Ching-Hon PuixChing-Hon PuiSearch for articles by this author Show More St. Jude Children's Research Hospital and the University of Tennessee Health Science Center, Memphis, TN https://doi.org/10.1200/JCO.2003.10.032 First Page Full Text PDF Figures and Tables © 2003 by American Society of Clinical Oncology
Control of delayed nausea and vomiting with granisetron plus dexamethasone or dexamethasone alone in patients receiving highly emetogenic chemotherapy: A double-blind, placebo-controlled, comparative study
Authors: L. Goedhals, J.-F. Heron, J.-P. Kleisbauer, O. Pagani, C. Sessa
Journal: Annals of Oncology (1998)
Right lateral position improves complete examination rate of capsule endoscope: a prospective randomized, controlled trial
Authors: Z. Liao, F. Li, Z.-S. Li
Journal: Endoscopy (2008)

See also: Commentaire de travail de Z. Liao et al., pp. 483Endoscopy 2008; 40(06): 545-545DOI: 10.1055/s-0032-1306842
Nitric oxide blocks hKv1.5 channels by S-nitrosylation and by a cyclic GMP-dependent mechanism
Authors: L NUNEZ, M VAQUERO, R GOMEZ, R CABALLERO, P MATEOSCACERES, C MACAYA, I IRIEPA, E GALVEZ, A LOPEZFARRE, J TAMARGO
Journal: Cardiovascular Research (2006)

Objective: This study was undertaken to analyze whether nitric oxide (NO) modulates the human potassium channel hKv1.5, which generates the ultrarapid delayed rectifier current (IKur) that determines the height and duration of atrial action potentials. Methods: Currents were recorded using the whole-cell patch-clamp in Ltk− cells expressing hKv1.5 channels. Results: The NO donors (±)-S-Nitroso-N-acetylpenicillamine (SNAP) and sodium nitroprusside, a NO solution, and l-Arginine inhibited hKv1.5 currents in a concentration-dependent manner. The NO concentration in the cell chamber was monitored using a sensor, and the IC50 for NO-induced hKv1.5 block was 340±70 nM. SNAP also inhibited the IKur recorded in mouse ventricular myocytes. The NO effects were partially mediated by the activation of the soluble guanylate cyclase (sGC)/cGMP/cGMP-dependent protein kinase (PKG) pathway. The biotin-switch assay demonstrated the presence of S-nitrosylated cysteines (Cys) on the hKv1.5 protein in SNAP-treated cells. Molecular modeling of hKv1.5 channel structure suggests that S-nitrosylation of Cys331 (segment 2, S2) and Cys346 (S2) would be stabilized by hydrogen bridge bonds with Ile262 (S1) and Arg342 (S2), respectively. Conclusions: NO inhibits the hKv1.5 current by a cGMP-dependent mechanism and by the S-nitrosylation of the hKv1.5 protein, an effect that contributes to shaping the human atrial action potentials.
Randomised, double blind, placebo controlled trial of intravenous antioxidant (n-acetylcysteine, selenium, vitamin C) therapy in severe acute pancreatitis
Authors: A. K Siriwardena, J. M Mason, S. Balachandra, A. Bagul, S. Galloway, L. Formela, J. G Hardman, S. Jamdar
Journal: Gut (2007)

Based on equivocal clinical data, intravenous antioxidant therapy has been used for the treatment of severe acute pancreatitis. To date there is no randomised comparison of this therapy in severe acute pancreatitis.We conducted a randomised, double blind, placebo controlled trial of intravenous antioxidant (n-acetylcysteine, selenium, vitamin C) therapy in patients with predicted severe acute pancreatitis. Forty-three patients were enrolled from three hospitals in the Manchester (UK) area over the period June 2001 to November 2004. Randomisation stratified for APACHE-II score and hospital site, and delivered groups that were similar at baseline.Relative serum levels of antioxidants rose while markers of oxidative stress fell in the active treatment group during the course of the trial. However, at 7 days, there was no statistically significant difference in the primary end point, organ dysfunction (antioxidant vs placebo: 32% vs 17%, p = 0.33) or any secondary end point of organ dysfunction or patient outcome.This study provides no evidence to justify continued use of n-acetylcysteine, selenium, vitamin C based antioxidant therapy in severe acute pancreatitis. In the context of any future trial design, careful consideration must be given to the risks raised by the greater trend towards adverse outcome in patients in the treatment arm of this study.
Contrast Peripheral Phlebography and Pulmonary Angiography for Diagnosis of Thromboembolism
Authors: R. Torrance Andrews
Journal: Circulation (2004)

At one time, direct intravascular contrast angiography was the standard method for confirmatory diagnosis of venous or pulmonary arterial thromboembolism. Although sensitive and specific, conventional catheter-based contrast imaging is invasive and associated with a risk of phlebitis and thrombosis. These procedures require specialized training and experience in catheter manipulation, as well as specialized vascular imaging equipment. In current practice, less invasive techniques have largely superceded conventional angiography because they can be performed by technologists using widely available, multifunctional apparatus under physician supervision. When results using these newer approaches are inconclusive or impractical, however, catheter-based techniques are still relied on for definitive diagnosis. The purpose of this article is to review the indications, techniques, and interpretations of contrast angiography as applied to venous thromboembolic disease.