tbuckley/cabot-search huggingface dataset:
Increased tryptophan uptake on PET has strong independent prognostic value in patients with a previously treated high-grade glioma
Authors: D. O. Kamson, S. Mittal, N. L. Robinette, O. Muzik, W. J. Kupsky, G. R. Barger, C. Juhasz
Journal: Neuro-Oncology (2014)

Previously, we demonstrated the high accuracy of alpha-[11C]methyl-L-tryptophan (AMT) PET for differentiating recurrent gliomas from radiation injury. The present study evaluated the prognostic value of increased AMT uptake in patients with previously treated high-grade glioma. AMT-PET was performed in 39 patients with suspected recurrence of World Health Organization grades III–IV glioma following surgical resection, radiation, and chemotherapy. Mean and maximum standardized uptake values (SUVs) and unidirectional AMT uptake (K) were measured in brain regions suspicious for tumor and compared with the contralateral cortex (ie, background). Optimal cutoff thresholds for 1-year survival prediction were determined for each AMT parameter and used for calculating the prognostic value of high (above threshold) versus low (below threshold) values for post-PET overall survival (OS). In univariate analyses, 1-year survival was strongly associated with 3 AMT parameters (SUVmax, SUVmean, and tumor-to-background K-ratio; odds ratios: 21.3–25.6; P ≤ .001) and with recent change in MRI contrast enhancement (odds ratio: 14.7; P = .02). Median OS was 876 days in the low- versus 177 days in the high-AMT groups (log-rank P < .001). In multivariate analyses, all 3 AMT parameters remained strong predictors of survival: high AMT values were associated with unfavorable 1-year survival (binary regression P ≤ .003) and shorter overall survival in the whole group (Cox regression hazard ratios: 5.3–10.0) and in patients with recent enhancement change on MRI as well (hazard ratios: 7.0–9.3; P ≤ .001). Increased AMT uptake on PET is highly prognostic for 1-year and overall survival, independent of MRI contrast enhancement and other prognostic factors in patients with a previously treated high-grade glioma.
Beneficial effects of nifedipine on rest and exercise myocardial energetics in patients with congestive heart failure.
Authors: R D Magorien, C V Leier, A J Kolibash, T J Barbush, D V Unverferth
Journal: Circulation (1984)

Rest and exercise systemic hemodynamic parameters, coronary blood flow, and myocardial energetics were assessed before and 15 min after the sublingual administration of 20 mg of nifedipine in 10 patients with idiopathic congestive cardiomyopathy. When compared with control, nifedipine increased rest and exercise cardiac index by 37% and 28%, respectively (p less than .001). Peripheral vasodilation was demonstrated with a drop in systemic arterial pressure, exercise pulmonary capillary wedge pressure, and systemic vascular resistance (p less than .05). The calcium-channel blocker did not alter myocardial oxygen consumption; however, coronary blood flow increased by 32% at rest (p less than .01) while coronary vascular resistance diminished both at rest and after exercise compared with control (p less than .05). Nifedipine elicited a decrease in the rest and exercise aortocoronary sinus oxygen difference while the coronary sinus oxygen saturation increased (p less than .01). In this group of patients with idiopathic congestive cardiomyopathy, nifedipine enhanced myocardial performance while increasing coronary blood flow and favorably altering the myocardial oxygen supply-demand balance.
Part “D” for “Defective” — The Medicare Drug-Benefit Chaos
Authors: Jerry Avorn
Journal: New England Journal of Medicine (2006)

Interview with Dr. Jerry Avorn on the problems that followed the implementation of the new Medicare Part D Plan. (07:26)Download A recent survey by the Kaiser Family Foundation quantifies what many of us have seen firsthand: the new Medicare drug benefit is having a troubled infancy (see bar graphs). The data reflect the experience of elderly people who were well enough to participate in a survey; other reports make clear that matters are far worse for those with medical or cognitive disabilities.True, the program provides drug benefits for some Americans who previously had none. But because of its strange design, enrollment is falling far short of expectations. Officials in the Bush administration boasted that 25 million people are receiving benefits . . .
Review of Emily Monosson, Ed.,<i>Motherhood, The Elephant in the Laboratory: Women Scientists Speak Out</i><sup>1</sup>
Authors: Sarah Rodriguez
Journal: The American Journal of Bioethics (2010)

"Review of Emily Monosson, Ed., Motherhood, The Elephant in the Laboratory: Women Scientists Speak Out 1 ." The American Journal of Bioethics, 10(11), pp. 28–29 Notes 1. Ithaca, NY: Cornell University Press, 2008. 219 pp. $ 27.95. Hardback.
<i>ETV6-NCOA2</i>: A Novel Fusion Gene in Acute Leukemia Associated with Coexpression of T-Lymphoid and Myeloid Markers and Frequent <i>NOTCH1</i> Mutations
Authors: Sabine Strehl, Karin Nebral, Margit König, Jochen Harbott, Herbert Strobl, Richard Ratei, Stephanie Struski, Bella Bielorai, Michel Lessard, Martin Zimmermann, Oskar A. Haas, Shai Izraeli
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The ETV6 gene has been reported to be fused to a multitude of partner genes in various hematologic malignancies with 12p13 aberrations. Cytogenetic analysis of six cases of childhood acute lymphoblastic leukemia revealed a novel recurrent t(8;12)(q13;p13), suggesting involvement of ETV6. Experimental Design: Fluorescence in situ hybridization was used to confirm the involvement of ETV6 in the t(8;12)(q13;p13) and reverse transcription-PCR was used to identify the ETV6 partner gene. Detailed immunologic characterization was done, and owing to their lineage promiscuity, the leukemic blast cells were analyzed for NOTCH1 mutations. Results: We have identified a novel recurrent t(8;12)(q13;p13), which results in a fusion between the transcriptional repressor ETV6 (TEL) and the transcriptional coactivator NCOA2 (TIF2) in six cases of childhood leukemia expressing both T-lymphoid and myeloid antigens. The ETV6-NCOA2 transcript encodes a chimeric protein that consists of the pointed protein interaction motif of ETV6 that is fused to the COOH terminus of NCOA2, including the cyclic AMP–responsive element binding protein–binding protein (CBP) interaction and the AD2 activation domains. The absence of the reciprocal NCOA2-ETV6 transcript in one of the cases suggests that the ETV6-NCOA2 chimeric protein and not the reciprocal NCOA2-ETV6 is responsible for leukemogenesis. In addition, ETV6-NCOA2 leukemia shows a high frequency of heterozygous activating NOTCH1 mutations, which disrupt the heterodimerization or the PEST domains. Conclusions: The ETV6-NCOA2 fusion may define a novel subgroup of acute leukemia with T-lymphoid and myeloid features, which is associated with a high prevalence of NOTCH1 mutations.
Identification of a Highly Immunogenic HLA-A*01-Binding T Cell Epitope of WT1
Authors: Anne Marie Asemissen, Ulrich Keilholz, Stefan Tenzer, Margret Müller, Steffen Walter, Stefan Stevanovic, Hansjörg Schild, Anne Letsch, Eckhard Thiel, Hans-Georg Rammensee, Carmen Scheibenbogen
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The transcription factor Wilms tumor protein 1 (WT1) belongs to a new generation of tumor antigens, as it is essential for tumor cell proliferation and is highly expressed in various hematologic and solid malignancies. The aim of this study was to apply a modified reverse immunology strategy to identify immunogenic epitopes of WT1 which could be useful for immunotherapy. Experimental Design: Potential HLA-A*01 epitopes predicted by a MHC binding algorithm were screened for recognition by peripheral blood mononuclear cells (PBMC) from patients with spontaneous T cell responses using intracellular cytokine cytometry. Epitope processing was shown by proteasomal cleavage. Epitope-specific T cells were generated from CD4+CD25+ regulatory T cell–depleted PBMC. Results: One of five predicted HLA-A*01-binding candidate epitopes showed high immunogenicity as 5 of 14 patients with hematologic malignancies had WT1.317-327–reactive T cells ranging from 0.4% to 1.5% of CD3+CD8+ T cells. Proteasomal degradation assays indicated the cleavage of WT1.317-327. The depletion of regulatory T cells from PBMCs enabled the rapid expansion of WT1.317-327–specific CTL, whereas no CTL could be generated from unfractionated PBMC. WT1.317-327–specific CTL efficiently lysed an autologous WT1-expressing tumor cell line but not HLA-A*01–negative WT1-expressing tumor cells. Immunogenicity of the epitope across histologies was verified by the demonstration of spontaneous ex vivo WT1.317-327–specific T cell responses in two of six patients with HLA-A*01–positive melanoma or lung cancer. Conclusion: In this study, a modified reverse immunology strategy was employed to identify a first immunogenic HLA-A*01–restricted T cell epitope of the tumor antigen WT1, which is of considerable interest for use in vaccination trials.
What medical catatonias tell us about top-down modulation
Authors: Brendan T. Carroll
Journal: Behavioral and Brain Sciences (2002)

Catatonia resulting from a general medical condition (as defined in the DSM-IV ) seems to account for a large percentage of patients presenting with catatonia in psychiatric settings. In view of Dr. Northoff's hypothesis, it is important to emphasize that medical catatonias provide additional information to support his neuropsychiatric hypothesis of the anatomical and biochemical mechanisms of catatonia.
Thrombin-induced exposure and prostacyclin inhibition of the receptor for factor VIII/von Willebrand factor on human platelets.
Authors: T Fujimoto, S Ohara, J Hawiger
Journal: Journal of Clinical Investigation (1982)

The receptor for Factor VIII/von Willebrand factor (F. VIIIVWF) is readily available on circulating platelets. We have found that the stimulation of platelets with traces of thrombin at concentrations that are generated physiologically (0.008 U-0.05 U/ml) induced concentration-dependent binding of 125I-labeled F. VIIIVWF in a steady-state system. The binding induced by thrombin was specific because it was inhibited by a 100-fold molar excess of unlabeled F. VIIIVWF factor, by rabbit monospecific antibody against Factor VIII, and was not inhibited by an excess of fibrinogen or fibronectin. Binding induced by thrombin required metabolically active platelets, in contrast to a system with ristocetin that also prompted binding to glutaraldehyde-treated platelets. The thrombin effects on binding of 125I-F. VIIIVWF was not observed when platelets were washed with EDTA-containing buffers; EDTA and EGTA both inhibited thrombin-induced binding. Platelet membrane glycoproteins were required because enzymatic stripping od them from the platelet surface with chymotrypsin reduced binding 2.5-5.0-fold. Prostacyclin, in the concentration range of 1 to 50 nM, had two distinct effects on the receptor for F. VIIIWVF: (a) it prevented exposure of this receptor when added 10 min before thrombin, and (b) it reversed the binding of 125I-F. VIIIVWF to the platelet receptor when added 30 min after thrombin and the ligand, ie., when binding was at equilibrium. The dual effect of prostacyclin on the receptor for F. VIIIVWF was reproduced by dibutyryl cyclic AMP.
The application of an alanine-substituted mutant of the C-terminal fragment of Clostridium perfringens enterotoxin as a mucosal vaccine in mice
Authors: Hidehiko Suzuki, Masuo Kondoh, Hideki Kakutani, Seiji Yamane, Hiroshi Uchida, Takao Hamakubo, Kiyohito Yagi
Journal: Biomaterials (2011)
Efficacy of Low Tidal Volume Ventilation in Patients with Different Clinical Risk Factors for Acute Lung Injury and the Acute Respiratory Distress Syndrome
Authors: MARK D. EISNER, TAYLOR THOMPSON, LEONARD D. HUDSON, JOHN M. LUCE, DOUGLAS HAYDEN, DAVID SCHOENFELD, MICHAEL A. MATTHAY
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

In patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), a recent ARDS Network randomized controlled trial demonstrated that a low tidal volume (Vt) mechanical ventilation strategy (6 ml/kg) reduced mortality by 22% compared with traditional mechanical ventilation (12 ml/kg). In this study, we examined the relative efficacy of low Vt mechanical ventilation among 902 patients with different clinical risk factors for ALI/ARDS who participated in ARDS Network randomized controlled trials. The clinical risk factor for ALI/ARDS was associated with substantial variation in mortality. The risk of death (before discharge home with unassisted breathing) was highest in patients with sepsis (43%); intermediate in subjects with pneumonia (36%), aspiration (37%), and other risk factors (35%); and lowest in those with trauma (11%) (p < 0.0001). Despite these differences in mortality, there was no evidence that the efficacy of the low Vt strategy varied by clinical risk factor (p = 0.76, for interaction between ventilator group and risk factor). There was also no evidence of differential efficacy of low Vt ventilation in the other study outcomes: proportion of patients achieving unassisted breathing (p = 0.59), ventilator-free days (p = 0.58), or development of nonpulmonary organ failure (p = 0.44). Controlling for demographic and clinical covariates did not appreciably affect these results. After reclassifying the clinical risk factors as pulmonary versus nonpulmonary predisposing conditions and infection-related versus non-infection-related conditions, there was still no evidence that the efficacy of low Vt ventilation differed among clinical risk factor subgroups. In conclusion, we found no evidence that the efficacy of the low Vt ventilation strategy differed among clinical risk factor subgroups for ALI/ARDS.Keywords: acute respiratory distress syndrome; mechanical ventilators; acute lung injury
Ventricular Function Curves in the Exercising Dog
Authors: JONATHAN KEROES, ROGER R. ECKER, ELLIOT RAPAPORT
Journal: Circulation Research (1969)

Ventricular function curves of cardiac output and stroke volume versus left ventricular end-diastolic pressure were obtained during rapid infusion of Tyrode's solution in dogs standing at rest and during near-maximal exercise both before and after administration of propranolol. Cardiac output and stroke volume ventricular function curves were expressions of first-order processes as indicated by the close fit of data points to computer-derived exponential curves. At near-maximal levels of exercise, the rapid infusion of Tyrode's solution increased stroke volume by an average of 12 ml, indicating that at near-maximal exercise the pumping ability of the heart may be limited by venous return rather than by ventricular performance. The heightened sympathetic activity during exercise increased myocardial contractility, since the plateaus of the ventricular function curves were significantly higher during exercise than at rest. Propranolol negated the increase in contractility associated with exercise and the plateaus of ventricular function curves were then not significantly different from those obtained at rest.
Identification of a Titin-Derived HLA-A1–Presented Peptide as a Cross-Reactive Target for Engineered MAGE A3–Directed T Cells
Authors: Brian J. Cameron, Andrew B. Gerry, Joseph Dukes, Jane V. Harper, Vivekanandan Kannan, Frayne C. Bianchi, Francis Grand, Joanna E. Brewer, Minnal Gupta, Gabriela Plesa, Giovanna Bossi, Annelise Vuidepot, Alex S. Powlesland, Alison Legg, Katherine J. Adams, Alan D. Bennett, Nicholas J. Pumphrey, Daniel D. Williams, Gwendolyn Binder-Scholl, Irina Kulikovskaya, Bruce L. Levine, James L. Riley, Angel Varela-Rohena, Edward A. Stadtmauer, Aaron P. Rapoport, Gerald P. Linette, Carl H. June, Namir J. Hassan, Michael Kalos, Bent K. Jakobsen
Journal: Science Translational Medicine (2013)

T cells engineered to express affinity-enhanced TCRs directed to a MAGE A3 peptide cross-react with a similar, but unrelated, self-peptide.
Genetic Testing for Children and Adolescents
Authors: Dorothy C. Wertz
Journal: JAMA (1994)

In the future there is likely to be a large array of DNA-based tests to diagnose single-gene disorders and to identify predispositions to genetically influenced disorders. This article focuses on ethical, legal, and psychological implications of testing healthy children and adolescents for such disorders. Testing may offer medical or psychological benefits but may harm parent-child bonds or the child's self-concept. Clinicians may encounter situations where they must weigh the child's or adolescent's wishes against wishes of parents. We examine the legal history and current status of minors as health care consumers; psychosocial research on their maturity to make choices; impact of testing on intrafamilial relationships; views of national commissions on appropriate ages of assent and full informed consent; ethical and legal requirements for competence in children and adolescents; and disclosure of genetic information. We propose guidelines for predictive genetic testing and counseling of children and discuss risks and benefits of testing.
Survival of Zidovudine-Treated Patients With AIDS Compared With That of Contemporary Untreated Patients
Authors: Stefano Vella
Journal: JAMA (1992)

<h3>Objective.</h3> —To assess the long-term effectiveness of zidovudine (AZT) in patients with acquired immunodeficiency syndrome (AIDS). This assessment has never been adequately done because controlled clinical trials were stopped early and survival comparisons were made with historical controls. <h3>Design.</h3> —Nonrandomized contemporary observational study of patients treated and not treated with zidovudine. <h3>Setting.</h3> —Twenty-three AIDS treatment centers throughout Italy that reported cases to the National Registry of AIDS Cases between July 1987 and March 1988. <h3>Patients.</h3> —One hundred fifty-nine zidovudine-treated and 112 untreated patients with AIDS, the majority of whom had acquired human immunodeficiency virus (HIV) infection through intravenous drug use. <h3>Outcome Measures.</h3> —Median survival and 1- and 2-year survival for treated and untreated groups, as estimated using the Kaplan-Meier method. Cox proportional hazards regression analysis was also used to identify independent predictors of survival among the variables studied. <h3>Results.</h3> —Patients were similar with respect to CD4/CD8 ratio, age, sex, clinical and immunological status at diagnosis, and source of HIV infection. After 24 months, survival was 45.9% (95% confidence interval [Cl], 36.1% to 55.7%) in the treated group and 20.5% (95% Cl, 12.6% to 28.3%) in the untreated group, with median survival of 21.2 and 9.6 months, respectively. <h3>Conclusions.</h3> —Possible biases of this study include imperfect matching for clinical status and better overall medical care of treated patients. Nevertheless, we believe that the observed differences in survival were primarily due to zidovudine treatment. (<i>JAMA</i>. 1992;267:1232-1236)
Necessity of tyrosine 719 and phosphatidylinositol 3′-kinase–mediated signal pathway in constitutive activation and oncogenic potential of c-kit receptor tyrosine kinase with the Asp814Val mutation
Authors: Koji Hashimoto, Itaru Matsumura, Tohru Tsujimura, Dae-Ki Kim, Hideki Ogihara, Hirokazu Ikeda, Shuji Ueda, Masao Mizuki, Hiroyuki Sugahara, Hirohiko Shibayama, Yukihiko Kitamura, Yuzuru Kanakura
Journal: Blood (2003)
What sort of model could account for an early autonomy and a late interaction revealed by ERPs?
Authors: Frédéric Isel
Journal: Behavioral and Brain Sciences (2000)

Norris, McQueen &amp; Cutler demonstrated that feedback is never necessary during lexical access and proposed a new autonomous model, that is, the Merge model, taking into account the known behavioral data on word recognition. For sentence processing, recent event-related brain potentials (ERPs) data suggest that interactions can occur but only after an initial autonomous stage of processing. Thus at this level too, there is no evidence in favor of feedback.
Dying Patients in the Intensive Care Unit: Forgoing Treatment, Maintaining Care
Authors: Kathy Faber-Langendoen
Journal: Annals of Internal Medicine (2000)

End-of-life care of patients in the intensive care unit (ICU) often requires dramatic shifts in attitudes and interventions, from traditional intensive rescue care to intensive palliative care. The care of patients dying in ICUs raises both clinical and ethical difficulties. Because fewer ICU patients are able to make decisions about withdrawing treatment, careful attention must be paid to previously expressed preferences and surrogate input. Cultural and spiritual values of patients and families may differ markedly from those of clinicians. Although prognostic models are increasingly able to predict mortality rates for groups of ICU patients, their usefulness in guiding specific decisions to forgo treatment has not been established. When a decision to forgo treatment is made, the focus should be on specifying the patient's goals of care and assessing all treatments in light of these goals; interventions that do not contribute to the patient's goals should be discontinued. Symptoms accompanying withdrawal of life support can almost always be controlled with appropriate palliative measures. After ICU interventions are forgone, patient comfort must be the paramount objective. Whether in the ICU or elsewhere, hospitals have an ethical obligation to provide settings that offer dignified, compassionate, and skilled care.
Biomechanics of Lower Limb Prosthetics
Authors: Brian M. Kelly
Journal: JAMA (2010)

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Getting risks right on inhaled corticosteroids and adrenal insufficiency
Authors: Laura Watkins, Joan B. Soriano, Kevin Mortimer
Journal: European Respiratory Journal (2013)

As Thomas Addison observed in his famous monograph written in 1855, the adrenal glands are “objects of deep interest” and so they remain [1]. In the monograph he described several patients who presented with generalised weakness and in whom abnormalities of the adrenal glands were found at post mortem . Addison had discovered primary hypoadrenalism, the disease that would later take his name. He observed that “the disease is by no means of very rare occurrence, and that were we better acquainted with its symptoms and progress, we should probably succeed in detecting many cases” [1].

With Addison's words ringing in our ears we reflect on the paper by Lapi et al. [2] in this issue of the European Respiratory Journal . Lapi et al. [2] describe a nested case–control study examining the association between inhaled corticosteroids and adrenal insufficiency conducted within a cohort of patients treated for respiratory conditions over a 15-year period, starting in 1990, in Quebec, Canada. They identified 392 cases of adrenal insufficiency from 368 238 prevalent users of respiratory medicines from the Regie de l'assurance medicale du Quebec database. They did not …