tbuckley/cabot-search huggingface dataset:
Dose-Intensified Compared With Standard Chemotherapy for Nonmetastatic Ewing Sarcoma Family of Tumors: A Children's Oncology Group Study
Authors: Linda Granowetter, Richard Womer, Meenakshi Devidas, Mark Krailo, Chenguang Wang, Mark Bernstein, Neyssa Marina, Patrick Leavey, Mark Gebhardt, John Healey, Robert Cooper Shamberger, Allen Goorin, James Miser, James Meyer, Carola A.S. Arndt, Scott Sailer, Karen Marcus, Elizabeth Perlman, Paul Dickman, Holcombe E. Grier
Journal: Journal of Clinical Oncology (2009)

The Ewing sarcoma family of tumors (ESFT) is a group of malignant tumors of soft tissue and bone sharing a chromosomal translocation affecting the EWS locus. The Intergroup INT-0091 demonstrated the superiority of a regimen of vincristine, cyclophosphamide, doxorubicin (VDC), and dactinomycin alternating with ifosfamide and etoposide (IE) over VDC for patients with nonmetastatic ESFT of bone. The goal of this study was to determine whether a dose-intensified regimen of VDC alternating with IE would further improve the outcome for patients with nonmetastatic ESFT of bone or soft tissue.Patients with previously untreated, nonmetastatic ESFT of bone or soft tissue were eligible. They were randomly assigned to receive standard doses of VDC/IE over 48 weeks or a dose-intensified regimen of VDC/IE over 30 weeks.Four hundred seventy-eight patients met eligibility requirements: 231 patients received the standard regimen; 247 patients received the intensified regimen. The 5-year event-free survival (EFS) and overall survival rates for all eligible patients were 71.1% (95% CI, 67.7% to 75.0%) and 78.6% (95% CI, 74.6% to 82.1%), respectively. There was no significant difference (P = .57) in EFS between patients treated with the standard (5-year EFS, 72.1%; 95% CI, 65.8% to 77.5%) or intensified regimen (5-year EFS, 70.1%; 63.9% to 75%). Patients with soft tissue tumors accounted for 20% of the study population; there was no difference in outcome between patients with soft tissue and bone primary sites.Dose escalation of alkylating agents as tested in this trial did not improve the outcome for patients with nonmetastatic ESFT of bone or soft tissue.
Lenalidomide Oral Monotherapy Produces Durable Responses in Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma
Authors: Thomas E. Witzig, Peter H. Wiernik, Timothy Moore, Craig Reeder, Craig Cole, Glen Justice, Henry Kaplan, Michael Voralia, Dennis Pietronigro, Kenichi Takeshita, Annette Ervin-Haynes, Jerome B. Zeldis, Julie M. Vose
Journal: Journal of Clinical Oncology (2009)

Lenalidomide is a novel immunomodulatory agent with antiproliferative activities. Given its efficacy in a wide range of hematologic malignancies, we conducted a phase II trial (NHL-001) of single-agent lenalidomide in indolent non-Hodgkin's lymphoma (NHL).Patients with relapsed/refractory indolent NHL were eligible, with no limit on the number of previous therapies. Oral lenalidomide 25 mg was self-administered once daily on days 1 to 21 of every 28-day cycle for up to 52 weeks as tolerated, or until disease progression. The primary end point was objective response rate (ORR), with secondary end points of duration of response (DR), progression-free survival (PFS), and safety.Forty-three enrolled patients were assessable for response and safety. Patients received a median of three prior systemic therapies (range, 1 to 17) and half were refractory to last therapy. ORR was 23% (10 of 43), including a 7% complete response (CR) or unconfirmed CR rate. Twenty-seven percent (six of 22) of patients with follicular lymphoma grade 1 or 2, and 22% (four of 18) with small lymphocytic lymphoma responded to therapy. Median DR was not reached, but was longer than 16.5 months with seven of 10 responses ongoing at 15 to 28 months. Median PFS for the whole group was 4.4 months (95% CI, 2.5 to 10.4 months). Adverse events were predictable and manageable; the most common grade 3 or 4 adverse events were neutropenia (30% and 16%, respectively) and thrombocytopenia (14% and 5%, respectively).Oral lenalidomide monotherapy produces durable responses with manageable adverse events in patients with relapsed/refractory indolent NHL, warranting further investigation of treatment for indolent NHL.
Computerized Adaptive Test–Depression Inventory Not Ready for Prime Time—Reply
Authors: Robert D. Gibbons, David J. Weiss, Paul A. Pilkonis, Ellen Frank, Tara Moore, Jong Bae Kim, David J. Kupfer
Journal: JAMA Psychiatry (2013)

In Reply The Carroll letter "Computerized Adaptive Test–Depression Inventory Not Ready for Prime Time" criticizes our recent article1 published in the November 2012 issue of this journal. Carroll suggests that:
COMMENTARY ON SOME OF THE MORE IMPORTANT BEARINGS OF THE CASE OF SUSPENSION OF THE MENTAL FACULTIES, ETC: WITH REMARKS UPON THE PHILOSOPHY OF THE HUMAN MIND, AND THE PHYSIOLOGICAL PSYCHOLOGY OF MAN
Authors: R. Dunn
Journal: BMJ (1855)

Case of Suspension of the MIental Faculties," etc., induces me to offer some observations on the most important of its psychological bearings, to the consideration of those of my profesonal brethren who are interested in such inquiries.My reason for doing this arises from the fact, that since the casewas first published,ten years ago,great progress has been made towards a more exact knowledge and a better under- standing of the functions and special endowments of the nervous centres of the encephalon, and from a conviction that the psychological bearings of the case are alike inte- resting and instructive.I need not say that the study of the human mind is a subject which has occupied the atten- tion of the greatest philosophers of every age; nor need I remark how long it was enveloped in the shades of mysti- cism, bewildered in the mazes of metaphysical subtlety, and in the conflicting dogmata of chimerical systems.To man.To my mind, he has fully established the following important positions:1.The independent charter of the sensory ganglia as
Improving Blood Pressure Control through Provider Education, Provider Alerts, and Patient Education
Authors: Christianne L. Roumie, Tom A. Elasy, Robert Greevy, Marie R. Griffin, Xulei Liu, William J. Stone, Kenneth A. Wallston, Robert S. Dittus, Vincent Alvarez, Janice Cobb, Theodore Speroff
Journal: Annals of Internal Medicine (2006)

Background: Inadequate blood pressure control is a persistent gap in quality care. Objective: To evaluate provider and patient interventions to improve blood pressure control. Design: Cluster randomized, controlled trial. Setting: 2 hospital-based and 8 community-based clinics in the Veterans Affairs Tennessee Valley Healthcare System. Patients: 1341 veterans with essential hypertension cared for by 182 providers. Eligible patients had 2 or more blood pressure measurements greater than 140/90 mm Hg in a 6-month period and were taking a single antihypertensive agent. Intervention: Providers who cared for eligible patients were randomly assigned to receive an e-mail with a Web-based link to the Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC 7) guidelines (provider education); provider education and a patient-specific hypertension computerized alert (provider education and alert); or provider education, hypertension alert, and patient education, in which patients were sent a letter advocating drug adherence, lifestyle modification, and conversations with providers (patient education). Measurements: Proportion of patients with a systolic blood pressure less than 140 mm Hg at 6 months; intensification of antihypertensive medication. Results: Mean baseline blood pressure was 157/83 mm Hg with no differences between groups (P = 0.105). Six-month follow-up data were available for 975 patients (73%). Patients of providers who were randomly assigned to the patient education group had better blood pressure control (138/75 mm Hg) than those in the provider education and alert or provider education alone groups (146/76 mm Hg and 145/78 mm Hg, respectively). More patients in the patient education group had a systolic blood pressure of 140 mm Hg or less compared with those in the provider education or provider education and alert groups (adjusted relative risk for the patient education group compared with the provider education alone group, 1.31 [95% CI, 1.06 to 1.62]; P = 0.012). Limitations: Follow-up blood pressure measurements were missing for 27% of study patients. The study could not detect a mechanism by which patient education improved blood pressure control. Conclusions: A multifactorial intervention including patient education improved blood pressure control compared with provider education alone.
Molecular subtyping of metastatic renal cell carcinoma: implications for targeted therapy
Authors: Lisha Wang, Sean R Williamson, Mingsheng Wang, Darrell D Davidson, Shaobo Zhang, Lee Ann Baldridge, Xiang Du, Liang Cheng
Journal: Molecular Cancer (2014)

Renal cell carcinoma (RCC) is known for its ability to metastasize synchronously or metachronously to various anatomic sites. Distinguishing histologic subtypes of metastatic RCC has become increasingly important, as prognosis and therapy can differ dramatically between subtypes. We propose a combination of immunohistochemistry (IHC) and molecular cytogenetics for subtyping metastatic RCC in light of these potential therapeutic implications. Specimens from 103 cases of metastatic RCC were retrieved, including 32 cases originally diagnosed as metastatic clear cell renal cell carcinoma (CCRCC), 8 as metastatic papillary renal cell carcinoma (PRCC), and 63 metastatic RCC without a specific subtype. Immunohistochemistry was performed with antibodies against cytokeratin 7 (CK7) and alpha-methylacyl-CoA racemase (AMACR). Dual color interphase fluorescence in situ hybridization was utilized to assess for deletion of chromosome 3p and trisomy of chromosomes 7 and 17 in all tumors. Chromosome 3p deletion was detected in 41% of all metastatic RCC specimens, and trisomy of chromosomes 7 and/or 17 was detected in 16%. Of metastatic CCRCC, chromosome 3p deletion was detected in 63%. Of metastatic PRCC, 75% showed trisomy of chromosomes 7 and/or 17. Of the tumors not previously classified, 6% were positive for CK7, and 64% were positive for AMACR; 35% showed chromosome 3p deletion, and 16% showed trisomy of chromosomes 7 and/or 17. Combined analysis of immunohistochemistry and cytogenetics enabled reclassification of 52% of these metastatic tumors not previously classified. Our findings support the utility of immunohistochemistry and cytogenetics for subtyping metastatic RCC.
Analysis of T cell stimulation by superantigen plus major histocompatibility complex class II molecules or by CD3 monoclonal antibody: costimulation by purified adhesion ligands VCAM-1, ICAM-1, but not ELAM-1.
Authors: G A van Seventer, W Newman, Y Shimizu, T B Nutman, Y Tanaka, K J Horgan, T V Gopal, E Ennis, D O'Sullivan, H Grey
Journal: The Journal of Experimental Medicine (1991)

Many ligands of adhesion molecules mediate costimulation of T cell activation. The generality of this emerging concept is best determined by using model systems which exploit physiologically relevant ligands. We developed such an "antigen-specific" model system for stimulation of resting CD4+ human T cells using the following purified ligands: (a) major histocompatibility complex class II plus the superantigen Staphylococcus enterotoxin A, to engage the T cell receptor (TCR); (b) adhesion proteins vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), and endothelial leukocyte adhesion molecule 1 (ELAM-1), to provide potential cell surface costimulatory signals; and (c) recombinant interleukin 1 beta (rIL-1 beta)/rIL-6 as costimulatory cytokines. In this biochemically defined system, we find that resting CD4+ T cells require costimulation in order to respond to TCR engagement. This costimulation can be provided by VCAM-1 or ICAM-1; however adhesion alone is not sufficient since ELAM-1 mediates adhesion but not costimulation. The cytokines IL-1 beta and IL-6 by themselves cannot mediate costimulation, but augment the adhesion ligand-mediated costimulation. Direct comparison with the model of TCR/CD3 engagement by CD3 monoclonal antibody demonstrated comparable costimulatory requirements in both systems, thereby authenticating the commonly used CD3 model. The costimulation mediated by the activation-dependent interaction of the VLA-4 and LFA-1 integrins with their respective ligands VCAM-1 and ICAM-1 leads to increased IL-2R alpha (CD25) expression and proliferation in both CD45RA+ CD4+ and CD45RO+ CD4+ T cells. The integrins also regulate the secretion of IL-2, IL-4, and granulocyte/macrophage colony-stimulating factor. In contrast the activation-independent adhesion of CD4+ T cell to ELAM-1 molecules does not lead to T cell stimulation as measured by proliferation, IL-2R alpha expression, or cytokine release. These findings imply that adhesion per se is not sufficient for costimulation, but rather that the costimulation conferred by the VLA-4/VCAM-1 and LFA-1/ICAM-1 interactions reflects specialized accessory functions of these integrin pathways. The new finding that VLA-4/VCAM-1 mediates costimulation adds significance to observations that VCAM-1 is expressed on a unique set of potential antigen-presenting cells in vivo.
P121 Ambulatory Treatment For Pneumothorax: A Systematic Review of the Literature and Case For Outpatient Orientated Care?: Abstract P121 Table 1
Authors: FJH Brims, N Maskell
Journal: Thorax (2012)

<h3>Introduction</h3> Spontaneous pneumothorax (SP) is broken down into primary (PSP: no known underlying lung disease), secondary (SSP: known lung disease) and non-spontaneous from trauma or iatrogenic pneumothorax (IP). PSP carries a very low mortality. Current recognised treatments include a conservative approach, needle aspiration, intercostal chest tube (ICT) and surgery. A Heimlich valve (HV) is a lightweight one-way valve specifically designed for the ambulatory treatment of pneumothorax when used with an intercostal catheter. This systematic review was designed to examine the evidence for the use of HV in the management of adults with SP or IP. <h3>Methods</h3> A systematic review was undertaken across nine electronic databases for studies reporting the use of HV for SP or IP. Randomised trials, case control studies and case series were included, unrestricted by year of publication. Post-thoracic surgery and traumatic pneumothorax reports were excluded. All publications were independently scored by two reviewers (FB &amp; NM). Measures of interest included: the use of a HV alone to manage SP or IP, successful treatment as outpatient (OP), complications and financial data. <h3>Results</h3> Eighteen studies were included reporting on the use of HV in 1235 patients, comprising 992 SP (of which 413 were reported as PSP) and 243 IP. The overall quality of the reports was low with only 2 RCTs (n=80 patients), 1 consecutive case series and 14 case reports. Table 1 presents a summary of the outcome measures. In some reports it was not possible to distinguish outcomes between pneumothorax type. There were highly variable protocols and treatment practise across the studies. No deaths were reported, complications included four haemothoraces and one chest wall haematoma. Three studies presented data with cost analysis, with OP HV vs. inpatient ICT cost ratios ranging from 1:3 to 1:5. <h3>Conclusions</h3> High quality data to support the use of HV for ambulatory treatment of pneumothorax is sparse. There are, however, data on &gt;1100 patients from case reports suggesting that the use of HV for SP and IP is safe, effective and may facilitate outpatient orientated treatment of pneumothorax. There is need for a carefully designed RCT to examine this further.
Quaalude Alley: A One-Way Street
Authors: T. PETER BRIDGE, EVERETT H. ELLINWOOD
Journal: American Journal of Psychiatry (1973)

Methaqualone (Quaalude), a nonbarbiturate sedative, was introduced to the American public as a nonaddicting drug with low abuse potential. Unfortunately, it has become the newest drug of abuse. The authors outline the effects of the drug and discuss two patients who had adverse effects after abusing Quaalude. They stress the need for tighter controls on nonbarbiturate sedatives.
Defective Oxidative Phosphorylation in Thyroid Oncocytic Carcinoma Is Associated with Pathogenic Mitochondrial DNA Mutations Affecting Complexes I and III
Authors: Elena Bonora, Anna Maria Porcelli, Giuseppe Gasparre, Annalisa Biondi, Anna Ghelli, Valerio Carelli, Alessandra Baracca, Giovanni Tallini, Andrea Martinuzzi, Giorgio Lenaz, Michela Rugolo, Giovanni Romeo
Journal: Cancer Research (2006)

Oncocytic tumors are characterized by cells with an aberrant accumulation of mitochondria. To assess mitochondrial function in neoplastic oncocytic cells, we studied the thyroid oncocytic cell line XTC.UC1 and compared it with other thyroid non-oncocytic cell lines. Only XTC.UC1 cells were unable to survive in galactose, a condition forcing cells to rely solely on mitochondria for energy production. The rate of respiration and mitochondrial ATP synthesis driven by complex I substrates was severely reduced in XTC.UC1 cells. Furthermore, the enzymatic activity of complexes I and III was dramatically decreased in these cells compared with controls, in conjunction with a strongly enhanced production of reactive oxygen species. Osteosarcoma-derived transmitochondrial cell hybrids (cybrids) carrying XTC.UC1 mitochondrial DNA (mtDNA) were generated to discriminate whether the energetic failure depended on mitochondrial or nuclear DNA mutations. In galactose medium, XTC.UC1 cybrid clones showed reduced viability and ATP content, similarly to the parental XTC.UC1, clearly pointing to the existence of mtDNA alterations. Sequencing of XTC.UC1 mtDNA identified a frameshift mutation in ND1 and a nonconservative substitution in cytochrome b, two mutations with a clear pathogenic potential. In conclusion, this is the first demonstration that mitochondrial dysfunction of XTC.UC1 is due to a combined complex I/III defect associated with mtDNA mutations, as proven by the transfer of the defective energetic phenotype with the mitochondrial genome into the cybrids.
CT Angiography for Safe Discharge of Patients with Possible Acute Coronary Syndromes
Authors: Harold I. Litt, Constantine Gatsonis, Brad Snyder, Harjit Singh, Chadwick D. Miller, Daniel W. Entrikin, James M. Leaming, Laurence J. Gavin, Charissa B. Pacella, Judd E. Hollander
Journal: New England Journal of Medicine (2012)

Admission rates among patients presenting to emergency departments with possible acute coronary syndromes are high, although for most of these patients, the symptoms are ultimately found not to have a cardiac cause. Coronary computed tomographic angiography (CCTA) has a very high negative predictive value for the detection of coronary disease, but its usefulness in determining whether discharge of patients from the emergency department is safe is not well established.
Converging Evidence in Support of the Serotonin Hypothesis of Dexfenfluramine-Induced Pulmonary Hypertension With Novel Transgenic Mice
Authors: Yvonne Dempsie, Ian Morecroft, David J. Welsh, Neil A. MacRitchie, Nigel Herold, Lynn Loughlin, Margaret Nilsen, Andrew J. Peacock, Anthony Harmar, Michael Bader, Margaret R. MacLean
Journal: Circulation (2008)

The incidence of pulmonary arterial hypertension secondary to the use of indirect serotinergic agonists such as aminorex and dexfenfluramine led to the "serotonin hypothesis" of pulmonary arterial hypertension; however, the role of serotonin in dexfenfluramine-induced pulmonary arterial hypertension remains controversial. Here, we used novel transgenic mice lacking peripheral serotonin (deficient in tryptophan hydroxylase-1; Tph1(-/-) mice) or overexpressing the gene for the human serotonin transporter (SERT; SERT(+) mice) to investigate this further.Dexfenfluramine administration (5 mg x kg(-1) x d(-1) PO for 28 days) increased systolic right ventricular pressure and pulmonary vascular remodeling in wild-type mice but not in Tph1(-/-) mice, which suggests that dexfenfluramine-induced pulmonary arterial hypertension is dependent on serotonin synthesis. Dexfenfluramine was also administered to normoxic SERT(+) mice and SERT(+) mice exposed to chronic hypoxia. Dexfenfluramine and SERT overexpression had additive effects in increasing pulmonary vascular remodeling; however, in hypoxic SERT(+) mice, dexfenfluramine reduced both systolic right ventricular pressure and pulmonary vascular remodeling. Pulmonary arterial fibroblasts from SERT(+) mice, but not wild-type mice, proliferated in response to hypoxia. Dexfenfluramine inhibited hypoxia-induced proliferation of pulmonary arterial fibroblasts derived from SERT(+) mice in a manner dependent on SERT activity. Dexfenfluramine also inhibited the hypoxia-mediated increase in phosphorylation of p38 mitogen-activated protein kinase in SERT(+) pulmonary arterial fibroblasts.The results suggest that peripheral serotonin is critical for the development of dexfenfluramine-induced pulmonary arterial hypertension and that dexfenfluramine and SERT overexpression have additive effects on pulmonary vascular remodeling. We propose that dexfenfluramine can also inhibit hypoxia-induced pulmonary vascular remodeling via SERT activity and inhibition of hypoxia-induced p38 mitogen-activated protein kinase.
<i>VKORC1</i> Haplotypes Are Associated With Arterial Vascular Diseases (Stroke, Coronary Heart Disease, and Aortic Dissection)
Authors: Yibo Wang, Weili Zhang, Yuhui Zhang, Yuejin Yang, Lizhong Sun, Shengshou Hu, Jilin Chen, Channa Zhang, Yi Zheng, Yisong Zhen, Kai Sun, Chunyan Fu, Tao Yang, Jianwei Wang, Jing Sun, Haiying Wu, Wayne C. Glasgow, Rutai Hui
Journal: Circulation (2006)

The haplotypes in the gene vitamin K epoxide reductase complex subunit 1 (VKORC1) have been found to affect warfarin dose response through effects on the formation of reduced-form vitamin K, a cofactor for gamma-carboxylation of vitamin K-dependent proteins, which is involved in the coagulation cascade and has a potential impact on atherosclerosis. We hypothesized that VKORC1-dependent effects on the coagulation cascade and atherosclerosis would contribute to susceptibility for vascular diseases.To test the hypothesis, we studied the association of polymorphisms of VKORC1 with stroke (1811 patients), coronary heart disease (740 patients), and aortic dissection (253 patients) compared with matched controls (n=1811, 740, and 416, respectively). Five common noncoding single-nucleotide polymorphisms of VKORC1 were identified in a natural haplotype block with strong linkage disequilibrium (D'>0.9, r2>0.9), then single-nucleotide polymorphism (SNP) +2255 in the block was selected for the association study. We found that the presence of the C allele of the +2255 locus conferred almost twice the risk of vascular disease (odds ratio [OR] 1.95, 95% confidence interval [CI] .58 to 2.41, P<0.001 for stroke; OR 1.72, 95% CI 1.24 to 2.38, P<0.01 for coronary heart disease; and OR 1.90, 95% CI 1.04 to 3.48, P<0.05 for aortic dissection). We also observed that subjects with the CC and CT genotypes had lower levels of undercarboxylated osteocalcin (a regulator for the bone), probably vascular calcification, and lower levels of protein induced in vitamin K absence or antagonism II (PIVKA-II, a des-gamma-carboxy prothrombin) than those with TT genotypes.The haplotype of VKORC1 may serve as a novel genetic marker for the risk of stroke, coronary heart disease, and aortic dissection.