tbuckley/cabot-search huggingface dataset:
The "Unemployable" Cardiac Patient
Authors: R. Lomax Wells
Journal: JAMA (1971)

A national unemployment rate of more than 6% is stimulating industry, labor, government at all levels, and many community agencies to lower this rate to a satisfactory level—perhaps around 3% to 3.5%—a figure that includes those designated as totally unemployable for one reason or another. The unemployment rates for returning Vietnam veterans and young disadvantaged males are considerably higher than 6% and offer many special problems in themselves.  The Medical Committee of the President's Committee on the Employment of the Handicapped over several years developed and published medical criteria for the employability of workers handicapped by certain diseases.1The committee's present concern is with the failure of our profession, along with management and labor, to bring into the work force new job applicants with a history of cardiovascular disease. Those already employed who suffer a cardiovascular accident are usually returned to the work force by their employers, with or
Potent Kinetic Stabilizers That Prevent Transthyretin-Mediated Cardiomyocyte Proteotoxicity
Authors: Mamoun M. Alhamadsheh, Stephen Connelly, Ahryon Cho, Natàlia Reixach, Evan T. Powers, Dorothy W. Pan, Ian A. Wilson, Jeffery W. Kelly, Isabella A. Graef
Journal: Science Translational Medicine (2011)

A high-throughput screen for transthyretin ligands that inhibit protein aggregation identifies agents that prevent amyloid formation and toxicity toward cardiomyocytes.
A phase I dose escalation trial of tremelimumab (CP-675,206) in combination with gemcitabine in chemotherapy-naive patients with metastatic pancreatic cancer
Authors: M. Aglietta, C. Barone, M.B. Sawyer, M.J. Moore, W.H. Miller, C. Bagalà, F. Colombi, C. Cagnazzo, L. Gioeni, E. Wang, B. Huang, K.D. Fly, F. Leone
Journal: Annals of Oncology (2014)
Intramuscular haemangioma of the thigh in a basketball player
Authors: R A Brown, K Crichton, G M Malouf
Journal: British Journal of Sports Medicine (2004)

Haemangioma is a common benign soft tissue tumour. Intramuscular haemangiomas may present as a perceived sporting injury. Magnetic resonance imaging is the investigation of choice. Intramuscular haemangioma should be considered in the differential diagnosis of unexplained pain and swelling in a muscle.
Contemporary Aspects of the Biology and Therapeutic Regulation of the Microsomal Triglyceride Transfer Protein
Authors: Amanda J. Hooper, John R. Burnett, Gerald F. Watts
Journal: Circulation Research (2014)

The microsomal triglyceride transfer protein (MTP), the product of the MTTP gene, is essential for the assembly and secretion of apolipoprotein B-containing lipoproteins, but when defective causes abetalipoproteinemia. Abetalipoproteinemia is a rare autosomal recessive disorder characterized by the inability to produce chylomicrons or very low-density lipoproteins, with the absence of apolipoprotein B-containing lipoproteins in the circulation. Knowledge of the molecular basis for abetalipoproteinemia has led to the development of therapies for dyslipidemia that inhibit MTP. Partial MTP inhibition using small molecule inhibitors, such as lomitapide, can effectively lower plasma low-density lipoprotein-cholesterol and apolipoprotein B levels, but is associated with gastrointestinal side effects and hepatic steatosis, whose long-term sequelae remain unclear; lomitapide has accordingly only been approved as a treatment for homozygous familial hypercholesterolemia. Intestine-specific inhibitors of MTP decrease chylomicron biogenesis and improve insulin sensitivity in experimental animals and, while overcoming hepatic steatosis, may have significant gastrointestinal side effects that could limit their use in humans. We review contemporary aspects of the biology and therapeutic regulation of MTP and their significance for lipid metabolism and cardiovascular disease.
Polycythemia Vera: An Appraisal of the Biology and Management 10 Years After the Discovery of<i>JAK2 V617F</i>
Authors: Brady L. Stein, Stephen T. Oh, Dmitriy Berenzon, Gabriela S. Hobbs, Marina Kremyanskaya, Raajit K. Rampal, Camille N. Abboud, Kenneth Adler, Mark L. Heaney, Elias J. Jabbour, Rami S. Komrokji, Alison R. Moliterno, Ellen K. Ritchie, Lawrence Rice, John Mascarenhas, Ronald Hoffman
Journal: Journal of Clinical Oncology (2015)

Polycythemia vera (PV) is a chronic myeloproliferative neoplasm that is associated with a substantial symptom burden, thrombohemorrhagic complications, and impaired survival. A decade after the seminal discovery of an activating mutation in the tyrosine kinase JAK2 in nearly all patients with PV, new treatment options are finally beginning to emerge, necessitating a critical reappraisal of the underlying pathogenesis and therapeutic modalities available for PV. Herein, we comprehensively review clinical aspects of PV including diagnostic considerations, natural history, and risk factors for thrombosis. We summarize recent studies delineating the genetic basis of PV, including their implications for evolution to myelofibrosis and secondary acute myeloid leukemia. We assess the quality of evidence to support the use of currently available therapies, including aspirin, phlebotomy, hydroxyurea, and interferon. We analyze recent studies evaluating the safety and efficacy of JAK inhibitors, such as ruxolitinib, and evaluate their role in the context of other available therapies for PV. This review provides a framework for practicing hematologists and oncologists to make rational treatment decisions for patients with PV.
Lack of Microvessels in Well-Differentiated Regions of Human Head and Neck Squamous Cell Carcinoma A253 Associated with Functional Magnetic Resonance Imaging Detectable Hypoxia, Limited Drug Delivery, and Resistance to Irinotecan Therapy
Authors: Arup Bhattacharya, Károly Tóth, Richard Mazurchuk, Joseph A. Spernyak, Harry K. Slocum, Lakshmi Pendyala, Rami Azrak, Shousong Cao, Farukh A. Durrani, Youcef M. Rustum
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Combination chemotherapy with irinotecan (CPT-11; 50 mg/kg/week × 4 intravenously), followed 24 hour later by 5-fluorouracil (50 mg/kg/week × 4 intravenously), results in 10 and 100% cure rates of animals bearing human head and neck squamous cell carcinoma xenografts A253 and FaDu, respectively. A253 consists of 30% well-differentiated and avascular and 70% poorly differentiated regions with low microvessel density (10/×400), whereas FaDu is uniformly poorly differentiated with higher microvessel density (19/×400). Studies were carried out for determining the role of well-differentiated and avascular regions in drug resistance in A253 and detection of such regions with noninvasive functional magnetic resonance (fMR) imaging. Experimental Design: Tumors were harvested for histopathologic evaluation and immunohistochemistry (CD31, CD34; differentiation marker: involucrin; hypoxia markers: carbonic anhydrase IX, pimonidazole; vascular endothelial factor (VEGF) and Ki67) immediately after fMR imaging following the 3rd dose of chemotherapy. High-performance liquid chromatography determination of intratumoral drug concentration of 7-ethyl-10-hydroxyl-camptothecin and autoradiography with 14C-labeled CPT-11 was done 2 hours after CPT-11 administration. Results: Although A253 xenografts showed three times higher concentration of 7-ethyl-10-hydroxyl-camptothecin, FaDu was more responsive to therapy. After therapy, A253 tumor consisted mostly (∼80%) of well-differentiated regions (positive for involucrin) lacking microvessels with a hypoxic rim (positive for carbonic anhydrase IX and pimonidazole) containing few proliferating (Ki67 positive) poorly differentiated cells. Autoradiography revealed that well-differentiated A253 tumor regions showed 5-fold lower 14C-labeled CPT-11 concentrations compared with poorly differentiated areas (P &amp;lt; 0.001). Blood oxygen level dependant fMR imaging was able to noninvasively distinguish the hypoxic and well-vascularized regions within the tumors. Conclusion: Avascular-differentiated regions in squamous cell carcinoma offer sanctuary to some hypoxic but viable tumor cells (carbonic anhydrase IX and Ki67 positive) that escape therapy because of limited drug delivery. This study provides direct evidence that because of a specific histologic structure, avascular, well-differentiated hypoxic regions in tumors exhibit low drug uptake and represent a unique form of drug resistance.
Sustained Receptor Activation and Hyperproliferation in Response to Granulocyte Colony-stimulating Factor (G-CSF) in Mice with a Severe Congenital Neutropenia/Acute Myeloid Leukemia–derived Mutation in the G-CSF Receptor Gene
Authors: Mirjam H.A. Hermans, Claudia Antonissen, Alister C. Ward, Angelique E.M. Mayen, Rob E. Ploemacher, Ivo P. Touw
Journal: The Journal of Experimental Medicine (1999)

In approximately 20% of cases of severe congenital neutropenia (SCN), mutations are found in the gene encoding the granulocyte colony-stimulating factor receptor (G-CSF–R). These mutations introduce premature stop codons, which result in truncation of 82–98 COOH-terminal amino acids of the receptor. SCN patients who develop secondary myelodysplastic syndrome and acute myeloid leukemia almost invariably acquired a GCSFR mutation, suggesting that this genetic alteration represents a key step in leukemogenesis. Here we show that an equivalent mutation targeted in mice (gcsfr-Δ715) results in the selective expansion of the G-CSF– responsive progenitor (G-CFC) compartment in the bone marrow. In addition, in vivo treatment of gcsfr-Δ715 mice with G-CSF results in increased production of neutrophils leading to a sustained neutrophilia. This hyperproliferative response to G-CSF is accompanied by prolonged activation of signal transducer and activator of transcription (STAT) complexes and extended cell surface expression of mutant receptors due to defective internalization. In view of the continuous G-CSF treatment of SCN patients, these data provide insight into why progenitor cells expressing truncated receptors clonally expand in vivo, and why these cells may be targets for additional genetic events leading to leukemia.
Prevention of Venous Thromboembolism in Total Knee and Hip Replacement
Authors: David Warwick
Journal: Circulation (2012)

C ase presentation: A 69-year-old woman had a cemented hip replacement 15 years previously, which initially fared well but then gradually failed because of aseptic loosening.She developed pain in her hip and was scheduled for a revision total hip replacement.A formal venous thromboembolism (VTE) risk assessment was undertaken before surgery according to the Hospital's policy for all orthopedic admissions.The risk assessment identified 2 conflicting issues.First, the patient had a particularly high risk of VTE, having had an above-knee deep vein thrombosis after her primary hip replacement and now required a major surgery, namely a revision hip arthroplasty.Second, she had a greater than usual risk of bleeding after surgery because of her obesity and the need for a large soft-tissue exposure, long-term aspirin, and supplementary bone graft from her iliac crest.The surgeon was faced with a common orthopedic problem, providing effective VTE prophylaxis without causing an equally important problem of surgical bleeding.
Quality of life following lung cancer surgery
Authors: G Myrdal
Journal: Thorax (2003)

Patients with non-small cell bronchogenic carcinoma have a limited survival. Quality of life (QoL) is therefore an issue of importance in this group of patients. The aim of the present study was to evaluate QoL in lung cancer patients after open surgery.During a 4 year period (1997-2000) 194 patients with primary bronchogenic carcinoma of the lung underwent surgery at the Department of Thoracic and Cardiovascular Surgery in Uppsala, Sweden; 132 patients were alive on 1 April 2001. These patients received the Short Form-36 (SF-36) health questionnaire, Hospital Anxiety and Depression (HAD) scale, and special questions related to pulmonary symptoms (response rate 85%). Patients who underwent coronary bypass surgery (CABG) served as a comparison group (response rate 91%). Corresponding estimates of QoL in healthy controls were obtained from the SF-36 manual for the Swedish population.Lung cancer patients differed from CABG patients in only one subgroup of the SF-36 (role physical), but had poorer QoL than healthy controls. No difference in anxiety was found between the lung cancer patients and the CABG patients, but the latter were more likely to suffer from depression (5.0% v 3.0%). Current smokers scored lower in the mental health dimension assessment.Lung cancer patients who undergo open traditional surgical resection have a QoL comparable to that of CABG patients. Lung cancer patients have poorer physical function because of reduced pulmonary function, but show no sign of increased anxiety or depression. Those who continued to smoke after surgery had impaired mental health.
Inclusion of CA-125 Does Not Improve Mathematical Models Developed to Distinguish Between Benign and Malignant Adnexal Tumors
Authors: Dirk Timmerman, Ben Van Calster, Davor Jurkovic, Lil Valentin, Antonia C. Testa, Jean-Pierre Bernard, Caroline Van Holsbeke, Sabine Van Huffel, Ignace Vergote, Tom Bourne
Journal: Journal of Clinical Oncology (2007)

Purpose To test the value of serum CA-125 measurements alone or as part of a multimodal strategy to distinguish between malignant and benign ovarian tumors before surgery based on a large prospective multicenter study (International Ovarian Tumor Analysis). Patients and Methods Patients with at least one persistent ovarian mass preoperatively underwent transvaginal ultrasonography using gray scale imaging to assess tumor morphology and color Doppler imaging to obtain indices of blood flow. Results Data from 809 patients recruited from nine centers were included in the analysis; 567 patients (70%) had benign tumors and 242 (30%) had malignant tumors—of these 152 were primary invasive (62.8%), 52 were borderline malignant (21.5%), and 38 were metastatic (15.7%). A logistic regression model including CA-125 (M2) resulted in an area under the receiver operating characteristic curve (AUC) of 0.934 and did not outperform a published (M1) without serum CA-125 information (AUC, 0.936). Specifically designed new models including CA-125 for premenopausal women (M3) and for postmenopausal women (M4) did not perform significantly better than the model without CA-125 (M1; AUC, 0.891 v AUC, 0.911 and AUC, 0.975 v AUC, 0.949, respectively). In postmenopausal patients, serum CA-125 alone (AUC, 0.920) and the risk of malignancy index (AUC, 0.924) performed very well. Results were very similar when the models were prospectively tested on a group of 345 new patients with adnexal masses of whom 126 had malignant tumors (37%). Conclusion Adding information on CA-125 to clinical information and ultrasound information does not improve discrimination of mathematical models between benign and malignant adnexal masses.
Breast screening programme.
Authors: J. A. Gray
Journal: BMJ (1989)

Referrals to hospital by general practitioners SIR,-We have recently completed an extensive study into non-attendance for psychiatric ap- pointments, and several points emerge from a comparison of the findings of Dr Kieran JMcGlade and others' with ours.Their 20% level of overall non-attendance for initial appointments in all specialties is far higher than that we encountered for the Grampian region of Scotland.Our figure of 8% is more in keeping with that of Grace and Armstrong.2More striking is the discrepancy between their figures and ours for psychiatric non- attendance.In contrast to their 40% rate we found that only 234 out of 2771 (8 4%) first appointments were not kept.This difference may of course reflect the small number of patients in the Belfast study.Furthermore, it is interesting to note that, at least in Grampian, appointment default is no more common in psychiatry than in other specialties.There are, however, two points on which the
Clearance of Benzo[a]pyrene From Hamster Lunis After Administration on Coated Particles2
Authors: M. C. Henry, D. G. Kaufman
Journal: JNCI Journal of the National Cancer Institute (1973)

The persistence of benzo[a] pyrene (BP) in the respiratory tract of hamsters was determined after intratracheal instillation of the particulate dusts carbon, aluminum oxide, and ferric oxide (in the 4 size ranges 0.5–1, 2–5, 5–10, and 15–30µ), each coated with BP. Because the 2% dust-2% carcinogen preparations were prepared on a weight basis, density differences required that more particles of carbon than of aluminum oxide or ferric oxide be given. Analysis of the BP content of hamster lungs immediately after instillation showed that the carbon reparations contained more carcinogen. BP was cleared much more slowly from lungs of carbon-treated animals, and there was a positive correlation between particle size and retention rate. The particles of aluminum oxide and ferric oxide retarded the clearance of the carcinogen, but retention rates did not correlate with particle size. These results were discussed in relation to the pathogenesis of lung cancer in hamsters treated by intratracheal instillations.
Comment on: Rogers et al. Blood Pressure Trajectories Prior to Death in Patients With Diabetes. Diabetes Care 2011;34:1534–1539
Authors: K.J.J. van Hateren, N. Kleefstra, H.J.G. Bilo
Journal: Diabetes Care (2011)

With great interest we read the article by Rogers et al. (1) in which they showed that both systolic and diastolic blood pressure declined more rapidly in the 4 years before death than in patients who remained alive. In a model adjusted for, among other factors, age, sex, use of ACE inhibitors and angiotensin receptor blockers (ARBs), and heart failure, mean systolic blood pressure decreased by 3.2 mmHg per year in the years prior …
Aspects of human language: Where motherese?
Authors: Emmanuel Gilissen
Journal: Behavioral and Brain Sciences (2004)

Human language is a peculiar primate communication tool because of its large neocortical substrate, comparable to the structural substrates of cognitive systems. Although monkey calls and human language rely on different structures, neural substrate for human language emotional coding, prosody, and intonation is already part of nonhuman primate vocalization circuitry. Motherese could be an aspect of language at the crossing or at the origin of communicative and cognitive content.
Mapping Genes for NIDDM: Design of the Finland—United States Investigation of NIDDM Genetics (FUSION) Study
Authors: Timo Valle, Jaakko Tuomilehto, Richard N Bergman, Soumitra Ghosh, Elizabeth R Hauser, Johan Eriksson, Stella J Nylund, Kimmo Kohtamäki, Liisa Toivanen, Gabriele Vidgren, Eva Tuomilehto-Wolf, Christian Ehnholm, Jillian Blaschak, Carl D Langefeld, Richard M Watanabe, Victoria Magnuson, Delphine S Ally, William A Hagopian, Edna Ross, Thomas A Buchanan, Francis Collins, Michael Boehnke
Journal: Diabetes Care (1998)

OBJECTIVE To map and identify susceptibility genes for NIDDM and for the intermediate quantitative traits associated with NIDDM. RESEARCH DESIGN AND METHODS We describe the methodology and sample of the Finland-United States Investigation of NIDDM Genetics (FUSION) study. The whole genome search approach is being applied in studies of several different ethnic groups to locate susceptibility genes for NIDDM. Detailed description of the study materials and designs of such studies are important, particularly when comparing the findings in these studies and when combining different data sets. RESULTS Using a careful selection strategy, we have ascertained 495 families with confirmed NIDDM in at least two siblings and no history of IDDM among the first-degree relatives. These families were chosen from more than 22,000 NIDDM patients, representative of patients with NIDDM in the Finnish population. In a subset of families, a spouse and offspring were sampled, and they participated in a frequently sampled intravenous glucose tolerance test (FSIGT) analyzed with the Minimal Model. An FSIGT was completed successfully for at least two nondiabetic offspring in 156 families with a confirmed nondiabetic spouse and no history of IDDM in first-degree relatives. CONCLUSIONS Our work demonstrates the feasibility of collecting a large number of affected sib-pair families with NIDDM to provide data that will enable a whole genome search approach, including linkage analysis.
American Society of Clinical Oncology Technology Assessment Working Group Update: Use of Aromatase Inhibitors in the Adjuvant Setting
Authors: Eric P. Winer, Clifford Hudis, Harold J. Burstein, John Bryant, Rowan T. Chlebowski, James N. Ingle, Stephen B. Edge, Eleftherios P. Mamounas, Richard Gelber, Julie Gralow, Lori J. Goldstein, Kathleen I. Pritchard, Susan Braun, Melody A. Cobleigh, Amy S. Langer, Judy Perotti, Trevor J. Powles, Timothy J. Whelan, George P. Browman
Journal: Journal of Clinical Oncology (2003)

Article Tools ASCO SPECIAL ARTICLE Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.04.596 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12732612 American Society of Clinical Oncology Technology Assessment Working Group Update: Use of Aromatase Inhibitors in the Adjuvant Setting Eric P. WinerxEric P. WinerSearch for articles by this author , Clifford HudisxClifford HudisSearch for articles by this author , Harold J. BursteinxHarold J. BursteinSearch for articles by this author , John BryantxJohn BryantSearch for articles by this author , Rowan T. ChlebowskixRowan T. ChlebowskiSearch for articles by this author , James N. InglexJames N. IngleSearch for articles by this author , Stephen B. EdgexStephen B. EdgeSearch for articles by this author , Eleftherios P. MamounasxEleftherios P. MamounasSearch for articles by this author , Richard GelberxRichard GelberSearch for articles by this author , Julie GralowxJulie GralowSearch for articles by this author , Lori J. GoldsteinxLori J. GoldsteinSearch for articles by this author , Kathleen I. PritchardxKathleen I. PritchardSearch for articles by this author , Susan BraunxSusan BraunSearch for articles by this author , Melody A. CobleighxMelody A. CobleighSearch for articles by this author , Amy S. LangerxAmy S. LangerSearch for articles by this author , Judy PerottixJudy PerottiSearch for articles by this author , Trevor J. PowlesxTrevor J. PowlesSearch for articles by this author , Timothy J. WhelanxTimothy J. WhelanSearch for articles by this author , George P. BrowmanxGeorge P. BrowmanSearch for articles by this author Show More From the American Society of Clinical Oncology, Alexandria, VA. https://doi.org/10.1200/JCO.2003.04.596 First Page Full Text PDF Figures and Tables © 2003 by American Society of Clinical Oncology
Interleukin 3 is a growth factor for human follicular B cell lymphoma.
Authors: C Clayberger, S Luna-Fineman, J E Lee, A Pillai, M Campbell, R Levy, A M Krensky
Journal: The Journal of Experimental Medicine (1992)

More than one-half of adults with non-Hodgkin's B cell lymphomas present with low-grade follicular lymphomas. These tumor cells are found in close association with follicular T lymphocytes and dendritic cells, suggesting that the surrounding cells may play a role in the support of follicular tumors. Supernatants from activated human peripheral blood lymphocytes were found to promote the in vitro proliferation of follicular tumor cells. This effect was entirely due to interleukin 3 (IL-3), a factor generally thought to cause the growth and differentiation of immature hematopoietic cells. IL-3 receptors were detected on fresh isolates of all primary follicular cell tumors examined. These findings suggest that follicular cell tumors may be dependent in vivo on IL-3 and that therapies directed against IL-3, its receptor, or the T cells that produce it may be effective treatment for follicular lymphoma.