tbuckley/cabot-search huggingface dataset:
Characterization of Human Platelet Vascular Permeability-Enhancing Activity
Authors: Ralph L. Nachman, Babette Weksler, Barbara Ferris
Journal: Journal of Clinical Investigation (1972)

Human platelet acid extract obtained from both whole platelets and from isolated subcellular granules was partially purified by DEAE-cellulose chromatography and Sephadex gel filtration. The heat-stable, nondialyzable cationic protein fraction with a mol wt of approximately 30,000 produced a biphasic increase in vascular permeability in rabbit skin and also had antiheparin activity. The acute (15 min) increase in vascular permeability was blocked by prior treatment of the animal with antihistamine and was characterized histologically by edema of perivascular tissues and dilation of capillaries and veinules. The delayed (3 hr) permeability effect was not blocked by antihistamine and was characterized histologically by leukocytic infiltration into the skin. The experiments described suggest that human platelet lysosomal release of cationic proteins may increase vascular permeability by several mechanisms including endogenous histamine release as well as delayed chemotaxis.
Managing back pain and osteoarthritis without paracetamol
Authors: C. Mallen, E. Hay
Journal: BMJ (2015)

Physical treatments are the way forward

Paracetamol (acetaminophen) is a drug we are all familiar with. It is cheap, readily available over the counter, and is common place in family medicine cabinets across the world. We rely on it in the middle of the night to settle childhood fevers, and it is usually our first choice drug for a wide range of painful musculoskeletal disorders, including osteoarthritis and spinal pain. Yet new evidence in a linked paper by Machado and colleagues (doi:10.1136/bmj.h1225) casts doubt on the efficacy and safety of paracetamol and questions its place as our first choice analgesic.1

In their systematic review and meta-analysis examining the efficacy and safety of paracetamol for spinal pain and osteoarthritis, Machado and colleagues synthesised evidence from 13 randomised controlled trials.1 They report that there is “high quality” evidence that paracetamol is ineffective for reducing pain intensity and disability in patients with low back pain and “high quality” evidence that paracetamol produces a significant but not clinically important effect on pain and disability in patients with osteoarthritis. While adverse events were reported at a similar …
Radiology of the Digestive System: A Radiological Companion to Truelove and Reynell's Diseases of the Digestive System
Authors: Paul B. Savory
Journal: JAMA (1966)

The English authors of this much needed text have successfully covered a subject of vast importance. Though much has been written on the radiologic findings of gastrointestinal diseases, very few attempts have been made to gather this information into a concise text. The first part of the book deals with radiographic technique as applied to the digestive system. There is considerable discussion of the preparation and use of contrast media. Then the authors proceed to deal with the anatomy and diseases of the digestive system from the top down, starting with the pharynx, through to the rectum. The last part of the book considers, in two separate chapters, the radiology of the acute abdomen and diseases of the intestinal tract in the newborn. The volume presents excellent reproductions of radiographs and the illustration of diseases is of the highest quality. The text tends to be concise and brief; though most
Downregulation of CuZn-superoxide dismutase contributes to β-adrenergic receptor-mediated oxidative stress in the heart
Authors: S SRIVASTAVA, B CHANDRASEKAR, Y GU, J LUO, T HAMID, B HILL, S PRABHU
Journal: Cardiovascular Research (2007)

Objective: Sustained β-adrenergic receptor (β-AR) activation augments oxidative stress in the heart; whether alterations in antioxidant enzymes contribute to this effect is unknown.
Learning from e-patients at Massachusetts General Hospital
Authors: John Lester, Stephanie Prady, Yolanda Finegan, Dan Hoch
Journal: BMJ (2004)

Patients and their care givers have created an impressive array of online health resources. Can healthcare professionals tap into them? 

In 1994, as a part of an initiative by the department of neurology of the Massachusetts General Hospital to develop promising new ways of using information technology, we began to study how patients with neurological concerns were using online health resources. To our surprise, we found that thousands of patients and their care givers had already created an impressive variety of online health resources. The online support groups, each devoted to a single neurological condition, were especially intriguing.

The opportunities that these electronic groups offered for meeting members' needs were more convenient, powerful, and complex than anything we had seen in face to face support groups. For example, patients attending medical centres around the world could compare the treatments their clinicians had recommended. Participants found it easy to send complex medical information (medical journal articles, research reports, etc) to other patients, complete with links to yet other sources. But the groups we observed were scattered and uncoordinated. And although groups existed for most of the common neurological concerns, patients with uncommon conditions had no way of finding one another.

We decided that our team of e-health researchers might be able to help—by providing better “homes” for existing support groups, and by encouraging the formation of needed groups. So in March 1995 the hospital's neurology service instituted a family of online groups called the Brain Talk Communities (http://www.braintalk.org/) to support e-patients with neurological concerns.

Most medical professionals who have set out to develop online resources for patients have created applications and content in a “top down” manner, directed by health professionals. Within such systems, end users (patients, their care givers, and their family members) usually have little or no input or …
Kidney-specific drug delivery system for renal fibrosis based on coordination-driven assembly of catechol-derived chitosan
Authors: Hongzhi Qiao, Minjie Sun, Zhigui Su, Ying Xie, Minglei Chen, Li Zong, Yahan Gao, Huipeng Li, Jianping Qi, Qun Zhao, Xiaochen Gu, Qineng Ping
Journal: Biomaterials (2014)
Experimental atrophy/hypertrophy complex (AHC) of the liver: portal vein, but not bile duct obstruction, is the main driving force for the development of AHC in the rat
Authors: Walter Schweizer, Petra Duda, Sandro Tanner, Daniel Balsiger, Frieder Hörlin, Leslie Harold Blumgart, Arthur Zimmermann
Journal: Journal of Hepatology (1995)
GP369, an FGFR2-IIIb–Specific Antibody, Exhibits Potent Antitumor Activity against Human Cancers Driven by Activated FGFR2 Signaling
Authors: Ailin Bai, Kristan Meetze, Nhi Y. Vo, Sriram Kollipara, Elizabeth K. Mazsa, William M. Winston, Solly Weiler, Laura L. Poling, Ting Chen, Nesreen S. Ismail, Jinwei Jiang, Lorena Lerner, Jeno Gyuris, Zhigang Weng
Journal: Cancer Research (2010)

Abstract Dysregulated fibroblast growth factor (FGF) signaling has been implicated in the pathogenesis of human cancers. Aberrant activation of FGF receptor 2 (FGFR2) signaling, through overexpression of FGFR2 and/or its ligands, mutations, and receptor amplification, has been found in a variety of human tumors. We generated monoclonal antibodies against the extracellular ligand-binding domain of FGFR2 to address the role of FGFR2 in tumorigenesis and to explore the potential of FGFR2 as a novel therapeutic target. We surveyed a broad panel of human cancer cell lines for the dysregulation of FGFR2 signaling and discovered that breast and gastric cancer cell lines harboring FGFR2 amplification predominantly express the IIIb isoform of the receptor. Therefore, we used an FGFR2-IIIb–specific antibody, GP369, to investigate the importance of FGFR2 signaling in vitro and in vivo. GP369 specifically and potently suppressed ligand-induced phosphorylation of FGFR2-IIIb and downstream signaling, as well as FGFR2-driven proliferation in vitro. The administration of GP369 in mice significantly inhibited the growth of human cancer xenografts harboring activated FGFR2 signaling. Our findings support the hypothesis that dysregulated FGFR2 signaling is one of the critical oncogenic pathways involved in the initiation and/or maintenance of tumors. Cancer patients with aberrantly activated/amplified FGFR2 signaling could potentially benefit from therapeutic intervention with FGFR2-targeting antibodies. Cancer Res; 70(19); 7630–9. ©2010 AACR.
In Vivo Assessment of Stent Expansion and Recoil in Normal Porcine Coronary Arteries
Authors: Joseph P. Carrozza, Susanne E. Hosley, David J. Cohen MD, Donald S. Baim
Journal: Circulation (1999)

Background —Despite the routine use of high pressure, coronary stents generally fail to achieve a cross-sectional area (CSA) &gt;60% to 80% of the nominal CSA of their dilating balloon. The extent to which incomplete balloon expansion and postdeflation stent recoil contribute to this failure has not been fully evaluated. Methods and Results —Thirty-two stents (8 Gianturco-Roubin II, 8 Palmaz-Schatz, 8 MultiLink, and 8 NIR) were deployed in nondiseased coronary arteries of 8 Yorkshire pigs. All stents were then expanded according to 1 of 3 balloon strategies: appropriately sized compliant balloons, oversized compliant balloons, or oversized noncompliant balloons. Continuous ultrasound imaging was performed during stepwise balloon inflation and deflation, with an 0.018-in imaging core positioned within the guidewire lumen of the balloon. In these normal arteries, balloon underexpansion relative to the nominal size was not observed. After balloon deflation, however, all stents showed significant recoil from their maximum inflated CSA. Recoil was significantly greater for the coil Gianturco-Roubin II stent (30% CSA) than for the 3 slotted-tube stent designs (15% to 17% CSA). Conclusions —In normal, compliant coronary arteries, stent recoil is the predominant mechanism by which stents fail to achieve the nominal CSA of their dilating balloon. The magnitude of this in vivo stent recoil is significantly greater than reported from bench testing and varies with stent design (coil versus slotted tube). Postdilatation strategies that result in controlled stent overexpansion are needed to overcome this recoil phenomenon and result in a final stent CSA that approximates the reference artery CSA.
ETS2 Mediated Tumor Suppressive Function and MET Oncogene Inhibition in Human Non–Small Cell Lung Cancer
Authors: Mohamed Kabbout, Melinda M. Garcia, Junya Fujimoto, Diane D. Liu, Denise Woods, Chi-Wan Chow, Gabriela Mendoza, Amin A. Momin, Brian P. James, Luisa Solis, Carmen Behrens, J. Jack Lee, Ignacio I. Wistuba, Humam Kadara
Journal: Clinical Cancer Research (2013)

Abstract Purpose: The ETS2 transcription factor is an evolutionarily conserved gene that is deregulated in cancer. We analyzed the transcriptome of lung adenocarcinomas and normal lung tissue by expression profiling and found that ETS2 was significantly downregulated in adenocarcinomas. In this study, we probed the yet unknown functional role of ETS2 in lung cancer pathogenesis. Experimental Design: Lung adenocarcinomas (n = 80) and normal lung tissues (n = 30) were profiled using the Affymetrix Human Gene 1.0 ST platform. Immunohistochemical (IHC) analysis was conducted to determine ETS2 protein expression in non–small cell lung cancer (NSCLC) histologic tissue specimens (n = 201). Patient clinical outcome, based on ETS2 IHC expression, was statistically assessed using the log-rank and Kaplan–Meier tests. RNA interference and overexpression strategies were used to assess the effects of ETS2 expression on the transcriptome and on various malignant phenotypes. Results: ETS2 expression was significantly reduced in lung adenocarcinomas compared with normal lung (P &amp;lt; 0.001). Low ETS2 IHC expression was a significant predictor of shorter time to recurrence in NSCLC (P = 0.009, HR = 1.89) and adenocarcinoma (P = 0.03, HR = 1.86). Moreover, ETS2 was found to significantly inhibit lung cancer cell growth, migration, and invasion (P &amp;lt; 0.05), and microarray and pathways analysis revealed significant (P &amp;lt; 0.001) activation of the HGF pathway following ETS2 knockdown. In addition, ETS2 was found to suppress MET phosphorylation and knockdown of MET expression significantly attenuated (P &amp;lt; 0.05) cell invasion mediated by ETS2-specific siRNA. Furthermore, knockdown of ETS2 augmented HGF-induced MET phosphorylation, cell migration, and invasion. Conclusion(s): Our findings point to a tumor suppressor role for ETS2 in human NSCLC pathogenesis through inhibition of the MET proto-oncogene. Clin Cancer Res; 19(13); 3383–95. ©2013 AACR.
Evaluation of 18F-FDG PET-CT for Differentiation of Pulmonary Pathology in an Approach of Outpatient Fast Track Assessment
Authors: Tjeerd S. Aukema, Renato A. Valdés Olmos, Houke M. Klomp, Hendrik J. Teertstra, José S.A. Belderbos, Wouter V. Vogel, Paul Baas, Sjaak A. Burgers, Michel M. van den Heuvel
Journal: Journal of Thoracic Oncology (2009)
CNS Metastases in Breast Cancer
Authors: Nancy U. Lin, Jennifer R. Bellon, Eric P. Winer
Journal: Journal of Clinical Oncology (2004)

As systemic therapy of metastatic breast cancer improves, CNS involvement is becoming a more widespread problem. This article summarizes the current knowledge regarding the incidence, clinical presentation, diagnosis, prognosis, and treatment of CNS metastases in patients with breast cancer. When available, studies specific to breast cancer are presented; in studies in which many solid tumors were evaluated together, the proportion of patients with breast cancer is noted. On the basis of data from randomized trials and retrospective series, neurosurgery and stereotactic radiosurgery (SRS) may prolong survival in patients with single brain metastases. The treatment of multiple metastases remains controversial, as does the routine use of whole-brain radiotherapy (WBRT) after either surgery or SRS. Although it is widely assumed that chemotherapy is of limited benefit, data from case series and case reports suggest otherwise. WBRT, neurosurgery, SRS, and medical therapy each have a role in the treatment of CNS metastases; however, neurologic symptoms frequently are not fully reversible, even with appropriate therapy. Studies specifically targeted toward this group of patients are needed.
Surgical management of heart failure
Authors: D. P Taggart, S. Westaby
Journal: BMJ (1997)

Over the past three decades mortality from cardiovascular disease has decreased in industrialised societies while the incidence and prevalence of heart failure has been increasing.1 Heart failure is now a major health problem, affecting up to 2% of the population and 10% of patients aged over 65 years.2 In 1990 heart failure accounted for 5% of all hospital admissions in Britain,3 at a cost to the NHS of £360m ($576m).4 In the United States, where 400 000 new cases are diagnosed annually, treatment costs in excess of $34bn (£21.2bn).5

The natural course of heart failure is progressive so that even with angiotensin converting enzyme inhibitors, the only medical treatment to have consistently improved prognosis, the annual mortality is 25-50%.5 This dismal outlook, particularly in severely symptomatic patients, often prompts surgical referral. A small proportion of patients may benefit from coronary revascularisation, albeit at a higher operative risk,6 while unsuspected or underestimated valvular disease may merit valve repair or replacement. For many, conventional cardiac surgery has little to offer and the only surgical option is transplantation. Newer surgical approaches include cardiomyoplasty, left ventricular volume reduction, and mechanical support.

Cardiac transplantation is presently the optimum surgical treatment for heart failure. Allograft transplantation results in 90% survival at one year and 50% survival at five years with return to a near normal quality of life.7 However, the scarcity of donor organs …
Epicardial Placement of Mesenchymal Stromal Cell-sheets for the Treatment of Ischemic Cardiomyopathy; In Vivo Proof-of-concept Study
Authors: Nobuko Tano, Takuya Narita, Masahiro Kaneko, Chiho Ikebe, Steven R Coppen, Niall G Campbell, Manabu Shiraishi, Yasunori Shintani, Ken Suzuki
Journal: Molecular Therapy (2014)

Transplantation of bone marrow mesenchymal stromal cells (MSCs) is an emerging treatment for heart failure. We have reported that epicardial placement of MSC-sheets generated using temperature-responsive dishes markedly increases donor MSC survival and augments therapeutic effects in an acute myocardial infarction (MI) model, compared to intramyocardial (IM) injection. This study aims to expand this knowledge for the treatment of ischemic cardiomyopathy, which is likely to be more difficult to treat due to mature fibrosis and chronically stressed myocardium. Four weeks after MI, rats underwent either epicardial MSC-sheet placement, IM MSC injection, or sham treatment. At day 28 after treatment, the cell-sheet group showed augmented cardiac function improvement, which was associated with over 11-fold increased donor cell survival at both days 3 and 28 compared to IM injection. Moreover, the cell-sheet group showed improved myocardial repair, in conjunction with amplified upregulation of a group of reparative factors. Furthermore, by comparing with our own previous data, this study highlighted similar dynamics and behavior of epicardially placed MSCs in acute and chronic stages after MI, while the acute-phase myocardium may be more responsive to the stimuli from donor MSCs. These proof-of-concept data encourage further development of the MSC-sheet therapy for ischemic cardiomyopathy toward clinical application. Transplantation of bone marrow mesenchymal stromal cells (MSCs) is an emerging treatment for heart failure. We have reported that epicardial placement of MSC-sheets generated using temperature-responsive dishes markedly increases donor MSC survival and augments therapeutic effects in an acute myocardial infarction (MI) model, compared to intramyocardial (IM) injection. This study aims to expand this knowledge for the treatment of ischemic cardiomyopathy, which is likely to be more difficult to treat due to mature fibrosis and chronically stressed myocardium. Four weeks after MI, rats underwent either epicardial MSC-sheet placement, IM MSC injection, or sham treatment. At day 28 after treatment, the cell-sheet group showed augmented cardiac function improvement, which was associated with over 11-fold increased donor cell survival at both days 3 and 28 compared to IM injection. Moreover, the cell-sheet group showed improved myocardial repair, in conjunction with amplified upregulation of a group of reparative factors. Furthermore, by comparing with our own previous data, this study highlighted similar dynamics and behavior of epicardially placed MSCs in acute and chronic stages after MI, while the acute-phase myocardium may be more responsive to the stimuli from donor MSCs. These proof-of-concept data encourage further development of the MSC-sheet therapy for ischemic cardiomyopathy toward clinical application.
Mechanoelectric feedback (transduction) in heart: concepts and implications
Authors: M. J. Lab
Journal: Cardiovascular Research (1996)

It seems that one could regard mechanoelectric feedback in normal heart as an intrinsic regulatory process that modulates normal electromechanical interactions (Fig. 6, left loop). Any physiological mechano-electro-mechano perturbation is self-adjusting and homeostatic. This preserves the status quo, or the heart adapts to form a new electro-mechanoelectric situation. The position in cardiac pathology is different (Fig. 6, right loop), particularly if the disease process produces inhomogeneities. A premature ventricular contraction can be mechanically induced by several of the accepted electrophysiological arrhythmic mechanisms. Thereafter, instantaneous feedback develops within and between regional heterogeneous mechanical conditions. These non-linear recovery processes compound interacting non-linear time courses of recovery of restitution and excitability. Changes in initial loading or mechanical conditions could initiate arrhythmia. Both mechanical and electrical inhomogeneities (also diagrammed in Fig. 5) compound the situation in the intact ventricle. This would enable a milieu of altered excitability, arrhythmogenic current flow and re-entry, to sustain the arrhythmia.
Utilization of pheromones in the population management of moth pests.
Authors: R T Cardé
Journal: Environmental Health Perspectives (1976)

Pheromones are substances emitted by one individual of a species and eliciting a specific response in a second individual of the same species. In moths (Lepidoptera) generally females lure males for mating by emission of a sex attractant pheromone comprised of either one or more components. Since 1966 the identification of the pheromone blends of many moth pests has allowed investigations into the use of these messengers for population manipulation. Pheromone-baited traps may be used both to detect pest presence and to estimate population density, so that conventional control tactics can be employed only as required and timed precisely for maximum effectiveness. Attractant traps also can be utilized for direct population suppression when the traps are deployed at a density effective in reducing mating success sufficiently to achieve control. A third use pattern of pheromones and related compounds is disruption of pheromone communication via atmospheric permeation with synthetic disruptants. The behavioral modifications involved in disruption of communication may include habituation of the normal response sequence (alteration of the pheromone response threshold) and "confusion" (inability of the organism to perceive and orient to the naturally emitted lure). Disruption of communication employing the natural pheromone components as the disruptant has been most successful, although nonattractant behavioral modifiers structurally similar to the pheromone components also may prove useful. Possible future resistance to direct pheromone manipulation may be expected to involve the evolution of behavioral and sensory changes that minimize the informational overlap between the natural pheromone system and the pheromone control technique.
George Henry Heyse-Moore
Authors: John Petri, William Notcutt
Journal: BMJ (2007)

George Heyse-Moore was brought up in Exeter, where his father was a general surgeon. He qualified from the Middlesex Hospital in 1970 and specialised in orthopaedics, undertaking his training in the Exeter area.

In 1983 he was appointed consultant orthopaedic surgeon at the James Paget Hospital, Great Yarmouth. His main interests were revision hip surgery and the management of back problems. He enjoyed both elective and emergency surgery.

A few months after he took up his consultant post, his wife, Monica, was killed in a horrific car …