tbuckley/cabot-search huggingface dataset:
Will clinical governance make a difference?
Authors: D. R Sandeman
Journal: BMJ (1999)

<h3>Abstract</h3> Microcrystal electron diffraction (MicroED) uses electron cryo-microscopy (cryo-EM) to collect diffraction data from small crystals during continuous rotation of the sample. As a result of advances in hardware as well as methods development, the data quality has continuously improved over the past decade, to the point where even macromolecular structures can be determined <i>ab initio</i>. Detectors suitable for electron diffraction should ideally have fast readout to record data in movie mode, and high sensitivity at low exposure rates to accurately report the intensities. Direct electron detectors are commonly used in cryo-EM imaging for their sensitivity and speed, but despite their availability are generally not used in diffraction. Primary concerns with diffraction experiments are the dynamic range and coincidence loss, which will corrupt the measurement if the flux exceeds the count rate of the detector. Here, we describe instrument setup and low-exposure MicroED data collection in electron-counting mode using K2 and K3 direct electron detectors and show that the integrated intensities can be effectively used to solve structures of two macromolecules between 1.2 Å and 2.8 Å. Even though a beam stop was not used in these studies we did not observe damage to the camera. As these cameras are already available in many cryo-EM facilities, this provides opportunities for users who do not have access to dedicated facilities for MicroED.
Comparison of biomarkers between allergic rhinitis only and allergic rhinitis with concomitant asthma
Authors: W. Y. Wang, J. D. Boot, M. A. Mascelli, R. Gerth van Wijk, Z. Diamant
Journal: Allergy (2009)

This post hoc analysis suggests distinct immunologic profiles in the allergic rhinitis (AR)‐only and the AR &amp; AA phenotypes.
Caspase 3–mediated stimulation of tumor cell repopulation during cancer radiotherapy
Authors: Qian Huang, Fang Li, Xinjian Liu, Wenrong Li, Wei Shi, Fei-Fei Liu, Brian O'Sullivan, Zhimin He, Yuanlin Peng, Aik-Choon Tan, Ling Zhou, Jingping Shen, Gangwen Han, Xiao-Jing Wang, Jackie Thorburn, Andrew Thorburn, Antonio Jimeno, David Raben, Joel S Bedford, Chuan-Yuan Li
Journal: Nature Medicine (2011)
The Hazards of Silicone Injections
Authors: Charles A. Vinnik
Journal: JAMA (1976)

The problems that have followed liquid silicone injections to the breast raise concern about and have implications for use of silicone injections in other sites. Similar clinical problems and histologic skin changes have been reported after silicone injections to the face, extremities, abdomen, and penis, as well as breasts. Facial skin discoloration, induration, and subcutaneous nodule formation may follow silicone injection, but these are relatively minor complications compared with the aesthetic problems that patients with hemifacial atrophy and lipodistrophy may have to endure without treatment by the silicone procedure. There is no argument that the benefits for these patients outweigh potential local risks. Quite the opposite may be true for patients seeking injections merely for cosmetic purposes. Here, the risks may far outweigh any possible benefit. Physicians have assumed that problems associated with silicone injections were caused by adulterated liquid silicone. This is not the case. In Las Vegas and
Cervical lymphadenopathy caused by Aspergillus terreus.
Authors: None Mahgoub el-S, S. A. Ismail, A. M. el-Hassan
Journal: BMJ (1969)

MEDICAL JOHRNAL 689motility disturbance in the colon and minimal changes on electromyography.Other acquired lesions of the colon should be considered in older patients.Chagas's disease is differentiated by its geographical distribution and characteristic histology.Pseudo- obstruction, the so-called colonic ileus, presents a much more acute picture and is reversible (Stephens, 1966 ; Bryk and Soong, 1967).Megasigmoid syndrome may also be diagnosed in older patients who are in mental institutions or who suffer from diabetes mellitus, Parkinson's disease, or traumatic paraplegia (Berenyi and Schwarz, 1967).In these patients disturb- ance of the autonomic nervous system is suspected, but conventionali histological studies are normal.Differentiation from Hirschsprung's disease is helped by the age of onset (though cases presenting in adult life have been recorded), the extent of the lesion, and histological and radiological differences.Patients in whom there is a long segment of agangliosis do not survive the first few years of life without surgical treatment.Treatment.-Among the many adult patients who complain of chronic constipation there will be a few who have adult megacolon, and in some of these the myenteric plexus may be damaged.The role of surgery in their management is still controversial and often disappointing.Resection may appear drastic but is the treatment of choice, since local procedures on the sphincters may not be of permanent benefit, and bypass operations may not prove adequate owing to a failure of progressive movements in the intestine.The extent of the lesion is difficult to assess and cannot always be determined by biopsy, as in Hirschsprung's disease, and so the initial colostomy may fail to function properly if it is affected by the disease, and a further more proximal stoma may be required.
CHADS2 and CHA2DS2-VASc Scoring Systems are not Useful for Predicting Postoperative Atrial Fibrillation after Coronary Artery Bypass Graft Surgery
Authors: Hasan Güngör, Cemil Zencir, Çağdaş Akgüllü, Ufuk Eryılmaz, Tunay Kurtoğlu, Mithat Selvi, Sevil Önay, Mustafa Çetin, Ceyhun Ceyhan, Alper Onbaşılı, Tarkan Tekten
Journal: Journal of the American College of Cardiology (2013)
Neoplastic Angiogenesis — Not All Blood Vessels Are Created Equal
Authors: Isaiah J. Fidler, Lee M. Ellis
Journal: New England Journal of Medicine (2004)

The primary cause of death from cancer is the progressive growth of metastases that are resistant to conventional therapies. The site of metastasis from primary neoplasms is not random. Indeed, in 1889, Stephen Paget proposed that the process of metastasis did not occur by chance but, rather, that certain favored tumor cells (the "seed") had a special affinity for the growth-enhancing milieu within specific organs (the "soil"). He concluded that metastases developed only when the seed and the soil were compatible. Our current version of the seed-and-soil hypothesis consists of two principles. First, neoplasms are heterogeneous: they consist of cells . . .
Public health staff will have pensions invested in tobacco under transfer to local government schemes
Authors: J. Gornall
Journal: BMJ (2013)

NHS public health professionals will have to join the Local Government Pension Scheme if they move post voluntarily when responsibility for public health is transferred from the NHS to local authorities on 1 April.

Only staff who are moved compulsorily to another post within the same local authority, and public health professionals and staff in the 1995 section of the NHS pension scheme who are within 10 years of pension age, will not have to move scheme.1

The decision, reached in December and now confirmed by letter, bears out fears highlighted by the BMJ …
The Clinical and Translational Science Award (CTSA) Consortium and the Translational Research Model
Authors: Alexander A. Kon
Journal: The American Journal of Bioethics (2008)

Click to increase image sizeClick to decrease image size ACKNOWLEDGMENT This publication was made possible by Grant Number UL1 RR024146 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. Information on Re-engineering the Clinical Research Enterprise can be obtained from http://nihroadmap.nih.gov/clinicalresearch/overview-translational.asp
Hyperglycemic Crises in Adult Patients With Diabetes
Authors: Abbas E. Kitabchi, Guillermo Umpierrez, John Miles, Joseph Fisher
Journal: Diabetes Care (2009)

Diabetic ketoacidosis (DKA) is a state of severe diabetic decompensation characterized by uncontrolled hyperglycemia, ketosis, and acidemia. Until recently, the most widely used diagnostic criteria for DKA were a blood glucose >250 mg/dl, an arterial pH <7.30, serum bicarbonate <15 mEq/l, and moderate degree of ketonemia and/or ketonuria (1). Accumulation of ketoacids usually results in an increased anion gap metabolic acidosis. Although these criteria for DKA served well for research purposes, they were somewhat restrictive …
Abstract 3495: Targeting gliomas with a dual kinase inhibitor and stem-cell delivered TRAIL
Authors: Tugba Bagci-Onder, Hiroaki Wakimoto, Maarten Anderegg, Khalid Shah
Journal: Cancer Research (2010)

Abstract Gliomas are difficult to eradicate due to several factors: a) the lack of efficient delivery of anti-tumor agents to the tumors without affecting the normal brain tissue; b) the inherent or acquired resistance of tumor cells to anti-tumor agents; and c) the highly invasive nature of tumor cells that escape the primary tumor mass and subsequently cause recurrence. We previously established that a secreted form of tumor necrosis factor-related apoptosis inducing ligand (S-TRAIL) specifically eradicates glioma cells when delivered by various stem cell types in culture and in orthotopic glioma models. However, recent evidence has shown that a number of established and primary glioma lines have varying degrees of resistance to TRAIL, due to the heterogeneity of genetic alterations and possibly due to the over-activation of phosphatidylinositol 3 kinase (PI3K) pathway. In this study, we report the effect of a novel PI3K inhibitor, PI-103, alone or in combination with neural stem cell (NSC)-delivered S-TRAIL in mouse models of malignant and invasive gliomas. Using established and primary CD133+ glioma initiating cells engineered to express fluorescent and bioluminescent markers, we show that PI-103 alone inhibits proliferation and invasion, and causes G0-G1 arrest in cell cycle of most of the glioma cells tested. Furthermore, PI-103 augments the response of glioma cells to stem cell delivered S-TRAIL in co-cultures of NSCs and glioma cells suggesting that it can synergize with S-TRAIL-induced apoptosis. Using orthotopic malignant glioma models and bioluminescence imaging, PI-103 treatment in combination with NSC-derived S-TRAIL was shown to result in significant reduction in tumor volumes compared to either treatment alone in vivo. Our results reveal that combination of the novel PI3K inhibitor, PI-103, and stem cell delivered TRAIL might represent a novel therapy for malignant gliomas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3495.
High-Dose Tri-Alkylator Chemotherapy With Autologous Stem Cell Rescue in Patients With Refractory Malignancies
Authors: Jill A. Moormeier, Stephanie F. Williams, Lynne S. Kaminer, Miriam Garner, Jacob D. Bitran
Journal: JNCI Journal of the National Cancer Institute (1990)

Forty patients with refractory solid tumors or non-Hodgkin's lymphoma were treated with high-dose cyclophosphamide, thiotepa, and carmustine (BCNU), followed by autologous stem cell rescue, in a phase I dose escalation study. The dose-limiting toxic effect was delayed drug-induced pulmonary disease, seen in three patients who received 660-750 mg of BCNU/m2 in combination with cyclophosphamide and thiotepa. The early death rate due to toxic effects was 20%; all deaths were attributed to sepsis or respiratory failure. The overall response rate was 63%. The median time to disease progression was 14 weeks. Although this regimen provided effective cytoreduction, its use in heavily pretreated patients with bulky disease is of limited value.
Three‐Dimensional Paper‐Based Model for Cardiac Ischemia
Authors: Bobak Mosadegh, Borna E. Dabiri, Matthew R. Lockett, Ratmir Derda, Patrick Campbell, Kevin Kit Parker, George M. Whitesides
Journal: Advanced Healthcare Materials (2014)

In vitro models of ischemia have not historically recapitulated the cellular interactions and gradients of molecules that occur in a 3D tissue. This work demonstrates a paper-based 3D culture system that mimics some of the interactions that occur among populations of cells in the heart during ischemia. Multiple layers of paper containing cells, suspended in hydrogels, are stacked to form a layered 3D model of a tissue. Mass transport of oxygen and glucose into this 3D system can be modulated to induce an ischemic environment in the bottom layers of the stack. This ischemic stress induces cardiomyocytes at the bottom of the stack to secrete chemokines which subsequently trigger fibroblasts residing in adjacent layers to migrate toward the ischemic region. This work demonstrates the usefulness of patterned, stacked paper for performing in vitro mechanistic studies of cellular motility and viability within a model of the laminar ventricle tissue of the heart.
Fifty Hours for the Poor
Authors: George D. Lundberg
Journal: JAMA (1989)

Doctors, lawyers, and the clergy belong to the classic learned professions, which are historically distinguished from trades and businesses. Although this distinction has blurred in modern times, one of the characteristics of a true profession remains its special relationship with the poor. Edmund Pellegrino, director of the Kennedy Institute of Ethics, states that a fundamental difference between a business and a profession is that "at some point in the professional relationship, when a difficult decision is to be made, you can depend on the one who is in a true profession to efface his own self-interest." The privilege to practice law or medicine has carried with it the obligation to serve the poor without pay. Doctors and lawyers today have tended to become overly concerned with their professional incomes and practice efficiencies, but they must not forget their higher duties. Many members of our professions have always cared for the
Mearl F. Stanton: Recollections
Authors: C J Dawe
Journal: JNCI Journal of the National Cancer Institute (1981)

Journal Article Mearl F. Stanton: Recollections Get access Clyde J. Dawe Clyde J. Dawe Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 67, Issue 5, November 1981, Page 963, https://doi.org/10.1093/jnci/67.5.963 Published: 01 November 1981 Article history Received: 30 July 1981 Published: 01 November 1981
Proteomic approach in the search of new cardiovascular biomarkers
Authors: Julio Gallego-Delgado, Alberto Lazaro, Julio J. Osende, Maria M. Barderas, Luis L. Blanco-Colio, Maria Carmen Duran, Jose J. Martin-Ventura, Fernando Vivanco, Jesus Egido
Journal: Kidney International (2005)

With the increasing incidence of cardiovascular diseases worldwide, specifically atherosclerosis and heart failure, the search for novel biomarkers remains a priority. As opposed to complex diagnostic techniques that may not be suitable to be applied to the wider population, biomarkers are useful for population screening. The search for novel biomarkers is based on knowledge of the molecular and cellular processes that take place in the development of a specific disease. Atherosclerosis and heart failure are characterized by a long period of silent disease progression, allowing early diagnosis and the potential of early therapeutic intervention. The use of the so-called proteomic techniques allows not only protein identification but partial characterization, which includes expression and also post-translational modification of these proteins. This allows for the discovery of previously unknown proteins involved in cardiovascular diseases, including some that may be suitable to be used as biomarkers. However, to approach this issue, we have to overcome difficulties such as tissue heterogeneity (vessel wall or myocardium) and the lack of fresh human samples. We discuss the proteomic study of human plaques, secreted proteins by pathologic and normal vessel wall, and left ventricular hypertrophy as potential sources of new biologic markers of cardiovascular disease.
ET-62 * HIGHLY SELECTIVE ACTIVITY OF MDM2 INHIBITOR RG7112 AGAINST MDM2-AMPLIFIED/TP53 WILD-TYPE GLIOBLASTOMAS
Authors: M. Verreault, C. Levasseur, C. Schmitt, J. Guehennec, M. Labussiere, Y. Marie, S. Haidar, K. Mokhtari, K. Hoang-Xuan, M. Sanson, K. Ligon, J.-Y. Delattre, A. Idbaih
Journal: Neuro-Oncology (2014)

Alteration of P53 pathway is one of the key molecular events involved in glioblastoma (GBM) biology. Genetic alterations which reduce TP53 function in GBM include MDM2 amplification (14% of patients), MDM4 amplification (7%), and TP53 gene mutations (35%), each of which is generally thought to be mutually exclusive. The study presented here aims to test the therapeutic activity of RG7112, a member of cis-imidazoline MDM2 inhibitors (Nutlins), in GBM cells according to their functional P53 pathway status. The effect of RG7112 was assessed in a panel of eleven GBM patient-derived cell lines (PDCLs) genetically selected to assess the drug response of the different alterations of P53 pathway. RG7112 was found to be able to induce cell death in all cell lines tested, with the highest cytotoxic efficacy against MDM2/MDM4-amplified GBM PDCL. Indeed, GBM cell lines carrying MDM2 or MDM4 gene amplification were 10 to 20 times more sensitive to the inhibitor than the other lines. TP53 mutant lines were the least sensitive lines. RG7112 treatment restored P53 and P21 protein levels in MDM2-amplified GBM cells. Most importantly, treatment of MDM2-amplified GBM orthotopic patient derived xenograft (PDX) bearing mice with 100 mg/kg RG7112 (Q5Dx3) reduced tumor growth rate and significantly increased survival duration compared to vehicle-treated mice. This data supports the research towards the development of RG7112 for clinical testing in MDM2/4-amplified glioblastoma patients. Studies assessing the capacity of RG7112 compound to cross the blood-brain barrier in healthy and GBM tumor tissue are currently ongoing.
PUERPERAL SEPSIS—LAPAROTOMY.Read by invitation before the Kansas City Academy of Medicine.
Authors: A. H. CORDIER
Journal: JAMA (1893)

For ages the cause of "Puerperal Fever" (which is a symptom—not a disease) was supposed to exist in the atmosphere of the lying-in hospital or chamber; it was believed that the fever was an<i>infectious, contagious disease</i>—that it was not necessary for actual contact to take place. The many opportunities both on the operating table and in the dead room for studying its pathology have cleared up the mystery. As a result of the recognition of its septic character within the last few years, the puerperal woman has been looked upon as a wounded woman and has been treated as such; so it is now a rare occurrence for a woman to have a "bad getting up" after confinement because practitioners recognize the principles of aseptic surgery and apply them intelligently to the treatment of the lying-in woman. With clean hands and surgically clean instruments used by a clean physician
Phase II study of pegylated liposomal doxorubicin, low‐dose dexamethasone, and lenalidomide in patients with newly diagnosed multiple myeloma
Authors: Rachid C. Baz, Kenneth H. Shain, Mohamad A. Hussein, Ji‐Hyun Lee, Daniel M. Sullivan, Elizabeth Finley Oliver, Lisa A. Nardelli, Lisa A. Nodzon, Xiuhua Zhao, Jose Leonel Ochoa‐Bayona, Taiga Nishihori, William S. Dalton, Melissa Alsina
Journal: American Journal of Hematology (2013)

Our previous phase I/II trial of pegylated liposomal doxorubicin (PLD), low-dose dexamethasone, and lenalidomide in patients with relapsed and refractory myeloma showed an overall response rate of 75%, with 29% achieving ≥ VGPR. Here, we investigated this combination (PLD 30 or 40 mg/m(2) intravenously, day 1; dexamethasone 40 mg orally, days 1-4; lenalidomide 25 mg orally, days 1-21; administered every 28 days) in a phase II study in patients with newly diagnosed symptomatic multiple myeloma to determine its efficacy and tolerability (ClinicalTrials.gov NCT00617591). At best response, patients could proceed with high-dose melphalan or with maintenance lenalidomide and dexamethasone. In 57 patients, we found that the overall response rate and rate of very good partial response and better on intent-to-treat, our primary endpoints, were 77.2% and 42.1%, respectively, with responses per the International Myeloma Working Group. Median progression-free survival was 28 months (95% CI 18.1-34.8), with 1- and 2-year overall survival rates of 98.1 and 79.6%. During induction, grade 3/4 toxicities were neutropenia (49.1%), anemia (15.8%), thrombocytopenia (7%), fatigue (14%), febrile neutropenia (8.8%), and venous thromboembolic events (8.8%). During maintenance, grade 3/4 toxicities were mainly hematologic. We found this combination to be active in patients with newly diagnosed myeloma, with results comparable to other lenalidomide-based induction strategies without proteasome inhibition. In addition, maintenance therapy with lenalidomide was well tolerated.
Sexually Transmitted Diseases: The Facts
Authors: Phil Gunby
Journal: JAMA (1980)

It perhaps is a sign of the times that books for the public about the sexually transmitted diseases (sexually transmitted disease having succeeded venereal disease) now are appearing, almost as companion volumes to the countless manuals on love-making techniques. These diseases clearly are major problems in this country, with gonorrhea ranking first and syphilis third among reported communicable diseases here and herpesvirus infections increasing ominously, and physicians may find the European (British) viewpoint of this book interesting. Barlow has not lost his sense of humor in dealing with a serious subject (ie, "Because sexual adventures or misadventures are not the prerogative of the dirty, thick, and ill-educated, a representative cross section of society will be found attending a typical clinic, including barristers, and barmaids, doorkeepers and doctors"), and the illustrations include some cartoons that poke gentle fun at some familiar physician-patient conversations ("It's not for me, doctor. I'm inquiring for
ULTRAVIOLET RADIATION AND ITS TRANSMISSION BY VARIOUS SUBSTANCES
Authors: CHARLES SHEARD
Journal: JAMA (1927)

The range of so-called radiant energy is very broad, extending from radiations having waves which are miles in length, on through radio frequencies, infra-red (popularly called heat), visible, ultraviolet, roentgen and gamma rays until the cosmic rays recently discovered by Millikan are reached. The wave lengths of radiation, other than in the case of electric waves, are generally recorded either in terms of the angstrom unit or in millimicrons. An angstrom unit is one ten-millionth part of a millimeter. The millimicron, mμ, is ten times larger than the angstrom unit, A., and the micron, μ, is 10,000 times greater. In table 1 are given the approximate limits of various spectral regions. The various wave lengths of radiant energy are due to vibrations or oscillations of matter in the molar, molecular, atomic or electronic states. Electric waves are due to molar vibrations, infra-red radiations to disturbances in molecules and atoms, and