tbuckley/cabot-search huggingface dataset:
Dissemination of Information on Potentially Fatal Adverse Drug Reactions for Cancer Drugs From 2000 to 2002: First Results From the Research on Adverse Drug Events and Reports Project
Authors: Lisa A. Ladewski, Steven M. Belknap, Jonathan R. Nebeker, Oliver Sartor, E. Allison Lyons, Timothy C. Kuzel, Martin S. Tallman, Dennis W. Raisch, Amy R. Auerbach, Glen T. Schumock, Hau C. Kwaan, Charles L. Bennett
Journal: Journal of Clinical Oncology (2003)

To describe the clinical findings, occurrence rates, causality evidence, and dissemination media for serious cancer drug-associated adverse drug reactions (ADRs) reported in the postmarketing setting.ADRs were termed serious if they resulted in death or severe organ failure. ADR information for oncology drugs from package insert (PI) revisions, so-called Dear Doctor letters, and journal articles was evaluated to identify serious ADRs reported from 2000 to 2002. Timing and content of information disseminated was assessed.Twenty-five serious ADRs associated with 22 oncology drugs were identified after approval. Approximately half of these serious ADRs are associated with drugs approved before 1995. ADRs were described in articles in medical journals (17 ADRs), PI revisions (18 ADRs), and Dear Doctor letters (12 ADRs). PI revisions occurred less than 1 year after peer-reviewed publication for four ADRs. These revisions often differed for similar ADRs that occurred with drugs of the same class. Five of the seven ADRs lacking PI changes occurred with off-label use, for which PI change is not recommended by US Food and Drug Administration (FDA) policy. No cancer drug was withdrawn from the market during the observation period.Our findings demonstrate that serious ADRs may be discovered as long as 36 years after a drug receives FDA approval. This suggests a need for continued vigilance and efficient strategies for dissemination of information about ADRs associated with cancer drugs.
Leeds students are angry at lack of information about final results delay
Authors: A. Ellis
Journal: BMJ (2003)

Final examination results at Leeds University were delayed by eight days, it emerged this week. Final year students were told by email that allegations of cheating had been made and that their results would be published the next week, pending an investigation.

The university had been made aware of a course run by a local GP and preregistration house officer who had paid former students to remember multiple choice questions that had been in the previous year's paper. Final year students who had been on this course were deemed to be at an advantage, and students who had not been on the course complained.

The university marked the paper for a …
John Chalmers DaCosta
Authors: Lawrence Parsons
Journal: JAMA (1963)

<h3>To the Editor:</h3> —The "Reflections on John Chalmers DaCosta" by Dr. Benjamin Lipshutz, of Philadelphia (<i>JAMA</i><b>181</b>: adv p 218 [Aug 18] 1962), is fascinating and most interesting, and I would like to add a personal observation. When I was a medical student in 1920, Dr. Wilburn Smith (FRCS, Edinburgh) was one of our clinical professors of surgery. He had been one of Dr. DaCosta's students and was a Rhodes scholar. He, himself, was not only a very fine surgeon and also a remarkably fine lecturer, he was a great admirer of his former teacher, as well. He told us the following story: One day DaCosta took a group of his "boys" to the bedside for their visual inspection of a greatly emaciated man with a markedly distended abdomen. They were not permitted to touch the patient or ask him any questions. DaCosta's purpose was to instruct them in the
Abstract 3961: Chemotherapy treatment induces an Interleukin-6 deficit in the bone marrow microenvironment
Authors: Stephanie Rellick, Debra Piktel, Cheryl Walton, Heather O'Leary, Sreekumar Othumpangat, Brett Hall, Michael Craig, Laura F. Gibson
Journal: Cancer Research (2010)

Abstract Bone marrow stromal cells (BMSC) are a critical component of the microenvironment that supports hematopoiesis, and hematopoietic recovery following bone marrow transplantation. Aggressive chemotherapy not only affects tumor cells, but also influences structural and functional components of the microenvironment, including BMSC and osteoblasts. Successful stem cell or bone marrow transplantation following immuno-suppressive or myeloablative chemotherapy is dependent on the ability of BMSC, and other cellular components of the microenvironment, to maintain their functionality. This includes secretion of soluble factors and expression of cellular adhesion molecules that are critical for the survival, proliferation, and differentiation of immature progenitor cells. In the current study, we have investigated the effects of chemotherapy treatment on BMSC and human osteoblast (HOB) expression of Interleukin-6 (IL-6). IL-6 is a pleiotrophic cytokine which has diverse effects on hematopoietic cell development. The treatment of BMSC or HOB with Melphalan or VP-16, which are clinically relevant drugs used in pre-transplant regimens, led to decreased IL-6 protein expression. This decrease in IL-6 protein is unique to Melphalan, as treatment with other chemotherapeutic agents does not result in a similar decrease in IL-6 protein. We have also observed a decrease in gp130, the transmembrane protein necessary for IL-6 signaling, in response to Melphalan treatment, but not VP-16 treatment. Additionally, pre-treatment of BMSC and HOB with Z-VAD-FMK or Leupeptin, a broad range caspase inhibitor and lysosomal inhibitor respectively, prior to chemotherapy treatment was not able to blunt the decrease in IL-6 protein detected in cell supernatants. These data suggest chemotherapy is not enhancing the degradation of IL-6 protein through caspase or lysosomal mediated mechanisms, but rather blunting the overall expression of IL-6. Melphalan treatment is also able to decrease IL-6 mRNA and further investigation is necessary to determine the mechanism by which chemotherapy affects transcription of IL-6. Collectively, these observations suggest that chemotherapy treatment induced alteration of bone marrow microenvironment function, which results in decreased or defective hematopoietic support of human embryonic stem cells and early progenitor cells may result, in part, from an IL-6 deficit. 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 3961.
Are British Physicians Agents of the State?-Reply
Authors: Fredrick R. Abrams
Journal: JAMA (1987)

<h3>In Reply.—</h3> I am sorry that Dr O'Malley inferred from my remarks that the point of my commentary was to contrast the health delivery systems and the morality of American physicians with that of their British colleagues. I was in fact lamenting the trend for physicians of both countries to abandon the traditional role of patient advocacy by accepting the role of fiscal gatekeeper for whomever pays the bill—whether it be a government or a private health care enterprise. If the president of the British Kidney Association was neither accurate nor representative when he said, "Usually the patient does not understand that he could have been treated and goes away to die quietly," then I am glad. I can only reiterate that "if the physician fails to inform because a beneficial treatment is politically (economically) unavailable, he has deceived the patient by implying a medical decision, not a political decision,
Noninvasive Neurovascular Tests for Carotid Artery Disease
Authors: RANDALL D. CEBUL
Journal: Annals of Internal Medicine (1982)

Indirect noninvasive neurovascular tests provide information on hemodynamic changes cephalad to the carotid bifurcation, whereas direct tests measure anatomic or physiologic changes at the bifurcation itself. Batteries of tests are often done and should combine both indirect and direct methods. Results with two ultrasonic techniques and digital subtraction intravenous angiography suggest a larger role for these methods. Carotid arteriography is the definitive procedure for evaluating the carotid artery, although it should only be done when carotid endarterectomy is contemplated. The relative risks and benefits of other diagnostic and therapeutic management strategies should guide the decision to do noninvasive neurovascular tests, or to proceed directly to arteriography.
Disorders of the Respiratory Tract in Children
Authors: Thomas C. Peebles
Journal: JAMA (1967)

This magnificent attempt to garner, from a host of well-known authorities, current facts, theories, and opinions about respiratory diseases in children and put them together in a readable, orderly presentation for practicing physicians is an excellent achievement. Certainly, the book is a must for those practicing pediatrics who finished their training more than five years ago, and it ought to be available as standard reference in community hospitals and teaching centers alike.  The book starts logically, if a bit heavily, with basic physiology, which in the respiratory area has seen many advances in the past decade. It then proceeds through several excellently documented chapters on general approach to the patient, diagnostic and therapeutic procedures, and considerations in the newborn. These set the stage for an exhaustive general-organ recital and further chapters on etiology. Like many texts of its kind compiled from numerous contributors, there is moderate variation in quality and
Radiation Induced Skeletal and Soft Tissue Bone Scan Changes
Authors: FRANK VIERAS
Journal: Clinical Nuclear Medicine (1977)

Intense thoracic soft tissue uptake and decreased bone uptake of 99 mTc-Sn-polyphosphate were demonstrated in a patient who had undergone 60Co radiotherapy for carcinoma of the lung. The changes are attributed to radiation effects and the distinction is made between tumor uptake in the chest and radiation induced increased soft tissue accumulation of the tracer.
Passing the contractual buck
Authors: D. Florin, S. Gillam
Journal: BMJ (2001)

Negotiations for a new contract for British general practitioners have begun. Following an announcement in July by Alan Milburn, the secretary of state for health, ministers and civil servants of the department of health no longer negotiate the terms of the national contract directly with general practitioners.1 NHS managers, represented by the NHS Confederation, now have this role.

This change took everyone in the general practice community by surprise, but it might just break the longstanding stalemate between the government and the medical profession. Currently, general practitioners are plumbing new depths of despair with their workload, with New Labour's consumerist vision for the NHS, and with the constant references to medical failures from Shipman to Bristol. While politicians assert sympathy with the position of health professionals, they have set up a host of new mechanisms to increase their control over doctors in the NHS. The lay press alternately paints a picture of special pleading by greedy doctors and exhausted caring professionals struggling to keep afloat in a system stretched to breaking point. In a pre-election ballot, over 80% of general practitioners who voted said they would be prepared to consider resigning from the NHS should the government fail to agree contractual changes with their leaders.2

Reform of primary care is linked intimately to …
A 13-year-old female with shortness of breath and pleuritic chest pain
Authors: S. Aliberti, M. Falleni, P. Tarsia, G. Vago, P. Zerbi, M. Barberis, V. Valenti, F. Blasi
Journal: European Respiratory Journal (2006)

A 13-yr-old Caucasian female was referred to the Dept of Paediatric Diseases (Havana, Cuba) with shortness of breath and pleuritic chest pain located in her right hemithorax.The pain had occurred the day before while doing physical activity and lasted ,1 h.The patient reported a 2-month history of recurrent episodes of pleuritic chest pain, which were either self-limited or relieved by paracetamol, as well as growing fatigue in the previous few weeks.Her past history was remarkable for a diagnosis of pneumonia after exposure to fumigation during a dengue haemorrhagic fever epidemic 2 yrs earlier, which was treated with steroids and antibiotics.On admission, the patient had no weight loss, no fever or dyspnoea.Physical examination showed decreased breathing sounds in the inferior part of both hemithoraces.Cardiovascular, abdominal and neurological examination, as well as ear, nose and ophthalmologic investigations were
Probenecid and Gum Soreness
Authors: D. N. Golding
Journal: BMJ (1964)

MEDILlHdue to neuromuscular block of respiratory muscles, since they could have completely recovered.With the existing knowledge, could I suggest another explanation of the events in the case reported by Dr. Ross and his colleagues ?The presence of curare-like block on E.M.G. could be due to recurarization as a result of 180 mg. of gallamine, used in a patient with poor circulation, poor renal function, and a very low serum calcium level.The respiratory inadequacy at the end of operation in spite of 2.5 mg. of neostigmine could be attributed to the existence of metabolic acidosis, maintained and accentuated by superadded respiratory acidosis with or without partial recurarization.Oral neomycin has a distinct advantage of its own in the prevention of complications after elective surgery on the colon ; therefore, before surgeons can accept the suggestion that "neomycin should be kept to a minimum" more convincing proof is required.-Iam, etc.,
A Clinical Correlative Study of the Electrocardiogram in Electrolyte Imbalance
Authors: L. S. DREIFUS, A. PICK
Journal: Circulation (1956)

There is no general agreement concerning the action of specific electrolyte disorders and acid-base balance upon the electrocardiogram nor concerning their interrelationships in this respect. In order to test the validity and limitations of the electrocardiographic diagnosis of such disorders in clinical practice, 133 records on 48 patients with suspected or established electrolyte imbalance were compared with chemical determinations, in part serial. Some difficulties encountered in the electrocardiographic diagnosis of mixed electrolyte disorders, and in the distinction of electrolyte from drug effects, are illustrated.
Perspectives in chemotherapy.
Authors: E F Gale
Journal: BMJ (1973)

The Water for Injection (WFI) System at the Upjohn Company was placed “on stream” in July of 1981. This presentation will discuss the design and operation of it. Although the WFI System at Upjohn is similar to many other systems in the pharmaceutical industry in that it complies with GMP and 3-A guidelines, there are several distinct features. These include separate WFI Product and Rinse systems, a lower circulating temperature, and reheating of water cooled but not used at the points-of-use. Included are descriptions of these features as well as the general design of the generation, storage, and distribution systems. Finally, operating experiences, including start-up, validation, and daily operations, are discussed.
Fallout at Three Mile Island
Authors: HARRY R. MAXON
Journal: Annals of Internal Medicine (1979)

Editorial Notes1 September 1979Fallout at Three Mile IslandHARRY R. MAXON, M.D.HARRY R. MAXON, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-91-3-486 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn the early morning hours of 28 March 1979, operational problems developed in the Three Mile Island Nuclear Station located a few miles south of Harrisburg, Pennsylvania. During the next 5 days, some radionuclides entered the atmosphere either as contaminants of intentional releases of steam and gases designed to lower pressure in the containment vessel or, rarely, as accidental releases. On 12 May 1979, a report on the magnitude of the attendant radiation exposure to the public during the period from 28 March through 7 April 1979 was released by the Ad Hoc Population Dose Assessment Group formed by the...References1. . Population Dose and Health Impact of the Accident at the Three Mile Island Nuclear Station: A Preliminary Assessment for the Period March 28 through April 7, 1979. Washington, D.C.: U.S. Government Printing Office; 1979. Google Scholar2. OAKLEY D. Natural Radiation Exposure in the United States, EPA Report ORP/SID 72-1. Washington, D.C.: U.S. Environmental Protection Agency; 1972. Google Scholar3. . The Effects on Populations of Exposure to Low Levels of Ionizing Radiation. Washington D.C.: National Research Council, National Academy of Sciences; 1972. Google Scholar4. . Sources and Effects of ionizing Radiation: 1977 Report to The General Assembly. New York: United Nations; 1977. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: HARRY R. MAXON, M.D.Affiliations: University of Cincinnati College of Medicine Cincinnati, Ohio PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byRisks of Nuclear PowerLEONARD R. SOLON, PH.D., VICTOR W. SIDEL, M.D. 1 September 1979Volume 91, Issue 3Page: 486-487KeywordsRadiation exposure ePublished: 1 December 2008 Issue Published: 1 September 1979 PDF downloadLoading ...
The Reagan Record on Health Care
Authors: John K. Iglehart
Journal: New England Journal of Medicine (1983)

Two years after assuming power, the Reagan administration has accomplished a number of the major health-policy goals it identified when Republican Ronald Reagan took office: it has introduced a more tight-fisted social contract between the federal government and the citizens that government, by law, is compelled to protect; it has taken a step toward devolving federal health programs to state and local governments; and it has developed a hospital payment scheme that would penalize institutions for their inefficiencies (a scheme discussed in detail in my last two Journal articles1 , 2).The administration also reinforced the policies of its Democratic predecessor . . .
Abstract 5297: Autocrine stimulation of VEGFR-2 by leptin is associated with Notch signaling pathway and cancer stem cell marker expression
Authors: Shanchun Guo, Corey Gillespie, Mingli Liu, Ruben Gonzalez-Perez
Journal: Cancer Research (2012)

Abstract Obesity-related cancer is an increasing health problem. Leptin, the major adipokine, has been suggested a major factor in these relationships. Leptin is a pro-inflammatory, pro-angiogenic and mitogenic factor for breast cancer cells. Recently, we described a comprehensive mechanism for leptin induction of VEGF, and unveiled a novel crosstalk between Notch, IL-1 and leptin (NILCO) in breast cancer. NILCO regulates VEGF/VEGR-2 in breast cancer cells and could represent the integration of developmental, pro-inflammatory and pro-angiogenic signals critical for leptin oncogenic actions. However, the specific mechanisms for leptin-induced VEGFR2 are unknown. To answer this question, we re-cloned mouse VEGFR-2 promoter and prepared VEGFR-2 luc, then analyzed VEGFR-2 regulation and expression by using several kinase inhibitors, leptin peptide antagonist 2 (LPrA2), a VEGFR-2 kinase inhibitor (SU5416), as well as siRNA against VEGFR-2, Notch1, Notch3 in 4T1 cells. Our results demonstrated that leptin-induced JAK2/STAT3, MAPK/ERK 1/2, PI-3K/AKT1, PKC, p38 and JNK signaling pathways may correlate with upregulated VEGFR-2. Moreover, leptin-induced activation of Notch/VEGFR-2 was linked to the upregulation of cancer stem cell markers CD44 and ALDH1. These leptin effects were inhibited by siRNA-Notch1&amp;3, leptin signaling antagonist (PEG-LPrA2), VEGFR2-kinase inhibitor (SU5416) and siRNA-VEGFR-2. Our results show for the first time how leptin's molecular signals regulate VEGFR-2 (an autocrine survival process) that was associated to Notch and cancer stem cell marker expression. These novel findings may help to design new strategies for prevention/treatment of breast cancer through the abrogation of tumor angiogenesis and breast cancer stem cell renewal in an obesity context. [This work was supported in part by NIH/NCI1SC1CA138658-02; NIH/ARRA/3SC1CA138658-02S1 and the Georgia Cancer Coalition Distinguished Cancer Scholar Award (to RRGP)]. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5297. doi:1538-7445.AM2012-5297
Isolating fetal cells in the maternal circulation
Authors: J. Simpson
Journal: Human Reproduction Update (1995)

Fetal cells exist in maternal blood and can be utilized for prenatal genetic diagnosis. The use of polymerase chain reaction (PCR) technology on maternal blood has enabled the detection of fetal sex, Mendelian disorders (e.g. (rβ-globin mutations), HLA polymorphisms and fetal Rhesus (D) blood type. Enrichment for erythro-blasts and trophoblasts by various density gradient and flow sorting techniques followed by fluorescence in-situ hybridization (FISH) with chromosome-specific DNA probes has allowed detection of trisomy 21, trisomy 18, Klinefelter syndrome (47,XXY) and 47,XYY. The fetal cell type that has generated the most success is the nucleated erythrocyte; however, trophoblasts, lymphocytes and granulocytes are also considered to be present in maternal blood. Fetal cells circulate in maternal blood during the first and second trimesters, with frequency increasing as gestation advances. Emphasis is thus now directed toward determining the most practical and efficacious manner for this technique to be applied to prenatal genetic diagnosis. A large scale collaboration of clinical evaluations is underway in the USA, upon completion of which assessment can be made of whether this technology can serve as an alternative to conventional invasive and non-invasive methods of prenatal cytogenetic diagnosis.