tbuckley/cabot-search huggingface dataset:
Evidence-Based Medicine
Authors: Oliver T. Fein, Mark E. Funk
Journal: JAMA (1997)

Physicians face an overwhelming deluge of new medical information. What should be read? What should be incorporated into practice?<i>Evidence-Based Medicine (EBM)</i>brings "the best evidence from clinical and health care research to the bedside, to the surgery or clinic, and to the community" to help the busy physician. The American College of Physicians and the BMJ Publishing Group jointly publish<i>EBM</i>, a new title based upon the successful<i>ACP Journal Club</i>. The earlier journal covered internla medicine, only wheres<i>EBM</i>expnds its coverge to include general and family practice, surgery, psychiatry, pediatrics, and obstetrics and gynecology as well as internal medicine. Each slim issue of 32 pages (blessedly devoid of pharmaceuticl ads) abstracts and comments on those original and review articles from the biomedicla literature "whose results are most likely to be both true and useful."<i>EBM</i>covers studies on treatment, prevention, diagnosis
Abstract 4581: Pim-1 kinase inhibition in the absence of FLT3 inhibition results in cytostatic effects in acute myeloid leukemia cells
Authors: Karthika Natarajan, Mehmet Burcu, Maria R. Baer
Journal: Cancer Research (2012)

Abstract The serine threonine kinase Pim-1 regulates expression of proteins involved in cell cycle, proliferation, apoptosis and drug resistance. Pim-1 has been identified as a potential therapeutic target in acute myeloid leukemia (AML). Notably, it is overexpressed downstream of FLT3 with internal tandem duplication (ITD), present in 30% of AML cases and associated with adverse treatment outcomes. SGI-1776 is the only Pim inhibitor in clinical testing to date, but testing was discontinued due to QTc prolongation. SGI-1776 has been used in laboratory studies of AML, but is also a FLT3 inhibitor, and effects of Pim-1 and FLT3 inhibition have been difficult to distinguish, particularly in cells with FLT3-ITD. To better characterize the effects of Pim-1 inhibition in AML, we compared SGI-1776 (from SuperGen, Inc., Dublin, CA) with two Pim inhibitors without FLT3 inhibitory activity, SMI-4a and quercetagetin in FLT3-wt and FLT3-ITD cells in 96-hour WST-1 cell viability, flow cytometric cell cycle and apoptosis, colony formation and liquid culture proliferation assays. SGI-1776 had no effect on cell cycle in FLT3-wt cells at concentrations up to 5 μM, and caused apoptosis at 10 μM, while G1 arrest and apoptosis occurred at 100 nM in FLT3-ITD cells, and SMI-4a and quercetagetin did not alter cell cycle nor induce apoptosis in FLT3-wt nor FLT3-ITD cell lines. IC50 (μM) comparisons are summarized below: In liquid culture assays, all three Pim inhibitors slowed proliferation of all cell lines, indicating a cytostatic effect. Thus FLT3 inhibition plays a substantial role in the cellular effects of SGI-1776, and Pim inhibitors without FLT3 inhibitory activity appear to have primarily cytostatic effects in AML cells. Other Pim kinase inhibitors in development should be characterized with regard to pro-apoptotic versus cytostatic effects. 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 4581. doi:1538-7445.AM2012-4581
L-Thyroxine Dosage: A Reevaluation of Therapy with Contemporary Preparations
Authors: JAMES V. HENNESSEY
Journal: Annals of Internal Medicine (1986)

Traditional L-thyroxine dosing formulas may overestimate the thyroid hormone requirement in patients treated with contemporary L-thyroxine preparations. We did clinical and laboratory assessments of 41 patients treated in successive periods with Levothroid (Armour Pharmaceuticals, Kankakee, Illinois) and Synthroid (Flint Division, Travenol Laboratories, Morton Grove, Illinois), obtaining 87 sets of data. Clinical subgroups were defined on the basis of the thyrotrophin response to thyrotrophin-releasing hormone. Normal responses were seen in 9 of 14 (64%) patients taking 100 µg/d and were associated with an average replacement dosage of 127 µg/d (1.7 µg/kg body weight). Nine of twenty-eight (32%) serum thyroxine values in the "physiologically replaced" group were elevated. Forty-three of fifty-four (80%) patients ingesting 125 µg or more had blunted responses (thyroxine "overreplaced"), averaging a daily dosage of 154 µg (2.14 µg/kg · d). No significant difference was found between Levothroid and Synthroid in predicting clinical group assignment. Guidelines for currently available L-thyroxine preparations should be revised and the recommended dosage reduced.
Converting tumors into vaccine manufacturing factories: DC recruitment, activation and clinical responses with a flt3L-primed in situ vaccine for low-grade lymphoma [nct01976585]
Authors: Nina Bhardwaj, Miriam Merad, Seunghee Kim-Schulze, Beth Crowley, Thomas Davis, Tibor Keler, Andres Salazar, Joshua Brody
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Lymphomas are the 5th most common cancer in the U.S. and the most prevalent amongst these, low-grade B cell lymphomas are incurable with standard therapy. Previously, we completed three trials combining low-dose radiotherapy (XRT) with intratumoral administration of a TLR9 agonist
Processus Supracondylaris Humeri
Authors: Franck Billmann
Journal: New England Journal of Medicine (2010)

A 24-year-old man presented with a 6-month history of paresthesia and numbness of the right hand. On clinical examination, paresthesia in the region of the right median nerve was elicited on elbow extension. Radiography of the right elbow revealed a supracondylar process of the humerus (processus supracondylaris humeri) (arrow). A supracondylar process of the humerus is an outgrowth of bone originating from the anterior–medial cortex of the distal humerus. It occurs in approximately 0.4 to 2.0% of whites and less frequently in blacks. It can measure up to 20 mm in length and is a congenital human anatomical variation that . . .
Abstract 1437: Polymorphisms in the Estrogen Receptor Genes and Endothelium-Dependent Vasodilation in Elderly
Authors: Erik Ingelsson, Ann-Christine Syvänen, Lars Lind
Journal: Circulation (2007)

Background: Single nucleotide polymorphisms (SNPs) in the estrogen receptor 1 ( ESR1 ) and 2 ( ESR2 ) genes have been associated with blood pressure, subclinical and overt cardiovascular disease, but their relation to endothelium-dependent vasodilation is unknown. Methods: We evaluated 959 70-year-old participants of the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study, using invasive forearm technique with intra-brachial infusion of acetylcholine (EDV; reflecting vasodilation in resistance arteries), and brachial artery ultrasound to assess flow-mediated vasodilation (FMD; reflecting vasodilation in conduit arteries). We analyzed 25 common SNPs in the ESR1 gene and 5 in the ESR2 gene by minisequencing, and related them to EDV and FMD using multivariable linear regression, adjusting for sex, systolic blood pressure, diastolic blood pressure, pulse rate, anti-hypertensive treatment, total cholesterol, high-density cholesterol, lipid-lowering medication, fasting glucose, anti-diabetic medication, body mass index, current smoking, and prior diagnosis of cardiovascular disease. Haplotypes were estimated using the PHASE software. Results: We observed an association between rs1709183 in the ESR1 gene and EDV (nominal P=0.0012), with a lower EDV in carriers of the minor allele (C). This association remained significant after adjustment for multiple testing (empirical P=0.031, obtained using bootstrap re-sampling). Two ESR1 haplotypes in the block containing rs1709183 were associated with EDV (individual haplotype P=0.0015 and P=0.025); the directions of effect were consistent with the individual SNP analyses. There were no associations between SNPs in the ESR2 gene and EDV with a nominal P=0.01. FMD was not associated with either ESR1 or ESR2 . Conclusions: In our community-based study of elderly, a polymorphism in the ESR1 gene was associated with endothelium-dependent vasodilation in resistance arteries, but not in conduit arteries. Our findings should stimulate to replication and further exploration in other settings.
Silymarin in the Treatment of Patients With Primary Biliary Cirrhosis With a Suboptimal Response to Ursodeoxycholic Acid
Authors: Paul Angulo, Tushar Patel, Roberta A. Jorgensen, Terry M. Therneau, Keith D. Lindor
Journal: Hepatology (2000)

Ursodeoxycholic acid (UDCA) is a safe and effective medical therapy for most patients with primary biliary cirrhosis (PBC), but some patients show an incomplete response. Silymarin is a potent antioxidant with immunomodulatory and antifibrotic properties. The aim of this study was to evaluate the safety and assess the efficacy of silymarin in patients with PBC who had shown a suboptimal response to UDCA. Twenty–seven patients with PBC who had been on UDCA (13–15 mg/kg/day) therapy for 7 to 221 months and had shown a persistent elevation of alkaline phosphatase activity at least 2 times the upper limit of normal for more than 6 months were enrolled. Oral silymarin, 140 mg 3 times daily was given for 1 year, and patients continued on the same dosage of UDCA. No significant changes in serum alkaline phosphatase activity (897 ± 84 vs. 876 ± 95, P = .5), total bilirubin (0.9 ± 0.1 vs. 1 ± 0.1, P = .07), aspartate transaminase (AST) (58 ± 5 vs. 56 ± 6, P = .4), albumin (4.0 ± .06 vs. 4.1 ± .06, P = .4), or Mayo risk score (3.82 ± 0.2 vs. 3.88 ± 0.2, P = .4) were noted after 1 year of treatment with combination therapy. Transitory gastrointestinal adverse events occurred in 2 patients. In conclusion, although silymarin was well tolerated, this medication did not provide benefit to patients with PBC responding suboptimally to UDCA. The results of this pilot study would seem to discourage further controlled trials of silymarin in patients with PBC.
TV≠TV≠TV≠TV
Authors: Leo L. Leveridge
Journal: JAMA (1972)

Let the literary critics and the horticultural experts argue the merits of Gertrude Stein's well-known "rose is a rose is a rose is a rose." Medical educators, however, and especially those who do research in medical education, should not blandly assume that a "movie is a movie is a movie is a movie" nor that "TV is TV is TV is TV." This false assumption has contaminated much consideration and most research into the value of media in education. Reports of studies fail to indicate whether the samples used are typical of their medium or whether they are superior. On the contrary, there are clues that discrimination, based on thorough knowledge of the media including their potentials and limitations, was lacking. A common example is when students' learning from a motion picture recording of a lecture is compared with their learning from a classroom lecture on the same topic. "No
METHYL-PHENIDYLACETATE HYDROCHLORIDE (RITALIN) IN THE TREATMENT OF CHRONIC SCHIZOPHRENIC PATIENTS
Authors: BLAINE CAREY, MARILYN WEBER, JACKSON A. SMITH
Journal: American Journal of Psychiatry (1956)

In this group of 50 chronic schizophrenic patients, half of whom received Ritalin and half an identical appearing placebo the Ritalin was without demonstrable effect. Six of those on Ritalin showed a decrease in appetite, abdominal discomfort, and weight loss during the test.
Authors' reply to Graudal and Jurgens
Authors: F. P. Cappuccio, S. Capewell, P. Lincoln, K. McPherson
Journal: BMJ (2011)

Graudal and Jurgens’s first statement is incorrect.1 The TOHP Trial, for example, was carried out on a background of a contemporary American diet with an average baseline daily sodium intake of 150-180 mmol. An average moderate reduction of 33-44 mmol/day reduced cardiovascular disease outcomes by 52% and 21% and all cause mortality by 24% and 17% at 18 months and 3-4 years, respectively. 

The Belgian study achieved no difference in salt intake, so unsurprisingly no effect was seen on measured …
Anticoagulants in Infarction
Authors: John S. Gilson
Journal: JAMA (1973)

<h3>To the Editor.—</h3> The article, "Anticoagulants in Acute Myocardial Infarction" (225:724, 1973) from the Veterans Administration Cooperative Clinical Trial, prompts a question concerning duration and type of limited activity, as well as duration of hospital stay. In our institution it has become common to hospitalize patients in the coronary care unit for three to six days, depending on the finding of arrhythmias or the development of other serious complications of myocardial infarction. In the absence of serious arrhythmias or other complications, the patient may be allowed out of bed with limited activity within the room, even prior to discharge from the unit. After leaving the unit, still in the absence of serious arrhythmia or other complications, the patient may leave the hospital with moderate restriction of activity at home sometime during the second week. It is our impression (and a more serious study is contemplated) that both our in-hospital morbidity
Dendritic cells are crucial for maintenance of tertiary lymphoid structures in the lung of influenza virus–infected mice
Authors: Corine H. GeurtsvanKessel, Monique A.M. Willart, Ingrid M. Bergen, Leonie S. van Rijt, Femke Muskens, Dirk Elewaut, Albert D.M.E. Osterhaus, Rudi Hendriks, Guus F. Rimmelzwaan, Bart N. Lambrecht
Journal: The Journal of Experimental Medicine (2009)

Tertiary lymphoid organs (TLOs) are organized aggregates of B and T cells formed in postembryonic life in response to chronic immune responses to infectious agents or self-antigens. Although CD11c+ dendritic cells (DCs) are consistently found in regions of TLO, their contribution to TLO organization has not been studied in detail. We found that CD11c(hi) DCs are essential for the maintenance of inducible bronchus-associated lymphoid tissue (iBALT), a form of TLO induced in the lungs after influenza virus infection. Elimination of DCs after the virus had been cleared from the lung resulted in iBALT disintegration and reduction in germinal center (GC) reactions, which led to significantly reduced numbers of class-switched plasma cells in the lung and bone marrow and reduction in protective antiviral serum immunoglobulins. Mechanistically, DCs isolated from the lungs of mice with iBALT no longer presented viral antigens to T cells but were a source of lymphotoxin (LT) beta and homeostatic chemokines (CXCL-12 and -13 and CCL-19 and -21) known to contribute to TLO organization. Like depletion of DCs, blockade of LTbeta receptor signaling after virus clearance led to disintegration of iBALT and GC reactions. Together, our data reveal a previously unappreciated function of lung DCs in iBALT homeostasis and humoral immunity to influenza virus.
Cervical cytology screening and government policy.
Authors: S. K. Ross
Journal: BMJ (1989)

Objective-To assess the coverage of cervical cytology screening in one general practice surgery according to the criteria in the new Scottish general practitioner contract and to explore the difficulties of defining performance in such screening.Design-Review of annual analysis of uptake of screening during 1984-8.Setting-Suburban general practice surgery in Glasgow serving 3000 patients.Patients-All women aged 35-64 registered in 1984 increasing in 1988 to all women aged 20-64.Main outcome measure-Assessment of uptake of smear tests and reasons for smear not being taken and of the effect of these outcomes on the new general practitioner contract.Results-The numbers and percentages of women having a smear test in the previous five and three years were recorded, and the reasons why a smear was not taken were defined in the remainder (hysterectomy, test not offered, risk not known, test declined, patient moved away, and patient un- accounted for).In 1988, 85% (608/719) of the women aged 30-64 and 80% (693/870) of those aged 20-64 had had a smear test in the previous five years.An appropriate or irreducible reason for the lack of a smear test was defined in all the others.Conclusions-The population studied contained a substantial number of women in whom cervical smear was unnecessary, inappropriate, or refused.These factors and the likely demographic variation in the uptake of smear tests have important implications for the setting and achieving of the government's targets for cervical cytology screening.
FDA Guidance on Off-Label Promotion and the State of the Literature From Sponsors
Authors: Bruce M. Psaty, Wayne Ray
Journal: JAMA (2008)

ALTHOUGH THE US FOOD AND DRUG ADMINISTRAtion (FDA) reviews and approves drugs for specific indications, the approval does not usually limit the use of those drugs in clinical practice. Indeed, prescribing for indications not reviewed by the FDA (“off-label”) is common. In a recent study of 160 frequently prescribed drugs, off-label use represented 21% of drug mentions, and 73% of these off-label uses had little or no scientific support. Off-label use has long been controversial because large numbers of patients may receive drugs that have had only limited testing for efficacy and safety, and some off-label uses may eventually be shown to have an unfavorable risk-benefit profile. High-profile examples include the use of the combination of fenfluramine and phentermine by millions of persons for weight loss and the widespread use of hormone therapy by postmenopausal women to prevent coronary artery disease. Although the FDA does not restrict physician prescribing for off-label indications, it does regulate the manufacturer’s promotion for such use. The FDA Modernization Act of 1997 permitted sponsors to disseminate peer-reviewed studies from scientific journals about off-label uses that had been or would form part of a supplementary New Drug Application (sNDA). These provisions expired in September 2006 with the result that current law prohibits any promotion of a drug for unapproved uses. Recently, the FDA proposed new guidelines that enable sponsors to distribute publications about unapproved uses of approved drugs and devices. For drugs, for example, an sNDA is no longer required. The journal that published the article to be distributed must have both an editorial board that uses independent reviewers and a policy of full disclosure of conflict of interest; the article must be peer-reviewed; and the article should not be in a supplement funded by the sponsor. The information should address adequate and well-controlled clinical investigations and not be false, misleading, or pose a significant threat to health. Distribution is to include the product label, a relevant bibliography, and a representative publication, if it exists, that reaches a different conclusion about the unapproved use. Are these proposed changes consistent with the FDA’s mission of protecting the public health by ensuring the efficacy and safety of medications? Although peer-reviewed literature serves as the gold standard for evidence-based medicine, there are major limitations in relying on sponsordistributed literature to regulate off-label use, including the selective publication of studies, the systematic manipulation of the literature, the absence from the literature of critical data necessary for evaluating off-label use, and the potential for undermining the NDA review process.
Antibiotics and acute purulent rhinitis: Are antibiotics effective for acute purulent rhinitis?
Authors: Joanne Rimmer, John Almeyda
Journal: BMJ (2006)

EDITOR—Arroll and Kenealy conclude that antibiotics are probably effective for acute purulent rhinitis but suggest that most patients will get better without them and hence advocate a “no antibiotics as first line” treatment plan.1 Their systematic review looked at seven studies comparing placebo with antibiotic treatment for “acute purulent rhinitis” and defined acute as “less than 10 days with this symptom.” They considered all papers …
Scarlet Fever and Tonsillitis in Relation to Acute Rheumatism
Authors: T. C. Macdonald
Journal: BMJ (1950)

While the infectious nature of rheumatic fever was lated by Hirsch the aetiologic agent is still not positively identified.The various hypotheses have been set forth by Hadfield and Garrod (1947), who say: It seems to us indisputable that more progress has been made towards identifying haemolytic streptococci as the cause of disease than in any other direction."Galabin (1932) and Longstaff showed the rzlationship between mortality rates of rheumatic fever, erysipelas, scarlet fever, septicaemia, and puerperal fev er. Atwater 1927) published similar figures.Accurate morbidity figures are not so easy to obtain.It was'felt, therefore, that some information might be drawn from R.A.F. and W.A.A.F.sickness records, as these had certain advantages not usually found.The numbers were large, the population at risk was known, medical care was at all times easy of access, and the recording system is well tried.There is no difference in nutrition, whether in quality or in quantity of food; clothing is identical, and living conditions vary very little.There is a rough standardization for age by the fact that children, adolescents, and the aged are not in the Service.The figures for the sexes are given separately.On the other hand, one condition which facilitates infectiotT by Streptococcus pyogenes is present.This is the communal living and, in particular, sleeping in barrack rooms.Other factors are overcrowding and constant influx of newcomers into each little community.I will consider only figures for the Forces in this country.
Can we equate iconic memory with visual awareness?
Authors: Rogier Landman, Ilja G. Sligte
Journal: Behavioral and Brain Sciences (2007)

Abstract Every time we look around we can see a rich and detailed world surrounding us. Nevertheless, the majority of visual information seems to slip out of our thoughts instantly. Can we still say that this fleeting percept of the entire world was a conscious percept in the first place, as Block proposes?
Misdiagnosis raises questions about extent of avian flu epidemic
Authors: Jane Parry
Journal: BMJ (2005)

The illness of a Vietnamese boy who died from the H5N1 strain of avian influenza last year was not correctly diagnosed at the time because he had not developed the severe respiratory symptoms normally associated with the disease.

That the actual cause of his death was not identified at the time suggests that the prevalence of avian flu in South East Asia was underestimated, experts from the World Health Organization say.

The 4 year old boy was admitted to hospital on 12 February 2004 with severe diarrhoea. An x ray film of his chest was normal. Three days later he became drowsy …
Clinical features of asthmatic patients with increased urinary leukotriene E4 excretion (hyperleukotrienuria)Involvement of chronic hyperplastic rhinosinusitis with nasal polyposis
Authors: Noritaka Higashi, Masami Taniguchi, Haruhisa Mita, Yukio Kawagishi, Toyota Ishii, Ai Higashi, Mitsuhiro Osame, Kazuo Akiyama
Journal: Journal of Allergy and Clinical Immunology (2004)
Age Cutoffs for Bioprosthetic vs Mechanical Aortic Valve Replacement—Reply
Authors: Joanna Chikwe, Natalia N. Egorova, David H. Adams
Journal: JAMA (2015)

In Reply Dr Head and colleagues outline 3 misconceptions on which a preference for mechanical valves in younger patients has historically been based: (1) the mortality risk attributed to bioprosthetic valve degeneration; (2) the effect of reoperation; and (3) the durability of mechanical valves.