tbuckley/cabot-search huggingface dataset:
Is This Patient Allergic to Penicillin?
Authors: Alan R. Salkind, Paul G. Cuddy, John W. Foxworth
Journal: JAMA (2001)

ContextClinicians frequently withhold antibiotics that contain penicillin based on patients' self-reported clinical history of an adverse reaction to penicillin and the clinicians' own misunderstandings about the characteristics of a true penicillin allergy.ObjectivesTo determine the likelihood of true penicillin allergy with consideration of clinical history and to evaluate the diagnostic value added by appropriate skin testing.Data SourcesMEDLINE was searched for relevant English-language articles dated 1966 to October 2000. Bibliographies were searched to identify additional articles.Study SelectionWe included original studies describing the precision of skin testing in diagnosis of penicillin allergy. We excluded studies that did not use both minor and major determinants, provide an explicit definition of penicillin allergy, or list the specific criteria necessary for a positive skin test result. Fourteen studies met the inclusion criteria.Data ExtractionThree authors independently reviewed and abstracted data from all articles and reached consensus about any discrepancies.Data SynthesisPatients' self-reported history has low accuracy for diagnosis of true penicillin allergy. By evaluating studies comparing clinical history to the skin test for penicillin allergy among patients with and without a positive history for penicillin allergy, positive and negative likelihood ratios were calculated. History of penicillin allergy had a positive likelihood ratio of 1.9 (95% confidence interval [CI], 1.5-2.5), while absence of history of penicillin allergy had a negative likelihood ratio of 0.5 (95% CI, 0.4-0.6).ConclusionsOnly 10% to 20% of patients reporting a history of penicillin allergy are truly allergic when assessed by skin testing. Taking a detailed history of a patient's reaction to penicillin may allow clinicians to exclude true penicillin allergy, allowing these patients to receive penicillin. Patients with a concerning history of type I penicillin allergy who have a compelling need for a drug containing penicillin should undergo skin testing. Virtually all patients with a negative skin test result can take penicillin without serious sequelae.
Genetic diversity of noroviruses from outbreaks, sporadic cases and wastewater in Luxembourg 2008–2009
Authors: J.R. Kremer, J. Langlet, S. Skraber, P. Weicherding, B. Weber, H.-M. Cauchie, S. De Landtsheer, J. Even, C.P. Muller, L. Hoffmann, J. Mossong
Journal: Clinical Microbiology and Infection (2010)
Ritonavir-boosted lopinavir plus nucleoside or nucleotide reverse transcriptase inhibitors versus ritonavir-boosted lopinavir plus raltegravir for treatment of HIV-1 infection in adults with virological failure of a standard first-line ART regimen (SECOND-LINE): a randomised, open-label, non-inferiority study
Authors: M A Boyd, N Kumarasamy, C L Moore, C Nwizu, M H Losso, L Mohapi, A Martin, S Kerr, A H Sohn, H Teppler, O Van de Steen, J-M Molina, S Emery, D A Cooper
Journal: The Lancet (2013)
A pilot study to detect airflow obstruction in smokers using spirometry in a local GP surgery
Authors: Bhupinder Mann, Essam Ramhamadany, Lesley Seddon, Emma Loveridge, Angela Glennon
Journal: European Respiratory Journal (2011)

COPD is under diagnosed worldwide. In our locality, it is thought that a fifth of all COPD cases have been identified.   Aim:  To carry out a pilot study to screen smokers and ex-smokers in a local GP practice with spirometry to allow earlier COPD diagnosis.   Methodology:  Over a 7 month period, subjects were identified from a GP practice database. The target population included smokers/ex-smokers over the age of 35 who had smoked a minimum of 10 pack years; recurrent or chronic respiratory symptoms; occupational exposure to respiratory irritants or family history of COPD. Patients known to have COPD or asthma were excluded.  Appropriate subjects completed a short questionnaire. Severity of airflow obstruction (AFO) was assessed using the UK NICE COPD 2004 guidelines: mild AFO FEV1 50-79% predicted, moderate AFO FEV1 30-49% predicted, severe AFO FEV1    Results:  Out of 5,500 patients, 723 subjects were contacted and 203 had spirometry. In total 169 subjects had reliable spirometry which showed normal results in 80 patients (47.3%). AFO was present in 32/169 (18.9%-using NICE criteria). A further 50/169 (corresponding to GOLD stage 1 disease but not in the NICE guidelines) may be at risk giving a figure of 48.4% with AFO and possible COPD.Out of 92 patients who completed the questionnaire, 71 (77.1%) had not heard of COPD and 51% had respiratory symptoms.   Conclusion:  Proactive screening of smokers with spirometry can increase COPD identification. We are planning to roll this project out using the new NICE COPD 2010 guidelines, which require post bronchodilator spirometry values.  This project was funded by Astra Zenica pharmaceutical company.
Proteomics and the Kidney
Authors: Mark A. Knepper
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Proteomics can be defined as “the systematic analysis of proteins for their identity, quantity, and function.” The central concept is “multiplexing,” i.e. , simultaneous analysis of all proteins in a defined protein population, rather than investigation of one protein at a time, as in traditional biochemistry. Two major approaches have been described: ( 1 ) mass spectrometry-based approaches and ( 2 ) protein micro-array approaches. The purpose of this Science Watch article is to describe the fundamental features of these two approaches and to speculate on how proteomics will be useful in nephrology and nephrology research in the coming years.
Abstract 19100: Medication Initiation Burden Required to Comply with Hospital Quality Measures for Heart Failure
Authors: Larry A Allen, Gregg C Fonarow, Li Liang, Phillip Schulte, Frederick A Masoudi, John S Rumsfeld, Michael Ho, Zubin J Eapen, Adrian F Hernandez, Paul A Heidenreich, Deepak L Bhatt, Eric D Peterson, Harlan M Krumholz
Journal: Circulation (2014)

Background:  Quality measures assess whether patients discharged from the hospital with heart failure (HF) are prescribed evidence-based medical therapies. The number of new medications indicated and actually prescribed, and the related burden for patients, has not been well described.   Methods:  Using data from 373 hospitals participating in Get With The Guidelines-HF registry between 2005-2013, we calculated the difference between the patient’s medication regimen at the time of admission and what would be recommended by current guidelines and quality measures at the time of discharge, as well as the number of new HF medications actually prescribed at discharge. Indications and contraindications were collected for angiotensin converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB), beta-blockers (BB), aldosterone antagonists (AldA), hydralazine with isosorbide dinitrate (H/ISDN), and anticoagulants.   Results:  Among 213,564 patients with a primary discharge diagnosis of heart failure, ACEI/ARB initiation was indicated in 18.0% of all patients (52.9% of those eligible for ACEI/ARB but not receiving it prior to admission), BB in 23.2% (57.3% of eligible), AldA in 24.6% (87.2% of eligible), H/ISDN in 9.1% (93.4% of eligible), and anticoagulant in 17.4% (56.6% of eligible). Cumulatively, 0.9% of patients were eligible for 5 new medication groups, 10.3% for 4, 18.3% for 3, 10.4% for 2, and 21.9% for 1; 38.3% were not eligible for any new medications (99.0% of whom did not have left ventricular systolic dysfunction). Compared with the number of new medications indicated (mean 1.49, SD±1.22), the number of actual new prescriptions at discharge was lower (mean 1.14, SD±0.97).   Conclusions:  Among patients hospitalized with HF, the majority need to start at least one new medication and 1 in 9 patients start 4 or more medications to comply with hospital HF quality measures alone. Systems for addressing medication initiation and polypharmacy are central to HF transitional care.
Hedgehog signaling is critical for normal liver regeneration after partial hepatectomy in mice
Authors: Begoña Ochoa, Wing-Kin Syn, Igotz Delgado, Gamze F. Karaca, Youngmi Jung, Jiangbo Wang, Ana M. Zubiaga, Olatz Fresnedo, Alessia Omenetti, Marzena Zdanowicz, Steve S. Choi, Anna Mae Diehl
Journal: Hepatology (2010)

Distinct mechanisms are believed to regulate growth of the liver during fetal development and after injury in adults, because the former relies on progenitors and the latter generally involves replication of mature hepatocytes. However, chronic liver injury in adults increases production of Hedgehog (Hh) ligands, developmental morphogens that control progenitor cell fate and orchestrate various aspects of tissue construction during embryogenesis. This raises the possibility that similar Hh-dependent mechanisms also might regulate adult liver regeneration. The current analysis of murine liver regeneration after 70% partial hepatectomy (PH), an established model of adult liver regeneration, demonstrated that PH induced production of Hh ligands and activated Hh signaling in liver cells. Treatment with a specific Hh signaling inhibitor interfered with several key components of normal liver regeneration, significantly inhibiting progenitor responses, matrix remodeling, proliferation of hepatocytes and ductular cells, and restoration of liver mass. These global inhibitory effects on liver regeneration dramatically reduced survival after PH. Conclusion: Mechanisms that mediate liver organogenesis, such as Hh pathway activation, are retained and promote reconstruction of adult livers after injury. Hepatology 2010
High Mortality Associated With Precluded Coronary Artery Bypass Surgery Caused by Severe Distal Coronary Artery Disease
Authors: Antônio Sérgio Cordeiro da Rocha, Nella Paula Rodrigues Dassa, Felipe José Monassa Pittella, Odilon Nogueira Barbosa, José Oscar Reis Brito, Bernardo Tura, Paulo Roberto Dutra da Silva
Journal: Circulation (2005)

Patients with extensive coronary artery disease (CAD) have better prognosis when treated with coronary artery bypass grafting surgery (CABG), especially when left ventricular dysfunction (LVD) is present. However, there are scanty data about the clinical course of patients not referred to CABG because of extensive and severe atherosclerotic involvement of distal coronary arteries (ENDCAD). The aim of this study was to evaluate patients with multivessel (MV) or left main CAD (LM) who had CABG precluded because of ENDCAD.Between August 1999 and July 2001, 51 patients who had clinical indication but were not eligible for CABG because of ENDCAD were followed for at least 12 months or until death. There were 32 men and 19 women (age 61+/-9 years). Previous acute myocardial infarction (AMI) was present in 31 (60.8%), diabetes mellitus (DM) in 28 (54.9%), systemic arterial hypertension in 37 (72.5%), LVD (left ventricular ejection fraction <40%) in 26 (51%), 3 vessel CAD in 31 (60.8%), and LM in 4 (7.8%). During follow-up there were 20 cardiac (39.2%) deaths, 19 (37.2%) AMI, and 3 (5.8%) patients developed congestive heart failure. There were 2 (3.9%) noncardiac deaths. Patients with DM (60.7% versus 13%; P=0.001; odds ratio [OR], 10.30; 95% confidence interval [CI], 2.46 to 43.09), LVD (76.9% versus 0%; P<0.0001; OR, 4.33; 95% CI, 2.14 to 8.74), 3-vessel CAD (51.6% versus 20%; P=0.039; OR, 4.26; 95% CI, 1.16 to 15.69), and LM (100% versus 34%; P=0.019; OR, 1.25; 95% CI, 1.004 to 1.556) were more likely to die. There was no deaths in patients with 2-vessel CAD but they had more nonfatal AMI (43.8% versus 14.3%; OR, 4.667; 95% CI, 1.188 to 18.332).Patients in whom CABG could not be performed because of ENDCAD had high mortality, especially in the presence of LVD. DM (particularly insulin-dependent), LM CAD, and 3-vessel CAD were independent markers of increased risk.
Readability Standards for Informed-Consent Forms as Compared with Actual Readability
Authors: Michael K. Paasche-Orlow, Holly A. Taylor, Frederick L. Brancati
Journal: New England Journal of Medicine (2003)

Institutional review boards (IRBs) are charged with safeguarding potential research subjects with limited literacy but may have an inadvertent role in promulgating unreadable consent forms. We hypothesized that text provided by IRBs in informed-consent forms falls short of the IRBs' own readability standards and that readability is influenced by the level of research activity, local literacy rates, and federal oversight.
Personality and the Risk of Cancer
Authors: N. Nakaya, Y. Tsubono, T. Hosokawa, Y. Nishino, T. Ohkubo, A. Hozawa, D. Shibuya, S. Fukudo, A. Fukao, I. Tsuji, S. Hisamichi
Journal: JNCI Journal of the National Cancer Institute (2003)

The role of personality in the causation of cancer has been controversial. We examined this question in a large, prospective study.From June through August 1990, 30 277 residents of Miyagi Prefecture in northern Japan completed a Japanese version of the short form of the Eysenck Personality Questionnaire-Revised and a questionnaire on various health habits. There were 671 prevalent cases of cancer at baseline, and 986 incident cases of cancer were identified during 7 years of follow-up, through December 1997. We used Cox proportional hazards regression to estimate the relative risk (RR) of incident cancer (total, stomach, colorectal, breast, and lung) according to four levels of each of four personality subscales (extraversion, neuroticism, psychoticism, and lie), with adjustment for sex, age, education, smoking, alcohol use, body mass index, and family history of cancer. Statistical tests were two-sided.Multivariable RRs of total cancer for individuals in the highest level of each personality subscale as compared with those in the lowest were 0.9 for extraversion (95% confidence interval [CI] = 0.7 to 1.1; P(trend) =.32), 1.1 for psychoticism (95% CI = 0.9 to 1.3; P(trend) =.96), 0.9 for lie (95% CI = 0.7 to 1.0; P(trend) =.19), and 1.2 for neuroticism (95% CI = 1.0 to 1.4; P(trend) =.06). There were no associations between any personality subscale and risk of specific cancers. Neuroticism showed statistically significant positive, linear associations with prevalent cancer at baseline (P(trend)<.001) and with the 320 incident cancer cases diagnosed within the first 3 years of follow-up (P(trend) =.03); however, it showed no association with the 666 cases diagnosed during the fourth through the seventh years of follow-up (P(trend) =.43).Our data do not support the hypothesis that personality is a risk factor for cancer incidence. The association between neuroticism and prevalent cancer may be a consequence, rather than a cause, of cancer diagnosis or symptoms.
Cancer Cell Lines for Drug Discovery and Development
Authors: Jennifer L. Wilding, Walter F. Bodmer
Journal: Cancer Research (2014)

Abstract Despite the millions of dollars spent on target validation and drug optimization in preclinical models, most therapies still fail in phase III clinical trials. Our current model systems, or the way we interpret data from them, clearly do not have sufficient clinical predictive power. Current opinion suggests that this is because the cell lines and xenografts that are commonly used are inadequate models that do not effectively mimic and predict human responses. This has become such a widespread belief that it approaches dogma in the field of drug discovery and optimization and has spurred a surge in studies devoted to the development of more sophisticated animal models such as orthotopic patient-derived xenografts in an attempt to obtain more accurate estimates of whether particular cancers will respond to given treatments. Here, we explore the evidence that has led to the move away from the use of in vitro cell lines and toward various forms of xenograft models for drug screening and development. We review some of the pros and cons of each model and give an overview of ways in which the use of cell lines could be modified to improve the predictive capacity of this well-defined model. Cancer Res; 74(9); 2377–84. ©2014 AACR.
The Transforming Growth Factor-β Superfamily Member Growth-Differentiation Factor-15 Protects the Heart From Ischemia/Reperfusion Injury
Authors: Tibor Kempf, Matthias Eden, Jens Strelau, Marian Naguib, Christian Willenbockel, Jörn Tongers, Jörg Heineke, Daniel Kotlarz, Jian Xu, Jeffery D. Molkentin, Hans W. Niessen, Helmut Drexler, Kai C. Wollert
Journal: Circulation Research (2006)

Data from the Women's Health Study show that serum levels of growth-differentiation factor-15 (GDF-15), a distant member of the transforming growth factor-beta superfamily, are an independent risk indicator for adverse cardiovascular events. However, the cellular sources, upstream regulators, and functional effects of GDF-15 in the cardiovascular system have not been elucidated. We have identified GDF-15 by cDNA expression array analysis as a gene that is strongly upregulated by nitrosative stress in cultured cardiomyocytes isolated from 1- to 3-day-old rats. GDF-15 mRNA and pro-peptide expression levels were also induced in cardiomyocytes subjected to simulated ischemia/reperfusion (I/R) via NO-peroxynitrite-dependent signaling pathways. GDF-15 was actively secreted into the culture supernatant, suggesting that it might exert autocrine/paracrine effects during I/R. To explore the in vivo relevance of these findings, mice were subjected to transient or permanent coronary artery ligation. Myocardial GDF-15 mRNA and pro-peptide abundance rapidly increased in the area-at-risk after ischemic injury. Similarly, patients with an acute myocardial infarction had enhanced myocardial GDF-15 pro-peptide expression levels. As shown by immunohistochemistry, cardiomyocytes in the ischemic area contributed significantly to the induction of GDF-15 in the infarcted human heart. To delineate the function of GDF-15 during I/R, Gdf-15 gene-targeted mice were subjected to transient coronary artery ligation for 1 hour followed by reperfusion for 24 hours. Gdf-15-deficient mice developed greater infarct sizes and displayed more cardiomyocyte apoptosis in the infarct border zone after I/R compared with wild-type littermates, indicating that endogenous GDF-15 limits myocardial tissue damage in vivo. Moreover, treatment with recombinant GDF-15 protected cultured cardiomyocytes from apoptosis during simulated I/R as shown by histone ELISA, TUNEL/Hoechst staining, and annexin V/propidium iodide fluorescence-activated cell sorting (FACS) analysis. Mechanistically, the prosurvival effects of GDF-15 in cultured cardiomyocytes were abolished by phosphoinositide 3-OH kinase inhibitors and adenoviral expression of dominant-negative Akt1 (K179M mutation). In conclusion, our study identifies induction of GDF-15 in the heart as a novel defense mechanism that protects from I/R injury.
Super athletes or gene cheats?
Authors: P McCrory
Journal: British Journal of Sports Medicine (2003)

Abstract. The 25-hydroxyvitamin D<sub>3</sub> 1α-hydroxylase, also referred to as CYP27B1, is a mitochondrial cytochrome P450 enzyme that catalyzes the biosynthesis of 1α, 25-dihydroxyvitamin D<sub>3</sub> (1α,25(OH)<sub>2</sub>D<sub>3</sub>) from 25-hydroxyvitamin D<sub>3</sub> in renal proximal tubular cells. Recently, human, mouse, and rat CYP27B1 cDNA have been cloned, however the gene regulation has not been fully elucidated. In the present study, porcine CYP27B1 cDNA was cloned, and the effects of cAMP and vitamin D<sub>3</sub> on the regulation of CYP27B1 mRNA expression in LLC-PK<sub>1</sub> cells were examined. PCR cloning revealed that porcine CYP27B1 cDNA consisted of 2316 bp, encoding a protein of 504 amino acids. The deduced amino acid sequence showed over 80% identity to the human, mouse, and rat enzyme. LLC-PK<sub>1</sub> cells were incubated with humoral factors, and expression of CYP27B1 mRNA was measured by a quantitative reverse transcription-PCR. At the completion of 3-, 6-, 12-, and 24-h incubations, 500 μmol/L 8-bromo-cAMP had significantly increased CYP27B1 mRNA expression (260 to 340%). The adenylate cyclase activator forskolin at 50 μmol/L also had a stimulatory effect at 6 h (190%). Moreover, the protein kinase A inhibitor H-89 reduced the cAMP effect. On the other hand, 1α,25(OH)<sub>2</sub>D<sub>3</sub> had no effect on CYP27B1 mRNA expression at 10 and 100 nmol/L, whereas expression of 25-hydroxyvitamin D<sub>3</sub> 24-hydroxylase (CYP24) mRNA was markedly increased by 1α,25(OH)<sub>2</sub>D<sub>3</sub>. These findings suggest that LLC-PK<sub>1</sub> cells express CYP27B1 mRNA, and that cAMP is an upregulating factor of the CYP27B1 gene in vitro.
Cell death provoked by loss of interleukin-3 signaling is independent of Bad, Bim, and PI3 kinase, but depends in part on Puma
Authors: Paul G. Ekert, Anissa M. Jabbour, Anand Manoharan, Jacki E. Heraud, Jai Yu, Miha Pakusch, Ewa M. Michalak, Priscilla N. Kelly, Bernard Callus, Thomas Kiefer, Anne Verhagen, John Silke, Andreas Strasser, Christoph Borner, David L. Vaux
Journal: Blood (2006)
Gefitinib versus Docetaxel for Previously Treated NSCLC—Letter
Authors: Davide Tassinari, Luigi Lazzari-Agli, Paola Tombesi, Sergio Sartori
Journal: Clinical Cancer Research (2011)

We read with great interest the recent article by Lee and colleagues, reporting the final results of the ISTANA trial (1). The authors affirm that these results prove the superiority of gefitinib over chemotherapy in the treatment of advanced, pretreated non–small-cell lung cancer (NSCLC) in terms of survival, safety, and quality of life (see Translational Relevance). However, as a matter of fact, the results show uniquely the superiority of gefitinib in progression-free survival (PFS). These data, for the first time, show the superiority of a single, molecular, targeted agent in comparison with standard chemotherapy. Furthermore, they seem to clash with the main results of the INTEREST trial and the V-15-32 trial, which showed the “non inferiority” of gefitinib in comparison with docetaxel in terms of response rate or overall survival (the INTEREST trial) and in terms of symptoms control and quality of life (the INTEREST and V-15–32 trials; refs. 2–4). The ISTANA trial differs from these 2 trials for some substantial aspects in the study design and conduction: Moreover, some issues about the ISTANA trial need to be clarified for a correct, final interpretation of the results: The authors of the ISTANA trial would aim at changing the actual perspective of second-line treatments of advanced NSCLC, but, unfortunately, the negligible entity of the final results and the lack of any significant effect on quality of life or symptoms control bring back the merit of the trial to its right perspective.Further trials are probably needed to better understand the role of gefitinib in the second-line treatment of NSCLC.See the Response, p. 4611No potential conflicts of interest were disclosed.