tbuckley/cabot-search huggingface dataset:
Abstract 4663: Genetic variation in the p38 signaling pathway as markers for postoperative pulmonary complications in lung cancer patients
Authors: Michelle A. Hildebrandt, Jack A. Roth, Ara A. Vaporciyan, Xia Pu, Yuanqing Ye, Arlene M. Correa, Jae Y. Kim, Stephen G. Swisher, Xifeng Wu
Journal: Cancer Research (2011)

Abstract Surgical resection is the primary treatment for patients with localized non-small cell lung cancer (NSCLC). Although often a successful treatment option, a portion of these individuals will experience postoperative pulmonary complications, such as pneumonia, acute respiratory distress syndrome, and atelectasis. These complications are difficult to predict and often characterized by a hyper-inflammatory response. The p38 signaling pathway is activated following stress stimuli and in response to inflammatory signals. Because of this important role, we hypothesized that genetic polymorphisms within the core components of this pathway may result in dysregulated response to inflammation following surgery causing unforeseen complications. Therefore, in this study we genotyped 242 common, germline genetic variants from 19 p38 pathway genes in 275 Caucasian NSCLC patients who underwent a lobectomy at MD Anderson. After controlling for clinical risk factors, twenty-three significant associations with any pulmonary complication were observed (P&amp;lt;0.05). Patients carrying at least one variant allele of IRAK2:rs778044 had a complication rate of 49.7% compared to 28.6% for patients with the common genotype for a highly significant 3.10-fold increase in risk (95% Confidence Interval [CI]: 1.76-5.47, P=9.6×10-5). A dose-response effect was evident between number of risk genotypes and risk of complication (P=2.08×10-7). Patients with the highest number of risk genotypes were nearly 14 times more likely to develop a pulmonary complication (95% CI: 5.30-36.87, P=9.73×10-8) compared to those with the fewest risk genotypes. Potential gene-gene interactions were also observed between IRAK2, MYD88, and IL1R1 that identified distinct risk groupings. Patients carrying both the variant genotypes for IRAK2:rs778044 and MYD88:rs11783456 were at highest risk, while those with the common genotype for IRAK2:rs778044 and the protective variant genotype for IL1R1:rs2287047 had the lowest risk. The increase in risk was 23.57-fold for high risk individuals compared to those with the low risk genetic profile (95% CI: 2.75-201.96, P=0.0039). These results strongly implicate the p38 pathway in modulating risk of pulmonary complications following lobectomy for NSCLC. Together with clinical and epidemiological variables, these variants may be useful biomarkers to better identify patients at high risk prior to surgery. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4663. doi:10.1158/1538-7445.AM2011-4663
Ionic Remodeling in the Heart
Authors: Stanley Nattel, Danshi Li
Journal: Circulation Research (2000)

Abstract —Heart disease has long been recognized to alter cardiac electrical function. Detailed studies of disease-induced remodeling of ionic transport processes that underlie ventricular electrophysiological alterations have been performed over the past 10 years, but our knowledge of atrial ionic remodeling is more limited and has emerged much more recently. The present review focuses on recent findings regarding ionic remodeling at the atrial level, particularly with respect to two conditions that promote atrial fibrillation (AF) in well-developed clinically relevant animal models: (1) sustained atrial tachycardia and (2) ventricular tachypacing–induced congestive heart failure. Complementary data from experimental models and from observations in atrial tissue samples from patients are examined critically and integrated. Consideration is also given to potential molecular mechanisms underlying remodeling, the relationship between atrial and ventricular ionic remodeling in response to similar stimuli, and the potential relevance of insights into ionic remodeling for understanding the pathophysiology of AF and developing improved therapeutic approaches.
Understanding Drug Effects in Older People: The Role of Pharmacology—Reply
Authors: Sarah D. Berry, David D. Dore
Journal: JAMA Internal Medicine (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Shared and Physician-Directed Decision Making in Clinical Practice—Reply
Authors: Alexander A. Kon
Journal: JAMA (2010)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Cbfβ Reduces Cbfβ-SMMHC–Associated Acute Myeloid Leukemia in Mice
Authors: Susan A. Heilman, Ya-Huei Kuo, Chantal S. Goudswaard, Peter J. Valk, Lucio H. Castilla
Journal: Cancer Research (2006)

Abstract The gene encoding for core-binding factor β (CBFβ) is altered in acute myeloid leukemia samples with an inversion in chromosome 16, expressing the fusion protein CBFβ-SMMHC. Previous studies have shown that this oncoprotein interferes with hematopoietic differentiation and proliferation and participates in leukemia development. In this study, we provide evidence that Cbfβ modulates the oncogenic function of this fusion protein. We show that Cbfβ plays an important role in proliferation of hematopoietic progenitors expressing Cbfβ-SMMHC in vitro. In addition, Cbfβ-SMMHC–mediated leukemia development is accelerated in the absence of Cbfβ. These results indicate that the balance between Cbfβ and Cbfβ-SMMHC directly affects leukemia development, and suggest that CBF-specific therapeutic molecules should target CBFβ-SMMHC function while maintaining CBFβ activity. (Cancer Res 2006; 66(23): 11214-8)
A FATAL CASE OF POISONING BY A NON-ARSENICAL WEED-KILLER
Authors: A. H. D. Smith
Journal: BMJ (1928)

POISONING BY A NON-ARSENICAL 'WEED-KILLER, [MEI1ALJOLR-wA a(f/ypti) were fed on the patient, and at the same time 4 c.cmi. of blood were collected and inoculated into a rh'esus monkey.Two days later this animal lhad a slight fever and was fouilnd dead on the eighth day after the inoculation.At the necropsy a slight jaundice was observed, and also lesions resenmblinig those of yellow fever.The blood and a suspension of liver were inioculated into two young guinea-pigs, which remained healtlhy, tlhus excluding the presence of Leptospi'ra icteroide.s.
Establishing generic remediation goals for the polycyclic aromatic hydrocarbons: critical issues.
Authors: P K LaGoy, T C Quirk
Journal: Environmental Health Perspectives (1994)

Polycyclic aromatic hydrocarbons (PAHs) were one of the first classes of compounds identified as carcinogens and are often chemicals of concern at hazardous waste sites. Remediation goals established by regulatory agencies for carcinogenic PAHs in soil are generally either risk based or based on the method detection limits. PAHs are products of incomplete combustion, are components of petroleum, and as such, are prevalent in the environment from both natural and anthropogenic sources. Background concentrations are often above risk- or detection limit-based criteria, and therefore these remediation goals are of limited practical use as target criteria. In addition, the approaches used to establish target criteria do not account for several factors that may produce over- or underestimates of risk associated with the PAHs. Because of the frequency with which these compounds are detected, it is imperative that reasonably achievable and practical remediation goals be established. This paper examines the various factors that contribute to over- and underestimates of risks associated with PAHs and presents an approach for establishing cleanup criteria that takes into account health risks, background concentrations, and achievability.
Soluble Tumor Necrosis Factor Receptor Abrogates Myocardial Inflammation but Not Hypertrophy in Cytokine-Induced Cardiomyopathy
Authors: Toru Kubota, George S. Bounoutas, Masayuki Miyagishima, Toshiaki Kadokami, Virginia J. Sanders, Christina Bruton, Paul D. Robbins, Charles F. McTiernan, Arthur M. Feldman
Journal: Circulation (2000)

Background —Transgenic mice with cardiac-specific overexpression of tumor necrosis factor (TNF)-α develop dilated cardiomyopathy. The present study was designed to evaluate therapeutic effects of adenovirus-mediated neutralization of TNF-α on this model. Methods and Results —An adenovirus encoding the 55-kDa TNF receptor–IgG fusion protein (AdTNFRI) was injected intravenously into 6-week-old transgenic mice, which resulted in high levels of TNFRI in both plasma and myocardium. AdTNFRI did not reverse cardiomegaly but abrogated myocardial inflammation. Furthermore, AdTNFRI blocked the myocardial expression of intercellular adhesion molecule-1 and downstream cytokines, including interleukin-1β and monocyte chemotactic protein-1. Downregulation of α-myosin heavy chain was restored by the treatment, whereas upregulation of β-myosin heavy chain was not reversed. In contrast, the downregulation of sarcoplasmic reticulum Ca 2+ -ATPase and phospholamban was normalized by AdTNFRI. Echocardiographic measurements showed that left ventricular end-systolic diameter was significantly larger in transgenic mice than in control mice, and this increase was reversed by the AdTNFRI treatment. However, left ventricular wall thickening was not reversed. Conclusions —These results suggest that anti-TNF therapy may hold promise in the treatment of end-stage heart failure.
Quinidine-related mortality in the short-to-medium-term treatment of ventricular arrhythmias. A meta-analysis.
Authors: J Morganroth, J E Goin
Journal: Circulation (1991)

The interim results of the Cardiac Arrhythmia Suppression Trial requires physicians to use a higher threshold for employing antiarrhythmic agents in the treatment of benign or potentially lethal ventricular arrhythmias. Many have managed patients by switching to the traditional class I quinidine despite its known proarrhythmic tendency.To evaluate the relation between quinidine therapy and mortality in patients with benign or potentially lethal ventricular arrhythmias, we performed a meta-analysis on four randomized double-blind active controlled parallel trials evaluating 1,009 patients in which quinidine (n = 502) was compared to flecainide (n = 141), mexiletine (n = 246), tocainide (n = 67), and propafenone (n = 53). All four trials had similar patient selection, protocols, and methodology (e.g., placebo lead-in and Holter monitoring) but varying lengths of drug exposure. A total of 12 deaths were reported on quinidine and four deaths on the other drugs: two on mexiletine, one on flecainide, and one on tocainide. The statistical analysis of the mortality rates was based on techniques for combining data across separate strata. Based on maximum likelihood estimation, the combined risk of dying on quinidine was statistically significantly higher compared to the other four drugs with a risk difference of 1.6%. The 95% confidence interval was 0-3.1% (p = 0.05). The likelihood ratio test for uniformity of the risk difference across strata showed the trials to be homogeneous (p = 0.88). There was one death recorded for the placebo lead-in period (2 weeks' exposure for 624 patients and 1 week for 385 patients), and seven deaths were reported within 2 weeks on active drug treatment--six on quinidine and one on mexiletine. Furthermore, proarrhythmia was reported in 20 patients on quinidine versus 11 patients on the four other drugs (p = 0.09).These data suggest that quinidine may have an adverse effect on mortality as compared to other class I antiarrhythmic agents and that individualized patient selection for the use of this agent be carefully weighed relative to its potential for harm and benefit.
The burden of evidence
Authors: J. L Rushton
Journal: BMJ (2001)

Evidence based medicine has advanced our science and helped doctors move from inconsistent, often unsupported, practices based on our last case and anecdotal experience to more uniform, effective care. Rigorous methodology has facilitated efforts to deliver high quality treatment and improve outcomes for large patient populations. We have elevated the science published in journals and presented at meetings. Elegant randomised controlled clinical trials, meta-analyses, and guidelines have changed the support of our recommendations from “because I said so” towards “because we know so.” Cost analyses have provided means to allocate our tightening resources efficiently and allow doctors and health systems to survive in an era of intense financial pressure.

> We must trust our own knowledge and individual “expert opinion” 

However, in the wake of these achievements, the burden of evidence based medicine may have untoward effects on relations between patients and doctors, on personal satisfaction, and on artistic components of the “art of medicine.”

Doctor scientists at all levels …
Medical Education and Managed Care
Authors: Robert Michels
Journal: New England Journal of Medicine (1999)

Students, residents, faculty members, and deans at medical schools in the United States don't like managed care. In this issue of the Journal, 1 Simon et al. report the results of a 1997 telephone survey of a national sample of medical students, residents, department chairs, directors of residency training, and deans to determine their views of managed care. Fee-for-service medicine was rated better than managed care in terms of the access of patients to care, minimizing ethical conflicts, the quality of the doctor–patient relationship, the continuity of care, care at the end of life, and care for patients with chronic illness. . . .
Sensing Muscle Ischemia: Coincident Detection of Acid and ATP via Interplay of Two Ion Channels
Authors: William T. Birdsong, Leonardo Fierro, Frank G. Williams, Valeria Spelta, Ligia A. Naves, Michelle Knowles, Josephine Marsh-Haffner, John P. Adelman, Wolfhard Almers, Robert P. Elde, Edwin W. McCleskey
Journal: Neuron (2010)
Cardiorespiratory effects of protamine after cardiopulmonary bypass in man
Authors: J. Jastrzebski, M. K. Sykes, D. G. Woods
Journal: Thorax (1974)

<b>Jastrzebski, J., Sykes, M. K., and Woods, D. G. (1974).</b><i>Thorax</i>, <b>29</b>, 534-538. <b>Cardiorespiratory effects of protamine after cardiopulmonary bypass in man.</b> The cardiorespiratory changes following the injection of protamine sulphate (6 mg/kg) were studied in 15 patients who had undergone cardiopulmonary bypass. There was a transient fall in arterial pressure and a more prolonged increase in pulmonary artery pressure. There was a significant fall in arterial oxygen tension which was mainly due to a reduction in mixed venous oxygen tension resulting from a fall in cardiac output. Dead space/tidal volume ratio and percentage shunt did not change significantly.
Comparison of Morning or Bedtime Insulin With and Without Glyburide in Secondary Sulfonylurea Failure
Authors: Ileana L Soneru, Lily Agrawal, John C Murphy, A M Lawrence, Carlos Abraira
Journal: Diabetes Care (1993)

OBJECTIVES— New treatment options are needed for glycemic control in NIDDM. We evaluated the effects of bedtime or morning insulin treatment, combined with daytime glyburide or given alone. RESEARCH DESIGN AND METHODS— Twenty-nine male patients with NIDDM, mean age 63 ± 1.7 yr, body weight 124 ± 2.98% of DBW, received a maximum glyburide dose (20 mg/day) for a minimum of 6 wk, to confirm sulfonylurea failure. Human lente insulin was added for 12 wk either AM (n = 14) or HS (n = 15) and adjusted to obtain fasting euglycemia (FPG; combination treatment phase). Glyburide was then stopped, and insulin was continued for 6 wk, aiming for normal FPG (insulin phase). RESULTS— After combination treatment phase, FPG decreased (P &amp;lt; 0.02) from 12.43 ± 0.68 to 5.73 ± 0.65 mM (AM) and from 12.68 ± 0.76 to 5.51 ± 0.48 mM (HS) (AM vs. HS, NS). Postbreakfast, presupper, and 0200 AM plasma glucose levels fell equally (P &amp;lt; 0.02) except for 1-h postprandial (AM 12.46 ± 0.51 mM, HS 10.88 ± 0.62 mM, AM vs. HS, P &amp;lt; 0.1). Mean HBA1c fell similarly in both AM and HS groups. At 2 wk of the insulin phase, FPG was higher in AM than HS, 9.8 ± 0.76 vs. 7.56 ± 0.7 mM (P &amp;lt; 0.1). At the end of insulin phase, plasma glucose levels were similar to the end of combination treatment phase, but the insulin dose had to be raised in AM by 39% (P &amp;lt; 0.02) and HS by 30% (P &amp;lt; 0.05). After the combination treatment phase, fasting C-peptide was significantly suppressed in HS group only, from 1.22 ± 0.12 to 0.82 ± 0.09 nM (P &amp;lt; 0.02). At the end of insulin phase, fasting C-peptide was further suppressed in both groups, but 2-h postprandial C-peptide levels decreased significantly in AM group only, from 1.85 ± 0.23 to 1.42 ± 0.13 nM (P &amp;lt; 0.02). Triglycerides and total and HDL cholesterol did not change significantly after either combination treatment phase or insulin phase. Mean weight gain was 6.5 lb during combination treatment phase (NS from baseline), without further change during insulin phase. Hypoglycemic reactions, all mild, were recorded at a rate of 1.35/patient in the AM group and 0.4/patient in the HS group (P &amp;lt; 0.025). CONCLUSIONS— Normal fasting glycemia and near-normal postprandial glucose profile could be obtained with combination therapy in NIDDM. Results were similar if insulin, alone or in combination with glyburide, was given before breakfast or at bedtime, but hypoglycemic reactions were more common with conventional morning insulin injections.
Rituximab for the treatment of refractory idiopathic thrombocytopenic purpura (ITP) and thrombotic thrombocytopenic purpura (TTP): Report of three cases
Authors: Lydia Koulova, Doru Alexandrescu, Janice P. Dutcher, Kevin P. O'Boyle, Saji Eapen, Peter H. Wiernik
Journal: American Journal of Hematology (2004)

Three patients (one with idiopathic thrombocytopenic purpura [ITP] and two with thrombotic thrombocytopenic purpura [TTP]) were treated with rituximab (anti-CD20 chimeric antibody) at a dose of 325 mg/m2 administered weekly after they failed standard therapies. The patient with ITP who did not respond to steroids and anti-D antibody administration achieved augmentation of her platelet counts up to 180 × 103/μL after four doses of rituximab. Six months later, when her counts started to decrease, she received maintenance therapy with an additional course of 4 standard doses of antibody that resulted in consolidation of her platelet counts around 100 × 103/μL. One patient with TTP and concurrent idiopathic nephropathy who was previously treated with plasmapheresis, steroids, and vincristine improved only after 4 weekly administrations of the antibody. Moreover, his nephrotic-range proteinuria resolved after he received rituximab. The other patient with chronic TTP who still relapsed after splenectomy received 5 doses of rituximab with concomitant plasmapheresis. His thrombocytopenia improved slowly, and his platelet count stabilized at 300 × 103/μL. All three patients showed evidence of response to anti-CD20 antibody with improvement in clinical outcome as well as augmentation of platelet counts to normal levels. We conclude that rituximab is a useful immunomodulating adjunct in the treatment of refractory ITP and TTP. Am. J. Hematol. 78:49–54, 2005. © 2004 Wiley-Liss, Inc.
Radiographic Evidence of Nonoccupational Asbestos Exposure from Processing Libby Vermiculite in Minneapolis, Minnesota
Authors: Bruce H. Alexander, Katherine K. Raleigh, Jean Johnson, Jeffrey H. Mandel, John L. Adgate, Gurumurthy Ramachandran, Rita B. Messing, Tannie Eshenaur, Allan Williams
Journal: Environmental Health Perspectives (2011)

Community exposure to asbestos from contaminated vermiculite ore from Libby, Montana, occurred in many processing sites in the United States, including a densely populated urban residential neighborhood of Minneapolis, Minnesota.We examined exposed community residents who never worked at the plant or never lived with a plant worker for radiographic evidence of lung changes consistent with asbestos exposure.We obtained posteroanterior chest radiographs to identify the prevalence of pleural abnormalities consistent with pneumoconiosis, as determined by consensus of two National Institute for Occupational Safety and Health-certified B-reader radiologists. We estimated cumulative asbestos exposure (fibers per cubic centimeters × months) with air dispersion model data and activity-based modeled exposure estimates for vermiculite processing waste contact. We modeled associations between pleural abnormalities and asbestos exposure using multiple logistic regression to adjust for year of birth, sex, and potential occupational asbestos exposure.Radiographs were obtained for 461 participants. The prevalence of pleural abnormalities by B-reader consensus was 10.8%. A history of direct contact with the waste and ever playing in the waste piles was associated with pleural abnormalities {odds ratio [OR] 2.78 [95% confidence interval (CI): 1.26, 6.10] and 2.17 (95% CI: 0.99, 4.78), respectively, when adjusted for background exposure}. The regression coefficients for log-transformed measures (fibers per cubic centimeters × months) of background exposure and activity-based exposure were 0.322 (95% CI: 0.078, 0.567) and 0.063 (95% CI: -0.013, 0.139), respectively, when adjusted for each other, and 0.283 (95% CI: 0.104, 0.463) for cumulative exposure from all sources.These results support the hypothesis that community exposure to asbestos-contaminated vermiculite originating from Libby, Montana, is associated with measurable effects based on radiographic evidence.