tbuckley/cabot-search huggingface dataset:
Cloning and Characterization of Two Toll/Interleukin-1 Receptor–Like Genes TIL3 and TIL4: Evidence for a Multi-Gene Receptor Family in Humans
Authors: Preet M. Chaudhary, Camari Ferguson, Vilaska Nguyen, Oanh Nguyen, Hillary F. Massa, Michael Eby, Alan Jasmin, Barbara J. Trask, Leroy Hood, Peter S. Nelson
Journal: Blood (1998)
Endometriosis
Authors: K. D Jones, C. Sutton, N. N Amso
Journal: BMJ (2002)

Promoting patient safety in primary care Honesty and openness may not be best policyEditor-We were both surprised by Wilson et al who, in their editorial, ask everybody to send in reports of their errors. 1Our concerns remain regardless of whether or not such accounts are published anonymously.After all, the police have used anonymous medical research data in their investigations.A conviction of culpable and reckless behaviour was secured against a man after he had sexual intercourse with his girlfriend without telling her he was infected with HIV.The scientific evidence that secured the conviction came from confidential research data that were obtained with a police warrant. 2 Furthermore, Wilson et all say that for doctors to report their errors, patient consent will be needed.This means that the patient will know that an account of his or her care is to be published and may read it.He or she may ask his lawyers to read it.The lawyers may then be able to substantiate this published account as a confession of guilt or negligence.Wherever and whoever we are, we must be careful as doctors what we say.For example, although we understand that no charges were brought, an incident last year highlights this point.Police are to hold a murder inquiry into the case of Peter Brand, a Member of Parliament for the Liberal Democrat Party for the Isle of Wight and a general practitioner, who mentioned during a parliamentary debate that he had withdrawn treatment from a two year old boy with leukaemia at the parents' request, to save him any more distress. 3This case had occurred in 1973, when he was a house officer.However regrettable, we do live in a culture of blame.To admit professional mistakes of a minor nature may be straightforwardly forgivable.The admission, however, of a serious offence or negligence by doctors may result in litigation against them.Before discussing such matters in public, doctors should seriously consider whether honesty and openness are the best policy.
Abstract 18946: A Complex Cardiac Rhythm and Conduction Abnormalities in Three Families Carrying a SCN5A Missense Mutation May Involve Single Nucleotide Polymorphisms in SCN5A and RYR2 genes
Authors: Erika Antunez-Arguelles, Argelia Medeiros-Domingo, Teresa Villarreal, Jonathan J Hernandez, Pedro Iturralde, Hector H Valdivia, Jonathan C Makielski, Carmen R Valdivia
Journal: Circulation (2014)

Background: Mutations in the gene encoding the cardiac sodium channel (SCN5A) have been implicated in arrhythmia syndromes including Brugada (BrS) and long-QT type 3 syndromes. Also, wide spectrums of mixed phenotypes, known as “overlap syndromes”, have been associated to SCN5A mutations. The contributions of single nucleotide polymorphisms (SNPs) add more complexity to the disease phenotype. Here we report a missense mutation in SCN5A (T1708N) in three Hispanic families with history of sudden cardiac death (SCD) and extensive variability and severity of symptoms, including syncope, atrial and ventricular tachycardia, and conduction abnormalities. Methods and Results: We used the Ion Torrent platform and AmpliSeq panel to sequence 19 genes associated with arrhythmia syndromes. In addition to SCN5A-T1708N mutation, the patients carry two common SNPs, SCN5A-H558R and the cardiac ryanodine receptor RYR2-Q2958R, which we previously reported to be highly prevalent (~30%) in Hispanics and to increase the risk of SCD in homozygous individuals. To study the functional properties of SCN5A-T1708N, the mutation was engineered by site-directed mutagenesis into SCN5A with or without the SCN5A-H558R and expressed in HEK cells for voltage clamp experiments. SCN5A-T1708N showed a significant increase of late INa compared to WT. Also, the kinetic properties of SCN5A-T1708N showed slower time constants of recovery and increase in slow inactivation, which would tend to reduce INa; these effects were not modified by the presence of SCN5A-H558R. On the other hand, INa density for SCN5A-T1708N was reduced compared to WT (289± 63 and 387± 62 pA/pF, respectively), yet, for the double mutant H558R-T1708N, INa was more severely depressed (145± 32 pA/pF). Conclusion: The profound biophysical phenotype of T1708N with loss and gain of function could account for the variability and the severity of the clinical phenotype in these families. The RYR2-Q2958R polymorphism may function as a pro-arrhythmic genetic modifier and it is conceivable that it may predispose to SCD in some members of these families. The study of these polymorphisms in large cohorts may identify common haplotypes associated to cardiac arrhythmias and facilitate identification of patients at high risk for SCD.
Early or Late Surgery for Supratentorial Gliomas? A Randomized Study
Authors: R. Knerich, G. Ubezzi, P. Buoncristiani, B. Tanghetti, D. Adinolfi, R. Assietti, M. Rolli, V. Silvani, L. Princi, D. Schiffer
Journal: Neuro-Oncology (1991)

The purpose of this study was to determine the value of sequential radiotherapy followed by cytoreductive surgery as compared with cytoreductive surgery followed by radiotherapy and chemotherapy in supratentorial malignant gliomas in adults. Since 1978 forty-seven patients were entered into this study and were randomly submitted to surgical procedure (early or late), whole-brain irradiation (6000 cGy) and chemotherapy with BCNU (80 mg/sqm/ iv × 3 days). Twenty-five patients were assigned to the control arm (early surgery) and 22 to the late surgery arm. The results demonstrate no statistical difference in survival or in recurrence time between patients treated with early or late surgery. Toxicity was similar among the two groups but late-surgery patients had a better quality of life. Late surgical procedure appears safe and feasible. The tumor was often necrotic and well demarcated from surrounding brain and therefore often easily removed. Late surgery might be a treatment of choice for tumors with poor surgical indications.
C-reactive protein and serum amyloid A overexpression in lung tissues of chronic obstructive pulmonary disease patients
Authors: Ana Montes-Worboys, Carmen Calero-Acuña, Elena Arellano-Orden, Belen Rojano, Jose Luis Lopez-Villalobos, Ana Blanco, Verónica Sanchez-López, Daniela Tobar, Jose-Luis Lopez-Campos
Journal: European Respiratory Journal (2012)

Background:  Although researchers have consistently demonstrated systemic inflammation in chronic obstructive pulmonary disease (COPD), its origin is yet unknown. We aimed to compare the lung bronchial and parenchymal tissues as potential sources of major acute-phase reactants in COPD patients and resistant smokers.   Material and methods:  Consecutive patients undergoing elective pneumectomy or lobectomy for suspected primary lung cancer were considered for the study. Patients were categorized as COPD or resistant smokers according to their spirometric results. Lung parenchyma and bronchus sections were obtained and C-reactive protein (CRP) and serum amyloid A (SAA1, SAA2 and SAA4) were studied by RT-PCR and immunohistochemistry.   Results:  Our study included 85 patients with COPD and 87 resistant smokers. In bronchial and parenchymal tissues, both CRP and SAA genes were overexpressed in COPD patients as compared to resistant smokers. In the bronchus, CRP, SAA1, SAA2, and SA4 expressions in COPD patients were 1.89-fold, 4.36-fold, 3.65-fold, and 3.9-fold the control values, respectively. In the parenchyma, CRP, SAA1, and SAA2 gene expressions were 2.41-, 1.97-, and 1.76-fold the control values, respectively. SAA4 was not overexpressed in the parenchyma. The expressions were higher in the parenchymal tissue than in bronchial tissue for both COPD and controls. The protein analysis supported the results obtained in the PCR.   Conclusions:  These results indicate an overexpression of CRP and SAA genes in both bronchial and parenchymal tissue in COPD. This expression differs between the parenchyma and bronchial tissue, indicating tissue/cell type specificity of these markers.
Low‐Dose Irinotecan Improves Advanced Lupus Nephritis in Mice Potentially by Changing DNA Relaxation and Anti–Double‐Stranded DNA Binding
Authors: Manuela Frese‐Schaper, Andreas Keil, Selina K. Steiner, Mathias Gugger, Meike Körner, Gregor J. Kocher, Lena Schiffer, Hans‐Joachim Anders, Uyen Huynh‐Do, Ralph A. Schmid, Steffen Frese
Journal: Arthritis & Rheumatology (2014)

Objective Despite clear advances in the treatment of systemic lupus erythematosus (SLE), many patients still present with refractory lupus nephritis, requiring new treatment strategies for this disease. This study was undertaken to determine whether reduced doses of the topoisomerase I (topo I) inhibitor irinotecan, which is known as a chemotherapeutic agent, suppress SLE in (NZB × NZW)F1 (NZB/NZW) mice, and to evaluate the potential mechanism by which irinotecan influences the course of SLE. Methods NZB/NZW mice were treated with low‐dose irinotecan beginning at either 24 weeks of age or established glomerulonephritis, defined as proteinuria of grade ≥3+. Binding of anti–double‐stranded DNA (anti‐dsDNA) antibodies was measured by enzyme‐linked immunosorbent assay (ELISA), and DNA relaxation was visualized by gel electrophoresis. Results Significantly reduced irinotecan doses improved lupus nephritis and prolonged survival in NZB/NZW mice. The lowest dose successfully used for the treatment of established murine lupus nephritis was &gt;50 times lower than the dose usually used for chemotherapy in humans. As a mechanism, low‐dose irinotecan reduced B cell activity. However, the levels of B cell activity in irinotecan‐treated mice were similar to those in BALB/c mice of the same age, suggesting that irinotecan did not induce clear immunosuppression. In addition, incubation of dsDNA with topo I increased binding of murine and human anti‐dsDNA antibodies, showing for the first time that relaxed DNA is more susceptible to anti‐dsDNA antibody binding. This effect was reversed by addition of the topo I inhibitor camptothecin. Conclusion Our findings indicate that topo I inhibition may be a novel and targeted therapy for SLE.
Heart monitoring may detect infections in newborns
Authors: David Spurgeon
Journal: BMJ (2001)

A new electronic monitoring system may enable earlier detection of severe infection in newborn infants. Infection may be detectable up to 24 hours earlier than if visible symptoms are relied on. The procedure, developed by researchers at the University of Virginia Health System, requires no contact with the infant other than skin patches that monitor heart rate.

The monitoring technique, described in January's edition of the journal Pediatrics uses a new kind of mathematical analysis and computer software devised by …
British guidelines on managing hypertension
Authors: B. M Psaty, C. D Furberg
Journal: BMJ (1999)

Education and debate p 630 

This issue of the BMJ includes a summary of the new British Hypertension Society guidelines for managing hypertension.1 Recently, one of the authors of these guidelines commented on the strengths of the fifth and sixth reports of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC): “The JNC reports score highly on two counts—they took note of important new evidence, and unlike the others, delivered a clear message.”2 The same can be said of this version of the British guidelines, which represent an outstanding summary of the existing evidence about the diagnosis and treatment of hypertension. In contrast to the World Health Organisation-International Society of Hypertension3 and the Joint National Committee VI guidelines,4 the brevity of this version will make the British Hypertension Society guidelines especially usefulto clinicians.

The authors aimed to produce an evidence based document, and in the full version (reference 1 in 1) they applied the North of England Group criteria to grade the evidence for most recommendations. For instance, a low dose thiazide diuretic is listed as the first line treatment for patients with uncomplicated hypertension. This evidence based recommendation, appropriately, received a grade A rating, which signifies evidence from at least one …
Abstract 16199: Mutation of the SERCA-Reactive Cysteine-674 to Serine Attenuates Myocyte Apoptosis and Heart Failure in Mice With Chronic Pressure Overload
Authors: Fuzhong Qin, Robert J Morgan, Deborah A Siwik, Xiaoyong Tong, Richard A Cohen, Wilson S Colucci
Journal: Circulation (2014)

Introduction: Irreversible oxidation of sarcoplasmic reticulum (SR) calcium ATPase (SERCA2) at cysteine 674 (C674) prevents redox regulation of enzyme activity. In mice with pressure overload due to aortic constriction, we previously showed that SERCA2 C674 is oxidized and that its oxidation as well as myocyte apoptosis and left ventricular (LV) failure are prevented by transgenic expression of catalase. Therefore, SERCA2 oxidation may contribute to impaired SR filling leading to mitochondrial dysfunction and apoptosis. Hypothesis: We tested whether oxidation of SERCA2 C674 is necessary for pressure overload-induced LV apoptosis and failure. Methods and Results: Heterozygote SERCA2 knock-in mice (SKI) in which 50% C674 is mutated to serine and wild-type mice (WT) 10 weeks of age were subjected to ascending aortic constriction (AAC) or sham operation (n=7-12 per group). Echocardiography and immunohistochemistry were performed 12 weeks after AAC. In WT, AAC caused LV failure with increased LV end diastolic ...
The Cytosolic Sensor cGAS Detects Mycobacterium tuberculosis DNA to Induce Type I Interferons and Activate Autophagy
Authors: Robert O. Watson, Samantha L. Bell, Donna A. MacDuff, Jacqueline M. Kimmey, Elie J. Diner, Joanna Olivas, Russell E. Vance, Christina L. Stallings, Herbert W. Virgin, Jeffery S. Cox
Journal: Cell Host & Microbe (2015)
Abstract 127: Pyruvate Improves Electrolyte Homeostasis Following Cardiac Arrest
Authors: Brandon H Cherry, Anh Q Nguyen, Roger A Hollrah, Myoung-Gwi Ryou, Arthur G Williams, Besim Hoxha, Albert H Olivencia-Yurvati, Robert T Mallet
Journal: Circulation (2013)

Purpose: Intravenous infusion of sodium pyruvate can protect internal organs from ischemia-reperfusion imposed by cardiac arrest and resuscitation and may improve patient outcome. Cardiac arrest di...
First‐line treatment of 102 chronic myeloid leukemia patients with imatinib: A long‐term single institution analysis
Authors: Ilaria Viganò, Nunzio Di Giacomo, Sofia Bozzani, Laura Antolini, Rocco Piazza, Carlo Gambacorti Passerini
Journal: American Journal of Hematology (2014)

Imatinib mesylate radically changed the natural history of chronic myeloid leukemia (CML). The recent availability of alternative tyrosine kinase inhibitors (TKIs) renders the clinical management of CML more complex. In this article, we summarize our long‐term single institution experience. From 2003 to 2012, 102 patients with newly diagnosed chronic phase CML were referred to our institution and treated with imatinib mesylate as first‐line therapy. All patients were followed inside a dedicated CML clinic. At 1 year, 82/95 patients (86.3%) achieved complete cytogenetic response (CCyR) using a treatment performed analysis (TPA); when using an intention to treat analysis, 85/102 patients (83.3%) obtained CCyR. At 3 months, 58 patients (64.4% TPA) obtained a BCR‐ABL transcripts level &lt;10%. A major molecular response (MMR) was obtained by 38% and 53% of patients at 1 and 2 years. Twenty patients (19.6%) discontinued treatment with imatinib; six of them did so in the initial 2 years of treatment (4 for resistance and 2 for adverse events). We observed seven deaths (6.86%). Overall survival (OS) at 6 years is 95.1% (95% C.I. 90–100%) and is not different from that of the general population. No patient experienced progression of disease (95% C.I.: 0–3%). Our results suggest that patient management is a crucial point to obtain a successful therapeutic outcome: at 1 year CCyR and MMR rates are similar to the results obtained with second generation TKIs and OS is not different from that of the general population.Am. J. Hematol. 89:E184–E187, 2014. © 2014 Wiley Periodicals, Inc.
Intervening in Abusive Relationships—Reply
Authors: Thomas E Finucane
Journal: JAMA (2003)

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Abstract 25: Site of Cardiac Arrest: At Home and in Public Places, 2 Different Realities
Authors: Fernando Rosell-Ortiz, Francisco J Mellado-Vergel, Manuel Ruiz-Bailén
Journal: Circulation (2011)

One of the current debates on strategies to improve survival in cardiac arrest (CA) is whether the approach must be different as it occurs at home or in a public place. Our objective was to compare survival at hospital discharge of patients resuscitated from CA according to the place of the event. Methods: prospective cohort study from the Andalusian Registry of Out-of-hospital CA (Spain). Consecutive patients with CA of cardiac aetiology cared for by out-of-hospital emergency teams from Jan-2008 to Dec-2010. Dependent variable: place of CA (CA at home vs CA at public place). Multivariate analysis. Results: Advance life support maneuvers were performed in 2960 patients. Cardiac aetiology was diagnosed in 2331(78.75%) cases. Of these, 1328(57%) cases occurred at home. Distribution by gender and age was male 69% vs 76.6% (p&lt;0.0001), age 63.53 vs 61.47 years (p=0.002) at home vs public place respectively. The event was not witnessed in 52.1% vs 68.8% (home/public, p&lt;0.0001) and there was basic life support by witness in 35.2% vs 56.7% (home/public, p&lt;0.001) cases. Initial rhythm was shockable in 13.26% vs 26.79% (home/public, p&lt;0.0001). The median interval between collapse and emergency team on scene was 11 vs 12 minutes (home/public, p=0.04). Return of spontaneous circulation and hospital admission were achieved in 22.8% vs 33.4%(p&lt;0.0001) patients and survival at hospital discharge with good neurological function (CPC 1-2 ) in 5.72% vs 13.35% (p=0.006) home/public patients respectively. In the multivariate analysis, variables associated with the site of event: witness (OR 0.412;CI 0.245-0.692, p=0.001) survival with CPC 1-2 (OR 2.294;CI 1.338-3-931.692, p=0.003). Conclusions: Cardiac arrest at home is less witnessed and shows a survival rate lower than that occurring in public places and may require a specific strategy to improve outcomes.
Biocompatible polymeric nanocomplexes as an intracellular stimuli-sensitive prodrug for type-2 diabetes combination therapy
Authors: Feng-Zhen Wang, Zhi-Shen Xie, Lei Xing, Bing-Feng Zhang, Jia-Liang Zhang, Peng-Fei Cui, Jian-Bin Qiao, Kun Shi, Chong-Su Cho, Myung-Haing Cho, Xiaojun Xu, Ping Li, Hu-Lin Jiang
Journal: Biomaterials (2015)
Aborted Off-Pump Coronary Artery Bypass Patients Have Much Worse Outcomes Than On-Pump or Successful Off-Pump Patients
Authors: Ruyun Jin, Loren F. Hiratzka, Gary L. Grunkemeier, Albert Krause, U. Scott Page
Journal: Circulation (2005)

Background— Off-pump coronary artery bypass graft (CABG) surgery is purported to reduce perioperative mortality and morbidity compared with on-pump coronary bypass graft surgery. However, the outcomes of patients for whom an off-pump strategy must be changed to an on-pump procedure during surgery have not been extensively studied. Methods and Results— The Merged Cardiac Registry (Health Data Research, Inc) contains 70 514 isolated CABG performed from January 1998 to March 2004 in 40 facilities. Among them, 62 634 patients begun and completed on-pump bypass (CPB); 7880 patients begun off-pump, of which 7424 (94.2%) completed off-pump coronary artery bypass (OPCAB), whereas 456 (5.8%) were converted to on-pump (CONVERT). CONVERT patients were more severely ill. The observed mortality of CONVERT, CPB, and OPCAB was 9.9%, 3.0%, and 1.6%, respectively, and the observed-to-predicted ratio was 2.77, 1.20, and 0.74, respectively. CONVERT also had more morbidity than either OPCAB or CPB. Finally, a risk model was created to identify patients who might be at risk for conversion from off-pump to on-pump CABG. Conclusions— Patients who are intended for an off-pump strategy and then require conversion to on-pump have significantly higher operative mortality and morbidity than either completed OPCAB or CPB patients. In addition, the operative mortality and morbidity are far in excess of that predicted preoperatively. Based on these results, strong consideration should be given for a planned strategy of CPB for those patients with preoperative hemodynamic instability requiring a salvage CABG operation, left ventricular hypertrophy, or previous CABG.