tbuckley/cabot-search huggingface dataset:
Generation of experimental allergic airways inflammation in the absence of draining lymph nodes
Authors: Beata U. Gajewska, David Alvarez, Mariana Vidric, Susanna Goncharova, Martin R. Stämpfli, Anthony J. Coyle, José-Carlos Gutierrez-Ramos, Manel Jordana
Journal: Journal of Clinical Investigation (2001)

The objective of this study was to investigate the contribution of secondary lymphoid organs in the generation and maintenance of experimental allergic airway inflammation. We employed a previously reported murine model of respiratory mucosal allergic sensitization, induced by repeated aerosolizations of ovalbumin in the context of a GM-CSF airway environment. We executed this protocol in wild-type (WT) and lymphotoxin-α–deficient mice (LTα-KO) mice, which are devoid of lymph nodes (LNs) and possess rudimentary spleen structures. Despite the lack of pulmonary LNs draining the airway compartment, LTα-KO mice were fully capable of mounting a robust inflammatory response in the airways, consisting of Th2 polarized CD4+ T cells and eosinophils. This was accompanied by IL-5, IL-13, and IFN-γ production by splenocytes and generation of ovalbumin-specific serum IgE. Exposure to the same antigen 7 weeks after complete resolution of airway inflammation once again induced a Th2 polarized infiltrate, demonstrating intact immunological memory. To investigate inherent plasticity in establishing antigen-specific immunity, mice were splenectomized before sensitization. Allergic sensitization was completely abrogated in splenectomized LTα-KO mice, compared with eusplenic LTα-KO controls. These data demonstrate that secondary lymphoid organs, either LN or spleen, are essential for the generation of allergic airway responses.
Further Evidence Linking Late-Onset Alzheimer Disease With Chromosome 12
Authors: W. K. Scott, J. M. Grubber, S. M. Abou-Donia, T. D. Church, A. M. Saunders, A. D. Roses, M. A. Pericak-Vance, P. M. Conneally, G. W. Small, J. L. Haines
Journal: JAMA (1999)
THE FIXATION AND PROTECTION OF VIRUSES BY THE CELLS OF SUSCEPTIBLE ANIMALS
Authors: Peyton Rous, Philip D. McMaster, Stephen S. Hudack
Journal: The Journal of Experimental Medicine (1935)

Methods were developed for a study of the relations existing between viruses and living cells. It was found that vaccinia and the virus causing the infectious fibroma of rabbits (Shope) rapidly become fixed upon tissue cells freed as individuals and submitted to virus in suspension. This happens whether the cells are alive or have been killed with heat or ultraviolet light. The virus does not come away during agitation of the cells with Tyrode solution and repeated washings with large amounts of it. The exposure to neutralizing antisera of cells carrying virus fails to affect this latter significantly if the cells are alive, whereas if they are dead the activity of the virus is nullified. Cells freed as individuals from tissue cultures of vaccinia and the Shope tumor carry these viruses in abundance through repeated washings, and, if living, protect them from the influence of a neutralizing serum, whereas killed cells exert no such protection. The findings would appear to throw light on the way in which viruses gain a foothold in the host; and they suggest reasons for the persistence of some viruses in recovered animals and for the unsatisfactory results of serum treatment instituted during the course of virus diseases. The virus causing the Shope fibroma has been successfully maintained in cultures of the growth. It is closely associated with the cells, almost none being present in the culture fluid. Certain of its other attributes have been determined. Vaccinia greatly damages the cells of cultures of rabbit embryo in which it is under propagation.
Particulate Air Pollution as a Risk Factor for ST-Segment Depression in Patients With Coronary Artery Disease
Authors: Kai Jen Chuang, Brent A. Coull, Antonella Zanobetti, Helen Suh, Joel Schwartz, Peter H. Stone, Augusto Litonjua, Frank E. Speizer, Diane R. Gold
Journal: Circulation (2008)

The association of particulate matter (PM) with cardiovascular morbidity and mortality is well documented. PM-induced ischemia is considered a potential mechanism linking PM to adverse cardiovascular outcomes.
Variant Creutzfeldt-Jakob disease: prion protein genotype analysis of positive appendix tissue samples from a retrospective prevalence study
Authors: James W Ironside, Matthew T Bishop, Kelly Connolly, Doha Hegazy, Suzanne Lowrie, Margaret Le Grice, Diane L Ritchie, Linda M McCardle, David A Hilton
Journal: BMJ (2006)

<h3>Abstract</h3> <b>Objective</b> To perform prion protein gene (<i>PRNP</i>) codon 129 analysis in DNA extracted from appendix tissue samples that had tested positive for disease associated prion protein. <b>Design</b> Reanalysis of positive cases identified in a retrospective anonymised unlinked prevalence study of variant Creutzfeldt-Jakob disease (vCJD) in the United Kingdom. <b>Study samples</b> Three positive appendix tissue samples out of 12 674 samples of appendix and tonsil tested for disease associated prion protein. The patients from whom these samples were obtained were aged 20-29 years at the time of surgery, which took place in 1996-9. <b>Setting</b> Pathology departments in two tertiary centres in England and Scotland. <b>Results</b> Adequate DNA was available for analysis in two of the three specimens, both of which were homozygous for valine at codon 129 in the <i>PRNP</i>. <b>Conclusions</b> This is the first indication that the valine homozygous subgroup at codon 129 in the <i>PRNP</i> is susceptible to vCJD infection. All tested clinical cases of vCJD have so far occurred in the methionine homozygous subgroup, and a single case of probable iatrogenic vCJD infection has been identified in one patient who was a methionine/valine heterozygote at this genetic locus. People infected with vCJD with a valine homozygous codon 129 <i>PRNP</i> genotype may have a prolonged incubation period, during which horizontal spread of the infection could occur either from blood donations or from contaminated surgical instruments used on these individuals during the asymptomatic phase of the illness.
Abstract 2269: Lapatinib and obatoclax kill cns tumor cells through blockade of erbb1 / 3 / 4 and through inhibition of bcl-xl and mcl-1
Authors: Nichola A. Cruickshanks
Journal: Cancer Research (2012)

Abstract Previous studies in breast cancer cells have shown that Lapatinib (Lap) and Obatoclax (GX) interact in a greater than additive manner to cause cell death. The present studies sought to expand our analyses to CNS (Glioblastoma &amp; Medulloblastoma) tumor cells and to further advance our understanding of the mechanisms of drug action. Combinational treatment with Lap / GX resulted in enhanced tumor cell death in multiple CNS tumor types. Moreover, it was discovered that cells lacking PTEN function were resistant to drug combination lethality and re-expression of PTEN in PTEN null cells restored drug sensitivity. Furthermore, PTEN expressing cancer cells, sensitive to Lap / GX treatment, demonstrated drug resistance upon knockdown of PTEN. Additionally, we established that inhibition of ERBB1 / 3 / 4 receptors was most significant for enhancing GX lethality, and that knockdown of BCL-XL and particularly MCL-1, interacted to facilitate Lap lethality. Pre-treatment of tumor cells in vitro and in vivo with GX enhanced the lethality of Lap to a greater extent than concomitant treatment and suppressed tumor growth. Treatment of animals carrying orthotopic CNS tumor isolates and those implanted with anoikis resistant breast tumors in the brain with Lap / GX prolonged survival. Collectively our data argues that combinational Lap / GX therapy could be of use in the treatment of tumors located in the CNS. Further studies must be carried out in order to elucidate whether autophagy or apoptosis plays the most predominant role in cell death in response to Lap / GX treatment. 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 2269. doi:1538-7445.AM2012-2269
Management of Venous Thromboembolism: Present and Future
Authors: Jeffrey I. Weitz
Journal: Circulation (2004)

Management of Venous Thromboembolism: Present and FutureA n estimated 2 million people in the United States develop venous thromboembolism (VTE) annually.Anticoagulant therapy is the mainstay of VTE treatment.Once the diagnosis of VTE is established, prompt anticoagulation is necessary to prevent thrombus growth and to reduce the risk of pulmonary embolism (PE).At present, rapid anticoagulation can only be effected with parenteral agents.Low-molecular-weight heparin (LMWH) is rapidly replacing unfractionated heparin as the drug of choice for the initial treatment of most VTE patients.Because it can be given subcutaneously once or twice daily without coagulation monitoring, LMWH allows out-of-hospital management of patients with uncomplicated VTE, an approach that reduces healthcare costs and improves patient satisfaction.Extended anticoagulant treatment is necessary to prevent recurrent VTE.Vitamin K antagonists are the agents most often used for this purpose, and warfarin is the current drug of choice in North America.Recent clinical trials have provided important information regarding the optimal duration and intensity of anticoagulation treatment for patients with VTE.Anticoagulation therapy must be continued until the benefits of such treatment no longer outweigh the bleeding risk associated with long-term anticoagulation.What we have learned in recent years is that the risk of recurrent VTE after stopping anticoagulant therapy is low in patients whose VTE occurred in the setting of well-recognized reversible risk factors, such as surgery.In contrast, the risk of recurrence is high with ongoing risk factors, such as metastatic cancer.Surprisingly, the risk of recurrent VTE also is high when anticoagulation therapy is stopped in patients whose thrombosis occurred in the absence of any identifiable risk factors, regardless of whether or not there is an underlying thrombophilic defect.Thus, unprovoked thrombosis represents a chronic disease that is characterized by an ongoing risk of recurrence.Extended anticoagulation therapy with warfarin markedly reduces this risk, but the benefit is offset, at least in part, by the increased risk of bleeding with long-term anticoagulation.The balance between these competing risks in each individual patient dictates the optimal duration of anticoagulation therapy.Although LMWH represents an advance over unfractionated heparin, new anticoagulants have the potential to further enhance VTE treatment.For example, fondaparinux, a synthetic analog of the pentasaccharide sequence in heparin and LMWH that mediates their anticoagulant activity, not only shares all the advantages of LMWH over heparin, but also has the added feature that it does not cause heparin-induced thrombocytopenia.Building on these properties, a modified version of fondaparinux, known as idraparinux, has a longer half-life that permits onceweekly subcutaneous injections.Consequently, idraparinux has the
Micturition Syncope
Authors: Wishwa N. Kapoor
Journal: JAMA (1985)

We prospectively studied 33 patients with micturition syncope. Of these, eight were young (mean age, 25 years), healthy individuals whose diagnostic evaluation gave normal findings. The remaining 25 patients were older (mean age, 60 years), and 16 were women. This group had an average of 3.8 acute and chronic illnesses per patient, and was taking 3.5 medications per patient. Physical examination disclosed orthostatic hypotension in 22 of these 25 patients. Therapy was directed at improving orthostasis. Over a mean of 15.3 months, no recurrent micturition syncope or sudden death occurred in the entire group. We conclude that there are two groups of patients with micturition syncope. A group consisting of young healthy men has been well described previously. Our larger group, however, consisted of older patients, more often women with multiple illnesses and the majority having orthostatic hypotension.
Managing challenging behaviour in dementia
Authors: Gavin J Andrews
Journal: BMJ (2006)

A person centred approach may reduce the use of physical and chemical restraints 

C hallenging behaviour is a catch-all term that, in the context of dementia, includes one or combinations of shouting, wandering, biting, throwing objects, repetitive talking, destroying personal possessions and other objects, agitation and general anger, physical attacks on others, and waking others at night. In short, this term describes any behaviour by patients that is deemed to be dangerous to themselves, their fellow patients, and staff, or is considered antisocial within environments where those patients have to coexist with others on a long term basis.

The treatment of such behaviours has traditionally been led by institutional policies of control and containment, consisting of combinations of environmental, mechanical, or chemical restraint.1 However, such approaches are increasingly being challenged both on ethical grounds and for their evidence base. Now a randomised controlled trial in this …
A future for NICE, and the world's poorest children
Authors: T. Delamothe
Journal: BMJ (2010)

Given the conflicting messages emanating from the government, it would be great if we could tell you exactly what the future holds for NICE, but we can’t. As Rebecca Coombes says in her Q&A on the subject (doi:10.1136/bmj.c6390), we should know more once the government releases its consultation document, probably by the end of this month. In the meantime, we’ve assembled the opinions of a range of commentators.

In their editorial Alan Maynard and Karen Bloor describe the coalition government’s response to the agency as “puzzling” (doi:10.1136/bmj.c6286). On the one hand the recent white paper talks of broadening NICE’s scope. Yet it also introduced a cancer drug fund to “help patients get the cancer drugs their doctors recommend,” apparently regardless of the views of NICE.

They discuss …
Appeal court says US cannot seek payout from tobacco firms
Authors: Anne Harding
Journal: BMJ (2005)

The US government's case against the tobacco industry received a major blow last week when an appeal court ruled that federal government had no right to recover $280bn (£150bn; €220bn) in past profits from the industry.

The Department of Justice has charged that tobacco companies made the huge sum by selling cigarettes to minors and must “disgorge” (hand over to the government) these profits as a punishment to help prevent future wrongdoing ( BMJ 2004;329: 701). It is suing six tobacco …
Socioeconomic Factors and the Odds of Vaginal Birth After Cesarean Delivery
Authors: Dale E. King
Journal: JAMA (1994)

<h3>Objective.</h3> —To determine the independent effect of socioeconomic, organizational, and professional liability factors on the odds of vaginal birth after cesarean delivery (VBAC) while controlling for important clinical factors. <h3>Design.</h3> —A retrospective study of 1989 New York State vital statistics data, supplemented with additional information on county- and hospital-specific variables. Using multiple logistic regression analysis, odds ratios (ORs) and 95% confidence intervals (CIs) were derived for 15 independent variables. <h3>Setting.</h3> —Births occurring in 104 New York State hospitals. <h3>Data Set.</h3> —A total of 13944 births occurring to New York State residents with a history of cesarean delivery of which 3068 (22%) were vaginal deliveries. <h3>Results.</h3> —The odds of VBAC increased with maternal education. The ORs were 1.15 (95% CI, 0.99 to 1.34) for 12 years of education; 1.36 (95% CI, 1.16 to 1.60) for 13 to 15 years; 1.59 (95% CI, 1.32 to 1.93) for 16 years, and 2.00 (95% CI, 1.64 to 2.45) for 17 years or more. The ORs also increased with the level of care provided by the hospital; they were 1.55 (95% CI, 1.34 to 1.81) and 1.30 (95% CI, 1.18 to 1.44) for hospitals with intensive and intermediate neonatal care facilities, respectively. The ORs were 1.15 (95% CI, 1.02 to 1.30) for health maintenance organization participants and 0.77 (95% CI, 0.63 to 0.94) for women giving birth in government hospitals. The ORs of VBAC for African-American and Hispanic mothers were 0.80 (95% Cl, 0.70 to 0.93) and 0.61 (95% CI, 0.51 to 0.73), respectively. The ORs for a $5000 increase in physician's yearly malpractice premium and the hospital's paid loss due to malpractice claim settlements were 0.98 (95% CI, 0.97 to 0.99) and 1.01 (95% CI, 0.99 to 1.03), respectively. <h3>Conclusions.</h3> —In addition to clinical factors, a mother's level of education and ethnicity and specific characteristics of the hospital in which she delivers affect the odds of a vaginal delivery after a previous cesarean delivery. From our analysis, we cannot conclude that professional liability factors affected VBAC rates. (<i>JAMA</i>. 1994;272:524-529)
Financial threats to hospital libraries
Authors: Robert J. Joynt, Joanne G. Marshall, Lucretia W. McClure
Journal: JAMA (1991)

To the Editor.  — Hospital libraries are continuing to be threatened as a result of a change in federal regulations passed in 1986 by the Health Care Financing Administration. This change eliminated the requirement that hospitals maintain a medical library in order to be eligible for Medicare and Medicaid funding. 1 As financial pressures on hospitals have increased, the New York State Department of Health has also eliminated the requirement for medical libraries. D.H. Philips, Jr, a representative of David Axelrod, MD, commissioner of the Department of Health, justified this decision to Jane Allen, president, Upstate New York and Ontario Chapter of the Medical Library Association, on the basis that the Department of Health could not find a useful linkage between the requirement for a hospital to maintain a medical library and any problems that occurred with the delivery of hospital patient care and services (written communication, March 20,1989).  Professional
Gene delivery by combination of novel liposomal bubbles with perfluoropropane and ultrasound
Authors: Ryo Suzuki, Tomoko Takizawa, Yoichi Negishi, Kosuke Hagisawa, Kumiko Tanaka, Kaori Sawamura, Naoki Utoguchi, Toshihiko Nishioka, Kazuo Maruyama
Journal: Journal of Controlled Release (2006)
The Risk of Transfusion-Transmitted Infection
Authors: Roger Y. Dodd
Journal: New England Journal of Medicine (1992)

Four key measures help keep the use of blood safe. First, all who prescribe blood should try to limit the frequency of homologous transfusion by responding only to patients' physiologic needs and by using alternatives such as autologous transfusion and intraoperative blood salvage. Second, the selection of safe donors provides the greatest safety. For example, the current detection rate for human immunodeficiency virus (HIV) infection among active blood donors in the United States is between 5 and 10 confirmed positive results per 100,000 — that is, 1/40 to 1/80 of the rate anticipated in a random sample of the population, . . .
The State of the Arteries in Bright's Disease
Authors: W. R. Gowers
Journal: BMJ (1876)

From December ioth to the 17th the wound gradually became smaller, and the depression was less marked.One ligature was re- moved.On the I3th she sat up for the first time, and on the I5th port wine was commenced.The patient completely recovered, became pregnant, and was safely delivered of a son on April 6th, I876, the labour being natural.Nothiing at all was remarkable during the period of gestation.
Mammography results in substantial overdiagnosis of breast cancer, concludes study
Authors: J. Wise
Journal: BMJ (2012)

Screening mammography has resulted in the overdiagnosis of breast cancer in 1.3 million women in the United States in the past 30 years, concludes a new study.

Overdiagnosis means that tumors are detected on screening that would never lead to clinical symptoms, so women undergo unnecessary surgery, radiotherapy, and chemotherapy. The study, in the New England Journal of Medicine ,1 estimated that more than 70 000 women in the US were overdiagnosed in 2008, representing almost a third of all cases of breast cancer diagnosed in women aged 40 or over.

This latest research adds to …
Creativity and Madness: New Findings and Old Stereotypes
Authors: John E. Gedo
Journal: JAMA (1991)

Albert Rothenberg has devoted the major part of a distinguished psychiatric career to a broad program of research on creativity. In this excellent, concise volume, he reports his current views on this fascinating subject. The book is by no means confined to the limited topic implied by its title; it addresses itself to the effects on creative endeavors of a variety of adaptive disturbances and also deals with nonpathological aspects. <i>Creativity and Madness</i>is written for a nonspecialist readership; most of its chapters were previously published in journals for the laity and do not include the apparatus of comprehensive scholarly references or even the full research data on which Rothenberg's conclusions are based. Although it is, as a consequence, a very personal statement of the author's views in a field still lacking wide consensus, it is well argued and judicious and, therefore, a useful introduction to the domain of creativity
Impact of Collateral Flow to the Occluded Infarct-Related Artery on Clinical Outcomes in Patients With Recent Myocardial Infarction: A Report From the Randomized Occluded Artery Trial
Authors: Ph. Gabriel Steg, Arthur Kerner, G. B. John Mancini, Harmony R. Reynolds, Antonio C. Carvalho, Viliam Fridrich, Harvey D. White, Sandra A. Forman, Gervasio A. Lamas, Judith S. Hochman, Christopher E. Buller
Journal: Circulation (2010)

Collateral flow to the infarct artery territory after acute myocardial infarction may be associated with improved clinical outcomes and may also impact the benefit of subsequent recanalization of an occluded infarct-related artery.To understand the association between baseline collateral flow to the infarct territory on clinical outcomes and its interaction with percutaneous coronary intervention of an occluded infarct artery, long-term outcomes in 2173 patients with total occlusion of the infarct artery 3 to 28 days after myocardial infarction from the randomized Occluded Artery Trial were analyzed according to angiographic collaterals documented at study entry. There were important differences in baseline clinical and angiographic characteristics as a function of collateral grade, with generally lower-risk characteristics associated with higher collateral grade. Higher collateral grade was associated with lower rates of death (P=0.009), class III and IV heart failure (P<0.0001) or either (P=0.0002) but had no association with the risk of reinfarction. However, by multivariate analysis, collateral flow was neither an independent predictor of death nor of the primary end point of the trial (composite of death, reinfarction, or class IV heart failure). There was no interaction between angiographic collateral grade and the results of randomized treatment assignment (percutaneous coronary intervention or medical therapy alone) on clinical outcomes.In recent myocardial infarction, angiographic collaterals to the occluded infarct artery are correlates but not independent predictors of major clinical outcomes. Late recanalization of the infarct artery in addition to medical therapy shows no benefit compared with medical therapy alone, regardless of the presence or absence of collaterals. Therefore, revascularization decisions in patients with recent myocardial infarction should not be based on the presence or grade of angiographic collaterals. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00004562.