tbuckley/cabot-search huggingface dataset:
Evidence‐based decision making and asthma in the internet age: the tools of the trade
Authors: A. R. Jadad
Journal: Allergy (2002)

At the dawn of the Information Age, the practice of evidence-based decision making (EBDM) is still hindered by many important barriers related to the decision makers, to the evidence per se or to the health system. Some of these barriers, particularly those related to the distillation, dissemination and packaging of research evidence, could be overcome by recent and ongoing developments in portable/wearable computers, internet appliances, multimedia and wireless broadband internet traffic. This article describes specific EBDM-related tools, with emphasis on internet-enabled "how to" books; and tools to improve the quality of reporting research, to formulate questions; to search for evidence; to access journals, systematic reviews and guidelines; to interact with organizations promoting EBDM; and to tailor evidence to individual cases. However, thinking that all barriers to the practice of EBDM could be solved by fancy information technology is naïve. Barriers related to the generation, interpretation, integration and use of the evidence demand more complex and perhaps unfeasible solutions, as overcoming them will require substantial changes in the structure of the health system, in the politics of science and in the way in which humans think and behave.
Inhibitory role of peroxisome proliferator-activated receptor gamma in hepatocarcinogenesis in mice and in vitro
Authors: Jun Yu, Bo Shen, Eagle S. H. Chu, Narci Teoh, Kin-Fai Cheung, Chung-Wah Wu, Shiyan Wang, Cleo N. Y. Lam, Hai Feng, Junhong Zhao, Alfred S. L. Cheng, Ka-Fai To, Henry L. Y. Chan, Joseph J. Y. Sung
Journal: Hepatology (2010)

Although peroxisome proliferator-activated receptor gamma (PPARγ) agonist have been shown to inhibit hepatocellular carcinoma (HCC) development, the role of PPARγ in hepatocarcinogenesis remains unclear. We investigated the therapeutic efficacy of PPARγ against HCC. PPARγ-deficient (PPARγ+/−) and wild-type (PPARγ+/+) littermates were used in a diethylnitrosamine (DEN)-induced HCC model and treated with PPARγ agonist (rosiglitazone) or the vehicle alone for 8 months. The effects of PPARγ on HCC cell growth and apoptosis were examined using PPARγ-expressing adenovirus (Ad-PPARγ). PPARγ+/− mice were more susceptible to DEN-induced HCC than PPARγ+/+ mice (94% versus 62%, P &lt; 0.05), and rosiglitazone significantly reduced the incidence of HCC in PPARγ+/+ mice (vehicle 62% versus treatment 24%, P &lt; 0.01), but not in PPARγ+/− mice, indicating that PPARγ suppresses hepatocellular carcinogenesis. A pronounced expression of PPARγ was observed in a HCC cell line (Hep3B) infected with Ad-PPARγ. Such induction markedly suppressed HCC cell viability ( P &lt; 0.01). Further, Hep3B infection with Ad-PPARγ revealed a decreased proportion of cells in S-phase (12.92% versus 11.58%, P &lt; 0.05), with arrest at G2/M phase (38.2% versus 55.68%, P &lt; 0.001), and there was concomitant phosphorylation of the key G2/M phase inhibitors cdc25C and cdc2. PPARγ overexpression increased cell apoptosis (21.47% versus 35.02%, P &lt; 0.01), mediated by both extrinsic (Fas and tumor necrosis factor-α) and intrinsic (caspase-9, caspase-3, caspase-7, and poly[ADP-ribose] polymerase) pathways. Moreover, PPARγ directly induced a putative tumor suppressor gene, growth differentiation factor-15. Conclusion: Loss of one PPARγ allele is sufficient to enhance susceptibility to HCC. PPARγ suppresses tumor cell growth through reducing cell proliferation and inducing G2/M phase arrest, apoptosis, and up-regulating growth differentiation factor-15. Thus, PPARγ acts as a tumor-suppressor gene in the liver. Hepatology 2010
Screening for the Risk for Bleeding or Thrombosis
Authors: Mark H. Eckman, John K. Erban, Sushil K. Singh, Grace S. Kao
Journal: Annals of Internal Medicine (2003)

Background: Numerous tests are available to assess patient risk for bleeding or thrombosis. Appropriate use of these tests must involve consideration of the clinical setting, disease prevalence, performance characteristics of the tests, cost, and consequences of false-positive and false-negative results. Purpose: To summarize information about coagulation testing in three common clinical settings: nonsurgical hospitalized patients, surgical patients, and patients having a first venous thromboembolic event. Data Sources: All English-language studies identified in searches of MEDLINE (1966 to April 2002) and reference lists of key articles. Study Selection: All published studies of blood coagulation testing as routine diagnostic tests or in the preoperative care of patients reporting postoperative bleeding complications, and all published studies of patients with the factor V Leiden mutation reporting venous thromboembolic outcomes. Data Extraction: 5 observational studies of routine coagulation testing in nonsurgical hospitalized patients and 12 observational studies of preoperative coagulation testing, from which both sensitivity and specificity could be calculated. Data Synthesis: Test performance characteristics for the partial thromboplastin time in predicting postoperative hemorrhage were pooled by type of surgery. Likelihood ratios for positive and negative results were calculated for each group; 95% confidence intervals were calculated. Patients with prolonged partial thromboplastin times did not have a statistically significantly increased risk for postoperative complications. Conclusion: For nonsurgical and surgical patients without synthetic liver dysfunction or a history of oral anticoagulant use, routine testing has no benefit in assessment of bleeding risk. Routine testing after a first episode of venous thromboembolism is not recommended for most patients.
P5-06-02: Response and Acquired Resistance of BRCA1-Deficient Triple-Negative Breast Cancer Xenografts to Alkylators or PARP Inhibitors.
Authors: Brugge P ter, der Burg E van, P Kristel, U Boon, Freixas C Moutinho, M Esteller, F Hogervorst, H Gevensleben, N Turner, J Wesseling, J Jonkers
Journal: Cancer Research (2011)

Abstract Background. BRCA1 mutated breast tumor cells are defective in DNA repair by homologous recombination and therefore especially sensitive to treatment with DNA double-strand break (DSB) inducing agents, such as alkylators or PARP inhibitors. However, such tumors can eventually develop therapy resistance. Understanding therapy resistance mechanisms may help in designing treatment strategies to overcome therapy resistance. Methods. We have developed BRCA1-deficient triple-negative breast cancer (TNBC) xenograft models by implantating fresh human breast tumor pieces and subsequent serial passaging. These models show epigenetic loss of BRCA1 due to promoter hypermethylation or genetic inactivation of BRCA1 due to a frameshift mutation (c.2210delC) resulting in a premature stop codon (p.Thr737LeufsX15). We have used these BRCA1-deficient TNBC models to study response and acquisition of resistance to alkylating therapy (cisplatin, melphalan) and the clinical PARP inhibitor olaparib. Results. Treated tumors were sensitive to the alkylators cisplatin or melphalan or the PARP inhibitor olaparib, in some cases resulting in complete remission with no palpable tumor left. However, relapses did occur in most cases and repeated treatment of recurrent tumors eventually led to aquired resistance. Since restoration of BRCA1 function has been suggested as a mechanism of therapy resistance (Swisher et al., Cancer Res 2008; 68: 2581), we determined BRCA1 expression in therapy-sensitive and -resistant tumors by Western blot analysis. While no full length BRCA1 protein could be detected in the therapy-sensitive tumors, expression of full length BRCA1 protein was found in the majority of cisplatin resistant and olaparib resistant tumors. BRCA1 reexpression in the therapy-resistant BRCA1-c.2210delC tumors was caused by genetic restoration of the reading frame due to reversion to the wildtype sequence or additional deletions near the c.2210delC mutation. BRCA1-re-expression in the therapy-resistant TNBC xenografts with epigenetic loss of BRCA1 was caused either by loss of BRCA1 promoter methylation or by complex rearrangements at the BRCA1 locus. Conclusion. Although BRCA1-deficient TNBC xenografts are initially very sensitive to alkylating agents and olaparib, resistance to treatment develops in almost all treated tumors. This acquired resistance is frequently associated with re-expression of BRCA1 due to secondary mutations or loss of promoter methylation. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-06-02.
Recommended treatment of paediatric tumours is misleading
Authors: C R Pinkerton, K. Pritchard-Jones, S J K Holmes
Journal: BMJ (1996)

Physicians working group, whose members included paediatricians, paediatric nephrologists, radiologists, microbiologists, general practitioners, paediatric urologists, and a parent.2The article makes no reference to the vital importance of the child's age to management, despite clear evidence that younger children are at far greater risk of developing renal scars with a urinary tract infection, infants under 1 year being especially vulnerable.This explains the
MPs praise treatment of injured soldiers but call for better contingency planning
Authors: J. Wise
Journal: BMJ (2010)

MPs have called for more robust contingency planning to cope with the possibility of greater casualties among soldiers in Iraq and Afghanistan.

A report on the Ministry of Defence from the House of Commons Public Accounts Committee praised the medical care provided for personnel injured as a result of fighting in Iraq and Afghanistan. It says that soldiers are surviving now who would never have survived in previous wars despite sustaining appalling injuries. Survival rates among these “unexpected survivors” are good in comparison with major trauma victims treated by the NHS.

Edward Leigh, the committee’s chairman, said; “The department [the Ministry of Defence] and its medical staff are providing …
Management of cardiac arrest in the community: a survey of resuscitation services.
Authors: R H Jones
Journal: BMJ (1983)

Container-grown Seyval blanc grapevines were subjected to varying crop and leaf levels. In adjusting leaf number, approximately 8 to 10 cm<sup>2</sup> leaf area per gram of fruit weight gave maximum total fruit weight, average berry weight, and °Brix. Leaf, stem, and root dry weights increased through 15 cm<sup>2</sup>/g, the maximum leaf area/ fruit weight measured. Titratable acidity (TA) and pH were not consistently changed. A reduction in leaf area affected vegetative growth first, °Brix next, and fruit weight last. In modifying leaf position in relation to a basal cluster, total fruit weight, °Brix, TA, pH, and vegetative growth were highest on plants with leaves distal to the clusters. These results were likely due to good exposure and greater area of leaves on these distal nodes. Regrowth from an apical node advanced fruit maturity and increased vegetative growth rather than compete with it. Shading lower leaves and the cluster (versus removing lower leaves) did not affect total fruit and average berry weights. Root dry weight was greater where leaves were shaded.
A Simple Visual Screening Test for Glucose-6-Phosphate Dehydrogenase Deficiency Employing Ascorbate and Cyanide
Authors: Harry S. Jacob, James H. Jandl
Journal: New England Journal of Medicine (1966)

HYPERSUSCEPTIBILITY to the hemolytic effects of such oxidant compounds as primaquine, acetylphenylhydrazine and sulfonamides may exist for a number of reasons, by far the most common of which is deficiency in the enzyme glucose-6-phosphate dehydrogenase (G6PD). Although this enzyme deficiency is best identified by quantitative assay, a number of presumptive, or screening, tests have been devised that are better suited to routine hematologic laboratories. These include the procedures originated by Beutler and his associates in which the representative hemolytic compound, acetylphenylhydrazine, was incubated with suspect blood and the red cells were examined for the number of Heinz bodies1 or for . . .
Future of Venereology
Authors: A. J. King
Journal: BMJ (1945)

theories of mental disorder are built up round wrong inter- pretations of the mechanism of these " cures."The medical profession should be reminded from time to time that these treatments are pure "shot-in-the-dark " affairs, and no theory of their action, even when they seem to work, is accepted even by the psychiatrists.The great example of this bad result of building on other than scientific foundations 'is provided by the treatment of mind disorder by operation on the brain.In good\faith mem-
American College of Physicians Ethics Manual
Authors: Lois Snyder
Journal: Annals of Internal Medicine (2012)

Medicine, law, and social values are not static. Reexamining the ethical tenets of medicine and their application in new circumstances is a necessary exercise. The sixth edition of the American College of Physicians (ACP) Ethics Manual covers emerging issues in medical ethics and revisits older ones that are still very pertinent. It reflects on many of the ethical tensions in medicine and attempts to shed light on how existing principles extend to emerging concerns. In addition, by reiterating ethical principles that have provided guidance in resolving past ethical problems, the Manual may help physicians avert future problems. The Manual is not a substitute for the experience and integrity of individual physicians, but it may serve as a reminder of the shared duties of the medical profession.
Mutations in KIT and RAS are frequent events in pediatric core-binding factor acute myeloid leukemia
Authors: B F Goemans, Ch M Zwaan, M Miller, M Zimmermann, A Harlow, S Meshinchi, A H Loonen, K Hählen, D Reinhardt, U Creutzig, G J L Kaspers, M C Heinrich
Journal: Leukemia (2005)
Mobilferrin is an intermediate in iron transport between transferrin and hemoglobin in K562 cells.
Authors: M E Conrad, J N Umbreit, E G Moore, D Heiman
Journal: Journal of Clinical Investigation (1996)

Iron is bound to transferrin in the plasma. A specific receptor on the cell surface binds transferrin and internalizes transferrin and the iron in clathrin-coated pits. These invaginate to form vesicles which release iron to the cytoplasm. Inorganic iron can be transported by an alternative pathway from iron citrate, utilizing a cell surface integrin and a cytoplasmic protein mobilferrin. This article shows that the two pathways donate iron to mobilferrin which acts as an intermediate between the iron bound to transferrin and the incorporation of iron into hemoglobin. Mobilferrin is found associated with the transferrin containing vesicles, and becomes labeled with iron released from transferrin in the vesicles. Mobilferrin is also found in the cytoplasm where pulse-chase experiments show that it, in turn, releases iron to be used for the synthesis of hemoglobin.
Egg Oral Immunotherapy (OIT) Induces Clinical Desensitization in a Double-Blind, Placebo-Controlled (DBPC) Trial in Egg Allergic Children from the Consortium of Food Allergy Research (CoFAR)
Authors: S.M. Jones, D.M. Fleischer, S.H. Sicherer, R.A. Wood, R. Lindblad, D. Stablein, A.H. Liu, W. Shreffler, D.Y.M. Leung, H.A. Sampson, A.W. Burks
Journal: Journal of Allergy and Clinical Immunology (2010)
Case of Mal-Assimilation of the Phosphates and Carbonates.-Reply
Authors: W. S. Christopher
Journal: JAMA (1892)

<h3>To the Editor of the Journal of the American Medical Association:</h3> I was recently asked to see a child, whom I had attended in its last illness, to determine whether or not it was actually dead. The child had been sick six weeks with influenza, and had finally succumbed to a complicating pneumonia. The illness had been very severe throughout, and it was only remarkable that it had lived as long as it did. I saw the child a few minutes before it died— at 6 P.M. Wednesday—at which time it was unconscious, and the respiration spasmodic and slow. On Saturday afternoon, nearly three days after death, I was asked to examine the body. The mother called attention to the fact that the lips were red, and feared lest the child was not really dead. The lips were indeed red, but upon parting them it was found that the redness
Monitoring muscle weakness in neonatal myasthenia gravis.
Authors: A A Hutchison, D J Lloyd, G Russell
Journal: BMJ (1975)

Paradoxical rise in blood pressure during propranolol treatment Common side effects of beta-blocking agents include nausea, vomiting, diarrhoea, ataxia, and psychosis.We record another, potentially lifethreatening reaction-namely, hypertension-which may be reversed by alpha-adrenergic-blocking agents.Patients, methods, and results
Hypocalcaemia-induced epilepsy during lactation.
Authors: R A Harrad, P G Kennedy
Journal: BMJ (1982)

Molluscum contagiosum: an unusual complication of tattooing Molluscum contagiosum is a common viral disease of the skin.The causative virus, from its size, shape, fine structure, cytoplasmic site of replication, and characteristic inclusion body, appears to be a member of the pox group.Transmission is thought to occur by direct contact, though the incubation period is not known and innoculation experiments have failed.Although any infective condition might theoretically be innoculated by tattooing, in practice the only diseases that have been reported are pyogenic infection, syphylis, tuberculosis, serum hepatitis, and one case of viral warts.' Case reportA 20-year-old mnan presented in September 1981.Seven months earlier he had had a tattoo professionally performed on his left upper arm with a single needle, using carbon, scarlet lake, and chlorinated copper pigments.Within three months of the tattooing a crop of seven lesions of molluscum contagiosum localised to the area of tattoo performed with carbon pigment had appeared.These had persisted until the tirne of consultation (figure).Direct microscopy of an unstained curetted lesion on a slide confirmed the diagnosis of molluscum contagiosum.A similar tattoo performed professionally on his right upper arm three years earlier had had no sequelae.He had had no other serious illnesses or skin diseases im the past apart from four common warts present on the palm of his right hand for four years.There was no family history of atopic disease.No treatment was given, and the lesions disappeared spontaneously within six months.Molluscum contagiosum localised to area of tattoo performed with carbon pigment.
Significance of Chymase-Dependent Angiotensin II–Forming Pathway in the Development of Vascular Proliferation
Authors: Masayoshi Nishimoto, Shinji Takai, Shokei Kim, Denan Jin, Atsushi Yuda, Masato Sakaguchi, Mayumi Yamada, Yoshihide Sawada, Keiichiro Kondo, Kunio Asada, Hiroshi Iwao, Shinjiro Sasaki, Mizuo Miyazaki
Journal: Circulation (2001)

Background Vascular tissues of humans and dogs contain chymase as an angiotensin II–forming enzyme. In this study, we investigated whether chymase-dependent angiotensin II formation plays a crucial role in the development of vascular proliferation in dog grafted veins. Methods and Results The right external jugular vein of dogs was grafted to the ipsilateral carotid artery. As a control group, the right external jugular veins in dogs that had not received grafts were used. In the chymase inhibitor–treated group, the vein was infiltrated with 10 μmol/L Suc-Val-Pro-Phe P (OPh) 2 and was grafted to the carotid artery. In the placebo-treated group, ACE activity in the grafted veins was significantly lower than that in the control veins up to 7 days after the operation, whereas chymase activity was increased significantly. After 7 days, the mRNA levels of collagen I, collagen III, and fibronectin, all of which are induced by an increase of angiotensin II action, were significantly increased in the grafted veins, and the intima-media ratio of the grafted veins was also increased. In the chymase inhibitor–treated group, the chymase activity in the grafted veins 7 days after the operation was suppressed to 12.1%. The elevated mRNA levels of fibronectin, collagen I, and collagen III in the grafted veins were significantly suppressed by treatment with the chymase inhibitor, and the intima-media ratio was also decreased significantly. Conclusions We demonstrate for the first time that chymase-dependent angiotensin II formation plays an important role in the development of vascular proliferation in the grafted veins.
What else can you expect at www.erj.ersjournals.com?
Authors: P. J. Sterk, K. F. Rabe
Journal: European Respiratory Journal (2006)

hat can you expect from the European Respiratory Journal (ERJ) in 2007?As we are all aware, the developments in respiratory science and medicine are more dynamic than ever.Scientific communication has become global and almost instantaneous, and as the Chief Editors we feel that it is our duty to present the ERJ to you as one of the main platforms highlighting the increasing advancements in the field.Effectively, this means that our mission to be ''rapid, reliable and responsive'' deserves an even more central position in our editorial and publishing strategy.So, what will be our priorities regarding the content of the Journal?How will this be pursued?And who is going to do it?
As AIDS epidemic approaches second decade, report examines what has been learned
Authors: M. F. Goldsmith
Journal: JAMA (1990)

ONCE UPON a time, no one in the world had ever heard of the acquired immunodeficiency syndrome (AIDS). Neither was the human immunodeficiency virus (HIV) known. That state of innocence ended forever less than 10 years ago.  A new report from the Committee on AIDS Research and the Behavioral, Social, and Statistical Sciences, a part of the National Research Council, sums up what has been learned in the past 9 years and discusses the evolving course of the epidemic in the United States.AIDS: The Second Decade(edited by Heather G. Miller, Charles F. Turner, and E. Lincoln Moses, National Academy Press, Washington, DC, 1990), was introduced in San Francisco in conjunction with the Sixth International Conference on AIDS.  Prevention, Intervention  The report addresses such topics as disease prevention and behavioral intervention, adolescents at risk, new problems concerning the blood supply, and issues involved in conducting the surveys deemed vital