tbuckley/cabot-search huggingface dataset:
Eculizumab in Paroxysmal Nocturnal Hemoglobinuria
Authors: Jaswinder Singh, Ashok K Malani, Maninder Pabla
Journal: New England Journal of Medicine (2006)

To the Editor: The study of eculizumab by Hillmen et al. (Sept. 21 issue)1 showed stabilization of hemoglobin levels and a reduction in transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria (PNH). However, there were more patients with a history of aplastic anemia in the placebo group than in the eculizumab group (27% vs. 14%), and the median duration of PNH was longer in the placebo group (9.2 years vs. 4.3 years). These differences may have favored the eculizumab group. Moreover, the more frequent use of anticoagulant agents in the eculizumab group (in 49% of patients, vs. 25% of those in the placebo group) might have prevented thrombosis in patients in the eculizumab group, apart from possible terminal complement inhibition. By the 26th week, about half the patients in the eculizumab group required blood transfusions despite continued use of the drug. Satheesh K. Kathula, M.D.
Glomerular hyperfiltration during sympathetic nervous system activation in early essential hypertension.
Authors: R E Schmieder, R Veelken, H Schobel, P Dominiak, J F Mann, F C Luft
Journal: Journal of the American Society of Nephrology (1997)

Glomerular hyperfiltration may be important for the development of essential hypertension. Both the renin-angiotensin system and the sympathetic nervous system influence renal hemodynamic regulation. To test the hypothesis that glomerular hyperfiltration can be unmasked by sympathetic nervous system activation, renal hemodynamics and humoral components of the renin-angiotensin system were examined at rest and during mental stress in 45 young normotensive healthy subjects and 37 young people with mild essential hypertension. GFR and renal plasma flow (RPF) were determined with inulin and para-aminohippuric acid clearance at rest and during stress. At rest, RPF, GFR, filtration fraction, plasma renin activity, angiotensin (Ang) II concentrations, and serum aldosterone values were similar in normotensive and hypertensive subjects. After stress, blood pressure increased (P < 0.01), but this was nearly identical in normotensive and hypertensive subjects (7.05 +/- 6.9 versus 7.03 +/- 4.6 mmHg, NS). The decrease in RPF (-27 +/- 54 versus -22 +/- 25 ml/min per 1.73 m2, NS) was also similar in the two groups. In contrast, the increase in GFR (+ 10.5 +/- 7.2 versus 6.08 +/- 5.7 ml/min per 1.73 m2, P < 0.001) and filtration fraction (+2.48 +/- 1.38 versus 1.82 +/- 1.49%, P < 0.05) was more marked in hypertensive than in normotensive subjects. The concomitant increase in Ang II concentrations was greater in hypertensive than in normotensive subjects (+4.6 +/- 1.0 versus -1.0 +/- 0.45 pg/ml, P < 0.001). The increase in GFR during mental stress was correlated with the increment in Ang II concentrations (r = 0.39, P < 0.001). Compared with the placebo control phase, blockade of the renin-angiotensin system with an angiotensin-converting enzyme inhibitor attenuated the increase in GFR during stress in hypertensive (8.04 +/- 5.01 versus 10.1 +/- 5.7 ml/min per 1.73 m2, P < 0.05), but not in normotensive, subjects. Even in early essential hypertension, glomerular hyperfiltration is evident during sympathetic nervous system activation, which is mediated by postglomerular vasoconstriction. This early stress-induced glomerular hyperfiltration may contribute to, or trigger, the development of essential hypertension.
Reduced dose of subcutaneous cladribine induces identical response rates but decreased toxicity in pretreated chronic lymphocytic leukaemia
Authors: D.C. Betticher, D. Ratschiller, S.-F. Hsu Schmitz, A. von Rohr, U. Hess, G. Zulian, M. Wernli, A. Tichelli, A. Tobler, M.F. Fey, T. Cerny
Journal: Annals of Oncology (1998)
Wasabi: An Integrated Platform for Evolutionary Sequence Analysis and Data Visualization
Authors: Andres Veidenberg, Alan Medlar, Ari Löytynoja
Journal: Molecular Biology and Evolution (2015)

Wasabi is an open source, web-based environment for evolutionary sequence analysis. Wasabi visualizes sequence data together with a phylogenetic tree within a modern, user-friendly interface: The interface hides extraneous options, supports context sensitive menus, drag-and-drop editing, and displays additional information, such as ancestral sequences, associated with specific tree nodes. The Wasabi environment supports reproducibility by automatically storing intermediate analysis steps and includes built-in functions to share data between users and publish analysis results. For computational analysis, Wasabi supports PRANK and PAGAN for phylogeny-aware alignment and alignment extension, and it can be easily extended with other tools. Along with drag-and-drop import of local files, Wasabi can access remote data through URL and import sequence data, GeneTrees and EPO alignments directly from Ensembl. To demonstrate a typical workflow using Wasabi, we reproduce key findings from recent comparative genomics studies, including a reanalysis of the EGLN1 gene from the tiger genome study: These case studies can be browsed within Wasabi at http://wasabiapp.org:8000?id=usecases. Wasabi runs inside a web browser and does not require any installation. One can start using it at http://wasabiapp.org. All source code is licensed under the AGPLv3.
Before I kick the bucket, I want to say thank you
Authors: John D Townsend
Journal: BMJ (2015)

In the years that followed the Institute of Medicine's "quality chasm" which inculcated the key elements of high-quality care, patient-centered care has moved from an abstract concept to the transformation of organizations and health systems.1 Towards this end, there has been much rumination about the structures and institutions that have served to keep the patient's role as mere recipient of health services, on the one hand, and the whipping boy for poor health status and outcomes as well as the high health expenditures, on the other hand.2But, at the same time that patient empowerment and shared-decision making gained prominence as key towards achieving patient-centered care, there have been musings that patient-centered care is going to a protracted and continuous pursuit, if not, an unattainable ideal.3The story of Mr. Townsend shows us not just what patient-centered care is in practice, but more importantly, that it can be done.Patient-centered care is possible when the patient is the focus in terms of what is meaningful and valuable to him/her and where the approach to treatment and care reflects both art of generalizations and the science of particulars.That the family and GP listened to, respected and honoured the wishes and worked with the individual patient to meet his needs is no mean feat.We are all aware of the family member(s) and health professional who configure decisions pertaining to the patient, if not make them in their own terms.As such, this is as much about Mr. Townsend as a person and patient as much as the kind of family, GP and indeed, health community that allowed for this wonderful case to be shared with the rest of the world.To you, Mr.Townsend, your GP and family and everyone in the NHS to whom our dear patient is grateful, my sincerest gratitude and best wishes as a comparative health systems and policy scholar and intermittent patient.
Mitomycin-C and vernal conjunctivitis11The following letter addresses an article in the February issue of the Journal: Akpek EK, Hasiripi H, Christen WG, Kalayci D. A randomized trial of low-dose, topical mitomycin-C in the treatment of severe vernal keratoconjunctivitis. (Ophthalmology 2000;107:263–9)
Authors: Suresh K Pandey, Jagjit S Saini, Liliana Werner, David J Apple
Journal: Ophthalmology (2000)
Evidence-Based Medicine applied to the control of communicable disease incidents when evidence is scarce and the time is limited
Authors: S Palmer, A Jansen, K Leitmeyer, H Murdoch, F Forland
Journal: Eurosurveillance (2013)

Control of acute communicable disease incidents demands rapid risk assessment, often with minimal peer-reviewed literature available but conducted in the public's view. This paper explores how methods of evidence-based medicine (EBM) can be applied in this scenario to improve decision making and risk communication. A working group with members from EBM organisations, public health institutions and the European Centre for Disease Prevention and Control used a six-stage framework for rapid risk assessments: preparation, risk detection/verification, risk assessment, development of advice, implementation, and evaluation. It concluded that data from observational studies, surveillance and modelling play a vital role in the evidence base. However, there is a need to further develop protocols and standards, to perform, report and register outbreak investigations more systematically and rigorously, and to allow rapid retrieval of the evidence in emergencies. Lack of evidence for risk assessment and advice (usual for new and emerging diseases) should be made explicit to policy makers and the public. Priorities are to improve templates for reporting and assessing the quality of case and outbreak reports, apply grading systems to evidence generated from field investigations, improve retrieval systems for incident reports internationally, and assess how to communicate uncertainties of scientific evidence more explicitly.
Sumatriptan: A Receptor-Targeted Treatment for Migraine
Authors: M. Moskowitz
Journal: Annual Review of Medicine (1993)

subtypes, neurogenic inflammation ABSTRACT Sumatriptan, recently introduced for the treatment of migraine, heralds the beginning of a molecular era in the pharmacological treatment of migraine headache. An indole (non-ergot alkaloid) derivative with agonist properties at a receptor resembling the 5-HTlD subtype (so-called 5-HT J- like receptor), J sumatriptan is the first antimigraine medication to exhibit receptor-selecti ve properties. Clinical data indicate that sumatriptan relieves headache, nausea, and photophobia in a majority of acute migraine patients, and it possesses favorable side effect and safety profiles. Of great importance, sumatriptan acts through a novel mechanism that we now know is shared by dihydroergotamin e and other useful compounds for the treatment of acute migraine headaches. In this summary, we briefly review the drug's mechanism of action and the emerging clinical experience with its use.
SupportScreen: A Model for Improving Patient Outcomes
Authors: Matthew Loscalzo, Karen Clark, Jeff Dillehunt, Redmond Rinehart, Rex Strowbridge, Daniel Smith
Journal: Journal of the National Comprehensive Cancer Network (2010)

As demands on physician time mount, and patients and families increasingly expect accommodation and understanding of their specific, personal situations, care providers must boost efficiency and minimize the expense of their clinic processes and draw on connections with community resources. Third-party payors may also expect that the biopsychosocial needs of patients and families be addressed as an essential part of cancer care. Quality of care, cost, patient satisfaction, adherence to treatment, safety, and allocation of limited resources are all related to the identification and effective management of the psychosocial elements of cancer care. Experts suggest that health care has lagged far behind other industries in using technology to improve efficiency, and slow adoption of this technology means that critical information about the biopsychosocial needs of patients fails to reach the right professionals in a timely way. Systematic and automated screening can promote physician control in managing time, the efficiency of the clinical encounter, and rapid triage to other professionals and community resources.
T cell regulation of autoimmune interstitial nephritis.
Authors: C J Kelly
Journal: Journal of the American Society of Nephrology (1990)

Research in organ-specific autoimmunity has been greatly facilitated over the past decade by advances in cellular and molecular immunology. Such studies have greatly expanded our understanding of autoimmune effector mechanisms and the nature of the target antigens recognized by these mediators. Another facet of organ-specific autoimmunity concerns the definition of those factors that determine host susceptibility to disease. This review outlines studies performed in two models of autoimmune interstitial nephritis that focus on issues of susceptibility and tolerance to parenchymal self antigens. In both models, antigen-specific regulatory T cells modulate the effector limb of the nephritogenic immune response and the pattern of interstitial injury. This modulation can be either stimulatory or inhibitory. The dominant regulatory effect is linked to genes in the major histocompatibility locus and is tightly correlated with disease expression. Regulatory T cells which inhibit the nephritogenic immune response can also be cultured in vitro and are highly efficacious as a therapeutic modality. These studies provide both the background and requisite reagents for delineating the mechanism(s) underlying antigen-specific T cell regulation.
Impaired atrial natriuretic factor systemic clearance contributes to its higher levels in uremia.
Authors: R Paniagua, M Franco, E Rodriguez, G Sanchez, G Morales, J Herrera-Acosta
Journal: Journal of the American Society of Nephrology (1992)

To evaluate the interaction between plasma levels and the systemic uptake of atrial natriuretic factor (ANF) with thyroid hormone levels during acute renal failure (ARF), seven groups of rats were analyzed: Group 1, Controls (C); Group 2, ARF; Group 3, filtering kidney with uremia; Group 4, ARF with thyroxine (T4) supplement (ARF + T4); Group 5, thyroidectomy (Tx); Group 6, ARF on Tx rats (Tx + ARF); Group 7, Tx + ARF supplemented with T4 (Tx + ARF + T4). Plasma creatinine (Cr), urea, T4, blood volume, and ANF were measured; ANF half-life (ANF t1/2; expressed in seconds) was calculated. Rats with ARF developed uremia (Cr, 377 +/- 58 versus 41 +/- 5 mumol/L), significant reduction in T4 (40 +/- 4 versus 89.2 +/- 6 nmol/L). elevation of ANF (287.7 +/- 35 versus 60.9 +/- 8 fmol/mL), and lengthening of ANF t1/2 (69.7 +/- 8 versus 37.2 +/- 6 s) compared with C (P less than 0.01). T4 supplements to ARF rats resulted in a lesser degree of uremia (Cr, 283 +/- 27; P less than 0.05) and normalization of ANF t1/2 (31.4 +/- 5); however, ANF levels remained higher than C (100.4 +/- 11.4 versus 60.9 +/- 8; P less than 0.01). Tx by itself did not change either parameter. The filtering kidney with uremia group developed mild uremia (Cr, 199 +/- 8), T4 fell (58 +/- 8), ANF levels rose (83.4 +/- 5.4), and ANF t1/2 was prolonged (54.5 +/- 12). Tx before ARF doubled the ANF level and lengthened ANF t1/2 similarly than in ARF. T4 addition (Tx + ARF + T4) normalized ANF t1/2 (29.8 +/- 3) in spite of a persistently high ANF (145.7 +/- 21). Blood volume did not change in any group.(ABSTRACT TRUNCATED AT 250 WORDS)
Time To Event Analyses in PANORAMA 2: A Phase 2 Study Of Panobinostat, Bortezomib, and Dexamethasone In Patients With Relapsed and Bortezomib-Refractory Multiple Myeloma
Authors: Paul G. Richardson, Robert L. Schlossman, Melissa Alsina, Donna M. Weber, Steven E. Coutre, Cristina Gasparetto, Sutapa Mukhopadhyay, Michael S. Ondovik, Mahmudul Khan, Carole S. Paley, Sagar Lonial
Journal: Blood (2013)
Lyme disease: time for a new approach?
Authors: Liesbeth Borgermans, Christian Perronne, Ran Balicer, Ozren Polasek, Valerie Obsomer
Journal: BMJ (2015)

Many more questions than answers

Lyme disease is the most common vector borne disease in North America and Europe, with 300 000 new cases in the United States1 and an estimated 100 000 new cases in Europe each year.2 These numbers are likely to be underestimates because case reporting is inconsistent3 and many infections go undiagnosed.4 Climate change may have contributed to a rapid increase in tick borne diseases, with migratory birds disseminating infected ticks.5 

Our common understanding of Lyme disease is that a tick bite is followed by the development of a classic rash pattern (erythema migrans). When treated early with a relatively short course of antibiotics, most patients have good outcomes.6 But the standard two tier testing for Lyme disease is inaccurate in the early …
Distribution and role of Na+?ase in endocardial endothelium
Authors: P Fransen
Journal: Cardiovascular Research (2001)

Objective: In mammalian cardiomyocytes, α isoforms of Na+/K+ ATPase have specific localisation and function, but their role in endocardial endothelium is unknown. Methods: Different α isoforms in endocardial endothelium and cardiomyocytes of rabbit were investigated by measuring contractile parameters of papillary muscles, by RT-PCR, by Western blots and by immunocytochemistry. Results: Inhibition of Na+/K+ ATPase by decreasing external K+ from 5.0 to 0.5 mmol/l caused biphasic inotropic effects. The maximal negative inotropic effect at external K+ of 2.5 mmol/l was significantly larger in +EE muscles (with intact endocardial endothelium) than in -EE muscles (with endocardial endothelium removed) (−22.5±2.4% versus −5.9±4.0%, n=7, P<0.05). Further decrease of K+ to 0.5 mmol/l caused endothelium-independent positive inotropy (27.8±11.8% for +EE versus 18.6±11.3% for −EE, n=7, P>0.05). Inhibition of Na+/K+ ATPase either by dihydro-ouabain (10−9 to 10−4 mol/l, n=4) or by K+ decrease following inhibition of Na+–H+ exchanger by dimethyl-amiloride (50 μmol/l, n=6) caused endothelium-independent positive inotropic effects only. RT-PCR and Western Blot demonstrated α1 and α2 Na-K-ATPase isoforms in cardiomyocytes, but only α1 in cultured endocardial endothelial cells. Immunohistochemistry showed that α1 in endocardial endothelium was predominantly present at the luminal side of the cell (n=7) and that α1 and α2 displayed different localisation in cardiomyocytes. Conclusions: These results suggested that negative and positive inotropic effects of Na+/K+ ATPase inhibition in +EE muscles could be attributed to inhibition of endocardial endothelial α1 and muscle α2 isoform, respectively. Accordingly, the endocardial endothelial α1 isoform of Na+/K+ ATPase may contribute to blood–heart barrier properties of this endothelium and may control cardiac performance via endothelial Na+/H+ exchange.
A prospective follow-up study of so-called borderline children
Authors: D P Lofgren, J Bemporad, J King, K Lindem, G O'Driscoll
Journal: American Journal of Psychiatry (1991)

The purpose of this study was to ascertain the current diagnosis in late adolescence or early adulthood of children who had previously been diagnosed as "borderline."This was a prospective follow-up study of 19 of a group of 32 children (ages 6-10) who had been diagnosed as "borderline" during their treatment at the Massachusetts Mental Health Center approximately 10-20 years earlier. Life history information was collected, and axis I and axis II diagnoses were assigned by use of the Structured Clinical Interview for DSM-III-R and unstructured clinical interviews.The most significant finding was that, contrary to expectations, there were no axis I diagnoses of affective disorders or schizophrenia. On the other hand, axis II diagnoses were prevalent, and the overall outcome for the subjects was poor. Family stability was the only significant predictor of the relatively good outcome of five of the subjects.The childhood borderline diagnosis appears to be an antecedent of an array of adult personality disorders, but it is not associated with the adult borderline personality disorder per se, nor with axis I diagnoses.
Abstract 1887: Calcium intake and milk product consumption in association with risk for colorectal adenomas
Authors: Caroline Um, Veronika Fedirko, W Dana Flanders, Roberd M. Bostick
Journal: Cancer Research (2015)

Abstract Calcium intake has been consistently, albeit modestly associated with lower risk of colorectal cancer and adenomas, and supplemental calcium reduced adenoma recurrence in large randomized controlled trials. Milk-based dairy products are the major source of dietary calcium in the US, but the association between milk product consumption and colorectal cancer is unclear. Conventionally produced milk contains significant levels of insulin-like growth factor 1 (IGF-1) from the use of bovine somatotropin hormone. Calcium intake has been positively associated with IGF-1 and IGF-1 binding protein 3 (IGFBP-3) levels. Higher circulating levels of IGF-1 and the IGF-1:IGFBP-3 ratio have been associated with higher risk of certain cancers, including breast, prostate, and colorectal, as well as with adenomatous polyps. To investigate associations of calcium and milk product intakes with risk for colorectal neoplasms, we pooled data from three colonoscopy-based case-control studies of incident, sporadic colorectal adenoma (n = 786 cases, 2,020 controls) conducted between 1991 and 2002, and analyzed the data using multivariable unconditional logistic regression. Dietary and supplemental intakes in all three studies were assessed using Willett food frequency questionnaires. For indirect indicators of IGF-1 intake from milk products, dietary calcium-adjusted residuals were calculated for total milk products and non-fat milk. For total, dietary, and supplemental calcium intakes, the multivariable-adjusted odds ratios (ORs) comparing the highest to the lowest quintiles of intake were 0.87 (95% confidence interval [CI] 0.63-1.20), 0.91 (95% CI 0.65-1.28), and 0.96 (95% CI 0.70-1.31), respectively. The corresponding ORs for consumption of total milk products, total milk, non-fat milk, total milk product residuals, and non-fat milk residuals were, 1.01 (95% CI 0.74-1.36), 0.97 (95% CI 0.73-1.29), 0.95 (95% CI 0.71-1.25), 0.92 (95% CI 0.70-1.22), and 0.97 (95% CI 0.70-1.34), respectively. For those who consumed any whole milk relative to those who consumed none, the OR was 1.15 (95% CI 0.89-1.50). These results are consistent with previous findings of modestly lower risk with higher total (dietary plus supplemental) calcium intakes, but suggest that neither the consumption of specific milk products nor all milk products combined, nor the non-calcium components of milk products are associated with risk for sporadic colorectal adenoma. Citation Format: Caroline Um, Veronika Fedirko, W Dana Flanders, Roberd M. Bostick. Calcium intake and milk product consumption in association with risk for colorectal adenomas. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1887. doi:10.1158/1538-7445.AM2015-1887
Initial Report of Cohort Study in Patients with Non-Small-Cell Lung Cancer (NSCLC) who were Treated with 1st-Line Platinum-Based Chemotherapy (Sapphire Study)
Authors: Y. Naito, K. Kishi, K. Yoh, Y. Goto, Y. Ohashi, H. Kunitoh
Journal: Annals of Oncology (2012)
Campagne de vaccination contre les infections à méningocoque dans une région rurale des Pays-Bas - Janvier 1998
Authors: J. E. van Steenbergen, A. G. Kraayeveld, L Spanjaard
Journal: Eurosurveillance (1999)

Neisseria meningitidis du groupe C est regulierement responsable d’epidemies en milieux scolaire et universitaire et dans des bases militaires. De telles epidemies communautaires ont ete decrites cette derniere decennie (1). Depuis qu’un vaccin polysaccharidique efficace et sans danger est disponible, la question de son administration et du moment de cette administration se pose regulierement. La delimitation du groupe cible a vacciner est toujours delicate et doit tenir compte de considerations variables suivant les situations.