tbuckley/cabot-search huggingface dataset:
Mechanisms of Hypertension Associated With BAY 43-9006
Authors: Maria Luisa Veronese, Ari Mosenkis, Keith T. Flaherty, Maryann Gallagher, James P. Stevenson, Raymond R. Townsend, Peter J. O'Dwyer
Journal: Journal of Clinical Oncology (2006)

Purpose BAY 43-9006 (sorafenib) is an inhibitor of Raf kinase, the vascular endothelial growth factor (VEGF) receptor-2, and angiogenesis in tumor xenografts. The current study investigated the incidence, severity, and mechanism of blood pressure (BP) elevation in patients treated with BAY 43-9006. Patients and Methods Twenty patients received BAY 43-9006 400 mg orally twice daily. BP and heart rate were measured at baseline and then every 3 weeks for 18 weeks. VEGF, catecholamines, endothelin I, urotensin II, renin, and aldosterone were measured at baseline and after 3 weeks of therapy. We assessed vascular stiffness at baseline, after 3 to 6 weeks of therapy, and again after 9 to 10 months of therapy. Results Fifteen (75%) of 20 patients experienced an increase of ≥ 10 mmHg in systolic BP (SBP), and 12 (60%) of 20 patients experienced an increase of ≥ 20 mmHg in SBP compared with their baseline value, with a mean change of 20.6 mmHg (P &lt; .0001) after 3 weeks of therapy. There were no statistically significant changes in humoral factors, although there was a statistically significant inverse relationship between decreases in catecholamines and increases in SBP, suggesting a secondary response to BP elevation. Measures of vascular stiffness increased significantly during the period of observation. Conclusion Treatment with BAY 43-9006 is associated with a significant and sustained increase in BP. The lack of significant change in circulating factors suggests that these humoral factors had little role in the increase in BP.
Phase II open-label study of erlotinib in combination with gemcitabine in unresectable and/or metastatic adenocarcinoma of the pancreas: relationship between skin rash and survival (Pantar study)
Authors: E. Aranda, J.L. Manzano, F. Rivera, M. Galán, M. Valladares-Ayerbes, C. Pericay, M.J. Safont, M.J. Mendez, A. Irigoyen, A. Arrivi, J. Sastre, E. Díaz-Rubio
Journal: Annals of Oncology (2011)
Soft networks for bridging the gap between research and practice: illuminative evaluation of CHAIN
Authors: Jill Russell, Trisha Greenhalgh, Petra Boynton, Marcia Rigby
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objectives</b> To explore the process of knowledge exchange in an informal email network for evidence based health care, to illuminate the value of the service and its critical success factors, and to identify areas for improvement. <b>Design</b> Illuminative evaluation. <b>Setting</b> Targeted email and networking service for UK healthcare practitioners and researchers. <b>Participants</b> 2800 members of a networking service. <b>Main outcome measures</b> Tracking of email messages, interviews with core staff, and a qualitative analysis of messages, postings from focus groups, and invited and unsolicited feedback to the service. <b>Results</b> The informal email network helped to bridge the gap between research and practice by serving as a rich source of information, providing access to members9 experiences, suggestions, and ideas, facilitating cross boundary collaboration, and enabling participation in networking at a variety of levels. Ad hoc groupings and communities of practice emerged spontaneously as members discovered common areas of interest. <b>Conclusion</b> This study illuminated how knowledge for evidence based health care can be targeted, personalised, and made meaningful through informal social processes. Critical success factors include a broad based membership from both the research and service communities; a loose and fluid network structure; tight targeting of messages based on members9 interests; the presence of a strong network identity and culture of reciprocity; and the opportunity for new members to learn through passive participation.
Attenuated Glycogenolysis Reduces Glycolytic Catabolite Accumulation During Ischemia in Preconditioned Rat Hearts
Authors: Robert G. Weiss, Cicero P. de Albuquerque, Koenraad Vandegaer, V.P. Chacko, Gary Gerstenblith
Journal: Circulation Research (1996)

Prior transient episodes of ischemia ("ischemic preconditioning") reduce lactate accumulation and attenuate acidosis during a subsequent prolonged ischemic insult. The mechanisms responsible for attenuated glycolytic catabolite accumulation have not been established but may include earlier exhaustion of glycogen stores, slowed glycogenolysis before complete glycogen depletion, and/or inhibition of glycolysis. Simultaneous repeated measures of myocardial glycogen and the rates of glycolysis, glycogenolysis, glucose utilization, and glycolytic ATP production were obtained during total ischemia by 13C nuclear magnetic resonance spectroscopy in control and ischemia-preconditioned isolated rat hearts. Both [13C]glycolytic and [13C]glycogenolytic rates were significantly lower during total ischemia in preconditioned compared with control hearts (0.77 +/- 0.04 versus 1.06 +/- 0.06 mumol/min per gram wet weight [P < .01] for glycolysis and 0.15 +/- 0.07 versus 0.78 +/- 0.12 mumol/ min per gram wet weight [P < .001] for glycogenolysis, respectively, at 2.5 minutes of ischemia). Slowed glycolysis was present even during the early minutes of ischemia, when significant amounts of available [13C]glycogen were still present. Importantly, the reduction in the rate of glycogenolysis was larger and out of proportion to the reduction in glycolysis and occurred despite an increase in glucose utilization in preconditioned hearts (2.23 +/- 0.15 versus 1.5 +/- 0.10 mumol/min per gram wet weight at 1.25 minutes, P < .01). During early ischemia, conversion of glycogen phosphorylase to the a or "active" form was less in preconditioned than in control hearts (29.1 +/- 2.6% versus 41.2 +/- 9.8%, respectively; P < .05). Taken together, these findings demonstrate that ischemic preconditioning significantly depresses glycolytic catabolite accumulation during sustained ischemia not by more severe glycolytic inhibition or exhaustion of glycogen stores but by depressed glycogenolysis from the onset of ischemia.
Assessing Decisional Capacity for Clinical Research or Treatment: A Review of Instruments
Authors: Laura B. Dunn, Milap A. Nowrangi, Barton W. Palmer, Dilip V. Jeste, Elyn R. Saks
Journal: American Journal of Psychiatry (2006)

Objective: The need to evaluate decisional capacity among patients in treatment settings as well as subjects in clinical research settings has increasingly gained attention. Decisional capacity is generally conceptualized to include not only an understanding of disclosed information but also an appreciation of its significance, the ability to use the information in reasoning, and the ability to express a clear choice. The authors critically reviewed existing measures of decisional capacity for research and treatment. Method: Electronic medical and legal databases were searched for articles published from 1980 to 2004 describing structured assessments of adults’ capacity to consent to clinical treatment or research protocols. The authors identified 23 decisional capacity assessment instruments and evaluated each in terms of format, content, administration features, and psychometric properties. Results: Six instruments focused solely on understanding of disclosed information, and 11 tested for understanding, appreciation, reasoning, and expression of a choice. The instruments varied substantially in format, degree of standardization of disclosures, flexibility of item content, and scoring procedures. Reliability and validity also varied widely. All instruments have limitations, ranging from lack of supporting psychometric data to lack of generalizability across contexts. Conclusions: Of the instruments reviewed, the MacArthur Competence Assessment Tools for Clinical Research and for Treatment have the most empirical support, although other instruments may be equally or better suited to certain situations. Contextual factors are important but understudied. Capacity assessment tools should undergo further empirically based development and refinement as well as testing with a variety of populations.
Fear ever young: the terrorist death toll in perspective
Authors: H. Gunasekera
Journal: Journal of the Royal Society of Medicine (2006)

Why are people not afraid of driving? There are plenty of people afraid of flying, and the terrorist attacks of 2001 can only have exacerbated this phobia. Whenever you board a plane you can see them: anxious passengers gripping their boarding passes so hard they jam the automated counters at the boarding gates. Where are the masses sweating and shaking with fear as they climb into their cars?
Recommendations for the Outpatient Surveillance of Renal Transplant Recipients
Authors: BERTRAM L. KASISKE, MIGUEL A. VAZQUEZ, WILLIAM E. HARMON, ROBERT S. BROWN, GABRIEL M. DANOVITCH, ROBERT S. GASTON, DAVID ROTH, JOHN D. SCANDLING, GARY G. SINGER
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Many complications after renal transplantation can be prevented if they are detected early. Guidelines have been developed for the prevention of diseases in the general population, but there are no comprehensive guidelines for the prevention of diseases and complications after renal transplantation. Therefore, the Clinical Practice Guidelines Committee of the American Society of Transplantation developed these guidelines to help physicians and other health care workers provide optimal care for renal transplant recipients. The guidelines are also intended to indirectly help patients receive the access to care that they need to ensure long-term allograft survival, by attempting to systematically define what that care encompasses. The guidelines are applicable to all adult and pediatric renal transplant recipients, and they cover the outpatient screening for and prevention of diseases and complications that commonly occur after renal transplantation. They do not cover the diagnosis and treatment of diseases and complications after they become manifest, and they do not cover the pretransplant evaluation of renal transplant candidates. The guidelines are comprehensive, but they do not pretend to cover every aspect of care. As much as possible, the guidelines are evidence-based, and each recommendation has been given a subjective grade to indicate the strength of evidence that supports the recommendation. It is hoped that these guidelines will provide a framework for additional discussion and research that will improve the care of renal transplant recipients.
Forced oscillation technique for the evaluation of severe sleep apnoea/hypopnoea syndrome: a pilot study
Authors: None Badia, R Farre, JM Montserrat, E Ballester, L Hernandez, M Rotger, R Rodriguez-Roisin, D Navajas
Journal: European Respiratory Journal (1998)

The forced oscillation technique (FOT) is a noninvasive method of potential clinical interest for quantitatively assessing airway mechanics during sleep. We investigated the applicability of FOT as a diagnostic tool for noninvasive assessment of airflow obstruction in patients with sleep apnoea/hypopnoea syndrome (SAHS) during sleep. In seven patients previously diagnosed with severe SAHS (mean+/-SD apnoea/ hypopnoea index (AHI) 67+/-14) we performed a full polysomnography (PSG) together with on-line measurement of respiratory impedance (IZI) using FOT. For each patient we determined: 1) number of respiratory events conventionally detected by full PSG, those obtained by FOT and their degree of concordance; and 2) the characteristics and values of IZI during the respiratory events. FOT was well tolerated and easily applied in conjunction with a conventional sleep setup. The mean number of respiratory events x h(-1) detected by PSG and FOT were 55+/-16 and 58+/-17, respectively, with a strong concordance. IZI increased from a baseline of 11+/-4 to 50+/-20 cmH2O x L(-1) x s during apnoea (mean+/-SD). In all but one patient intermittent increases of IZI occurred immediately before each obstructive apnoea. In four patients, the increases of IZI developed at end-expiration whereas in two others occurred during inspiration. During hypopnoea most of the patients showed decreases of IZI during expiration. In conclusion, forced oscillation technique can be used as a noninvasive and complementary tool for the diagnosis of respiratory events and provides an on-line quantitative approach for continuous monitoring of airflow obstruction during sleep in patients with sleep apnoea/hypopnoea syndrome.
Lung function, genetics and ethnicity
Authors: P. Burney, R. Hooper
Journal: European Respiratory Journal (2014)

Professor Quanjer's editorial makes several errors in reporting our views on ethnicity and lung function [1], views that had been fairly summarised by Braun et al . [2] in the paper on which the editorial comments. Among his more unfortunate assertions is that our conclusions are reminiscent of the racist views of Hoffman. As the purpose of the paper to which the editorial refers was precisely to question the residual support that current assumptions provide for a racial explanation of ethnic differences [3], this seems particularly inappropriate.

The observed differences in vital capacity between different ethnic groups raise two principal questions, “What accounts for these differences?” and “What implications do they have for health?” The first question is unanswerable on the current evidence but the prevalent view, and one that would seem to be encouraged by Prof. Quanjer's peroration on the development of genetic diversity, is that it is explained by genetics. As Prof. Quanjer himself points out, however, associations are not necessarily causal, and low ventilatory function is also strongly associated with poverty.

Disentangling the contributions of genetics and poverty has not yet been possible. One technique used recently is liable to be over interpreted. Recognising that gene pools are increasingly mixed and that genetic structure may confound the interpretation of studies, geneticists have developed methods for quantifying genetic ancestry from the genome [4]. These methods are essential for adjusting for likely confounding in genetic studies, but they cannot be used to demonstrate a genetic origin for associated phenotypes. The greater the “African” component of the genome, the lower the lung function [5, 6], but this does not imply that the cause of …
Glycemic index, glycemic load, dietary carbohydrate, and dietary fiber intake and risk of liver and biliary tract cancers in Western Europeans
Authors: V. Fedirko, A. Lukanova, C. Bamia, A. Trichopolou, E. Trepo, U. Nöthlings, S. Schlesinger, K. Aleksandrova, P. Boffetta, A. Tjønneland, N.F. Johnsen, K. Overvad, G. Fagherazzi, A. Racine, M.C. Boutron-Ruault, V. Grote, R. Kaaks, H. Boeing, A. Naska, G. Adarakis, E. Valanou, D. Palli, S. Sieri, R. Tumino, P. Vineis, S. Panico, H. B(as). Bueno-de-Mesquita, P.D. Siersema, P.H. Peeters, E. Weiderpass, G. Skeie, D. Engeset, J.R. Quirós, R. Zamora-Ros, M.J. Sánchez, P. Amiano, J.M. Huerta, A. Barricarte, D. Johansen, B. Lindkvist, M. Sund, M. Werner, F. Crowe, K.T. Khaw, P. Ferrari, I. Romieu, S.C. Chuang, E. Riboli, M. Jenab
Journal: Annals of Oncology (2012)
Does rugby headgear prevent concussion? Attitudes of Canadian players and coaches
Authors: J A Pettersen
Journal: British Journal of Sports Medicine (2002)

Objectives: To examine the attitudes of players and coaches to the use of protective headgear, particularly with respect to the prevention of concussion. Methods: A questionnaire designed to assess attitudes to headgear was administered to 63 players from four different Canadian teams, each representing a different level of play (high school, university, community club, national). In addition, coaches from all four levels were questioned about team policies and their personal opinions about the use of headgear to prevent concussion. Results: Although the players tended to believe that the headgear could prevent concussion (62%), the coaches were less convinced (33%). Despite the players' belief that headgear offers protection against concussion, only a minority reported wearing headgear (27%) and few (24%) felt that its use should be made mandatory. Common reasons for not wearing headgear were “its use is not mandatory”, “it is uncomfortable”, and “it costs too much”. Conclusion: Although most players in the study believe that rugby headgear may prevent concussion, only a minority reported wearing it. Coaches tended to be less convinced than the players that rugby headgear can prevent concussion.
Effect of Vitamin D<sub>3</sub>Supplementation on Upper Respiratory Tract Infections in Healthy Adults
Authors: David R. Murdoch, Sandy Slow, Stephen T. Chambers, Lance C. Jennings, Alistair W. Stewart, Patricia C. Priest, Christopher M. Florkowski, John H. Livesey, Carlos A. Camargo, Robert Scragg
Journal: JAMA (2012)

Observational studies have reported an inverse association between serum 25-hydroxyvitamin D (25-OHD) levels and incidence of upper respiratory tract infections (URTIs). However, results of clinical trials of vitamin D supplementation have been inconclusive.To determine the effect of vitamin D supplementation on incidence and severity of URTIs in healthy adults.Randomized, double-blind, placebo-controlled trial conducted among 322 healthy adults between February 2010 and November 2011 in Christchurch, New Zealand.Participants were randomly assigned to receive an initial dose of 200,000 IU oral vitamin D3, then 200,000 IU 1 month later, then 100,000 IU monthly (n = 161), or placebo administered in an identical dosing regimen (n = 161), for a total of 18 months.The primary end point was number of URTI episodes. Secondary end points were duration of URTI episodes, severity of URTI episodes, and number of days of missed work due to URTI episodes.The mean baseline 25-OHD level of participants was 29 (SD, 9) ng/mL. Vitamin D supplementation resulted in an increase in serum 25-OHD levels that was maintained at greater than 48 ng/mL throughout the study. There were 593 URTI episodes in the vitamin D group and 611 in the placebo group, with no statistically significant differences in the number of URTIs per participant (mean, 3.7 per person in the vitamin D group and 3.8 per person in the placebo group; risk ratio, 0.97; 95% CI, 0.85-1.11), number of days of missed work as a result of URTIs (mean, 0.76 days in each group; risk ratio, 1.03; 95% CI, 0.81-1.30), duration of symptoms per episode (mean, 12 days in each group; risk ratio, 0.96; 95% CI, 0.73-1.25), or severity of URTI episodes. These findings remained unchanged when the analysis was repeated by season and by baseline 25-OHD levels.In this trial, monthly administration of 100,000 IU of vitamin D did not reduce the incidence or severity of URTIs in healthy adults.anzctr.org.au Identifier: ACTRN12609000486224.
Long term trends introduce a potential bias when evaluating the impact of the pneumococcal conjugate vaccination programme in England and Wales
Authors: S Flasche, M Slack, E Miller
Journal: Eurosurveillance (2011)

A pneumococcal conjugate vaccine (PCV7) was introduced into the United Kingdom's childhood immunisation schedule in September 2006. Evaluation of its impact on the incidence of invasive pneumococcal disease (IPD) as assessed by routine reports of laboratory-confirmed cases should take into account possible long-term trends due to factors like changes in case ascertainment. To this end, we compared pre-PCV7 trends in reported IPD incidence in England and Wales identified by blood culture with those for two other bacteraemias, Escherichia coli and non -pyogenic streptococci, for which there has not been any public health intervention. While no trend was detected in the age group 65 years and older, there was an annual increase of 3% and 11% in those aged under five years and between five and 64 years, respectively, which was similar for IPD and the other two pathogens. After PCV7 introduction, a continuing trend was only found for non-pyogenic streptococci in under five year-olds. These trends in the incidence for bacteraemias for which there has been no intervention could suggest that there have been changes in case ascertainment because of increased reporting or blood culturing. Accounting for them will improve the evaluation of the impact of PCV7 on IPD.
Addition of topical pimecrolimus to once-daily mid-potent steroid confers no short-term therapeutic benefit in the treatment of severe atopic dermatitis; a randomized controlled trial
Authors: J.M. Spergel, M. Boguniewicz, A.S. Paller, A.A. Hebert, P.R. Gallagher, C. McCormick, A. Parneix-Spake, T. Hultsch
Journal: British Journal of Dermatology (2007)

Combination therapy with pimecrolimus cream 1%, a topical calcineurin inhibitor (TCI), and fluticasone propionate cream 0.05% (FP), a mid-potency topical corticosteroid, may have a synergistic effect for treatment of atopic dermatitis (AD) because their mechanism of action differs.To assess the efficacy of concomitant pimecrolimus twice daily/FP once daily vs. vehicle twice daily/FP once daily in patients with severe AD.An exploratory, 2-week, double-blind, randomized, within-patient study was conducted (n = 45). Two target areas of similar severity, size and location were assessed. Assessments included the modified Eczema Area and Severity Index (0-12 scale) (primary variable), localized investigator global assessment (0-4 scale) and Patients' Self-Assessment of Disease Severity (0-4 scale).Data for all variables were similar for the TCI/FP and vehicle/FP treatments.The efficacy observed for treatment of severe AD flares with this TCI/FP combination regimen was equivalent to that of vehicle/FP.
Role of the Sinus Node in the Mechanism of Cholinergic Atrial Fibrillation
Authors: REGINALD A. NADEAU, FERNAND A. ROBERGE, JACQUES BILLETTE
Journal: Circulation Research (1970)

The effect of suppressing sinus rhythm on initiation and maintenance of atrial fibrillation was studied in 17 thoracotomized and artificially ventilated dogs. Atrial fibrillation was evoked by methacholine chloride applied to the right atrium followed by light mechanical stimulation. Episodes of fibrillation were compared before and after sinus rhythm had been suppressed by injection of absolute alcohol or concentrated sodium pentobarbital into the sinus node artery. Sixty-nine control episodes of atrial fibrillation lasting 6.00 ± 0.36 ( SE ) minutes were easily initiated while the heart was in sinus rhythm. The response to methacholine application plus mechanical stimulation depended on the type of escape rhythm obtained after suppression of sinus rhythm. In ten dogs with no sign of supra A-V junctional pacemaker activity, only 50% of the attempts to initiate fibrillation were successful. The 26 episodes of atrial fibrillation observed in this group of animals lasted 0.65 ± 0.23 ( SE ) minutes. In seven other dogs, supra A-V junctional pacemaker activity persisted after injection into the sinus node artery. In these seven dogs, 60% of the attempts at initiating fibrillation were successful, and the 18 episodes of fibrillation lasted 4.44 ± 0.30 ( SE ) minutes. In dogs showing no supra A-V junctional pacemaker activity, a more sustained arrhythmia was obtained after recovery of sinus node activity or during electrical pacing of the right atrial appendage. These observations suggest that the sinus node participates in the mechanism of cholinergic atrial fibrillation and that an equivalent role can be played by a natural or artificial supra A-V junctional pacemaker.