tbuckley/cabot-search huggingface dataset:
Effect of an Increase in C-Reactive Protein Level during a Hemodialysis Session on Mortality
Authors: Johanna C. Korevaar, Jeannette G. van Manen, Friedo W. Dekker, Dirk R. de Waart, Elisabeth W. Boeschoten, Raymond T. Krediet
Journal: Journal of the American Society of Nephrology (2004)

The prevalence of chronic inflammation is high in dialysis patients. Moreover, it is associated with an increased mortality risk, yet the origin of chronic inflammation in dialysis patients remains unclear. The aim of this study was to determine the effect of a hemodialysis session (HD) on C-reactive protein (CRP) levels and to study the relation with survival. As part of a large, prospective, multicenter study in the Netherlands (Netherlands Cooperative Study on the Adequacy of Dialysis), patients who were started on dialysis treatment between September 1997 and May 1999 were included. Demographic data, clinical data, and serum samples were collected at regularly timed intervals. From this cohort, a random sample of patients was taken. CRP levels were determined before and after an HD session and before the next session. Date of death or censoring was recorded until September 2002. A total of 186 HD patients were included. Mean age was 65 yr (SD, 13); 56% were male. A total of 71 patients had a CRP level below the detection limit (3 mg/L), 68 patients showed no increase in CRP during an HD session (no-increase group), and 47 (25%) patients showed an increase in CRP level during an HD session (increase-group). No statistically difference in mean CRP levels before the dialysis session was found between the increase group (22.3 mg/L) and the no-increase group (19.4 mg/L). In the subsequent interdialytic period, CRP levels returned to the levels of the initial CRP value. Two-year survival was 44% in the increase group and 66% in the no-increase group (P = 0.09). Independent of CRP level before the session and adjusted for age, comorbidity, nutritional status, and primary kidney disease, a raise of 1 mg/L CRP during a session was associated with a 9% increased mortality risk (adjusted hazard ratio, 1.09; 95% CI, 1.02 to 1.16). The present study showed an increase in CRP level during a single dialysis session in 25% of the patients; during the succeeding interdialytic period, CRP level returned to its original value. More important, however, an increase in CRP level during an HD session was independently associated with a higher mortality risk.
The role of proximal dynamic joint stability in the development of exertional medial tibial pain: a prospective study
Authors: Ruth Verrelst, Dirk De Clercq, Jos Vanrenterghem, Tine Willems, Tanneke Palmans, Erik Witvrouw
Journal: British Journal of Sports Medicine (2013)

Objective To prospectively determine risk factors contributing to the development of exertional medial tibial pain (EMTP). Methods Data were prospectively collected on healthy female students in physical education, who were freshmen in 2010–2011 and 2011–2012. Eighty-six female students aged 19.38±0.85 years, were tested at the beginning of their first academic year. Kinematic parameters in the frontal and transverse plane were measured during a single-leg drop jump (SLDJ). For further analysis, the SLDJ task was divided in two phases: touchdown until maximal knee flexion (MKF) and then MKF until take-off, representing landing and push-off phase, respectively. The injury follow-up of the students was assessed using a weekly online questionnaire and a 3-monthly retrospective control questionnaire. EMTP was diagnosed by an experienced medical doctor. Cox regression analysis was used to identify the potential risk factors for the development of EMTP. Results During injury follow-up (1–2 years), 22 participants were diagnosed with EMTP. The results of this study identified that increased range of motion (ROM) in the transverse plane of hip and thorax during landing (p=0.010 and 0.026, respectively) and during push off (p=0.019 and 0.045, respectively) are predictive parameters for the development of EMTP in women. Conclusions Increased ROM values of hip and thorax in the transverse plane, which can be interpreted as impaired ability to maintain dynamic joint stability resulting in increased accessory movements, are significant contributors to the development of EMTP in women.
Q Fever Endocarditis in the United States
Authors: ROBERT C. KIMBROUGH
Journal: Annals of Internal Medicine (1979)

A patient with Q fever endocarditis, which is almost unknown in the United States, was followed for a total of 32 months; the study was begun 3 1/2 months before aortic valve replacement. Diagnosis was confirmed by serology, visualization of Coxiella burnetii in excised aortic valve tissue by direct and immunofluorescence staining, and isolation of C. burnetii from aortic valve tissue. Serum antibodies against phase I and phase II antigens of C. burnetii were identified. Almost all phase I and phase II antibodies were IgG. These findings are compared with those in an uncomplicated case of acute Q fever. New findings on the immune response to chronic Q fever are presented.
HCN2 Overexpression in Newborn and Adult Ventricular Myocytes
Authors: Jihong Qu, Andrea Barbuti, Lev Protas, Bina Santoro, Ira S. Cohen, Richard B. Robinson
Journal: Circulation Research (2001)

Abstract —Ventricular pacemaker current ( I f ) shows distinct voltage dependence as a function of age, activating outside the physiological range in normal adult ventricle, but less negatively in neonatal ventricle. However, heterologously expressed HCN2 and HCN4, the putative molecular correlates of ventricular I f , exhibit only a modest difference in activation voltage. We therefore prepared an adenoviral construct (AdHCN2) of HCN2, the dominant ventricular isoform at either age, and used it to infect neonatal and adult rat ventricular myocytes to investigate the role of maturation on current gating. The expressed current exhibited an 18-mV difference in activation (V 1/2 −95.9±1.9 in adult; −77.6±1.6 mV in neonate), comparable to the 22-mV difference between native I f in adult and neonatal cultures (V 1/2 −98.7 versus −77.0 mV). This did not result from developmental differences in basal cAMP, because saturating cAMP in the pipette caused an equivalent positive shift in both preparations. In the neonate, AdHCN2 caused a significant increase in spontaneous rate compared with control (88±5 versus 48±4 bpm). In adult, where HCN2 activates more negatively, the effect was evident only during anodal excitation, requiring significantly less stimulus energy than control (2149±266 versus 3140±279 mV · ms). Thus, ventricular maturational state influences the voltage dependence of expressed HCN2, resulting in distinct physiological impact of expressed channels in neonate and adult myocytes. The full text of this article is available at http://www.circresaha.org.
Patients with active inflammatory bowel disease lack immature peripheral blood plasmacytoid and myeloid dendritic cells
Authors: D C Baumgart
Journal: Gut (2005)

<b>Background:</b> Breakdown of tolerance against the commensal microflora is believed to be a major factor in the pathogenesis of inflammatory bowel disease (IBD). Dendritic cells (DC) have been implicated in this process in various animal models, but data on human DC in IBD are very limited. <b>Aim:</b> To characterise plasmacytoid DC (PDC) and myeloid DC (MDC) in patients with active versus inactive IBD and healthy controls. <b>Patients and Methods:</b> Peripheral blood was obtained from 106 patients (Crohn’s disease (CD) n = 49, ulcerative colitis (UC) n = 57) and healthy controls (n = 19). Disease activity was scored using the modified Truelove Witts (MTWSI) for UC and the Harvey Bradshaw severity indices (HBSI) for CD. Four colour flow cytometric analysis was used to identify, enumerate, and phenotype DC. DC from patients with acute flare ups and healthy controls were cultured and stimulated with CpG ODN 2006 or lipopolysaccharide (LPS). <b>Results:</b> IBD patients in remission (PDC UC, 0.39%; CD, 0.35%; MDC-1 UC, 0.23%; CD, 0.22% of PBMC) have slightly lower numbers of circulating DC compared with healthy controls (PDC 0.41%, MDC-1 0.25% of PBMC). In acute flare ups IBD patients experience a significant drop of DC (PDC UC, 0.04%; CD, 0.11%; MDC-1 UC, 0.11%; CD, 0.14% of PBMC) that correlates with disease activity (correlation coefficients: PDC MTWSI, 0.93; HBSI, 0.79; MDC-1 MTWSI, 0.75; HBSI, 0.81). Moreover, both express α4β7 integrin and display an immature phenotype. Freshly isolated PDC and MDC-1 from untreated flaring IBD patients express higher baseline levels of CD86 which increases further in culture and upon stimulation compared with healthy controls. <b>Conclusion:</b> IBD patients lack immature blood DC during flare ups which possibly migrate to the gut. An aberrant response to microbial surrogate stimuli suggests a disturbed interaction with commensals.
Caveolin-deficient mice: insights into caveolar function human disease
Authors: Babak Razani, Michael P. Lisanti
Journal: Journal of Clinical Investigation (2001)

In the past several decades, the discovery and detailed characterization of the various subcellular organelles has revealed the intricate workings of the cell. It is of great interest then, that one of the most prominent structures at the plasma membrane, the caveola, has remained the most enigmatic organelle found in cells. Together with their marker proteins, the caveolins, caveolae are present in large numbers in a variety of cell types. Although they were initially proposed to act as mere conduits for cellular uptake, akin to clathrin-coated vesicles, it is now clear that caveolae and caveolins have pleiotropic functions that modulate numerous cellular processes. Many proposed physiological roles for caveolae are controversial, making a rigorous analysis of their function imperative. A giant leap in this regard is the recent series of reports on the phenotypic characterization of caveolin-deficient mice. As loss of caveolin expression causes a concomitant loss in morphologically identifiable caveolae, such animals allow for the first definitive studies of the role of these organelles in various cells in vivo. In this review, we will discuss the known and proposed functions of caveolae in the context of these caveolin-deficient animal models, give a synopsis of the rapidly emerging themes in the field, and discuss the relevance of caveolae to the understanding of human disease.
Dispersion of the QT interval. A marker of therapeutic efficacy in the idiopathic long QT syndrome.
Authors: S G Priori, C Napolitano, L Diehl, P J Schwartz
Journal: Circulation (1994)

BACKGROUND QT interval dispersion, measured as interlead variability of QT, is a marker of dispersion of ventricular repolarization and, hence, of cardiac electrical instability. We tested the hypothesis that dispersion of ventricular repolarization may be differently affected by interventions destined to provide complete or incomplete protection against malignant arrhythmias in patients with long QT syndrome (LQTS). Twenty-eight patients affected by the Romano Ward form of LQTS entered the study and were divided into three groups: LQTS patients before institution of therapy, patients who did respond to beta-blocker therapy, and patients who continued to have syncope and cardiac arrest despite beta-blockade and who underwent left cardiac sympathetic denervation. A group of 15 healthy volunteers served as control subjects. METHODS AND RESULTS Dispersion of QT and QTc were calculated using two indexes: the difference between the longest and the shortest value measured in each of the 12 ECG leads (QTmax-QTmin, QTcmax-QTcmin) and the relative dispersion of QT and QTc (standard deviation of QT/QT average x100, standard deviation of QTc/QTc average x100). Both indexes of dispersion of repolarization were higher in the LQTS patients than in control subjects; also, patients not responding to beta-blockers had a significantly higher dispersion of repolarization than responders. A cutoff value of 100 milliseconds for QTmax-QTmin had an 80% sensitivity and 82% specificity in discriminating between responders and nonresponders. A cutoff value of 6 for QT relative dispersion yielded similar results. The LQTS patients who did not respond to beta-blockade underwent left cardiac sympathetic denervation and thereafter remained asymptomatic (mean follow-up, 5 +/- 4 years). In this group, dispersion of repolarization was significantly reduced by the surgical denervation to values similar to that of the responders to beta-blockade. CONCLUSIONS These data indicate that QT dispersion is a useful clinical tool to predict efficacy of antiadrenergic therapy in LQTS patients.
DNA methylation protects hematopoietic stem cell multipotency from myeloerythroid restriction
Authors: Ann-Marie Bröske, Lena Vockentanz, Shabnam Kharazi, Matthew R Huska, Elena Mancini, Marina Scheller, Christiane Kuhl, Andreas Enns, Marco Prinz, Rudolf Jaenisch, Claus Nerlov, Achim Leutz, Miguel A Andrade-Navarro, Sten Eirik W Jacobsen, Frank Rosenbauer
Journal: Nature Genetics (2009)
Tumor Vascular Changes Mediated by Inhibition of Oncogenic Signaling
Authors: Naseer Qayum, Ruth J. Muschel, Jae Hong Im, Lukxmi Balathasan, Cameron J. Koch, Sonal Patel, W. Gillies McKenna, Eric J. Bernhard
Journal: Cancer Research (2009)

Abstract Many inhibitors of the epidermal growth factor receptor (EGFR)-RAS-phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway are in clinical use or under development for cancer therapy. Here, we show that treatment of mice bearing human tumor xenografts with inhibitors that block EGFR, RAS, PI3K, or AKT resulted in prolonged and durable enhancement of tumor vascular flow, perfusion, and decreased tumor hypoxia. The vessels in the treated tumors had decreased tortuosity and increased internodal length accounting for the functional alterations. Inhibition of tumor growth cannot account for these results, as the drugs were given at doses that did not alter tumor growth. The tumor cell itself was an essential target, as HT1080 tumors that lack EGFR did not respond to an EGFR inhibitor but did respond with vascular alterations to RAS or PI3K inhibition. We extended these observations to spontaneously arising tumors in MMTV-neu mice. These tumors also responded to PI3K inhibition with decreased tumor hypoxia, increased vascular flow, and morphologic alterations of their vessels, including increased vascular maturity and acquisition of pericyte markers. These changes are similar to the vascular normalization that has been described after the antiangiogenic treatment of xenografts. One difficulty in the use of vascular normalization as a therapeutic strategy has been its limited duration. In contrast, blocking tumor cell RAS-PI3K-AKT signaling led to persistent vascular changes that might be incorporated into clinical strategies based on improvement of vascular flow or decreased hypoxia. These results indicate that vascular alterations must be considered as a consequence of signaling inhibition in cancer therapy. [Cancer Res 2009;69(15):6347–54]
Tuberculosis of the female genital tract
Authors: A. M Sutherland
Journal: BMJ (1978)

In a recent investigation on 31 male twin pairs cardiovascular reactions during stressful psychiatric interview were studied.5It was found that intrapair variance did not differ between monozygotic and dizygotic pairs at rest either for systolic or for diastolic blood pressure, but during psychological strain the intrapair variances were significantly less within monozygotic than dizygotic pairs for both measures of blood pressure.These data imply that a significant genetic influence on the variability of blood pressure might first be revealed in stressful situations.It was finally stated in your leading article that "clearly the best precaution a newborn baby can take over its arterial blood pressure and therefore its cardiovascular risk in later life is to choose its parents carefully."This hopeful piece of advice could be supplemented with another, more hopeful one: learn to cope with stressful situations.
Deformational Dynamics of the Aortic Root : Modes and Physiologic Determinants
Authors: P Dagum, G R Green, F J Nistal, G T Daughters, T A Timek, L E Foppiano, A F Bolger, N B Ingels, D C Miller
Journal: Circulation (1999)

Current surgical methods for treating aortic valve and aortic root pathology vary widely, and the basis for selecting one repair or replacement alternative over another continues to evolve. More precise knowledge of the interaction between normal aortic root dynamics and aortic valve mechanics may clarify the implications of various surgical procedures on long-term valve function and durability.To investigate the role of aortic root dynamics on valve function, we studied the deformation modes of the left, right, and noncoronary aortic root regions during isovolumic contraction, ejection, isovolumic relaxation, and diastole. Radiopaque markers were implanted at the top of the 3 commissures (sinotubular ridge) and at the annular base of the 3 sinuses in 6 adult sheep. After a 1-week recovery, ECG and left ventricular and aortic pressures were recorded in conscious, sedated animals, and the 3D marker coordinates were computed from biplane videofluorograms (60 Hz). Left ventricular preload, contractility, and afterload were independently manipulated to assess the effects of changing hemodynamics on aortic root 3D dynamic deformation. The ovine aortic root undergoes complex, asymmetric deformations during the various phases of the cardiac cycle, including aortoventricular and sinotubular junction strain and aortic root elongation, compression, shear, and torsional deformation. These deformations were not homogeneous among the left, right, and noncoronary regions. Furthermore, changes in left ventricular volume, pressure, and contractility affected the degree of deformation in a nonuniform manner in the 3 regions studied, and these effects varied during isovolumic contraction, ejection, isovolumic relaxation, and diastole.These complex 3D aortic root deformations probably minimize aortic cusp stresses by creating optimal cusp loading conditions and minimizing transvalvular turbulence. Aortic valve repair techniques or methods of replacement using unstented autograft, allograft, or xenograft tissue valves that best preserve this normal pattern of aortic root dynamics should translate into a lower risk of long-term cusp deterioration.
Genome-wide association study of survival from sepsis due to pneumonia: an observational cohort study
Authors: Anna Rautanen, Tara C Mills, Anthony C Gordon, Paula Hutton, Michael Steffens, Rosamond Nuamah, Jean-Daniel Chiche, Tom Parks, Stephen J Chapman, Emma E Davenport, Katherine S Elliott, Julian Bion, Peter Lichtner, Thomas Meitinger, Thomas F Wienker, Mark J Caulfield, Charles Mein, Frank Bloos, Ilona Bobek, Paolo Cotogni, Vladimir Sramek, Silver Sarapuu, Makbule Kobilay, V Marco Ranieri, Jordi Rello, Gonzalo Sirgo, Yoram G Weiss, Stefan Russwurm, E Marion Schneider, Konrad Reinhart, Paul A H Holloway, Julian C Knight, Chris S Garrard, James A Russell, Keith R Walley, Frank Stüber, Adrian V S Hill, Charles J Hinds
Journal: The Lancet Respiratory Medicine (2014)

Sepsis continues to be a major cause of death, disability, and health-care expenditure worldwide. Despite evidence suggesting that host genetics can influence sepsis outcomes, no specific loci have yet been convincingly replicated. The aim of this study was to identify genetic variants that influence sepsis survival.
Regional refractoriness within the ventricular conduction system. An evaluation of the "gate" hypothesis.
Authors: R Lazzara, N El-Sherif, B Befeler, B J Scherlag
Journal: Circulation Research (1976)

We studied the refractoriness of Purkinje fibers with the intent of localizing critical sites of block of premature impulses. To preserve the ventricular conducting system (VCS) nearly intact in vitro, we used a modification of the Elizari preparation. This was superfused with a physiologic salt solution. Action potential durations increased progressively from the His bundle to the distal Purkinje fibers along three pathways: (1) the main right bundle branch and moderator band; (2) the anterior border fibers of the left bundle and anterior false tendons; (3) the posterior border fibers of the left bundle and posterior false tendons. The action potential durations near the terminations of the false tendons were the longest ones found. The interior fibers of the left bundle branch had action potentials of shorter duration and greater variability than those of simultaneously activated fibers in the right bundle branch or the border fibers of the left bundle branch. Similarly, on the right side, the septal branches of the right bundle had action potentials of shorter duration than those of the moderator band. We also found that the fibers with short action potential durations provided the quickest pathways to septal myocardium. When extrastimuli were applied to the His bundle, block in a bundle branch always occurred in the proximal 1 or 2 cm of the main bundle branch. Experiments performed in vivo in which extrastimuli were delivered to the atrium or His bundle and recordings made from the terminations of false tendons and the distal ends of the main right bundle branch confirmed the finding that the critical sites of block were located in the proximal main bundle branches.
Undeclared motives in withdrawing a publication
Authors: Peter C Gøtzsche, Jan Mæhlen, Per-Henrik Zahl
Journal: The Lancet (2007)

In our Comment (Nov 25, p 1854),1Gøtzsche PC Mæhlen J Zahl PH What is publication?.Lancet. 2006; 368: 1854-1856Summary Full Text Full Text PDF PubMed Scopus (11) Google Scholar we described how our article that challenged the reliability of the Swedish Two-County trial of screening mammography,2Tabár L Fagerberg CJ Gad A et al.Reduction in mortality from breast cancer after mass screening with mammography. Randomised trial from the Breast Cancer Screening Working Group of the Swedish National Board of Health and Welfare.Lancet. 1985; 325: 829-832Summary Scopus (1434) Google Scholar although already published, was removed from the website of the European Journal of Cancer without cause. In a subsequent letter, Sabine Kleinert (March 17, p 901)3Kleinert S A withdrawn prepublication.Lancet. 2007; 369: 901Summary Full Text Full Text PDF PubMed Google Scholar explained that the Committee on Publication Ethics, after having discussed this case, concluded that it was correct of The Lancet to bring the case into the public domain and that our paper should not have been removed without due process. In the same issue of the journal, Peter Dean4Dean P A withdrawn prepublication.Lancet. 2007; 369: 901Summary Full Text Full Text PDF PubMed Google Scholar responded with arguments; that they are all false can easily be seen by comparing his letter with our Comment1Gøtzsche PC Mæhlen J Zahl PH What is publication?.Lancet. 2006; 368: 1854-1856Summary Full Text Full Text PDF PubMed Scopus (11) Google Scholar and our now-republished paper.5Zahl P-H Gøtzsche PC Andersen JM Mæhlen J Results of the Two-County trial of mammography screening are not compatible with contemporaneous official Swedish breast cancer statistics.Dan Med Bull. 2006; 53: 438-440PubMed Google Scholar Dean ends by stating that he has no conflict of interest, but hides his title of professor of radiology by giving his address as “Faculty of Medicine”. This is striking, since a Medline database search shows that Dean and the lead author of the Two-County trial, László Tabár, have collaborated for decades—since 1979, they have co-authored 16 mammography-related papers. They have also co-authored at least three books on the topic, including a teaching atlas of mammography. Finally, we have seen a copy of a letter that shows that Dean organised the process that led to removal of our paper from the European Journal of Cancer. PCG did a systematic review of the breast screening trials, which questioned the value of screening. JM and P-HZ declare that they have no conflict of interest.