tbuckley/cabot-search huggingface dataset:
Timing, Predictive Factors, and Prognostic Value of Cerebrovascular Events in a Large Cohort of Patients Undergoing Transcatheter Aortic Valve Implantation
Authors: Luis Nombela-Franco, John G. Webb, Peter P. de Jaegere, Stefan Toggweiler, Rutger-Jan Nuis, Antonio E. Dager, Ignacio J. Amat-Santos, Anson Cheung, Jian Ye, Ronald K. Binder, Robert M. van der Boon, Nicolas Van Mieghem, Luis M. Benitez, Sergio Pérez, Javier Lopez, José A. San Roman, Daniel Doyle, Robert DeLarochellière, Marina Urena, Jonathon Leipsic, Eric Dumont, Josep Rodés-Cabau
Journal: Circulation (2012)

Background— The objective of this study was to evaluate the timing, predictive factors, and prognostic value of cerebrovascular events (CVEs) after transcatheter aortic valve implantation. Methods and Results— The study included 1061 consecutive patients who underwent transcatheter aortic valve implantation with a balloon-expandable (64%) or self-expandable (36%) valve. CVEs were classified as acute (≤24 hours), subacute (1–30 days), or late (&gt;30 days). CVEs occurred in 54 patients (5.1%; stroke, 4.2%) within 30 days after transcatheter aortic valve implantation (acute in 54% of cases). The predictors of acute CVEs were balloon postdilation of the valve prosthesis (odds ratio, 2.46; 95% confidence interval,1.07–5.67) and valve dislodgment/embolization (odds ratio, 4.36; 95% CI, 1.21–15.69); new-onset atrial fibrillation (odds ratio, 2.76; 95% CI, 1.11–6.83) was a predictor of subacute CVEs. Late CVEs occurred in 35 patients (3.3%; stroke, 2.1%) at a median follow-up of 12 months (3–23 months). The predictors of late CVEs were chronic atrial fibrillation (2.84; 95% CI, 1.46–5.53), peripheral vascular disease (hazard ratio, 2.02; 95% CI, 1.02–3.97), and prior cerebrovascular disease (hazard ratio, 2.04; 95% CI, 1.01–4.15). Major stroke was associated with 30-day (odds ratio, 7.43; 95% CI, 2.45–22.53) and late (hazard ratio, 1.75; 95% CI, 1.01–3.04) mortality. Conclusions— In a large cohort of patients undergoing transcatheter aortic valve implantation, the rates of acute and subacute CVEs were 2.7% and 2.4%, respectively. While balloon postdilation and valve dislodgment/embolization were the predictors of acute CVEs, new-onset atrial fibrillation determined a higher risk for subacute events. Late events were determined mainly by a history of chronic atrial fibrillation and peripheral and cerebrovascular disease. The occurrence of major stroke was associated with increased early and late mortality. These results provide important insights for the implementation of preventive measures for CVEs after transcatheter aortic valve implantation.
Human very low density lipoproteins and chylomicrons can protect against endotoxin-induced death in mice.
Authors: H W Harris, C Grunfeld, K R Feingold, J H Rapp
Journal: Journal of Clinical Investigation (1990)

Endotoxemia stimulates many physiologic responses including disturbances in lipid metabolism. We hypothesized that this lipemia may be part of a defensive mechanism by which the body combats the toxic effects of circulating endotoxin. We tested the effects of mixtures of endotoxin, lipoproteins, and lipoprotein-free plasma and determined the ability of varying concentrations of human very low density lipoproteins (VLDL) and chylomicrons, as well as low density lipoproteins (LDL) and high density lipoproteins (HDL), and of the synthetic lipid emulsion SOYACAL to prevent endotoxin-induced death in mice. This study demonstrates that the triglyceride-rich VLDL and chylomicrons, as well as cholesterol-rich LDL and HDL, and cholesterol-free SOYACAL can protect against endotoxin-induced death. Protection required small amounts of lipoprotein-free plasma, and depended on the incubation time and the concentration of lipoprotein lipid. Despite stringent techniques to prevent exogenous endotoxin contamination eight of ten duplicate VLDL preparations contained endotoxin (5,755 +/- 3,514 ng endotoxin/mg triglyceride, mean +/- SEM) making the isolation of endotoxin-free VLDL difficult. In contrast, simultaneous preparations of LDL and HDL were relatively free of endotoxin contamination (3 +/- 3 and 320 +/- 319 ng/mg total cholesterol, respectively), suggesting that the contamination of VLDL occurs in vivo and not during the isolation procedure. These observations suggest a possible role for increased triglyceride-rich lipoproteins in the host's defense against endotoxemia and infection.
Outcome Reporting in Industry-Sponsored Trials of Gabapentin for Off-Label Use
Authors: S. Swaroop Vedula, Lisa Bero, Roberta W. Scherer, Kay Dickersin
Journal: New England Journal of Medicine (2009)

There is good evidence of selective outcome reporting in published reports of randomized trials.We examined reporting practices for trials of gabapentin funded by Pfizer and Warner-Lambert's subsidiary, Parke-Davis (hereafter referred to as Pfizer and Parke-Davis) for off-label indications (prophylaxis against migraine and treatment of bipolar disorders, neuropathic pain, and nociceptive pain), comparing internal company documents with published reports.We identified 20 clinical trials for which internal documents were available from Pfizer and Parke-Davis; of these trials, 12 were reported in publications. For 8 of the 12 reported trials, the primary outcome defined in the published report differed from that described in the protocol. Sources of disagreement included the introduction of a new primary outcome (in the case of 6 trials), failure to distinguish between primary and secondary outcomes (2 trials), relegation of primary outcomes to secondary outcomes (2 trials), and failure to report one or more protocol-defined primary outcomes (5 trials). Trials that presented findings that were not significant (P > or = 0.05) for the protocol-defined primary outcome in the internal documents either were not reported in full or were reported with a changed primary outcome. The primary outcome was changed in the case of 5 of 8 published trials for which statistically significant differences favoring gabapentin were reported. Of the 21 primary outcomes described in the protocols of the published trials, 6 were not reported at all and 4 were reported as secondary outcomes. Of 28 primary outcomes described in the published reports, 12 were newly introduced.We identified selective outcome reporting for trials of off-label use of gabapentin. This practice threatens the validity of evidence for the effectiveness of off-label interventions.
Lipid lowering drugs in diabetes: Lipid lowering has ophthalmic benefits
Authors: Hiten G Sheth, Sher Aslam, Nigel Davies
Journal: BMJ (2006)

EDITOR—Lipid lowering treatment in diabetes has ophthalmic benefits.1 Diabetic maculopathy is a common cause of loss of sight in diabetic patients and is characterised by retinal oedema and lipid exudates. The use of atorvastatin in diabetic maculopathy has recently been shown in a randomised controlled trial to decrease visible lipid exudates and …
Open access approach to medical research publishing will continue to grow, experts predict
Authors: A. O'Dowd
Journal: BMJ (2011)

An online, open access approach to publishing scientific and medical research is proving successful and will continue to develop, MPs have been told.

Experts in publishing who were giving evidence to the parliamentary science and technology select committee on 23 May said that the approach used by Public Library of Science ( PLoS ) One —an online, open access journal for the communication of peer reviewed scientific and medical research—was being increasingly adopted by other organisations.

PLoS One and others such as the BMJ , which had followed its example, were speeding up research and enabling more research to be published, MPs were told as part of their inquiry into peer review.

The committee asked how much faster the PLoS website was …
Spectrum and Prevalence of Atherogenic Risk Factors in 27,358 Children, Adolescents, and Young Adults With Type 1 Diabetes
Authors: K. Otfried Schwab, Jürgen Doerfer, Wolfgang Hecker, Jürgen Grulich-Henn, Dagobert Wiemann, Olga Kordonouri, Peter Beyer, Reinhard W. Holl
Journal: Diabetes Care (2006)

OBJECTIVE—The aim of this data analysis was to ascertain the type and prevalence rate as well as age and sex distribution of cardiovascular risk factors in type 1 diabetic patients up to 26 years of age. RESEARCH DESIGN AND METHODS—Cardiovascular risk factors such as obesity, hypertension, dyslipidemia, poor glycemic control, and smoking were analyzed in 27,358 patients who were divided into three groups (prepubertal, pubertal, and adult) using specifically designed diabetes software for prospective disease documentation. RESULTS—More than half of the patients per age-group had at least one cardiovascular risk factor. Two risk factors were age dependently found in 6.2–21.7% and three or four risk factors in 0.5–4.7%. Elevated values of HbA1c, total cholesterol, and BMI were found most frequently. Hypertension, smoking, and HDL cholesterol were observed more frequently in males, and elevated BMI, total cholesterol, and LDL cholesterol more often in females. Although 28.6% of the patients had dyslipidemia, merely 0.4% of them received medical treatment, and of the 8.1% of the patients with hypertension, only 2.1% of them were given antihypertensive medication. CONCLUSIONS—With increasing age, a greater number of patients with cardiovascular risk factors were observed. Significant sex differences were seen in the majority of risk factors. Despite the high prevalence of risk factors, only a small minority of patients received antihypertensive or lipid-lowering treatment. Early identification, prevention, and treatment of additional risk factors seem to be necessary, particularly in light of the high incidence of future cardiovascular disease.
Effects of inspiratory muscle training and respiratory exercise at muscle function, thoracoabdominal mobility and dyspnea in patients with COPD
Authors: Renata Basso-Vanelli, Eloisa Regueiro, Ivana Labadessa, Valéria Di Lorenzo, Mauricio Jamami, Dirceu Costa
Journal: European Respiratory Journal (2013)

Background: as a method of therapeutic approaches to respiratory muscles we found in the literature the inspiratory muscle training (IMT) and respiratory exercises (RE). Even the RE is a method well used in the clinical practice, it is necessary scientific evidence, especially regarding the difference that could be observed when compared the RE to IMT. Aims: to compare the effects of IMT and RE added to physical training (PT) as to gain strength and endurance of the inspiratory muscles, thoracoabdominal mobility and dyspnea in COPD patients. Methods: 25 patients completed the study: 13 (67.5 ±12.8 years; FEV1, 46.9±18.5 % predictive) composed IMT group (GPT+IMT) and 12 (mean ± SD age, 66±7.6 years; FEV1, 36.1±9.7% predictive) RE group (GPT+RE). Patients were assessed before and after 48 sessions of training; spirometry; measures of maximum inspiratory (MIP) and expiratory pressure (MEP), inspiratory muscle endurance test in which it was determined the sustained maximum inspiratory pressure (SMIP) and the limit time (Tlim), cirtometry and reported the modified Medical Research Council (mMRC). Results: both groups showed significant increased (p<0.05) strength and endurance of the inspiratory muscles, thoracoabdominal mobility. The GPT+IMT showed higher increase of MIP, SMIP, abdominal mobility values and decreased in the mMRC score. Conclusion: both interventions showed gain strength and endurance of the inspiratory muscles and thoracoabdominal mobility. Although, only the GPT+IMT showed clinically rise in the inspiratory muscle strength and endurance due to specificity of training, which caused larger fall of dyspnea.
Clinical and Molecular Characterization of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia
Authors: Silvia G. Priori, Carlo Napolitano, Mirella Memmi, Barbara Colombi, Fabrizio Drago, Maurizio Gasparini, Luciano DeSimone, Fernando Coltorti, Raffaella Bloise, Roberto Keegan, Fernando E.S. Cruz Filho, Gabriele Vignati, Abraham Benatar, Angelica DeLogu
Journal: Circulation (2002)

Background — Mutations in the cardiac ryanodine receptor gene ( RyR2 ) underlie catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited arrhythmogenic disease occurring in the structurally intact heart. The proportion of patients with CPVT carrying RyR2 mutations is unknown, and the clinical features of RyR2 -CPVT as compared with nongenotyped CPVT are undefined. Methods and Results — Patients with documented polymorphic ventricular arrhythmias occurring during physical or emotional stress with a normal heart entered the study. The clinical phenotype of the 30 probands and of 118 family members was evaluated, and mutation screening on the RyR2 gene was performed. Arrhythmias documented in probands were: 14 of 30 bidirectional ventricular tachycardia, 12 of 30 polymorphic ventricular tachycardia, and 4 of 30 catecholaminergic idiopathic ventricular fibrillation; RyR2 mutations were identified in 14 of 30 probands (36% bidirectional ventricular tachycardia, 58% polymorphic ventricular tachycardia, 50% catecholaminergic idiopathic ventricular fibrillation) and in 9 family members (4 silent gene carriers). Genotype-phenotype analysis showed that patients with RyR2 CPVT have events at a younger age than do patients with nongenotyped CPVT and that male sex is a risk factor for syncope in RyR2 -CPVT (relative risk=4.2). Conclusions — CPVT is a clinically and genetically heterogeneous disease manifesting beyond pediatric age with a spectrum of polymorphic arrhythmias. β-Blockers reduce arrhythmias, but in 30% of patients an implantable defibrillator may be required. Genetic analysis identifies two groups of patients: Patients with nongenotyped CPVT are predominantly women and become symptomatic later in life; patients with RyR2 CPVT become symptomatic earlier, and men are at higher risk of cardiac events. These data provide a rationale for prompt evaluation and treatment of young men with RyR2 mutations.
Carbapenemase-producing Enterobacteriaceae in Europe: a survey among national experts from 39 countries, February 2013
Authors: C Glasner, B Albiger, G Buist, A Tambić Andrašević, R Cantón, Y Carmeli, A W Friedrich, C G Giske, Y Glupczynski, M Gniadkowski, D M Livermore, P Nordmann, L Poirel, G M Rossolini, H Seifert, A Vatopoulos, T Walsh, N Woodford, T Donker, D L Monnet, H Grundmann
Journal: Eurosurveillance (2013)

The spread of carbapenemase-producing Enterobacteriaceae (CPE) is a threat to healthcare delivery, although its extent differs substantially from country to country. In February 2013, national experts from 39 European countries were invited to self-assess the current epidemiological situation of CPE in their country. Information about national management of CPE was also reported. The results highlight the urgent need for a coordinated European effort on early diagnosis, active surveillance, and guidance on infection control measures.
Increased Endothelin Activity Mediates Augmented Distal Nephron Acidification Induced by Dietary Protein
Authors: Apurv Khanna, Jan Simoni, Callenda Hacker, Marie-Jose[Combining Acute Accent]e Duran, Donald E. Wesson
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. The hypothesis that increased dietary protein augments distal nephron acidification and does so through an endothelin (ET-1)-dependent mechanism was tested. Munich-Wistar rats that ate minimum electrolyte diets of 50% (HiPro) and 20% (CON) casein-provided protein, the latter comparable to standard diet, were compared. HiPro <i>versus</i> CON had higher distal nephron net HCO<sub>3</sub> reabsorption by <i>in vivo</i> microperfusion (37.8 ± 3.2 <i>versus</i> 16.6 ± 1.5 pmol/mm per min; <i>P</i> &lt; 0.001) as a result of higher H<sup>+</sup> secretion (41.3 ± 4.0 <i>versus</i> 23.0 ± 2.1 pmol/mm per min; <i>P</i> &lt; 0.002) and lower HCO<sub>3</sub> secretion (−3.5 ± 0.4 <i>versus</i> −6.4 ± 0.8 pmol/mm per min; <i>P</i> &lt; 0.001). Perfusion with H<sup>+</sup> inhibitors support that increased H<sup>+</sup> secretion was mediated by augmented Na<sup>+</sup>/H<sup>+</sup> exchange and H<sup>+</sup>-ATPase activity without augmented H<sup>+</sup>,K<sup>+</sup>-ATPase activity. HiPro <i>versus</i> CON had higher levels of urine ET-1 excretion, renal cortical ET-1 addition to microdialysate <i>in vivo</i>, and renal cortical ET-1 mRNA, consistent with increased renal ET-1 production. Oral bosentan, an ET A/B receptor antagonist, decreased distal nephron net HCO<sub>3</sub> reabsorption (22.4 ± 1.9 <i>versus</i> 37.8 ± 3.2 pmol/mm per min; <i>P</i> &lt; 0.001) as a result of lower H<sup>+</sup> secretion (28.4 ± 2.4 <i>versus</i> 41.3 ± 4.0 pmol/mm per min; <i>P</i> &lt; 0.016) and higher HCO<sub>3</sub> secretion (−6.0 ± 0.7 <i>versus</i> −3.5 ± 0.4 pmol/mm per min; <i>P</i> &lt; 0.006). The H<sup>+</sup> inhibitors had no additional effect in HiPro ingesting bosentan, supporting that ET mediated the increased distal nephron Na<sup>+</sup>/H<sup>+</sup> exchange and H<sup>+</sup>-ATPase activity in HiPro. Increased dietary protein augments distal nephron acidification that is mediated through an ET-sensitive increase in Na<sup>+</sup>/H<sup>+</sup> exchange and H<sup>+</sup>-ATPase activity.
Meta-Analysis of Randomized Controlled Trials of Prophylactic Granulocyte Colony-Stimulating Factor and Granulocyte-Macrophage Colony-Stimulating Factor After Autologous and Allogeneic Stem Cell Transplantation
Authors: Allison Dekker, Sean Bulley, Joseph Beyene, L. Lee Dupuis, John J. Doyle, Lillian Sung
Journal: Journal of Clinical Oncology (2006)

The primary objective of our meta-analysis was to determine whether prophylactic hematopoietic colony-stimulating factors (CSFs) after hematopoietic autologous and allogeneic stem-cell transplantation (SCT) reduced documented infections. Our secondary objectives were to determine whether prophylactic CSFs affected other outcomes including parenteral antibiotic therapy duration, infection-related mortality, graft-versus-host disease (GVHD), or treatment-related mortality.We included studies if there was random assignment between CSFs and placebo/no therapy and CSFs were given after SCT and before recovery of neutrophils. From 3,778 reviewed study articles, 34 were included based on predefined inclusion criteria. All analyses were conducted using a random effects model.CSFs reduced the risk of documented infections (relative risk [RR] 0.87; 95% CI, 0.76 to 1.00; P = .05) and duration of parenteral antibiotics (weighted mean difference, -1.39 days, 95% CI, -2.56 to -0.22; P = .02) but did not reduce infection-related mortality (RR, 0.76; 95% CI, 0.41 to 1.44; P = .4). CSFs did not increase grade 2 to 4 acute GVHD (RR, 1.03; 95% CI, 0.81 to 1.31; P = .8) or treatment-related mortality (RR, 1.00; 95% CI, 0.78 to 1.29; P = .98).CSFs were associated with a small reduction in the risk of documented infections but did not affect infection or treatment-related mortality.
Pathology of Pinealomas: An Immunohistochemical and Ultrastructural Study
Authors: H. Cravioto, S. Cortesi, M. T. Giordana, A. Migheli, T. Pezzulo, B. Pollo, M. C. Vigliani
Journal: Neuro-Oncology (1991)

Histologic and ultrastrucural features of primitive pineal tumors are reviewed. The distribution of immunohistochemical and ultrastructural markers closely relate pinealomas to the normal pineal gland.
IgA Interaction with Carboxy-Terminal 43-kD Fragment of Fibronectin in IgA Nephropathy
Authors: SHINOBU WAGA, KAZUHIKO SUGIMOTO, HIROSHI TANAKA, TATSUO ITO, TOHRU NAKAHATA, TAKASHI TATEYAMA, YOSHIKI KAKIZAKI, MASARU YOKOYAMA
Journal: Journal of the American Society of Nephrology (1999)

Abstract. IgA deposition in the glomerular mesangial matrix is a prerequisite for the diagnosis of IgA nephropathy, and circulating IgA-containing complex has been implicated in this process. Since fibronectin is known to be involved in the assembly of extracellular matrix, this study was conducted to investigate whether fibronectin and its fragments are present in sera of patients and are capable of binding IgA1. Sera from patients with IgA nephropathy were purified by heparin-affinity chromatography, and column eluate were analyzed for the presence of fibronectin using Western blot and a set of anti-fibronectin monoclonal antibodies. Native fibronectin was digested with cathepsin D to obtain fragments similar to those of serum fibronectin. The capacity of fibronectin to bind IgA was examined with a mixture of purified IgA1 and cathepsin D-digested fibronectin fragments. A 43-kD carboxy-terminal fragment of fibronectin was detected in samples derived from sera of patients with IgA nephropathy but not in healthy control subjects. A similar-sized fragment was generated by cathepsin D digestion of the native molecule and was shown to bind to IgA1 in vitro . Since the carboxy-terminal domain is known to be critical in assembling exogenous fibronectin into the extracellular matrix, the affinity to IgA1 to a fragment found in patients may have pathogenic potential to mediate extracellular IgA deposition in IgA nephropathy.
A New Mechanism for Blocking Myeloid-Derived Suppressor Cells by CpG
Authors: Melissa G. Lechner, Alan L. Epstein
Journal: Clinical Cancer Research (2011)

In this issue of Clinical Cancer Research, Zoglmeier and colleagues show that CpG, via the induction of IFN-α, matures myeloid-derived suppressor cells to abrogate immune suppression in 2 murine solid tumor models.
Nitric Oxide-Mediated Regulation of Connexin43 Expression and Gap Junctional Intercellular Communication in Mesangial Cells
Authors: Jian Yao, Nobuhiko Hiramatsu, Ying Zhu, Tetsuo Morioka, Masayuki Takeda, Takashi Oite, Masanori Kitamura
Journal: Journal of the American Society of Nephrology (2004)

This study investigated a potential role of nitric oxide (NO) in the regulation of gap junctional intercellular communication (GJIC). Incubation of mesangial cells (MC) with NO donor S-nitroso-N-acetylpenicillamine (SNAP) enhanced both basal and 8-bromo-cAMP-stimulated GJIC as well as expression of gap junction protein connexin43 (Cx43). This potentiating action of SNAP on Cx43 expression was mimicked by two other NO donors and significantly blocked by soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3,-alpha]quinoxalin-1-1. Guanosine 3',5'-cyclic monophosphate (cGMP) analogue 8-bromo-cGMP exerted an effect similar to NO, whereas another cGMP analogue, 8-pCPT-cGMP, which selectively activates cGMP-dependent kinase without affecting cGMP-inhibited phosphodiesterase (PDE3), had no effect. Moreover, the synergistic action of NO on Cx43 expression was completely prevented by protein kinase A inhibitor H89 but not by cGMP-dependent kinase inhibitor Rp-8-Br-PET-cGMP. These results suggested a possible involvement of NO-cAMP interaction via cGMP-mediated inhibition of PDE3. Indeed, PDE3 inhibitor cilostamide caused potentiation of 8-bromo-cAMP-elicited elevations of Cx43 expression that is similar to the effect of SNAP, and an elevation of intracellular cAMP was detected in SNAP-treated cells. With the use of genetically engineered reporter MC that express secreted alkaline phosphatase under the control of the cAMP response element, significant potentiation of cAMP-elicited activation of cAMP response element by SNAP was found. This effect was abrogated in the presence of PDE3 inhibitor cilostamide. Taken together, the results suggest that NO is involved in the control of GJIC and Cx43 expression. This effect of NO is due to activation of protein kinase A via cGMP-dependent inhibition of PDE3 activity.