tbuckley/cabot-search huggingface dataset:
Reduction in Cardiovascular Events With Atorvastatin in 2,532 Patients With Type 2 Diabetes
Authors: Peter S. Sever, Neil R. Poulter, Björn Dahlöf, Hans Wedel, Rory Collins, Gareth Beevers, Mark Caulfield, Sverre E. Kjeldsen, Arni Kristinsson, Gordon T. McInnes, Jesper Mehlsen, Markku Nieminen, Eoin O’Brien, Jan Ostergren
Journal: Diabetes Care (2005)

OBJECTIVE—This study aims to establish the benefits of lowering cholesterol in diabetic patients with well-controlled hypertension and average/below-average cholesterol concentrations, but without established coronary disease. RESEARCH DESIGN AND METHODS—In the lipid-lowering arm of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT-LLA), 10,305 hypertensive patients with no history of coronary heart disease (CHD) but at least three cardiovascular risk factors were randomly assigned to receive 10 mg atorvastatin or placebo. Effects on total cardiovascular outcomes in 2,532 patients who had type 2 diabetes at randomization were compared. RESULTS—During a median follow-up of 3.3 years, concentrations of total and LDL cholesterol among diabetic participants included in ASCOT-LLA were ∼1 mmol/l lower in those allocated atorvastatin compared with placebo. There were 116 (9.2%) major cardiovascular events or procedures in the atorvastatin group and 151 (11.9%) events in the placebo group (hazard ratio 0.77, 95% CI 0.61–0.98; P = 0.036). For the individual components of this composite end point, the number of events occurring in the diabetes subgroup was small. Therefore, although fewer coronary events (0.84, 0.55–1.29; P = 0.14) and strokes (0.67, 0.41–1.09; P = 0.66) were observed among the patients allocated atorvastatin, these reductions were not statistically significant. CONCLUSIONS—Atorvastatin significantly reduced the risk of major cardiovascular events and procedures among diabetic patients with well-controlled hypertension and without a history of CHD or markedly elevated cholesterol concentrations. The proportional reduction in risk was similar to that among participants who did not have diagnosed diabetes. Allocation to atorvastatin prevented ∼9 diabetic participants from suffering a first major cardiovascular event or procedure for every 1,000 treated for 1 year.
Diagnostic Potential of Urine Proteome
Authors: Michael S. Goligorsky, Francesco Addabbo, Edmond O'Riordan
Journal: Journal of the American Society of Nephrology (2007)

This brief overview of studies into the urine proteome illustrates its potential value for diagnostic, prognostic, and pathophysiologic discovery. Hypothesis-targeted investigations of individual proteins as well as proteome-wide searches for urinary biomarkers of various diseases and their progression are reviewed. The majority of urine proteins appear as cleavage products that are found not only as free solutes but also in secreted membrane vesicles called exosomes. Described are several recent examples of important diagnostic findings using urine proteomics along with the idea that signature profiles of injury to individual nephron segments can be measured by this technology. Shared are some thoughts on the most challenging step: Integration of seemingly unrelated findings of various protein fragments into a rational pathogenetic pathway(s). The future chance that the centuries-old technique of uroscopy will reveal its secrets using modern proteomic approaches makes gradual improvement.
Prostaglandin E <sub>2</sub> —Mediated Relaxation of the Ductus Arteriosus
Authors: Nahid Waleh, Hiroki Kajino, Anne Marilise Marrache, David Ginzinger, Christine Roman, Steven R. Seidner, Timothy J.M. Moss, Jean-Claude Fouron, Alejandro Vazquez-Tello, Sylvain Chemtob, Ronald I. Clyman
Journal: Circulation (2004)

In the preterm newborn, a patent ductus arteriosus is in large part a result of the increased sensitivity of the immature ductus to prostaglandin E2 (PGE2). PGE2 acts through 3 G protein-coupled receptors (EP2, EP3, and EP4) that activate both adenyl cyclase and K(ATP) channels. We explored these pathways to identify the mechanisms responsible for the increased sensitivity of the immature ductus to PGE2.We measured EP receptor content (mRNA and protein), receptor binding, cAMP production, and isometric tension in rings of ductus taken from immature (65% gestation) and mature (95% gestation) sheep and baboon fetuses. Ductus relaxation and cAMP generation were augmented in response to selective EP receptor agonists in the immature ductus. 8-Br-cAMP, a stable cAMP analogue, produced greater relaxation in the immature ductus. In the presence of a selective protein kinase A inhibitor, Rp-8-CPT cAMPS, the developmental differences in sensitivity to PGE2 could no longer be demonstrated. EP2, EP3, and EP4 receptor densities were higher in immature ductus, despite similar receptor mRNA and protein contents at the 2 gestational ages. In contrast, forskolin and NaF, direct activators of adenyl cyclase and Gs, respectively, elicited comparable increases in cAMP in both age groups. KATP channel inhibition also had similar effects on PGE2-induced relaxation in both age groups.Two mechanisms explain the increased sensitivity of the immature ductus to PGE2: (1) increased cAMP production because of increased binding of PGE2 to the individual EP receptors and (2) increased potency of cAMP on protein kinase A-regulated pathways.
Long-Term Effectiveness and Safety of Sirolimus Stent Implantation for Coronary In-Stent Restenosis
Authors: Francesco Liistro, Massimo Fineschi, Simone Grotti, Paolo Angioli, Arcangelo Carrera, Kenneth Ducci, Tommaso Gori, Giovanni Falsini, Carlo Pierli, Leonardo Bolognese
Journal: Journal of the American College of Cardiology (2010)
Association of Cancer With Geriatric Syndromes in Older Medicare Beneficiaries
Authors: Supriya G. Mohile, Lin Fan, Erin Reeve, Pascal Jean-Pierre, Karen Mustian, Luke Peppone, Michelle Janelsins, Gary Morrow, William Hall, William Dale
Journal: Journal of Clinical Oncology (2011)

To identify whether a history of cancer is associated with specific geriatric syndromes in older patients. PATIENTS AND METHODS; Using the 2003 Medicare Current Beneficiary Survey, we analyzed a national sample of 12,480 community-based elders. Differences in prevalence of geriatric syndromes between those with and without cancer were estimated. Multivariable logistic regressions were used to evaluate whether cancer was independently associated with geriatric syndromes.Two thousand three hundred forty-nine (18%) reported a history of cancer. Among those with cancer, 60.3% reported one or more geriatric syndromes as compared with 53.2% of those without cancer (P < .001). Those with cancer overall had a statistically significantly higher prevalence of hearing trouble, urinary incontinence, falls, depression, and osteoporosis than those without cancer. Adjusting for possible confounders, those with a history of cancer were more likely to experience depression (adjusted odds ratio [OR], 1.15; 95% CI, 1.02 to 1.30; P = .023), falls (adjusted OR, 1.17; 95% CI, 1.04 to 1.32; P = .010), osteoporosis (adjusted OR, 1.21; 95% CI, 1.06 to 1.38; P = .004), hearing trouble (adjusted OR, 1.28; 95% CI, 1.08 to 1.52; P = .005), and urinary incontinence (adjusted OR, 1.42; 95% CI, 1.20 to 1.69; P < .001). Analysis of specific cancer subtypes showed that lung cancer was associated with vision, hearing, and eating trouble; prostate cancer was associated with incontinence and falls; cervical/uterine cancer was associated with falls and osteoporosis; and colon cancer was associated with depression and osteoporosis.Elderly patients with cancer experience a higher prevalence of geriatric syndromes than those without cancer. Prospective studies that establish the causal relationships between cancer and geriatric syndromes are necessary.
Association of chromosome 22q11 deletion with isolated anomalies of aortic arch laterality and branching
Authors: Doff B McElhinney, Bernard J Clark, Paul M Weinberg, Maura L Kenton, Donna McDonald-McGinn, Deborah A Driscoll, Elaine H Zackai, Elizabeth Goldmuntz
Journal: Journal of the American College of Cardiology (2001)
The effect of peroxisome proliferator-activated receptor- ligands on in vitro and in vivo models of COPD
Authors: S. Lea, J. Plumb, H. Metcalfe, D. Spicer, P. Woodman, J. C. Fox, D. Singh
Journal: European Respiratory Journal (2013)

Peroxisome proliferator-activated receptor (PPAR)-γ is expressed in alveolar macrophages. The anti-inflammatory potential of the PPAR-γ ligands rosiglitazone and pioglitazone were investigated using <i>in vitro</i> alveolar macrophage models and <i>in vivo</i> animal models relevant to chronic obstructive pulmonary disease (COPD). PPAR-γ protein and gene expression in COPD alveolar macrophages was compared with control smokers and never-smokers. COPD macrophages were used to investigate the effects of PPAR-γ ligands and corticosteroids on lipopolysaccharide-induced cytokine production, alternative macrophage activation (M2) gene expression and efferocytosis. The effects of PPAR-γ ligands in a subchronic tobacco smoke model in mice were investigated. PPAR-γ protein expression was similar in COPD patients compared to controls, although increased gene expression levels were observed in COPD patients and control smokers compared to never-smokers. PPAR-γ ligands reduced tumour necrosis factor-α and CC chemokine ligand-5, but not CXC chemokine ligand-8, in COPD alveolar macrophages; these effects were generally less than those of the corticosteroid dexamethasone. Rosiglitazone increased M2 gene expression and enhanced efferocytosis of apoptotic neutrophils. Rosiglitazone and pioglitazone attenuated airway neutrophilia in a corticosteroid-resistant mouse model of pulmonary inflammation. We show biological actions of PPAR-γ agonists on corticosteroid-resistant disease, tobacco smoke-induced pulmonary inflammation, skewing of macrophage phenotype and clearance of apoptotic neutrophils.
Cancer Incidence in World Trade Center Rescue and Recovery Workers, 2001–2008
Authors: Samara Solan, Sylvan Wallenstein, Moshe Shapiro, Susan L. Teitelbaum, Lori Stevenson, Anne Kochman, Julia Kaplan, Cornelia Dellenbaugh, Amy Kahn, F. Noah Biro, Michael Crane, Laura Crowley, Janice Gabrilove, Lou Gonsalves, Denise Harrison, Robin Herbert, Benjamin Luft, Steven B. Markowitz, Jacqueline Moline, Xiaoling Niu, Henry Sacks, Gauri Shukla, Iris Udasin, Roberto G. Lucchini, Paolo Boffetta, Philip J. Landrigan
Journal: Environmental Health Perspectives (2013)

Background: World Trade Center (WTC) rescue and recovery workers were exposed to a complex mix of pollutants and carcinogens.Objective: The purpose of this investigation was to evaluate cancer incidence in responders during the first 7 years after 11 September 2001.Methods: Cancers among 20,984 consented participants in the WTC Health Program were identified through linkage to state tumor registries in New York, New Jersey, Connecticut, and Pennsylvania. Standardized incidence ratios (SIRs) were calculated to compare cancers diagnosed in responders to predicted numbers for the general population. Multivariate regression models were used to estimate associations with degree of exposure.Results: A total of 575 cancers were diagnosed in 552 individuals. Increases above registry-based expectations were noted for all cancer sites combined (SIR = 1.15; 95% CI: 1.06, 1.25), thyroid cancer (SIR = 2.39; 95% CI: 1.70, 3.27), prostate cancer (SIR = 1.21; 95% CI: 1.01, 1.44), combined hematopoietic and lymphoid cancers (SIR = 1.36; 95% CI: 1.07, 1.71), and soft tissue cancers (SIR = 2.26; 95% CI: 1.13, 4.05). When restricted to 302 cancers diagnosed ≥ 6 months after enrollment, the SIR for all cancers decreased to 1.06 (95% CI: 0.94, 1.18), but thyroid and prostate cancer diagnoses remained greater than expected. All cancers combined were increased in very highly exposed responders and among those exposed to significant amounts of dust, compared with responders who reported lower levels of exposure.Conclusion: Estimates should be interpreted with caution given the short follow-up and long latency period for most cancers, the intensive medical surveillance of this cohort, and the small numbers of cancers at specific sites. However, our findings highlight the need for continued follow-up and surveillance of WTC responders.
Effect of formaldehyde/bleach reprocessing on in vivo performances of high-efficiency cellulose and high-flux polysulfone dialyzers.
Authors: B V Murthy, S Sundaram, B L Jaber, C Perrella, K B Meyer, B J Pereira
Journal: Journal of the American Society of Nephrology (1998)

Among the several disadvantages of reprocessed dialyzers is the concern that reuse could decrease the clearance of uremic toxins, leading to a decrease in the delivered dose of dialysis. To examine this possibility in the clinical setting, the clearances of small molecular weight solutes (urea and creatinine) and middle molecular weight substances (beta 2 microglobulin) were compared during dialysis with "high-efficiency" cellulose (T220L) and "high-flux" polysulfone (F80B) dialyzers reprocessed with formaldehyde and bleach. In a crossover study, six chronic hemodialysis patients were alternately assigned to undergo 21 dialysis treatments with a single T220L dialyzer or F80B dialyzer. Each patient was studied during first use (0 reuse), 2nd reuse (3rd use), and 5th, 10th, 15th, and 20th reuse of each dialyzer. Urea, creatinine, and beta 2 microglobulin clearances were measured at blood flow rates of 300 ml/min (Qb 300) and 400 ml/min (Qb 400). Total albumin loss into the dialysate was measured during each treatment. Urea or creatinine clearance of new T220L dialyzers was not significantly different from that of new F80B dialyzers at either Qb. Urea clearance of F80B dialyzers at Qb 300 decreased from 241 +/- 2 ml/min for new dialyzers to 221 +/- 5 ml/min after 20 reuses (P < 0.001), and Qb 400 from 280 +/- 4 ml/min for new dialyzers to 253 +/- 7 ml/min after 20 reuses (P = 0.001). Similarly, with reuse, creatinine clearance of F80B dialyzers also decreased at Qb 300 (P = 0.07) and Qb 400 (P = 0.03). In contrast, urea or creatinine clearance of T220L dialyzers did not decrease with reuse at either Qb. Urea clearance of T220L dialyzers was significantly higher than that of F80B at Qb 300 at the 5th, 10th, 15th, and 20th reuse (P < 0.001, = 0.005, = 0.004, and = 0.006, respectively), and Qb 400 at the 2nd, 5th, 10th, 15th, and 20th reuse (P = 0.04, 0.008, 0.03, 0.02, and 0.008, respectively). Beta 2 microglobulin clearance of T220L dialyzers was < 5.0 ml/min across the reuses studied. Beta 2 microglobulin clearance of F80B was < 5.0 ml/min for new dialyzers, but increased to 21.2 +/- 5.3 ml/min (Qb 300) and 23.6 +/- 3.3 ml/min (Qb 400) after 20 reuses (P < 0.001). Throughout the study, albumin was undetectable in the dialysate with T220L dialyzers. With F80B dialyzers, albumin was detected in the dialysate in four instances (total loss during dialysis, 483 mg to 1.467 g). In summary, the results of this study emphasize the greater need for information on dialyzer clearances during clinical dialysis, especially with reprocessed dialyzers. A more accurate knowledge of dialyzer performance in vivo would help to ensure that the dose of dialysis prescribed is indeed delivered to the patients.
Inducible nitric oxide synthase polymorphism in asthmatic patients
Authors: Margarida Cortez e Castro, Andreia Matos, Joana Ferreira, Ridhi Prabhudas, Manuel Bicho
Journal: European Respiratory Journal (2014)

Aim of the study: To analyze the association between inducible nitric oxide synthase (iNOS) gene polymorphism iNOS: + 14C T (Ex16 + 14C T) rs 2297518; with asthma severity compared with a control group of healthy blood donors.

Material and Methods:Asthmatic patients (n= 100) compared with a control group (n=72); polymorphisms analyzed by PCR-RFLP. Control of asthma assessed by (ACQ7 and PAQLQ). Statistical analysis with PASW version 18 establishing a significance level of p< 0.05.

Results: Mean age of 100 asthmatics: 38.1±18.6 years(7 - 86 years); 65 females and 35 males .Mean age of control-group (n=72) was 41.68±11.71 years (19 - 69 years); 25 females and 47 males. In asthmatics the frequencies of Allele C 0.81 and of Allele T 0.19; in controls: 0.92 and 0.08 respectively. There is statistical difference between these groups (p=0.003).Being the allele T more frequent in asthmatics. Genotypes in the asthmatics- CC: 66%; CT: 30%; TT: 4%; in control group- CC: 86.1%; CT:12.5%; TT: 1.4%. There is statistical difference between these groups (p=0.010). When we associate genotypes (CC vs CT+TT; p = 0.003), the genotypes who express allele T were more frequent in the asthma-group.The risk (OR) associated is 3.338 (CI 95% [1.524 - 7.313], (p =0.003).In asthmatics, there is no statistical differences in genotype frequencies (p>0.05) between: atopics and non atopics; controlled and uncontrolled asthma; males and females; and in the different age-groups.

Conclusion: With this results we might conclude that Inducible nitric oxide synthase (iNOS ) polymorphism(Ex16 + 14C T), could be a risk factor for asthma, we also concluded that the genotypes who express the allele T are more prevalent in asthmatics.
Reappraisal of Routine Oral Care With Chlorhexidine Gluconate for Patients Receiving Mechanical Ventilation
Authors: Michael Klompas, Kathleen Speck, Michael D. Howell, Linda R. Greene, Sean M. Berenholtz
Journal: JAMA Internal Medicine (2014)

Regular oral care with chlorhexidine gluconate is standard of care for patients receiving mechanical ventilation in most hospitals. This policy is predicated on meta-analyses suggesting decreased risk of ventilator-associated pneumonia, but these meta-analyses may be misleading because of lack of distinction between cardiac surgery and non-cardiac surgery studies, conflation of open-label vs double-blind investigations, and insufficient emphasis on patient-centered outcomes such as duration of mechanical ventilation, length of stay, and mortality.To evaluate the impact of routine oral care with chlorhexidine on patient-centered outcomes in patients receiving mechanical ventilation.PubMed, Embase, CINAHL, and Web of Science from inception until July 2013 without limits on date or language.Randomized clinical trials comparing chlorhexidine vs placebo in adults receiving mechanical ventilation. Of 171 unique citations, 16 studies including 3630 patients met inclusion criteria.Eligible trials were independently identified, evaluated for risk of bias, and extracted by 2 investigators. Differences were resolved by consensus. We stratified studies into cardiac surgery vs non-cardiac surgery and open-label vs double-blind investigations. Eligible studies were pooled using random-effects meta-analysis.Ventilator-associated pneumonia, mortality, duration of mechanical ventilation, intensive care unit and hospital length of stay, antibiotic prescribing.There were fewer lower respiratory tract infections in cardiac surgery patients randomized to chlorhexidine (relative risk [RR], 0.56 [95% CI, 0.41-0.77]) but no significant difference in ventilator-associated pneumonia risk in double-blind studies of non-cardiac surgery patients (RR, 0.88 [95% CI, 0.66-1.16]). There was no significant mortality difference between chlorhexidine and placebo in cardiac surgery studies (RR, 0.88 [95% CI, 0.25-2.14]) and nonsignificantly increased mortality in non-cardiac surgery studies (RR, 1.13 [95% CI, 0.99-1.29]). There were no significant differences in mean duration of mechanical ventilation or intensive care length of stay. Data on hospital length of stay and antibiotic prescribing were limited.Routine oral care with chlorhexidine prevents nosocomial pneumonia in cardiac surgery patients but may not decrease ventilator-associated pneumonia risk in non-cardiac surgery patients. Chlorhexidine use does not affect patient-centered outcomes in either population. Policies encouraging routine oral care with chlorhexidine for non-cardiac surgery patients merit reevaluation.
Use of topical lithium succinate for seborrhoeic dermatitis.
Authors: J Boyle, J L Burton, J Faergemann
Journal: BMJ (1986)

Use of topical lithium succinate for seborrhoeic dermatitisIn a small screening study topical lithium succinate ointment was observed to produce a striking improvement in several patients with seborrhoeic dermatitis of the face.We therefore performed a double blind controlled study of this effect.As pityrosporum yeasts can cause seborrhoeic dermatitis' and lithium inhibits the growth of some fungi2 we also tested the inhibitory effect of lithium succinate on the growth of yeasts.
Mesenchymal stem cell therapy in acute lung injury: is it time for a clinical trial?
Authors: Rob Mac Sweeney, Daniel Francis McAuley
Journal: Thorax (2012)

Despite decades of research, no specific pharmacological therapy to treat acute lung injury (ALI) has been identified. At present, the only effective therapies act by limiting iatrogenic injury associated with positive fluid balance1 or mechanical ventilation.2 3 As efforts to pharmacologically modulate the complex inflammatory process which leads to alveolar injury have been unsuccessful,4 focus has changed to cell based therapy, aimed at utilising stems cells which have pleiotropic effects and which respond appropriately to local signalling molecules.

Stem cells have the capacity for limitless self-renewal and differentiation. Mesenchymal stem cells (MSC) are multipotent adult stem cells with the capacity to differentiate into many different cell types, including alveolar cells. There are several mechanisms through which MSCs could potentially be used for attenuating lung injury and augmenting repair.5 On the basis of the currently available data, and supported by two papers,6 7 the most important therapeutic effect of exogenously administered MSCs is probably through the paracrine secretion of mediators such as growth factors and cytokines to modulate localised inflammation and tissue repair.8 Gupta et al found treatment with MSCs improved bacterial clearance in a mouse model of gram-negative pneumonia, which was due in part to lipocalin 2 production by MSCs,6 while Curley et al showed that MSC therapy improved lung repair via a paracrine mechanism that was keratinocyte growth factor (KGF)-dependent.7 However, cell contact-dependent mechanisms, via the gap junction channel protein connexin-43, have also been described.9 The other main effect of exogenously administered MSCs is their localisation to the site of …