tbuckley/cabot-search huggingface dataset:
Increased Cyclooxygenase-2 Expression in Duodenal Compared with Colonic Tissues in Familial Adenomatous Polyposis and Relationship to the −765G → <i>C COX-2</i> Polymorphism
Authors: Lodewijk A.A. Brosens, Christine A. Iacobuzio-Donahue, Josbert J. Keller, Steven R. Hustinx, Ralph Carvalho, Folkert H. Morsink, Linda M. Hylind, G. Johan Offerhaus, Francis M. Giardiello, Michael Goggins
Journal: Clinical Cancer Research (2005)

Colorectal cancers arising in patients with familial adenomatous polyposis (FAP) can be largely prevented by polyp surveillance and prophylactic colectomy. As a result, duodenal adenocarcinoma has become a leading cause of death in patients with FAP. Cyclooxygenase 2 (COX-2) inhibition is effective against colorectal polyposis in FAP, but is less effective in treating duodenal polyps. We compared the expression of COX-2 in duodenal and colorectal adenomas from patients with FAP and from patients with sporadic neoplasms and correlated expression to a COX-2 promoter polymorphism (-765G/-->C) that is reported to influence COX-2 expression.The study population included 36 FAP patients with colonic adenomas, 22 FAP patients with duodenal adenomas, 22 patients with sporadic duodenal adenomas, and 17 patients with sporadic duodenal adenocarcinoma. Neoplastic and corresponding normal tissue COX-2 expressions were determined using immunohistochemistry on tissue microarrays. The prevalence and ethnic distribution of a polymorphism in the COX-2 promoter that influences COX-2 expression (-765G --> C) were determined in DNA from 274 individuals by real-time quantitative PCR.Among patients with FAP, histologically normal duodenal mucosa showed higher COX-2 expression than normal colonic mucosa (P < 0.02), and duodenal adenomas had higher COX-2 expression than colonic adenomas (P </= 0.01). In addition, the normal duodenum of patients with FAP showed higher COX-2 expression than the normal duodenal mucosa of patients with sporadic adenomas (P < 0.05). COX-2 expression was significantly higher in the normal-appearing (P < 0.01) mucosa of patients with FAP carrying the -765GG genotype compared with those carrying the -765GC or -765CC genotypes. The -765C genotype was more common in African Americans than in Caucasians (52% versus 33%, P < 0.01).High COX-2 expression in the normal and adenomatous duodenal mucosa of patients with FAP may explain the poorer response of these neoplasms to chemoprevention with COX-2 inhibitors.
Increased Perioperative N-Terminal Pro-B-Type Natriuretic Peptide Levels Predict Atrial Fibrillation After Thoracic Surgery for Lung Cancer
Authors: Daniela Cardinale, Alessandro Colombo, Maria T. Sandri, Giuseppina Lamantia, Nicola Colombo, Maurizio Civelli, Michela Salvatici, Giulia Veronesi, Fabrizio Veglia, Cesare Fiorentini, Lorenzo Spaggiari, Carlo M. Cipolla
Journal: Circulation (2007)

Postoperative atrial fibrillation (AF) is a complication of thoracic surgery for lung cancer, with a reported incidence that can run as high as 42%. Recently, it has been observed retrospectively that B-type natriuretic peptide predicts AF after cardiac surgery. We performed a prospective study to evaluate the role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) as a marker for risk stratification of postoperative AF in patients undergoing thoracic surgery for lung cancer.We measured NT-proBNP levels in 400 patients (mean age, 62+/-10 years; 271 men) 24 hours before and 1 hour after surgery. The primary end point of the study was the incidence of postoperative AF. Overall, postoperative AF occurred in 72 patients (18%). Eighty-eight patients (22%) showed an elevated perioperative NT-proBNP value. When patients with either preoperatively or postoperatively elevated NT-proBNP were pooled, a greater incidence of AF was observed compared with patients with normal values (64% versus 5%; P<0.001). At multivariable analysis, adjusted for age, gender, major comorbidities, echocardiography parameters, pneumonectomy, and medications, both preoperative and postoperative NT-proBNP values were independent predictors of AF (relative risk, 27.9; 95% CI, 13.2 to 58.9; P<0.001 for preoperative NT-proBNP elevation; relative risk, 20.1; 95% CI, 5.8 to 69.4; P<0.001 for postoperative NT-proBNP elevation).Elevation of perioperative NT-proBNP is a strong independent predictor of postoperative AF in patients undergoing thoracic surgery for lung cancer. This finding should facilitate studies of therapies to reduce AF in selected high-risk patients.
Ileal Pouch Symptoms Do Not Correlate With Inflammation of the Pouch
Authors: Ofer Ben–Bassat, Andrea D. Tyler, Wei Xu, Richard Kirsch, David F. Schaeffer, Joanna Walsh, A. Hillary Steinhart, Gordon R. Greenberg, Zane Cohen, Mark S. Silverberg, Robin S. McLeod
Journal: Clinical Gastroenterology and Hepatology (2013)
Inflammatory Cytokines Stimulated C-Reactive Protein Production by Human Coronary Artery Smooth Muscle Cells
Authors: Paolo Calabró, James T. Willerson, Edward T.H. Yeh
Journal: Circulation (2003)

Background— Serum C-reactive protein (CRP) levels are good predictors of the development of cardiovascular events in apparently healthy men and women. CRP has been believed to be produced exclusively by hepatocytes during the acute-phase response. Several lines of evidence have suggested that atherosclerotic arteries can also produce CRP. However, the cell types that produce CRP locally in the atherosclerotic arterial wall have not been clearly identified. Methods and Results— Human coronary artery smooth muscle cells (HCASMCs) and human umbilical vein endothelial cells (HUVECs) were incubated with interleukin-1β (IL-1β), IL-6, their combination, tumor necrosis factor-α (TNF-α), or lipopolysaccharide (LPS) at different concentrations. The supernatants were concentrated and analyzed by a high-sensitivity enzyme-linked immunosorbent assay specific for human CRP. RNA was extracted from the HCASMCs for reverse transcriptase-polymerase chain reaction (RT-PCR) using specific primers for the CRP. Maximal CRP production was observed in HCASMCs after 48 hours of incubation with the combination of 25 ng/mL of IL-1β and 10 ng/mL of IL-6, whereas incubation with IL-1β or IL-6 alone only modestly induced CRP. Incubation with TNF-α (50 ng/mL) or LPS (1000 EU/mL) resulted in an increase in CRP production comparable to the IL-1β and IL-6 combination. The induction of CRP in HCASMCs was independently confirmed by RT-PCR comparing the relative CRP mRNA levels. The induction of CRP production by HCASMCs was not reproduced in HUVECs, however. Conclusions— These results demonstrated that HCASMCs, but not HUVECs, could produce CRP in response to inflammatory cytokines. The locally produced CRP could directly participate in atherogenesis and the development of cardiovascular complications.
The Safety and Intraocular Pressure–Lowering Efficacy of Brimonidine Tartrate 0.15% Preserved with Polyquaternium-1
Authors: Jess T. Whitson, Katherine I. Ochsner, Marlene R. Moster, E. Kenneth Sullivan, Russell M. Andrew, Lewis H. Silver, David T. Wells, John E. James, Charles F. Bosworth, Jaime E. Dickerson, Theresa A. Landry, Michael V.W. Bergamini
Journal: Ophthalmology (2006)
Proteomic analysis of secreted proteins in early rheumatoid arthritis: anti-citrulline autoreactivity is associated with up regulation of proinflammatory cytokines
Authors: W. Hueber, B. H Tomooka, X. Zhao, B. A Kidd, J. W Drijfhout, J. F Fries, W. J van Venrooij, A. L Metzger, M. C Genovese, W. H Robinson
Journal: Annals of the Rheumatic Diseases (2006)

<b>Objectives:</b> To identify peripheral blood autoantibody and cytokine profiles that characterise clinically relevant subgroups of patients with early rheumatoid arthritis using arthritis antigen microarrays and a multiplex cytokine assay. <b>Methods:</b> Serum samples from 56 patients with a diagnosis of rheumatoid arthritis of &lt;6 months' duration were tested. Cytokine profiles were also determined in samples from patients with psoriatic arthritis (PsA) and ankylosing spondylitis (n = 21), and from healthy individuals (n = 19). Data were analysed using Kruskal–Wallis test with Dunn's adjustment for multiple comparisons, linear correlation tests, significance analysis of microarrays (SAM) and hierarchical clustering software. <b>Results:</b> Distinct antibody profiles were associated with subgroups of patients who exhibited high serum levels of tumour necrosis factor (TNF)α, interleukin (IL)1β, IL6, IL13, IL15 and granulocyte macrophage colony-stimulating factor. Significantly increased autoantibody reactivity against citrullinated epitopes was observed in patients within the cytokine "high" subgroup. Increased levels of TNFα, IL1α, IL12p40 and IL13, and the chemokines eotaxin/CCL11, monocyte chemoattractant protein-1 and interferon-inducible protein 10, were present in early rheumatoid arthritis as compared with controls (p&lt;0.001). Chemokines showed some of the most impressive differences. Only IL8/CXCL8 concentrations were higher in patients with PsA/ankylosing spondylitis (p = 0.02). <b>Conclusions:</b> Increased blood levels of proinflammatory cytokines are associated with autoantibody targeting of citrullinated antigens and surrogate markers of disease activity in patients with early rheumatoid arthritis. Proteomic analysis of serum autoantibodies, cytokines and chemokines enables stratification of patients with early rheumatoid arthritis into molecular subgroups.
Effect of single dose resin-cathartic therapy on serum potassium concentration in patients with end-stage renal disease.
Authors: C Gruy-Kapral, M Emmett, C A Santa Ana, J L Porter, J S Fordtran, K D Fine
Journal: Journal of the American Society of Nephrology (1998)

Hyperkalemia in patients with renal failure is frequently treated with a cation exchange resin (sodium polystyrene sulfonate, hereafter referred to as resin) in combination with a cathartic, but the effect of such therapy on serum potassium concentration has not been established. This study evaluates the effect of four single-dose resin-cathartic regimens and placebo on 5 different test days in six patients with chronic renal failure. Dietary intake was controlled. Fecal potassium output and serum potassium concentration were measured for 12 h. Phenolphthalein alone caused an average fecal potassium output of 54 mEq. The addition of resin caused an increase in insoluble potassium output but a decrease in soluble potassium output; therefore, there was no significant effect of resin on total potassium output. Sorbitol plus resin caused less potassium output than phenolphthalein plus resin. On placebo therapy, the average serum potassium concentration increased slightly (0.4 mEq/L) during the 12-h experiment. This rise was apparently abrogated by some of the regimens that included resin; this may have been due in part to extracellular volume expansion caused by absorption of sodium released from resin. Phenolphthalein regimens were associated with a slight rise in serum potassium concentrations (similar to placebo); this may have been due to extracellular volume contraction produced by high volume and sodium-rich diarrhea and acidosis secondary to bicarbonate losses. None of the regimens reduced serum potassium concentrations, compared with baseline levels. Because single-dose resin-cathartic therapy produces no or only trivial reductions in serum potassium concentration, and because this therapy is unpleasant and occasionally is associated with serious complications, this study questions the wisdom of its use in the management of acute hyperkalemic episodes.
Epidemiology of gout and hyperuricaemia in Italy during the years 2005–2009: a nationwide population-based study
Authors: Gianluca Trifirò, Paolo Morabito, Lorenzo Cavagna, Carmen Ferrajolo, Serena Pecchioli, Monica Simonetti, Elisa Bianchini, Gerardo Medea, Claudio Cricelli, Achille P Caputi, Giampiero Mazzaglia
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> To assess the epidemiology of gout and hyperuricaemia in the Italian general population during the years 2005–2009. <h3>Methods</h3> Using the Italian primary care database (Health Search/CSD Longitudinal Patient Database), the prevalence, incidence and recurrence rates of gout and/or hyperuricaemia (serum urate level &gt;360 mmol/l (6 mg/dl)) in outpatients aged ≥18 years during the years 2005–2009 were estimated. Rates together with 95% CI were measured overall and stratified by age, gender and calendar year. The characteristics of patients with newly diagnosed gout and hyperuricaemia were investigated and compared with the general population. <h3>Results</h3> The prevalence of gout increased from 6.7 per 1000 inhabitants in 2005 to 9.1 per 1000 inhabitants in 2009. It increased with advancing age and was fourfold higher in men. A similar trend was observed for asymptomatic hyperuricaemia (85.4 per 1000 inhabitants in 2005 vs 119.3 per 1000 inhabitants in 2009). The incidence of gout remained stable during the observation years (0.93 per 1000 person years in 2005 vs 0.95 in 2009). Recurrent episode rate was 19.1% during the first year following the first gout attack and 31.6% during the following 5 years. Advanced age, increased levels of uric acid, nephrolithiasis and concomitant use of ciclosporin were the main predictors of recurrence of gout attacks. <h3>Conclusion</h3> The prevalence of gout and hyperuricaemia increased in Italy from 2005 to 2009. A high recurrence rate for gout attack was observed during the first year following the first episode. Early management of hyperuricaemia in patients at higher risk of recurrent gout attack should be considered in primary care.
Disorders of cellular electrophysiology produced by ischemia of the canine His bundle.
Authors: R Lazzara, N El-Sherif, B J Scherlag
Journal: Circulation Research (1975)

In the first 4 hours after occlusion of the anterior septal coronary artery, 18 dogs developed bundle branch block, heart block, or both. The hearts were then excised, and preparations were dissected to expose the His bundle and the bundle branches, which were superfused with modified Tyrode's solution at 37 degrees C. In the His bundle and the most proximal bundle branches, resting potentials were reduced and diminutive action potentials had slow upstrokes, often with notches or steps. Action potentials were generated by fibers that had resting potentials between--40 and --50 mv. Conduction was impaired; conduction velocities less than 0.01 m/sec were sometimes observed. In more severely affected cells, refractoriness outlasted repolarization. Encroachment on the prolonged refractory period resulted in further diminution of action potentials and continuous rather than intermittent block. More commonly, the response to rapid rate took the form of intermittent block with progressive conduction delay in the series of conducted beats, culminating in a blocked beat (Wenckebach sequence). There was a fatigue factor that accumulated at short cycle lengths and depressed the action potential. Automaticity was not enhanced, but pacemaker function was abnormal. The threshold potential shifted erratically, and pacemaker potentials sometimes were intermittently diminished, resulting in intermittent failure to propagate. During prolonged superfusion, there was a tendency to recover with a drift of the maximum diastolic potentials toward more negative levels. None of these changes were found in ten hearts excised from dogs in which the coronary artery had not been ligated.
Adolescents' Compliance With the Use of Oral Contraceptives
Authors: S. Jean Emans
Journal: JAMA (1987)

To elucidate the factors that might influence compliance with oral contraceptive use among sexually active adolescents, we undertook a study of 209 unmarried adolescents initiating use of oral contraceptives in three different settings: an inner-city adolescent clinic (I), a birth control clinic in a midsized industrial city (II), and a suburban private practice (III). At the three-month follow-up visit, factors associated with compliance included older age, suburban residence, white race, health care in the suburban private practice, payment status, prior use of contraception, mother's unawareness of oral contraceptives, married parents, older boyfriend, lack of worry about being pregnant, and satisfaction with pill use. Compliance at long-term follow-up (13.5 ± 3.7 months) was additionally associated with educational goals, father's education level, and absence of side effects. Ten pregnancies occurred during the study period among noncompliant site I patients. Inner-city clinic patients were at high risk of noncompliance and unplanned pregnancy. (<i>JAMA</i>1987;257:3377-3381)
Interferon- release assays for the diagnosis of active tuberculosis: a systematic review and meta-analysis
Authors: M. Sester, G. Sotgiu, C. Lange, C. Giehl, E. Girardi, G.B. Migliori, A. Bossink, K. Dheda, R. Diel, J. Dominguez, M. Lipman, J. Nemeth, P. Ravn, S. Winkler, E. Huitric, A. Sandgren, D. Manissero
Journal: European Respiratory Journal (2010)

Interferon-γ release assays (IGRAs) are now established for the immunodiagnosis of latent infection with Mycobacterium tuberculosis in many countries. However, the role of IGRAs for the diagnosis of active tuberculosis (TB) remains unclear. Following preferred reporting items for systematic reviews and meta-analyses (PRISMA) and quality assessment of diagnostic accuracy studies (QUADAS) guidelines, we searched PubMed, EMBASE and Cochrane databases to identify studies published in January 2001-November 2009 that evaluated the evidence of using QuantiFERON-TB® Gold in-tube (QFT-G-IT) and T-SPOT.TB® directly on blood or extrasanguinous specimens for the diagnosis of active TB. The literature search yielded 844 studies and 27 met the inclusion criteria. In blood and extrasanguinous fluids, the pooled sensitivity for the diagnosis of active TB was 80% (95% CI 75-84%) and 48% (95% CI 39-58%) for QFT-G-IT, and 81% (95% CI 78-84%) and 88% (confirmed and unconfirmed cases) (95% CI 82-92%) for T-SPOT.TB®, respectively. In blood and extrasanguinous fluids, the pooled specificity was 79% (95% CI 75-82%) and 82% (95% CI 70-91%) for QFT-G-IT, and 59% (95% CI 56-62%) and 82% (95% CI 78-86%) for T-SPOT.TB®, respectively. Although the diagnostic sensitivities of both IGRAs were higher than that of tuberculin skin tests, it was still not high enough to use as a rule out test for TB. Positive evidence for the use of IGRAs in compartments other than blood will require more independent and carefully designed prospective studies.
Regression of low-grade squamous intra-epithelial lesions in young women
Authors: Anna-Barbara Moscicki, Stephen Shiboski, Nancy K Hills, Kimberly J Powell, Naomi Jay, Evelyn N Hanson, Susanna Miller, Lisa K Canjura-Clayton, Sepidah Farhat, Jeanette M Broering, Teresa M Darragh
Journal: The Lancet (2004)
The stream of precursors that colonizes the thymus proceeds selectively through the early T lineage precursor stage of T cell development
Authors: Claudia Benz, Vera C. Martins, Freddy Radtke, Conrad C. Bleul
Journal: The Journal of Experimental Medicine (2008)

T cell development in the thymus depends on continuous colonization by hematopoietic precursors. Several distinct T cell precursors have been identified, but whether one or several independent precursor cell types maintain thymopoiesis is unclear. We have used thymus transplantation and an inducible lineage-tracing system to identify the intrathymic precursor cells among previously described thymus-homing progenitors that give rise to the T cell lineage in the thymus. Extrathymic precursors were not investigated in these studies. Both approaches show that the stream of T cell lineage precursor cells, when entering the thymus, selectively passes through the early T lineage precursor (ETP) stage. Immigrating precursor cells do not exhibit characteristics of double-negative (DN) 1c, DN1d, or DN1e stages, or of populations containing the common lymphoid precursor 2 (CLP-2) or the thymic equivalent of circulating T cell progenitors (CTPs). It remains possible that an unknown hematopoietic precursor cell or previously described extrathymic precursors with a CLP, CLP-2, or CTP phenotype feed into T cell development by circumventing known intrathymic T cell lineage progenitor cells. However, it is clear that of the known intrathymic precursors, only the ETP population contributes significant numbers of T lineage precursors to T cell development.
Patient-reported outcomes improve with etanercept plus methotrexate in active early rheumatoid arthritis and the improvement is strongly associated with remission: the COMET trial
Authors: J Kekow, R J Moots, P Emery, P Durez, A Koenig, A Singh, R Pedersen, D Robertson, B Freundlich, R Sato
Journal: Annals of the Rheumatic Diseases (2009)

Objectives: To compare the effects of etanercept (ETN) 50 mg once weekly plus methotrexate (MTX) versus MTX alone on patient-reported outcomes (PROs) and the relationship between remission and PRO improvement. Methods: In this double-blind, randomised clinical trial (COMET), PROs included: the Health Assessment Questionnaire (HAQ), EuroQoL health status, fatigue and pain visual analogue scales, Hospital Anxiety and Depression Scale, and Medical Outcomes Short-Form-36. Mean changes from baseline were analysed by analysis of covariance using the last observation carried forward method. Results from week 52 are presented. Results: Most PROs demonstrated significantly greater improvements with ETN+MTX than MTX alone, including physical functioning, pain, fatigue and overall health status. A significantly greater improvement in HAQ score was observed in the ETN+MTX than the MTX group (−1.02 vs −0.72; p&lt;0.001) and a greater proportion reached the minimal clinically important difference of 0.22 (88% vs 78%; p&lt;0.006). The relationship between PRO score and clinical status indicated that improvement was greatest among patients achieving remission. Conclusions: Early treatment with ETN+MTX leads to significantly greater improvements in multiple dimensions of PROs than MTX alone. The close relationship between disease activity and PRO improvement suggests that early treatment, with remission as a goal, should maximise the chance of restoring normal functioning and HRQoL.