tbuckley/cabot-search huggingface dataset:
Hepatic arterial 5-fluorouracil in patients with liver metastases of colorectal cancer: Single-centre experience in 145 patients
Authors: J.M.G.H. van Riel, C.J. van Groeningen, S.H.M. Albers, M. Cazemier, S. Meijer, R. Bleichrodt, F.G. van den Berg, H.M. Pinedo, G. Giaccone
Journal: Annals of Oncology (2000)
Asthma follow-up and treatment in a group of 28 patients with eosinophilic granulomatosis with polyangiitis (EGPA)
Authors: Manuela Latorre, Federica Novelli, Chiara Baldini, Elena Bacci, Veronica Seccia, Silvana Cianchetti, Stefano Bombardieri, Pier Luigi Paggiaro
Journal: European Respiratory Journal (2013)

Background: patients with EGPA and severe chronic asthma often do not receive an adequate inhaled therapy and a regular follow-up for asthma.

Aims: to establish in EGPA patients the main tools to monitoring asthma; to evaluate the effects of inhaled therapy on asthma control and quality of life.

Methods: we enrolled 28 EGPA patients, all treated with oral steroids or immunosuppressive drugs for systemic illness;18 of them were poorly or not treated for asthma (NT),10 was adequately treated (AT). We assessed: lung function, bronchial hyperreactivity, sputum eosinophilia, exhaled nitric oxide, asthma severity and control according to GINA guidelines and ACT test, asthma quality of life by specific questionnaire (AQLQ). The inhaled therapy was appropriate to the asthma severity and control; a follow-up was made after 6 months.

Results: at baseline NT group significantly differed from the AT group in the asthma control (GINA p<0.009;ACT: p<0.036) and AQLQ (p<0.002). At the follow-up the group in which inhaled therapy was increased significantly improved in sputum eosinophilia (p<0.004) and AQLQ score (p<0.006).

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No significant differences were still present between groups for asthma control, AQLQ, lung function, airway inflammation.

Conclusions: immunosuppressive drugs are effective in controlling systemic disease in EGPA but not asthma that requires a specific inhaled therapy to improve asthma control and quality of life. Sputum analysis may represent a good tool in monitoring asthma and tailoring patients’ treatment.
Molecular Comparison of Calcineurin Inhibitor–Induced Fibrogenic Responses in Protocol Renal Transplant Biopsies
Authors: Marian C. Roos-van Groningen, Eduard M. Scholten, Patrick M. Lelieveld, Ajda T. Rowshani, Hans J. Baelde, Ingeborg M. Bajema, Sandrine Florquin, Frederike J. Bemelman, Emile de Heer, Johan W. de Fijter, Jan A. Bruijn, Michael Eikmans
Journal: Journal of the American Society of Nephrology (2006)

The calcineurin inhibitor cyclosporine (CsA) induces a fibrogenic response that may lead to scarring of the renal allograft. This study investigated whether tacrolimus, a novel calcineurin inhibitor, exerts fibrogenic effects to a similar extent. Sixty patients were enrolled in a randomized study: 29 received CsA, and 31 received tacrolimus. Patients were subjected to tailored exposure-controlled calcineurin inhibitor regimens. Protocol biopsies were obtained at the time of transplantation and 6 and 12 mo after transplantation. Cortical TGF-beta and collagens alpha1(I) and alpha1(III) mRNA steady-state levels were determined with real-time PCR. The extent of protein deposition of TGF-beta, alpha-smooth muscle actin, and interstitial collagens in the renal cortex was quantified with computer-assisted image analysis. The extent of interstitial collagen deposition measured with Sirius red and the accumulation of alpha-smooth muscle actin and TGF-beta protein after 6 and 12 mo were similar for both immunosuppressive regimens. mRNA levels of TGF-beta and collagens alpha1(I) and alpha1(III) were not significantly different in the treatment groups either. It is concluded that the fibrogenic response in renal allografts is similar in patients who receive CsA-based regimens and patients who receive tacrolimus-based regimens.
Upregulation of CD40 and CD40 Ligand (CD154) in Patients With Moderate Hypercholesterolemia
Authors: C.D. Garlichs, S. John, A. Schmeißer, S. Eskafi, C. Stumpf, M. Karl, M. Goppelt-Struebe, R. Schmieder, W.G. Daniel
Journal: Circulation (2001)

Background Hypercholesterolemia, a risk factor for cardiovascular disease, is associated with inflammation and hypercoagulability. Both can be mediated by the CD40 system. This study investigated whether the CD40 system is upregulated in patients with moderate hypercholesterolemia and whether it is influenced by therapy with a hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor. Methods and Results Fifteen patients with moderate hypercholesterolemia and 15 healthy control subjects were investigated. CD154 and P-selectin were analyzed on platelets and CD40 was analyzed on monocytes before and under therapy with the statin cerivastatin by double-label flow cytometry. Blood concentrations of soluble CD154 and monocyte chemoattractant protein-1 (MCP-1) were evaluated. Our main findings were as follows. Patients with moderate hypercholesterolemia showed a significant increase of CD154 and P-selectin on platelets and CD40 on monocytes compared with healthy subjects. Soluble CD154 showed a nonsignificant trend for higher plasma levels in patients. A positive correlation was found for total or LDL cholesterol and CD154, but not for CD40 on monocytes. The latter was upregulated in vitro by C-reactive protein, which was found to be significantly elevated in patients with moderate hypercholesterolemia. CD154 on platelets proved to be biologically active because it enhanced the release of MCP-1, which was markedly elevated in an in vitro platelet-endothelial cell coculture model and in the serum of patients. Short-term therapy with a HMG-CoA reductase inhibitor significantly downregulated CD40 on monocytes and serum levels of MCP-1. Conclusion Patients with moderate hypercholesterolemia show upregulation of the CD40 system, which may contribute to the known proinflammatory, proatherogenic, and prothrombotic milieu found in these patients.
A large multicentre analysis of CTGF -945 promoter polymorphism does not confirm association with systemic sclerosis susceptibility or phenotype
Authors: B Rueda, C Simeon, R Hesselstrand, A Herrick, J Worthington, N Ortego-Centeno, G Riemekasten, V Fonollosa, M C Vonk, F H J van den Hoogen, J Sanchez-Roman, M A Aguirre-Zamorano, R Garcia-Portales, A Pros, M T Camps, M A Gonzalez-Gay, M F Gonzalez-Escribano, M J Coenen, N Lambert, J L Nelson, T R D J Radstake, J Martin
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objective:</h3> To conduct a replication study to investigate whether the −945 <i>CTGF</i> genetic variant is associated with systemic sclerosis (SSc) susceptibility or specific SSc phenotype. <h3>Methods:</h3> The study population comprised 1180 patients with SSc and 1784 healthy controls from seven independent case–control sets of European ancestry (Spanish, French, Dutch, German, British, Swedish and North American). The −945 <i>CTGF</i> genetic variant was genotyped using a Taqman 5′ allelic discrimination assay. <h3>Results:</h3> An independent association study showed in all the case–control cohorts no association of the <i>CTGF</i> −945 polymorphism with SSc susceptibility. These findings were confirmed by a meta-analysis giving a pooled OR = 1.12 (95% CI 0.99 to 1.25), p = 0.06. Investigation of the possible contribution of the −945 <i>CTGF</i> genetic variant to SSc phenotype showed that stratification according to SSc subtypes (limited or diffuse), selective autoantibodies (anti-topoisomerase I or anticentromere) or pulmonary involvement reached no statistically significant skewing. <h3>Conclusion:</h3> The results do not confirm previous findings and suggest that the <i>CTGF</i> −945 promoter polymorphism does not play a major role in SSc susceptibility or clinical phenotype.
Serum adipokine zinc α2-glycoprotein and lipolysis in cachectic and noncachectic heart failure patients: relationship with neurohormonal and inflammatory biomarkers
Authors: Stefano Tedeschi, Elisabetta Pilotti, Elisabetta Parenti, Vanni Vicini, Pietro Coghi, Alberto Montanari, Giuseppe Regolisti, Enrico Fiaccadori, Aderville Cabassi
Journal: Metabolism (2011)
The rationing debate: Rationing health care by age: The case against
Authors: J G. Evans
Journal: BMJ (1997)

<h3>Background</h3> From October 2015, an Antimicrobial Stewardship Programme (ASP) was implemented in an internal medicine department by a multidisciplinary team. One of the interventions developed within this ASP was to promote the early switch of intravenous antimicrobial therapy to oral therapy through the introduction of Early Oral Switch Therapy (EOST) recommendations. <h3>Purpose</h3> We aimed to assess the impact on consumption, cost and duration of intravenous antimicrobials of the introduction of EOST recommendations by clinical pharmacists as a part of an ASP. <h3>Material and methods</h3> The study was prospective with a before–after design, divided into a pre-intervention phase (January–May 2015) and a post-intervention phase (January–May 2016). The intervention consisted of writing the advice of the EOST by the clinical pharmacist on the patient’s clinical chart. Target patients were those admitted to hospital internal medicine floors. They had all received more than 72 hours of selected intravenous antimicrobial treatment (co-amoxiclav, ceftriaxone, levofloxacin) and had clinical and analytical stability. Variables compared between the study phases were: consumption of selected and general antimicrobials calculated by defined daily dose per 100 stays (DDD/100 stays); cost of selected and general antimicrobial treatment, calculated by total spending per 100 stays; duration of selected and general antimicrobial treatments, calculated by total days of antimicrobial treatment per patient. All statistical analysis were performed using SPSS v.19.0, with a significance level of p&lt;0.05. <h3>Results</h3> During the pre-intervention phase, mean consumption of IV antimicrobials was 6.3 DDD/100 stays (4.7–7.9), and during the post-intervention phase it was 6.1 DDD/100 stays (4.3–7.9) (p=0.07). The associated mean costs were of €8.9/100 stays versus €8.1/100 stays (p=0.90). In terms of duration, the length of intravenous antimicrobial treatment during the pre-intervention phase was 4.3 days/patient (4.2–4.5), and during the post-intervention phase it was 3.5 days/patient (3.4–3.7) (p=0.05). <h3>Conclusion</h3> This study suggests successful implementation of an EOST. Differences were not statistically significant, but we found a trend towards decreasing intravenous antimicrobial duration, consumption and cost. ASP carried out by a multidisciplinary teams may result in a decrease in the overuse of intravenous antimicrobial treatments. <h3>References and/or acknowledgements</h3> Martínez Vazquez, MJ. Estrategia de conversion de la vía intravenosa a la vía oral. Vigo: Ediciones Mayo 2002. No conflict of interest
Increasing Body Mass Index and Obesity in the Incident ESRD Population
Authors: Holly J. Kramer, Anand Saranathan, Amy Luke, Ramone A. Durazo-Arvizu, Cao Guichan, Susan Hou, Richard Cooper
Journal: Journal of the American Society of Nephrology (2006)

An increase in obesity prevalence among patients who initiate dialysis may influence the growth of the total ESRD population as a result of improved survival and decreased likelihood for transplantation. Temporal trends in mean body mass index (BMI) and obesity prevalence were examined among incident patients with ESRD by year of dialysis initiation between 1995 and 2002, and these trends were compared with those in the US population during this same period. Among incident dialysis patients, BMI was calculated with the height and estimated dry weight collected from the Centers for Medicare and Medicaid Services End-Stage Renal Disease Medical Evidence Form. In the US population, self-reported height and weight were used. Prevalence of total obesity and obesity stage > or =2 were defined as a BMI > or =30 and > or =35 kg/m(2), respectively. Among incident patients with ESRD, mean BMI increased from 25.7 to 27.5 kg/m(2), and total obesity and obesity stage > or =2 increased by 33 and 63%, respectively, among incident patients with ESRD (P < 0.0001 for obesity trends). BMI slope was approximately two-fold higher in the incident ESRD population compared with the US population for all age groups. However, temporal increases in obesity prevalence were similar between the two populations. As a result of the survival advantage associated with obesity and decreased likelihood for transplantation, these trends most likely will influence the total number of patients who receive dialysis in the next decade.
Procalcitonin Algorithm in Critically Ill Adults with Undifferentiated Infection or Suspected Sepsis. A Randomized Controlled Trial
Authors: Yahya Shehabi, Martin Sterba, Peter Maxwell Garrett, Kanaka Sundaram Rachakonda, Dianne Stephens, Peter Harrigan, Alison Walker, Michael J. Bailey, Bronwyn Johnson, David Millis, Geoff Ding, Sandra Peake, Helen Wong, Jane Thomas, Kate Smith, Loretta Forbes, Miranda Hardie, Sharon Micallef, John F. Fraser
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

The role of procalcitonin (PCT), a widely used sepsis biomarker, in critically ill patients with sepsis is undetermined.To investigate the effect of a low PCT cut-off on antibiotic prescription and to describe the relationships between PCT plasma concentration and sepsis severity and mortality.This was a multicenter (11 Australian intensive care units [ICUs]), prospective, single-blind, randomized controlled trial involving 400 patients with suspected bacterial infection/sepsis and expected to receive antibiotics and stay in ICU longer than 24 hours. The primary outcome was the cumulative number of antibiotics treatment days at Day 28.PCT was measured daily while in the ICU. A PCT algorithm, including 0.1 ng/ml cut-off, determined antibiotic cessation. Published guidelines and antimicrobial stewardship were used in all patients. Primary analysis included 196 (PCT) versus 198 standard care patients. Ninety-three patients in each group had septic shock. The overall median (interquartile range) number of antibiotic treatment days were 9 (6-21) versus 11 (6-22), P = 0.58; in patients with positive pulmonary culture, 11 (7-27) versus 15 (8-27), P = 0.33; and in patients with septic shock, 9 (6-22) versus 11 (6-24), P = 0.64; with an overall 90-day all-cause mortality of 35 (18%) versus 31 (16%), P = 0.54 in the PCT versus standard care, respectively. Using logistic regression, adjusted for age, ventilation status, and positive culture, the decline rate in log(PCT) over the first 72 hours independently predicted hospital and 90-day mortality (odds ratio [95% confidence interval], 2.76 [1.10-6.96], P = 0.03; 3.20 [1.30-7.89], P = 0.01, respectively).In critically ill adults with undifferentiated infections, a PCT algorithm including 0.1 ng/ml cut-off did not achieve 25% reduction in duration of antibiotic treatment. Clinical trial registered with http://www.anzctr.org.au (ACTRN12610000809033).
The Structure of Genetic and Environmental Risk Factors for Dimensional Representations of<i>DSM-5</i>Obsessive-Compulsive Spectrum Disorders
Authors: Benedetta Monzani, Fruhling Rijsdijk, Juliette Harris, David Mataix-Cols
Journal: JAMA Psychiatry (2013)

<h3>Importance</h3> The new<i>DSM-5</i>"Obsessive-Compulsive and Related Disorders" chapter contains a series of conditions thought to be etiologically related to obsessive-compulsive disorder (OCD). However, the evidence to support this relatedness remains incomplete. <h3>Objective</h3> To estimate the degree to which genetic and environmental risk factors are shared and/or unique to dimensionally scored OCD, body dysmorphic disorder (BDD), hoarding disorder (HD), trichotillomania (hair-pulling disorder) (TTM), and excoriation (skin-picking) disorder (SPD). <h3>Design, Setting, and Participants</h3> Multivariate twin modeling methods involving 5409 female members of the TwinsUK adult population-based twin register. <h3>Main Outcomes and Measures</h3> Scores on the Obsessive-Compulsive Inventory–Revised, the Dysmorphic Concern Questionnaire, the Hoarding Rating Scale, the Massachusetts General Hospital Hairpulling Scale, and the Skin Picking Scale. <h3>Results</h3> A 2–latent factor common pathway model fitted the data best; the first latent factor loaded on all 5 phenotypes, particularly on OCD, BDD, and HD. A second factor loaded exclusively on TTM and SPD. Disorder-specific genetic (for OCD, BDD, and HD only) and particularly nonshared environmental risk factors were also evident. Shared environmental influences were negligible. <h3>Conclusions and Relevance</h3> Obsessive-compulsive and related disorders may be influenced by 2 distinct liability factors rather than a single liability factor. One of these factors was common to all disorders, and another was exclusive to TTM and SPD. Disorder-specific genetic factors unique to OCD, BDD, and HD were also apparent, whereas TTM and SPD were largely influenced by the same latent genetic factor. Environmental influences were largely disorder specific. The results help explain the apparent similarities as well as some important differences between the disorders included in the new Obsessive-Compulsive and Related Disorders chapter.
Induction of protein synthesis in cardiac fibroblasts by cardiotrophin-1: integration of multiple signaling pathways
Authors: D Freed
Journal: Cardiovascular Research (2003)

Cardiotrophin-1 (CT-1) is a member of the IL-6 family of cytokines and is expressed in various cardiovascular disease states. CT-1 induces cardiomyocyte hypertrophy, and protects myocytes from ischemia reperfusion injury. We sought to elucidate CT-1 signaling in cardiac fibroblasts with respect to initiation of protein synthesis.Cardiac fibroblasts were isolated from the ventricles of 200-g Sprague-Dawley rats and stimulated with CT-1 at specified concentrations with or without inhibitors of cell signaling pathways. Activation of intracellular signaling pathways was determined by Western analysis and immunocytochemistry. Protein synthesis was measured by incorporation of [3H]leucine.CT-1 treatment resulted in activation of the Jak/STAT, MAPK, and Akt pathways in addition to protein synthesis regulatory proteins with resultant increase in overall protein synthesis. Analysis with phospho-specific antibodies revealed that AG490 (Jak inhibitor), PD98059 (MEK1/2 inhibitor), SB203580 (p38 MAPK inhibitor), LY294002 (PI3-K inhibitor) and rapamycin (mTOR inhibitor) act at different levels in the signaling cascade to inhibit CT-1 induced protein synthesis.Cardiotrophin-1 activates the Jak/STAT, PI3K/Akt, p38 and p42/44 MAPK pathways in cardiac fibroblasts. Use of pharmacologic inhibitors reveals that each of these pathways play a role in CT-1 induced protein synthesis.
Predictive value of normal sperm morphology in intrauterine insemination (IUI): a structured literature review
Authors: J Van Waart, T F Kruger, C J Lombard, W Ombelet
Journal: Human Reproduction Update (2001)

The aim of the study was to conduct a structured review of the literature published on the use of normal sperm morphology, as an indicator of male fertility potential in intrauterine insemination (IUI) programmes. Published literature in which normal sperm morphology was used to predict pregnancy outcome in IUI during the period 1984–1998 was reviewed. In total, 421 articles were identified via Medline searches. Eighteen provided data that could be tabulated and analysed. Eight of the analysed studies provided sufficient data for statistical analysis, six studies used the Tygerberg 'strict' criteria, and two the WHO guidelines (1987, 1992). A meta-analysis of the six studies in the strict morphology group yielded a risk difference (RD) between the pregnancy rates achieved in the patients below and above the 4% strict criteria threshold of –0.07 (95% CI: –0.11 to –0.03; P < 0.001). The WHO criteria group (1987, 1992) had insufficient data to be analysed. Meta-analysis showed a significant improvement in pregnancy rate above 4% threshold for strict criteria. Accurate evaluation of normal sperm morphology results should be an integral part of evaluating the male factor.
Brachyury, a Driver of the Epithelial–Mesenchymal Transition, Is Overexpressed in Human Lung Tumors: An Opportunity for Novel Interventions against Lung Cancer
Authors: Mario Roselli, Romaine I. Fernando, Fiorella Guadagni, Antonella Spila, Jhessica Alessandroni, Raffaele Palmirotta, Leopoldo Costarelli, Mary Litzinger, Duane Hamilton, Bruce Huang, Joanne Tucker, Kwong-Yok Tsang, Jeffrey Schlom, Claudia Palena
Journal: Clinical Cancer Research (2012)

The epithelial-mesenchymal transition (EMT) is emerging as a critical factor for the progression and metastasis of carcinomas, as well as drug resistance. The T-box transcription factor Brachyury has been recently characterized as a driver of EMT in human carcinoma cells. The purpose of this study was to characterize Brachyury as a potential target for lung cancer therapy.The expression of Brachyury was evaluated by PCR and by immunohistochemistry in human lung tumors and adult normal tissues. Brachyury gene copy number and promoter methylation status were analyzed in tumor tissues with various levels of Brachyury expression. Lung carcinoma cells' susceptibility to T-cell lysis and EGF receptor (EGFR) kinase inhibition were also evaluated relative to the levels of Brachyury.Our results showed Brachyury protein expression in 41% of primary lung carcinomas, including 48% of adenocarcinomas and 25% of squamous cell carcinomas. With the exception of normal testis and some thyroid tissues, the majority of normal tissues evaluated in this study were negative for the expression of Brachyury protein. Brachyury-specific T cells could lyse Brachyury-positive tumors and the level of Brachyury corresponded to resistance of tumor cells to EGFR kinase inhibition.We hypothesize that the elimination of Brachyury-positive tumor cells may be able to prevent and/or diminish tumor dissemination and the establishment of metastases. The ability of Brachyury-specific T-cell lines to lyse Brachyury-positive tumor cells, in vitro, supports the development of Brachyury-based immunotherapeutic approaches for the treatment of lung cancer.
Lack of relationship between serum gp70 levels and the severity of systemic lupus erythematosus in MRL/l mice.
Authors: J Andrews, L Hang, A N Theofilopoulos, F J Dixon
Journal: The Journal of Experimental Medicine (1986)

In the MRL/l mouse, gp70 apparently plays a role as an autoantigen in the development of SLE. However, while gp70 may be an important pathogenetic element, it is not essential to MRL SLE, since elimination of most of the serum gp70 and virtually all of the immune complex gp70 from MRL/l-low gp70 congenic lines had no observable effect on the course or nature of the disease. Thus, while gp70 in the MRL/l mouse appears to be a convenient autoantigenic target when present in significant levels, in its absence the host appears capable of directing its aberrant immunologic responsiveness elsewhere with undiminished pathogenicity.