tbuckley/cabot-search huggingface dataset:
Clinical Impact of Folfirinox Dose/Schedule Modifications (Mfolforinox) and Additional Supportive Measures in the Management of Pancreatic Cancer (Pdac) Patients (Pts)
Authors: V. Vaccaro, I. Sperduti, D. Melisi, E. Bria, E. Vasile, M. Santoni, G. Giordano, P. Bertocchi, E. Lucchini, M.S. Pino, A. Gelibter, C. Garufi, M. Zeuli, A. Zaniboni, A. Febbraro, S. Cascinu, A. Falcone, G. Tortora, F. Cognetti, M. Milella
Journal: Annals of Oncology (2014)
Laser-induced autofluorescence of human arteries.
Authors: M Sartori, D Weilbaecher, G L Valderrama, S Kubodera, R C Chin, M J Berry, F K Tittel, R Sauerbrey, P D Henry
Journal: Circulation Research (1988)

A new technique for imaging the intimal surface of arteries through optic fibers has been devised. With the aid of an optical multichannel analyzer, we recorded in real time fluorescence spectra during excitation of the arterial surface with an argon ion laser. Spectral parameters were used to detect atherosclerotic plaques and to discriminate normal tissue from lipid rich and calcified atheromas. By digitizing relative intensity values and the ratios of the peak at 550 nm to that at 520 nm into a gray scale, we generated pseudocolor maps of the arterial wall of 10 human aortas. Specific color distributions were congruent with the distribution of calcified tissue visualized by soft x-ray radiography and the distribution of lipid delineated by staining with Sudan IV. Thus, bidimensional maps obtained by laser spectroscopy can be used to identify the presence and composition of atherosclerotic lesions. Fluorescence imaging may prove to be an important application of laser techniques for the diagnosis and treatment of atherosclerosis.
The Transatlantic Trade and Investment Partnership: Trojan horse or positive force for health?
Authors: Marine Faure, Brian Ward
Journal: European Respiratory Journal (2015)

For centuries, Greek mythology strove to reflect human behaviour through its myths. One of the more well-known myths is that of the Trojan horse, a poisoned chalice offered to the Trojans in which the Greeks were hidden to invade the city, and which has come to symbolise human deceit. Today, this link between the myth and actual facts is in the limelight with respect to the Transatlantic Trade and Investment Partnership (TTIP), which is currently being negotiated between the European Union (EU) and the USA. Some see the EU citizens as the trapped Trojans and the EU and the USA leaders as the cunning Greeks. Roughly speaking, the TTIP aims at removing trade barriers (tariffs, unnecessary regulations and restrictions on investments etc. ) in a wide range of economic sectors including health. The purpose is to facilitate the purchase and sale of goods and services between the EU and the USA, as well as to facilitate the investment of companies [1]. On the one hand, proponents guarantee that the treaty will be the opportunity to create growth and employment and promote healthcare in a Eurozone still struggling [2]. On the other hand, opponents argue it could lower the health protection standards of Europeans and challenge the right of the EU to regulate. While the public debate remains heated, it is crucial to consider both sides in order to understand the potential benefits and risks from the TTIP for the European health community. This piece aims to set out the most controversial elements and how they may impact on the health care system. Is the Transatlantic Trade and Investment Partnership (TTIP) a Trojan horse or a positive for health? <http://ow.ly/NOVdp>
Presence of antinuclear antibodies and coronary heart disease
Authors: I Brusca
Journal: Annals of the Rheumatic Diseases (2002)

Recent reports have shown the importance of new risk factors for ischaemic stroke and myocardial infarction. An article by Grainger et al reports that antinuclear antibodies (ANA) are more prevalent in subjects with severe coronary atherosclerosis than in healthy subjects.1

The authors’ statement that the association is a potential indicator of increased risk of coronary heart disease is not fully supported by data obtained in our study. The authors affirm that ANA, determined by the immunofluorescent method in HEp-2000 cells, were detected at a titre of at least 1/40 in 28/40 (70%) subjects with severe stenoses of three main coronary arteries. In contrast ANA were detected in 5/30 (17%) subjects with no evidence of coronary atherosclerosis.

Our study mainly aimed at investigating the relationship between anticardiolipin antibodies (aCL), and β2-glycoprotein I antibodies (a-β2GPI), their association with increased risk of ischaemic stroke (IS) and myocardial infarction (MI), and the occurrence of clinical recurrence of ischaemic events as IS, MI, unstable angina or transient ischaemic attack (TIA). The study group comprised 139 …
Adherence Barriers to Chronic Dialysis in the United States
Authors: Kevin E. Chan, Ravi I. Thadhani, Franklin W. Maddux
Journal: Journal of the American Society of Nephrology (2014)

Hemodialysis patients often do not attend their scheduled treatment session. We investigated factors associated with missed appointments and whether such nonadherence poses significant harm to patients and increases overall health care utilization in an observational analysis of 44 million hemodialysis treatments for 182,536 patients with ESRD in the United States. We assessed the risk of hospitalization, emergency room visit, or intensive-coronary care unit (ICU-CCU) admission in the 2 days after a missed treatment relative to the risk for patients who received hemodialysis. Over the 5-year study period, the average missed treatment rate was 7.1 days per patient-year. In covariate adjusted logistic regression, the risk of hospitalization (odds ratio [OR], 3.98; 95% confidence interval [95% CI], 3.93 to 4.04), emergency room visit (OR, 2.00; 95% CI, 1.87 to 2.14), or ICU-CCU admission (OR, 3.89; 95% CI, 3.81 to 3.96) increased significantly after a missed treatment. Overall, 0.9 missed treatment days per year associated with suboptimal transportation to dialysis, inclement weather, holidays, psychiatric illness, pain, and gastrointestinal upset. These barriers also associated with excess hospitalization (5.6 more events per patient-year), emergency room visits (1.1 more visits), and ICU-CCU admissions (0.8 more admissions). In conclusion, poor adherence to hemodialysis treatments may be a substantial roadblock to achieving better patient outcomes. Addressing systemic and patient barriers that impede access to hemodialysis care may decrease missed appointments and reduce patient morbidity.
Nebulizer calibration using lithium chloride: an accurate, reproducible and user-friendly method
Authors: RJ Ward, DW Reid, RF Leonard, DP Johns, EH Walters
Journal: European Respiratory Journal (1998)

Conventional gravimetric (weight loss) calibration of jet nebulizers overestimates their aerosol output by up to 80% due to unaccounted evaporative loss. We examined two methods of measuring true aerosol output from jet nebulizers. A new adaptation of a widely available clinical assay for lithium (determined by flame photometry, LiCl method) was compared to an existing electrochemical method based on fluoride detection (NaF method). The agreement between the two methods and the repeatability of each method were examined. Ten Mefar jet nebulizers were studied using a Mefar MK3 inhalation dosimeter. There was no significant difference between the two methods (p=0.76) with mean aerosol output of the 10 nebulizers being 7.40 mg x s(-1) (SD 1.06; range 5.86-9.36 mg x s(-1)) for the NaF method and 7.27 mg x s(-1) (SD 0.82; range 5.52-8.26 mg x s(-1)) for the LiCl method. The LiCl method had a coefficient of repeatability of 13 mg x s(-1) compared with 3.7 mg x s(-1) for the NaF method. The LiCl method accurately measured true aerosol output and was considerably easier to use. It was also more repeatable, and hence more precise, than the NaF method. Because the LiCl method uses an assay that is routinely available from hospital biochemistry laboratories, it is easy to use and, thus, can readily be adopted by busy respiratory function departments.
The cAMP response element binding protein modulates expression of the transient outward current: Implications for cardiac memory
Authors: K PATBERG, M OBREZTCHIKOVA, S GIARDINA, A SYMES, A PLOTNIKOV, J QU, P CHANDRA, D MCKINNON, S LIOU, A RYBIN
Journal: Cardiovascular Research (2005)

Objective: Long-term cardiac memory (LTCM), expressed as a specific pattern of T-wave change on ECG, is associated with 1) reduced transient outward potassium current (Ito), 2) reduced mRNA for the pore-forming protein of Ito, Kv4.3, 3) reduced cAMP response element binding protein (CREB), and 4) diminished binding to its docking site on the DNA, the cAMP response element (CRE). We hypothesized a causal link between the decrease of the transcription factor CREB and down-regulation of Ito and one of its channel subunits, KChIP2, in LTCM. Methods: After three weeks of left ventricular pacing to induce LTCM (8 paced, 7 sham control dogs), epicardial KChIP2 mRNA and protein levels were assessed by real-time PCR and Western blotting. Mimicking the CREB down-regulation in LTCM, CREB was knocked down in situ in other dogs using adenoviral anti-sense. Effects on the action potential notch, reflecting Ito, were investigated in situ using monophasic action potential (MAP) recordings and at the cellular level by the whole-cell patch clamp technique. CREB binding in the KChIP2 promoter region was ascertained by electrophoretic mobility-shift assays. Results: In LTCM, epicardial KChIP2 mRNA and protein were reduced by 62% and 76%, respectively, compared to shams (p<0.05). CREB binding by the canine KChIP2 promoter region was demonstrated. CREB knockdown led to disappearance of the phase1 notch in MAP and ablation of Ito. Conclusions: These results strengthen the hypothesis that down-regulation of CREB-mediated transcription underlies the attenuation of epicardial Ito in LTCM. They also emphasize that ventricular pacing exerts effects at a subcellular level contributing to memory and conceivably to other forms of cardiac remodeling.
Targeted expression of tumor necrosis factor-related apoptosis-inducing ligand TRAIL in skin protects mice against chemical carcinogenesis
Authors: Valerie Kedinger, Stephanie Muller, Hinrich Gronemeyer
Journal: Molecular Cancer (2011)

Abstract Background Gene ablation studies have revealed that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL, Apo2L, TNFSF10) plays a crucial role in tumor surveillance, as TRAIL-deficient mice exhibit an increased sensitivity to different types of tumorigenesis. In contrast, possible tumor-protective effect of increased levels of endogenous TRAIL expression in vivo has not been assessed yet. Such models will provide important information about the efficacy of TRAIL-based therapies and potential toxicity in specific tissues. Methods To this aim, we engineered transgenic mice selectively expressing TRAIL in the skin and subjected these mice to a two-step chemical carcinogenesis protocol that generated benign and preneoplastic lesions. We were therefore able to study the effect of increased TRAIL expression at the early steps of skin tumorigenesis. Results Our results showed a delay of tumor appearance in TRAIL expressing mice compared to their wild-type littermates. More importantly, the number of tumors observed in transgenic animals was significantly lower than in the control animals, and the lesions observed were mostly benign. Interestingly, Wnt/β-catenin signaling differed between tumors of wild-type and TRAIL transgenics. Conclusion Altogether, these data reveal that, at least in this model, TRAIL is able on its own to act on pre-transformed cells, and reduce their tumorigenic potential.
The polymorphism interleukin 8 -251 A/T influences the susceptibility of Helicobacter pylori related gastric diseases in the Japanese population
Authors: M Ohyauchi
Journal: Gut (2005)

Helicobacter pylori infection is associated with variable clinical outcomes, including gastroduodenal diseases, and genetic factors may be relevant in this process.We investigated the effects of an interleukin 8 (IL-8) gene polymorphism on the risk of gastroduodenal diseases, the degree of H pylori induced gastritis, and IL-8 gene transcription.The study was performed in 244 healthy control subjects and 690 H pylori positive patients with non-cardia gastric cancer, gastric ulcer, duodenal ulcer, or gastritis.We identified the IL-8 -251 A/T polymorphism by direct sequence analysis, and measured the gastritis score and serum pepsinogen (PG). The transcriptional promoter activity of the IL-8 gene was assessed by luciferase assay.IL-8 -251A was associated with a higher risk of gastric cancer and gastric ulcer. Patients carrying IL-8 -251A showed an increased risk of gastric cancer (odds ratios (OR) 2.01 (95% confidence interval (CI) 1.38-2.92)) and gastric ulcer (OR 2.07 (95% CI 1.37-3.12)). Compared with patients younger than 49 years, atrophy and metaplasia scores in the antrum were significantly higher and the PG I/II ratio significantly lower in -251A carriers than in T/T carriers. In the in vitro assay, IL-8 -251A showed enhanced promoter activity in response to IL-1beta or tumour necrosis factor alpha.The IL-8 -251A allele may be associated with progression of gastric atrophy in patients with H pylori infection, and may increase the risk of gastric cancer and gastric ulcer in Japanese people.
Platelet-activating factor reduces endothelial nitric oxide production: role of acid sphingomyelinase
Authors: Y. Yang, J. Yin, W. Baumgartner, R. Samapati, E.A. Solymosi, E. Reppien, W.M. Kuebler, S. Uhlig
Journal: European Respiratory Journal (2009)

Platelet-activating factor (PAF) is a mediator of pulmonary oedema in acute lung injury that increases vascular permeability within minutes, partly through activation of acid sphingomyelinase (ASM). Since caveolae are rich in sphingomyelin and caveolin-1, which block endothelial nitric oxide (NO) synthase (eNOS) by direct binding, we examined the relationship between ASM, caveolin-1 and eNOS activity in the regulation of vascular permeability by PAF. In caveolar fractions from pulmonary vascular endothelial cells (isolated from perfused rat lungs) the abundance of caveolin-1 and eNOS increased rapidly after PAF perfusion. PAF treatment decreased endothelial NO (eNO) formation as assessed by in situ fluorescence microscopy. Restoration of eNO levels with PAPA-NONOate ((Z)-1-[N-(3-ammoniopropyl)-N-(n-propyl)amino]diazen-1-ium-1,2-diolate) mitigated the PAF-induced oedema. PAF treatment increased the ASM activity in caveolar fractions and perfusion with ASM decreased eNO production. Pharmacological inhibition of the ASM pathway with imipramine, D609 or dexamethasone blocked the PAF-induced increase of caveolin-1 and eNOS in caveolae, and the decrease in eNO production and oedema formation. We conclude that PAF causes ASM-dependent enrichment of caveolin-1 in caveolae of endothelial cells, leading to decreased eNO production which contributes to pulmonary oedema formation. These findings suggest rapid reduction in eNO production as a novel mechanism in the regulation of vascular permeability.
Double blind, randomised, placebo controlled study of leflunomide in the treatment of active ankylosing spondylitis
Authors: J C van Denderen
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objective:</b> To assess the efficacy and safety of leflunomide in active ankylosing spondylitis (AS) compared with placebo in a 24 week pilot study. <b>Methods:</b> In a single centre randomised, double blind, placebo controlled study, 45 patients with active AS were randomised to either leflunomide 20 mg daily (n = 30) or placebo (n = 15). Active disease was defined as a score of ⩾4 on the Bath ankylosing spondylitis disease activity index (0–10), and pain of ⩾4 on a visual analogue scale (0–10). The primary efficacy variable at week 24 was the 20% response rate, as recommended by the Assessments in Ankylosing Spondylitis (ASAS) working group. Secondary outcome variables included general wellbeing, metrology index, swollen joint count, erythrocyte sedimentation rate, and C reactive protein. <b>Results:</b> In all, 13 women and 32 men were studied. Demographic and disease indices were comparable between the two treatment groups at baseline. The rate of ASAS 20% responders was not significantly different: 27% in the leflunomide treated patients and 20% in the placebo group (95% confidence interval, −32% to 19%). No significant differences were found between the treatment groups in mean changes of the secondary outcome variables. Eleven patients were withdrawn prematurely from the study because of adverse events (7), lack of efficacy (3), and non-compliance (1). Most frequently adverse events were gastrointestinal side effects and skin disorders. <b>Conclusions:</b> In this placebo controlled study, leflunomide treatment did not result in a significant improvement of the ASAS 20% response in active ankylosing spondylitis. No unexpected or severe adverse events occurred.
Antibodies reacting with Simian Virus 40 capsid protein mimotopes in serum samples from patients affected by uveal melanoma
Authors: Ilaria Bononi, Paolo Perri, Alice Begnardi, Alessandra Martini, Elisa Mazzoni, Silvia Bosi, Silvia Pietrobon, Adolfo Sebastiani, Mauro Tognon, Fernanda Martini
Journal: Journal of Hematology & Oncology (2014)

The uveal melanoma (UM) is the most common human intraocular tumour. Simian Virus 40 (SV-40) is a small DNA tumor virus detected in some malignancies, including the cutaneous melanoma. In this study an indirect ELISA using synthetic peptides that mimic SV-40 antigens, was employed to detect antibodies against SV-40 in serum samples from UM patients. Our report indicates a significant higher prevalence of antibodies against SV-40 capsid protein antigens in serum samples from UM patients compared to controls. Our data suggest an association between UM and SV-40, indicating that patients affected by uveal melanoma tested SV-40-positive could be treated by innovative therapies.
CELL-TO-CELL INTERACTION IN THE IMMUNE RESPONSE
Authors: Christina Cheers, J. F. A. P. Miller
Journal: The Journal of Experimental Medicine (1972)

Mice primed to horse erythrocytes (HRBC) produced greatly enhanced 3,5-dinitro,4-hydroxyphenylacetic (NNP)-specific indirect plaque-forming cell (7S PFC) responses when given NNP.HRBC but no difference in hapten-specific direct (19S PFC) responses in comparison to non-carrier-primed mice. The effect was carrier specific and could not be produced by simultaneous challenge of rabbit erythrocyte (RRBC)-primed mice with RRBC and NNP.HRBC. When spleen cells from HRBC-primed mice were transferred to irradiated recipients, there was again an enhanced 7S response to NNP.HRBC. The primed spleen cells could be replaced by giving activated thymus cells to HRBC together with normal spleen as a source of B cells. It is concluded that T cells influence not only the amount but also the class of antibody formed by hapten-sensitive B cells.
Secondary Prevention of Renal and Cardiovascular Disease
Authors: Wendy E. Hoy, Zhiqiang Wang, Philip R. A. Baker, Angela M. Kelly
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Australian Aborigines are experiencing an epidemic of renal and cardiovascular disease. In late 1995 we introduced a treatment program into the Tiwi community, which has a three- to fivefold increase in death rates and a recent annual incidence of treated ESRD of 2760 per million. Eligible for treatment were people with hypertension, diabetics with micro or overt albuminuria, and all people with overt albuminuria. Treatment centered around use of perindopril (Coversyl, Servier), with other agents added to reach BP goals; attempts to control glucose and lipid levels; and health education. Thirty percent of the adult population, or 267 people, were enrolled, with a mean follow up of 3.39 yr. Clinical parameters were followed every 6 mo, and rates of terminal endpoints were compared with those of 327 historical controls matched for baseline disease severity, followed in the pretreatment program era. There was a dramatic reduction in BP in the treatment group, which was sustained through 3 yr of treatment. Albuminuria and GFR stabilized or improved. Rates of natural deaths were reduced by an estimated 50% (P = 0.012); renal deaths were reduced by 57% (P = 0.038); and nonrenal deaths by 46% (P = 0.085). Survival benefit was suggested at all levels of overt albuminuria, and regardless of diabetes status, baseline BP, or prior administration of angiotensin converting enzyme inhibitors (ACEI). No significant benefit was apparent among people without overt albuminuria, nor among those with GFR less than 60 ml/min. An estimated 13 renal deaths and 10 nonrenal deaths were prevented, with the number-needed-to-treat to avoid one terminal event of only 11.6. Falling deaths and renal failure in the whole community support these estimates. The program was extremely cost-effective. Programs like this should be introduced to all high-risk communities as a matter of urgency. E-mail: [email protected]
Exercise Intolerance in Adult Congenital Heart Disease
Authors: Gerhard-Paul Diller, Konstantinos Dimopoulos, Darlington Okonko, Wei Li, Sonya V. Babu-Narayan, Craig S. Broberg, Bengt Johansson, Beatriz Bouzas, Michael J. Mullen, Philip A. Poole-Wilson, Darrel P. Francis, Michael A. Gatzoulis
Journal: Circulation (2005)

Background— Although some patients with adult congenital heart disease (ACHD) report limitations in exercise capacity, we hypothesized that depressed exercise capacity may be more widespread than superficially evident during clinical consultation and could be a means of assessing risk. Methods and Results— Cardiopulmonary exercise testing was performed in 335 consecutive ACHD patients (age, 33±13 years), 40 non–congenital heart failure patients (age, 58±15 years), and 11 young (age, 29±5 years) and 12 older (age, 59±9 years) healthy subjects. Peak oxygen consumption (peak V̇ o 2 ) was reduced in ACHD patients compared with healthy subjects of similar age (21.7±8.5 versus 45.1±8.6; P &lt;0.001). No significant difference in peak V̇ o 2 was found between ACHD and heart failure patients of corresponding NYHA class ( P =NS for each NYHA class). Within ACHD subgroups, peak V̇ o 2 gradually declined from aortic coarctation (28.7±10.4) to Eisenmenger (11.5±3.6) patients ( P &lt;0.001). Multivariable correlates of peak V̇ o 2 were peak heart rate ( r =0.33), forced expiratory volume ( r =0.33), pulmonary hypertension ( r =−0.26), gender ( r =−0.23), and body mass index ( r =−0.19). After a median follow-up of 10 months, 62 patients (18.5%) were hospitalized or had died. On multivariable Cox analysis, peak V̇ o 2 predicted hospitalization or death (hazard ratio, 0.937; P =0.01) and was related to the frequency and duration of hospitalization ( P =0.01 for each). Conclusions— Exercise capacity is depressed in ACHD patients (even in allegedly asymptomatic patients) on a par with chronic heart failure subjects. Lack of heart rate response to exercise, pulmonary arterial hypertension, and impaired pulmonary function are important correlates of exercise capacity, as is underlying cardiac anatomy. Poor exercise capacity identifies ACHD patients at risk for hospitalization or death.
Incidence of bacteremia and value of antibiotic phophylaxis during esophageal sclerotherapy: A prospective study
Authors: M. Bourlière, M. Antoni, A. Maillot, D. Botta-Fridlund, J.M. Escoffier, P. Bres, M. Pons, D. Raoult, A.P. Gautnier
Journal: Journal of Hepatology (1990)