tbuckley/cabot-search huggingface dataset:
Evaluation of mechanisms determining endothelial function in patients with COPD
Authors: Christian F. Clarenbach, Anne C. Stoewhas, Arnoldus J.R. van Gestel, Giovanni Camen, Valentina A. Rossi, Noriane Sievi, Oliver Senn, Robert Thurnheer, Erich W. Russi, Malcolm Kohler
Journal: European Respiratory Journal (2012)

Background: COPD is associated with increased cardiovascular mortality. Factors contributing to vascular damage in patients with COPD are mostly unknown. However, it has been suggested that airflow limitation, systemic inflammation, oxidative stress, sympathetic activation, hypoxia and impaired physical activity may lead to endothelial dysfunction and underpin this association. Objective: To determine the impact of airflow obstruction, systemic inflammation, oxidative stress, sympathetic activation, hypoxia and physical activity on endothelial function in COPD. Methods: In patients with stable COPD (GOLD stage I-IV) assessments of endothelial function by flow-mediated dilatation (FMD), conventional cardiovascular risk factors (Pocock-score), airflow obstruction (FEV1), systemic inflammation (CRP), oxidative stress (malondialdehyde), sympathetic activation (baroreflex-sensitivity), hypoxia (blood gases) and physical activity (steps per day) were performed. Associations between endothelial function and these potential underlying mechanisms were assessed in univariate and multivariate analysis. Results: 106 patients (35% GOLD stage I/II, 25% III, 40% IV) were included. In univariate analysis FMD correlated with FEV1 (r=0.53, p<0.001), baroreflex-sensitivity (r=0.25, p=0.01), and steps per day (r=0.27, p=0.01) but not with CRP, malondialdehyde, hypoxia or Pocock-score. In multivariate analysis including all proposed mechanisms only FEV1 and steps per day were independently associated with FMD. Conclusions: Endothelial function in COPD seems to be primarily determined by the severity of airflow obstruction and the level of physical activity.
Abstract 3269: Association of Aortic Regurgitation with Cardiovascular Morbidity and Mortality in Hypertensive Patients with Left Ventricle Hypertrophy: The LIFE study
Authors: Zhibin Li, Kristian Wachtell, Sverre E. Kjeldsen, Stevo Julius, Michael H. Olsen, Eva Gerdts, Markku S. Nieminen, Sverker Jern, Peter M. Okin, Björn S Dahlöf, Richard B. Devereux
Journal: Circulation (2007)

Background : Whether aortic regurgitation (AI) is associated with higher cardiovascular (CV) morbidity and mortality in hypertension with electrocardiographic (ECG) left ventricular hypertrophy (LVH) is unknown. Methods : Hypertensive patients with ECG-LVH were randomized to losartan- or atenolol-based treatment and followed for 4.8 years in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. In the LIFE echo substudy, echocardiograms were used to detect AI. Baseline clinical, echocardiographic variables and cardiovascular endpoints data were used in current analyses. Results: The presence of AI was detected in 132 participants (68 women; 68.4 ± 7.3 years). AI was associated with older age (p &lt; 0.001) but not gender. After adjustment for age, AI was associated with significantly increased LV mass indexed by body surface area (BSA) and height 2.7 (both p &lt; 0.005), echocardiographic eccentric LVH (p &lt; 0.05) but not concentric left ventricular (LV) geometry (p &lt; 0.05). After adjusting for significant confounders including history of CV disease, Framingham risk score, randomized antihypertensive therapy, LV eccentric geometry, LV mass indexed by BSA and height 2.7 , multivariate Cox regression analyses showed that AI was independently associated with 2.83-fold more CV death (95% confidence interval [CI] 1.12 to 7.13), 2.24-fold more all-cause mortality (95% CI 1.17 to 4.28) (both p &lt; 0.05). Conclusion : In hypertensive patients with ECG-LVH, AI independently identifies patients at increased risk of CV and all-course mortality.
Tests of competency to consent to treatment
Authors: Loren H. Roth, Alan Meisel, Charles W. Lidz
Journal: American Journal of Psychiatry (1977)

The authors describe the various tests of competency to consent to treatment used today, which include the following: 1)evidencing a choice, 2)"reasonable" outcome of choice, 3)choice based on "rational" reasons, 4)ability to understand, and 5)actual understanding. They analyze the applicability of these tests to patients' decisions to accept or refuse psychiatric treatment and illustrate the problems of ap-lying these tests by citing clinical case examples. They find that the circumstances in which competency becomes an issue determine which elements of which tests are stressed and which are underplayed.
Ara h 2 and Ara 6 are the best predictors of severe peanut allergy: a double‐blind placebo‐controlled study
Authors: A. K. Kukkonen, A. S. Pelkonen, S. Mäkinen‐Kiljunen, H. Voutilainen, M. J. Mäkelä
Journal: Allergy (2015)

Component-resolved diagnostics offers a modern tool in peanut allergy, but studies applying consistently double-blind placebo-controlled challenges are lacking. We aimed to optimize diagnostics for moderate-to-severe peanut allergy in a birch-endemic region and to create an oral-peanut challenge with its allergen activity characterized.We performed double-blind placebo-controlled peanut challenges for a referred sample of 6- to 18-year-olds with peanut sensitization or a high suspicion of peanut allergy, including anaphylaxis. We measured specific IgE (sIgE) to Ara h 1, 2, 3, 6, 8, and 9. Testing of allergen activity of the challenge products was by IgE microarray inhibition.Of the 102 patients, 69 were challenge positive: 25 (36%) had severe, 36 (52%) moderate, and 8 (12%) mild symptoms; 38 (37%) received adrenalin. SIgE to Ara h 6 AUC 0.98 (95%CI, 0.96-1.00) was the best marker of moderate-to-severe allergy. When sIgE to Ara h 2 and Ara h 6 was measured together, all (100%) severe reactions at low doses were successfully diagnosable. SIgE to Ara h 8 had no diagnostic value, AUC 0.42 (95%CI, 0.30-0.52). Both nonroasted and roasted peanut inhibited 100% of IgE binding to Ara h 1, 2, 3, and 6. Nonroasted peanut inhibited 87% of IgE binding to Ara h 8, roasted inhibited 30%. The products lacked Ara h 9 activity.Co-sensitization to Ara h 2 and Ara h 6 was associated with severe reactions distinguishing severe allergy from mild symptoms. SIgE to Ara h 8 added no diagnostic value. Component-resolved diagnostics reduce the need for oral challenges in peanut allergy.
Abstract 6145: Low Fetuin-A Concentrations Predict the Progression of Aortic Valve Calcification in Non-Dialyzed Patients
Authors: Ralf Koos, Vincent Brandenburg, Andreas Horst Mahnken, Georg Mühlenbruch, Sven Stanzel, Malte Kelm, Harald Peter Kühl
Journal: Circulation (2008)

Human fetuin-A (alpha 2 -Heremans Schmid glycoprotein) has been identified as the most potent circulating inhibitor of vascular and soft-tissue calcification. We aimed to investigate the relationship between the serum fetuin-A level and the progression of aortic valve calcification (AVC) assessed by retrospectively ECG-gated Multislice Spiral Computed Tomography (MSCT) in patients with calcific aortic valve disease. A prospective study in 77 non-dialyzed patients (mean age 70 ± 8 years) with echocardiographically proven aortic valve disease was performed. In all patients serum fetuin-A levels were measured by nephelometry (BNII, Dade Behring Holding, Liederbach, Germany) using a polyclonal rabbit anti-human antibody against fetuin-A. For quantification of AVC all patients underwent 16-slice MSCT (Sensation 16, Siemens, Forchheim, Germany with scan parameters as follows: 420ms tube rotation time, 12× 0.75mm collimation, tube voltage 120KV). After a mean follow-up of 12.6 ± 1.4 months a second non-enhanced MSCT examination for quantification of AVC was performed. Images were reconstructed at 60% of the RR interval. AVC was assessed using Agatston AVC score. In multifactorial analysis of covariance including fetuin-A levels, baseline AVC score, the covariables sex, age, body mass index, C-reactive protein, glomerular filtration rate, serum lipids, diabetes, smoking status and hypertension, only fetuin-A levels revealed a significant effect on the progression of AVC (p&lt;0.001). Post-hoc analysis demonstrated that patients with baseline fetuin-A levels lower than the median of the cohort (0.72g/l) showed a significantly higher increase of AVC scores (34.6 ± 31.4%, n=39) than patients with fetuin-A levels larger than the median (10.0 ± 11.2%, p&lt;0.001) despite comparable baseline AVC scores. Vice versa, patients with progressive AVC &gt; 10% (n=48, 62%) had lower fetuin-A serum levels at baseline than non-progressors (n=29, 38%; 0.66±0.13g/L versus 0.82±0.11 g/L, p&lt;0.001). The present study suggests that low fetuin-A serum levels indicating systemic calcification inhibitor deficiency were associated with increased progression of AVC independently of the renal function.
Abstract 2998: Aortic Stiffness Is Correlated With Albuminuria and Glomerular Filtration Rate in Essential Hypertension: The Hippokration Hellenic Hypertension (3H) Study
Authors: Kyriakos Dimitriadis, Costas Tsioufis, Eirini Andrikou, Costas Thomopoulos, Ioannis Giatrakos, Vanessa Tzamou, Ioannis Kallikazaros
Journal: Circulation (2008)

Introduction: Arterial stiffness is an established marker of cardiovascular risk, whereas albuminuria and impaired renal function are associated with atherosclerosis progression. Hypothesis: Arterial stiffness may be associated with urinary albumin excretion, expressed as the albumin to creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) in a large cohort of hypertensives. Methods: A total of 893 consecutive essential hypertensives [482 men, mean age = 56 years, office blood pressure (BP) = 145/90 mmHg] that were included in the Hippokration Hellenic Hypertension (3H) Study, an ongoing Greek registry of hypertension-related target organ damage, were considered for analysis. In all participants, ACR values were determined as the mean of two non-consecutive morning spot urine and eGFR was calculated using the Modification of Diet in Renal Disease equation. Moreover, aortic stiffness was evaluated on the basis of carotid to femoral pulse wave velocity (PWV), by means of a computerized method (Complior SP). The distribution of PWV was split by the median (8 m/sec) and accordingly subjects were stratified into those with high and low values. Results: Hypertensive patients with high PWV (n = 414) compared to those with low PWV values (n = 479) were older (61 ± 10 vs 51 ± years, p &lt; 0.0001), had higher office systolic BP (150 ± 9 vs 142 ± 6mmHg, p &lt; 0.0001) and left ventricular mass index (107.7 ± 16 vs 99 ± 13 g/m 2 , p &lt; 0.0001). Moreover, hypertensives with high PWV compared to those with low PWV exhibited higher ACR (18.7 ± 9.5 vs 14.8 ± 7.5 mg/g, p &lt; 0.05), whereas had lower eGFR (76 ± 17 vs 82 ± 17 ml/min/1.73m 2 , p = 0.006). In the total population, PWV was related to age (r = 0.525, p &lt; 0.0001), office systolic BP (r = 0.242, p = 0.0001), ACR (r = 0.012, p &lt; 0.001) and negatively associated with eGFR (r = −0.221, p &lt; 0.0001). Analysis of covariance revealed that ACR and eGFR levels remained significantly different between groups after adjustment for confounders (p &lt; 0.05). Conclusions: In essential hypertension, heightened PWV values are associated with pronounced albuminuria and impaired kidney function. These findings further support that aortic stiffening is a hallmark of diffuse renal and vascular atherosclerotic disease.
Abstract 16675: Assessment of Initial U.S. Dabigatran Utilization and Short-Term Persistence
Authors: Eric J Stanek, Barnabie C Agatep, Vivian Herrera, Gosia S Hawk, Bruce J Schrader, Donald G Pittman, Felix W Frueh, Scott L Charland
Journal: Circulation (2011)

Background: The U.S. Food and Drug Administration approved dabigatran in October 2010 to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation, and it became available in November 2010. The purpose of this analysis is to assess early US dabigatran utilization patterns and short-term persistence. Methods: A retrospective analysis of a de-identified, integrated pharmacy-medical claims database is described. Patients with a prescription claim for dabigatran Nov 1-Dec 31, 2010, and with continuous eligibility of ≥12 months prior to and up to 4 months after initial dabigatran claim date were included. Demographic and clinical characteristics of patients, prescriber specialty, and 4-month persistence to dabigatran therapy were assessed. Medical diagnoses were determined by the presence of at least 2 ICD-9 or CPT codes in medical claims on 2 separate dates in the prior 12 months. Persistence at 120 days was calculated allowing a 45-day supply gap. Categorical and continuous variables were analyzed using chi-squared and t-tests, respectively (significance at p&lt;0.05). Results: A total of 1,143 patients received dabigatran mainly through retail pharmacy distribution (Table). Of these, 152 (13%) did not have a claims history for atrial fibrillation. Overall, cardiologists were the highest prescribers (62%), however primary care physicians prescribed in 23%. Warfarin therapy was prescribed in 71% of patients during the prior 6 months. Conclusion: The 13% of patients with an unclear dabigatran indication appear distinct from those with atrial fibrillation. Overall, 17% do not persist on dabigatran therapy for 120 days, which may adversely affect stroke outcomes. Ongoing review and action on dabigatran patient selection and therapy maintenance to optimize clinical outcomes, as well as real-world comparative effectiveness with optimized warfarin therapy, are needed.
Inhibition of paclitaxel-resistant MCF-7 RAg cell growth by Vernonia amygdalina extract
Authors: Carolyn B. Howard, Ernest B. Izevbigie, Michael M. Opata
Journal: Clinical Cancer Research (2006)

B49  The aqueous extract of Vernonia amygdalina (V.A.), a plant native to Nigeria, has been shown to inhibit growth of various cancer cell types without harmful side effects. Since drug resistance is a major obstacle for successful anticancer therapy, combined treatment regimens which 1) render the desired anti-cancerous effects, obtain synergistic effects, and 3) allow significant dose reductions of both drugs are desirable. The objectives of this study were to determine the effects of exposure to V.A., ethanol, or a combination of V.A. and ethanol, on doxorubicin or paclitaxel-resistant MCF-7 (MCF-7 RAg) breast cancer cell growth. MCF-7 RAg cells were cultured and exposed to 100ug/ml or 300ug/ml of V.A., with either 0.3% or 3% ethanol, or a combination and cell number was determined after exposure for at the 24hr, 48hr, 72hr or 7d time points. Results indicate that treatment with V.A. extract alone led to a 30 fold decrease in cell count at each of the timepoints, and 0.3% ethanol exposure alone was stimulatory at the 7d timepoint by 50 fold. Interestingly, the most noticeable effects were observed following combined exposure at the 72 hr and 7d timepoints. Following 72 hr exposure, combined treatment led to a 30 fold decrease in the cell count compared to the effects observed following either V.A. only treatment or 0.3% ethanolonly treatment. Additionally, following 7d exposure, combined led to a 50 fold decrease in cell count compared to the effect observed following V.A. only treatment, and a 70 fold decrease in cell count compared to the stimulatory effect observed following 0.3% ethanolonly treatment. In that combined exposure led to enhanced inhibition, these findings indicate that V.A.  treatment reverses the ethanol-induced stimulatory response in paclitaxel-sensitive human cancer cell growth, and shows that V.A. inhibits the growth of MCF-7 RAg cells in culture. Perhaps V.A. may be a useful agent against breast tumor cells which survive chemotherapy with taxol.Key Words: Vernonia amygdalina extract, anti-carcinogens, ethanol, drug resistance, and paclitaxel.Acknowledgments: This research was financially supported in part through the NIH-Project EXPORT Grant No. 5P20MD000534-02, the NIH-EARDA grant, Grant No. 1G11HDO46519-01, and through the NIH/RCMI-CEH at JSU, Grant No. 1G12RR13459. Special thanks to Dr. Ernest Izevbigie for the V. A. extract, and Dr. Mandip Sachdeva, Florida A & M University, for the MCF-7 RAg cells, both of which were provided as generous gifts.
History and Perspectives of A<sub>2A</sub>Adenosine Receptor Antagonists as Potential Therapeutic Agents
Authors: Delia Preti, Pier Giovanni Baraldi, Allan R. Moorman, Pier Andrea Borea, Katia Varani
Journal: Medicinal Research Reviews (2015)

Growing evidence emphasizes that the purine nucleoside adenosine plays an active role as a local regulator in different pathologies. Adenosine is a ubiquitous nucleoside involved in various physiological and pathological functions by stimulating A1, A2A, A2B, and A3 adenosine receptors (ARs). At the present time, the role of A2AARs is well known in physiological conditions and in a variety of pathologies, including inflammatory tissue damage and neurodegenerative disorders. In particular, the use of selective A2A antagonists has been reported to be potentially useful in the treatment of Parkinson's disease (PD). In this review, A2AAR signal transduction pathways, together with an analysis of the structure–activity relationships of A2A antagonists, and their corresponding pharmacological roles and therapeutic potential have been presented. The initial results from an emerging polypharmacological approach are also analyzed. This approach is based on the optimization of the affinity and/or functional activity of the examined compounds toward multiple targets, such as A1/A2AARs and monoamine oxidase-B (MAO-B), both closely implicated in the pathogenesis of PD.
Endoscopic Findings in End-Stage Renal Disease
Authors: R Sotoudehmanesh, A Ali Asgari, R Ansari, M Nouraie
Journal: Endoscopy (2003)

Patients with end-stage renal disease (ESRD) may demonstrate a number of gastrointestinal lesions and suffer subsequent complications. Our aim was to investigate the endoscopic findings in these patients and identify the predisposing factors.During a 1-year period (February 2000 to January 2001), we studied consecutive patients with end-stage renal disease who were undergoing routine endoscopy before renal transplantation. The rapid urease test was also performed to detect Helicobacter pylori infection. Demographic and clinical data were collected. Logistic regression analysis was used to determine the risk factors for important endoscopic lesions, including esophagitis, gastroduodenal erosions, and peptic ulcers.We studied 206 patients (124 male, 82 female, mean age 38.9). Of the patients 73.8% were asymptomatic but some patients experienced nausea (12.6%), heartburn (8.7%), and abdominal pain (7.3%). Endoscopy was normal in 74 patients (35.9%). Abnormal endoscopic findings were duodenal erosions (32.0%), antral erosions (22.8%), diffuse antral erythema (27.8%), duodenal ulcer (7.3%), esophagitis (5.8%), angiodysplasia (4.4%), nodular duodenum (2%), and inflammatory gastric polyps (1.5%). The rapid urease test was positive in 58.8% of patients. Important endoscopic lesions were more common in men and in H. pylori-infected patients. Age, duration of dialysis, cause of the ESRD, presence of any symptoms, and hemoglobin levels were not found to be related to these lesions. Most patients with peptic ulcers were asymptomatic.Duodenal erosions (32.0%), gastric erosions (22.8%), diffuse antral erythema (27.8%) and duodenal ulcer (7.3%) are common lesions in patients with end-stage renal disease. Male gender and H. pylori infection are associated with a higher risk of these lesions. As there is no association between patients' symptoms and gastroduodenal lesions, which may increase the risk of post-transplant complications, the development of diagnostic strategies for the detection of these lesions is recommended.
Phase II trial of sunitinib malate and lomustine in patients with temozolomide refractory recurrent low-grade and anaplastic gliomas.
Authors: Johnny Duerinck, Stephanie Du Four, An Van Binst, Hendrik Everaert, Alex Michotte, Jean D'haens, Bart Neyns
Journal: Journal of Clinical Oncology (2012)

2050 Background: Recurrent low-grade and anaplastic gliomas eventually transform to a higher grade that is characterized by neo-angiogenesis. Sunitinib inhibits multiple tyrosine kinase receptors (including VEGFR, PDGFR and c-Kit) but has no meaningful activity as a mono-therapy for recurrent glioblastoma when given at a daily dose of 37,5 mg (Neyns et al. J Neurooncol. 2011). We investigated sunitinib in combination with lomustine (CCNU) for the treatment of patients (pts) with temozolomide (TMZ) refractory recurrent low-grade or anaplastic glioma. Methods: Pts received a daily dose of 25 mg sunitinib for 28 consecutive days followed by a 14 days treatment-free interval. CCNU was administered as a single dose (80 mg/m²) on day 14 of a 6w cycle. T1 ± Gd and T2/FLAIR weighted MRI images were obtained q6 wks. 18FET-PET was performed at baseline and reassessed in responding pts. Results: 13 pts were enrolled (mean age 40 [range 33-49]; M/F 8/5; KPS 80-90/70-60: 8/5 pts). All pts had PD following surgery, RT and TMZ. In 7 pts, treatment was initiated at 2nd recurrence, in 4 pts at 3rd recurrence and in 2 pts at the 4th recurrence. Most frequent AEs where fatigue (gr 2: n= 3; gr 3: n= 1), thrombopenia (gr 2: n= 1 gr 3: n= 3 gr4: n= 1), neutropenia (gr 2: n= 2; gr3: n= 2; gr4: n= 2) and lymphopenia (gr 2: n=1; gr 3: n=2; gr 4: n=1). In 5/13 pts CCNU had to be discontinued because of AEs. Treatment with sunitinib was continued in these cases without reoccurrence of AEs. BOR according to RANO criteria: 1 CR, 1 PR (not-confirmed) and 2 SD (DCR: 4/13= 31%). In the patient with CR, FET-PET indicated a complete metabolic response. After a mean FU of 7 mths (range 2 -19), 5 pts are alive. The 6-month PFS is 23% (3/13 pts); median PFS is 1,8 mths (95%CI 1.0 - 2,7). A durable disease control was obtained in 3 pts (TTP respectively 14.8, 11.8+ and 19.2+ mths). Conclusions: in this heavily pretreated population with recurrent low-grade and anaplastic glioma the combination of sunitinib and CCNU is associated with acceptable toxicity and offers a durable progression-free survival in a subgroup of pts. Molecular predictive factors identifying the sensitive population would be needed to justify further clinical investigation of this combination.