tbuckley/cabot-search huggingface dataset:
Measuring Blood Pressure for Decision Making and Quality Reporting: Where and How Many Measures?
Authors: Benjamin J. Powers, Maren K. Olsen, Valerie A. Smith, Robert F. Woolson, Hayden B. Bosworth, Eugene Z. Oddone
Journal: Annals of Internal Medicine (2011)

Background: The optimal setting and number of blood pressure (BP) measurements that should be used for clinical decision making and quality reporting are uncertain. Objective: To compare strategies for home or clinic BP measurement and their effect on classifying patients as having BP that was in or out of control. Design: Secondary analysis of a randomized, controlled trial of strategies to improve hypertension management. (ClinicalTrials.gov registration number: NCT00237692) Setting: Primary care clinics affiliated with the Durham Veterans Affairs Medical Center. Patients: 444 veterans with hypertension followed for 18 months. Measurements: Blood pressure was measured repeatedly by using 3 methods: standardized research BP measurements at 6-month intervals; clinic BP measurements obtained during outpatient visits; and home BP measurements using a monitor that transmitted measurements electronically. Results: Patients provided 111 181 systolic BP (SBP) measurements (3218 research, 7121 clinic, and 100 842 home measurements) over 18 months. Systolic BP control rates at baseline (mean SBP <140 mm Hg for clinic or research measurement; <135 mm Hg for home measurement) varied substantially, with 28% classified as in control by clinic measurement, 47% by home measurement, and 68% by research measurement. Short-term variability was large and similar across all 3 methods of measurement, with a mean within-patient coefficient of variation of 10% (range, 1% to 24%). Patients could not be classified as having BP that was in or out of control with 80% certainty on the basis of a single clinic SBP measurement from 120 mm Hg to 157 mm Hg. The effect of within-patient variability could be greatly reduced by averaging several measurements, with most benefit accrued at 5 to 6 measurements. Limitation: The sample was mostly men with a long-standing history of hypertension and was selected on the basis of previous poor BP control. Conclusion: Physicians who want to have 80% or more certainty that they are correctly classifying patients' BP control should use the average of several measurements. Hypertension quality metrics based on a single clinic measurement potentially misclassify a large proportion of patients. Primary Funding Source: U.S. Department of Veterans Affairs Health Services Research and Development Service.
Mucosal 5-aminosalicylic acid concentration inversely correlates with severity of colonic inflammation in patients with ulcerative colitis
Authors: G Frieri
Journal: Gut (2000)

The treatment of ulcerative colitis (UC) with 5-aminosalicylic acid (5-ASA) does not have the same therapeutic effect in all patients. We tested the hypothesis that the effectiveness of the drug is related to its mucosal concentration.Twenty one UC patients receiving oral 5-ASA (2.4-3.2 g/day) were enrolled in the study. Four were also receiving topical treatment (2 g/day).Six endoscopic biopsies were taken from the rectum for measurement of 5-ASA concentrations (ng/mg) by HPLC; soluble interleukin 2 receptor (sIL-2R) concentrations (U/ml) were measured by ELISA and histology. Endoscopic and histological appearance was graded on a four point scale (0-3). The Wilcoxon's rank test and Pearson's correlation coefficient were used for statistical analysis.Mucosal concentrations of 5-ASA were significantly higher (p=0.03) in patients with endoscopic scores of 0-1 compared with those with scores of 2-3 (16.1 (range 10.2-45) v 5. 5 (3.5-17.4), respectively) and in patients with lower histological inflammation compared with those with more severe scores (17.4 (10. 5-45) v 8.9 (3.5-17.2), respectively) (p<0.01). In contrast, mucosal sIL2-R concentrations were significantly lower in patients with slight endoscopic and histological lesions than in those with more severe disease. A significative inverse correlation (r=-0.85) was found between 5-ASA and sIL-2R mucosal concentrations (p=0.00008).In patients with UC, in the same area of the intestinal tract, we found that the higher the 5-ASA mucosal concentrations, the lower the IL-2R levels and endoscopic and histological scores. We hypothesise that maintenance of high mucosal 5-ASA concentrations in all colonic segments could contribute to improve clinical outcome in UC patients.
The characterisation and determinants of quality of life in ANCA associated vasculitis
Authors: Neil Basu, Andrew McClean, Lorraine Harper, Esther Nicole Amft, Neeraj Dhaun, Raashid A Luqmani, Mark A Little, David RW Jayne, Oliver Flossmann, John McLaren, Vinod Kumar, Lars P Erwig, David M Reid, Gareth T Jones, Gary J Macfarlane
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To contextualise and identify the determinants of poor health related quality of life (QOL) among patients with antineutrophil cytoplasm antibody (ANCA) associated vasculitis (AAV). <h3>Methods</h3> A multicentre AAV case–control study was conducted using two matched groups of population and chronic disease controls. Measures of physical and mental QOL as well as putative bio-psychosocial determinants of QOL impairment were collected. Concurrently, putative clinical QOL determinants were recorded. Conditional logistic regression analyses characterised group differences while multivariable logistic regression identified within-case QOL associations which were further quantified using population attributable risks (PAR). <h3>Results</h3> Cases (n=410) experienced similar QOL to chronic disease controls (n=318) (physical QOL: OR 0.7, 95% CI 0.4 to 1.1; mental QOL: OR 1.1, 95% CI 0.8 to 1.6). However, they were substantially more likely to report poor QOL compared to general population controls (n=470) (physical QOL: OR 7.0, 95% CI 4.4 to 11.1; mental QOL: OR 2.5, 95% CI 1.7 to 3.6). A few clinical, but many more bio-psychosocial factors were independently associated with poor QOL. In population terms, fatigue was found to be of principal importance (physical QOL: PAR 24.6%; mental QOL: PAR 47.4%). <h3>Conclusions</h3> AAV patients experienced significant QOL impairment compared to the general population, but similar to those with other chronic diseases whose considerable needs are already recognised. Potentially modifiable clinical determinants have been identified; however bio-psychosocial interventions are likely to provide the greater QOL gains in this patient population.
Hypertensive End-Organ Damage and Premature Mortality Are p38 Mitogen-Activated Protein Kinase–Dependent in a Rat Model of Cardiac Hypertrophy and Dysfunction
Authors: Thomas M. Behr, Sandhya S. Nerurkar, Allen H. Nelson, Robert W. Coatney, Tina N. Woods, Anthony Sulpizio, Sudeep Chandra, David P. Brooks, Sanjay Kumar, John C. Lee, Eliot H. Ohlstein, Christiane E. Angermann, Jerry L. Adams, Joseph Sisko, Jonathan D. Sackner-Bernstein, Robert N. Willette
Journal: Circulation (2001)

Numerous pathological mediators of cardiac hypertrophy (eg, neurohormones, cytokines, and stretch) have been shown to activate p38 MAPK. The purpose of the present study was to examine p38 MAPK activation and the effects of its long-term inhibition in a model of hypertensive cardiac hypertrophy/dysfunction and end-organ damage.In spontaneously hypertensive stroke-prone (SP) rats receiving a high-salt/high-fat diet (SFD), myocardial p38 MAPK was activated persistently during the development of cardiac hypertrophy and inactivated during decompensation. Long-term oral treatment of SFD-SP rats with a selective p38 MAPK inhibitor (SB239063) significantly enhanced survival over an 18-week period compared with the untreated group (100% versus 50%). Periodic echocardiographic analysis revealed a significant reduction in LV hypertrophy and dysfunction in the SB239063-treatment groups. Little or no difference in blood pressure was noted in the treatment or vehicle groups. Basal and stimulated (lipopolysaccharide) plasma tumor necrosis factor-alpha concentrations were reduced in the SB239063-treatment groups. In vitro vasoreactivity studies demonstrated a significant preservation of endothelium-dependent relaxation in animals treated with the p38 MAPK inhibitor without effects on contraction or NO-mediated vasorelaxation. Proteinuria and the incidence of stroke (53% versus 7%) were also reduced significantly in the SB239063-treated groups.These results demonstrate a crucial role for p38 MAPK in hypertensive cardiac hypertrophy and end-organ damage. Interrupting its function with a specific p38 MAPK inhibitor halts clinical deterioration.
Validation of the COPD severity score for use in primary care: the NEREA study
Authors: M. Miravitlles, C. Llor, R. de Castellar, I. Izquierdo, E. Baro, E. Donado
Journal: European Respiratory Journal (2009)

Spirometry is underused for the assessment of severity of chronic obstructive pulmonary disease (COPD) in primary care (PC). Therefore, simple assessment tools are required in this setting. The aim of the present study was to validate the COPD severity score (COPDSS) for use in PC. A multicentric study was carried out in stable COPD patients in PC. The concurrent validity of the COPDSS was evaluated by examining the association between COPDSS, COPD clinical indicators and the London Chest Activity of Daily Living (LCADL) scale, European quality of life (EuroQOL) questionnaires and Charlson comorbidity index. A total of 837 patients with COPD were analysed (males 84.3%; mean±sd age 68±11 yrs; forced expiratory volume in one second 54.6±17.7% of the predicted value). A strong correlation was found between COPDSS and dyspnoea level and a moderate correlation between COPDSS and exacerbation number. The COPDSS discriminated between patients with varying degrees of dyspnoea (area under receiver operating characteristic (ROC) curve 0.837), and according to number of exacerbations in the last year (area under ROC curve 0.773). Higher COPDSS scores were significantly associated with lower EuroQOL scores, lower EuroQOL visual analogue scale scores and higher LCADL scores. The present results indicate that the chronic obstructive pulmonary disease severity score is a useful and reliable tool for assessing the severity of chronic obstructive pulmonary disease in primary care.
Eruptive squamous cell carcinomas with keratoacanthoma-like features in a patient treated with ruxolitinib
Authors: A. Fabiano, P. Calzavara-Pinton, P. Monari, E. Moggio, G. Pellacani, A.M. Manganoni, G. Gualdi
Journal: British Journal of Dermatology (2015)

Funding sources: none. Conflicts of interest: none declared. Dear Editor, Ruxolitinib is a Janus kinase (JAK)1 and JAK2 inhibitor, approved by the US Food and Drug Administration (FDA) in November 2011. It is highly effective in the clinical management of myelofibrosis and associated complications (splenomegaly consequent to extramedullary haematopoiesis, cytopenias). We describe a case of ruxolitinib‐induced eruptive squamous cell carcinomas with keratoacanthoma‐like features in a patient with myelofibrosis. A 74‐year‐old woman was diagnosed with myelofibrosis in 2013 and was put on ruxolitinib, without association with other immunosuppressive drugs. Her family and personal history were negative for skin tumours and autoimmune diseases. The patient appeared as Fitzpatrick skin type III with moderate bilateral photodamage of the forearms, face, neck and lower legs. After 2 months of ruxolitinib treatment, multiple, simultaneous crateriform nodules appeared on her forehead (Fig. 1), lower jaw and clavicle (Fig. 2), and eruptive squamous cell carcinomas with keratoacanthoma‐like features were suspected. Surgical excision under local anaesthesia was performed, and histopathological examination confirmed the clinical diagnosis and negative involvement of the margin. Because of the suspected association between recently introduced myelofibrosis treatment and skin lesions, administration of ruxolitinib was discontinued. After 10 months of clinical follow‐up, additional skin lesions did not appear.
Effect of strength and proprioception training on eversion to inversion strength ratios in subjects with unilateral functional ankle instability
Authors: T W Kaminski, B D Buckley, M E Powers, T J Hubbard, C Ortiz
Journal: British Journal of Sports Medicine (2003)

To examine the effect of six weeks of strength and proprioception training on eversion to inversion isokinetic strength ratios (E/I ratios) in subjects with unilateral functional ankle instability.Thirty eight subjects were randomly assigned to one of four treatment groups: strength training (S); proprioception training (P); strength + proprioception training (B); control (C). Isokinetic strength was tested before and after training using a Kin Com 125 automatic positioning isokinetic dynamometer. Subtalar joint eversion and inversion motions were tested both concentrically and eccentrically through a range of motion involving 40 degrees. All peak torque and average torque values were normalised for body mass. E/I ratios were calculated from average torque and peak torque measures by taking the concentric eversion value and combining it with the eccentric inversion value. Data were analysed using a mixed model analysis of variance with repeated measures on the test factor. Average torque and peak torque E/I ratios at 30 and 120 degrees/s were analysed separately.There were no significant differences in average torque and peak torque E/I ratios of the functionally unstable ankle for any of the groups after training compared with before.Six weeks of strength and proprioception training (either alone or combined) had no effect on isokinetic measures of strength in subjects with self reported unilateral functional instability. Further studies examining this agonist (concentric) to antagonist (eccentric) muscle group strength ratio are needed.
Dietary Fiber-Induced Improvement in Glucose Metabolism Is Associated with Increased Abundance of Prevotella
Authors: Petia Kovatcheva-Datchary, Anne Nilsson, Rozita Akrami, Ying Shiuan Lee, Filipe De Vadder, Tulika Arora, Anna Hallen, Eric Martens, Inger Björck, Fredrik Bäckhed
Journal: Cell Metabolism (2015)
Caspase-3 and Tissue Factor Expression in Lipid-Rich Plaque Macrophages
Authors: Randolph Hutter, Carolina Valdiviezo, Bernhard V. Sauter, Mikko Savontaus, Igor Chereshnev, Francine E. Carrick, Gerhard Bauriedel, Berndt Lüderitz, John T. Fallon, Valentin Fuster, Juan J. Badimon
Journal: Circulation (2004)

Macrophages associated with arterial wall lipid deposition contribute to inflammatory processes. Tissue factor (TF) has been implicated in the thrombogenicity of atherosclerotic plaques. Intimal cells undergoing apoptosis have been postulated as a source for TF. However, there is only limited knowledge of cell type, plaque component, and conditions associated with TF expression and apoptosis. We examined the hypothesis that macrophages exposed to conditions of lipid-rich plaque undergo apoptosis and express TF.In human carotid (n=15) and coronary (n=6) atherosclerotic plaques, TF and caspase-3 mRNA and protein expression (evaluated by in situ hybridization and immunohistochemistry) were increased significantly in lipid-rich compared with fibrous plaque components (P<0.01) and correlated with high macrophage content (P<0.05). Double-labeling studies demonstrated colocalization of TF and active caspase-3. In hyperlipidemic mice, expression of TF and active caspase-3 was observed simultaneously and colocalized in neointimal macrophages after arterial injury. In neointima of normolipidemic animals, TF and active caspase-3 were absent after arterial injury. In monocytes cultured in the presence of oxidized LDL, strong induction and colocalization of TF and active caspase-3 were found compared with baseline (P<0.05). Both antigens were significantly decreased after cotreatment with a caspase inhibitor (P<0.05) and were absent in untreated control cells.The expression of TF as the primary cell-associated activator of the coagulation pathway proves to be closely related to macrophages undergoing apoptosis in conditions of lipid-rich plaque, pointing to a key role of lipid content and inflammatory cell viability in determining plaque thrombogenicity.
Synergistic Cytotoxicity and Pharmacogenetics of Gemcitabine and Pemetrexed Combination in Pancreatic Cancer Cell Lines
Authors: Elisa Giovannetti, Valentina Mey, Romano Danesi, Irene Mosca, Mario Del Tacca
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Gemcitabine is an inhibitor of ribonucleotide reductase (RR) and DNA synthesis and is an effective agent in the treatment of pancreas cancer. The present study investigates whether the multitargeted antifolate pemetrexed would be synergistic with gemcitabine against MIA PaCa-2, PANC-1, and Capan-1 pancreatic cancer cell lines. Experimental Design: Cells were treated with gemcitabine and pemetrexed, and the type of drug interaction was assessed using the combination index. Cytotoxicity of gemcitabine was examined with inhibitors of (a) deoxycytidine kinase (dCK), which activates gemcitabine by phosphorylation, and (b) 5′-nucleotidase (drug dephosphorylation) and cytidine deaminase (drug deamination), the main inactivating enzymes. The effects of gemcitabine and pemetrexed on cell cycle were analyzed by flow cytometry, and apoptosis was examined by fluorescence microscopy. Finally, quantitative, real-time PCR was used to study the pharmacogenetics of the drug combination. Results: Synergistic cytotoxicity and enhancement of apoptosis was demonstrated, mostly with the sequence pemetrexed→gemcitabine. Pemetrexed increased cells in S phase, the most sensitive to gemcitabine, and a positive correlation was found between the expression ratio of dCK:RR and gemcitabine sensitivity. Indeed, pemetrexed significantly enhanced dCK gene expression (+227.9, +86.0, and +135.5% in MIA PaCa-2, PANC-1, and Capan-1 cells, respectively), and the crucial role of this enzyme was confirmed by impairment of gemcitabine cytotoxicity after dCK saturation with 2′-deoxycytidine. Conclusions: These data demonstrate that the gemcitabine and pemetrexed combination displays schedule-dependent synergistic cytotoxic activity, favorably modulates cell cycle, induces apoptosis, and enhances dCK expression in pancreatic cancer cells.
Generation of Induced Pluripotent Stem Cells from Urine
Authors: Ting Zhou, Christina Benda, Sarah Duzinger, Yinghua Huang, Xingyan Li, Yanhua Li, Xiangpeng Guo, Guokun Cao, Shen Chen, Lili Hao, Yau-Chi Chan, Kwong-Man Ng, Jenny Cy Ho, Matthias Wieser, Jiayan Wu, Heinz Redl, Hung-Fat Tse, Johannes Grillari, Regina Grillari-Voglauer, Duanqing Pei, Miguel A. Esteban
Journal: Journal of the American Society of Nephrology (2011)

Forced expression of selected transcription factors can transform somatic cells into embryonic stem cell (ESC)-like cells, termed induced pluripotent stem cells (iPSCs). There is no consensus regarding the preferred tissue from which to harvest donor cells for reprogramming into iPSCs, and some donor cell types may be more prone than others to accumulation of epigenetic imprints and somatic cell mutations. Here, we present a simple, reproducible, noninvasive method for generating human iPSCs from renal tubular cells present in urine. This procedure eliminates many problems associated with other protocols, and the resulting iPSCs display an excellent ability to differentiate. These data suggest that urine may be a preferred source for generating iPSCs.
Prevention of chemotherapy-induced ovarian damage: possible roles for hormonal and non-hormonal attenuating agents
Authors: Hadassa Roness, Lital Kalich-Philosoph, Dror Meirow
Journal: Human Reproduction Update (2014)

Current options for female fertility preservation in the face of cytotoxic treatments include embryo, oocyte and ovarian tissue cryopreservation. However these methods are limited by the patient age, status or available timeframe before treatment and they necessitate invasive procedures. Agents which can prevent or attenuate the ovotoxic effects of treatment would provide significant advantages over the existing fertility preservation techniques, and would allow patients to retain their natural fertility without the necessity for costly, invasive and risky procedures. Recent studies have contributed to our understanding of the mechanisms involved in cytotoxicity-induced ovarian follicle loss and highlight a number of agents that may be able to prevent or reduce this loss. This paper reviews the relevant literature (research articles published in English up to December 2013) on the mechanisms of cytotoxic-induced ovarian damage and the implications for fertility preservation. We present a comprehensive discussion of the potential agents that have been shown to preserve the ovarian follicle reserve in the face of cytotoxic treatments, including an analysis of their respective advantages and risks, and mechanisms of action. Multiple molecular pathways are involved in the cellular response to cytotoxic treatments, and specific cellular reactions depend on variables including the drug class and dose, cell type, and cell stage. A number of agents acting on different elements of these pathways have demonstrated potential for preventing or reducing ovarian follicle loss, although in most cases, the studies are still very preliminary. Advances in our understanding of the mechanisms and pathways involved in both cytotoxic ovarian damage and follicle growth and development have opened up new directions for fertility preservation. In order to bring these agents from the lab to the clinic, it will be vital to accurately evaluate the efficacy of each agent and additionally to demonstrate that co-treatment with these agents will not interfere with the anti-cancer activity of the chemotherapy drugs, or produce genetically comprised embryos.
Key Role of Kv1 Channels in Vasoregulation
Authors: Tim T. Chen, Kevin D. Luykenaar, Emma J. Walsh, Michael P. Walsh, William C. Cole
Journal: Circulation Research (2006)

Small arteries play an essential role in the regulation of blood pressure and organ-specific blood flow by contracting in response to increased intraluminal pressure, ie, the myogenic response. The molecular basis of the myogenic response remains to be defined. To achieve incremental changes in arterial diameter, as well as blood pressure or organ-specific blood flow, the depolarizing influence of intravascular pressure on vascular smooth muscle membrane potential that elicits myogenic contraction must be precisely controlled by an opposing hyperpolarizing influence. Here we use a dominant-negative molecular strategy and pressure myography to determine the role of voltage-dependent Kv1 potassium channels in vasoregulation, specifically, whether they act as a negative-feedback control mechanism of the myogenic response. Functional Kv1 channel expression was altered by transfection of endothelium-denuded rat middle cerebral arteries with cDNAs encoding c-myc epitope-tagged, dominant-negative mutant or wild-type rabbit Kv1.5 subunits. Expression of mutant Kv1.5 dramatically enhanced, whereas wild-type subunit expression markedly suppressed, the myogenic response over a wide range of intraluminal pressures. These effects on arterial diameter were associated with enhanced and reduced myogenic depolarization by mutant and wild-type Kv1.5 subunit expression, respectively. Expression of myc-tagged mutant and wild-type Kv1.5 subunit message and protein in transfected but not control arteries was confirmed, and isolated myocytes of transfected but not control arteries exhibited anti-c-myc immunofluorescence. No changes in message encoding other known, non-Kv1 elements of the myogenic response were apparent. These findings provide the first molecular evidence that Kv1-containing delayed rectifier K+ (K(DR)) channels are of fundamental importance for control of arterial diameter and, thereby, peripheral vascular resistance, blood pressure, and organ-specific blood flow.