tbuckley/cabot-search huggingface dataset:
Expression of Hypoxia-related Tissue Factors Correlates with Diminished Survival of Adjuvantly Treated Patients with Chromosome 1p Aberrant Oligodendroglial Neoplasms and Therapeutic Implications
Authors: Peter Birner, Matthias Preusser, Ellen Gelpi, Johannes Berger, Brigitte Gatterbauer, Inge M. Ambros, Peter F. Ambros, Till Acker, Karl H. Plate, Adrian L. Harris, Johannes A. Hainfellner
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Oligodendroglial neoplasms with chromosome 1p deletion are chemosensitive, and stratified adjuvant therapies have been proposed on the basis of 1p status. In this study, we evaluated expression of hypoxia-related factors and its influence on survival in oligodendroglial brain tumors with chromosome 1p aberrations. Experimental Design: Forty-four primary and 16 recurrent oligodendroglial neoplasms with 1p aberrations (deletion or imbalance) were investigated immunohistochemically for expression of hypoxia-inducible factor 1α and carbonic anhydrase-9. We used in situ hybridization to investigate expression of vascular endothelial growth factor-mRNA. We defined as “low hypoxia score” expression of no or only one marker and as “high hypoxia score” expression of two or three markers. The predominant vascular patterns of tumors were defined as classic or bizarre vascular formations, based on anti-CD34–immunostaining. Results: High hypoxia score was evident in 16 of 44 (36.4%) primary tumor specimens and in 14 of 16 (87.5%) recurrent tumors (P = 0.001). High hypoxia score was associated with the presence of bizarre vascular proliferations and WHO grade III. In the subgroup of patients who received adjuvant therapy, univariate analysis showed significantly shorter survival of patients with high hypoxia score (n = 27; P = 0.0145). For all of the primary tumors, hypoxia score was an independent prognostic factor (P = 0.045). Conclusions: A fraction of oligodendroglial neoplasms with 1p aberrations shows evidence of tissue hypoxia, which significantly influences survival of patients receiving adjuvant therapy. Evaluation of tissue hypoxia could become useful for recruitment of patients for individualized therapy strategies, e.g., selection of patients with hypoxic tumors for hyperbaric oxygenation preceding radiotherapy.
Combined versus sequential diuretic treatment of ascites in non-azotaemic patients with cirrhosis: results of an open randomised clinical trial
Authors: P Angeli, S Fasolato, E Mazza, L Okolicsanyi, G Maresio, E Velo, A Galioto, F Salinas, M D'Aquino, A Sticca, A Gatta
Journal: Gut (2009)

<h3>Objective:</h3> The aim of the study was to compare sequential versus combined diuretic therapy in patients with cirrhosis, moderate ascites and without renal failure. <h3>Design:</h3> One hundred patients were randomly assigned to the two diuretic treatments. The sequential treatment provided potassium canrenoate at the initial dose of 200 mg/day, then increased to 400 mg/day. Non-responders were treated with 400 mg/day of potassium canrenoate and furosemide at an initial dose of 50 mg/day, then increased to 150 mg/day. The combined treatment provided the initial dose of 200 mg/day of potassium canrenoate and 50 mg/day of furosemide, then increased to 400 mg/day and 150 mg/day, respectively. <h3>Results:</h3> Most patients who received sequential treatment responded to potassium canrenoate alone (19% to 200 mg/day and 52.63% to 400 mg/day, respectively). Most patients who received the combined treatment responded to the first two steps (40% to the first step and 50% to the second, ie, 400 mg/day of potassium canrenoate plus 100 mg/day of furosemide). Adverse effects (38% vs 20%, p&lt;0.05), in particular, hyperkalaemia (18% vs 4%, p&lt;0.05), were more frequent in patients who received sequential therapy. As a consequence, the per cent of patients who resolved ascites without changing the effective diuretic step was higher in those who received the combined treatment (56% vs 76%, p&lt;0.05). <h3>Conclusions:</h3> The combined diuretic treatment is preferable to the sequential one in the treatment of moderate ascites in patients with cirrhosis and without renal failure. <h3></h3> NCT00741663. This work is an open randomised clinical trial.
Clinical Imaging of the High-Risk or Vulnerable Atherosclerotic Plaque
Authors: Z. A. Fayad, V. Fuster
Journal: Circulation Research (2001)

The study of atherosclerotic disease during its natural history and after therapeutic intervention will enhance our understanding of disease progression and regression and aid in selecting appropriate treatments. Several invasive and noninvasive imaging techniques are available to assess atherosclerotic vessels. Most of the standard techniques identify luminal diameter, stenosis, wall thickness, and plaque volume; however, none can characterize plaque composition and therefore identify the high-risk plaques. We will present the different imaging modalities that have been used for the direct assessment of the carotid, aortic, and coronary atherosclerotic plaques. We will review in detail the use of high-resolution, multicontrast magnetic resonance for the noninvasive imaging of vulnerable plaques and the characterization of plaques in terms of their various components (ie, lipid, fibrous, calcium, or thrombus).
Safe To Walk? Neighborhood Safety and Physical Activity Among Public Housing Residents
Authors: Gary G Bennett, Lorna H McNeill, Kathleen Y Wolin, Dustin T Duncan, Elaine Puleo, Karen M Emmons
Journal: PLoS Medicine (2007)

Background Despite its health benefits, physical inactivity is pervasive, particularly among those living in lower-income urban communities. In such settings, neighborhood safety may impact willingness to be regularly physically active. We examined the association of perceived neighborhood safety with pedometer-determined physical activity and physical activity self-efficacy. Methods and Findings Participants were 1,180 predominantly racial/ethnic minority adults recruited from 12 urban low-income housing complexes in metropolitan Boston. Participants completed a 5-d pedometer data-collection protocol and self-reported their perceptions of neighborhood safety and self-efficacy (i.e., confidence in the ability to be physically active). Gender-stratified bivariate and multivariable random effects models were estimated to account for within-site clustering. Most participants reported feeling safe during the day, while just over one-third (36%) felt safe at night. We found no association between daytime safety reports and physical activity among both men and women. There was also no association between night-time safety reports and physical activity among men (p = 0.23) but women who reported feeling unsafe (versus safe) at night showed significantly fewer steps per day (4,302 versus 5,178, p = 0.01). Perceiving one's neighborhood as unsafe during the day was associated with significantly lower odds of having high physical activity self-efficacy among both men (OR 0.40, p = 0.01) and women (OR 0.68, p = 0.02). Conclusions Residing in a neighborhood that is perceived to be unsafe at night is a barrier to regular physical activity among individuals, especially women, living in urban low-income housing. Feeling unsafe may also diminish confidence in the ability to be more physically active. Both of these factors may limit the effectiveness of physical activity promotion strategies delivered in similar settings.
Outcome of urgent and elective percutaneous coronary interventions after pharmacologic reperfusion with tenecteplase combined with unfractionated heparin, enoxaparin, or abciximab
Authors: Christophe L Dubois, Ann Belmans, Christopher B Granger, Paul W Armstrong, Lars Wallentin, Paolo M Fioretti, José L López-Sendón, Freek W Verheugt, Jürgen Meyer, Frans Van de Werf
Journal: Journal of the American College of Cardiology (2003)
Still awaiting a useful tool for predicting severe CAP
Authors: P G P Charles, P D R Johnson, M L Grayson, K L Buising
Journal: Thorax (2006)

<h3>Abstract</h3> We employed the widely-tested biophysiological modeling software, Niche Mapper™ to investigate the metabolic function of Late Triassic dinosaurs <i>Plateosaurus</i> and <i>Coelophysis</i> during global greenhouse conditions. We tested them under a variety of assumptions about resting metabolic rate, evaluated within six microclimate models that bound paleoenvironmental conditions at 12° N paleolatitude, as determined by sedimentological and isotopic proxies for climate within the Chinle Formation of the southwestern United States. Sensitivity testing of metabolic variables and simulated “metabolic chamber” analyses support elevated “ratite-like” metabolic rates and intermediate “monotreme-like” core temperature ranges in these species of early saurischian dinosaur. Our results suggest small theropods may have needed partial to full epidermal insulation in temperate environments, while fully grown prosauropods would have likely been heat stressed in open, hot environments and should have been restricted to cooler microclimates such as dense forests (under any vegitative cover) or those seen at higher latitudes and elevations. This is in agreement with the Late Triassic fossil record and may have contributed to the latitudinal gap in the Triassic prosauropod record.
Cisplatin Induces Apoptosis in LLC-PK1 Cells via Activation of Mitochondrial Pathways
Authors: Moon Soo Park, Maryely De Leon, Prasad Devarajan
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Cisplatin, a commonly used chemotherapeutic agent, has a major limitation because of its nephrotoxicity. Recent studies have shown that cisplatin causes apoptotic cell death in renal tubule cells, but the underlying molecular mechanisms remain to be elucidated. In this study, cisplatin was found to induce apoptosis in a dose- and duration-dependent manner in cultured proximal tubule (LLC-PK1) cells, as evidenced by DNA laddering and TdT-mediated dUTP nick end-labeling assay. Pretreatment with the specific caspase 9 inhibitor LEHD-CHO completely prevented the apoptosis, whereas the caspase 8 inhibitor IETD-fmk had no effect. Furthermore, the activity of caspase 9 was upregulated about sixfold by cisplatin in a dose-dependent manner. These results implicated the caspase 9–dependent mitochondrial apoptotic pathways. Indeed, cisplatin triggered a duration-dependent translocation of cytochrome c from the mitochondria to the cytosol, by immunofluorescence and Western blots. Cisplatin treatment also resulted in the duration-dependent activation and mitochondrial translocation of the pro-apoptotic molecule Bax, by immunofluorescence. Finally, cisplatin induced a duration-dependent onset of the mitochondrial permeability transition. Our results indicate that cisplatin induces apoptosis in LLC-PK1 cells via activation of mitochondrial signaling pathways. The sequence of events may be summarized as follows: activation of Bax induces mitochondrial permeability transition, leading to release of cytochrome c, activation of caspase 9, and entry into the execution phase of apoptosis. Inhibition of this specific pathway may provide a strategy to minimize cisplatin-induced nephrotoxicity.
Short-time infusion of oxaliplatin in combination with capecitabine (XELOX30) as second-line therapy in patients with advanced colorectal cancer after failure to irinotecan and 5-fluorouracil
Authors: P. Pfeiffer, H. Sørbye, H. Ehrsson, T. Fokstuen, J.P. Mortensen, L. Baltesgard, K.M. Tveit, D. Øgreid, H. Starkhammar, I. Wallin, C. Qvortrup, B. Glimelius
Journal: Annals of Oncology (2005)
Diabetes Numeracy
Authors: Chandra Y. Osborn, Kerri Cavanaugh, Kenneth A. Wallston, Richard O. White, Russell L. Rothman
Journal: Diabetes Care (2009)

OBJECTIVE Understanding the reasons and eliminating the pervasive health disparities in diabetes is a major research, clinical, and health policy goal. We examined whether health literacy, general numeracy, and diabetes-related numeracy explain the association between African American race and poor glycemic control (A1C) in patients with diabetes. RESEARCH DESIGN AND METHODS Adults with type 2 diabetes (n = 383) were enrolled in a cross-sectional study at primary care and diabetes clinics at three medical centers. Data collected included the following: self-reported race, health literacy, general numeracy, diabetes-related numeracy, A1C, and sociodemographic factors. A series of structural equation models were estimated to explore the interrelations between variables and test for mediation. RESULTS In model 1, younger age (r = −0.21, P &amp;lt; 0.001), insulin use (r = 0.27, P &amp;lt; 0.001), greater years with diabetes (r = 0.16, P &amp;lt; 0.01), and African American race (r = 0.12, P &amp;lt; 0.01) were all associated with poorer glycemic control. In model 2, diabetes-related numeracy emerged as a strong predictor of A1C (r = −0.46, P &amp;lt; 0.001), reducing the association between African American and poor glycemic control to nonsignificance (r = 0.10, NS). In model 3, African American race and older age were associated with lower diabetes-related numeracy; younger age, insulin use, more years with diabetes, and lower diabetes-related numeracy were associated with poor glycemic control. CONCLUSIONS Diabetes-related numeracy reduced the explanatory power of African American race, such that low diabetes-related numeracy, not African American race, was significantly related to poor glycemic control. Interventions that address numeracy could help to reduce racial disparities in diabetes.
Clustering of Gene Hypermethylation Associated With Clinical Risk Groups in Neuroblastoma
Authors: M. Alaminos, V. Davalos, N.-K. V. Cheung, W. L. Gerald, M. Esteller
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: Neuroblastoma is the most common extracranial solid malignancy in infancy and childhood, but the biological factors involved in its development and progression are still unclear. Transcriptional silencing of tumor suppressor genes mediated by hypermethylation of promoter CpG islands is a hallmark of human tumors. We addressed the clinical relevance of promoter hypermethylation in neuroblastoma. Methods: We examined the methylation status of 45 candidate genes representative of many cellular pathways in 10 neuroblastoma cell lines and of 10 of these genes in 145 tumor samples (118 of them were primary neuroblastomas). We used Fisher's exact test to examine the association of CpG island methylation and clinical subgroups and Kaplan–Meier analysis to determine the association between methylation and survival in primary tumors. Cluster analysis was used to group cell lines and tumors by gene methylation status. Bonferroni-corrected statistical tests were two-sided. Results: Clustering of neuroblastoma cell lines on the basis of hypermethylation distinguished lines with MYCN amplification (a negative prognostic factor) from those without it ( P = .012). Promoter hypermethylation of the developmental gene HOXA9 was associated with mortality in noninfant patients ( P = .04) and in tumors lacking MYCN amplification ( P = .023). Hypermethylation of the proapoptotic gene TMS1 and the cell cycle gene CCND2 was associated with stage 4–progressing tumors ( P <.001), but the genes were never methylated in stage 4S tumors, which undergo spontaneous regression. Hypermethylation of the differentiation gene RARβ2 was associated with patient survival ( P = .032). Unsupervised hierarchical cluster analysis of all tumors based on methylation of the 10 genes separated several clinically relevant groups of tumors. Conclusions: Profiling the status of CpG island hypermethylation in human primary neuroblastomas may have clinicopathologic value.
Mechanism of Reduced Glomerular Filtration Rate in Chronic Malnutrition
Authors: Iekuni Ichikawa, Mabel L. Purkerson, Saulo Klahr, Julia L. Troy, Manuel Martinez-Maldonado, Barry M. Brenner
Journal: Journal of Clinical Investigation (1980)

To determine the physiological basis for the low glomerular filtration rate in chronic malnutrition, micropuncture studies were performed in Munich-Wistar rats chronically pair-fed isocaloric diets of either low (group 1, nine rats) or high protein content (group 2, nine rats). Despite the absence of hypoalbuminemia, average values for single nephron and total kidney glomerular filtration rate were nearly 35% lower in group 1 than in group 2. Mean values for glomerular capillary and Bowman's space hydraulic pressures were essentially identical in the two groups, thereby excluding glomerular transcapillary hydraulic pressure difference as the cause for the low filtration rates in group 1 animals. On the other hand, average glomerular capillary plasma flow rate and glomerular capillary ultrafiltration coefficient were significantly lower (by ∼25 and ∼50%, respectively) in group 1 than in group 2. The fall in glomerular capillary plasma flow rate was the consequence of increased afferent and efferent arteriolar resistances. Plasma and erythrocyte volumes were found to be equal in five additional pairs of group 1 and group 2 rats. Thus, the substantial alterations in the ultrafiltration coefficient, glomerular capillary plasma flow rate, and renal arteriolar resistances responsible for the low filtration rate in group 1 animals were not merely a consequence of decreased circulating blood or plasma volumes. Mean values for glomerular cross sectional area were significantly lower in group 1 than in group 2 despite similar values for kidney weight in the two groups. This reduction in glomerular cross sectional area in group 1 rats is presumed to reflect a decrease in effective filtration surface area and therefore likely accounts, at least in part, for the decline in ultrafiltration coefficient observed in this group.
Effect of cyclosporin A on interleukin-6 and soluble interleukin-2 receptor in patients with rheumatoid arthritis.
Authors: A Crilly, S Kolta, M Dougados, R D Sturrock, B Amor, H A Capell, R Madhok
Journal: Annals of the Rheumatic Diseases (1995)

OBJECTIVE--To investigate the effect of cyclosporin A (CyA) therapy on circulating concentrations of interleukin-6 (IL-6) and soluble interleukin-2 receptor (sIL-2R) in patients with rheumatoid arthritis (RA). METHODS--Twenty four RA patients with active disease were studied. Plasma was collected before and after 16 weeks of CyA treatment. IL-6 was measured by B9 bioassay and sIL-2R by enzyme linked immunosorbent assay (ELISA). RESULTS--The initial median IL-6 concentration of 165 IU/ml decreased significantly to 71 IU/ml after 16 weeks (p &lt; 0.05). Similarly, the initial median plasma sIL-2R value of 665 U/ml decreased significantly to 570 U/ml (p &lt; 0.05). This decrease was accompanied by an improvement in clinical parameters of disease activity. Some association between sIL-2R, IL-6, haemoglobin, and platelets was also observed. CONCLUSIONS--This study has demonstrated that, in vivo, CyA therapy in RA can significantly reduce circulating concentrations of IL-6 and sIL-2R. Modulation of both T and non-T cell derived cytokines may be one mechanism by which CyA improves rheumatoid disease. Whether this is a direct effect of CyA on the cells within the rheumatoid joint producing these cytokines or an indirect effect mediated by other cytokines which can influence IL-6 and Il-2R values remains to be determined.
Complications with Heparin-Lock Needles
Authors: ROBERT L. FERGUSON
Journal: Annals of Internal Medicine (1976)

Because the frequency of complications related to heparin-lock needle usage is unknown, 221 heparin-lock needle insertions in 78 patients were observed for the development of complications. Upon removal of 119 heparin-lock needles from 42 patients, specimens were obtained for culture. Phlebitis was associated with 27 (12%) heparin-lock needle insertions. Only a positive flush culture of the heparin-lock needle system correlated with the development of phlebitis. Phlebitis developed during the first 4 days after heparin-lock needle insertion in two instances and later than 4 days after insertion in 25 instances. All positive flush cultures were obtained from heparin-lock needles in use for longer than 4 days. No patient developed clinically apparent systemic infection. These data suggest that heparin-lock needles should not be used for more than 4 days because, after 4 days of use, there is a significant risk of developing phlebitis, a lesser risk of developing contamination of the infusate in the heparin-lock needle system, and a potential risk of developing nosocomial infection.
αB-Crystallin Suppresses Pressure Overload Cardiac Hypertrophy
Authors: Asangi R.K. Kumarapeli, Huabo Su, Wei Huang, Mingxin Tang, Hanqiao Zheng, Kathleen M. Horak, Manxiang Li, Xuejun Wang
Journal: Circulation Research (2008)

AlphaB-crystallin (CryAB) is the most abundant small heat shock protein (HSP) constitutively expressed in cardiomyocytes. Gain- and loss-of-function studies demonstrated that CryAB can protect against myocardial ischemia/reperfusion injury. However, the role of CryAB or any HSPs in cardiac responses to mechanical overload is unknown. This study addresses this issue. Nontransgenic mice and mice with cardiomyocyte-restricted transgenic overexpression of CryAB or with germ-line ablation of the CryAB/HSPB2 genes were subjected to transverse aortic constriction or sham surgery. Two weeks later, cardiac responses were analyzed by fetal gene expression profiling, cardiac function analyses, and morphometry. Comparison among the 3 sham surgery groups reveals that CryAB overexpression is benign, whereas the knockout is detrimental to the heart as reflected by cardiac hypertrophy and malfunction at 10 weeks of age. Compared to nontransgenic mice, transgenic mouse hearts showed significantly reduced NFAT transactivation and attenuated cardiac hypertrophic responses to transverse aortic constriction but unchanged cardiac function, whereas NFAT transactivation was significantly increased in cardiac and skeletal muscle of the knockout mice at baseline, and they developed cardiac insufficiency at 2 weeks after transverse aortic constriction. CryAB overexpression in cultured neonatal rat cardiomyocytes significantly attenuated adrenergic stimulation-induced NFAT transactivation and hypertrophic growth. We conclude that CryAB suppresses cardiac hypertrophic responses likely through attenuating NFAT signaling and that CryAB and/or HSPB2 are essential for normal cardiac function.