tbuckley/cabot-search huggingface dataset:
Virological response is associated with decline in hemoglobin concentration during pegylated interferon and ribavirin therapy in hepatitis C virus genotype 1
Authors: William Sievert, Gregory J. Dore, Geoffrey W. McCaughan, Motoko Yoshihara, Darrell H. Crawford, Wendy Cheng, Martin Weltman, William Rawlinson, Bishoy Rizkalla, Jean K. DePamphilis, Stuart K. Roberts
Journal: Hepatology (2011)

Anemia may increase the likelihood of achieving a sustained virological response (SVR) during pegylated interferon and ribavirin treatment of hepatitis C virus (HCV) infection. To determine whether hemoglobin decline is associated with SVR, we retrospectively evaluated the CHARIOT study of 871 treatment-naïve HCV genotype 1 patients. Anemia (serum hemoglobin &lt;100 g/L) occurred in 137 (16%) patients, of whom only 14 (10%) received erythropoietin. Hemoglobin decline &gt;30g/L from baseline occurred in 76% of patients overall, including 526 patients who did not become anemic. Virological responses were higher in anemic patients compared with those who did not develop anemia (end of treatment, 80% versus 65%, P = 0.003; SVR, 61% versus 50%, P = 0.02); these differences remained significant when patients receiving erythropoietin were excluded from analysis. SVR was also higher in patients with hemoglobin decline &gt;30 g/L compared with patients without a similar decline. In multiple logistic regression analyses with treatment group and baseline characteristics, the odds ratio for SVR was 1.97 (95% confidence interval, 1.08-3.62) for anemia and 2.17 (95% confidence interval, 1.31-3.62) for hemoglobin decline &gt;30 g/L. Patients who first developed a hemoglobin decline &gt;30 g/L during weeks 5-12 and 13-48 were more likely to achieve SVR than those who first developed such changes in weeks 0-4 or who never experienced them. Conclusion: Patients with HCV genotype 1 infection who develop anemia or experience a hemoglobin decline &gt;30 g/L during weeks 5-48 of therapy achieve higher virological responses to pegylated interferon and ribavirin therapy that are unrelated to erythropoietin use. (HEPATOLOGY 2011;)
NHS must tackle its ignorance over patients with autism, says watchdog
Authors: A. O'Dowd
Journal: BMJ (2009)

Clinicians and NHS organisations do not know how many of their patients have autism or the best way to treat them, a report by public spending watchdog the National Audit Office has found.

Eight hundred of the 1000 GPs in England who responded to a survey for the report said that they need additional guidance and training to be able to identify and treat patients with autism better.

An estimated 400 000 adults and 100 000 children in England have autism, many of whom may require specialist support. Autism costs the UK economy …
Deposition of Platelet RANTES Triggering Monocyte Recruitment Requires P-Selectin and Is Involved in Neointima Formation After Arterial Injury
Authors: Andreas Schober, David Manka, Philipp von Hundelshausen, Yuqing Huo, Peter Hanrath, Ian J. Sarembock, Klaus Ley, Christian Weber
Journal: Circulation (2002)

Background— Chemokines expressed on atherosclerotic endothelium or deposited by activated platelets have been implicated in monocyte recruitment during atherogenesis and restenosis. Although the involvement of P-selectin in these processes is evident from studies in knockout mice, it has not been elucidated whether delivery of platelet chemokines requires P-selectin, thus serving as a P-selectin-dependent effector function. Methods and Results— Using immunofluorescence and laminar flow assays, we found that the deposition of the platelet-derived chemokine RANTES and monocyte arrest subsequently triggered by RANTES immobilized on inflamed endothelium are more efficient after preperfusion than after static preincubation of platelets and appear to depend on interactions of platelet but not endothelial P-selectin. This was revealed by the effects of P-selectin antibodies and comparison of P-selectin-deficient and wild-type platelets. Immunohistochemistry detected a substantial luminal expression of RANTES on neointimal lesions in wire-injured carotid arteries of apolipoprotein E (apoE)-deficient mice but not of mice with a combined deficiency in apoE and P-selectin (or platelet P-selectin). As assessed by histomorphometry, treatment of apoE-deficient mice with the RANTES receptor antagonist Met-RANTES markedly reduced neointimal plaque area and macrophage infiltration. Conclusions— Our data suggest that RANTES deposition and subsequent monocyte arrest are promoted by platelet P-selectin and involved in wire-induced intimal hyperplasia, and that blocking RANTES receptors attenuates neointima formation and macrophage infiltration. This mechanism represents an important component explaining the protection against neointimal growth in P-selectin-deficient mice and may represent a novel approach to the treatment of restenosis or atherosclerosis by the administration of chemokine receptor antagonists.
Violence in youth sports: hazing, brawling and foul play
Authors: S K Fields, C L Collins, R D Comstock
Journal: British Journal of Sports Medicine (2009)

By separating hazing, brawling, and foul play and failing to recognise that their connection to sport binds them together into a cohesive subset of sport injury and youth violence, past research has failed to show how sports-related violence is a broad example of interpersonal violence. The acceptance of violence within the sporting culture may, in part, explain why sports-related violence has not yet been widely recognised as a public health concern. This review shows that sports-related violence, including hazing, brawling and foul play, occurs among youth athletes of all ages and in a variety of different sports. The few studies to address this issue have all acknowledged the dangers of sports-related violence; however, no incident tracking method has been developed. Future research must provide accurate national estimates of the incidence of sports-related violence among youth, identify associated risk factors, evaluate preventive interventions and identify effective methods of distributing and implementing evidence-based interventions. Monitoring the magnitude and distribution of the burden of sports-related violence and building the scientific infrastructure necessary to support the development and widespread application of effective sports-related prevention interventions are essential first steps toward a reduction in the incidence of sports-related violence.
Molecular insights into renal interstitial fibrosis.
Authors: A A Eddy
Journal: Journal of the American Society of Nephrology (1996)

Progressive interstitial fibrosis accompanied by loss of renal tubules and interstitial capillaries typifies all progressive renal diseases. Dynamic and complex, the process evidently overlaps with matrix remodeling; it may even be reversible. The interstitial fibrous tissue comprises several normal and novel matrix proteins, proteoglycans, and glycoproteins. Interstitial myofibroblasts are a major site of matrix protein overproduction, although resident fibroblasts, tubular cells, and inflammatory cells may contribute. Inadequate matrix degradation also appears to contribute to the fibrogenic process. Two protease cascades, the metalloproteinases and the plasminogen activator/ plasmin family of serine proteases, are implicated in the turnover of interstitial matrix proteins; upregulated expression of protease inhibitors has been observed in each. Increased tissue inhibitor of metalloproteinase-1 and plasminogen activator inhibitor-1 levels suggest that the intrinsic renal activity of the metalloproteinases and serine proteases are inhibited while matrix proteins accumulate in the interstitium. Several signals that may direct the interstitial fibrogenic process have been identified, but not yet proved to cause it. Upregulated expression of transforming growth factor beta-1, the proteotypic fibrogenic cytokine, has been observed in experimental and human models; it probably does not act alone. There may be supportive roles for platelet-derived growth factor, interleukin-1, basic fibroblast growth factor, angiotensin II, and endothelin-1. Although it is not known why interstitial fibrosis compromises renal function, atrophy of renal tubules may be pivotal. Ischemic necrosis and/or apoptosis may generate nonfunctioning atubular and sclerotic glomeruli. Future studies must delineate the molecular basis of the differences between renal repair and renal destruction by fibrosis, two processes that share many common features.
T lymphocyte-dependent B lymphocyte proliferative response to antigen. I Genetic restriction of the stimulation of B lymphocyte proliferation.
Authors: H Y Tse, J J Mond, W E Paul
Journal: The Journal of Experimental Medicine (1981)

For the purpose of examining more closely the interaction between T and B lymphocytes, we have developed an in vitro T lymphocyte-dependent B lymphocyte proliferation assay. Proliferation of B lymphocytes in response to antigen was found to depend on the presence of primed T lymphocytes; the B lymphocytes could be derived from nonprimed animals. It appears that these B cells were nonspecifically recruited to proliferate. This nonspecific recruitment, however, was found to be Ir-gene restricted in that B lymphocytes from B10.S mice, which are genetic nonresponders to the polymer Glu60-Ala30-Tyr10 (GAT), could not be stimulated by GAT-primed (responder X nonresponder) F1 T cells. The apparent lack of antigen specificity in the face of Ir gene-restricted T-B interaction may have important implications in our understanding of the recognition unit(s) on T lymphocytes.
Adjunctive Diagnostic Procedures for Percutaneous Coronary Intervention
Authors: Auras R. Atreya, Amir Lotfi
Journal: JAMA Internal Medicine (2015)

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Randomized Phase II Trial of Everolimus in Combination With Tamoxifen in Patients With Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer With Prior Exposure to Aromatase Inhibitors: A GINECO Study
Authors: Thomas Bachelot, Céline Bourgier, Claire Cropet, Isabelle Ray-Coquard, Jean-Marc Ferrero, Gilles Freyer, Sophie Abadie-Lacourtoisie, Jean-Christophe Eymard, Marc Debled, Dominique Spaëth, Eric Legouffe, Djelila Allouache, Claude El Kouri, Eric Pujade-Lauraine
Journal: Journal of Clinical Oncology (2012)

Cross-talk between signal transduction pathways likely contributes to hormone resistance in metastatic breast cancer (mBC). Everolimus, an oral inhibitor of the mammalian target of rapamycin, has restored sensitivity in endocrine-resistance models and shown anticancer activity in early-phase mBC clinical trials. This analysis evaluated efficacy and safety of everolimus in combination with tamoxifen in patients with mBC resistant to aromatase inhibitors (AIs).This open-label, phase II study randomly assigned postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative, AI-resistant mBC to tamoxifen 20 mg/d plus everolimus 10 mg/d (n = 54) or tamoxifen 20 mg/d alone (n = 57). Randomization was stratified by primary and secondary hormone resistance. Primary end point was clinical benefit rate (CBR), defined as the percentage of all patients with a complete or partial response or stable disease at 6 months. No formal statistical comparison between groups was planned.The 6-month CBR was 61% (95% CI, 47 to 74) with tamoxifen plus everolimus and 42% (95% CI, 29 to 56) with tamoxifen alone. Time to progression (TTP) increased from 4.5 months with tamoxifen alone to 8.6 months with tamoxifen plus everolimus, corresponding to a 46% reduction in risk of progression with the combination (hazard ratio [HR], 0.54; 95% CI, 0.36 to 0.81). Risk of death was reduced by 55% with tamoxifen plus everolimus versus tamoxifen alone (HR, 0.45; 95% CI, 0.24 to 0.81). The main toxicities associated with tamoxifen plus everolimus were fatigue (72% v 53% with tamoxifen alone), stomatitis (56% v 7%), rash (44% v 7%), anorexia (43% v 18%), and diarrhea (39% v 11%).This study suggests that tamoxifen plus everolimus increased CBR, TTP, and overall survival compared with tamoxifen alone in postmenopausal women with AI-resistant mBC.
Epigenetic Inactivation of RASSF1A in Lung and Breast Cancers and Malignant Phenotype Suppression
Authors: D. G. Burbee, E. Forgacs, S. Zochbauer-Muller, L. Shivakumar, K. Fong, B. Gao, D. Randle, M. Kondo, A. Virmani, S. Bader, Y. Sekido, F. Latif, S. Milchgrub, S. Toyooka, A. F. Gazdar, M. I. Lerman, E. Zabarovsky, M. White, J. D. Minna
Journal: JNCI Journal of the National Cancer Institute (2001)

Background: The recently identified RASSF1 locus is located within a 120-kilobase region of chromosome 3p21.3 that frequently undergoes allele loss in lung and breast cancers. We explored the hypothesis that RASSF1 encodes a tumor suppressor gene for lung and breast cancers. Methods: We assessed expression of two RASSF1 gene products, RASSF1A and RASSF1C, and the methylation status of their respective promoters in 27 non-small-cell lung cancer (NSCLC) cell lines, in 107 resected NSCLCs, in 47 small-cell lung cancer (SCLC) cell lines, in 22 breast cancer cell lines, in 39 resected breast cancers, in 104 nonmalignant lung samples, and in three breast and lung epithelial cultures. We also transfected a lung cancer cell line that lacks RASSF1A expression with vectors containing RASSF1A complementary DNA to determine whether exogenous expression of RASSF1A would affect in vitro growth and in vivo tumorigenicity of this cell line. All statistical tests were two-sided. Results: RASSF1A messenger RNA was expressed in nonmalignant epithelial cultures but not in 100% of the SCLC, in 65% of the NSCLC, or in 60% of the breast cancer lines. By contrast, RASSF1C was expressed in all nonmalignant cell cultures and in nearly all cancer cell lines. RASSF1A promoter hypermethylation was detected in 100% of SCLC, in 63% of NSCLC, in 64% of breast cancer lines, in 30% of primary NSCLCs, and in 49% of primary breast tumors but in none of the nonmalignant lung tissues. RASSF1A promoter hypermethylation in resected NSCLCs was associated with impaired patient survival (P = .046). Exogenous expression of RASSF1A in a cell line lacking expression decreased in vitro colony formation and in vivo tumorigenicity. Conclusion: RASSF1A is a potential tumor suppressor gene that undergoes epigenetic inactivation in lung and breast cancers through hypermethylation of its promoter region.
Tobacco use in 3 billion individuals from 16 countries: an analysis of nationally representative cross-sectional household surveys
Authors: Gary A Giovino, Sara A Mirza, Jonathan M Samet, Prakash C Gupta, Martin J Jarvis, Neeraj Bhala, Richard Peto, Witold Zatonski, Jason Hsia, Jeremy Morton, Krishna M Palipudi, Samira Asma
Journal: The Lancet (2012)
Glycemic Control Is a Predictor of Survival for Diabetic Patients on Hemodialysis
Authors: Tomoaki Morioka, Masanori Emoto, Tsutomu Tabata, Tetsuo Shoji, Hideki Tahara, Hiroshi Kishimoto, Eiji Ishimura, Yoshiki Nishizawa
Journal: Diabetes Care (2001)

OBJECTIVE—To investigate the impact of glycemic control on the survival of diabetic subjects with end-stage renal disease (ESRD) starting hemodialysis treatment. RESEARCH DESIGN AND METHODS—This single-center prospective observational study enrolled 150 diabetic ESRD subjects (109 men and 41 women; age at hemodialysis initiation, 60.5 ± 10.2 years) at start of hemodialysis between January 1989 and December 1997. The subjects were divided into groups according to their glycemic control level at inclusion as follows: good HbA1c &amp;lt;7.5%, n = 93 (group G), and poor HbA1c ≥7.5%, n = 57 (group P); and survival was followed until December 1999, with a mean follow-up period of 2.7 years. RESULTS—Group G had better survival than group P (the control group) (P = 0.008). At inclusion, there was no significant difference in age, sex, systolic blood pressure (SBP), BMI, cardio-to-thoracic ratio (CTR) on chest X-ray, and serum creatinine (Cre) or hemoglobin (Hb) levels between the two groups. After adjustment for age and sex, HbA1c was a significant predictor of survival (hazard ratio 1.133 per 1.0% increment of HbA1c, 95% CI 1.028–1.249, P = 0.012), as were Cre and CTR. CONCLUSIONS—Good glycemic control (HbA1c &amp;lt;7.5%) predicts better survival of diabetic ESRD patients starting hemodialysis treatment.
Effects of estrogen and medroxyprogesterone acetate on subpopulations of triglyceride-rich lipoproteins and high-density lipoproteins
Authors: Stefania Lamon-Fava, Borbala Posfai, Bela F Asztalos, Katalin V Horvath, Gerard E Dallal, Ernst J Schaefer
Journal: Metabolism (2003)
Fasting Blood Sample-Based Assessment of Insulin Sensitivity in Kidney-Pancreas-Transplanted Patients
Authors: Gianluca Perseghin, Andrea Caumo, Lucia Piceni Sereni, Alberto Battezzati, Livio Luzi
Journal: Diabetes Care (2002)

To ascertain whether simple indexes of insulin sensitivity based on a fasting blood sample may be reliable measures of insulin sensitivity in combined kidney-pancreas- transplanted patients.Estimates of insulin sensitivity based on fasting plasma glucose, insulin (homeostasis model assessment of insulin sensitivity [HOMA-IS], Quantitative Insulin Sensitivity Check Index [QUICKI]), and free fatty acid (revised QUICKI) concentrations were compared with insulin sensitivity as assessed with the gold standard technique (euglycemic-hyperinsulinemic clamp) in 22 patients who had undergone kidney-pancreas transplantation (KP-Tx) and 18 matched healthy subjects (NOR).In KP-Tx patients, indexes based on the glucose-insulin product, HOMA-IS (r = 0.47, P = 0.03) and QUICKI (r = 0.47, P = 0.03), were shown to be reliable measures of insulin sensitivity. The introduction of fasting plasma free fatty acid concentration in the revised QUICKI (r = 0.76, P < 0.0001) considerably improved the power of prediction of the clamp-based measure of insulin sensitivity as observed in the healthy control subjects (r = 0.83, P < 0.0001).This study shows that in KP-Tx patients, HOMA-IS and QUICKI are reliable measures of insulin sensitivity; the additional incorporation of fasting plasma free fatty acid concentration into the glucose-insulin product (revised QUICKI) resulted in a considerably more powerful index.
Use of HbA1c in the diagnosis of diabetes
Authors: A. Farmer
Journal: BMJ (2012)

Be aware of clinical circumstances in which results may mislead

Before 2010, guidelines recommended the measurement of blood glucose for diagnosing diabetes. Improved standardisation in the measurement of glycated haemoglobin (HbA1c) and wider availability of the assay led to a recommendation in 2011 by the World Health Organization that HbA1c should be used instead.1 This recommendation was included within a recent UK public health guidance for the identification of people at high risk of diabetes.2 In addition, a UK expert advisory body convened by the Department of Health has—after an extended period of consultation—now stated how the WHO recommendations should be implemented.3

The expert advisory group recommends that an HbA1c cut-off point of 48 mmol/mol or more (6.5%) be used for the diagnosis of diabetes. Unless the clinical diagnosis is clear, a second confirmatory measurement is needed as soon as possible. If either the initial or follow-up measurement is less than 48 mmol/mol, the diagnosis of diabetes should not be made.3 The group recommended that patients with an HbA1c of 42-47 mmol/mol should be considered at high risk of diabetes and provided with intensive lifestyle advice and retested annually. Those with an HbA1c of less than 42 mmol/mol may still have a high risk of diabetes and should be treated according to clinical indication, with retesting at least …
Phosphate-induced autophagy counteracts vascular calcification by reducing matrix vesicle release
Authors: Xiao-Yan Dai, Ming-Ming Zhao, Yan Cai, Qing-Cong Guan, Ying Zhao, Youfei Guan, Wei Kong, Wei-Guo Zhu, Ming-Jiang Xu, Xian Wang
Journal: Kidney International (2013)
Transfection of Human Hepatocyte Growth Factor Gene Ameliorates Secondary Lymphedema via Promotion of Lymphangiogenesis
Authors: Yukihiro Saito, Hironori Nakagami, Ryuichi Morishita, Yoichi Takami, Yasushi Kikuchi, Hiroki Hayashi, Tomoyuki Nishikawa, Katsuto Tamai, Nobuyoshi Azuma, Tadahiro Sasajima, Yasufumi Kaneda
Journal: Circulation (2006)

Lymphedema is a disorder of the lymphatic vascular system characterized by impaired lymphatic return and swelling of the extremities. Treatment for this disabling condition remains limited and largely ineffective. The goal of the present study was to investigate the therapeutic efficacy of hepatocyte growth factor (HGF) in animal models of lymphedema.Immunofluorescent analysis demonstrated that canine primary lymphatic endothelial cells (cLECs) were positive for lymphatic-specific markers (vascular endothelial growth factor receptor-3, LYVE-1, podoplanin, and Prox1) and the HGF receptor c-Met. Treating cLECs with human recombinant HGF resulted in a dose-dependent increase in cell growth and migration and increased activity of extracellular signal-regulated kinase and Akt. In human LECs, c-Met also was expressed, and treatment with HGF increased cell growth and migration in a dose-dependent manner. Transfection of human HGF plasmid DNA in cLECs also increased the c-fos promoter activity. Furthermore, weekly HGF gene transfer in a rat tail lymphedema model by disruption of lymphatic vessels resulted in a decrease in lymphedema thickness. Although expression of the endothelial cell marker PECAM-1 was increased in both HGF- and vascular endothelial growth factor 165-injected groups, expression of LEC markers (LYVE-1 and Prox1) was increased only in the HGF-injected group.These data demonstrate that expression of HGF via plasmid transfer improves lymphedema via promotion of lymphangiogenesis. Further studies to determine the clinical utility of this approach would be of benefit to patients with lymphedema.