tbuckley/cabot-search huggingface dataset:
Differences in Control of Cardiovascular Disease and Diabetes by Race, Ethnicity, and Education: U.S. Trends From 1999 to 2006 and Effects of Medicare Coverage
Authors: J. Michael McWilliams
Journal: Annals of Internal Medicine (2009)

Background: Efforts to improve the care of cardiovascular disease and diabetes or expand insurance coverage for adults with these conditions may reduce differences in clinical outcomes. Objective: To assess recent national trends in disease control, trends in sociodemographic differences in control, and changes in sociodemographic differences after age 65 years associated with near-universal Medicare coverage. Design: Observational and quasi-experimental analyses of repeated cross-sectional data. Setting: National Health and Nutrition Examination Survey, 1999 to 2006. Participants: Adults age 40 to 85 years with relevant clinical conditions. Measurements: Blood pressure control (<140/90 mm Hg) and mean systolic blood pressure among adults with hypertension (n = 4521); glycemic control (hemoglobin A1c levels <7.0%) and mean hemoglobin A1c levels among those with diabetes (n = 1733); and total cholesterol level control (<5.2 mmol/L [<200 mg/dL]) and mean total cholesterol levels among those with coronary heart disease, stroke, or diabetes (n = 2928). Temporal trends in these measures were compared by race, ethnicity, and education, and sociodemographic differences were compared above and below eligibility for Medicare at age 65 years. Results: Disease control improved significantly between 1999 and 2006 for all 6 measures (P < 0.001). These trends did not differ by race or ethnicity or by education (P ≥ 0.185 for group–time interactions), except that white–Hispanic differences in glycemic control widened (P = 0.042). Black–white differences in systolic blood pressure were smaller among adults age 65 to 85 years than among adults age 40 to 64 years (reduction in difference, 4.2 mm Hg; P = 0.009). Black–white differences in hemoglobin A1c levels were also smaller after age 65 years (reduction in difference, 0.7%; P = 0.005), as were Hispanic–white differences (reduction in difference, 0.7%; P = 0.007) and differences between less and more educated adults (reduction in difference, 0.5%; P = 0.033). Limitation: Data were cross-sectional, and estimates may have been biased by coincidental events at age 65 years, such as retirement, that may affect disease control. Conclusion: Control of blood pressure and glucose and cholesterol levels has improved since 1999 for adults with cardiovascular disease and diabetes, but racial, ethnic, or socioeconomic differences have not narrowed significantly. Medicare coverage after age 65 years is associated with reductions in these differences. Primary Funding Source: The Commonwealth Fund.
Comparability of self rated health: cross sectional multi-country survey using anchoring vignettes
Authors: Joshua A Salomon, Ajay Tandon, Christopher J L Murray
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objective</b> To examine differences in expectations for health using anchoring vignettes, which describe fixed levels of health on dimensions such as mobility. <b>Design</b> Cross sectional survey of adults living in the community. <b>Setting</b> China, Myanmar, Sri Lanka, Pakistan, Turkey, and United Arab Emirates. <b>Participants</b> 3012 men and women aged 18 years and older (self ratings); subsample of 406 (vignette ratings). <b>Main outcome measures</b> Self rated mobility levels and ratings of hypothetical vignettes using the same questions and response categories. <b>Results</b> Consistent rankings of vignettes are evidence that vignettes are understood in similar ways in different settings, and internal consistency of orderings on two mobility questions indicates good comprehension. Variation in vignette ratings across age groups suggests that expectations for mobility decline with age. Comparison of responses to two different mobility questions supports the assumption that individual ratings of hypothetical vignettes relate to expectations for health in similar ways as self assessments. <b>Conclusions</b> Anchoring vignettes could provide a powerful tool for understanding and adjusting for the influence of different health expectations on self ratings of health. Incorporating anchoring vignettes in surveys can improve the comparability of self reported measures.
Combination Therapy Targeting the Chk1 and Wee1 Kinases Shows Therapeutic Efficacy in Neuroblastoma
Authors: Mike R. Russell, Kirill Levin, JulieAnn Rader, Lili Belcastro, Yimei Li, Daniel Martinez, Bruce Pawel, Stuart D. Shumway, John M. Maris, Kristina A. Cole
Journal: Cancer Research (2012)

Neuroblastoma is uniquely sensitive to single-agent inhibition of the DNA damage checkpoint kinase Chk1, leading us to examine downstream effectors of this pathway and identify mitotic regulator Wee1 as an additional therapeutic target in this disease. Wee1 was overexpressed in both neuroblastoma cell lines and high-risk patient tumors. Genetic or pharmacologic abrogation of Wee1 signaling results in marked cytotoxicity in 10 of 11 neuroblastoma cell lines with a median IC(50) of 300 nmol/L for the Wee1-selective small-molecule inhibitor MK-1775. Murine tumor lines derived from mice that were either heterozygous or homozygous for MycN were particularly sensitive to single-agent inhibition of Wee1 (IC(50)s of 160 and 62 nmol/L, respectively). Simultaneous pharmacologic inhibition of Chk1 and Wee1 acted in a synergistic fashion to further impede neuroblastoma cell growth in vitro, in a manner greater than the individual inhibitors either alone or combined with chemotherapy. Combination Chk1 and Wee1 inhibition also revealed in vivo efficacy in neuroblastoma xenografts. Taken together, our results show that neuroblastoma cells depend on Wee1 activity for growth and that inhibition of this kinase may serve as a therapeutic for patients with neuroblastoma.
Haemophilus influenzae pneumonia in Melanesian adults: report of 15 cases.
Authors: D J Barnes, S Naraqi, J D Igo
Journal: Thorax (1987)

In a prospective study of 170 adult patients with acute pneumonia, Haemophilus influenzae was found to be the aetiological agent in 15 cases (8.8%). The diagnosis in all cases was based on positive cultures of blood or percutaneous lung aspirate, or both. Chronic lung disease was significantly more common in patients with H influenzae pneumonia than in patients with pneumonia due to other organisms but age, sex, and smoking history did not differ significantly. Lobar consolidation was the most common radiological pattern, being present in 10 of the 15 cases. Type b was the commonest serotype isolated, but three cases were due to non-typable (non-capsulate) strains. All patients survived, responding well to treatment with penicillin, ampicillin, or chloramphenicol. Haemophilus influenzae should be considered as a possible cause of pneumonia in adults, particularly those with underlying chronic lung disease.
Pharmacological inhibition of quorum sensing for the treatment of chronic bacterial infections
Authors: Morten Hentzer, Michael Givskov
Journal: Journal of Clinical Investigation (2003)

Traditional treatment of infectious diseases is based on compounds that aim to kill or inhibit bacterial growth. A major concern with this approach is the frequently observed development of resistance to antimicrobial compounds. The discovery of bacterial-communication systems (quorum-sensing systems), which orchestrate important temporal events during the infection process, has afforded a novel opportunity to ameliorate bacterial infection by means other than growth inhibition. Compounds able to override bacterial signaling are present in nature. Herein we discuss the known signaling mechanisms and potential antipathogenic drugs that specifically target quorum-sensing systems in a manner unlikely to pose a selective pressure for the development of resistant mutants.
Prognostic Value of Elevated Levels of Intestinal Microbe-Generated Metabolite Trimethylamine-N-Oxide in Patients With Heart Failure
Authors: W.H. Wilson Tang, Zeneng Wang, Yiying Fan, Bruce Levison, Jennie E. Hazen, Lillian M. Donahue, Yuping Wu, Stanley L. Hazen
Journal: Journal of the American College of Cardiology (2014)
Dynamic distribution of muscle-specific calpain in mice has a key role in physical-stress adaptation and is impaired in muscular dystrophy
Authors: Koichi Ojima, Yukiko Kawabata, Harumi Nakao, Kazuki Nakao, Naoko Doi, Fujiko Kitamura, Yasuko Ono, Shoji Hata, Hidenori Suzuki, Hiroyuki Kawahara, Julius Bogomolovas, Christian Witt, Coen Ottenheijm, Siegfried Labeit, Henk Granzier, Noriko Toyama-Sorimachi, Michiko Sorimachi, Koichi Suzuki, Tatsuya Maeda, Keiko Abe, Atsu Aiba, Hiroyuki Sorimachi
Journal: Journal of Clinical Investigation (2010)

Limb-girdle muscular dystrophy type 2A (LGMD2A) is a genetic disease that is caused by mutations in the calpain 3 gene (CAPN3), which encodes the skeletal muscle-specific calpain, calpain 3 (also known as p94). However, the precise mechanism by which p94 functions in the pathogenesis of this disease remains unclear. Here, using p94 knockin mice (termed herein p94KI mice) in which endogenous p94 was replaced with a proteolytically inactive but structurally intact p94:C129S mutant protein, we have demonstrated that stretch-dependent p94 distribution in sarcomeres plays a crucial role in the pathogenesis of LGMD2A. The p94KI mice developed a progressive muscular dystrophy, which was exacerbated by exercise. The exercise-induced muscle degeneration in p94KI mice was associated with an inefficient redistribution of p94:C129S in stretched sarcomeres. Furthermore, the p94KI mice showed impaired adaptation to physical stress, which was accompanied by compromised upregulation of muscle ankyrin-repeat protein-2 and hsp upon exercise. These findings indicate that the stretch-induced dynamic redistribution of p94 is dependent on its protease activity and essential to protect muscle from degeneration, particularly under conditions of physical stress. Furthermore, our data provide direct evidence that loss of p94 protease activity can result in LGMD2A and molecular insight into how this could occur.
Mammaglobin Expression in Leukapheresis Products Is a Predictive Marker of Poor Prognosis in Women with High-Risk Breast Cancer
Authors: Pier Francesco Ferrucci, Cristina Rabascio, Chiara Mazzetta, Emilia Cocorocchio, Alberto Agazzi, Anna Vanazzi, Saverio Cinieri, Fedro A. Peccatori, Mara Paolucci, Francesco Bertolini, Giovanni Martinelli
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The purpose of this study was to investigate the incidence and prognostic relevance of tumor cell detection in granulocyte colony-stimulating factor–mobilized peripheral blood progenitor cell collections (PBPCCs) using cytokeratin (CK), maspin (MAS), and mammaglobin (MAM) genes as epithelial cell markers. The population on which the study was conducted was drawn from stage III breast cancer patients undergoing high-dose chemotherapy and autologous transplantation with PBPCCs. Experimental Design: One hundred and ninety-four patients were enrolled in the study and analyzed for tumor cell detection on the basis of 481 PBPCCs gathered before administration of chemotherapy. CK, MAS, and MAM gene expressions were investigated by means of the reverse transcription nested polymerase chain reaction, and those samples expressing CK were further hybridized with a radiolabeled internal probe to reduce false-positive results. Sensitivity and specificity were assessed on 37 controls (12 cell lines, 12 healthy donors, and 13 nonepithelial malignancies). Each of the known prognostic variables (age, stage, lymph node status, receptor status, c-ErbB2 status, and Ki67 status) was then analyzed (both individually and together with CK, MAS, and MAM expression on PBPCCs) in relation to patient overall survival (OS) and relapse-free survival (RFS). Results: After a 3-year follow-up, an estimated 83% (95% confidence interval, 77.1–88.8%) of the patients were alive and an estimated 67% (95% confidence interval, 60.1–74.6%) were free of relapse. One hundred and seventy-six of the 194 patients (91%) had contaminated PBPCCs evidenced by at least one positive sample for any of the markers evaluated. The PBPCC frequency of CK, MAS, and MAM positivity (+) was 71%, 36%, and 16%, respectively. MAM expression on PBPCC was associated with an increased risk of relapse (P = 0.003), whereas CK and MAS expressions were not associated with changes in either RFS or OS. Conclusions: MAM gene expression on leukapheresis products of high-risk breast cancer patients is an indicator of poor prognosis. The method of evaluation is simple and reproducible and provides new tools for evaluating the role played by tumor cells in apheresis products and their potential in causing metastasis.
Purkinje and ventricular activation sequences of canine papillary muscle. Effects of quinidine and calcium on the Purkinje-ventricular conduction delay.
Authors: R D Veenstra, R W Joyner, D A Rawling
Journal: Circulation Research (1984)

We have studied in vitro preparations of canine right and left papillary muscles to determine the excitation sequences of the Purkinje and ventricular cells, using both monopolar surface electrodes and intracellular microelectrodes. Our results show, for right papillary muscles, that the Purkinje layer covers the basal part of the muscle, and that activation from the right bundle branch propagates over all of the Purkinje layer, but directly activates the underlying ventricular layer only at specific junctional sites. Left papillary muscles have attachments to both apical and basal Purkinje strands and the Purkinje layer covers the entire muscle, but, as for right papillary muscles, activation from the Purkinje layer to the ventricular layer occurs only at basal junctional sites. Antidromic conduction in papillary muscles (propagation from the ventricular layer to the Purkinje layer) can occur at regions other than the specific sites through which the Purkinje layer activates the ventricular layer. At the identified junctional sites, the Purkinje cell action potential duration is significantly shorter than in the free-running strand, but it remains longer than that of the ventricular cells. The time delay at the junctional sites is increased by quinidine, increased calcium concentration, and increased pacing frequency.
Receptors for prostaglandin E2 that regulate cellular immune responses in the mouse
Authors: Chandra Nataraj, Dennis W. Thomas, Stephen L. Tilley, MyTrang Nguyen, Roslyn Mannon, Beverly H. Koller, Thomas M. Coffman
Journal: Journal of Clinical Investigation (2001)

Production of prostaglandin E2 (PGE2) is enhanced during inflammation, and this lipid mediator can dramatically modulate immune responses. There are four receptors for PGE2 (EP1–EP4) with unique patterns of expression and different coupling to intracellular signaling pathways. To identify the EP receptors that regulate cellular immune responses, we used mouse lines in which the genes encoding each of the four EP receptors were disrupted by gene targeting. Using the mixed lymphocyte response (MLR) as a model cellular immune response, we confirmed that PGE2 has potent antiproliferative effects on wild-type responder cells. The absence of either the EP1 or EP3 receptors did not alter the inhibitory response to PGE2 in the MLR. In contrast, when responder cells lacked the EP2 receptor, PGE2 had little effect on proliferation. Modest resistance to PGE2 was also observed in EP4–/– responder cells. Reconstitution experiments suggest that EP2 receptors primarily inhibit the MLR through direct actions on T cells. Furthermore, PGE2 modulates macrophage function by activating the EP4 receptor and thereby inhibiting cytokine release. Thus, PGE2 regulates cellular immune responses through distinct EP receptors on different immune cell populations: EP2 receptors directly inhibit T cell proliferation while EP2 and EP4 receptors regulate antigen presenting cells functions.
Symptom Structure in Japanese Patients With Obsessive-Compulsive Disorder
Authors: Hisato Matsunaga, Kensei Maebayashi, Kazuhisa Hayashida, Kenya Okino, Tokuzo Matsui, Tosiya Iketani, Nobuo Kiriike, Daniel J. Stein
Journal: American Journal of Psychiatry (2007)

Obsessive-compulsive disorder (OCD) comprises a number of specific symptom dimensions. The authors factor analyzed data on the Yale-Brown Obsessive Compulsive Scale symptom checklist in a large group of Japanese OCD patients to examine whether symptom dimensions were stable across cultures.A principal components analysis of Yale-Brown Obsessive Compulsive Scale major symptom categories was performed on Japanese OCD patients (N=343). The association between symptom dimensions and clinical variables, including 1-year outcome after combination treatment, was also examined using Pearson correlations.Four factors explaining 57.7% of the variance were identified: 1) contamination/washing, 2) hoarding, 3) symmetry/repeating and ordering, and 4) aggressive/checking symptoms. The symmetry dimension was associated with early age at onset, and both the symmetry and hoarding dimensions were associated with decreased functioning and treatment resistance.The findings in this study support transcultural stability in the symptom structure of OCD, which is consistent with the hypothesis that OCD is mediated by universal psychobiological mechanisms.
2013 ACCF/ACR/ASE/ASNC/SCCT/SCMR Appropriate Utilization of Cardiovascular Imaging in Heart Failure
Authors: Manesh R. Patel, Richard D. White, Suhny Abbara, David A. Bluemke, Robert J. Herfkens, Michael Picard, Leslee J. Shaw, Marc Silver, Arthur E. Stillman, James Udelson, Peter Alagona, Gerard Aurigemma, Javed Butler, Don Casey, Ricardo Cury, Scott Flamm, Tim Gardner, Rajesh Krishnamurthy, Joseph Messer, Michael W. Rich, Henry Royal, Gerald Smetana, Peter Tilkemeier, Mary Norine Walsh, Pamela K. Woodard, G. Michael Felker, Victor Ferrari, Myron Gerson, Michael M. Givertz, Daniel J. Goldstein, Jill E. Jacobs, Warren R. Janowitz, Scott Jerome, John Lesser, Michael McConnell, Sherif F. Nagueh, Karen G. Ordovas, Prem Soman, Kirk Spencer, Raymond F. Stainback, Krishnaswami Vijayaraghavan, W. H Wilson Tang
Journal: Journal of the American College of Cardiology (2013)
Pituitary-ovarian dysfunction and endometriosis
Authors: D.J. Cahill
Journal: Human Reproduction Update (2000)

Significant association between endometriosis, including minor endometriosis, and infertility (or strictly subfertility) is shown by prevalence studies, but a causal relationship has not been established. This review focuses on evidence for pituitary–ovarian dysfunction as a cause for the subfertility. A methodological problem is lack of fertile controls with endometriosis. Group comparison with tubal infertility cases as controls have demonstrated: impaired follicular growth, reduction in circulating oestradiol concentrations during the pre-ovulatory phase and of oestradiol and progesterone during the early luteal phase, and disturbed luteinizing hormone (LH) surge patterns. Reduction in LH concentrations in pre-ovulatory follicular fluid has also been found, and granulosa cells collected at the same time have demonstrated impaired steroidogenic capacity in vitro, but these were not consistently proven findings. Pooled data from published studies show significantly reduced oocyte fertilization rates (49%) compared with controls (69%), even after maximal stimulation with exogenous follicle stimulating hromone (FSH) and human chorionic gonadotrophin (HCG) (54 versus 69%). The implantation rate is also slightly (though significantly) reduced (11 versus 13%). The findings suggest an inherent disorder of follicular function, with LH surge impairment probably being a secondary phenomenon. The resulting reduction in the chance of fertilization of the oocyte would contribute substantially to the subfertility associated with endometriosis. It seems that the benefit of in-vitro fertilization is gained through the excessive number of oocytes obtained by stimulation.
CHK2-decreased protein expression and infrequent genetic alterations mainly occur in aggressive types of non-Hodgkin lymphomas
Authors: Frederic Tort, Silvia Hernàndez, Silvia Beà, Antonio Martı́nez, Manel Esteller, James G. Herman, Xavier Puig, Emma Camacho, Montse Sánchez, Iracema Nayach, Armando Lopez-Guillermo, Pedro L. Fernández, Dolors Colomer, Luis Hernàndez, Elias Campo
Journal: Blood (2002)
Community development and its impact on health: South Asian experience
Authors: S M Moazzem Hossain, Abbas Bhuiya, Alia Rahman Khan, Iyorlumun Uhaa
Journal: BMJ (2004)

Most South Asian governments have concentrated on emulating a Western style of healthcare service, with the result that an elite few are overmedicalised whereas the majority are neglected. However, community participation in the development of local health services could provide a solution 

Despite a remarkable improvement during recent decades in many countries' overall health and nutrition statistics and macro-economic indicators,1 some 10.8 million children aged under 5 years still die annually worldwide, of which 34% occur in South Asia alone.2 It is too simplistic to relate improvements in economic indicators with better health because this does not take account of inequality, change in focus of public health priorities, and, most importantly, the involvement of the community in improving health. This article discusses some of the most prominent examples in South Asia of involvement of the community in planning, managing, and evaluating health projects. However, showing a direct relation between community development and improved health remains a challenge.

Community development is becoming one of the most popular subjects in the context of public health interventions. Although an accurate definition of community development is problematic, a reasonable description would be the empowerment of a community to obtain self reliance and control over the factors that affect their health. Unfortunately, South Asia, so richly endowed with natural and human resources, has suffered for centuries from poverty and consequent ill health. It has, however, a rich heritage of community initiatives such as the establishment of education facilities, religious institutions, and orphanages and the construction of roads. It is unfortunate that health has remained the responsibility of governments, outside agencies, and, of course, the private sector (both formal and informal) and the provision of medical services has become big business.3

Most of the public and private health services in South Asia have …