tbuckley/cabot-search huggingface dataset:
Effects of Aging on Left Ventricular Relaxation in Humans
Authors: Tetsu Yamakado, Eiji Takagi, Setsuya Okubo, Kyoko Imanaka-Yoshida, Toshiaki Tarumi, Mamoo Nakamura, Takeshi Nakano
Journal: Circulation (1997)

Background Some experimental studies in animals have shown that myocardial relaxation is prolonged with aging. However, it is not known whether aging alters ventricular isovolumic relaxation in human subjects. Methods and Results We analyzed high-fidelity left ventricular pressures, measured by use of a catheter-tipped manometer, and biplane left ventriculograms in 55 normal subjects who underwent diagnostic cardiac catheterization but who were found to have normal cardiac anatomy and function. There were 38 men and 17 women, ranging in age from 20 to 77 years. Left ventricular isovolumic relaxation was assessed by the exponential time constants of isovolumic pressure decay with (Tb) and without (Tw) an asymptote pressure. Left ventricular volume, ejection fraction, and wall thickness or mass were calculated from left ventricular angiograms. Neither of the time constants of left ventricular relaxation correlated with age (Tb: r =.001 to .10, P =NS; Tw: r =.02 to .05, P =NS). Left ventricular systolic function (ie, ejection fraction and end-systolic volume index), heart rate, and left ventricular wall thickness or mass, which are major hemodynamic determinants of left ventricular relaxation, were not significantly affected by aging. The multivariate analysis of age and hemodynamic variables against the time constants of left ventricular relaxation also indicated that no significant relation was found between age and left ventricular relaxation. Conclusions In the absence of coronary artery disease, systemic hypertension, left ventricular systolic dysfunction, or hypertrophy, left ventricular relaxation assessed by the time constant of isovolumic pressure decay remains essentially unchanged with normal adult aging, at least until the eighth decade.
Influence of the Vitreomacular Interface on Outcomes of Ranibizumab Therapy in Neovascular Age-related Macular Degeneration
Authors: Ulrike Mayr-Sponer, Sebastian M. Waldstein, Michael Kundi, Markus Ritter, Isabelle Golbaz, Ursula Heiling, Andrea Papp, Christian Simader, Ursula Schmidt-Erfurth
Journal: Ophthalmology (2013)
Glycation of Apoprotein A-I Is Associated With Coronary Artery Plaque Progression in Type 2 Diabetic Patients
Authors: Li Jin Pu, Lin Lu, Rui Yan Zhang, Run Du, Ying Shen, Qi Zhang, Zheng Kun Yang, Qiu Jing Chen, Wei Feng Shen
Journal: Diabetes Care (2012)

To investigate whether glycation level of apoprotein (apo)A-I is associated with coronary artery disease (CAD) and plaque progression in patients with type 2 diabetes.Among 375 consecutive type 2 diabetic patients undergoing quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS), 82 patients with nonsignificant stenosis (luminal diameter narrowing <30% [group I]) and 190 patients with significant CAD (luminal diameter stenosis ≥70% [group II]) were included for analysis of apoA-I glycation level and serum activity of lecithin: cholesterol acyltransferase (LCAT). The control group had 136 healthy subjects. At the 1-year follow-up, angiography and IVUS were repeated mainly in group II patients for plaque progression assessment.Relative intensity of apoA-I glycation by densitometry was increased, and serum LCAT activity was decreased stepwise across groups control, I, and II. These two measurements were associated with the number of diseased coronary arteries and extent index in group II. During 1-year follow-up, QCA detected 45 patients with plaque progression in 159 subjects, and IVUS found 38 patients with plaque progression in 127 subjects. Baseline relative intensity of apoA-I glycation was significantly increased in patients with plaque progression compared with those without, with values associated with changes in QCA and IVUS measurements. Multivariable regression analysis revealed that baseline relative intensity of apoA-I glycation was an independent determinant of CAD and plaque progression in type 2 diabetic patients.ApoA-I glycation level is associated with the severity of CAD and coronary artery plaque progression in type 2 diabetic patients.
Role of the thymus in directing the development of a subset of B lymphocytes.
Authors: J J Mond, I Scher, J Cossman, S Kessler, P K Mongini, C Hansen, F D Finkelman, W E Paul
Journal: The Journal of Experimental Medicine (1982)

In an effort to evaluate the role of the thymus in influencing the development of Lyb-5- B lymphocytes, mice expressing both the xid and nu gene defects were studied. Mice expressing either of these defects respond to both trinitrophenylated Brucellus abortus and lipopolysaccharide; whereas mice with the combined defect show markedly suppressed responses. The other abnormalities included: (a) greater than 80 percent diminution of serum Ig levels; (b) significant increase in the number of sIgM+ sIgD- B lymphocytes; (c) reduced expression of IgD on sIgD+ cells; and (d) a strikingly abnormal histology of their lymphoid tissue. Because nu/nu mice that do not express the xid defect appear relatively normal, it would suggest that the development of Lyb-5- B lymphocytes require a thymic influence for normal maturation, whereas, Lyb-5+ B lymphocytes are relatively independent of such influences.
Comorbidities in patients with gout prior to and following diagnosis: case-control study
Authors: Chang-Fu Kuo, Matthew J Grainge, Christian Mallen, Weiya Zhang, Michael Doherty
Journal: Annals of the Rheumatic Diseases (2014)

To determine the burden of comorbidities in patients with gout at diagnosis and the risk of developing new comorbidities post diagnosis.There were 39 111 patients with incident gout and 39 111 matched controls identified from the UK Clinical Practice Research Data-link. The risk of comorbidity before (ORs) and after the diagnosis of gout (HRs) were estimated, adjusted for age, sex, diagnosis year, body mass index, smoking and alcohol consumption.Gout was associated with adjusted ORs (95% CIs) of 1.39 (1.34 to 1.45), 1.89 (1.76 to 2.03) and 2.51 (2.19 to 2.86) for the Charlson index of 1-2, 3-4 and ≥5, respectively. Cardiovascular and genitourinary diseases, in addition to hyperlipidaemia, hypothyroidism, anaemia, psoriasis, chronic pulmonary diseases, osteoarthritis and depression, were associated with a higher risk for gout. Gout was also associated with an adjusted HR (95% CI) of 1.41 (1.34 to 1.48) for having a Charlson index ≥1. Median time to first comorbidity was 43 months in cases and 111 months in controls. Risks for incident comorbidity were higher in cardiovascular, genitourinary, metabolic/endocrine and musculoskeletal diseases, in addition to liver diseases, hemiplegia, depression, anaemia and psoriasis in patients with gout. After additionally adjusting for all comorbidities at diagnosis, gout was associated with a HR (95% CI) for all-cause mortality of 1.13 (1.08 to 1.18; p<0.001).The majority of patients with gout have worse pre-existing health status at diagnosis and the risk of incident comorbidity continues to rise following diagnosis. The range of associated comorbidities is broader than previously recognised and merits further evaluation.
Graduate Medical Education in the United States
Authors: Beverley Davies Rowley
Journal: JAMA (1990)

This annual report on graduate medical education in the United States for the 1989-1990 academic year contains data on the number of programs accredited by the Accreditation Council for Graduate Medical Education (ACGME), by specialty and by region, and provides information on some characteristics of the programs and the persons in these programs. This year for the first time data on graduate medical education were gathered by means of an electronic data collection system. This major change in the data collection system resulted in a response rate lower than that in recent years. While actual response figures are reported herein, many tables include an extra column that provides a statistical projection for the expected number of residents. In view of the lower response rate, the reader is advised to interpret the data in this report with caution. In 1989, the ACGME began to accredit, through the Residency Review Committees, programs
The oral multitarget tumour growth inhibitor, ZK 304709, inhibits growth of pancreatic neuroendocrine tumours in an orthotopic mouse model
Authors: A Scholz, K Wagner, M Welzel, F Remlinger, B Wiedenmann, G Siemeister, S Rosewicz, K M Detjen
Journal: Gut (2008)

<h3>Background and aims:</h3> Current systemic therapies for neuroendocrine tumours (NETs) do not provide sufficient control of tumour growth. However, efficient evaluation of novel drugs is hindered by the lack of a suitable preclinical animal model. Here an orthotopic mouse model of pancreatic NET is established and used to study the action of ZK 304709, a first in class, oral multitarget tumour growth inhibitor. ZK 304709 is an inhibitor of cyclin-dependent kinases (Cdks) 1, 2, 4, 7 and 9, vascular endothelial growth factor receptor-type kinases (VEGF-RTKs) 1–3 and platelet-derived growth factor receptor-type kinase β (PDGF-RTKß). <h3>Methods:</h3> BON and QGP-1 human NET cells were used to study proliferation, survival and cell cycle distribution in vitro. For induction of orthotopic NETs, BON cells were injected into the pancreas of NMRI<sup>nu/nu</sup> mice. Primary tumour growth and metastatic spread were recorded after 9 weeks, and apoptosis, microvessel density and lymphatic vessel density were determined. <h3>Results:</h3> ZK 304709 dose-dependently suppressed proliferation and colony formation of NET cells. Direct effects on NET cells were consistent with Cdk inhibition and involved G<sub>2</sub> cell cycle arrest and apoptosis induction, which was associated with reduced expression of MCL1 (myeloid cell leukaemia sequence 1), survivin and hypoxia-inducible factor 1α (HIF1α). Apoptosis similarly occurred in vivo in ZK 304709-treated orthotopic BON tumours, resulting in a 80% reduction of primary tumour growth. In contrast, treatment with lanreotide or 5-fluorouracil and streptozotocin failed to inhibit tumour gowth. ZK 304709 also reduced tumour microvessel density, implicating antiangiogenic mechanisms. <h3>Conclusion:</h3> BON orthotopic tumours provide an informative model for preclinical drug evaluation in NETs. In this model, ZK 304709 achieved efficacious tumour growth control via induction of apoptosis and inhibition of tumour-induced angiogenesis.
A 10-year prospective surveillance of Mycobacterium tuberculosis drug resistance in France 1995 2004
Authors: P. M. Khuê, C. Truffot-Pernot, J. Texier-Maugein, V. Jarlier, J. Robert
Journal: European Respiratory Journal (2007)

Drug resistance surveillance and trend monitoring resistance rates bring some insights into tuberculosis (TB) control. The current study reports the characteristics of TB and drug resistance during a 10-yr prospective surveillance of culture-positive TB in France. Data for the current study was collected from 1995–2004 via a sentinel network of laboratories from university hospitals that complied with the international recommendations for the surveillance of drug resistance. Susceptibility test results were performed in each individual laboratory. Data on 13,283 patients were collected during the 10-yr period, 49% of whom had been born in France, 10% were HIV co-infected and 8% had previously been treated. As expected, previously treated and HIV co-infected patients were more likely to harbour resistant strains, especially rifampicin (RMP)-resistant strains. Among new patients, the mean resistance rate to at least one drug was 8.8%, and there was an upward trend in resistance to isoniazid and RMP (0.8–1%) related to the increase in the proportion of patients who had been born outside of France (38–53%). Among previously treated patients, the mean resistance rate to one drug was 20.6% and there was no significant time trend in resistance rates. The sentinel network provided valuable data on trends regarding the characteristics of tuberculosis and on drug resistance rates and reinforced the interest of analysing data by country of birth and history of treatment.
Prevailing publishing system is irrevocably broken
Authors: Gavin Yamey, Andy Gass
Journal: BMJ (2005)

Secondary prevention of heart disease with statins Groups were as different as chalk and cheeseEditor-Wei et al say that the results of their observational study of treatment with statins in routine clinical practice in Tayside are consistent with, and similar to, those reported in clinical trials. 1 This conclusion is hardly justified.A cohort of patients, defined by a discharge diagnosis of myocardial infarction between January 1993 and December 2001, was studied to compare the outcomes in those treated with statins and those not receiving these drugs.The data clearly show that the two groups differed substantially in terms of age, sex, comorbidity, and other cardiovascular drug treatment-all of these factors were biased in favour of a poorer outcome in patients not given statins.Furthermore, the two groups belonged to different time periods, most of the untreated patients to the earlier part and most of those given statins to the later part of the study.Given the changes between 1993 and 2001-including, for example, those related to the management of acute myocardial infarction and the criteria for diagnosis-it is only to be expected that the untreated group would have a higher risk of subsequent cardiovascular events.Multivariate analysis was reported as showing that statins reduced all cause mortality by 31% and the composite end point of myocardial infarction plus cardiovascular mortality by 18%.These results should be greeted with scepticism.Firstly, many trials of statins have failed to show any reduction whatsoever in all cause mortality. [2]][4][5] Secondly, as observed in other studies, any reduction in all cause mortality would be expected to be much less than that for composite cardiovascular end points. 2 4 5 The two groups in this study were as different as chalk and cheese.It should come as no surprise, therefore, that the results were anomalous.In such circumstances, no amount of statistical trickery could be expected to furnish anything of value.
Presentation of a self-peptide for in vivo tolerance induction of CD4+ T cells is governed by a processing factor that maps to the class II region of the major histocompatibility complex locus.
Authors: E V Fedoseyeva, R C Tam, P L Orr, M R Garovoy, G Benichou
Journal: The Journal of Experimental Medicine (1995)

Self-proteins are regularly processed for presentation to autoreactive T cells in association with both class I and class II major histocompatibility complex (MHC) molecules. The presentation of self-peptides plays a crucial role in the acquisition of T cell repertoire during thymic selection. We previously reported that the self-MHC class I peptide Ld 61-80 was immunogenic in syngeneic B10.A mice (H-2a). We showed that despite its high affinity for self-MHC class II molecules, Ld 61-80 peptide failed to induce elimination of autoreactive CD4+ T cells, presumably due to incomplete processing and presentation in the B10.A's developing thymus (cryptic-self peptide). In this report, we showed that the cryptic phenotype was not an intrinsic property of the self-peptide Ld 61-80 since it was found to be naturally presented and subsequently tolerogenic in BALB/c mice (H-2d) (dominant self-peptide). In addition, the self-peptide Ld 61-80 was found to be immunogenic in different H-2a mice while it was invariably tolerogenic in H-2d mice regardless of their background genes. We observed that Ld 61-80 bound equally well to H-2d and H-2k MHC class II molecules. Also, no correlation was found between the quantity of self-Ld protein and the tolerogenicity of Ld 61-80. Surprisingly, Ld 61-80 was not naturally presented in (H-2d x H-2a) F1 mice, indicating that the H-2a MHC locus contained a gene that impaired the presentation of the self-peptide. Analyses of T cell responses to the self-peptide in several H-2 recombinant mice revealed that the presentation of Ld 61-80 was controlled by genes that mapped to a 170-kb portion of the MHC class II region. This study shows that (a) endogenously processed self-peptides presented by MHC class II molecules are involved in shaping the CD4+ T cell repertoire in the thymus; (b) The selection of self-peptides for presentation by MHC class II molecules to nascent autoreactive T cells is influenced by nonstructural MHC genes that map to a 170-kb portion of the MHC class II region; and (c) the MHC locus of H-2a mice encodes factors that prevent or abrogate the presentation by MHC class II molecules of the self-peptide Ld 61-80. These findings may have important implications for understanding the molecular mechanisms involved in T cell repertoire acquisition and self-tolerance induction.
The Relationship of Urinary Metabolites of Carbaryl/Naphthalene and Chlorpyrifos with Human Semen Quality
Authors: John D. Meeker, Louise Ryan, Dana B. Barr, Robert F. Herrick, Deborah H. Bennett, Roberto Bravo, Russ Hauser
Journal: Environmental Health Perspectives (2004)

Most of the general population is exposed to carbaryl and other contemporary-use insecticides at low levels. Studies of laboratory animals, in addition to limited human data, show an association between carbaryl exposure and decreased semen quality. In the present study we explored whether environmental exposures to 1-naphthol (1N), a metabolite of carbaryl and naphthalene, and 3,5,6-trichloro-2-pyridinol (TCPY), a metabolite of chlorpyrifos and chlorpyrifos-methyl, are associated with decreased semen quality in humans. Subjects (n=272) were recruited through a Massachusetts infertility clinic. Individual exposures were measured as spot urinary concentrations of 1N and TCPY adjusted using specific gravity. Semen quality was assessed as sperm concentration, percent motile sperm, and percent sperm with normal morphology, along with sperm motion parameters (straight-line velocity, curvilinear velocity, and linearity). Median TCPY and 1N concentrations were 3.22 and 3.19microg/L, respectively. For increasing 1N tertiles, adjusted odds ratios (ORs) were significantly elevated for below-reference sperm concentration (OR for low, medium, and high tertiles = 1.0, 4.2, 4.2, respectively; p-value for trend =0.01) and percent motile sperm (1.0, 2.5, 2.4; p-value for trend = 0.01). The sperm motion parameter most strongly associated with 1N was straight-line velocity. There were suggestive, borderline-significant associations for TCPY with sperm concentration and motility, whereas sperm morphology was weakly and nonsignificantly associated with both TCPY and 1N. The observed associations between altered semen quality and 1N are consistent with previous studies of carbaryl exposure, although suggestive associations with TCPY are difficult to interpret because human and animal data are currently limited.
Hepatocellular Carcinoma and Other Liver Disease Among Greenlanders Chronically Infected with Hepatitis B Virus: A Population-Based Study
Authors: M. L. Borresen, A. Koch, R. J. Biggar, M. Andersson, J. Wohlfahrt, K. Ladefoged, M. Melbye
Journal: JNCI Journal of the National Cancer Institute (2011)

In Greenland, the prevalence of hepatitis B surface antigen carriers, reflecting chronic hepatitis B virus (HBV) infection, is 5%-10%. However, the incidence of cirrhosis and hepatocellular carcinoma in this population has been reported to be low. We investigated this discrepancy in a large population-based cohort study.In total, 8879 Greenlanders (16% of the population) were recruited for population-based surveys performed from May 5 to July 7, 1987, and from November 1 to November 21, 1998, with follow-up until March 31, 2010. HBV status was based on serological testing, supplemented by data from all available HBV registries in Greenland to determine changes in HBV status over time. Information on morbidity and mortality was obtained from the Patient Discharge Registry, the Cancer Registry, and the Central Registration System. Sex, age, ethnicity, and period-adjusted incidence rate ratios (IRRs) were estimated using Poisson regression. World standardized rates were derived from these and World Health Organization data.The 650 chronically HBV-infected persons had higher rates of hepatocellular carcinoma (adjusted IRR = 8.70; 95% CI = 2.06 to 36.7), liver disease (adjusted IRR = 5.73, 95% CI = 3.52 to 9.34), and all-cause mortality (adjusted IRR = 1.47; 95% CI = 1.21 to 1.79) than the 5160 HBV-negative persons. However, the world standardized incidence rates of hepatocellular carcinoma (38.5 cancers per 100 000 person-years) and cirrhosis (24 cases per 100 000 person-years) among chronically HBV-infected persons were low compared with results from population-based studies from countries with low, intermediate, and high rates of endemic HBV infection.The relatively low incidence of hepatocellular carcinoma and other HBV-related morbidity among chronic HBV-infected persons in Greenland suggest a more benign course of HBV among the Greenlandic Inuit than in populations in other parts of the world.
Dissemination of Evidence-based Practice Center Reports
Authors: David B. Matchar
Journal: Annals of Internal Medicine (2005)

The Evidence-based Practice Center (EPC) program within the Agency for Healthcare Research and Quality (AHRQ) provides detailed evidence reports for partner organizations that they can translate into activities that improve patient care. A review of these dissemination activities provides a rich opportunity to understand how to create more successful linkages between best evidence and best practice. On the basis of interviews with EPC directors, AHRQ staff, and representatives of public and private users of EPC reports, we summarize the variety of efforts to disseminate the work of the EPCs. We also identify a case example of a successful dissemination of an EPC report. Experience to date reinforces the importance of creating close ties between researchers and the policymakers, clinicians, and other decision makers who use EPC evidence reports; developing a conceptual framework to guide the process; and establishing the resource foundation for the entire effort.
Transcriptional regulation of the murine promoter by cardiac factors Nkx2-5, GATA4 and Tbx5
Authors: V LINHARES, N ALMEIDA, D MENEZES, D ELLIOTT, D LAI, E BEYER, A CAMPOSDECARVALHO, M COSTA
Journal: Cardiovascular Research (2004)

Connexin40 (Cx40) is a gap junction protein expressed specifically in developing and mature atrial myocytes and cells of the conduction system. In this report, we identify cis-acting elements within the mouse Cx40 promoter and unravel part of the complex pathways involved in the cardiac expression of this gene.To identify the factors involved in the cardiac expression of Cx40, we used transient transfections in mammalian cells coupled with electrophoretic mobility shift assays (EMSA) and RT-PCR.Within the promoter region, we identified the minimal elements required for transcriptional activity within 150 base pairs (bp) upstream of the transcriptional start site. Several putative regulatory sites for transcription factors were predicted within this region by computer analysis, and we demonstrated that the nuclear factors Sp1, Nkx2-5, GATA4 and Tbx5 could interact specifically with elements present in the minimal promoter region of the Cx40. Furthermore, co-transfection experiments showed the ability of Nkx2-5 and GATA4 to transactivate the minimal Cx40 promoter while Tbx5 repressed Nkx2-5/GATA4-mediated activation. Mutagenesis of the Nkx2-5 core site in the Cx40 promoter led to significantly decreased activity in rat smooth muscle cell line A7r5. Consistent with this, mouse embryos lacking Nkx2-5 showed a marked decrease in Cx40 expression.In this work, we cloned the promoter region of the Cx40 and demonstrated that the core promoter was modulated by cardiac transcriptional factors Nkx2-5, Tbx5 and GATA4 acting together with ubiquitous Sp1.