bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-Term Benefits and Limitations of Combined Antianginal Drug Therapy in Elderly Patients with Symptomatic Chronic Coronary Artery Disease
Authors: Bonetti Piero O. , Kaiser Christoph , Zellweger Michael J. , Grize Leticia , Erne Paul , Schoenenberger Ronald A. , Pfisterer Matthias E. ,   TIME Investigators
Published: March 2006

Background: Chronic angina is a common and disabling disorder in the elderly. Combined antianginal drug treatment represents the mainstay of therapy in this population. However, there is a paucity of data regarding the effect of this strategy on long-term outcome in the elderly. Methods: To assess the long-term effect of combined antianginal drug therapy in elderly individuals, we performed a long-term follow-up analysis of all 148 patients of the Trial of Invasive versus Medical therapy in Elderly (TIME) patients with chronic symptomatic coronary-artery disease assigned to an optimized medical therapy strategy. Angina severity, measures of quality of life (QOL), and survival were assessed after a median of 3.7 (0.1-6.9) years. Results: At baseline, patients were 79.8 ± 3.5 years old with Canadian Cardiovascular Society (CCS) class angina 3.0 ± 0.7 despite the use of 2.4 ± 0.6 antianginal drugs. Although antianginal drugs were increased to 2.8 ± 0.9 ( P < .01), 63 (43%) patients needed revascularization for refractory symptoms during the first year of observation (REVASC). At baseline, REVASC patients had more frequently CCS class 4 angina (37% vs 20%, P < 0.05) but reported less prior heart failure (5% vs 20%, P < 0.01), fewer prior cerebral events (3% vs 13%, P < .05) and a lower rate of two or more comorbidities (10% vs 33%, P < .01) than patients on continued drug therapy (DRUG). At long-term follow-up, angina severity was still higher in DRUG compared to REVASC patients (CCS class, 1.8 ± 1.6 vs 1.0 ± 1.4, P < .05) despite more antianginal drugs (2.1 ± 1.1 vs 1.5 ± 1.0, P < .01), whereas measures of QOL had improved similarly in both groups. In addition, long-term mortality was significantly higher in DRUG than in REVASC patients (38% vs 13%, P < .01). Conclusion: Combined antianginal drug therapy successfully relieved symptoms in most elderly patients with chronic angina but failed to do so in 43%. Patients who needed revascularization for refractory symptoms reported less angina, despite lower drug use during long-term follow-up and had a better long-term survival. Thus, the widely used strategy to increase antianginal drug therapy in elderly patients instead of evaluating them for revascularization should be reconsidered.
Simple Clinical Criteria to Determine the Prognosis of Heart Failure
Authors: Heywood J. Thomas , Elatre Wafaa , Pai Ramdas G. , Fabbri Sharon , Huiskes Bonnie 
Published: March 2006

Objective: To determine whether easily obtained clinical parameters serve as predictors of survival in patients with congestive heart failure. Several scoring systems to predict heart failure survival have been developed; however, many of these deal principally with transplant recipients or do not account for a patient’s response to therapy. Methods: A total of 680 patients with an ejection fraction of less than 40% were included in the analysis. Baseline assessments were performed and treatment regimens were identified; patients were then followed for up to 5 years. Univariate and multivariate Cox regression models were used to determine clinically important predictors of survival. Kaplan-Meier survival functions for patients with and without the prognostic variable were constructed and mortality was calculated at 1 year and 5 years. Results: Ejection fraction improvement at 6 months, diabetes mellitus, age, serum creatinine, and blood urea nitrogen (BUN) were significant predictors for survival in the univariate model. Ejection fraction improvement, age, and BUN were significant predictors in the multivariate model. These findings were used to construct a model for predicting patient mortality. Improved ejection fraction (>15 ejection fraction units) gave a 1-year mortality of 2% and a 5-year mortality of 11%. Mortality rates according to patient age and BUN levels were also calculated. Conclusion: Ejection fraction improvement was the most important predictor for survival in patients with systolic dysfunction; monitoring ejection fraction changes through repeat echocardiograms has important prognostic value. In patients without ejection fraction improvement, age and renal function are important survival determinants.
Beneficial Cardiovascular Actions of Eplerenone in the Spontaneously Hypertensive Rat
Authors: Susic Dinko , Varagic Jasmina , Ahn Jwari , Matavelli Luis C. , Frohlich Edward D. 
Published: March 2006

Background: Aldosterone has been implicated as a potential mediator of cardiac and vascular damage in a variety of disorders. This study examined the role of aldosterone and its interplay with the renin-angiotensin system in the pathogenesis of hypertension. To this end, the effects of the aldosterone antagonist eplerenone and the angiotensin converting enzyme inhibitor lisinopril on cardiovascular mass, myocardial collagen, and coronary circulation were examined in spontaneously hypertensive rats.Methods: Male, 22-week-old rats were randomly divided into 4 groups (12 in each). The control group received no treatment, the second group was given eplerenone (100 mg/kg/day), the third received lisinopril (3 mg/kg/day), and the fourth was given eplerenone and lisinopril. After 12 weeks of respective treatments, systemic and regional hemodynamics and cardiovascular mass indexes were measured in conscious instrumented rats.Results: Eplerenone decreased arterial pressure but did not affect left ventricular mass or hydroxyproline concentration (an estimate of collagen). It did, however, reduce minimal coronary vascular resistance and increased coronary flow reserve. Lisinopril decreased arterial pressure and ventricular mass but did not affect regional hemodynamics. The combination therapy produced synergistic effects.Conclusion: Aldosterone antagonism improved coronary and systemic hemodynamics in adult spontaneously hypertensive rats but did not affect cardiovascular mass indexes. The finding that lisinopril and eplerenone decreased arterial pressure to the same extent but had different cardiovascular effects suggested that these effects might be pressure independent.
Mandate for Creation of a National Peripheral Arterial Disease Public Awareness Program: An Opportunity to Improve Cardiovascular Health
Authors: Hirsch Alan T. , Gloviczki Peter , Drooz Alain , Lovell Marge , Creager Mark A. 
Published: March 2006

Background:There has been increasing recognition of the detrimental effect of peripheral arterial disease (PAD) on the health of Americans, and yet there is no common national program of public PAD education designed to diminish this effect. Format:To heighten awareness of this problem, a 2-day PAD Public Education Strategy Meeting was recently attended by representatives of 17 professional societies and public health associations whose missions support the prevention, diagnosis, treatment, and rehabilitation of vascular diseases. This Public Education Strategy Meeting was intended to provide the rationale and structure to create a national PAD public awareness campaign to diminish the health effect of PAD and to improve cardiovascular outcomes in the United States. This document (1) provides the rationale for creation of a national PAD public education program; (2) reviews the development and success of national hypertension, hypercholesterolemia, and Women's Heart Health public education programs as models of educational efficacy; (3) elucidates how the work of many vascular professionals has led to a national consensus for creation of a national PAD public educational program; (4) provides an overview of the National Heart, Lung, and Blood Institute PAD education meeting; and (5) outlines the “next steps” required to accomplish these goals. Outcome:This meeting achieved consensus that we share responsibility for developing accurate, unified messages to promote PAD awareness and improved care. Participants agreed that the creation of such messages should be linked to plans to disseminate them to all Americans at risk. A consensus was reached that such messages, when commonly created and offered to the public, are most likely to achieve the rewards in better health that all Americans deserve. The Vascular Disease Foundation, a not-for-profit foundation whose mission includes public education about the prevention, diagnosis, treatment, and rehabilitation of PAD, will devote its resources to guide a new coalition in this process and to create a national PAD awareness campaign. During 2003 and 2004, the coalition will create the organizational underpinnings and time line for what will undoubtedly be a multiyear effort. Conclusion:Participants of the Public Education Strategy Meeting agreed to create a broad coalition to develop a National PAD Public Awareness Program, with the objectives to develop and disseminate public education messages on PAD. A successful national PAD education program will contribute to creation of a broader mandate to improve global cardiovascular health in the United States.
Design and Rationale of the PREVENT III Clinical Trial: Edifoligide for the Prevention of Infrainguinal Vein Graft Failure
Authors: Conte Michael S. , Lorenz Todd J. , Bandyk Dennis F. , Clowes Alexander W. , Moneta Gregory L. , Seely B. Lynn 
Published: March 2006

Surgical bypass of peripheral arterial occlusive disease with autologous vein grafts provides an effective means of restoring blood flow to the lower extremity, and has been a standard therapy for patients with disabling claudication or critical limb ischemia (CLI). However, failure rates may run as high as 50% within 5 years. These graft failures occur as a result of neointimal hyperplasia, a ubiquitous biologic response of blood vessel walls to injury, which is characterized by the migration and proliferation of smooth muscle cells (SMC). The E2F family of transcription factors regulates the expression of genes controlling SMC proliferation. Edifoligide (E2F Decoy) is a novel therapy that inhibits E2F function, thus attenuating neointimal hyperplasia. Its use in conjunction with a patented drug delivery pressurization chamber is under investigation. Using this system, edifoligide is administered to vein grafts in a single, ex vivo treatment following vein harvest and before implantation, resulting in minimal systemic drug exposure and excellent patient compliance. This Phase 3, randomized, double-blind, multicenter clinical trial is designed to evaluate the safety and efficacy of edifoligide in a population of approximately 1400 patients with CLI undergoing infrainguinal bypass for peripheral arterial disease (PAD). The primary outcome measure will be the time to occurrence of non-technical graft failure resulting in either graft revision or major amputation at 12 months after enrollment. A governing Clinical Events Classification committee (CEC) will adjudicate each graft failure to determine its etiology. The PREVENT III trial is the largest multicenter trial ever performed in patients receiving autologous vein bypass grafts for CLI. This landmark study will determine if edifoligide is safe and effective at preventing vein graft failure in patients undergoing lower extremity bypass, but it also provides a unique opportunity to observe current treatment practices in vascular surgery.
Identification of the nonreceptor tyrosine kinase MATK/CHK as an essential regulator of immune cells using Matk/CHK-deficient mice
Authors: Lee Byeong-Chel , Avraham Shalom , Imamoto Akira , Avraham Hava Karsenty 
Published: March 2006

AbstractMatk/CHK knockout mice were reported to show no apparent phenotypic abnormalities. This was thought to be due to the homologous kinase Csk that compensates for Matk/CHK. Here, we present the first evidence that the nonreceptor tyrosine kinase, Matk/CHK, is an important modulator of immune cell signaling. We found that the frequency of primitive hematopoietic cells, the side population c-kit+ Lin– Sca-1+ (SPKLS) cells, in Matk/CHK–/– mice was increased 2.2-fold compared with the control mice. Moreover, Matk/CHK deficiency led to significantly higher pre–B cell colony formation following IL-7 stimulation. Interestingly, when mice received the in vivo antigen challenge of TNP-ovalbumin followed by restimulation, the Matk/CHK–/– lymph node and spleen cells produced significantly lower IFN-γ levels compared with the respective wild-type cells. Our study indicates that Matk/CHK is not functionally redundant with Csk, and that this tyrosine kinase plays an important role as a regulator of immunologic responses.
Diagnostic application of flow cytometric characteristics of CD34+ cells in low-grade myelodysplastic syndromes
Authors: Ogata Kiyoyuki , Kishikawa Yoshifumi , Satoh Chikako , Tamura Hideto , Dan Kazuo , Hayashi Akio 
Published: March 2006

AbstractThe diagnosis of myelodysplastic syndromes (MDS) without an increase in blasts and ringed sideroblasts (low-grade MDS without ringed sideroblasts [LGw/oRS]) may be problematic because dysplastic features are not specific to MDS and approximately 50% of patients with LGw/oRS lack chromosomal aberrations. Here, we report the usefulness of flow cytometric characteristics of CD34+ cells for LGw/oRS diagnosis. Bone marrow cells from LGw/oRS patients and controls (eg, cytopenic individuals without MDS) were analyzed using 4-color flow cytometry (FCM). We objectively determined reference ranges of 13 parameters related to CD34+ cells with data from controls. In LGw/oRS patients, various abnormalities of CD34+ cells—eg, decrease in CD34+ B-cell precursors, aberrant expression or overexpression of various antigens on CD34+ myeloblasts—were observed. We constructed a reproducible, flow cytometric scoring system for LGw/oRS diagnosis. High scores were observed in 16 of 27 LGw/oRS patients, regardless of the presence or absence of chromosomal aberrations, but not in any of the 90 controls. Among LGw/oRS patients with chromosomal aberrations, patients with trisomy 8 or del20(q) had low FCM scores (P = .002). As a result, most LGw/oRS patients were identified based on high FCM score, chromosomal aberration, or both.
Glucocorticoid-induced glucocorticoid-receptor expression and promoter usage is not linked to glucocorticoid resistance in childhood ALL
Authors: Tissing Wim J. E. , Meijerink Jules P. P. , Brinkhof Bas , Broekhuis Mathilde J. C. , Menezes Renee X. , den Boer Monique L. , Pieters Rob 
Published: March 2006

AbstractGlucocorticoid (GC) resistance is an adverse prognostic factor in childhood acute lymphoblastic leukemia (ALL), but little is known about causes of GC resistance. Up-regulation of the glucocorticoid receptor (GR) has been suggested as an essential step to the induction of apoptosis in leukemic cells. In this study we investigated whether baseline mRNA expression levels of the 5 different GR promoter transcripts (1A1, 1A2, 1A3, 1B, and 1C) or differences in the degree of regulation of the GR or GR promoter transcripts upon GC exposure are related to GC resistance. Therefore, mRNA levels of the 5 GR promoter transcripts and of the GR were measured by quantitative real-time reverse transcriptase–polymerase chain reaction (RT-PCR; Taqman) technology in primary ALL cells prior to and after 3, 8, and 24 hours of prednisolone exposure. GR expression is induced upon GC exposure in primary ALL patient samples, which is opposite to what is found in tissues in which GCs do not induce apoptosis. GC resistance in childhood ALL cannot be attributed to an inability of resistant cells to up-regulate the expression of the GR upon GC exposure, nor to differences in GR promoter usage (at baseline and upon GC exposure).
Amelioration of experimental autoimmune uveoretinitis (EAU) with an inhibitor of nuclear factor-κB (NF-κB), pyrrolidine dithiocarbamate
Authors: Kitamei Hirokuni , Iwabuchi Kazuya , Namba Kenichi , Yoshida Kazuhiko , Yanagawa Yoshiki , Kitaichi Nobuyoshi , Kitamura Mizuki , Ohno Shigeaki , Onoé Kazunori 
Published: March 2006

Abstract
Experimental autoimmune uveoretinitis (EAU) is a T helper type 1 cell-mediated autoimmune disease, which serves as a model of human chronic uveitis. In this model, cells of a monocyte/macrophage lineage and retinal antigen (Ag)-specific T cells infiltrate into the retina and cause inflammatory lesion, where proinflammatory cytokines and various stimuli activate a transcriptional factor, nuclear factor-κB (NF-κB), which modulates inflammation and enhances immune responses. In the present study, the therapeutic effect of administration of a NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), was examined in a murine EAU model. It was shown that PDTC ameliorated the clinical symptoms of EAU mice and significantly reduced the histopathological score compared with those in untreated mice. mRNA expressions of tumor necrosis factor α and interleukin-1β were suppressed in eyes of PDTC-treated EAU mice. However, when T cells from PDTC-treated EAU mice, Ag-presenting cells (APC), and the retinal Ag peptides were cocultured, these T cells showed the same level of proliferation as those from control mice. Furthermore, addition of PDTC in the culture of T cells from EAU mice, Ag, and APC completely abrogated the T cell-proliferative response and cytokine production. Pretreatment of Ag-primed T cells or APC with PDTC in vitro also reduced these responses. These results indicate that the inhibitory effect of PDTC is attributed mainly to the suppression of effector-phase responses including inflammation but not to the inhibition of T cell priming. Regulation of NF-κB pathway in the lesion could be a novel target for the successful control of uveoretinitis.
On the production of TNF-related apoptosis-inducing ligand (TRAIL/Apo-2L) by human neutrophils
Authors: Cassatella Marco A 
Published: March 2006

Abstract
Contrary to their traditional characterization as terminally differentiated effectors of inflammation, neutrophils are remarkably versatile cells. Indeed, their capacity to change phenotype under specific circumstances, their active involvement in the regulation and resolution of inflammation, their response to a wide variety of cytokines and chemotactic molecules, and their regulatory role in angiogenesis and tumor fate have made it clear that they represent far more than “short-lived cells devoid of transcriptional activities, that only release preformed mediators and kill pathogens”. The multiple and amazing functional capacities of this cell type are also illustrated by the fact that the neutrophil may function as an important source of cytokines, at levels comparable with and in some cases, higher than those made by other leukocytes. To date, the families of cytokines, which in vitro or in vivo have been convincingly reported as being produced by neutrophils, include proinflammatory/anti-inflammatory cytokines, immunoregulatory cytokines, chemokines, angiogenic/fibrogenic factors, and tumor necrosis factor (TNF) superfamily members. The latter molecules are multifaceted cytokines whose integrated actions not only influence the development, homeostasis, and adaptive responses of many cells and tissue types but are also implicated in the antitumoral response. The recent findings that neutrophils produce in a finely regulated manner a TNF superfamily member involved in tumor cell killing and autoimmunity, namely TNF-related apoptosis-inducing ligand, open an additional perspective to exploit neutrophils for novel roles in anticancer responses and modulation of autoimmune diseases.
Naltrexone inhibits alcohol-mediated enhancement of HIV infection of T lymphocytes
Authors: Wang Xu , Douglas Steven D , Peng Jin-Song , Metzger David S , O’Brien Charles P , Zhang Ting , Ho Wen-Zhe 
Published: March 2006

Abstract
Acute and chronic alcohol abuse impairs various functions of the immune system and thus, has been implicated as a cofactor in the immunopathogenesis of human immunodeficiency virus (HIV) disease progression. We determined whether naltrexone, an opioid receptor antagonist widely used in the treatment of alcoholism, inhibits alcohol-mediated enhancement of HIV infection of T cells. Alcohol enhanced HIV infection of peripheral blood lymphocytes (PBL) and a human lymphoid cell line (CEMX174). Alcohol increased HIV X4 envelope (Env), not murine leukemia virus Env-pseudotyped infection of CEMX174 cells. Naltrexone antagonized the enhancing effect of alcohol on HIV infection of PBL and CEMX174 cells. The specific μ-opioid receptor antagonist, Cys2, Tyr3, Arg5, Pen7 (CTAP) amide, also blocked the enhancing effect of alcohol on HIV infection. Investigation of the underlying mechanism for the alcohol action showed that alcohol significantly increased endogenous β-endorphin production and induced μ-opioid receptor mRNA expression in PBL and CEMX174 cells. The role of β-endorphin in alcohol-mediated enhancement of HIV infection was indicated by the observations that naltrexone and CTAP antagonized ether alcohol- or exogenous β-endorphin-mediated enhancement of HIV infection. These findings suggest a biological mechanism for the potential therapeutic benefit of naltrexone in treating HIV-infected alcoholics.
Patient preference randomised controlled trials in mental health research
Authors: Howard Louise , Thornicroft Graham 
Published: March 2006

SummaryThe relationship between psychiatric patients' preferences for different treatments and the outcome of interventions is unclear, as the few relevant trials have tended to be underpowered. Strong patient preferences result in patients refusing to enter a trial. This leads to bias and limits generalisability, and the patient preference randomised controlled trial (RCT) design has been proposed as an alternative. Limitations and advantages of patient preference RCTs are discussed.
Duloxetine in the prevention of relapse of major depressive disorder
Authors: Perahia David G. , Gilaberte Inmaculada , Wang Fujun , Wiltse Curtis G. , Huckins Stacy A. , Clemens Jeffrey W. , Montgomery Stuart A. , Montejo Angel L. , Detke Michael J. 
Published: March 2006

BackgroundRelapse rates may be as high as 50% in people with major depressive disorder (MDD) previously treated to remission.AimsDuloxetine, an inhibitor of serotonin and noradrenaline reuptake that is licensed in Europe, the USA and elsewhere for the treatment of depressive episodes, was evaluated with regard to its efficacy, safety and tolerability in the prevention of relapse of MDD.MethodAdult out-patients with MDD received duloxetine (60 mg daily) for 12 weeks (n=533). Patients who responded to the drug were then randomised to duloxetine (60 mgdaily) (n=136) or placebo (n=142) for 26 weeks. The primary measure of efficacy was time to relapse.ResultsPatients who received duloxetine (60 mg daily) experienced significantly longer times to relapse of MDD, and better efficacy global well-being, and quality-of-life outcomes compared with patients who received placebo. It should be noted that adverse events which occur in discontinuation may mimic some signs of depressive relapse, and were not specifically elicited in this study.ConclusionsDuloxetine (60 mg daily) is effective in the prevention of relapse of MDD during continuation treatment.