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Background. Granulocyte-colony-stimulating factor (G-CSF) has been investigated in trials aiming to promote recovery of myocardial function after myocardial infarction. Long-term safety-data have never been reported. A few studies indicated an increased risk of in-stent re-stenosis. We aimed to investigate clinical events 5 years after inclusion into a randomized trial of G-CSF versus placebo. Methods. Seventy-eight patients were randomized, from 2003-2005, to G-CSF or placebo after myocardial infarction. Four patients withdrew consent prior to study treatment and were excluded leaving 36 and 38 in the placebo- and G-CSF groups. Information about all hospital admittances of included patients until 2010 was extracted from a national register. The only censoring event was immigration. The events were combined into four prespecified endpoints: Time to (1) first hospital admittance (all cause), (2) first cardiovascular-related hospital admittance, (3) first major cardiovascular event, and (4) death. Results. One patient (1%) was lost to follow-up. Four patients (4%) died in the follow-up period, three in the G-CSF group and one in the placebo group ( p = 0.4). Hazard ratio for all cause hospital admittance was 0.7 (95% CI 0.38-1.29). The incidence of both new myocardial infarction ( p = 1.0) and revascularization procedures ( p = 0.4) were similar in the two groups. Survival analyses showed no differences in the occurrence of any of the four prespecified composite endpoints between the two groups ( p = 0.6; 0.5; 0.8; 0.3). Conclusions. We found no indication of increased risk of adverse events up to 5 years after G-CSF treatment. These results support the continued investigation of G-CSF for cardiac therapy. [ABSTRACT FROM AUTHOR]

Objective: To test the hypothesis that mutations in the vascular endothelial growth factor (VEGF) gene are associated with plasma concentration of VEGF and subsequently the ability to influence coronary collateral arteries in patients with coronary heart disease (CHD). Methods: Blood samples from patients with chronic ischemic heart disease (n=53) and acute coronary syndrome (n=61) were analysed. Coronary collaterals were scored from diagnostic biplane coronary angiograms. Results: The plasma concentration of VEGF was increased in patients with acute compared to chronic CHD (p=0.01). The genotype frequencies differed significantly from Hardy-Weinberg equilibrium in three of 15 examined loci. Four new mutations in addition to the already described were identified. The VEGF haplotype did not seem to predict plasma VEGF concentration (p=0.5). There was an association between the genotype in locus VEGF-1154 and coronary collateral size (p=0.03) and a significant association between the VEGF plasma concentration and the collateral size (p=0.03). Conclusion: VEGF plasma concentration seems related to coronary collateral function in patients with CHD. The results did not support the hypothesis that polymorphisms in the untranslated region of the VEGF gene were associated with the concentration of circulating VEGF. Increased understanding of VEGF in the regulation of myocardial collateral flow may lead to new therapies in CHD. [ABSTRACT FROM AUTHOR]

Objectives. Angiographic late lumen loss measured 6 to 9 month after bare metal stent implantation in the coronary arteries is a validated restenosis parameter. Design. We performed a second angiographic follow-up after 4 years in event free survivors from the DANSTENT trial cohort. Results. Quantitative comparison of paired coronary angiograms at 6 months and 4 years showed a reduction of late loss from 0.68±0.52mm to 0.42 (±0.52) (mean difference 0.26 (0.17 to 0.36), p<0.0001). Minimal instent lumen diameter had increased from 2.39±0.62mm to 2.64±0.56mm (mean difference: -0.24mm, 95% confidence interval: -0.34mm to -0.14mm, p<0.0001). Instent diameter stenosis decreased from 24.8±14.2% to 18.6±9.3% (mean difference 6.16%, 95% confidence interval: 2.82 to 9.48%, p=0.0006). This observed spontaneous decrease of instent restenosis corresponds to a 19% increase of minimal cross-sectional vessel area and a 39% reduction of the binary restenosis rate over time. Conclusions. Instent late lumen loss in bare metal stents decreases spontaneously over time. Maturation of early hyperplastic tissue reaction after stent implantation with subsequent thinning of fibrotic tissue might explain this phenomenon. [ABSTRACT FROM AUTHOR]

Investigates the therapeutic angiogenesis of vascular growth factors in patients with ischemic coronary artery disease in Scandinavia. Prevention and treatment of atherosclerotic vascular heart disease; Causes of morbidity and mortality in industrialized countries; Methods for gene therapy.

Examines a number of "non-conclusive" verbs which will be subjected to a fairly close scrutiny with regard to their possible use in the progressive, and with regard to a possible "change of meaning" in this connection. Love's usage is predominantly women's language; Remember, like, understand, misunderstand; More.

Discusses the actual behavior of the verb 'used to' plus an infinitive in contemporary English. Trends in the use of the verb; Difficulty arising from the treatment of the verb as a full verb and as an anomalous verb in all relevant syntactical functions; Non-existence of a present tense form of the verb.

Discusses the semantic distinction between the phrases 'to amuse oneself' and 'to enjoy oneself.' Room in practice for some semantic overlapping of the two phrases; Indication that 'to amuse oneself' may sometimes come to express the same notion as 'to enjoy oneself'; Connection between the verbal phrase and the prepositional phrase.

Discusses syntactical and semantic peculiarities which attach to the use of the phrases in which 'charge' constitutes the crucial element. Active function of the phrase in the contemporary English language; Common synonymous construction of 'to have charge of'; Rarity of inchoative versions of '(to be) in charge of.'

Reports on the adherence of linguists to distinctions of reciprocal pronouns, each other and one another. Establishment of semantic distinctions; Reference of infinitive phrase to injunctions; Consideration for ingenuity in the reciprocal activity.

Comments on Frits Stuurman's article in the journal 'English Studies' about a distinction between the reciprocal pronouns 'each other' and 'one another.' Ways in which 'each other' expresses a chain relation; Argument that 'one another' expresses a true reciprocal relation; Rehabilitation of deductive approaches to the problem.

Examines the use of for + (pro)noun as an adjective complement. Examples of sentences that use the adjective complement; Prepositions used in prepositional phrases serving as adjective complements.

Background. YKL-40 is a glycoprotein secreted by macrophages and neutrophils in tissues with inflammation. Plasma YKL-40 is increased in patients with coronary artery disease (CAD) and associated with cardiovascular and all-cause mortality. Furthermore, plasma YKL-40 seems related to the number of diseased main vessels in patients with stable CAD. The aim was to further study the relation between YKL-40 and stenosis degree, stenosis type and actual ischemia in stable CAD patients. Methods. Plasma YKL-40 and hsCRP levels were determined from 206 consecutive patients with stable angina pectoris admitted for coronary angiography. Plasma YKL-40 in 245 healthy subjects was used for comparison. In addition to one to three vessel stenosis scores, two new scores for evaluating coronary angiographies were established for discriminating between focal and diffuse CAD and the extent of myocardial ischemia. Results. YKL-40 levels in CAD patients (median: 52 μg/L and quartiles: 37-85 μg/L) were significantly increased ( p < 0.001) compared to the healthy controls. In univariate analyses plasma YKL-40 was significantly associated with ischemic myocardium score, age, hypertension, peripheral vascular disease and serum creatinine levels. In multivariate analyses YKL-40 was related to hsCRP, peripheral artery disease, hypertension, and statin treatment. Conclusions. Plasma YKL-40 was increased in patients with CAD compared to controls. YKL-40 was related to the ischemic myocardium, but not to degree of CAD using different scoring systems. Therefore, YKL-40 is not related to the extent of CAD, but to some other pathophysiological mechanisms of importance for the prognosis. [ABSTRACT FROM AUTHOR]

Objectives. To investigate the mobilization of non-haematopoietic and haematopoietic cells from the bone marrow induced by intramyocardial VEGF gene therapy and G-CSF treatment alone or in combination in patients with chronic ischemic heart disease (IHD). Secondly, we tested the hypothesis that the quantity of circulating stem cells correlated with improvement in symptoms. Design. We treated I) 16 patients with intramyocardial placebo injections, II) 16 patients with intramyocardial VEGF-A165 gene injections, III) 13 patients with low dose G-CSF, and IV) 16 patients with intramyocardial VEGF-A165 gene followed by high dose G-CSF. Results. Circulating CD34+ cells and CD45 - CD34 - cells increased by G-CSF in a dose-dependent manner, but did not increase with VEGF gene therapy. The CD45 - /CD34- cells subgroups increased in both G-CSF treated groups. No association was found between the concentration of mobilized stem cells in the circulation and improvement in symptoms. Conclusions. G-CSF mobilized both haematopoietic and non-haematopoietic cells from the bone marrow in a dose-dependent manner in patients with chronic IHD. However, even high levels of circulating stem cells did not improve symptoms of IHD. [ABSTRACT FROM AUTHOR]

Examines clinical impact of vascular growth factors and endothelial progenitor cells in the acute coronary syndrome. Vascular growth factors which are of clinical relevance; Categories of endothelium-specific vascular endothelial growth factors (VEGF); Characteristics of fibroblast growth factor polypeptides; Role of VEGF in stimulating the development of collateral arteries in an ischemic area of the myocardium.

Aim: To investigate whether an intensified antiplatelet regimen could improve prognosis in stable or non-ST elevation in acute coronary syndrome (ACS) patients exhibiting high on-treatment platelet reactivity (HTPR) on clopidogrel and treated with percutaneous coronary intervention (PCI). There is a wide variability in the platelet reactivity to clopidogrel and HTPR has been associated with a poor prognosis.Methods: In this observational study, 923 consecutive patients without ST-elevation myocardial infarction (STEMI) and adequately pre-treated with clopidogrel were screened for HTPR with multiple electrode aggregometry after assessment of the coronary anatomy. Patients were grouped based on their response to clopidogrel and the assigned antiplatelet strategy. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, or stent thrombosis.Results: HTPR was demonstrated in 237 patients (25.7%). Of these, 114 continued on conventional clopidogrel therapy, while the remaining 123 received intensified antiplatelet therapy with either double-dose clopidogrel (150 mg daily,n = 55) or the newer P2Y12-inhibitors, prasugrel or ticagrelor (n = 68) for at least 30 days after the index procedure. The median follow-up was 571 days (interquartile range, 373–746). Intensifying antiplatelet therapy reduced the rate of the composite endpoint (p < 0.001). After adjustment for potential confounders, HTPR in combination with conventional clopidogrel therapy remained independently associated with an increased risk of cardiovascular events (hazard ratio (HR), 2.92; 95% CI, 1.90–4.48), whereas intensified treatment reduced the risk to a level equivalent to that of patients exhibiting normal platelet reactivity (HR, 1.08; 95% CI, 0.59–1.99).Conclusion: Tailored antiplatelet therapy significantly reduced the event rate in patients exhibiting HTPR prior to PCI. [ABSTRACT FROM PUBLISHER]

High on-treatment platelet reactivity (HTPR) is associated with poor prognosis in patients undergoing percutaneous coronary intervention (PCI). The antiplatelet effect and safety of prasugrel was compared to that of double-dose clopidogrel in patients with stable coronary artery disease or acute coronary syndrome (ACS) exhibiting HTPR on clopidogrel and treated with PCI, using multiple electrode aggregometry (MEA) to assess platelet reactivity. Of 923 patients screened, 237 (25.7%) exhibited HTPR. Of these, 106 were eligible for participation in a randomized trial comparing two intensified antiplatelet regimen: 52 were assigned to double maintenance-dose clopidogrel and 54 to standard-dose prasugrel. At 1 month, tailoring antiplatelet therapy improved platelet inhibition to a level considered as therapeutic in 73.1% of patients. Prasugrel entailed greater platelet inhibition ( p = 0.02) and a lower rate of persisting HTPR at follow-up compared to double-dose clopidogrel (HTPR persisted in 20.4% and 42% respectively, p = 0.02). Within the 30-day follow-up, no major bleeds were observed and the incidence of major adverse cardiovascular events (MACE) was similar in the two treatment arms. Prasugrel demonstrated superiority to double-dose clopidogrel in overcoming HTPR and reducing platelet activity. Intensifying antiplatelet therapy in both ACS and stable angina pectoris (SAP) patients exhibiting HTPR prior to PCI was well tolerated. [ABSTRACT FROM AUTHOR]

Aims. To investigate the incidence of contrast media-induced nephropathy (CIN) in patients with stable coronary artery disease (CAD) referred for elective coronary intervention following hydration routines. The reversibility of CIN was followed in a 6 month-period. Methods and results. A total of 447 patients referred for elective coronary intervention due to suspected CAD were included. Blood samples were collected before and 24 h after intervention and medical records were obtained. Patients had no drinking fluid restrictions and were routinely treated with a 1000 ml saline infusion. All patients were invited to a 6-month examination and collection of blood samples. Results. A total of 19 patients (4.3%) developed CIN. CIN patients had a pre-investigation higher estimated glomerular filtration rate (eGRF), lower level of kidney failure and lower creatinine level than non-CIN patients. Kidney function was not normalized in CIN patients 6 months after the intervention. Two patients still met the definition of CIN. Conclusion. With no restriction in fluid intake and supplementary infusion of saline, only a few patients with stable CAD developed early indications of CIN during elective coronary interventions. Kidney function and the amount of contrast media used was not a predictor of CIN development. The induced CIN was not completely normalized in a 6-month follow-up period. [ABSTRACT FROM AUTHOR]

Aims. We evaluated the feasibility, safety and efficacy of intra-myocardial injection of autologous mesenchymal stromal cells derived endothelial progenitor cell (MSC) in patients with stable coronary artery disease (CAD) and refractory angina in this first in man trial. Methods and results. A total of 31 patients with stable CAD, moderate to severe angina and no further revascularization options, were included. Bone marrow MSC were isolated and culture expanded for 6--8 weeks. It was feasible and safe to establish in-hospital culture expansion of autologous MSC and perform intra-myocardial injection of MSC. After six months follow-up myocardial perfusion was unaltered, but the patients increased exercise capacity (p < 0.001), reduction in CCS Class (p < 0.001), angina attacks (p < 0.001) and nitroglycerin consumption (p < 0.001), and improved Seattle Angina Questionnaire (SAQ) evaluations (p < 0.001). For all parameters there was a tendency towards improved outcome with increasing numbers of cells injected. In the MRI substudy: ejection fraction (p < 0.001), systolic wall thickness (p == 0.03) and wall thickening (p == 0.03) all improved. Conclusions. The study demonstrated that it was safe to treat patients with stable CAD with autologous culture expanded MSC. Moreover, MSC treated patients had significant improvement in left ventricular function and exercise capacity, in addition to an improvement in clinical symptoms and SAQ evaluations. [ABSTRACT FROM AUTHOR]

Objectives. Reports of long-term survival and the risk of sudden cardiac death (SCD) after percutaneous transluminal septal myocardial ablation (PTSMA) in patients with hypertrophic obstructive cardiomyopathy (HOCM) are sparse. Design. Survival and SCD in 77 PTSMA-treated patients (follow-up 3.5 ±± 2.8 years) were analyzed. The future risk of SCD was assessed by risk stratification for SCD in 57 PTSMA patients at long-term follow-up (3.8 ±± 2.8 years). Results. The five years survival of the PTSMA cohort (age 61 ±± 12 years) was 83% compared to 79% in a control cohort (n == 90) of patients (age 52 ±± 17 years) with hypertrophic cardiomyopathy (HCM) (Log Rank p == 0.8), and 91% (p == 0.01) in the background population. Five-year survival free of SCD was 94% after PTSMA compared to 99% (p == 0.13) in the HCM control cohort. Eight percent of patients had two or more risk factors for SCD at follow-up. Conclusion. The survival in the PTSMA-treated patients and in the HCM control cohorts was similar. The incidence of SCD and the future risk of SCD assessed by risk factors were not increased in the PTSMA cohort compared to the HCM control cohort. The excess mortality in the PTSMA cohort compared to the background population seems to be related to HCM rather than PTSMA. [ABSTRACT FROM AUTHOR]

Background: Plasma YKL-40 is increased early in patients with ST-elevation myocardial infarction (STEMI). It is not known whether plasma YKL-40 is related to infarct size and recovery of ventricular function after primary percutaneous coronary intervention (PCI) of STEMI and whether granulocyte colony-stimulating factor (G-CSF) therapy influence plasma YKL-40 concentration. Materials and methods: A total of 72 patients (age: 56 ± 9 years (mean ± SD), 56 men and 16 women) with STEMI treated with PCI were included in a double-blind, randomized, placebo-controlled trial with subcutaneous G-CSF or placebo injections from day 1 to 7 after the STEMI. Plasma YKL-40, high-sensitivity C-reactive protein (hs-CRP) and CK-MB concentrations were measured at baseline and during the first month. Infarct size and left ventricular ejection fraction (LVEF) were measured by magnetic resonance imaging at baseline and after 6 months. Results: Baseline plasma YKL-40 was increased (median 92 μg/L) compared to healthy subjects (median 34 μg/L, p <0.001). In the placebo group hs-CRP and YKL-40 correlated at baseline ( p = 0.04) and day 3 ( p = 0.01), but not at day 7 and 30. Moreover, YKL-40 correlated negatively to LVEF recovery ( p = 0.04) but not infarct size. G-CSF injections increased YKL-40 compared to placebo ( p <0.001), but were not associated with infarct size or LVEF recovery. Conclusion: Plasma YKL-40 was significantly increased in STEMI patients at admission and G-CSF treatment caused a further increase in YKL-40. Plasma YKL-40 may be an indirect marker of LVEF recovery, independent of hs-CRP, and higher plasma YKL-40 indicates a lower recovery. [ABSTRACT FROM AUTHOR]

Background. YKL-40 is involved in remodelling and angiogenesis in non-cardiac inflammatory diseases. Aim was to quantitate plasma YKL-40 in patients with ST-elevation myocardial infarction (STEMI) or stable chronic coronary artery disease (CAD), and YKL-40 gene activation in human myocardium. Methods and results. We included 73 patients: I) 20 patients with STEMI; II) 28 patients with stable CAD; III) 15 CAD patients referred for coronary by-pass surgery. YKL-40 mRNA expression was measured in myocardium subtended by stenotic or occluded arteries and areas with no apparent disease; and IV) 10 age-matched healthy controls. Plasma YKL-40 was significantly increased in patients with STEMI (88 µg/l, median) and CAD (66 µg/l) compared to controls (16 µg/l, p<0.01 for both). Plasma YKL-40 correlated with CRP at baseline in STEMI (r=0.53, p=0.02) and CAD patients (r=0.41, p=0.031).YKL-40 gene expression was similar in ischemic and non-ischemic myocardium. Conclusions. Plasma YKL-40 was significantly increased in patients with STEMI and stable CAD. Further studies will define the role of YKL-40 as a clinically useful marker for myocardial ischemia, remodelling and maybe prognosis. [ABSTRACT FROM AUTHOR]

Not all coronary angiograms can be acquired through the femoral route. The transradial catheterisation procedure in patients with occlusive atherosclerotic iliofemoral disease is described. Transfemoral left-sided cardiac catheterisation was performed in approximately 99.5% of patients referred for coronary angiography, while out of 48 patients in whom transfemoral access was impossible, transradial coronary angiography was successful in 37. With the exception of one, all patients with coronary artery disease had lesions of the right coronary artery, more than 70% had multivessel disease and 14% had stenosis of the left main coronary artery. Ten patients had angioplasty performed during the same procedure. Complications occurred in 5 out of 39 cases, 2 (5%) of these were severe. Although the femoral route was used in more than 99% of an unselected population referred for coronary angiography, it was found that transradial angiography and angioplasty can be performed in patients with occlusive atherosclerotic iliofemoral disease with considerable success and an acceptable complication rate. [ABSTRACT FROM AUTHOR]