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Biomedical subjects

R A Tio

Publications and source records attributed to R A Tio.

At least 19 recordsLinked to original sources
PubMed2006

Interleukin 10: a new risk marker for the development of restenosis after percutaneous coronary intervention.

Genetic factors appear to be important in the process of restenosis after percutaneous coronary intervention (PCI), as well as in inflammation, a pivotal factor in restenosis. An important mediator in the inflammatory response is interleukin (IL)-10. Our aim was to study whether genetic variants in IL-10 predispose to the risk of restenosis. The GENetic DEterminants of Restenosis (GENDER) study included 3104 patients treated with successful PCI. Target vessel revascularization (TVR) was chosen as primary end point. Genotyping of the -2849G/A, -1082G/A, -592C/A and +4259A/G polymorphisms of the IL-10 gene was performed by MassArray platform. After adjusting for clinical variables, three polymorphisms significantly increased the risk of restenosis (-2849AA: relative risk (RR), 1.7, 95% confidence interval (CI), 1.2-2.5; -1082AA: RR, 1.4, 95% CI, 1.1-1.8 and +4259GG: RR, 2.0, 95% CI, 1.4-2.8). To further exclude possible involvement of neighboring genes due to LD in the IL-10 locus, additional polymorphisms were genotyped. The results reveal that association of the IL-10 gene with restenosis is independent of flanking genes. Our findings demonstrate that IL-10 is associated with restenosis and therefore support the hypothesis that anti-inflammatory genes also may be involved in developing restenosis. Furthermore, they may provide a new targeting gene for drug-eluting stents.

3' Untranslated Regions↗
PubMed2006

The benefit of 64-MDCT prior to invasive coronary angiography in symptomatic post-CABG patients.

PURPOSE: The purpose of this study is to assess the diagnostic accuracy of 64-MDCT in symptomatic patients after CABG and to explore the advantages of the 64-MDCT results on the CAG procedure. MATERIAL AND METHODS: From December 2004 until August 2005, 34 post-CABG patients (29 men, mean age 63.5 +/- 8.5 years) with 69 coronary artery bypass grafts were scanned on a 64-MDCT (Somatom Sensation 64, Siemens AG, Forchheim, Germany) prior to CAG. Angiograms and 64-MDCT images were evaluated for the existence of occlusions or significant stenosis (>or=50% lumen reduction) in bypass grafts and native coronary arteries. RESULTS: 64-MDCT had a sensitivity, a specificity, and a diagnostic accuracy of 100% for occlusion detection. For stenosis detection, sensitivity was 100%, specificity 98.7% and diagnostic accuracy 98.7%. For detecting significant stenosis in native coronary arteries, 64-MDCT had a sensitivity of 80.0%, specificity of 90.8%, and a diagnostic accuracy of 87.1%. Seventeen patients (50.0%) did not need invasive treatment, 14 patients (41.2%) underwent a percutaneous coronary intervention (PCI), and 3 patients (8.8%) underwent surgery. Treatment advice based on 64-MDCT was correct in 88.2% of patients and when 64-MDCT results would have been known 58.8% of diagnostic CAG procedures could have been prevented. CONCLUSION: In conclusion, 64-MDCT has a high diagnostic accuracy in detecting bypass graft stenosis and occlusions, and 64-MDCT based treatment advice was correct in 88.2% of patients.

Aged↗
PubMed2006

Quantification of global left ventricular function: comparison of multidetector computed tomography and magnetic resonance imaging. a meta-analysis and review of the current literature.

Cardiac morbidity and mortality are closely related to cardiac volumes and global left ventricular (LV) function, expressed as left ventricular ejection fraction. Accurate assessment of these parameters is required for the prediction of prognosis in individual patients as well as in entire cohorts. The current standard of reference for left ventricular function is analysis by short-axis magnetic resonance imaging. In recent years, major extensive technological improvements have been achieved in computed tomography. The most marked development has been the introduction of the multidetector CT (MDCT), which has significantly improved temporal and spatial resolutions. In order to assess the current status of MDCT for analysis of LV function, the current available literature on this subject was reviewed. The data presented in this review indicate that the global left ventricular functional parameters measured by contemporary multi-detector row systems combined with adequate reconstruction algorithms and post-processing tools show a narrow diagnostic window and are interchangeable with those obtained by MRI.

Humans↗
PubMed2006

Treatment with intramuscular vascular endothelial growth factor gene compared with placebo for patients with diabetes mellitus and critical limb ischemia: a double-blind randomized trial.

Despite advances in revascularization techniques, limb salvage and relief of pain cannot be achieved in many diabetic patients with diffuse peripheral vascular disease. Our objective was to determine the effect of intramuscular administration of phVEGF165 (vascular endothelial growth factor gene-carrying plasmid) on critical limb ischemia (CLI) compared with placebo (0.9% NaCl). A double-blind, placebo-controlled study was performed in 54 adult diabetic patients with CLI. The primary end point was the amputation rate at 100 days. Secondary end points were a 15% increase in pressure indices (ankle-to-brachial index and toe-to-brachial index), clinical improvement (skin, pain, and Quality of Life score), and safety. In patients (n=27) treated with placebo versus phVEGF165-treated patients (n=27) the following results were found: 6 amputations versus 3 (p=not significant [NS]); hemodynamic improvement in 1 versus 7 (p=0.05); improvement in skin ulcers, 0 versus 7 (p=0.01); decrease in pain, 2 versus 5 (p=NS); and overall, 3 versus 14 responding patients (p=0.003). No grade 3 or 4 adverse effects were seen in these patients. We conclude that this small, randomized gene therapy study failed to meet the primary objective of significant amputation reduction. However, significant and meaningful improvement was found in patients treated with a VEGF165-containing plasmid. There were no substantial adverse events.

Adult↗
PubMed2005

[Delirium attributed to the use of metoprolol].

A 53-year-old man with a known history of alcohol abuse was admitted to hospital after a minor collapse. He had a laceration to the forehead and three rib fractures. Laboratory blood-analysis showed raised non-cholestatic liver-enzyme levels suggesting alcohol-abuse. On history taking the patient was shown to have been suffering from personality changes and multiple hallucinogenic episodes for the previous two years. He had been seen and evaluated by a neurologist to that effect. The patient's family had accepted the situation and thought of it as dementia, probably caused by alcohol abuse. He had been treated for atrial flutter and was taking acenocoumerol, atorvastatin, quinapril and metoprolol 50 mg twice daily as medication. During admission the patient appeared to be suffering from a delirium with complex visual and auditory hallucinations, for which he was given haloperidol. Revision of medication use led to the stopping of metoprolol, which had been started two years earlier. Within 24 hours the delirium had disappeared completely. There was spontaneous fall in the liver enzymes. At his last follow-up, the patient had had no psychiatric symptoms for 6 months. The relationship between stopping metoprolol and the disappearance of the psychosis appeared to be a causal one and this is supported by the limited literature available on this subject.

Adrenergic beta-Antagonists↗
PubMed2005

Assessment of coronary artery bypass graft patency by multidetector computed tomography and electron-beam tomography.

This case report describes the use of retrospectively ECG-gated 16-slice multidetector computed tomography (MDCT) and electron-beam tomography (EBT) for assessing bypass graft patency in two patients with recurrent angina after coronary artery bypass graft surgery. The results of each tomographic modality were compared to the findings of traditional coronary angiography. In the first patient MDCT showed occlusion of the left internal mammary artery (LIMA) and saphenous vein graft after the second anastomosis. Coronary angiography confirmed these findings. In the second patient EBT showed patency of the LIMA and saphenous vein graft. After the first anastomosis of the saphenous vein graft, the connected vessel filled poorly. Coronary angiography confirmed both grafts to be patent, and detected an occlusion distal to the first anastomosis. These findings support the evidence that both MDCT and EBT are suitable techniques for establishing bypass graft patency by non-invasive means.

Angina Pectoris↗
PubMed2005

Signaling factors in stem cell-mediated repair of infarcted myocardium.

Myocardial infarction leads to scar formation and subsequent reduced cardiac performance. The ultimate therapy after myocardial infarction would pursue stem cell-based regeneration. The aim of stem cell-mediated cardiac repair embodies restoration of cardiac function by regeneration of healthy myocardial tissue, which is accomplished by neo-angiogenesis and cardiogenesis. A major reservoir of adult autologous stem cells distal from the heart is the bone marrow. Adequate regulation of signaling between the bone marrow, the peripheral circulation and the infarcted myocardium is important in orchestrating the process of mobilization, homing, incorporation, survival, proliferation and differentiation of stem cells, that leads to myocardial regeneration. In this review, we discuss key signaling factors, including cytokines, chemokines and growth factors, which are involved in orchestrating the stem cell driven repair process. We focus on signaling factors known for their mobilizing and chemotactic abilities (SDF-1, G-CSF, SCF, IL-8, VEGF), signaling factors that are expressed after myocardial infarction involved in the patho-physiological healing process (TNF-alpha, IL-8, IL-10, HIF-1alpha, VEGF, G-CSF) and signaling factors that are involved in cardiogenesis and neo-angiogenesis (VEGF, EPO, TGF-beta, HGF, HIF-1alpha, IL-8). The future therapeutic application and capacity of secreted factors to modulate tissue repair after myocardial infarction relies on the intrinsic potency of factors and on the optimal localization and timing of a combination of signaling factors to stimulate stem cells in their niche to regenerate the infarcted heart.

Animals↗
PubMed2004

Vascular endothelial growth factor: the link between cardiovascular risk factors and microalbuminuria?

BACKGROUND: Microalbuminuria, i.e. slightly elevated urinary albumin excretion, is associated with increased cardiovascular risk factors and cardiovascular morbidity in the general population. Microalbuminuria has been proposed to indicate increased endothelial permeability. Unknown are the mechanisms underlying this increased vascular permeability. Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, increases endothelial permeability. We hypothesised that plasma VEGF levels may be associated with microalbuminuria in a large sample of the general population. METHODS: Out of a large sample of the general population, we studied 189 control subjects (urinary albumin excretion (UAE): 0-30 mg/24 h) and 194 microalbuminuric subjects (UAE: 30-300 mg/24 h), matched for age, sex and the presence of ischemia on the electrocardiogram. RESULTS: Subjects with microalbuminuria had significant higher plasma levels of VEGF (p<0.05). The correlation between plasma levels of VEGF and systolic and diastolic blood pressure, cholesterol, glucose, diabetes and body mass index were statistically significant. Using logistic regression analysis, microalbuminuria was significantly associated with VEGF (odds ratio 1.62; 95% confidence interval: 1.15-2.27; p<0.01). This association was dependent on cardiovascular risk factors. CONCLUSION: This study suggests a relation between increased plasma VEGF levels and subsequent occurrence of microalbuminuria.

Albuminuria↗
PubMed2004

The role of coronary endothelial function testing in patients suspected for angina pectoris.

Coronary vasomotor function plays an important role in onset and progression of coronary artery disease. Suwaidi [Circulation 101 (2000) 948] and Schächinger [Circulation 101 (2000) 1899] demonstrated that vasomotor dysfunction has a significant impact on events in patients with minimal coronary artery disease. Endothelial specific testing can be performed in coronary as well as peripheral arteries. However, non-coronary tests have a low correlation with the coronary vasomotor response, as assessed by acetylcholine. In large clinical prospective placebo-controlled trials, angiotensin-converting enzyme (ACE) inhibitors and lipid-lowering drugs reduce morbidity and mortality after myocardial infarction or myocardial infarction-induced heart failure. The same drugs restore endothelial dysfunction after myocardial infarction, as was demonstrated in small experimental and clinical studies. Recent studies in patients with coronary artery disease showed a relation with endothelial dysfunction and the occurrence of adverse coronary events. For this reason, it is important to develop methods to evaluate endothelial function.

Angina Pectoris↗
PubMed2003

Electrical neuromodulation improves myocardial perfusion and ameliorates refractory angina pectoris in patients with syndrome X: fad or future?

At present, there is no reliable antianginal drug therapy for patients with cardiac syndrome X. Therefore, the effect of electrical neuromodulation on refractory angina pectoris and myocardial perfusion in cardiac syndrome X was assessed. Eight patients (aged 55+/-7 years) with heterogeneous myocardial perfusion and no esophageal abnormalities were included. The subjects were nonresponders to antianginal drug therapy. Angina pectoris attacks and myocardial perfusion dynamics were evaluated by positron emission tomography at baseline and following 4 weeks of (transcutaneous electrical nerve stimulation) TENS. Following TENS there was a reduction of angina pectoris episodes (baseline 20+/-3, TENS 3+/-1; p=0.012), and short acting nitroglycerin intake per week (baseline 10+/-3, TENS 2+/-1; p=0.008). The rate pressure product (mmHg min(-1)) during the cold pressor test (CPT) was reduced during TENS (baseline 12800+/-1200, TENS 11500+/-900; p=0.02). Following TENS, the perfusion reserve ratio between rest and dipyridamole flow increased (baseline 1.59+/-0.15, TENS 1.90+/-0.11 ml min(-1)x 100g; p=0.05). The coronary vascular resistance had a trend towards a reduction (baseline 0.96+/-0.04, TENS 0.85+/-0.06 mmHg min(-1)x 100 g/ml; p=0.06) during CPT. This observation may suggest that neurostimulation improves angina pectoris with a concomitant improvement of myocardial perfusion in cardiac syndrome X.

Adult↗
PubMed2003

Therapeutic angiogenesis with vascular endothelial growth factor in peripheral and coronary artery disease: a review.

Therapeutic angiogenesis constitutes an alternative treatment for patients with extensive tissue ischaemia in whom primary vascular reconstruction procedures are not feasible or have previously failed. At present vascular endothelial growth factor (VEGF) has been the most widely used angiogenic factor in experimental and human clinical trials. Early clinical data provide evidence that gene transfer of the VEGF gene can achieve beneficial angiogenesis, with minimal side-effects. Ongoing phase III clinical studies will reveal definitive efficacy.

Animals↗
PubMed2002

Cardiac tissue engineering: characteristics of in unison contracting two- and three-dimensional neonatal rat ventricle cell (co)-cultures.

Patients with heart failure have, in spite of improved palliative therapies, bad prognosis. Cardiac tissue engineering by use of a temporary bioscaffold and cardiomyocytes may help to find answers for future treatments in heart failure. For that purpose two neonatal rat heart ventricular cell fractions were obtained after a gradient cell separation. Time related characteristics of Fractions I and II were established in two-dimensional (2-D) and three-dimensional (3-D) cell cultures. The 3-D cardiac constructs were obtained by use of a bovine type I collagen matrix after culturing either under static conditions or in the HARV bioreactor. With the 2-D cultures contracting cells were present after 1 day, and reached confluency from day 5 on and this was maintained up to 135 days. In Fraction-I some non-contracting cells were always noticed between the (in time in unison) contracting cells. Transmission electron microscopy (TEM) revealed that these mainly concerned fibroblasts. Differences in the expression of alpha-SM-1 actin and troponin-T were observed between the two fractions. In both fractions endothelial cells and macrophages were only sporadically observed. All through the 3-D matrix pendant-like single cell and clustered cell contractions were present after 1-2 days, resulting in time in unison contracting of cells with the collagen matrices. The whole event was faster with Fraction-I and was observed up to 3 weeks. At this time point clusters of troponin-T positive cells were found scattered through the collagen matrices. Additionally, TEM revealed healthy layers of connected cardiomyocytes with intercalated discs, in this case on and in between the collagen fibres. These findings provide evidence that in unison contracting structurally organized cell-matrix cardiac constructs can be engineered by use of co-cultures (neonatal cardiomyocytes and fibroblasts) and collagen matrices, which is very promising for the repair of larger scar areas of the myocardium.

Actins↗
PubMed2002

Recombinant Semliki Forest virus as a vector system for fast and selective in vivo gene delivery into balloon-injured rat aorta.

Previously, we demonstrated that recombinant Semliki Forest virus (SFV) vector rapidly and selectively transfers genes into cultured vascular smooth muscle cells (VSMC), leaving endothelial cells (EC) unaffected. From this, we hypothesized that recombinant SFV in vivo only transfers genes into the media of balloon-injured but not intact vessel, that gene expression in VSMC is fast, and that the specificity of SFV for VSMC is caused by specific binding sites. To address these hypotheses, we studied the time course of in vivo SFV-LacZ and Ad-LacZ expression in balloon-injured rat aorta. In addition, the fusion characteristics of fluorescent pyrene-labeled SFV were explored in cultured VSMC and EC. In intact aorta, no LacZ expression was found in the intima or media at 24 h. In contrast, in denuded aorta, LacZ expression was detected in as early as 12 h after incubation. LacZ expression was predominantly present in the media. Ad-LacZ expression started after 12 h, but was predominantly present in the adventitia. Ad-LacZ expression in the media started after 72 h. In vitro transfection with SFV showed that fusion was higher and, moreover, saturable in VSMC as compared with EC, indicating the presence of specific SFV binding sites on VSMC, but not EC. From this we conclude that in vivo selectivity of SFV in balloon-injured vessels is based on the removal of the endothelium, which results in accessibility of VSMC in the media that carry specific binding sites for the SFV vector.

Adenoviridae↗
PubMed2002

Safety evaluation of routine intracoronary acetylcholine infusion in patients undergoing a first diagnostic coronary angiogram.

BACKGROUND: Recent findings imply prognostic significance of intracoronary acetylcholine infusion for endothelial function testing. We evaluated whether routine use of this test in coronary angiography patients is safe. METHODS: Patients undergoing a first diagnostic coronary angiography were selected to receive intracoronary acetylcholine for endothelial function evaluation. The relation between adverse reactions during infusion and risk factors was analyzed with a logistic regression model. Included in the multiple logistic regression model were the variables with a univariate P value < 0.20. RESULTS: Adverse reactions occurred in 16% (49/299) of the patients. This included two life-threatening events caused by occlusive spasm and flow limitation in the left coronary artery. Other adverse events were chest pain (n = 38), AV block or sinus bradycardia (n = 10), dyspnea (n = 3). Adverse reactions were more likely to occur in patients younger than 60 years of age (relative risk, 5.6 [2.2-14.3]). CONCLUSION: Intracoronary acetylcholine infusion is safe, but may lead to serious adverse reactions. Care should be taken especially in patients younger than 60 years of age. Routine use of acetylcholine infusion can thus only be justified if it has important prognostic significance. This has to be proven further in large prospective studies.

Acetylcholine↗
PubMed2001

Ventricular septal rupture caused by myocardial bridging.

A 70-year-old woman was referred to us with postinfarction angina. During cardiac catheterization the only coronary abnormality found was myocardial bridging in the mid and distal parts of the left anterior descending coronary artery, despite a large ventricular septal rupture. The pulmonary-to-systemic flow ratio was 2.5:1. Her operation was successful.

Aged↗