Diagnostic and therapeutic radiation exposure in children: new evidence and perspectives from a biomarker approach.
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Biomarkers, Tumor↗
Biomedical subjects
Maria Grazia Andreassi
Publications and source records attributed to Maria Grazia Andreassi.
Chronic low-dose radiation exposure from interventional cardiology procedures induces chromosomal abnormalities in originally genetically identical twins.
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Adult↗
Cardiac imaging: the biological effects of diagnostic cardiac ultrasound.
Diagnostic cardiac ultrasounds are an environment-friendly and non-ionising imaging technology. However, ultrasounds are not biologically inert, and their use might have profound clinical impact. This paper summarizes the known effects of cardiac ultrasound--compared to other major imaging techniques--to exposed patients and to clinically exposed physicians practising ultrasound imaging. Furthermore, this review also provides an overview of the evidences on the biological effects of diagnostic ultrasound--which suggest that ultrasound with frequency, intensity and duration fully in the diagnostic range have significant molecular, cellular and organ effects. A better understanding of these effects may improve our understanding of the complex interactions between ultrasound and biological tissues and may open new avenues to therapeutic applications based on the ultrasound-modulated cell functions, such as membrane transduction, apoptosis, cell permeability and thrombolysis.
Echocardiography↗
An increased platelet-leukocytes interaction at the culprit site of coronary artery occlusion in acute myocardial infarction: a pathogenic role for "no-reflow" phenomenon?
BACKGROUND: Distal protection devices have been shown to reduce the incidence of "no flow" phenomenon during primary percutaneous coronary intervention (PCI). So far, it has not been well clarified which mechanism is mainly involved in distal coronary protection. AIM: To investigate the activation state of leukocytes and platelets locally present within the blood from the site of coronary occlusion. METHODS: Ten patients with acute myocardial infarction (AMI) underwent primary PCI with an embolization protection device and aspiration catheter (PercuSurge GuardWire) were included. The following functional parameters: a) monocyte and neutrophils surface molecules; b) platelet surface activatory antigens; c) leukocytes-platelet conjugates were studied by flow cytometry in blood obtained from the site of coronary occlusion and from peripheral femoral artery. RESULTS: The leukocyte-platelet adhesion index was significantly higher in the aspirated blood at the site of coronary occlusion than in the peripheral arterial blood for both monocytes (0.226+/-0.04 vs. 0.084+/-0.01; p=0.004) and neutrophils (1.372+/-0.3 vs. 0.524+/-0.1; p=0.02). Moreover, the volume of coaggregates exhibited a significant increase in coronary blood for both populations (p=0.02 for monocytes and for neutrophils). Interestingly, a significant up-regulation of the adhesive molecule CD18 was observed in coronary blood respect to systemic circulation either in monocytes (p=0.01) than in neutrophils (p=0.003). A significant up-regulation of monocyte (HLA-DR) and neutrophil (CD66b) activatory molecules expression was also observed in the aspirated coronary compared to peripheral artery blood (p=0.02 and p=0.03 for HLA-DR and CD66b, respectively). CONCLUSIONS: These data indicate an increased leukocyte-platelet functional interaction in AMI at the site of plaque rupture relative to the systemic circulation, which may be one of the pathogenetic mechanisms responsible for myocardial "no-reflow" phenomenon.
Angioplasty, Balloon, Coronary↗
Cardiac catheterization and long-term chromosomal damage in children with congenital heart disease.
AIMS: Medical radiological exposure is associated with an additional risk of cancer. Children with repaired congenital heart disease (CHD) are theoretically at a relatively greater cancer risk as the radiological exposure can be intensive in these patients. Chromosomal aberrations test (CA) and micronucleus assay (MN) in peripheral blood lymphocytes are biomarkers of chromosomal damage and intermediate endpoints in carcinogenesis. METHODS AND RESULTS: The frequency of CA and MN was assessed in three groups of patients: Group I, 32 exposed patients (17 males, age=15.5+/-8.3 years) who underwent cardiac procedures employing ionizing radiation (mostly cardiac catheterization) for CHD between 1965 and 2000; Group II, 32 healthy age- and sex-matched subjects (17 males, age=14.1+/-12.3 years), and Group III, 10 newborn non-exposed patients (7 males) with CHD. Exposed patients of Group I had a mean value of 2.9+/-1.4 cardiac catheterization (range 1-5) procedures per person. The mean frequency of CA was higher in the exposed patients (Group I=2.8+/-1.9% vs. Group II=0.7+/-0.7%; vs. Group III=0.8+/-0.8%; P<0.0001). Similarly, the mean values of MN were higher in the exposed patients (Group I =12.3+/-5.1 per thousand vs. Group II=6.0+/-3.8 per thousand; vs. Group III=4.4+/-1.4 per thousand; P<0.0001). CONCLUSION: Cardiac ionizing procedures are associated with a long-lasting mark in the chromosomal damage of exposed children with CHD.
Adolescent↗
Factor V Leiden, prothrombin G20210A substitution and hormone therapy: indications for molecular screening.
Venous thromboembolism is a well-known complication of oral contraception and hormonal replacement therapy. Inherited thrombophilia is viewed as an important determinant in modulating the effects of estrogens on thrombotic risk. An increasing number of kits for thrombophilic mutations [factor V Leiden, G20210A prothrombin and methylenetetrahydrofolate reductase (MTHFR) C677T genes] are becoming commercially available, and screening for inherited thrombotic risk is among the most requested genetic tests in molecular diagnostic laboratories. However, the question of routine genetic screening for thrombophilia before prescribing hormones is still a matter of debate. The purpose of this article is to discuss the usefulness and practical applications of thrombotic genetic testing to identify which women should be tested to improve both the safety and efficacy of individualized estrogen therapy.
Animals↗
Lack of radiological awareness among physicians working in a tertiary-care cardiological centre.
BACKGROUND: Medical irradiation is the most important artificial source of exposure to ionising radiations in Europe and implies biorisks. AIM: To assess the level of radiological awareness in a tertiary-care referral centre of adult-pediatric cardiological excellence. METHODS: One hundred physicians (31 women, age=41+/-8 years) were polled with a simple, one-page, multiple choice questionnaire. Twenty-five physicians worked in a pediatric, 75 in an adult cardiology centre. RESULTS: Eighty-nine of the polled physicians wrongly estimated the contribution of nuclear and radiological tests in overall radiation exposure of average US inhabitant as <0.01% (36% of physicians) or <1% (31%) or <10% (22%) (correct answer given by 11% of physicians: >10%). Ninety-five physicians wrongly estimated the risk of fatal cancer associated with a stress myocardial perfusion scintigraphy procedure as "zero" (48%) or "<1 in 10 million"(19%) or "<1 in 1 million" (28%) (correct answer given by 5%: >1 in 10,000 tests). Seventy-one wrongly estimated the dose exposure of a myocardial stress perfusion scintigraphy as equal to one (13%), or one-half (9%), or three times (49%) that of a chest X-ray (correct answer given by 29%: 500 times). The average level of radiological awareness was not correlated to the number of radiological-nuclear exams performed/prescribed per year and to the type of (adult or pediatric) working environment. CONCLUSION: Physicians working in an adult and pediatric cardiological environment of excellence are largely unaware of environmental impact, biorisks and dose exposure of the ionising exams they prescribe and/or perform daily.
Adult↗
Genomic medicine and thrombotic risk: who, when, how and why?
Major advances in Human Genome research could significantly change the clinical medical practice, providing new possibilities for both diagnosing and treating common pathologies. Many genetic tests are now commercially available for predicting future risk of common disorders. However, genetic testing has potential benefits but also limitations for the patients, and it should not be used to 'screen' the general population. Diagnostic assays for a predisposition of both venous and arterial thrombosis are among the most requested genetic tests in molecular diagnostics laboratories. However, there is considerable uncertainty as to how this information should be utilized in patient management. Both the medical community and the patients need to obtain accurate information concerning the appropriate use of genetic testing. The purpose of this article is to discuss the usefulness and the practical applications of thrombotic genetic testing in order to define which patients should be tested for both venous and arterial thrombotic risk as well as to have an acceptable cost/benefit ratio and to prevent patients' anxiety.
Ethics, Medical↗
Hormone replacement therapy: one-year follow up of DNA damage.
Although hormone replacement therapy (HRT) may offer considerable benefits for menopausal women, the potential cancer risk may limit its use. This work aimed at assessing whether HRT is able to induce DNA damage in postmenopausal women monitored by the micronucleus (MN) test, which provides a reliable biomarker of genotoxicity and cancer risk assessment. A group of 16 healthy women (non-smokers) in spontaneous menopause were given oral estradiol (2 mg oral micronized 17-beta estradiol daily) for 1 month, followed by a 30-day wash-out period and a transdermal treatment with 17-beta estradiol (1.5 mg gel daily) during 1 month. Oral intake of dihydrogesterone (10 mg/day for 12 days/month) was cyclically combined with oral or transdermal estradiol during the next 9 months. Venous blood samples were collected before the treatment, and after 1, 3, 6 and 12 months of therapy. Slides were scored blind and MN frequency was evaluated as number of micronuclei per 1000 binucleated cells. The baseline plasma levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) were simultaneously measured. The means of MN frequency were 18.2+/-1.6, 18.6+/-2.1, 14.8+/-1.5, 15.9+/-1.0 and 17.7+/-1.3 for samples collected before and at 1, 3, 6 and 12 months, respectively. The MN frequencies at every sampling time did not statistically differ from the basal values. In addition, no statistically significant associations between MN values and hormone levels of E2 and FSH were observed throughout the entire study. This study shows the absence of any significant increase of MN frequencies in women undergoing oral and/or transdermal HRT, sequentially monitored for up to 12 months of therapy.
Administration, Cutaneous↗
AMPD1 (C34T) polymorphism and clinical outcomes in patients undergoing myocardial revascularization.
BACKGROUND: C34T variant of adenosine monophosphate deaminase 1 (AMPD1) gene has been associated with a prolonged survival in heart failure and coronary artery disease, hypothetically linked to an enhanced production of adenosine. DESIGN: Since adenosine administration is a promising approach for the prevention of the ischemia-reperfusion in myocardial revascularization, the aim of this study was to investigate whether the AMPD1 (-) allele is associated with a favorable prognosis after coronary revascularization. In addition, we assessed the association between AMPD1 polymorphism and plasma adenosine levels. METHODS: We investigated a total of 161 patients receiving coronary revascularization (70 percutaneous transluminal coronary angioplasty and 91 coronary artery bypass graft). They were investigated for a composite endpoint including recurrent angina, non-fatal MI, target vessel revascularization, heart failure and cardiac death. Plasma adenosine was also measured by high-performance liquid chromatography methods on a subset of 25 patients. RESULTS: During the follow-up period (7.0+/-0.3 months), the overall combined endpoint accounted for 17 events (10 cardiac-related deaths, 6 revascularization procedures and 1 congestive heart failure). The composite endpoint was 9.8% for AMPD1 (-) allele carriers vs. 11.5% for non-carriers (log-rank statistic, p=n.s.). In the logistic analysis only low (</=40%) ejection fraction was an independent predictor of adverse events (p=0.01, OR=3.8, 95% CI 1.3-11.4). Plasma adenosine levels were similar for AMPD1 (-) allele patients (n=7) as compared for AMPD1 (+) allele (n=18) subjects (290.5+/-31.0 vs. 303.3+/-28.5 nM, p=n.s.). CONCLUSIONS: Our results indicate that AMPD1 (-) allele is not associated with a more favorable outcome after coronary revascularization. Alternative cardioprotective pathways of the AMPD1 gene-involving an enhanced chronic long-term production of adenosine-might be responsible for survival.
AMP Deaminase↗
Somatic DNA damage in interventional cardiologists: a case-control study.
Interventional cardiologists who work in cardiac catheterization laboratories are exposed to low doses of ionizing radiation that could pose a health hazard. DNA damage is considered to be the main initiating event by which radiation damage to cells results in development of cancer and hereditary disease. The aim of the present study was to assess the effects of chronic low-dose X-ray radiation exposure on somatic DNA damage of interventional cardiologists working in high-volume cardiac catheterization laboratories. For this analysis, we used peripheral lymphocytes and the assay for micronuclei (MNs), which is considered to be a reliable biological dosimeter for radiation exposure. We obtained peripheral blood from 62 physicians (mean age+/-se = 40.6+/-1.5 years): 31 interventional cardiologists (group I, exposed) and 31 age- and sex-matched clinical cardiologists (group II, nonexposed). Interventional cardiologists showed higher MN values (group I=20.5+/-1.6 vs. group II=12.8+/-1.3, P=0.001), although some overlap was apparent in the individual subject analysis. A correlation between years of professional activity and MN frequency value was detectable for interventional cardiologists (r=0.428, P=0.02) but not for clinical cardiologists (r=0.253, P=0.17). The results indicated that, overall, interventional cardiologists working in a high-volume catheterization laboratory have higher levels of somatic DNA damage when compared with clinical cardiologists working outside the catheterization laboratory. The amount of this damage varies and is only weakly related to the duration of professional exposure, which suggests that a dominant modulation of the underlying genetic substrate by environmental factors has a role in determining the harm in individual physicians.
Adult↗
Diabetes and chronic nitrate therapy as co-determinants of somatic DNA damage in patients with coronary artery disease.
Somatic DNA damage has been linked to coronary artery disease (CAD). However, whether genetic instability is linked to CAD per se or to concomitant potentially genotoxic metabolic and pharmacological factors remains still unclear. The aim of this study was to evaluate the determinants of somatic DNA damage in a large population of patients undergoing coronary angiography. A total of 278 in-hospital patients (215 men, age 61.8+/-0.7 years) were studied by using micronucleus assay (MN) in human lymphocytes, which is one of the most commonly used biomarker for somatic DNA damage. Significant CAD (>50% diameter stenosis) was present in 210 patients (179 men, age 62.3+/-0.7 years). Normal coronary arteries were observed in 68 patients (35 men, age 60.2+/-1.7 years). There were no significant differences between patients with and without CAD, but patients with multivessel disease had the highest MN levels (P=0.01). MN frequency was also found significantly higher in presence of type 2 diabetes (P<0.0001), dyslipidemia (P=0.048) and nitrate therapy (P=0.0002). A significant additive effect was also observed between diabetes and nitrate therapy (P=0.02). On multivariate logistic regression analysis, diabetes [odds ratio=6.8 (95% confidence interval, 3.2-14.5), P<0.0001] and nitrate therapy [odds ratio=2.4 (95% confidence interval, 1.3-4.7), P=0.01] remained the only significant determinants for the 50th percentile of MN (>12 per thousand). These results indicated that diabetes and, to a lesser extent, chronic nitrate therapy are major determinants of somatic DNA instability in patients with CAD. DNA damage might represent an additional pathogenetic dimension and a possible therapeutic target in the still challenging management of coronary artery disease concerning diabetics.
Coronary Angiography↗
Detection of mtDNA with 4977 bp deletion in blood cells and atherosclerotic lesions of patients with coronary artery disease.
Recent evidence suggests that somatic mutations in nuclear and mitochondrial DNA accumulated during aging, may significantly contribute to the pathogenesis of chronic-degenerative illness such as coronary artery disease (CAD). Mitochondrial DNA with 4977 bp deletion mutation (mtDNA4977) is a common type of mtDNA alteration in humans. However, little attempt has been made to detect the presence of mtDNA4977 deletion in cells and tissues of cardiovascular patients. This study investigated the presence of mtDNA4977 in blood samples of 65 cardiovascular patients and 23 atherosclerotic plaques of human coronaries with severe atherosclerosis. Moreover, the presence of the deletion has been investigated in blood cells from 22 healthy age-matched subjects. The detection of mtDNA4977 has been performed by using a nested polymerase chain reaction (PCR) protocol and normalized to wild-type mtDNA. A significant higher incidence of mtDNA4977 was observed in CAD patients with respect to healthy subjects (26.2% versus 4.5%; P=0.03). Furthermore, the relative amount of the deletion was significantly higher in the patients compared to the control group (P=0.02). The mtDNA4977 was detected in 17 of the 65 patients blood samples (26.2%) and deletion levels ranged from 0.18 to 0.46% of the total mtDNA (mean: 0.34+/-0.02%). For what concerns atherosclerotic lesions, 5 patients (21.7%) showed the deletion ranging from 0.13 to 0.45% of the total mtDNA (mean: 0.35+/-0.06%). In both samples from patients, the incidence and the relative amount of mtDNA4977 was not significantly influenced by atherogenic risk factors and clinical parameters. The obtained results may suggest that the increase of oxidative stress in cardiovascular disease may be responsible for the accumulation of mtDNA damage in coronary artery disease patients.
Base Sequence↗
The biological effects of diagnostic cardiac imaging on chronically exposed physicians: the importance of being non-ionizing.
Ultrasounds and ionizing radiation are extensively used for diagnostic applications in the cardiology clinical practice. This paper reviewed the available information on occupational risk of the cardiologists who perform, every day, cardiac imaging procedures. At the moment, there are no consistent evidence that exposure to medical ultrasound is capable of inducing genetic effects, and representing a serious health hazard for clinical staff. In contrast, exposure to ionizing radiation may result in adverse health effect on clinical cardiologists. Although the current risk estimates are clouded by approximations and extrapolations, most data from cytogenetic studies have reported a detrimental effect on somatic DNA of professionally exposed personnel to chronic low doses of ionizing radiation. Since interventional cardiologists and electro-physiologists have the highest radiation exposure among health professionals, a major awareness is crucial for improving occupational protection. Furthermore, the use of a biological dosimeter could be a reliable tool for the risk quantification on an individual basis.
Body Burden↗
8-iso-prostaglandin F2alpha as a risk marker in patients with coronary heart disease.
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Biomarkers↗
C677T polymorphism of the methylenetetrahydrofolate reductase gene is a risk factor of adverse events after coronary revascularization.
BACKGROUND: A common point mutation (C677T) in the gene for 5,10-methylenetetrahydrofolate reductase (MTHFR) is associated with hyperhomocysteinemia, an independent risk factor and a strong predictor of mortality in patients with coronary artery disease (CAD). The aim of this study was to investigate whether C677T polymorphism can be a predictor of major adverse cardiac events after myocardial revascularization. METHODS: We determined MTHFR genotype in 159 patients with CAD undergoing myocardial revascularization [72 percutaneous transluminal coronary angioplasty (PTCA) and 87 coronary artery bypass graft (CABG)]. Recurrent angina, nonfatal myocardial infarction (MI), target vessel revascularization, heart failure and cardiac death were considered major adverse cardiac events that occurred after discharge from index hospitalization. RESULTS: During the follow-up (6.9+/-0.3 months, mean+/-S.E.M.), the composite endpoint accounted for 25.9%, 11.4% and 4.3% for TT, CT and CC genotype (log-rank statistic 5.2, p=0.02), respectively. Subjects with mutant TT genotype had a threefold increase of any cardiac event (hazard ratio [HR]=3.0; 95% [CI], 1.1-8.1). In multiple-variable regression Cox, predictors of events were TT genotype (HR=2.8; 95% CI, 1.01-7.62, p=0.047), low-ejection fraction<40% (HR=4.5; 95% CI, 1.62-12.6, p=0.004) and revascularization procedure (HR=6.1; 95% CI, 1.86-20.34, p=0.003). CONCLUSIONS: These data indicate that the TT genotype seems to be significantly associated with major adverse cardiac events after myocardial revascularization in CAD patients, suggesting a potential pathological influence of homocysteine in the clinical outcome.
Aged↗
Interactive effect of the glutathione S-transferase genes and cigarette smoking on occurrence and severity of coronary artery risk.
Cardiovascular diseases and cancer are the main causes of death in developed countries. Mortality trends for these diseases suggest that they share common pathogenetic mechanisms. Glutathione S-transferase (GST) is a family of enzymes that detoxify reactive electrophiles, particularly present in tobacco smoke. Glutathione S-transferase null M1 and T1 (GSTM1 and GSTT1) genotypes have often been associated with increased risk of developing cancer. Our hypothesis was that the polymorphic GSTM1 and GSTT1 genes modulate the risk of smoking-coronary artery disease (CAD). We evaluated the distribution of GST genotypes in 430 angiographically defined patients (308 CAD and 122 non-CAD). The frequencies of GST null genotypes did not differ significantly between patients with CAD and without CAD. However, smokers with GSTM1 and GSTT1 null genotypes had a significantly higher risk of CAD than never-smokers with these genotypes present (OR 2.2 and 3.4 for smokers with null GSTM1 and GSTT1 genes, respectively). There was also evidence of multiple interaction between GSTM1 and GSTT1 deleted genotypes and smoking. In nonsmokers carrying both null genotypes the risk of CAD was 0.66. In smokers with both present genotypes the OR was 1.5 and was significantly increased in smokers with concurrent lack for GSTM1 and GSTT1 genes (OR=4.0). Moreover, smokers lacking GST genes had both more stenosed vessels and a higher Duke score than smokers expressing the genes. We also examined the levels of DNA damage in 66 men patients using the micronucleus test, a sensitive assay for evaluating chromosome damage. Micronucleus levels were higher in smokers with null genes than in smokers with present genes. These observations suggest that GST-null genotypes strengthen the effect of smoking on CAD risk by modulating the detoxification of genotoxic atherogens.
Coronary Artery Disease↗
DNA damage as a new emerging risk factor in atherosclerosis.
Atherosclerosis is the leading cause of illness and death in Western societies. It is now clear that the disease is a result of a chronic fibroproliferative-inflammatory response of the arterial intima leading to the formation of atherosclerotic plaque. There is, however, strong experimental evidence for a "mutation theory of atherosclerosis," underlining the similarity between atherosclerotic and carcinogenic processes. This review provides an overview of the studies that support the role of genetic alterations in the disease. The demonstration of microsatellite instability and loss of heterozygosity in smooth muscle cells of human plaques suggests that genomic destabilization may play a pivotal role in atherosclerotic mechanisms. Furthermore, the use of accepted biomarkers of carcinogenic exposure-such as DNA adducts and cytogenetic end points-recently has provided evidence consistent with the view that somatic cell alterations are critical in atherogenic process. It follows that the study of DNA damage may provide new insights into the pathogenesis of atherosclerosis and lead to the development of novel therapeutic approaches.
Arteriosclerosis↗