Caterina Anania

Sapienza University of Rome, Roma, Latium, Italy

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Publications (18)67.02 Total impact

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    ABSTRACT: Over the last two decades, the rise in the prevalence rates of overweight and obesity explains the emergence of nonalcoholic fatty liver disease (NAFLD) as the leading cause of chronic liver disease worldwide. As described in adults, children and adolescents with fatty liver display insulin resistance, glucose intolerance, and dyslipidemia. Thus NAFLD has emerged as the hepatic component of the metabolic syndrome (MetS) and a strong cardiovascular risk factor even at a very early age. Several studies, including pediatric populations, have reported independent associations between NAFLD and markers of subclinical atherosclerosis including impaired flow-mediated vasodilation, increased carotid artery intima-media thickness, and arterial stiffness, after adjusting for cardiovascular risk factors and MetS. Also, it has been shown that NAFLD is associated with cardiac alterations, including abnormal left ventricular structure and impaired diastolic function. The duration of these subclinical abnormalities may be important, because treatment to reverse the process is most likely to be effective earlier in the disease. In the present review, we examine the current evidence on the association between NAFLD and atherosclerosis as well as between NAFLD and cardiac dysfunction in the pediatric population, and discuss briefly the possible biological mechanisms linking NAFLD and cardiovascular changes. We also address the approach to treatment for this increasingly prevalent disease, which is likely to have an important future global impact on the burden of ill health, to prevent not only end-stage liver disease but also cardiovascular disease.
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    ABSTRACT: Childhood obesity is a worldwide health problem and its prevalence is increasing steadily and dramatically all over the world. Obese subjects have a much greater likelihood than normal-weight children of acquiring dyslipidemia, elevated blood pressure, and impaired glucose metabolism, which significantly increase their risk of cardiovascular and metabolic diseases. Elevated TSH concentrations in association with normal or slightly elevated free T4 and/or free T3 levels have been consistently found in obese subjects, but the mechanisms underlying these thyroid hormonal changes are still unclear. Whether higher TSH in childhood obesity is adaptive, increasing metabolic rate in an attempt to reduce further weight gain, or indicates subclinical hypothyroidism or resistance and thereby contributes to lipid and/or glucose dysmetabolism, remains controversial. This review highlights current evidence on thyroid involvement in obese children and discusses the current controversy regarding the relationship between thyroid hormonal derangements and obesity-related metabolic changes (hypertension, dyslipidemia, hyperglycemia and insulin resistance, nonalcoholic fatty liver disease) in such population. Moreover, the possible mechanisms linking thyroid dysfunction and pediatric obesity are reviewed. Finally, the potential role of lifestyle intervention as well as of therapy with thyroid hormone in the treatment of thyroid abnormalities in childhood obesity is discussed.
    Clinica chimica acta; international journal of clinical chemistry 11/2011; 413(3-4):396-405. DOI:10.1016/j.cca.2011.11.013 · 2.76 Impact Factor
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    ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) encompasses a range of liver histology severity and outcomes in the absence of chronic alcohol use. The mildest form is simple steatosis in which triglycerides accumulate within hepatocytes. A more advanced form of NAFLD, non-alcoholic steatohepatitis, includes inflammation and liver cell injury, progressive to cryptogenic cirrhosis. NAFLD has become the most common cause of chronic liver disease in children and adolescents. The recent rise in the prevalence rates of overweight and obesity likely explains the NAFLD epidemic worldwide. NAFLD is strongly associated with abdominal obesity, type 2 diabetes, and dyslipidemia, and most patients have evidence of insulin resistance. Thus, NAFLD shares many features of the metabolic syndrome (MetS), a highly atherogenic condition, and this has stimulated interest in the possible role of NAFLD in the development of atherosclerosis. Accumulating evidence suggests that NAFLD is associated with a significantly greater overall mortality than in the general population, as well as with increased prevalence of cardiovascular disease (CVD), independently of classical atherosclerotic risk factors. Yet, several studies including the pediatric population have reported independent associations between NAFLD and impaired flow-mediated vasodilatation and increased carotid artery intimal medial thickness-two reliable markers of subclinical atherosclerosis-after adjusting for cardiovascular risk factors and MetS. Therefore, the rising prevalence of obesity-related MetS and NAFLD in childhood may lead to a parallel increase in adverse cardiovascular outcomes. In children, the cardiovascular system remains plastic and damage-reversible if early and appropriate interventions are established effectively. Therapeutic goals for NAFLD should address nutrition, physical activity, and avoidance of smoking to prevent not only end-stage liver disease but also CVD.
    World Journal of Gastroenterology 07/2011; 17(26):3082-91. DOI:10.3748/wjg.v17.i26.3082 · 2.43 Impact Factor
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    ABSTRACT: To determine in obese children with nonalcoholic fatty liver disease (NAFLD) the accuracy of magnetic resonance imaging (MRI) in assessing liver fat concentration. A case-control study was performed. Cases were 25 obese children with biopsy-proven NAFLD. Controls were 25 obese children matched for age and gender, without NAFLD at ultrasonography and with normal levels of aminotransferases and insulin. Hepatic fat fraction (HFF) by MRI was obtained using a modification of the Dixon method. HFF ranged from 2% to 44% [mean, 19.0% (95% CI, 15.1-27.4)] in children with NAFLD, while in the controls this value ranged from 0.08% to 4.69% [2.0% (1.3-2.5), P < 0.0001]. HFF was highly correlated with histological steatosis (r = 0.883, P < 0.0001) in the NAFLD children. According to the histological grade of steatosis, the mean HFF was 8.7% (95% CI, 6.0-11.6) for mild, 21.6% (15.3-27.0) for moderate, and 39.7% (34.4-45.0) for severe fatty liver infiltration. With a cutoff of 4.85%, HFF had a sensitivity of 95.8% for the diagnosis of histological steatosis ≥ 5%. All control children had HFF lower than 4.85%; thus, the specificity was 100%. After 12 mo, children with weight loss displayed a significant decrease in HFF. MRI is an accurate methodology for liver fat quantification in pediatric NAFLD.
    World Journal of Gastroenterology 07/2011; 17(25):3012-9. DOI:10.3748/wjg.v17.i25.3012 · 2.43 Impact Factor
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    Hepatitis Monthly 06/2011; 11(6):479-80. · 1.80 Impact Factor
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    ABSTRACT: Over the last two decades, there have been many studies on children who have sought an effective and safe treatment to eradicate Helicobacter pylori infection, but as yet, no therapy regimen has been found which is always effective and safe. Differences in drug response among pediatric patients are common. Such individual variability in drug response is multifactorial, including environmental, genetic, development and disease determinants that affect the disposition of a given drug. In pediatric efficacy studies for the management of H. pylori eradication in children, the most commonly tested regimen has contained a combination of proton pump inhibitor (PPI), clarithromycin and amoxicillin, followed by triple therapies containing PPI, clarithromycin and nitroimidazoles. Thus, PPIs are an integral part of triple therapy for H. pylori eradication in children with gastroduodenal disease. In this article, we comprehensively review, from a pediatric point of view, the literature on the clinical, pharmacologic and microbiologic properties of PPIs. We also discuss genetic, developmental and other host-related factors that may affect the efficacy of these drugs. Finally, we provide some guidance regarding their potential role and limitations for H. pylori eradication in children.
    Chemotherapy 02/2011; 57(1):85-93. DOI:10.1159/000323619 · 1.55 Impact Factor
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    ABSTRACT: Although evidence is emerging that the prevalence of Helicobacter pylori (H. pylori) is declining in all age groups, the understanding of its disease spectrum continues to evolve. If untreated, H. pylori infection is lifelong. Although H. pylori typically colonizes the human stomach for many decades without adverse consequences, children infected with H. pylori can manifest gastrointestinal diseases. Controversy persists regarding testing (and treating) for H. pylori infection in children with recurrent abdominal pain, chronic idiopathic thrombocytopenia, and poor growth. There is evidence of the role of H. pylori in childhood iron deficiency anemia, but the results are not conclusive. The possibility of an inverse relationship between H. pylori and gastroesophageal reflux disease, as well as childhood asthma, remains a controversial question. A better understanding of the H. pylori disease spectrum in childhood should lead to clearer recommendations about testing for and treating H. pylori infection in children who are more likely to develop clinical sequelae.
    World Journal of Gastroenterology 11/2010; 16(41):5181-94. · 2.43 Impact Factor
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    ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) has been consistently found to be associated with features of the metabolic syndrome (MS), a condition carrying a high risk of cardiovascular events. The present study aimed to determine whether, in children and adolescents, NAFLD is atherogenic beyond its association with MS and its components. We assessed both flow-mediated dilation of the brachial artery (FMD) and carotid intima-media thickness (cIMT), along with lipid profile, glucose, insulin, insulin resistance, and high-sensitivity C-reactive protein (CRPHS), in 250 obese children, 100 with and 150 without NAFLD, and 150 healthy normal-weight children. NAFLD was diagnosed by ultrasound examination and persistently elevated alanine aminotransferase, after exclusion of infectious and metabolic disorders. Compared to controls and children without liver involvement, those with ultrasound-diagnosed NAFLD (and elevated alanine aminotransferase) demonstrated significantly impaired FMD and increased cIMT. Patients with NAFLD had more features of MS and elevated CRPHS levels. In addition, percent FMD was remarkably reduced, whereas cIMT was increased in obese children with MS compared to those without MS. Using logistic regression analysis, the presence of NAFLD was found to be an independent predictor of low percent FMD (odds ratio, 2.25 [95% confidence interval, 1.29 to 3.92]; P = 0.004) as well as of increased cIMT (1.98 [1.16 to 3.36]; P = 0.031), after adjustment for age, gender, Tanner stage, and presence of MS. When we analyzed the relations between cIMT and measures of FMD in patients with NAFLD, the disease was associated with increased cIMT in children with impaired FMD status. CONCLUSION: The presence of liver disease entails more severe functional and anatomic changes in the arterial wall. Its detection may help identify individuals with increased cardiometabolic risk.
    Hepatology 11/2010; 52(5):1643-51. DOI:10.1002/hep.23890 · 11.19 Impact Factor
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    ABSTRACT: Ghrelin, a peptide mainly derived from the stomach, plays a pivotal role in the regulation of food intake, energy metabolism, and storage, as well as in insulin sensitivity. Ghrelin circulates in acylated (A-Ghr) and nonacylated (NA-Ghr) forms, and their potential differential associations with insulin resistance (IR) in childhood obesity remain undefined. We investigated the associations of ghrelin forms with IR in normal weight and obese children and the impact of metabolic syndrome (MS) on their plasma values. A total of 210 children in four subgroups of normal weight/obese children with and without components of MS were studied. Fasting blood glucose, insulin, lipid profile, and acylated and total ghrelin were examined. IR was determined by a homeostasis model assessment (HOMA) of IR. In the entire population, plasma insulin and HOMA-IR were associated negatively with T-Ghr and NA-Ghr, but positively with the ratio of A/NA-Ghr after adjustment for age, gender, and Tanner stage. Obese metabolically abnormal children had lower T-Ghr and NA-Ghr, but comparable A-Ghr and a higher A/NA-Ghr ratio than obese metabolically normal subjects. Compared with lean healthy children, lean metabolically abnormal subjects had higher A-Ghr and the A/NA-Ghr ratio, but comparable T-Ghr and NA-Ghr. A multiple regression analysis showed that A-Ghr and the A/NA-Ghr ratios were positively associated with HOMA-IR, independent of age, gender, Tanner stage, and body mass index (or waist circumference) and other components of MS. A-Ghr excess may negatively modulate insulin action in obese and nonobese children, and may contribute to the association of IR and MS.
    European Journal of Endocrinology 09/2009; 161(6):861-70. DOI:10.1530/EJE-09-0375 · 3.69 Impact Factor
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    ABSTRACT: Bodyweight is a significant predictor of bone mass. Hormonal factors are thought to play a role in the mechanisms controlling the association of body weight and fat mass with bone mass. Very recently, the orexigenic hormone ghrelin has also been implicated in bone metabolism. In this study we examined the associations of circulating acylated and des-acyl ghrelin concentrations with measures of bone in a group of obese children and adolescents as well as in a group of healthy control children. We also determined whether the associations were independent of body composition, chronological age, gender, Tanner stage, and leptin, glucose, insulin and insulin-like growth factor (IGF)-1 levels. We performed a prospective cross-sectional study of 100 obese children [age, 8.9 (8.3 to 9.4); BMI-Standard Deviation Score (SDS), 2.2 (2.0 to 2.3)], and 100 age-matched lean healthy subjects. Fasting insulin, leptin, IGF-1, acylated and total ghrelin were measured by radioimmunoassay. Des-acyl ghrelin values were calculated as total ghrelin minus acylated ghrelin. Whole body (WB) and lumbar spine (LS) BMD, and BMC as well as body composition were assessed by DXA (Hologic QDR-4500W). LS volumetric BMD (BMAD) was estimated using the formula of Katzman (BMC/area(1.5)), while WB BMC data were expressed as BMC/height. Backward linear regression analysis was performed for individual groups, with age, gender, Tanner stage, weight, height, body composition (lean and fat mass), acylated ghrelin, des-acyl ghrelin, leptin, glucose, insulin, and IGF-1, entered into the model. In healthy children, acylated ghrelin was a significant and independent negative predictor of WB BMD, and WB BMC/height, while lean mass was positively associated significantly with these bone measures. In contrast, in obese children, a positive significant association was observed between des-acyl ghrelin and WB BMD as well as WB BMC/height, along with lean mass, and to a lesser degree, with fat mass. Acylated as well as des-acyl ghrelin were not significant predictors of LS BMD and LS BMAD in obese as well as control children. The results of this investigation indicate that the influence of the two distinct isoforms of ghrelin on BMD is mediated by specific body composition parameters in obese and control healthy children.
    Bone 05/2009; 45(2):274-9. DOI:10.1016/j.bone.2009.04.204 · 4.46 Impact Factor
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    ABSTRACT: The association between hyperuricemia, metabolic syndrome (MS), and atherosclerotic vascular disease has been reported in adults, but very little is known about this association in children. The aims of our study were to ascertain the correlates of uric acid (UA) in a sample of obese children, and to investigate whether UA is associated with carotid intima-media thickness (IMT) independently from classical risk factors including MS. We analyzed carotid IMT along with serum triglycerides, total and high-density lipoprotein cholesterol, glucose, insulin, insulin resistance index (as homeostasis model assessment of insulin resistance), alanine aminotransferase, gamma-glutamyltransferase, creatinine, and UA in 120 obese children and 50 healthy control children. UA concentrations were significantly higher in obese children compared with controls; moreover, they correlated with the most established cardiovascular risk factors. In the group of obese children, after adjustment for age, sex, pubertal stage, and creatinine, an independent association between UA levels and the presence of MS syndrome was observed (unstandardized coefficient, 0.044 (95% confidence intervals (CI) 0.015-0.072); P<0.01). Carotid IMT significantly increased in the fourth quartile of UA compared with that in the first, second, and third quartile (0.49 (0.46-0.53), 0.53 (0.49-0.56), and 0.55 (0.52-0.59) vs 0.61 (95% CI, 0.58-0.64); P<0.01). When multivariate analysis was performed after adjusting for age, gender, pubertal stage, creatinine, and MS (considered as a single clinical entity), or the individual components of MS simultaneously included, the association between UA and carotid IMT was significant (P<0.01). In obese children and adolescents, increased UA levels are associated with carotid atherosclerosis.
    European Journal of Endocrinology 10/2008; 160(1):45-52. DOI:10.1530/EJE-08-0618 · 3.69 Impact Factor
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    ABSTRACT: In order to reduce the need for invasive diagnostic tests in pediatrics, there has been a rapid development of tests based on the analysis of exhaled air for the investigation of a wide range of conditions. These tests are frequently extensions of procedures that have been developed and more intensively investigated for use in adults. Consequently, when these tests are used for children, the procedures are modified and diagnostic cut-off values are changed, and this results in lack of standardization and the possibility of differences of clinical interpretation.
    Clinica Chimica Acta 08/2008; 397(1-2):1-12. DOI:10.1016/j.cca.2008.07.023 · 2.76 Impact Factor
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    ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is closely associated with several metabolic syndrome features, including obesity, dyslipidemia, insulin resistance, and increased cardiovascular risk. The present study was undertaken to assess whether NAFLD in children is associated with increased carotid artery intima-media thickness (IMT), a marker of early-generalized atherosclerosis. We analyzed carotid IMT along with serum triglycerides, total, low-density lipoprotein and high-density lipoprotein cholesterol, glucose, insulin, insulin resistance index (as homeostasis model assessment of insulin resistance), aminotransferases, leptin, and adiponectin in 29 obese children with NAFLD, 33 obese children without liver involvement, and 30 control children. The diagnosis and severity of NAFLD was based on ultrasound scan, after exclusion of infectious and metabolic disorders. Obese children with NAFLD had significantly increased carotid IMT [mean 0.58 (95% confidence intervals 0.54-0.62 mm)] than obese children without liver involvement [0.49 (0.46-0.52) mm; p = 0.001] and control children [0.40 (0.36-0.43) mm; p < 0.0005]. In a stepwise multiple regression model, after adjusting for age, gender, Tanner stage, and cardiovascular risk factors, the severity of fatty liver was significantly associated with maximum IMT (b = 0.08; p < 0.0005). Our results suggest that NAFLD is strongly associated with carotid atherosclerosis even in childhood.
    Pediatric Research 04/2008; 63(4):423-7. DOI:10.1203/PDR.0b013e318165b8e7 · 2.84 Impact Factor
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    ABSTRACT: Helicobacter pylori, and the chronic gastric inflammation that it causes, may compromise the function and survival of ghrelin-producing cells, resulting in a decrease of circulating ghrelin levels. This finding raises the possibility that the infection might affect growth in children by reducing the ghrelin production. To determine baseline circulating levels of ghrelin and leptin in prepubertal children with and without H. pylori infection and to evaluate the long-term effects of H. pylori eradication on circulating levels of ghrelin and leptin as well as on body composition. Thirty children with H. pylori-associated gastritis, 35 children with H. pylori-negative gastric mucosa, and 20 healthy controls were studied. At baseline, while leptin levels were significantly lower in H. pylori-positive patients, ghrelin concentrations did not differ among the three study groups. However, a significant inverse correlation between ghrelin concentrations and histological severity of gastritis was found. Eradication of the organism was associated with a progressive decrease in ghrelin concentrations over baseline at both 6- and 12-month follow-ups. SDS-body mass index (BMI), lean and fat mass, as well as leptin concentrations, significantly increased over baseline at both follow-ups. In prepubertal children, serum ghrelin concentrations are inversely related to the severity of H. pylori-associated gastritis. In these youngsters, long-term eradication of H. pylori infection is associated with a significant increase in BMI, lean and fat mass along with a significant decrease in circulating ghrelin levels and an increase in leptin levels.
    European Journal of Endocrinology 04/2008; 158(3):323-32. DOI:10.1530/EJE-07-0438 · 3.69 Impact Factor
  • Acta Paediatrica 09/2007; 96(9):1374-1375. DOI:10.1111/j.1651-2227.2007.00423.x · 1.84 Impact Factor
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    ABSTRACT: The aims of this study were to evaluate hepatic steatosis severity in a series of obese children through both magnetic resonance imaging (MRI) and ultrasound, and to correlate imaging findings to clinical and metabolic characteristics of the study population. Fifty obese children presenting hepatomegaly and/or elevated aminotransferases were candidates for assessment of hepatic fat fraction (HFF) by MRI. All subjects underwent dual energy X-ray absorptiometry scan measurement, and liver ultrasound scanning. Fasting blood samples were taken for the estimation of serum concentrations of glucose, insulin, leptin, aminotransferases and serum lipid profile. A diagnosis of fatty liver was established by MRI in 20 (40%) children; of these, 12 had HFF of 9-18%, while the remaining ones had HFF of 19% or higher. HFF was not correlated to age, SDS-BMI, pubertal status and fat mass. HFF was positively associated with serum concentrations of alanine aminotransferase (ALT; r=0.62; p<0.0001) and AST (r=0.39; p=0.006), as well as with insulin (r=0.44; p=0.001) and insulin resistance (r=0.49; p<0.0001). Overall, ultrasound correlated well with MRI (p<0.0001). However, HFF ranged greatly in subjects with moderate (2-37%) as well as with severe (11-25%) degree of ultrasound hepatic steatosis. In fact, the mean hepatic fat fraction in children with severe steatosis was not statistically different from that found in patients with moderate steatosis (p=0.98). In multiple regression analysis, the most powerful predictors of elevated ALT, after correction for age, gender, BMI and pubertal status, were insulin resistance (p<0.01) and MRI HFF (p<0.0001). Unlike sonography, an operator-dependent procedure, MRI is not subject to interpretation or inter-observer variation, and may be more useful than ultrasound for the monitoring of young patients with hepatic steatosis.
    Acta Paediatrica 04/2007; 96(4):542-7. DOI:10.1111/j.1651-2227.2007.00186.x · 1.84 Impact Factor
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    ABSTRACT: Leptin, an adipocyte-secreted hormone, has emerged as a potential candidate for the link between obesity and the proinflammatory state. Specifically, leptin modulates T-helper (Th) cells toward a Th1 phenotype, with the secretion of proinflammatory cytokines. The aim of this study was to evaluate the Th1/Th2 balance in obese children and its relation with hormonal and metabolic features. Study design: In 50 obese children and 20 control children, we measured the CD4-positive Th cells that secrete interferon (IFN)-gamma or interleukin (IL)-2 (taken as an index of Th1 cells), and IL-4 (taken as an index of Th2 cells) as well as serum glucose, insulin, insulin resistance (IR) index (as homeostasis model assessment model (HOMA)), lipid profile, aminotransferases, leptin and ghrelin. Obese children also underwent dual energy X-ray absorptiometry scan measurements, and liver ultrasound scanning. Geometric mean percentages of IL-2- and IL-4-CD4 secreting cells in obese children were not significantly different from those found in control children. However, the geometric mean percentage of CD4-positive T cells secreting IFN-gamma was significantly higher in the obese than in the control (P < 0.0001, t-test) group. Within the entire group of study children, the percentage of IFN-gamma-positive cells was positively associated with leptin (P = 0.002), insulin (P < 0.00 005), and HOMA-IR values (P < 0.00 005). However, when these associations were restricted to the group of obese subjects, insulin and HOMA-IR values, but not leptin, retained statistical significance. Yet, in the obese group, the percentage of IFN-gamma-positive cells was associated with nonalcoholic steatohepatitis (NASH) (P = 0.001), but not with body mass index-standard deviation score and total body fat mass. In obese children, a shift to Th1-cytokine profile dominated by the production of IFN-gamma is related to insulin resistance as well as to NASH independently of anthropometric features and other metabolic characteristics. The prevalent Th1 pattern of secreted cytokines may be regarded as a mechanism contributing to inflammation in obesity.
    European Journal of Endocrinology 06/2006; 154(5):691-7. DOI:10.1530/eje.1.02138 · 3.69 Impact Factor
  • Gastroenterology 04/2003; 124(4, Suppl. S):A200. DOI:10.1016/S0016-5085(03)81002-8 · 13.93 Impact Factor