Caterina Anania

Sapienza University of Rome, Roma, Latium, Italy

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Publications (35)79.92 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.
    World journal of gastroenterology : WJG. 07/2014; 20(27):9055-9071.
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    ABSTRACT: Several studies suggest that a substantial number of patients with normal serum alanine aminotransferase (ALT) levels, defined by current thresholds, have ongoing hepatic necro-inflammation and fibrosis, and are at risk of liver disease progression. A major problem lies in the definition of normality. The current upper limit of normal (ULN) for ALT was established in the 1980s when reference populations were likely to include many persons with hepatitis C virus infection and nonalcoholic fatty liver disease. Because ALT may be influenced, not only by liver disease, but also by other medical conditions, changing lifestyle factors and demographic determinants, the current ALT ULN threshold has recently been challenged. This review highlights current evidence on why and how ALT ULN should be redefined, but also discusses the current concerns about updating the ULN threshold for ALT.
    Clinica chimica acta; international journal of clinical chemistry 04/2013; · 2.54 Impact Factor
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    ABSTRACT: BACKGROUND AND AIMS: Lifestyle modification has been the mainstay of controlling childhood obesity and has proved to be effective in reducing cardiovascular risk factors. However, it is currently unknown whether the subclinical atherosclerotic changes associated with nonalcoholic fatty liver disease (NAFLD) in such population are reversible. METHODS AND RESULTS: We analyzed changes of brachial flow-mediated dilation (FMD), carotid intima-media thickness (cIMT), clinical, laboratory, and imaging data in 120 obese children with NAFLD, at the end of a 1-year intervention program with diet and physical exercise. The lifestyle intervention led to a significant mean decrease of body mass index (BMI)-standard deviation score (SDS), waist circumference (WC) and fat mass, along with diastolic blood pressure, triglycerides, liver enzymes, insulin, insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR), and high-sensitivity C-reactive protein. At the end of the study, FMD improved (P < 0.0001), while cIMT did not change significantly (P = 0.20). A significant decrease in hepatic fat content as measured by magnetic resonance imaging was also observed. Changes in FMD were inversely associated with changes in BMI-SDS, WC, total cholesterol, non-HDL cholesterol, liver enzymes, HOMA-IR, physical activity, and hepatic fat content. After including in the model all the significant variables as well as age, gender, pubertal status, and baseline FMD values, changes in FMD were significantly and independently associated with changes in WC and total cholesterol. CONCLUSION: Also in obese children with NAFLD arterial function may be restored by improving metabolic risk factors and reducing visceral adiposity following a 1-year lifestyle intervention.
    Nutrition, metabolism, and cardiovascular diseases: NMCD 09/2012; · 3.52 Impact Factor
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    ABSTRACT: BACKGROUND: Because of the decrease in the Helicobacter pylori eradication rate after standard triple therapy with a proton pump inhibitor and two antibiotics, bismuth-based therapy has recently been recommended as alternate first-line regimen in children. AIM: To comprehensively review the clinical, pharmacologic and microbiologic properties of bismuth salts, and to summarise the evidence for the therapeutic efficacy of bismuth-based therapy for H. pylori eradication in children. METHODS: Bibliographical searches were performed in MEDLINE. Results on the efficacy of bismuth-containing regimens on H. pylori eradication were combined using the inverse variance method. RESULTS: Bismuth monotherapy showed a very low efficacy. Overall, the mean eradication rate with bismuth-based dual therapy was 68% (95% CI, 60-76%) (intention-to-treat analysis-ITT) and 73% (95% CI, 64-81%) (per protocol-PP). In case series, the overall percentages of children with successful eradication for triple therapy containing bismuth were 82% (95% CI, 76-88%) and 86% (95% CI, 80-92%) according to ITT and PP respectively. In comparative studies, H. pylori eradication rates ranged between 69% and 85% according to ITT and between 74% and 96% PP. Side effects included dark stools, urine discoloration, black tongue, burning tongue, and marked darkness of the gums. CONCLUSIONS: The evidence in favour of bismuth compounds for treating infected children is still not clear. Well-designed, randomised, multi-centre studies of H. pylori eradication trials in children comparing bismuth-based triple therapy with the best available recommended first-line therapies are needed. The evidence obtained from audited case series that produce an eradication rate of >95% on PP analysis should also be considered.
    Alimentary Pharmacology & Therapeutics 03/2012; · 4.55 Impact Factor
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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. · 2.54 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. · 2.55 Impact Factor
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    ABSTRACT: Evidence of the association between vitamin D and cardiovascular risk factors in the young is limited. We therefore assessed the relationships between circulating 25-hydroxyvitamin D(3) (25(OH)D(3)) and metabolic syndrome (MetS), its components, and early atherosclerotic changes in 452 (304 overweight/obese and 148 healthy, normal weight) Caucasian children. We determined serum 25(OH)D(3) concentrations in relation to MetS, its components (central obesity, hypertension, low high-density lipoprotein (HDL)-cholesterol, hypertriglyceridemia, glucose impairment, and/or insulin resistance (IR)), and impairment of flow-mediated vasodilatation (FMD) and increased carotid intima-media thickness (cIMT) - two markers of subclinical atherosclerosis. Higher 25(OH)D(3) was significantly associated with a reduced presence of MetS. Obesity, central obesity, hypertension, hypertriglyceridemia, low HDL-cholesterol, IR, and MetS were all associated with increased odds of having low 25(OH)D(3) levels, after adjustment for age, sex, and Tanner stage. After additional adjustment for SDS-body mass index, elevated blood pressure (BP) and MetS remained significantly associated with low vitamin D status. The adjusted odds ratio (95% confidence interval) for those in the lowest (<17 ng/ml) compared with the highest tertile (>27 ng/ml) of 25(OH)D(3) for hypertension was 1.72 (1.02-2.92), and for MetS, it was 2.30 (1.20-4.40). A similar pattern of association between 25(OH)D(3), high BP, and MetS was observed when models were adjusted for waist circumference. No correlation was found between 25(OH)D(3) concentrations and either FMD or cIMT. Low 25(OH)D(3) levels in Caucasian children are inversely related to total adiposity, MetS, and hypertension.
    European Journal of Endocrinology 07/2011; 165(4):603-11. · 3.14 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. · 2.55 Impact Factor
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    ABSTRACT: Concomitantly with the increasing prevalence of childhood obesity, the prevalence of metabolic syndrome (MS) is rising among children and adolescents, leading to fears for future epidemics of type 2 diabetes mellitus and cardiovascular disease in the young. This makes the accurate identification and the appropriate treatment of children and adolescents with MS an important priority for health care systems. This review will focus on the management of each component of MS, including the nonalcoholic fatty liver disease (NAFLD), which is currently considered as the hepatic component of the syndrome. The most relevant target of treatment of MS in children and adolescents is the abdominal obesity. To this end, we will discuss the efficacy of dietary approaches, possibly coupled with regular physical activity, on eliciting visceral fat reduction. We will also highlight several aspects of the treatment of the high triglyceride/low high-density lipoprotein cholesterol phenotype, including the use of non-pharmacological measures, and indications for instituting drug therapies. Part of this review will address treatment of glucose abnormalities, including the benefits of lifestyle modification alone, and the potential adjunctive role of hypoglycemic drugs. The treatment of hypertension in children with MS also requires a multifaceted approach and the available data of this topic will be examined. The remainder of this review will address treatment to reverse NAFLD and prevent progression to end-stage disease.
    Nutrition, metabolism, and cardiovascular diseases: NMCD 06/2011; 21(6):455-66. · 3.52 Impact Factor
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    Hepatitis Monthly 06/2011; 11(6):479-80. · 1.25 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. · 2.07 Impact Factor
  • Digestive and Liver Disease - DIG LIVER DIS. 01/2011; 43.
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    ABSTRACT: Non-alcoholic 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 (NASH), includes inflammation and liver cell injury, progressive to cryptogenic cirrhosis. Although prevalence in children is very difficult to establish, NAFLD is probably the most common cause of liver disease in preadolescent and adolescent groups. Over the last two decades the 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, a highly atherogenic condition, and its presence could signify a substantial cardiovascular risk. Accurate diagnosis and staging of NAFLD requires liver biopsy. The development of non-invasive surrogate markers and the advancement in imaging technology will aid in the screening of large populations at risk for NAFLD. While the optimal treatment has yet to be determined, lifestyle modification through diet and exercise should be attempted in children diagnosed with NAFLD. This review outlines current understanding, recent advances and challenges on pediatric NAFLD for both clinicians and researchers. Key words: Fatty liver.
    Minerva pediatrica 12/2010; 62(6):569-84. · 0.64 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. · 2.55 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 08/2010; 52(5):1643-51. · 12.00 Impact Factor
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    ABSTRACT: Helicobacter pylori is one of the most common infections found in humans. It was first identified in 1982 and by 1989 had been associated with gastric inflammation and ulcers in adults and children. During the 1990's evidence emerged of its etiologic role in stomach cancers in adults. That the infection is common and may have serious consequences, has led to an avalanche of research during the last twenty years. During this time, there have been many studies on children which have sought an effective and safe treatment to eradicate the infection, but as yet, no therapy regimen has been found which is always effective and safe. This article provides information, from a pediatric point of view, on the major developments in the therapeutics and therapy of H. pylori infection. It examines first-line treatment regimens, evaluates the efficacy of the main drugs used in the management of (primary) H. pylori infection in children, assesses the potential for the use of probiotics and sequential therapy, examines therapeutic options after failure of initial treatment, and discusses factors affecting eradication rate, including antibiotic resistance, adherence to therapy, and bacterial factors.
    International journal of immunopathology and pharmacology 01/2010; 23(2):405-16. · 2.99 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. · 3.14 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. · 3.82 Impact Factor
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    ABSTRACT: Breath tests represent a valid and non-invasive diagnostic tool in many gastroenterological conditions. The rationale of hydrogen-breath tests is based on the concept that part of the gas produced by colonic bacterial fermentation diffuses into the blood and is excreted by breath, where it can be quantified easily. There are many differences in the methodology, and the tests are increasingly popular. The Rome Consensus Conference was convened to offer recommendations for clinical practice about the indications and methods of H2-breath testing in gastrointestinal diseases. Experts were selected on the basis of a proven knowledge/expertise in H2-breath testing and divided into Working Groups (methodology; sugar malabsorption; small intestine bacterial overgrowth; oro-coecal transit time and other gas-related syndromes). They performed a systematic review of the literature, and then formulated statements on the basis of the scientific evidence, which were debated and voted by a multidisciplinary Jury. Recommendations were then modified on the basis of the decisions of the Jury by the members of the Expert Group. The final statements, graded according to the level of evidence and strength of recommendation, are presented in this document; they identify the indications for the use of H2-breath testing in the clinical practice and methods to be used for performing the tests.
    Alimentary Pharmacology & Therapeutics 04/2009; 29 Suppl 1:1-49. · 4.55 Impact Factor
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    Aliment Pharmacol Ther. 01/2009; 29(Suppl.1):1-49.