Spontaneous atlantoaxial subluxation as a presenting manifestation of juvenile ankylosing spondylitis in a female HLA-B27-negative patient.
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Adolescent↗
Biomedical subjects
Francesco Chiarelli
Publications and source records attributed to Francesco Chiarelli.
Increased oxidative stress in prepubertal severely obese children: effect of a dietary restriction-weight loss program.
Oxidant-antioxidant status was investigated in a group of severely obese prepubertal children in comparison with healthy subjects and in relation to a dietary restriction-weight loss program. All subjects underwent anthropometric measurements and determination of lipid profile, lag phase, malondialdehyde (MDA), and vitamin E. Compared with controls, obese children had a significantly higher body mass index (BMI) (28.97 +/- 2.42 vs. 16.03 +/- 1.88 kg/m2; P = 0.0002) and waist-to-hip ratio (WHR) (0.89 +/- 0.03 vs. 0.80 +/- 0.01; P = 0.0004); lag phase and vitamin E levels were significantly decreased [24.05 +/- 16.21 vs. 43.16 +/- 10 min (P = 0.004) and 21.12 +/- 14.96 vs. 35.54 +/- 13.62 micromol/liter (P = 0.02), respectively], whereas MDA was significantly increased (0.90 +/- 0.31 vs. 0.45 +/- 0.24 nmol/mg; P = 0.001). Both lag phase and MDA significantly correlated with BMI [respectively, r = -0.34 (P = 0.004) and r = 0.57 (P = 0.002)] and WHR [respectively, r = -0.63 (P = 0.0001) and r = 0.38 (P = 0.04)]. Oxidant status normalized after 6 months of dietary restriction [lag phase, 59.11 +/- 14.74 min (P = 0.002); MDA, 0.47 +/- 0.09 nmol/mg (P = 0.003)], which was associated with a reduction of BMI (27.34 +/- 1.87 kg/m2; P = 0.003), WHR (0.87 +/- 0.02; P = 0.001), and fat mass (34.49 +/- 2.68%; P = 0.008), but returned to baseline levels together with fatness indexes after another 6 months of free diet. Altered oxidant-antioxidant status is already present in prepubertal severely obese children and is reversible with a dietary restriction-weight loss program, which should be highly encouraged and maintained over time in this age group.
Body Mass Index↗
Thyroid function and morphology in patients affected by Williams syndrome.
OBJECTIVE: To evaluate the prevalence of abnormalities of thyroid function and morphology in a cohort of patients with Williams syndrome (WS). METHODS: Serum concentrations of free-T3, free-T4, TSH, thyroperoxidase antibodies (TPOA) and thyroglobulin antibodies (TgA), as well as ultrasonographic data, of 20 patients with WS (12 females and eight males), aged 1.7-34.9 years, were evaluated. RESULTS: Three cases (15%) of subclinical hypothyroidism were identified. Overt hypothyroidism was diagnosed in two cases (10%). Thyroid antibodies were negative in all patients. Fourteen patients (70%) showed thyroid hypoplasia involving the entire gland. In these patients, the left thyroid lobe appeared usually, but not significantly, reduced compared with the right thyroid lobe. One patient (5%) showed thyroid hemiagenesis. Only five patients (25%) showed a thyroid with normal volume, and of these five, one patient showed marked thyroid hypoplasia of the left lobe. In all WS patients with diagnosis of subclinical or overt hypothyroidism, thyroid hypoplasia was detected. No cases of subclinical or overt hypothyroidism were found in WS with normal thyroid volume. CONCLUSIONS: This study confirms the presence of alterations of thyroid function in WS and also suggests the frequent occurrence of abnormalities of thyroid morphology in these patients. Patients with WS should be monitored for thyroid function and a thyroid ultrasound screening should be considered, especially in those patients with changes in thyroid function.
Adolescent↗
Alterations in the oxidant-antioxidant status in prepubertal children with growth hormone deficiency: effect of growth hormone replacement therapy.
OBJECTIVE: Growth hormone deficiency (GHD) in adults is associated with increased oxidative stress determined by the underlying GH-IGF-1 axis alterations. Despite GHD being a common diagnosis in children with short stature, no data on the oxidant/antioxidant status are available in this age group. This study was designed to detect differences in oxidative stress parameters between prepubertal GH-deficient children and healthy controls. Furthermore, the effect of 12 months of conventional GH replacement (rGH) on oxidant-antioxidant status was evaluated in the GHD group only. PATIENTS: Ten (nine males and one female) prepubertal children (mean age 9.1 +/- 1.3 years) with GHD were recruited and matched for sex and age (9.2 +/- 1.9 years) with 20 healthy controls (18 males and two females). MEASUREMENTS: At study entry, lag phase, an index of susceptibility of low density lipoprotein (LDL) to in vitro oxidation, malondialdehyde (MDA) and vitamin E were measured in all subjects. These parameters were also evaluated in GH-deficient children after 12 months of rGH treatment. RESULTS: The lag phase was significantly decreased in GH-deficient children compared to healthy controls (15.50 +/- 7.4 vs. 43.00 +/- 9.2 min; P = 0.0007), while MDA was significantly increased (1.33 +/- 0.38 vs. 0.46 +/- 0.10 nmol/mg; P = 0.0006). Vitamin E levels were significantly decreased (22.44 +/- 9.57 vs. 35.38 +/- 16.49 micromol/l; P = 0.001). IGF-1 and IGFBP-3 correlated directly to lag phase (r = 0.48; P = 0.01; r = 0.63, P = 0.002, respectively) and to vitamin E (r = 0.59, P = 0.003; r = 0.58, P = 0.006, respectively). By contrast, IGF-1 and IGFBP-3 correlated indirectly to MDA (r = -0.47, P = 0.01; r =-0.65, P = 0.002, respectively). After 1 year of rGH therapy, lag phase (39.32 +/- 15.24 min; P = 0.005) and vitamin E (34.9 +/- 7.7 micromol/l; P = 0.005) increased significantly, while MDA decreased significantly (0.71 +/- 0.42 nmol/mg; P = 0.005), reaching normal levels. CONCLUSIONS: These data show that children with GHD have substantially increased oxidative stress parameters compared to healthy controls and demonstrate a normalization of these parameters after 1 year of rGH therapy.
Antioxidants↗
Endocrine and metabolic changes in epileptic patients receiving valproic acid.
It has been well known for many years that valproic acid (VPA) therapy can induce obesity and important endocrine dysfunctions; among these dysfunctions, the most common are hyperandrogenism, menstrual disorders, polycystic ovary syndrome, hyperinsulinism, and changes in LH, FSH, and sexual and thyroid hormones. Moreover, abnormalities in pubertal development and impaired skeletal growth have been reported. The aim of this review is to analyze the main effects of VPA on endocrinological functions in patients with epilepsy in order to understand in depth the pathophysiological mechanisms and, consequently, to improve the care of these patients.
Anticonvulsants↗
Hypoglycemia, hypoglycemia unawareness and counterregulation in children and adolescents with type 1 diabetes mellitus.
Three clinical phenomena have been defined in the last decade in patients with diabetes mellitus as a dangerous iatrogenic sequel of hypoglycemia. These are hypoglycemia unawareness, defective glucose counterregulation and a lowered hypoglycemic threshold for hypoglycemic symptoms. Former mild hypoglycemia episodes cause a decrease and a delay in the protective hormonal counterregulatory response and warning symptoms in subsequent episodes, and in the absence of these, risk of severe hypoglycemia increases considerably. It has been demonstrated that when protection is provided against hypoglycemia with strict monitoring programs designed to avoid even mild hypoglycemia episodes, blunted autonomic symptoms and counterregulatory hormonal responses are rectified. Therefore, the best course of action in the treatment of pediatric diabetes mellitus is frequent blood sugar measurements, flexible multiple dose insulin regimens facilitating insulin dose adjustments as required, and a diet. In order to implement this, it is essential to organize an intensive training program with the patient and family, and to provide psychological support and close coordination with the diabetes treatment team.
Adolescent↗
Osteoprotegerin serum levels in children with type 1 diabetes: a potential modulating role in bone status.
OBJECTIVE: Children and adolescents with type 1 (insulin-dependent) diabetes mellitus (T1DM) show several impairment of bone metabolism and structure, resulting in a higher risk of decreased bone mass and its related complications later in life. Alterations of the nuclear factor-kappaB ligand (RANKL)/osteoprotegerin (OPG) system have been implicated in several metabolic bone diseases characterized by increased osteoclast differentiation and activation and enhanced bone resorption. DESIGN: We aimed to assess OPG levels and to investigate the possible relation between OPG levels, bone status and glycemic control in a group of prepubertal children with T1DM without microvascular complications. METHODS: Twenty-six prepubertal T1DM children (median age 9.9 years, range 4.1-13.1 years) were studied. In all patients, serum OPG, hemoglobin (Hb)A1c, parathyroid hormone (PTH) and 25-dihy-droxyvitamin D (25-D) levels were evaluated. Bone quality was determined by measuring the attenuation of ultrasound waves by bone (broadband ultrasound attenuation (BUA)) at the calcaneal site. The data were compared with those of a group of 45 age-, sex-and body-size-matched healthy children. RESULTS: Children with T1DM showed a reduced Z-score BUA in comparison with the control group (Student's t-test, P < 0.0001). Plasma OPG levels were significantly higher in diabetic children than in controls (Student's t-test, P < 0.0001). In T1DM children, Z-score BUA values displayed a significant correlation with OPG (Student's t-test, r = -0.62; P = 0.001), and HbA1c (r = -0.59; P = 0.007). OPG levels were significantly correlated with HbA1c (r = 0.56; P = 0.008). In a multiple regression analysis including age, duration of diabetes, physical activity, calcium intake, mean HbA1c and Z-score BUA, only HbA1c significantly predicted serum OPG levels (beta 0.67; P = 0.003). CONCLUSIONS: Prepubertal children with T1DM have a significant increase of OPG levels. OPG serum concentrations are correlated to calcaneal BUA and HbA1c values. OPG could be a new marker of reduced bone mass in children with T1DM.
Adolescent↗
Is homeostasis model assessment better than the quantitative insulin-sensitivity check index and fasting glucose/insulin ratio?
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Adolescent↗
Effects of irbesartan on intracellular antioxidant enzyme expression and activity in adolescents and young adults with early diabetic angiopathy.
OBJECTIVE: Defective intracellular antioxidant enzyme production (IAP) has been demonstrated in adults with diabetic nephropathy. The objective of this study was to evaluate the effects of irbesartan, an angiotensin II receptor antagonist, on IAP in adolescents and young adults with type 1 diabetes and early signs of retinopathy and nephropathy. RESEARCH DESIGN AND METHODS: This prospective, matched case-control study was conducted between November 2001 and December 2002 among 14 type 1 diabetic patients with early signs of angiopathy (ages 14-21 years), 11 type 1 diabetic patients without angiopathy (ages 12-22 years), and 10 healthy volunteers (ages 16-22 years). Skin fibroblasts were obtained by skin biopsies from the anterior part of the forearm and cultured in Dulbecco's modified Eagle's medium. The activity and mRNA expression of CuZn superoxide dismutase (CuZnSOD), Mn superoxide dismutase (MnSOD), catalase (CAT), and glutathione peroxidase (GPX) were measured before and after 6 months of treatment with irbesartan (150 mg/day); on both occasions, antioxidant enzyme activity was evaluated at different glucose concentrations (5 and 22 mmol/l). RESULTS: At a normal glucose concentration (5 mmol/l), the activity and mRNA expression of CuZnSOD (0.50 +/- 0.21 units/mg protein, 4.4 +/- 1.5 mRNA/glyceraldehyde-3-phosphate dehydrogenase), MnSOD (0.26 +/- 0.04 units/mg protein, 0.08 +/- 0.07 mRNA), CAT (0.32 +/- 0.08 units/mg protein, 4.8 +/- 1.3 mRNA), and GPX (0.53 +/- 0.09 units/mg protein, 2.2 +/- 0.9 mRNA) were not different among the three groups (only values of diabetic subjects with angiopathy are shown). At high glucose concentrations, the activity and mRNA expression of CuZnSOD increased similarly in all groups (diabetic subjects with angiopathy: 0.93 +/- 0.26 units/mg protein, 9.4 +/- 2.1 mRNA); that of CAT and GPX increased in only control subjects and diabetic subjects without angiopathy (diabetic subjects with angiopathy: 0.33 +/- 0.09 units/mg protein and 5.0 +/- 1.4 mRNA; 0.54 +/- 0.10 units/mg protein and 2.3 +/- 1.0 mRNA, respectively). MnSOD did not change in any group. Treatment with irbesartan in adolescents with diabetic angiopathy was able to restore CAT and GPX activity and mRNA expression after exposure to high glucose concentrations. Markers of oxidative stress (serum malondialdehyde, fluorescent products of lipid peroxidation, monocyte chemoattractant protein-1, and 8-isoprostanes prostaglandin F(2alpha)) were significantly reduced after treatment with irbesartan. CONCLUSIONS: Adolescents and young adults with early signs of diabetic angiopathy have defective intracellular antioxidant enzyme production and activity. Treatment with irbesartan can substantially improve the activity and production of these enzymes in skin fibroblasts.
Adolescent↗
Treating diabetic retinopathy by tackling growth factor pathways.
Diabetic retinopathy (DR) remains a major cause of new cases of blindness onset in adults. The prevalence of diabetic eye disease is strongly related to the duration of diabetes, blood pressure and glycemic control, although a multifactorial pathogenesis is likely to be probable. Despite the effectiveness of current prevention (by tight metabolic and blood pressure control) and treatment (with laser photocoagulation) methods, and with the help of screening programs, diabetic eye disease is still a problem. Recent advances in our understanding of the pathogenesis of microvascular complications and particularly of the role of growth factors (GFs) in retinal changes have allowed significant advances in the medical management of DR. Studies of the biochemical process underlying DR have clearly demonstrated an important role for a number of aberrantly expressed GFs or their second messengers (eg, vascular endothelial growth factor, growth hormone, insulin-like growth factor-1, protein kinase C and pigment epithelium derived factor) possibly acting together in the development of structural changes characterizing early stages of vascular DR. The critical role of GF expression has led to new experimental therapeutic intervention in DR. In fact, timely pharmacological intervention in GF synthesis and activities may arrest the development of early vascular changes. As the effects of GFs become better understood, pharmacological manipulation of GF synthesis and action will be useful in the early stages of vascular change with the potential to prevent diabetes-related visual loss.
Animals↗
Childhood obesity.
In March 2004 a group of 65 physicians and other health professionals representing nine countries on four continents convened in Israel to discuss the widespread public health crisis in childhood obesity. Their aim was to explore the available evidence and develop a consensus on the way forward. The process was rigorous, although time and resources did not permit the development of formal evidence-based guidelines. In the months before meeting, participants were allocated to seven groups covering prevalence, causes, risks, prevention, diagnosis, treatment, and psychology. Through electronic communication each group selected the key issues for their area, searched the literature, and developed a draft document. Over the 3-d meeting, these papers were debated and finalized by each group before presenting to the full group for further discussion and agreement. In developing a consensus statement, this international group has presented the evidence, developed recommendations, and provided a platform aimed toward future corrective action and ongoing debate in the international community.
Child↗
Effects of vitamin E supplementation on intracellular antioxidant enzyme production in adolescents with type 1 diabetes and early microangiopathy.
Defective intracellular antioxidant enzyme production (IAP) has been demonstrated in adults with diabetic nephropathy. To evaluate the effects on IAP of vitamin E administration in adolescents with type 1 diabetes and early signs of microangiopathy, 12 adolescents (aged 11-21 y; diabetes duration 10-18) were studied. Eight had retinopathy [background (four), preproliferative (three), or proliferative (one)], four had persistent microalbuminuria, and seven had both. Skin fibroblasts were obtained by biopsies and cultured in Dulbecco's modified Eagle's medium. CuZn superoxide dismutase (SOD), MnSOD, catalase (CAT), and glutathione-peroxidase (GPX) activity and mRNA expression were measured before and after 3 mo of synthetic vitamin E supplementation (600 mg twice daily); on both occasions, IAP was evaluated at different ex vivo glucose concentrations (5 and 22 mM). Ten adolescents with type 1 diabetes (aged 12-20 y) without angiopathy and eight healthy volunteers (aged 15-22 y) participated as control subjects. Vitamin E serum levels were measured throughout the study. In normal glucose concentrations, CuZnSOD, MnSOD, CAT, and GPX activity and mRNA expression were not different among the groups. In high glucose, CuZnSOD activity and mRNA increased similarly in all groups [angiopathics: 0.96 +/- 0.30 U/mg protein; 9.9 +/- 3.2 mRNA/glyceraldehyde-3-phosphate dehydrogenase). CAT and GPX activity and mRNA did not increase in high glucose only in adolescents with angiopathy (0.35 +/- 0.09; 4.2 +/- 0.1 and 0.52 +/- 0.14; 2.4 +/- 0.9, respectively). MnSOD did not change in any group. Vitamin E supplementation had no effect on any enzymatic activity and mRNA in both normal and hyperglycemic conditions. Adolescents with early signs of diabetic angiopathy have defective IAP and activity, which are not modified by vitamin E.
Adolescent↗
Balance between PGD synthase and PGE synthase is a major determinant of atherosclerotic plaque instability in humans.
OBJECTIVE: Inducible cyclooxygenase (COX-2) catalyzes the first step in prostanoid biosynthesis and is considered a proinflammatory enzyme. COX-2 and type 1 inducible PGE synthase (mPGES-1) have a role in metalloproteinase (MMP) release leading to plaque rupture. In contrast, lipocalin-type PGD synthase (L-PGDS) has been shown to exert antiinflammatory actions. Thus, in this study we investigated whether a shift from a PGDS-oriented to a PGES-oriented profile in arachidonate metabolism leads to inflammatory activation in rupture-prone plaque macrophages. METHODS AND RESULTS: Atherosclerotic plaques were obtained from 60 patients who underwent carotid endarterectomy, symptomatic (n=30) and asymptomatic (n=30) according to evidence of recent transient ischemic attack or stroke. Plaques were analyzed for COX-2, mPGES-1, L-PGDS, PPARgamma, IkappaBalpha, NF-kappaB, and MMP-9 by immunocytochemistry, Western blot, reverse-transcriptase polymerase chain reaction, enzyme immunoassay, and zymography. Prostaglandin E2 (PGE2) pathway was significantly prevalent in symptomatic plaques, whereas PGD2 pathway was overexpressed in asymptomatic ones, associated with NF-kappaB inactivation and MMP-9 suppression. In vitro COX-2 inhibition in monocytes was associated with reduced MMP-9 release only when PGD2 pathway overcame PGE2 pathway. CONCLUSIONS: These results suggest that COX-2 may have proinflammatory and antiinflammatory properties as a function of expression of downstream PGH2 isomerases, and that the switch from L-PGDS to mPGES-1 in plaque macrophages is associated with cerebral ischemic syndromes, possibly through MMP-induced plaque rupture.
Arachidonic Acid↗
Obesity and plasma concentrations of alpha-tocopherol and beta-carotene in epileptic girls treated with valproate.
To investigate whether epileptic patients who become obese after valproic acid (VPA) therapy can have a high risk of atherosclerosis related to the oxidation of low-density lipoprotein, we prospectively studied the plasma concentrations of lipid-soluble antioxidant vitamins in a group of 20 epileptic girls and 20 controls. After 1 year of VPA treatment, epileptic patients who gained weight had decreased plasma concentrations of alpha-tocopherol and alpha- and beta-carotene, the main lipid-soluble antioxidants. Moreover, 5 patients who gained weight were reevaluated 6 months after withdrawal from VPA therapy and showed normal body mass indices and normalized plasma levels of antioxidants. In conclusion, the data suggest that epileptic patients who gain weight after VPA therapy have reduced plasma concentrations of antioxidant vitamins and that these reductions are reversible after VPA withdrawal.
Adolescent↗
Persistence of impaired pancreatic beta-cell function in children treated for acute lymphoblastic leukaemia.
Treatment for acute lymphoblastic leukaemia can induce alterations of glucose metabolism, but long-term follow-up data on this topic are still absent. We aimed to study glucose metabolism by intravenous and oral glucose tolerance testing in 32 children affected by acute lymphoblastic leukaemia and who were off-therapy for at least 1 year. 22 (69%) children presented with impaired first-phase insulin response, which in nine children was associated with impaired glucose tolerance and in one child with overt diabetes. Fasting insulin (4.65 mU/L, 95% CI 1.1-8.1; p=0.008), insulinogenic index (0.46; 0.02-0.98; p=0.03), and homoeostatic model assessment beta-cell function (80.1, 7.2-153; p=0.02) were reduced in the children with impaired insulin response. Chemotherapy for acute lymphoblastic leukaemia is associated with beta-cell function damage, which persists even after therapy has been stopped.
Antineoplastic Agents↗
Intermittent oral diazepam prophylaxis in febrile convulsions: its effectiveness for febrile seizure recurrence.
In order to evaluate the effectiveness of diazepam for the reduction in the recurrence of febrile seizures we carried out a prospective study in two groups of children; Group A: 45 children (25 female, 20 male), receiving oral prophylaxis with diazepam, and Group B: 65 children (35 female, 30 male) who did not receive any oral prophylaxis. All subjects of both groups were followed for at least 4 years and finally re-evaluated at the mean age of 6.7+/-1.4 years. Among the patients of Group A, recurrent febrile seizures (FS) occurred in five of the 45 children (11.1%). Among the 65 children of Group B, 20 (30.7%) went on to have one or more additional episodes. In conclusion, our study demonstrates that oral diazepam, given only when fever is present, is an effective means of reducing the risk of recurrences of FS.
Administration, Oral↗
Photosensitivity and epilepsy: a follow-up study.
To understand the evolution of photosensitivity and to evaluate if its disappearance is related to the response to anticonvulsant therapy, we performed a long-term study of 42 patients (17 males, 25 females; age at onset 6 years 9 months, SD 5 years 2 months, range 5 years to 12 years 1 month) who had electroencephalography (EEG) evidence of photosensitive epilepsy. Of the patients, 36 were treated with valproate (VPA) monotherapy and four received VPA in combination with other antiepileptic drugs (AEDs), which were carbamazepine and lamotrigine. Two patients were given no drugs, but treated with stimuli avoidance. All patients were investigated with EEG by using intermittent photic stimulation. The photoparoxysmal response indicated the presence of photosensitivity. At the end of follow-up, the photoparoxysmal response had disappeared in 25 patients. Thirty-three patients became seizure-free. Our study confirms that photosensitive epilepsy has a good prognosis for seizure control that is independent of the persistence or disappearance of photosensitivity.
Adolescent↗
Diabetic neuropathy in children and adolescents.
Diabetic neuropathy (DN) represents a major complication of type 1 diabetes mellitus (T1DM) but there is considerable uncertainty as to its incidence, prevalence, diagnosis and prognosis in pediatric population. Generally, DN is classified as polyneuropathy, focal neuropathy and autonomic neuropathy. The latter seems to be detectable even in asymptomatic children and adolescents with diabetes and is associated with the most serious consequences, such as hypoglycemia unawareness and cardiovascular dysfunction. A near-normal control of blood glucose in the early years after onset of diabetes may delay the development of clinically significant nerve impairment and, therefore, children and adolescents with diabetes represent a critical target for primary prevention of this complication. The aim of this review is to focus on the main clinical, epidemiological and prognostic aspects of DN in children and adolescents with T1DM. Etiopathogenetic theories and diagnostic tools are also reviewed from in a pediatric perspective.
Adolescent↗