[Show abstract][Hide abstract] ABSTRACT: Iron overload in hemoglobinopathies is secondary to blood transfusions, chronic hemolysis, and increased iron absorption and leads to tissue injury requiring the early use of chelating agents. The available agents are parenteral deferoxamine and oral deferiprone and deferasirox. There are limited data on the safety and efficacy of deferiprone at a very young age. The aim of our study was the presentation of data regarding the use of oral solution of deferiprone in 9 children (mean age 6.5, range 2-10) with transfusion dependent hemoglobinopathies (6 beta thalassemia major, 1 thalassemia intermedia, and 2 sickle cell beta thalassemia). The mean duration of treatment was 21.5 months (range 15-31). All children received the oral solution without any problems of compliance. Adverse reactions were temporary abdominal discomfort and diarrhea (1 child), mild neutropenia (1 child) that resolved with no need of discontinuation of treatment, and transient arthralgia (1 child) that resolved spontaneously. The mean ferritin levels were significantly reduced at the end of 12 months (initial 2440 versus final 1420 μ g/L, P < 0.001). This small study shows that oral solution of deferiprone was well tolerated by young children and its use was not associated with major safety concerns. Furthermore, it was effective in decreasing serum ferritin.
[Show abstract][Hide abstract] ABSTRACT: In humans, microbial colonisation of the intestine begins just after birth. However, development of the normal flora is a gradual process, which is initially determined by factors such as genetic aspects, the maternal-foetal interaction, place and mode of delivery, early feedings strategies, and the use of antibiotics. Current knowledge on the significance and impact of the gut microflora on the development of the gut immune system indicates that a close relationship between allergic sensitisation and the development of the intestinal microflora may occur in infancy. Intestinal micro-organisms could downregulate the allergic inflammation by counterbalancing type 2 T-helper cell responses and by enhancing allergen exclusion through an immunological response.
Allergologia et Immunopathologia 07/2013; 42(1). DOI:10.1016/j.aller.2013.03.010 · 1.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Unlabelled:
Kearns-Sayre syndrome (KSS) is a rare mitochondrial DNA deletion syndrome defined as the presence of ophthalmoplegia, pigmentary retinopathy, onset less than age 20 years, and one of the following: cardiac conduction defects, cerebellar syndrome, or cerebrospinal fluid protein above 100 mg/dl. KSS may affect many organ systems causing endocrinopathies, encephalomyopathy, sensorineural hearing loss, and renal tubulopathy. Clinical presentation at diagnosis is quite heterogeneous and, usually, few organs are affected with progression to generalized disease early in adulthood. We present the case of a boy with KSS presenting at the age of 5 years with myopathy, Addison's disease, primary hypoparathyroidism, and Fanconi syndrome. The proper replacement treatment along with the administration of mitochondrial metabolism-improving agents had a brief ameliorating effect, but gradual severe multisystemic deterioration was inevitable over the next 5 years.
This report highlights the fact that in case of simultaneous presentation of polyendocrinopathies and renal disease early in childhood, KSS should be considered.
European Journal of Pediatrics 08/2012; 172(4). DOI:10.1007/s00431-012-1798-1 · 1.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The adipocytokines leptin and adiponectin represent a critical link between metabolism, immunity and chronic inflammation. A chronic vascular inflammatory state plays an important role in the pathophysiology of thalassaemia. We aimed to analyze the levels of these adipocytokines and determine any possible correlations with disease severity or vascular inflammation markers in beta-thalassaemia.
Serum leptin, adiponectin, high-sensitivity C-reactive protein, endothelins, vascular adhesion molecule-1, intracellular adhesion molecule-1 and L- and E-selectin were measured in 28 beta-thalassaemia patients and compared with levels in healthy controls.
Leptin was significantly lower in patients compared to controls (2.23 ± 1.8 vs. 10.24 ± 5.78 μg/l; p = 0.0018), whereas adiponectin was elevated (11.75 ± 5.67 vs. 6.83 ± 2.75 μg/l; p = 0.009). For both adipocytokines, no correlations were found with characteristics such as age, gender, type of chelation, body mass index z score or haemoglobin. Leptin, but not adiponectin, was negatively correlated with ferritin (p = 0.032, r = -0.61). No correlations were found between leptin and the inflammation markers. However, adiponectin was positively correlated with endothelin-1 (p = 0.022, r = 0.63).
Serum leptin is low in beta-thalassaemia, perhaps due to the toxic effect of iron overload on adipose tissue. Paradoxically, adiponectin levels are high and positively correlated with endothelin-1, raising questions about the pro- or anti-inflammatory role of this adipocytokine in beta-thalassaemia.
[Show abstract][Hide abstract] ABSTRACT: Viral meningitis is characterized by cerebrospinal fluid (CSF) lymphocyte pleocytosis, although neutrophils may predominate in the early phase. The T helper 1 (Th1)/Th2 cytokine balance and expression of adhesion molecules seem to be involved in the CSF chemotaxis. We aimed to determine expression of cytokines and adhesion molecules in enteroviral meningitis. We investigated the serum and CSF levels of adhesion molecules (E-selectin, L-selectin, vascular cell adhesion molecule-1 [VCAM-1], and intracellular adhesion molecule-1 [ICAM-1]) and cytokines (interleukin-12 [IL-12] and IL-4) in 105 children during an outbreak of enteroviral meningitis. Diagnosis was confirmed with positive polymerase chain reaction (PCR) and/or serology for echovirus or Coxsackie virus, and matched with control subjects for clinical features but with negative PCR and/or serology. Apart from VCAM-1, the CSF levels of all investigated inflammatory molecules were significantly increased. In serum, sL-selectin and ICAM-1 levels were significantly higher than control subjects. Serum and CSF L-selectin, serum VCAM-1, and CSF IL-12 were all observed to be expressed in significantly higher levels in the neutrophil-dominant subgroup (72% had duration of symptoms <24 h) than in the lymphocyte-dominant group (87.5% had duration of symptoms >24 h). Serum and CSF ICAM-1 was found at significantly higher levels in the latter group. Evolving expression of adhesion molecules and cytokines indicates a shift from Th1 to Th2 immune responses as infection progresses.
Journal of interferon & cytokine research: the official journal of the International Society for Interferon and Cytokine Research 09/2010; 30(9):661-5. DOI:10.1089/jir.2009.0113 · 2.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Diamond-Blackfan anemia (DBA) is a rare, congenital, pure red blood cell aplasia owing to gene defects affecting the function of ribosomal proteins, essential for erythroid maturation. Iron overload is a serious complication of chronic transfusions, which may lead to cardiac toxicity and endothelial damage. We report a case of pulmonary embolism, observed after viper bite in a transfusion-dependent child with DBA without known inherited thrombophilic factors. Embolic events are uncommon after viper bites, which they usually cause consumption coagulopathy, resulting in hypocoagulable state. DBA has not been earlier correlated with thrombotic episodes. In our patient, we suggest an iron overload-induced hypercoagulability state, which in the presence of a procoagulant substance lead to the development of a thromboembolic event.
[Show abstract][Hide abstract] ABSTRACT: Sweet's syndrome characterized by fever, blood neutrophilia and inflammatory skin lesions, is rarely diagnosed in children. It presents in three clinical settings: classical Sweet's syndrome, usually after a respiratory tract infection; malignancy-associated, frequently related to acute myelogeneous leukemia; and drug-induced. We present, to the best of our knowledge, the first case of a rotavirus -infection-related Sweet's syndrome.
An 18-month-old boy of Hellenic origin was referred to us with diarrhea, fever, neutrophilia, typical skin lesions, asymmetrical hip arthritis and oropharyngeal involvement. A skin biopsy confirmed the diagnosis. Thorough screening did not reveal any underlying systemic illness, except for the confirmation of an overt rotavirus infection. The syndrome responded promptly upon corticosteroid administration; no recurrence was observed.
Besides describing the connection of Sweet's syndrome to a rotavirus infection, this case report is also a reminder that in a child presenting with a febrile papulo-nodular rash with neutrophilia Sweet's syndrome should be included in the differential.
Journal of Medical Case Reports 08/2010; 4(1):281. DOI:10.1186/1752-1947-4-281
[Show abstract][Hide abstract] ABSTRACT: Brucellosis is characterized by chronicity and relapses despite efficacious treatment. Cytokines and especially the Th1/Th2 balance may be involved in the susceptibility or resistance to the Brucella species. In order to identify predictors of treatment outcome, we measured the pre and posttreatment levels of serum interleukin-2 (IL-2) and soluble IL-2 receptor alpha (sIL-2Ralpha) in 20 children with brucellosis. All children were treated for 6 weeks and three of them (15%) presented with a relapse at 2, 3 and 8 months after treatment had ended.
Serum IL-2 levels, both pretreatment and posttreatment, did not significantly differ between patients and controls. By contrast, pretreatment sIL-2Ralpha levels were significantly higher in patients (P< or =0.0001) than in controls. sIL-2Ralpha levels significantly declined (P<0.001) after the 6-week antibiotic regimen in the 17 children who subsequently had a good outcome without relapses, but not in the three patients who relapsed.
A decline in serum sIL-2Ralpha levels might be used as a marker of treatment efficacy in brucellosis.
The Journal of infection 11/2005; 51(3):206-10. DOI:10.1016/j.jinf.2004.10.013 · 4.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Intracranial hydatidosis is more common in children than in adults. The most severe complication is anaphylactic response after direct rupture into the subarachnoid spaces. We report a case of brain hydatid cyst that was accidentally drained into the peritoneal cavity and was not complicated by an anaphylactic response or dissemination.
[Show abstract][Hide abstract] ABSTRACT: An increased incidence of cardiovascular disease has been found in rheumatic disorders. Changes in the variables of aortic elasticity in patients with juvenile idiopathic arthritis (JIA) were evaluated and their relationship to inflammation, anti-rheumatic drugs and traditional cardiovascular risk factors were investigated in this study.
Phase contrast MR was performed in 31 patients with JIA and 28 age and sex matched controls to evaluate the aortic distensibility and pulse wave velocity (PWV). Disease activity variables, plasma lipid profile, homocysteine, thyroid hormones, glucose and insulin were assessed in the patients.
Eighteen patients had oligoarticular, 6 polyarticular and 7 systemic disease. Distensibility was lower (mean: 10.25; SD: 4.18) and PWV was higher (mean: 3.68; SD: 1.59) in the patients compared to the controls (mean: 13.4; SD: 4.99), (mean: 1.38; SD: 0.54) respectively (p < 0.01). A positive correlation between PWV and age was observed in the patients (rs = 0.47, p < 0.01) and controls (rs = 0.72, p < 0.01), and a negative correlation between distensibility and age in the patients (rs = -0.59, p < 0.01) and controls (rs = -0.63, p < 0.01). No statistically significant correlations were found between distensibility and PWV and metabolic and disease activity parameters. When distensibility and PWV were adjusted for age no significant differences were found between the three subtypes of JIA.
JIA is associated with increased aortic stiffness that might suggest subclinical atherosclerosis. Early detection and follow-up by non-invasive methods may be useful in the prevention of future cardiovascular disease.
Clinical and experimental rheumatology 11/2003; 21(6):794-7. · 2.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The short-term effects of corticosteroids (CS) administered intravenously (IV) on biochemical parameters of bone metabolism were followed in infants and children. Forty-nine patients from 2 months to 10 years of age, admitted to Pediatrics Department for bronchiolitis, viral-associated wheezing and croup, were treated with IV hydrocortisone or methylprednisolone (10 or 2 mg/Kg/day, respectively) for 3 days. Blood and fasting urine were collected on admission (day 1), 2 days later (day 3) and 12 days after the end of therapy (day 15). Fifty-one children of similar age and gender without respiratory problems or bone diseases were used as controls. On day 3, suppression of the bone formation markers osteocalcin (OC) (P < 0.001) and total alkaline phosphatase (ALP) (P < 0.05) was observed, but not of the bone resorption markers of hydroxyproline, pyridinoline and calcium excretion (UHyp/UCr, UPYD/UCr and UDPD/UCr, UCa/UCr). Significant decreases were indicated in serum phosphate (Pi) and the maximum renal tubular Pi reabsorption (TmP/GFR) compared to basal (P < 0.001). No significant changes were noticed in the circulating levels of calcium (Ca), parathyroid hormone (iPTH), 25OHD, 24,25(OH)2D, 1,25(OH)2D, the insulin-like growth factor-I (IGF-I) and its binding protein-3 (IGFBP-3). Two weeks after therapy, the increase of OC to higher than basal (P < 0.01) indicated a probable activation of the osteoblasts. Serum Pi and the TmP/GFR index values that had significantly decreased by day 3 returned to pretreatment levels by day 15. When assessing the effects of the CS in relation to age, no changes were detected in the levels of OC and total ALP in the <12-month-old children, but a fall of OC was observed in the >1-year-old group (P < 0.001). In contrast to the OC, the effects on serum and renal tubular reabsorption of phosphate were similar for both groups. In conclusion, short-term IV administered CS led to significant but reversible inhibition of bone formation markers, especially detectable in the >1-year-old children, without affecting the bone resorption ones. The adverse effects on phosphate metabolism were also significant, but temporal and irrespective of age.
Calcified Tissue International 10/2003; 73(4):319-25. DOI:10.1007/s00223-002-2099-x · 3.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to evaluate the role of MRI in the assessment of hip joint involvement in clinical subtypes of juvenile idiopathic arthritis (JIA). 28 patients (mean age 12.5 years) with JIA (oligoarthritis 8, polyarthritis 13, systemic arthritis 7) were examined with T(2) weighted turbo spin echo and T(1) weighted spin echo (plain and contrast enhanced) sequences. The severity of joint involvement was evaluated using an MR grading score: grade 1=no contrast enhancement; grade 2=focal synovial contrast enhancement; grade 3=diffuse synovial contrast enhancement; grade 4=grade 3+diffuse synovial thickening; grade 5=grade 4+villonodular synovial thickening; and grade 6=grade 5+cartilage and subchondral bone erosions. MRI was abnormal in 57.1% of cases (25% of oligoarthritis, 53.8% of polyarthritis and 100% of systemic arthritis). Clinical examination was positive in 32.1% of cases and was associated with higher MR grades (mean 4.6, SD 1.34) compared with a negative clinical examination, which was associated with lower MR grades (mean 1.78, SD 1.13) (p<0.001). Patients with active disease (mean grade 3.9, SD 2) had higher MR grades than those with inactive disease (mean grade 2.1, SD 1.4) (p<0.01). The MR grades were different in the three clinical subtypes: oligoarticular (mean 1.5, SD 1.06); polyarticular (mean 2.38, SD 1.55); and systemic (mean 4.85, SD 1.21) (F:12.3, p<0.001), with a significant difference between systemic arthritis and oligoarthritis, and between systemic arthritis and polyarthritis (p<0.001). MRI of the hip might be considered for inclusion in the study protocol of patients with JIA since it reveals joint involvement at early stages and provides a detailed evaluation of the extent of joint disease.
British Journal of Radiology 03/2002; 75(891):229-33. DOI:10.1259/bjr.75.891.750229 · 2.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to follow the changes in bone mineral density (BMD) and biochemical markers of bone turnover in 10 children (7.5-17.5 years of age) with severe juvenile idiopathic arthritis (JIA), during a 3-year therapy with salmon calcitonin (100 IU/day 2 months on and 2 off for a year and 200 IU/day for 2 years) and calcium (500 mg/day). All patients were functional classes III and IV and were measured at yearly intervals with a dual photon absorptiometer at the lumbar spine. The changes observed were 7.2-9.5% per year for BMD and 2.0-6.0% for volumetric bone mineral density (BMDvol). The bone resorption markers showed significant decreases after a year's treatment (Pyr/Cr from 175+/-15 to 108+/-15 nm/mm, P < 0.001, Pyr-D/Cr from 24.3+/-3.5 to 13.3+/-1.9 nm/mm, P < 0.05, and OHPr/Cr from 57.4+/-11 to 35.1+/-8.4 microg/mg) and smaller changes thereafter. No significant changes were observed in the bone formation markers of osteocalcin and alkaline phosphatase. Serum iPTH, the vitamin D metabolites, and calcium concentrations fluctuated within normal, while calcium excretion increased from 0.3+/-0.1 to 1.9+/-0.4 mg/kg/24 hours, P < 0.001. In conclusion, the present study, despite its limitations of not being placebo controlled, shows possible beneficial effects of intranasal calcitonin on bone resorption and pain relief in JIA patients.
Calcified Tissue International 07/2001; 69(1):25-30. DOI:10.1007/s00223-001-0008-3 · 3.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The case of an otherwise well 9-y-old boy with fever, papular rash, jaundice and impaired liver function is presented. Streptococcus mitis sensitive to penicillin grew in blood culture. The boy had an excellent outcome. The clinical spectrum of viridans streptococci may be wider than currently anticipated, and Streptococcus mitis may cause septicaemia and hepatitis in immunocompetent individuals.