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ABSTRACT: Human rhinoviruses (HRVs) and house dust mites (HDMs) are among the most common environmental factors able to induce airway inflammation in asthma. Although epidemiological studies suggest that they also synergize in inducing asthma exacerbations, there is no experimental evidence to support this, nor any information on the possible mechanisms involved.
To investigate their interaction on the induction of airway epithelial inflammatory responses in vitro.
BEAS-2B cells were exposed to activated HDM Dermatophagoides pteronyssinus major allergen I (Der p I), HRVs (HRV1b or HRV16) or both in different sequences. IL-8/CXCL8 release, intercellular adhesion molecule (ICAM)-1 surface expression and nuclear factor kappaB (NF-kappaB) translocation were evaluated. Complementary, primary human bronchial epithelial cells (HBECs) exposed to both Der p I and RVs and IL-8, IL-6, IFN-gamma-induced protein (IP)-10/CXCL10, IFN-lambda1/IL-29, regulated upon activation normal T lymphocyte expressed and secreted (RANTES)/CCL5 release were measured.
RV and Der p I up-regulated IL-8 release, ICAM-1 expression and NF-kappaB translocation in BEAS-2B cells. Simultaneous exposure to both factors, as well as when cells were initially exposed to HRV and then to Der p I, resulted in further induction of IL-8 in a synergistic manner. Synergism was not observed when cells were initially exposed to Der p I and then to HRV. This was the pattern in ICAM-1 induction although the phenomenon was not synergistic. Concurrent exposure induced an early synergistic NF-kappaB translocation induction, differentiating with time, partly explaining the above observation. In HBECs, both HRV and Der p I induced IL-8, IL-6, IL-29 and IP-10, while RANTES was induced only by HRV. Synergistic induction was observed only in IL-8.
HRV and enzymatically active Der p I can act synergistically in the induction of bronchial epithelial IL-8 release, when HRV infection precedes or is concurrent with Der p I exposure. Such a synergy may represent an important mechanism in virus-induced asthma exacerbations.
Clinical & Experimental Allergy 10/2008; 38(10):1615-26. · 5.03 Impact Factor
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ABSTRACT: A hospital referral centre for childhood tuberculosis in Athens.
To evaluate the effectiveness of the screening programme implemented for childhood tuberculosis, through its impact on the epidemiological index.
In Greece, tuberculosis has been systematically screened for in children since 1991 using the tuberculin skin test. The epidemiological and clinical profiles of all tuberculous children who attended the TB clinic were compared. The children were divided into those who attended in 1982-1990 and those who did so in 1991-1999.
A total of 1122 TB patients were screened. In the second period there was an increase in numbers of immigrant children (3% vs. 28%, P = 0.0001), the rate of extra-pulmonary TB decreased (16% vs. 7.6%, P = 0.0001), patients identified by the screening programme increased (19% vs. 57%, P = 0.0001) and the number of symptomatic children fell (51% vs. 16%, P = 0.0001). The proportion of children who failed to attend for regular follow-up was lower during the second period (20% vs. 7%, P = 0.0001).
Our study suggests that the screening programme applied in Greece during the last decade has contributed to the early identification of tuberculosis, and the limitation of symptomatic patients and extrapulmonary TB cases.
The international journal of tuberculosis and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease 04/2003; 7(3):248-53. · 2.73 Impact Factor
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ABSTRACT: Coeliac disease is a genetic, immunologically mediated small bowel enteropathy that causes malabsorption. The immune inflammatory response to gluten frequently causes damage to many other tissues of the body. We report the association of coeliac disease and alopecia areata in two children, a 13-year-old girl and a 29-month-old girl. Both of our patients had immunoglobulin A (IgA) class endomysial antibodies, IgA and immunoglobulin G (IgG) antigliadin antibodies and subtotal villous atrophy on jejunal biopsy. Administration of a gluten-free diet to our patients resulted in complete hair growth and improved the gastrointestinal symptoms.
Journal of Paediatrics and Child Health 04/2003; 39(2):152-4. · 1.28 Impact Factor
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ABSTRACT: The authors investigated whether the considerable variability in serum bilirubin levels (STB) found in transfusion-dependent beta-thalassemia, beta-thal intermedia, and heterozygous beta-thalassemia individuals could be related to the coexistence of Gilbert syndrome (GS). The promoter region [A(TA)nTAA] of the bilirubin UDP-glucuronosyltransferase gene (UGT1A1) was analyzed in a total of 128 beta-thalassemia individuals (108 transfusion-dependent beta-thal patients, 20 very mild beta-thal intermedia) and in 33 beta-thal heterozygotes. The control group consisted of 70 healthy children with no history of anemia. The frequency of GS genotype (TA)7/(TA)7 did not differ significantly between the groups studied. A significant difference was observed between serum bilirubin levels (STB) and GS genotypes (TA)7/(TA)7 and (TA)6/(TA)7 and also between (TA)7/(TA)7 and (TA)6/(TA)6 for all groups examined. These results confirm that the (TA)7/(TA)7 GS genotype is one of the factors accounting for the hyperbilirubinemia observed in beta-thalassemia major, intermedia, and heterozygous individuals.
Pediatric Hematology and Oncology 01/2002; 18(8):477-84. · 0.89 Impact Factor
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ABSTRACT: Levels of circulating interleukin (IL)-2, IL-6, and IL-10, measured by enzyme-linked immunosorbent assay, were significantly higher in patients with cat scratch disease (CSD) than in healthy control subjects; no induction of IL-12 was observed, and levels of interferon-gamma and IL-4 were generally not detectable. This is the first report showing increased circulating cytokine levels in patients with CSD. The induction of these mediators can partly explain some clinical and pathological features of the disease.
Clinical Infectious Diseases 10/2001; 33(6):e54-6. · 9.15 Impact Factor
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ABSTRACT: Acute lymphoblastic leukemia (ALL) among children may be a rare outcome of a delayed non-specific infection in situations of overall low herd immunity. We evaluated the hypothesis as to whether newly diagnosed ALL cases, compared to their controls, are characterized by lower herd immunity, as reflected in a more seronegative spectrum to several agents, with the exception of a strongly positive response to a single infectious agent, assumed to trigger ALL.
The study included 94 incident cases of ALL, from all pediatric hematology-oncology units of Greece, and 94, matched for age and gender, controls hospitalized with minor non-infectious conditions. The past exposure to common infections was assessed using 10 serological markers.
There was little evidence for an association of ALL with the serology of any of the studied infectious agents among the very young children. In contrast, among children aged 5 years or older, leukemia was inversely associated with seropositivity to Epstein-Barr virus, human herpes virus-6, Mycoplasma pneumoniae and parvovirus B19.
Among children aged 5 years or older the risk of leukemia may be higher when the low herd immunity for several agents is challenged by late infection from an agent that, as a rule, would attack children at a younger age.
Cancer Causes and Control 10/2001; 12(7):645-52. · 2.88 Impact Factor
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ABSTRACT: The association of leptin with body fat concentration is well established. There is also experimental evidence of a direct effect of leptin on lipid metabolism. The aim of this study was to evaluate whether leptin levels are related to the corresponding serum lipid levels independently of body fat mass. The study population consisted of 294 phenotypically healthy school children aged 6 to 12 years. Age, sex, body weight, height, Tanner stage, and triceps skinfold thickness were recorded for all participating subjects. A blood sample was drawn in the morning after a 12-hour fast, and serum total, high-density lipoprotein (HDL), and low-density lipoprotein cholesterol; triglyceride; and leptin levels were determined. Multiple regression analysis showed that triglyceride values were positively correlated with the ln(log(e))-transformed leptin levels (beta =.01, P <.001), whereas HDL levels were inversely associated with lnleptin values (beta = -.06, P =.05) after controlling for age, sex, Tanner stage, and body mass index when each of the lipid parameters was tested separately in the regression model. However, the introduction of both triglycerides and HDL values in the same model eliminated the significance of association of HDL with lnleptin, and the positive relationship of triglycerides with lnleptin remained significant. Our results indicate that triglycerides are independently associated with leptin levels after controlling for any known confounder.
Metabolism 09/2001; 50(9):1091-4. · 2.66 Impact Factor
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Journal of Pediatric Gastroenterology and Nutrition 09/2001; 33(2):211-3. · 2.30 Impact Factor
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ABSTRACT: The purpose of the present study was to investigate whether idiopathic hypercalciuria may be implicated in the pathogenesis of febrile convulsions.
We studied 38 children (22 boys) with febrile convulsions (mean (+/- SD) age 3.25 +/- 1.09 years) and 45 healthy children (28 boys) of similar age who served as controls. Twenty-four hour urine calcium and phosphate, as well as serum calcium, phosphate, alkaline phosphatase and intact parathyroid hormone (PTH) concentrations were determined.
Hypercalciuria (urine Ca >4.0 mg/kg bodyweight per 24 h) was found in nine children with febrile convulsions (23.7%) and in three controls (6.7%). Hypercalciuric children excreted significantly more phosphate in their urine (37.0 +/- 11.6 mg/kg bodyweight per 24 h) than normocalciuric children (18.7 +/- 8.7 mg/kg bodyweight per 24 h) and controls (20.2 +/- 7.6 mg/kg bodyweight per 24 h). They also had higher serum intact PTH concentrations (49.87 +/- 15.36 pg/mL) than normocalciuric (35.39 +/- 15.67 pg/mL) and control children (28.21 +/- 14.00 pg/mL). According to the calcium-loading test, eight of nine children with hypercalciuria had the renal type of the disorder. Furthermore, hypercalciuric children had significantly more convulsive episodes (2.77 +/- 1.98) than normocalciuric children (1.86 +/- 1.24).
Our results suggest that renal hypercalciuria may be implicated in the pathogenesis of febrile convulsions.
Pediatrics International 06/2001; 43(3):231-4. · 0.63 Impact Factor
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ABSTRACT: The relationship between reactive thrombocytosis and the level of urinary tract infections was studied in 48 children. Platelets were counted before, during and after treatment. Reactive thrombocytosis was noticed in 74% of children with upper and in 14% with lower urinary tract infections. A significant rise in the platelet count presented in another five children (15%) with upper urinary tract infections. Conclusion: Reactive thrombocytosis was found almost exclusively in the renal parenchymal infections, usually during the recovery phase.
Acta Paediatrica 05/2001; 90(4):448-9. · 2.07 Impact Factor
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ABSTRACT: Cat scratch disease (CSD) commonly manifests as regional self-limited lymphadenitis. However, dissemination of the infection to distant multiple sites may occur even in immunocompetent patients. We report a series of 11 children with fever and extralymphocutaneous manifestations of CSD, in order to highlight potential multiorgan involvement in patients with febrile CSD. To be eligible for enrollment, patients had to present with involvement of sites other than regional lymph nodes. The diagnosis was based on suggestive clinical criteria, histological findings and positive serology. The utilization of ultrasound imaging revealed hepatic lesions in 3 children and splenic lesions in 8 children, whereas osteolytic lesions were observed in 4 children by bone scan. Hepatic or splenic involvement was not suggested by clinical signs or biochemical investigation in 2/3 and 6/8 children, respectively. Bone involvement was supported either by relative symptoms or signs. Our findings indicate that, in the presence of fever, extralymphocutaneous manifestations have to be anticipated in patients with clinically suspected CSD. The systematic use of imaging modalities in patients with serologically documented Bartonella henselae infection could contribute to a better understanding of the clinical spectrum of CSD.
Scandinavian Journal of Infectious Diseases 02/2001; 33(8):599-603. · 1.72 Impact Factor
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ABSTRACT: Poly(inosinic) and poly(cytidylic) acids (Poly I:Poly C) have been used to induce the production of endogenous interferon or release preformed interferon in mammals. Interferon increases the resistance of the cells. Sixty guinea pigs were used to investigate whether Poly I:Poly C gave protection from gentamicin nephrotoxicity. The animals were divided into six equal groups. Group 1 were controls; group 2 received gentamicin intramuscularly; group 3 received gentamicin and 12 h later frusemide; group 4 received gentamicin and 12 h later 1-deamino-8-D-argine vasopressin (DDAVP) intramuscularly; group 5 received subcutaneously Poly I:Poly C; group 6 received Poly I:Poly C and 24 h later gentamicin. Frusemide in group 3 potentiated gentamicin nephrotoxicity while DDAVP in group 4 ameliorated gentamicin nephrotoxicity. Poly I:Poly C itself had no toxic effect on renal tissue, while Poly I:Poly C followed 24 h later by gentamicin indicated a protective effect from the gentamicin nephrotoxicity as the functional and histological investigations indicated.
Cytobios 02/2001; 106(412):139-46.
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ABSTRACT: Visceral focal lesions are rarely encountered in patients with leishmaniasis despite the fact that splenomegaly, and to a lesser extent hepatomegaly, predominate among the clinical features of the disease. We present, using high resolution ultrasonography, the first 3 reported cases of focal splenic involvement in immunocompetent children with visceral leishmaniasis. All patients showed a prompt response to the conventional anti-leishmanial treatment administered. This favorable outcome indicates that localized splenic lesions should not be considered as a poor prognostic factor and that alteration of the standard anti-leishmanial regimens is not justified.
Scandinavian Journal of Infectious Diseases 02/2001; 33(11):865-7. · 1.72 Impact Factor
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European Journal of Pediatrics 12/2000; 159(11):873-4. · 1.88 Impact Factor
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ABSTRACT: Records were reviewed of 82 immunocompetent children (median age, 2. 5 years) from southern Greece who were diagnosed with visceral leishmaniasis from 1986 through 1998. Forty-nine (58%) patients originated from the city of Athens; of them, 46 (94%) lived by hills bordering the city. The median interval from the onset of symptoms to admission was 10 days. Fever and splenomegaly were observed in >95% of the patients. Thrombocytopenia was the most frequent hematological finding (80%). All patients were treated with meglumine antimonate; 20 (24%) of them were partially treated on an outpatient basis. Rapid clinical response was noted in all patients but one. Five patients relapsed; 3 responded to reintroduction of meglumine antimonate, 1 responded to liposomal amphotericin B, and 1 underwent splenic artery ligation. We conclude that pentavalent antimonials remain the first choice of treatment for visceral leishmaniasis in immunocompetent children in areas where resistance has not become a problem. It is possible to treat affected patients with outpatient administration of these agents, making them feasible options for therapy.
Clinical Infectious Diseases 11/2000; 31(5):1139-43. · 9.15 Impact Factor
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ABSTRACT: Plasma immunoreactive endothelin levels were determined in 31 children and adolescents with cystic fibrosis and it was examined whether these levels correlated with the severity of the disease. The study comprised 16 cystic fibrosis patients (mean (SD) age 13.0 (4.9) y) with impaired lung function (Group A), 15 cystic fibrosis patients (11.2 (5.5) y) with unimpaired lung function (Group B) and 28 healthy controls (10.6 (4.3) y) (Group C). The selection and classification of patients into groups was based on criteria including the grade of finger-clubbing, the Brasfield chest radiograph score and spirometric and arterial blood gas values. In all subjects, plasma immunoreactive endothelin, atrial natriuretic peptide, renin, serum aldosterone levels and serum and urine electrolytes were measured. CONCLUSIONS: Plasma endothelin levels were significantly higher in Group A (range 2.5-8.4 pg/ml, median 3.2 pg/ml) than those in Group B (1.3-3.8 pg/ml, median 2.0 pg/ml, p < 0.001) and Group C (1.5-3.5 pg/ml, median 2.5 pg/ml, p < 0.001), whereas they did not differ between groups B and C. They correlated positively with the severity of finger-clubbing, heart rate, arterial blood PCO2, plasma atrial natriuretic peptide levels and serum aldosterone levels and negatively with the arterial blood PO2, forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1) and the Brasfield chest radiograph score. In multivariate regression analysis PO2 was the only independent factor found to significantly affect plasma endothelin levels. In conclusion, plasma immunoreactive endothelin levels are increased in cystic fibrosis patients with impaired pulmonary function and are related to the severity of the disease.
Acta Paediatrica 09/2000; 89(8):915-20. · 2.07 Impact Factor
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ABSTRACT: We measured plasma atrial natriuretic peptide (ANP) levels in 30 children with idiopathic hypercalciuria (IH) and 19 normal controls (NC). A calcium (Ca) loading test was performed in all patients to determine the type of IH. Subsequently plasma ANP, cAMP and renin activity (PRA), serum total and ionized Ca, intact parathyroid hormone, aldosterone, and 1,25-dihydroxyvitamin D as well as urine Ca, cAMP, and electrolytes were determined in all subjects. The mean (SD) plasma ANP levels were significantly lower in patients with renal hypercalciuria (RH) [21.4 (4.8) pg/ml] than in those with absorptive hypercalciuria (AH) [26.8 (7.6) pg/ml, P<0.05] and NC [27.6 (6.6) pg/ml, P<0.001]. PRA was significantly lower in AH [2.9 (1.3) ng/ml per hour] than in RH patients [7.8 (6.8) ng/ml per hour, P<0.01] and in NC [6.8 (4.6) ng/ml per hour, P<0.005]. Serum aldosterone values were significantly lower in AH [14.5 (11.4) ng/dl] than in RH patients [25.4 (14.1) ng/dl, P<0.05] and in NC [32.6 (20.5), P<0.001]. The lower plasma ANP levels in RH than in AH patients and in NC may be due to Ca depletion. The lower PRA and serum aldosterone levels in AH than in RH patients and in NC may be attributed to Ca excess.
Pediatric Nephrology 08/2000; 14(8-9):853-5. · 2.52 Impact Factor
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ABSTRACT: Increased echogenicity of the pancreas, due to hemosiderosis, is a frequent laboratory finding in children and adolescents with beta-thalassemia. The aim of this study was to investigate whether increased echogenicity of the pancreas is associated with dysfunction. The ultrasonic image of the pancreas was examined in 34 children aged 12+/-3.8 years old and was compared to the endocrine and exocrine functioning of the gland. Oral glucose tolerance test (OGTT) was performed with simultaneous measurement of insulin and serum trypsin. Twenty-six of the 34 patients (76.5%) presented increased echogenicity, while 8 (23.5%) had a normal ultrasonic pancreatic image. 77% of the patients with increased echogenicity had abnormal OGTT, 46%, with subnormal or increased insulin values, and 32.5% manifested low levels of trypsin. Among the patients with normal ultrasound, 25% had abnormal OGTT and 37.5% abnormal insulin values. Statistical analysis with Student's t-test revealed that patients with increased echogenicity had significantly higher glucose values on OGTT at 60: 7.6 +/- 1.8 mmol/l (137.3 +/- 33.7 mg/dl) as compared to the patients with normal ultrasound: 6.1 +/- 1.2 mmol/l (110.75 +/- 21.72 mg/dl) (p<0.05). Insulin values were significantly affected at 30, 60, and 90 min: 570+/-301, 332+/-156, 294+/-158 pmol/l (79.54 +/- 42, 46.4 +/- 21.8, 41.04 +/- 22 mU/l) respectively in patients with increased echogenicity in comparison to those with normal ultrasonographic image of the gland: 301 +/- 170, 192 +/- 52, 135 +/- 63 pmol/l (42 +/- 23.7, 26.85 +/- 7.36, 18.9 +/- 8.8 mU/l) (p<0.05). No statistical significance was observed between the two groups regarding trypsin levels, even though abnormal values were observed in more children with increased echogenicity than in patients with a normal ultrasound. The above findings confirm that increased echogenicity of the pancreas is associated with disturbance of its function. This simple imaging method could be used as a rough early index of detection of an increased risk for developing diabetes mellitus in patients with beta-thalassemia.
Journal of pediatric endocrinology & metabolism: JPEM 03/2000; 13(3):303-6. · 0.88 Impact Factor
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ABSTRACT: In this study, we report the further results of an ongoing project on the delineation of the spectrum of mutations on the ATP7B gene in Wilson disease (WD) patients of Greek origin. We have analyzed 24 additional families and detected 16 mutations (five frameshifts, two splice site, two nonsense, and seven missense), of which six are novel. On adding these results to the ones already published by us, we conclude that WD shows a marked allelic heterogeneity in the Greek population. Of the total number of mutations so far detected, the most common eight account for the molecular defect in 72.8% of the WD chromosomes. The most frequent mutation is the His0169Gln, which has a frequency of 28.5%, similar to those reported in North European populations. Using these data, an efficient strategy of mutation screening for WD is possible in this population, thus improving the possibility of preclinical diagnosis.
Genetic Testing 02/2000; 4(4):399-402. · 1.17 Impact Factor
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ABSTRACT: The cases of 2 siblings with cat scratch disease are described who presented with symptoms suggestive of acute febrile gastroenteritis. The first patient, a 7.5-y-old girl, developed mesenteric lymphadenitis, hepatosplenic granulomas and osteolytic bone lesions only late in the course of her protracted illness. Her 3-y-old brother had a shorter, self-limited illness without complications. Cat scratch disease is often unrecognized and the full spectrum of its clinical manifestations remains to be investigated.
Scandinavian Journal of Infectious Diseases 02/2000; 32(3):317-9. · 1.72 Impact Factor
