Nikolaos Chaliasos

Modulation of gut microbiota downregulates the development of food allergy in infancy

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.

Determinants of pulmonary hypertension in patients with Beta-thalassemia major and normal ventricular function.

Background/Aims: We sought to define the incidence and predictive factors of pulmonary hypertension in β-thalassemia major. Methods: We studied 27 consecutive patients (19 male, 38 ± 9 years of age) with β-thalassemia major. All the patients had normal (left and right) ventricular (systolic and diastolic) function and underwent echocardiographic assessment of pulmonary artery systolic pressure. Univariate regression and discriminant function analyses were used to identify predictive factors of pulmonary hypertension. Results: Pulmonary hypertension was observed in 18.5% of the patients, but clinically significant disease was detected in only 3.7%. A total of 14 (51.8%) patients had been receiving a combined administration of deferoxamine and deferiprone for 7.0 ± 1.3 years. Amidst a large number of variables examined, ferritin levels and delayed onset of chelation therapy were the only predictors of pulmonary hypertension. Conclusion: Pulmonary hypertension in β-thalassemia major is relatively infrequent and generally mild due to improved chelation therapy. The role of hemochromatosis in pulmonary hypertension development merits further study.

Serum Adipocytokine and Vascular Inflammation Marker Levels in Beta-Thalassaemia Major Patients

Background/Aim: 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. Methods: 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. Results: 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). Conclusions: 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.

Chelation Therapy with Oral Solution of Deferiprone in Transfusional Iron-Overloaded Children with Hemoglobinopathies

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 μg/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.

Acute febrile neutrophilic dermatosis (Sweet's syndrome) in a child, associated with a rotavirus infection: a case report

IntroductionSweets syndrome characterized by fever, blood neutrophilia and inflammatory skin lesions, is rarely diagnosed in children. It presents in three clinical settings: classical Sweets 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 Sweets syndrome.Case presentationAn 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.ConclusionBesides describing the connection of Sweets 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 Sweets syndrome should be included in the differential.

Cytokine and Adhesion Molecule Expression Evolves Between the Neutrophilic and Lymphocytic Phases of Viral Meningitis

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.

Pulmonary embolism after snake bite in a child with Diamond-Blackfan anemia.

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.

Adipocytokines are related to haemolytic and inflammatory biomarkers in sickle cell beta thalassaemia.

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Impact of meteorological factors on the emergence of bronchiolitis in North-western Greece

OBJECTIVE To evaluate the relationship between meteorological factors in North-western Greece and the incidence of bronchiolitis. METHODS Meteorological data (air temperature and rainfall) for Ioannina city in North-western Greece and medical data from hospitalised patients at University Hospital of Ioannina were collected between January 2002 and December 2013. The association between meteorological factors and rate of hospitalisation due to bronchiolitis was investigated. The data processing was done using the Pearson product-moment correlation coefficient and applying the chi-square test at contingency tables of the parameters. RESULTS Of the 792 hospitalised cases, 670 related to infants (<1 year) and 122 concerned patients aged 1-2 years old. The disease is more common among boys (59.5%) than girls (40.5%). The disease course through the year has a double variation with a main maximum in March and a main minimum in August. The statistical study showed statistically significant correlation of bronchiolitis with: (a) the temperature parameters on an annual basis; (b) precipitation in autumn and dryness in spring; and (c) with sudden changes in diurnal temperature range on an annual basis. CONCLUSION A peak incidence of bronchiolitis was noticed in cold and wet seasons during the five days preceding hospitalisation.

Severe Thrombocytopenic Purpura in a Child with Brucellosis: Case Presentation and Review of the Literature

Brucellosis is still endemic and a significant public health problem in many Mediterranean countries, including Greece. It is a multisystemic disease with a broad spectrum of clinical manifestations including hematological disorders, such as anemia, pancytopenia, leucopenia, and thrombocytopenia. Thrombocytopenia is usually moderate and attributed to bone marrow suppression or hypersplenism. Rarely, autoimmune stimulation can cause severe thrombocytopenia with clinically significant hemorrhagic manifestations. We present the case of a girl with severe thrombocytopenic purpura as one of the presenting symptoms of Brucella melitensis infection. Treatment with intravenous immunoglobulin and the appropriate antimicrobial agents promptly resolved the thrombocyte counts. A review of similar published cases is also presented.