Cerebrospinal Fluid Concentrations of Neurotransmitters in a Greek Pediatric Reference Population.

BACKGROUND: Biogenic amines and pterins analysis in cerebrospinal fluid (CSF) are reliable biomarkers for the diagnosis of inherited disorders of monoamine neurotransmitters. OBJECTIVE: The objectives of this study were the establishment of reference values of CSF biogenic amine metabolites in a cohort of Greek children, the detection of primary defects of biogenic amine metabolism, and the assessment of biogenic amine metabolites in children with different neurological disorders. METHODS: CSF biogenic amine metabolites and pterins (biopterin and neopterin) were analyzed using high-performance liquid chromatography with electrochemical and fluorescence detection. Three hundred sixty-three samples were analyzed: 60 infants and children with no history of neurological disorder, 6 with inherited disorders of monoamine neurotransmitters, and 297 with diverse neurological disorders. RESULTS: Reference values were stratified into six age groups. A strong correlation between homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5HIAA) levels with age was detected (p < 0.001). Two patients were diagnosed with a defect of the biogenic amine synthetic pathway and three with a defect of tetrahydrobiopterin cofactor production. HVA and 5HIAA abnormalities were detected within different groups of neurological disorders, but none followed a specific pattern of HVA and 5HIAA abnormalities. CONCLUSION: In the current study, Greek reference values of biogenic amines and pterins in CSF are presented. Five new patients with inherited monoamine neurotransmitter disorders are described. Nonspecific secondary biogenic amine disturbances can be seen in patients with different neurological disorders.

Immunogenicity and safety of the inactivated hepatitis A vaccine in children with juvenile idiopathic arthritis on methotrexate treatment: a matched case-control study.

OBJECTIVES: To describe the immunogenicity and side effects of immunisation against hepatitis A virus (HAV) in JIA patients on methotrexate treatment, who have not been previously exposed to HAV. METHODS: Case-control study performed in JIA patients and healthy controls matched on age and gender. The subjects received two doses of inactivated anti-HAV vaccine (720 mIU/ml) intramuscularly at 0 and 6 months. Seroconversion, seroprotection rates and anti-HAV-IgG titres were measured at 1, 7 and 18 months. Children were monitored for adverse events. RESULTS: 83 JIA patients and 76 controls were enrolled in the study. At one month, seroprotection rates were lower in children with, as compared to those without JIA (48.2% vs. 65%; p=0.05). At 7 and 18 months, rates of seroprotection rose significantly and were similar in both groups. The titre of anti-HAV-IgG was lower in children with JIA than healthy children at all time points (p<0.001). Vaccines were well tolerated. CONCLUSIONS: Two doses of inactivated HAV vaccine were well tolerated and immunogenic in most immunosuppressed children with JIA; however, a single dose of HAV vaccine was insufficient to induce seroprotection in half of the patients. Further studies are required to analyse the long-term immunity against HAV in this population and optimal HAV immunisation regimen.

Bioactive Edible Gel Films Based on Wheat Flour and Glucose for Food Packaging Applications.

In order to prepare bioactive edible gel films with enhanced properties, the feasibility of using wheat flour as a raw material with glucose added at several concentrations was studied in this investigation. Films were prepared with glucose concentrations of 0.5, 0.7 and 1 g/g of flour and characterized for their physicochemical properties, including water content, solubility, degree of swelling, chemical structure by FT-IR (ATR) spectroscopy, morphology by SEM microscopy, thermal properties by DSC, gas and water vapor permeability and antioxidant activity. Biodegradation studies were also carried out in soil for 27 days and evaluated by weight loss measurements. It was found that the gel film with the higher glucose concentration exhibits a homogeneous and continuous structure with no cracks and no fragility, accompanied by an increased thickness and solubility and a decreased degree of swelling compared to those with lower concentrations. The chemical structure of all films was verified. Moreover, the increase in glucose content leads to better gas barrier properties with lower oxygen, CO2 and water vapor transmission rates and increased water vapor permeability. A slightly elevated melting temperature was observed in the films with higher glucose content. Higher antioxidant activity was also associated with higher percentage of glucose. Finally, the biodegradation of the films ranged from 13 to nearly 70%. Therefore, it can be concluded that the addition of glucose to wheat flour in concentration up to 1 g/g could result in edible gel films with excellent properties to be used in food packaging applications.

The role of novel biomarkers in early diagnosis and prognosis of acute kidney injury in newborns.

Acute kidney injury (AKI) refers to the rapid loss of renal function. In clinical practice, AKI is common among hospitalized patients of all age groups including neonates and remains an important cause of morbidity and mortality due to its late diagnosis and therefore delayed therapeutic intervention. Although the precise incidence of AKI in newborn is unknown, several studies have reported that 8 to 24% of all critically ill newborns in neonatal intensive care units may develop the condition. We aim at reviewing the existing literature on novel serum and urinary biomarkers and discuss their role in the early diagnosis and prognosis of AKI in newborns. Specifically, this review will focus on cystatin C (CysC), neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18) in serum and on CysC, NGAL, kidney injury molecule-1, and IL-18 in urine.

Vigabatrin-Induced Encephalopathy in a 5.5-Month-Old Girl with Infantile Spasms due to Tuberous Sclerosis.

A 5.5-month-old female infant with tuberous sclerosis complex presented with infantile spasms and was treated with vigabatrin. As her condition did not improve, she was given adrenocorticotropic hormone (ACTH) intramuscularly which stopped the spasms and improved the electroencephalogram (EEG) abnormalities. However, she developed encephalopathy with apathy, drowsiness, and generalized slowing in the EEG. Discontinuation of vigabatrin quickly improved her symptoms and reversed the EEG slowing. A high index of suspicion is required in order to diagnose vigabatrin-induced encephalopathy, especially as the underlying disorders of these patients can be erroneously considered the cause of the observed encephalopathy.

Childhood Visceral Leishmaniasis: Distinctive Features and Diagnosis of a Re-emerging Disease. An 11-year Experience From a Tertiary Referral Center in Athens, Greece.

BACKGROUND: Visceral leishmaniasis (VL) remains a public health issue in Greece. The aim of this study was to describe the clinical and epidemiologic characteristics of pediatric VL in our region as well as to evaluate the laboratory findings and the diagnostic techniques that are applied. METHODS: We retrospectively reviewed the medical records of all children diagnosed with VL in an 11-year period at a tertiary public hospital in the region of Athens. Demographic features, clinical information and laboratory findings were accessed. RESULTS: A total of 43 cases were recorded during 2005-2015. Median age of the patients was 3.7 years. Pallor (100%), fever (98%), hepatosplenomegaly (55.8%) and appetite loss (32.6%) were the most common presentations of the disease. The predominant laboratory abnormalities were anemia (100%), thrombocytopenia (90.7%), elevated inflammatory markers (86.1%) and decreased albumin/globulin (A/G) ratio (72.1%). Four patients developed secondary hemophagocytic lymphohistiocytosis syndrome, whereas in 3 others abdominal ultrasound showed splenic nodules. Bone marrow aspiration detected Leishmania parasites in 92.7% of cases and the rapid rK39 strip test indicated anti-Leishmania antibodies in 97.1% of children. In addition, all patients in whom indirect immunofluorescent antibody test was implemented had positive results. CONCLUSIONS: VL still affects children in our area. Fever, splenomegaly, anemia and appetite loss are the typical findings in children. Noninvasive techniques (immunofluorescent antibody test, rK39) in combination with bone marrow microscopy are useful in the diagnosis of pediatric VL.

Short-course Regimens of Liposomal Amphotericin B for the Treatment of Mediterranean Visceral Leishmaniasis in Children: An 11-year Retrospective Study at a Tertiary Care Center.

BACKGROUND: Visceral leishmaniasis (VL) remains an important public health problem in endemic regions. Current antileishmanial agents share several limitations including potentially serious side effects and the risk of clinical failure. OBJECTIVES: Aim of this study was to examine the effectiveness and safety of short-course liposomal amphotericin B (L-AmB) regimens in the treatment of childhood VL in our area. METHODS: The cases of 43 VL patients (20 males; 23 females; mean age: 4.6 years) treated at a tertiary children's hospital over an 11-year period were retrospectively reviewed. Diagnosis was confirmed with identification of Leishmania spp. in bone marrow samples and/or a positive serologic test. All patients were treated with 5 different L-AmB regimens at a dose of 18-22 mg/kg. RESULTS: Initial response to treatment was attained in all patients (100%), while definitive cure at 6 months was achieved in 98% of patients. Adverse effects were recorded in 14 children and consisted mostly of infusion reactions and electrolyte disorders. Self-limiting nephrotoxicity was observed in 3 patients including a 12-year-old girl in whom acute kidney injury was developed. In addition, ventricular arrhythmias developed in a 13-year-old boy necessitating drug discontinuation. Although side effects were more frequent with the 2-day regimen, the difference with regard to toxicity between dosing regimens was not significant. CONCLUSIONS: Short-course L-AmB regimens are effective and safe for the treatment of childhood VL in our area. Our findings suggest that large L-AmB doses can possibly account for a higher rate of adverse events including nephrotoxicity.

Histopathology of renal asphyxia in newborn piglets: Individual susceptibility to tubular changes.

AIM: To analyze the effects on the kidney of hypoxia-reoxygenation in an experimental model of normocapnic asphyxia. METHODS: To this end, 40 newborn Landrace/Large-White piglets aged 1-4 d were studied in this work. Hypoxia was induced by decreasing the inspired fiO2 to 0.06-0.08. Animals were resuscitated with different fiO2 and subdivided into 4 groups: group 1, 2, 3 and 4 received 18%, 21%, 40% and 100% O2 respectively. Macroscopic examination was carried out to evidence possible pathological features. Tissue sample were obtained from both kidneys. Four or five micron paraffin sections were stained with H-E and PAS stain and examined under an optical microscope. RESULTS: Pathological changes, mainly affecting tubular cells, were observed in the vast majority of kidneys of asphyxiated piglets. The most frequent tubular changes were: tubular casts (95%), tubular dilatation (87.5%), tubular vacuolization (70%), tubular eosinophilia (52.5%), sloughing (50%), fragmentation of the brush border (50%), oedema (32.5%), apoptosis (15%) and glomerular changes (meningeal cell proliferation, capsular adhesion between the flocculus and Bowman's capsule, glomerulosclerosis and fibrous or cellular crescents associated with collapse of the glomerular tuft). Statistical analysis was carried out on changes observed when the animals were allocated in the 4 groups (χ(2)-test 0.05). The statistical analysis showed no evidence of differences regarding kidney lesions among the animals groups. CONCLUSION: Our data show that renal pathology in newborn piglets is characterized by interindividual variability to hypoxia and is not associated with oxygen concentration.

An experimental model of neonatal normocapnic hypoxia and resuscitation in Landrace/Large White piglets.

OBJECTIVE: The aim of this study is to describe and evaluate an experimental model of neonatal normocapnic hypoxia and resuscitation. METHODS: Ten male Landrace/Large White neonatal piglets were studied. Following anaesthesia and intubation, the animals were mechanically ventilated. Surgical procedures included catheterization of the right internal jugular vein and the carotid artery. After stabilization with 21% O(2), normocapnic hypoxia was induced by decreasing the inspired O(2) to 6-8%. When piglets developed bradycardia (heart rate < 60 beats/min), reoxygenation was initiated by administering 21% O(2). Arterial blood samples were taken during baseline, hypoxia and reoxygenation in order to measure interleukine-6 and interleukine-8. RESULTS: Nine out of ten animals were successfully resuscitated (one of these required chest compressions and a dose of adrenaline) and one died despite resuscitation efforts. After returning to baseline haemodynamic values, euthanasia was performed using thiopental overdose. CONCLUSIONS: Haemodynamic fluctuations at baseline, during normocapnic hypoxia and reoxygenation in Landrace/Large White piglets are comparable to that in human neonates, making the breed a favorable model of human neonatal hypoxia investigation.