Browsing by Author "Nikolić, Dimitrije (8279362600)"

Childhood leukemia bottleneck phenomenon is the most mysterious corollary of the prenatal origin discovery of leukemogenic chromosome translocations. The bottleneck is evidence that leukemia initiation, by in utero acquired chromosome translocations that generate functional fusion genes, is far more common than the incidence rate of corresponding leukemia. For childhood TEL-AML1 + acute lymphoblastic leukemia (ALL) this equates to approximately 100 times. Practically this means that among a hundred children born with TEL-AML1 fusion gene, only one child will later in its life develop ALL. The key data necessary for unraveling of this mystery were discovered in 2002. It was the level of TEL-AML1 + cells' frequency. The bottleneck is caused by the very low body TEL-AML1 + cell count. Only one out of a thousand B cells carries TEL-AML1 fusion gene. TEL-AML1 + body cell count is low because TEL-AML1 fusion is generated at cell level of 10- 3 to 10- 4 just during the late fetal lymphopoiesis i.e. after the 36th gestational week.

[No abstract available]

Celiac disease (CD) is a common autoimmune condition. Previously it was considered to be a rare childhood disorder, but is actually considered a relatively common condition, present at any age, which may have multiple complications and manifestations. Hematological disorders of the disease are not uncommon. Among these disorders, the most frequently reported are anemias as a result of iron deficiency, often associated with folate and/or B12 deficiency. Anemias caused by hemolysis are very rarely reported in celiac patients. An 11-year-old girl with a previous uneventful medical history presented with severe hemolytic anemia. Hemolysis was Coombs negative, accompanied by inappropriate low reticulocyte count, despite exaggerated bone marrow hyperplasia of the erythroid precursors which showed normal maturation. Serology for recent infections, including Epstein- Barr virus, parvovirus B19, cytomegalovirus and mycoplasma, were all negative. Levels of serum IgA, IgG and IgM, were all within normal ranges for age. Screening for anti-DNA, antinuclear, antineutrophil cytoplasmic, antimicrosomal, antithyroglobulin, and antimitochondrial antibodies and lupus anticoagulants, was negative. She was also negative for human immunodeficiency virus. Conventional therapy with corticosteroids and intravenous immunoglobulin failed. CD was serendipitously discovered upon screening for anti-tissue transglutaminase autoantibodies. The disease was confirmed by biopsy of the small intestine mucosa. The patient recovered with gluten-free diet. A unique case of CD is presented. CD should be serologically screened in each patient with Coombs negative "immune" hemolytic anemia, particularly if accompanied by "reticulocytopenia". A new hemolytic mechanism and very speculative explanation for "reticulocytopenia" are discussed. © 2010 Baishideng. All rights reserved.

Background: Antiepileptic drugs (AEDs) can cause hypersensitivity reactions in children. These reactions are mainly cutaneous, self-limiting, and benign, but life-threatening severe cutaneous adverse reactions can occur. Infections can lead to skin eruptions and mimic drug hypersensitivity reactions, if a drug is taken at the same time. The aims of our study were to confirm or rule out the diagnosis of hypersensitivity reactions to AEDs in children and to detect an infection which mimics these reactions. Methods: A prospective survey was conducted in a group of 100 children with histories of hypersensitivity reactions to AEDs by performing patch tests, delayed-reading intradermal test, and, in case of negative results, challenge test. In all children, a study was performed to detect infections by viruses or Mycoplasma pneumoniae. Results: Maculopapular exanthema and delayed-appearing urticaria were the most reported hypersensitivity reactions to AEDs. Sixty-six (66%) of 100 children had confirmed hypersensitivity reactions to AEDs. Fifty-nine children had positive patch test. No children had positive challenge tests. The most common AEDs causing hypersensitivity reactions were carbamazepine (45.4%) and lamotrigine (43.6%). Thirty-two children had positive tests for viruses or M pneumoniae, and nine of them had also a positive allergy work-up. Conclusion: Considering that there are no specific tests to distinguish between a viral infection and hypersensitivity reactions to AEDs in the acute phase, a diagnostic work-up should be performed in all children with suspected hypersensitivity reactions to AEDs, as well as infectious agent study, to remove a false label of hypersensitivity. © 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Background: Antiepileptic drugs (AEDs) can cause hypersensitivity reactions in children. These reactions are mainly cutaneous, self-limiting, and benign, but life-threatening severe cutaneous adverse reactions can occur. Infections can lead to skin eruptions and mimic drug hypersensitivity reactions, if a drug is taken at the same time. The aims of our study were to confirm or rule out the diagnosis of hypersensitivity reactions to AEDs in children and to detect an infection which mimics these reactions. Methods: A prospective survey was conducted in a group of 100 children with histories of hypersensitivity reactions to AEDs by performing patch tests, delayed-reading intradermal test, and, in case of negative results, challenge test. In all children, a study was performed to detect infections by viruses or Mycoplasma pneumoniae. Results: Maculopapular exanthema and delayed-appearing urticaria were the most reported hypersensitivity reactions to AEDs. Sixty-six (66%) of 100 children had confirmed hypersensitivity reactions to AEDs. Fifty-nine children had positive patch test. No children had positive challenge tests. The most common AEDs causing hypersensitivity reactions were carbamazepine (45.4%) and lamotrigine (43.6%). Thirty-two children had positive tests for viruses or M pneumoniae, and nine of them had also a positive allergy work-up. Conclusion: Considering that there are no specific tests to distinguish between a viral infection and hypersensitivity reactions to AEDs in the acute phase, a diagnostic work-up should be performed in all children with suspected hypersensitivity reactions to AEDs, as well as infectious agent study, to remove a false label of hypersensitivity. © 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Introduction Acute otitis media is a very common disease in the early childhood age, with typical symptoms such as otalgia and fever. Otogenic complications are divided into extracranial and intracranial. Although the introduction of antibiotics has significantly reduced the incidence of intracranial complications, they are still present. Clinical picture usually develops fast, with the predominance of neurologic symptoms. Case outline An 11-year-old boy was admitted to a tertiary health care children’s hospital because of fever, agitation, altered behavior and disorder of consciousness. Based on the anamnesis, clinical examination, CT, MRI, and lumbar puncture, it has been established that it is a case of meningoencephalitis as complications of acute otitis media. Besides intense antibiotic and symptomatic therapy, surgical treatment too was conducted as well. Firstly, mastoidectomy with the implantation of ventilation tube was done, followed by radical tympanomastoidectomy, because there was no improvement. The treatment was followed by numerous complications, such as toxic hepatitis, mycoplasma pneumoniae infection, and hemolytic anemia. The treatment lasted for 71 days, and the patient was discharged from the hospital in a good general condition, without the focal motor failure. Conclusion Meningoencephalitis is unusual and rare complication of acute otitis media that requires urgent diagnostic procedure and multidisciplinary approach to the treatment. Surgical treatment of the ear that caused complications should not be postponed, and the choice of surgical method must be adapted to each patient individually. Hospital treatment of these patients is often prolonged and auditory and neurological sequelae are substantial and require long-term treatment. © 2019 Serbia Medical Society. All rights reserved.

Neuromyelitis optica is a rare and severe autoimmune demyelinating disease of the central nervous system, clinicaly presented as optic neuritis and transverse myelitis that affects more than 3 spinal cord segments. Its initial course usually doesn't affect the brain. This feature differentiates it from the multiple sclerosis. It has a usual course of form with frequent relapses and rarely has a monophasic form. Frequent relapses often lead to a severe neurological deterioration (blindness, para/tetraplegia). The onset ranges from early childhood to late adulthood with the mean age in the forthies. Discovery of the autoantibodies directed toward aquaporine-4 receptor has significantnly revealed its pathogenesis. These antibodies are highly specific (99%) and sensitive (48- 72%) for the diagnosis of optic neuromyelitis. Current therapy strategy is directed toward intensive treatment of the acute relapse with i.v. methylprednisolone and plasmapheresis and remision prevention with imunosupressive drugs like azathioprine, mycophenolate mofetil and rituximab.

Introduction. Empyema thoracis, defined as the accumulation of pus in the pleural space, is rare in the neonatal population. Limited data are reported in the medical literature, and still, no treatment guidelines are available for this age. Case report. We present a term 12-day-old neonate (born healthy) who developed sepsis caused by methicillin-resistant Staphylococcus aureus (MRSA) and pneumonia associated with advanced-stage empyema. The child was admitted to our hospital with a few-hours history of difficulty breathing and lethargy. On admission, the child was cyanotic with desaturation and in severe respiratory distress; therefore, the child was intubated, and mechanical ventilation was started. Imaging tests were performed in an emergency, hence chest computed tomography (CT) scan was done without contrast. Suspected congenital pulmonary airway malformation with trapped air collections, significant mediastinal shift on CT scan, and deterioration of the patient’s condition indicated urgent surgery. Intraoperatively, the diagnosis of stage II empyema was established, and decortication of thickened parietal and visceral pleura was performed. Afterward, the baby showed quick and progressive clinical improvement. Conclusion. The diagnosis and management of empyema in neonates may be challenging, especially in the case of unremarkable history, fulminant progression of the disease, and incomplete imaging tests. © 2023 Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved.

Introduction: Biomarkers capable of reflecting disease onset and short- and long-term therapeutic effects in individuals with spinal muscular atrophy (SMA) are still an unmet need and phosphorylated neurofilament heavy chain (pNF-H) holds significant promise. Methods: We conducted a longitudinal prospective study to evaluate pNF-H levels in the cerebrospinal fluid (CSF) and plasma of 29 individuals with childhood-onset SMA treated with Nuinersen (SMA type 1: n = 6, 2: n = 17, 3: n = 6). pNF-H levels before and during treatment were compared with the levels of controls (n = 22), patients with Duchenne muscular dystrophy (n = 17), myotonic dystrophy type 1 (n = 11), untreated SMA individuals with chronic type 3 disease (n = 8), and children with presymptomatic SMA (n = 3). Results: SMA type 1 showed the highest mean CSF pNF-H levels before treatment initiation. All Nusinersen-treated individuals (types 1, 2, and 3) showed significantly elevated mean baseline CSF pNF-H compared to controls, which inversely correlated with age at disease onset, age at first dose, disease duration and the initial CHOP INTEND result (SMA type 1 and 2). During 22 months of treatment, CSF pNF-H levels declined during loading doses, stabilizing at reduced levels from the initial maintenance dose in all individuals. Baseline plasma pNF-H levels in type 1 and 2 SMA were significantly increased compared to other cohorts and decreased notably in type 1 after 2 months of treatment and type 2 after 14 months. Conversely, SMA type 3, characterized by lower baseline pNF-H levels, did not show significant fluctuations in plasma pNF-H levels after 14 months of treatment. Conclusion: Our findings suggest that CSF pNF-H levels in untreated SMA individuals are significantly higher than in controls and that monitoring of CSF pNF-H levels may serve as an indicator of rapid short-term treatment response in childhood-onset SMA individuals, irrespective of the subtype of the disease, while also suggesting its potential for assessing long-term suppression of neurodegeneration. Plasma pNF-H may serve as an appropriate outcome measure for disease progression and/or response to treatment in types 1 and 2 but not in type 3. Presymptomatic infants with SMA may show elevated pNF-H levels, confirming early neuronal degeneration. Copyright © 2024 Brkušanin, Kosać, Branković-Srećković, Jovanović, Perić, Karanović, Matijašević Joković, Garai, Pešović, Nikolić, Stević, Brajušković, Milić-Rašić and Savić-Pavićević.

Introduction: Biomarkers capable of reflecting disease onset and short- and long-term therapeutic effects in individuals with spinal muscular atrophy (SMA) are still an unmet need and phosphorylated neurofilament heavy chain (pNF-H) holds significant promise. Methods: We conducted a longitudinal prospective study to evaluate pNF-H levels in the cerebrospinal fluid (CSF) and plasma of 29 individuals with childhood-onset SMA treated with Nuinersen (SMA type 1: n = 6, 2: n = 17, 3: n = 6). pNF-H levels before and during treatment were compared with the levels of controls (n = 22), patients with Duchenne muscular dystrophy (n = 17), myotonic dystrophy type 1 (n = 11), untreated SMA individuals with chronic type 3 disease (n = 8), and children with presymptomatic SMA (n = 3). Results: SMA type 1 showed the highest mean CSF pNF-H levels before treatment initiation. All Nusinersen-treated individuals (types 1, 2, and 3) showed significantly elevated mean baseline CSF pNF-H compared to controls, which inversely correlated with age at disease onset, age at first dose, disease duration and the initial CHOP INTEND result (SMA type 1 and 2). During 22 months of treatment, CSF pNF-H levels declined during loading doses, stabilizing at reduced levels from the initial maintenance dose in all individuals. Baseline plasma pNF-H levels in type 1 and 2 SMA were significantly increased compared to other cohorts and decreased notably in type 1 after 2 months of treatment and type 2 after 14 months. Conversely, SMA type 3, characterized by lower baseline pNF-H levels, did not show significant fluctuations in plasma pNF-H levels after 14 months of treatment. Conclusion: Our findings suggest that CSF pNF-H levels in untreated SMA individuals are significantly higher than in controls and that monitoring of CSF pNF-H levels may serve as an indicator of rapid short-term treatment response in childhood-onset SMA individuals, irrespective of the subtype of the disease, while also suggesting its potential for assessing long-term suppression of neurodegeneration. Plasma pNF-H may serve as an appropriate outcome measure for disease progression and/or response to treatment in types 1 and 2 but not in type 3. Presymptomatic infants with SMA may show elevated pNF-H levels, confirming early neuronal degeneration. Copyright © 2024 Brkušanin, Kosać, Branković-Srećković, Jovanović, Perić, Karanović, Matijašević Joković, Garai, Pešović, Nikolić, Stević, Brajušković, Milić-Rašić and Savić-Pavićević.

[No abstract available]

[No abstract available]

Aim To determine changes in the quality of life associated with epilepsy in school-age children with newly diagnosed uncomplicated epilepsy over the first six months after diagnosis to find points relevant for the early prevention of deterioration in quality of life. Methods This prospective follow-up study, performed in University Children’s Hospital in Belgrade, enrolled 60 school-aged children with recently diagnosed epilepsy, along with their parents. The respondents completed the Children with Epilepsy Quality of Life immediately following the diagnosis of epilepsy and six months later. Results Significant decline was observed in the domains related to intrapersonal/emotional relationships by both children (P < 0.001) and their parents (P = 0.03), and in the need to keep epilepsy a secret as observed by parents (P = 0.04). Significant improvement was found in the Interpersonal/Social domain as rated by parents (P = 0.001). Total quality-of-life scores, as assessed by children and parents, did not change significantly. Conclusion Bearing in mind that stigma and intrapersonal struggles are the major factors affecting the quality of life in children with epilepsy, psychological and social support is highly recommended in the first six months following an epilepsy diagnosis. Since intrapersonal relationships improved over six months, compensating for other deteriorations in the quality of life, children with epilepsy should be encouraged to socialize with their peers and to join organizations and actions that encourage social contact. © 2024, Medicinska Naklada Zagreb. All rights reserved.

Background: Prediabetes is characterized by isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), and combined IFG/IGT. This study aimed to establish the prevalence of prediabetes and examine possible contributory factors in a cohort of obese adolescents.; Methods: In this prospective study, we recruited 85 obese patients from the Obesity Clinic at the University Children's Hospital and 17 normal weight controls. All patients were of Caucasian origin, 60 males/42 females, aged 7.4-18.3 years, with at least Tanner 2 stage of puberty.; Conclusion: Prediabetes occurrence was fairly high in our obese adolescents. Further studies should establish what would be the most appropriate screening test to diagnose these patients at risk for type 2 diabetes and initiate treatment without delay.; Results: Depending on criteria we used, insulin resistance was confirmed in 62-100% of obese patients, predominantly in the group with BMI SDS > 3. oGTT revealed isolated impaired fasting glucose (IFG) in 13.9%, impaired glucose tolerance (IGT) in 20.8% and combined IFG and IGT only in 2.8% of the obese patients. Patients in the prediabetes group were older (14±2.4 vs 12.8±2.5 p=0.04) and had higher glucose levels (p<0.001) during the whole oGTT compared to normal glucose tolerance (NGT) group. There was no difference between groups in respect to family history, BMI, lipids and fasting insulin. Insulinogenic index, WBISI and HOMA%B were significantly lower in the prediabetes group compared to the NGT group (p=0.07, 0.01 and 0.04 respectively). HbA1c level was measured in 58% of patients and was significantly higher in the prediabetes group (5.4±0.3 vs 5.7±0.4, p=0.002). © by Mirjana Kocova 2014.

Background: Prediabetes is characterized by isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), and combined IFG/IGT. This study aimed to establish the prevalence of prediabetes and examine possible contributory factors in a cohort of obese adolescents.; Methods: In this prospective study, we recruited 85 obese patients from the Obesity Clinic at the University Children's Hospital and 17 normal weight controls. All patients were of Caucasian origin, 60 males/42 females, aged 7.4-18.3 years, with at least Tanner 2 stage of puberty.; Conclusion: Prediabetes occurrence was fairly high in our obese adolescents. Further studies should establish what would be the most appropriate screening test to diagnose these patients at risk for type 2 diabetes and initiate treatment without delay.; Results: Depending on criteria we used, insulin resistance was confirmed in 62-100% of obese patients, predominantly in the group with BMI SDS > 3. oGTT revealed isolated impaired fasting glucose (IFG) in 13.9%, impaired glucose tolerance (IGT) in 20.8% and combined IFG and IGT only in 2.8% of the obese patients. Patients in the prediabetes group were older (14±2.4 vs 12.8±2.5 p=0.04) and had higher glucose levels (p<0.001) during the whole oGTT compared to normal glucose tolerance (NGT) group. There was no difference between groups in respect to family history, BMI, lipids and fasting insulin. Insulinogenic index, WBISI and HOMA%B were significantly lower in the prediabetes group compared to the NGT group (p=0.07, 0.01 and 0.04 respectively). HbA1c level was measured in 58% of patients and was significantly higher in the prediabetes group (5.4±0.3 vs 5.7±0.4, p=0.002). © by Mirjana Kocova 2014.