Dimitrije Nikolic

Stevens–Johnson syndrome and toxic epidermal necrolysis in children

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the most severe forms of hypersensitivity reactions affecting the skin. Current terminology is based on maximal extent of epidermal detachment. SJS indicates cases with epidermal necrolysis that involve less than 10% of the body surface area, TEN with more than 30%, and overlap of SJS/TEN in between (1). Clinically, SJS/TEN are characterized by polymorphic lesions like erythematous macules, papules, plaque, vesicles, and bullae with Nikolsky’s sign positive. Oral, genital, and conjunctival mucosae are often involved in the form of erosion or ulceration (2). Fever and malaise are the first symptoms of the disease (3). Incidence of SJS/TEN is 0.05–3 persons per million populations per year (2, 4). Several drugs are highly suspected to cause SJS/TEN in adults, such as anti-epileptics, anti-infective sulfonamides, nonsteroidal anti-inflammatory drugs, nevirapin, allopurinol, and antimicrobials (cephalosporins, aminopenicillins, quinolones, tetracyclines, and imidazole antifungals) (4–12). The list of causative drugs may vary from country to country (4). In children, anti-infective sulfonamides, phenobarbital, carbamazepine, lamotrigine, and acetaminophen are frequently associated with SJS/TEN (12). However, SJS/TEN are rare in children with mortality rate of 7.5% (12). In this article, evaluation of children with SJS/TEN, investigation of causative drug/drugs, treatment, clinical outcome, and complications are presented in three cases.

Association between pet‐keeping and asthma in school children

The role of pet exposure in childhood asthma and allergy is still controversial. The aim of this study was to investigate the association between pet‐keeping during different periods of childhood and asthma and sensitization in school children.

GSTA1, GSTM1, GSTP1 and GSTT1 polymorphisms in progressive myoclonus epilepsy: A Serbian case–control study

PURPOSE Oxidative stress is recognized as an important factor in progressive myoclonus epilepsy (PME). Genetic polymorphism of glutathione S-transferases (GSTs), which are involved in both protection from oxidative damage and detoxification, might alter the capacity for protecting tissues from exogenous and endogenous oxidants. We aimed to assess a possible association between GST polymorphism and PME, as well as, correlation between GST genotypes and oxidative phenotype in PME patients. METHODS GSTA1, GSTM1, GSTP1 and GSTT1 genotypes were determined in 26 patients with PME and 66 controls. Byproducts of protein oxidative damage (thiol groups (P-SH) and nitrotyrosine), superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities were determined. RESULTS The frequency of GSTA1, GSTM1 and GSTP1 genotypes was not significantly different between PME patients and controls, while individuals with GSTT1-null genotype were at 5.44-fold higher risk of PME than carriers of GSTT1-active genotype. Moreover, significant risk of PME was obtained in carriers of both GSTT1-null and GSTM1-null genotypes. Carriers of combined GSTA1- active and GSTT1-null genotype were at highest, 7.55-fold increased risk of PME. Byproducts of protein damage did not reach statistical significance, while SOD and GPX activities were significantly higher in PME patients then in controls. When stratified according to GST genotype, P-SH groups were significantly lower only in patients with GSTT1-null genotype in comparison to carriers of active genotype. Only SOD activity was increased in GSTT1-null when compared to corresponding active genotype. CONCLUSIONS GSTT1-null genotype might be associated with the increased risk and enhanced susceptibility to oxidative stress in PME patients.

Childhood-onset myasthenia gravis with thymoma.

Juvenile myasthenia gravis is an acquired, autoimmune disease occurring before age 16 years. Thymoma is exceedingly rare in children, especially in association with juvenile myasthenia gravis. We describe a 14-year-old boy with juvenile myasthenia gravis and thymoma. He presented with difficulties chewing and swallowing, nasal speech, and fluctuating weakness of the leg muscles. Neurologic examination revealed masticatory and bulbar muscle weakness with nasal speech, proximal muscle weakness, fatigability of the arms and legs, and distal muscle weakness of the legs. A diagnosis of juvenile myasthenia gravis was confirmed by a positive neostigmine test, a decremental response on repetitive nerve stimulation, and increased titers of serum anti-acetylcholine receptor antibodies. The patient received anticholinesterases, corticosteroids, azathioprine, and thymectomy. A pathohistologic analysis of the thymus gland indicated thymoma, Masaoka grade II. After 2 years of an unstable disease course, remission was achieved. Because only 10 cases of thymoma-associated myasthenia gravis are described in the pediatric population, this report offers an important contribution to a better understanding of this rare association.

Mitotic crossover - an evolutionary rudiment which promotes carcinogenesis of colorectal carcinoma

Mitotic crossover is a natural mechanism that is a main source of the genetic variability of primitive organisms. In complex organisms such as mammals, it represents an evolutionary rudiment which persisted as one of the numerous DNA repair mechanisms, and results in the production of homozygous allele combinations in all heterozygous genes located on the chromosome arm distal to the crossover. This event is familiar as loss of heterozygosity, which is one of the key mechanisms responsible for the development and progression of almost all cancers. We propose the hypothesis in which mitotic crossover is a principal source of the increased loss of heterozygosity that leads to the initiation and progression of colorectal carcinoma. The hypothesis could be tested by in vitro inhibition of Rad51 protein, orthotopic grafting of human colon cancer tissue into the gut of mice, and treatment with potential inhibitors. After these procedures, the frequency of mitotic crossover would be estimated. The development of selective inhibitors of mitotic crossover could stop further carcinogenesis of colorectal carcinoma, as well as many other neoplastic events. Loss of heterozygosity is an event responsible for carcinogenesis, its reduction by selective inhibitors of mitotic crossover could have a positive effect on cancer chemoprevention, as well as on growth reduction and a cessation in the progression of earlier developed tumors.

[Camptomelic dysplasia--a case report].

Campomelic/camptomelic dysplasia is a very rare, severe osteochondrodysplasia characterised by severe skeletal and nonskeletal malformations and lethal outcome mainly in neonatal period. Characteristic abnormality by which the syndrome got its name is short, bowed long bones of lower extremities, most often of femur, manifested by short and bowed legs. Skin dimpling on tibial anterior side is another prominent characteristic of this syndrome. Severe cases are inherited by autosomal dominant trait, by mutation Sox9 gene on chromosome 17, with lethal outcome in the first days of life. Less severe forms of the disease are due to balanced translocation t (13;17) with life span up to the third decade of life. A majority of karyotypic males present as phenotypic females. We report a case of a female neonate, without consanguinity between parents, with characteristic signs of camptomelic dysplasia with short birth length of 46 cm, macrocephaly (head circumference 39 cm), dolichocephaly, hydrocephalus, short trunk and legs. Narrow rib cage, bowed lower extremities, short hand and foot phalanges, nail hypoplasia were noticed. Anterior fontanelle was enlarged, high forehead, face small and flat, hypertelorism, low nasal bridge, micrognathia, low set ears, cleft palate, were found. Characteristc skin dimpling on anterior side of tibia was present on both legs. Bone X-ray studies presented the following changes: anterior bowing of shortened femurs, hip dislocation, cervical vertebrae, scapulas, eleven pairs of slender ribs. Hip luxation. Karyotype was normal for a female, 46 XX. Respiratory insufficiency was present since birth, exacerbated, and led to lethal outcome in the second day of life, as described in the majority of these patients.

The Diagnosis of Prediabetes in Adolescents/Dijagnoza Predijabetesa Kod Adolescenata

Summary 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. 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). 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. Kratak sadržaj Uvod: Stanja kao što su izolovana povišena glikemija našte ili poremećaj tolerancije glukoze i kombinacija ova dva poremećaja glukoze mogu se definisati kao predijabetes. Cilj nam je bio ispitati prevalencu predijabetesa i odrediti potencijalne pridružene faktore u grupi gojaznih adolesce- nata. Metode: Prospektivna studija, sprovedena u Univerzitetskoj dečjoj klinici, uključila je 85 gojaznih ispitanika i 17 nor- malno uhranjenih pacijenata. Svi pacijenti su bili bele rase, 60 muškog, 42 ženskog pola, uzrasta 7,4-18,3 godina, sa prisutnim znacima puberteta. Rezultati: Zavisno od kriterijuma koje smo koristili, insulin- ska rezistencija je postojala kod 62-100% gojaznih pacije- nata, posebno izražena u grupi pacijenata sa ITM SDS > 3. Nakon oGTT-a, dijagnoza izolovane povišene glikemije našte je postavljena kod 13,9% pacijenata, poremećaj to- lerancije glukoze kod 20,8%, a udruženost ova dva pore- mećaja kod samo 2,8 gojaznih pacijenata. Pacijenti sa predijabetesom su bili stariji (14±2,4 vs 12,8±2,5 p=0,04) i imali više nivoe glukoze tokom celog testa (p<0,001). Nije na|ena statistički značajna razlika u odno- su na porodičnu anamnezu za tip 2 dijabetesa, ITM, vred- nosti lipida i insulina našte. Insulinogeni, ukupni indeks senzitivnosti, kao i HOMA%B bili su značajno niži u predijabetesnoj grupi u pore|enju sa grupom koja je imala normalnu toleranciju glukoze (p=0,07, 0,01 i 0,04). HbA1c je odre|en kod 58% pacijenata i bio je značajno viši u pre- dijabetesnoj grupi (5,4±0,3 vs 5,7±0,4, p=0,002). Zaključak: Dijagnoza pre-dijabetesa je postavljena u viso- kom procentu kod naših gojaznih adolescenata. Neop- hodna su dalja ispitivanja koja bi pokazala koji je najbolji test za rano prepoznavanje i lečenje ovih pacijenata sa rizikom za tip 2 dijabetesa.

Inhaled nitric oxide therapy for acute respiratory distress syndrome in children.

The aim of this study was to evaluate the effects of inhaled nitric oxide (iNO) therapy on oxygenation and mortality in children with acute respiratory distress syndrome (ARDS). Thirty-three children with ARDS and an arterial SatO2 <88% despite mechanical ventilation were analyzed. Patients in the iNO group were prospectively enrolled and treated with conventional therapy plus iNO. The control group consisted of retrospectively analyzed patients treated only with conventional therapy. A significant increase in PaO2/FiO2 ratio (25.6%) and decrease in oxygenation index (19.5%) was observed after 4 h of iNO treatment, when compared to baseline values. A positive response to iNO was detected in 69% of patients, and there was no difference between pulmonary and extrapulmonary ARDS. There was no difference in mortality and duration of mechanical ventilation between iNO and control group.