Publications (24)14.83 Total impact
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Article: Two Siblings with Niemann-Pick Disease (NPD) Type B: Clinical Findings and Novel Mutations of the Acid Sphingomyelinase Gene.
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ABSTRACT: Acid sphingomyelinase deficiency leads to the accumulation of sphingomyelin in cells, causing Niemann-Pick disease (NPD) types A/B. RF (13.66 y) and HF (3 y) are brother and sister. RF growth was markedly delayed at the age of 12.66 y (123 cm; -3.25 SD), while at the age 3 y his sister is 86 cm (-2.75 SD). The brother had a huge liver (13 cm) and spleen (12 cm). His sister also had an enlarged liver, but presented no other symptoms. The fibroblast cultivation had a reduced sphingomyelinase activity in the fibroblasts (0.68 mkat/kg protein), β-galaktosidase (937 mkat/kg) and glucosilceramidase (125.4 mkat/kg) were elevated. Mutational analysis demonstrated the siblings are compound heterozygotes (V112M and H554Y). The mother is carrier of V112M and the father carries H554Y. This is the first report of NPD type B in Macedonia. The novel mutation results in a moderately severe phenotype of NPD type B.The Indian Journal of Pediatrics 02/2012; · 0.52 Impact Factor -
Chapter: QEEG Characteristics and Biofeedback Modalities in Children with ADHD
02/2012; , ISBN: 978-953-307-868-7 -
Article: Quantitative EEG Spectrum-weighted Frequency (Brain Rate) Distribution in Adults with ADHD.
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ABSTRACT: Objective: The aim of this study is to explore the applicability of brain rate (ƒb) for the diagnosis of attention-deficit/hyperactivity disorder (ADHD), analyzing the spatial distribution of ƒb through analysis of its values in sagittal and lateral electrodes' positions, recorded in four conditions (eyes closed, eyes opened, visual continuous performance task and emotional continuous performance task). Methods: Sixty-seven adults diagnosed with ADHD according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and 50 age-matched control subjects participated in the study. The brain activity of the subjects was recorded by 19 channel quantitative electroencephalography (QEEG) system and ƒb was calculated with the ƒb software. Results: Maximum values of ƒb for sagittal topography are obtained in central region and the minimum in frontal region, while lateral topography maximum values are found in the left and right sides and the minimum in midline region. A positive correlation between the ƒb values and the QEEG spectra subtypes was obtained, with lower values for normals, first and second subtype, and higher values for the third and fourth subtype. On the other hand, there was no correlation between behavioral symptoms and ƒb values. Conclusion: The applicability of an ƒb indicator in the diagnosis of ADHD is especially pronounced for the higher subtypes (ADHD III and IV), corresponding to heterogeneous and multifactorial character of this disorder.CNS spectrums 05/2011; · 2.20 Impact Factor -
Article: Childhood craniopharyngioma in Macedonia: incidence and outcome after subtotal resection and cranial irradiation.
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ABSTRACT: craniopharyngioma is a frequent tumor in children with challenging surgical, endocrine, and visual consequences. We evaluated our experience in treating craniopharyngioma and its incidence in Macedonia. Thirteen children (9 male and 4 female) with craniopharyngioma (age 9.55 ± 3.74 years; range 2.90-15.11) who had been treated between 1989 and 2008 in Macedonia were reviewed. initial signs were vision disturbances (10 children), seizures (1), growth retardation (13), and diabetes insipidus (DI) (2). All children were subjected to subtotal surgical removal. Cranial irradiation was performed in 12 of the 13 children, and intracystic bleomycin was given to one child. The patients were followed up for 6-229 months (mean ± SD: 107.00 ± 74.04 months). All children had multiple pituitary deficiencies after surgical removal of the tumor. Body mass index increased from 16.93 ± 6.34 standard deviation scores (SDS) at diagnosis to 26.33 ± 5.91 SDS (P>0.005) at the last follow-up. DI was permanent in 9 of the 13 children, and multiple pituitary deficiencies were seen in all children. Treatment with growth hormone resulted in normalization of adult height from -1.27 ± 1.52 SDS at the start of the treatment to -0.13 ± 1.39 SDS at the last followup. The final height was not significantly lower than the genetic target height (P>0.005). The permanent deficit was visual impairment: blindness in one or both eyes in 4 children, bitemporal hemianopsia in 4, and other defects in 2. Recurrence of the disease was ruled out in one child after 31 months. No mortality was observed in the observation period of 104.92 ± 76.11 months. the overall incidence of craniopharyngioma in the period of 1989-2008 in Macedonia was 1.43 per 1 000 000 person-years. Subtotal resection and systematic irradiation showed good life quality of survivors.World Journal of Pediatrics 02/2011; 7(1):74-8. · 1.22 Impact Factor -
Article: Spectrum-weighted EEG frequency as an indicator of mental arousal in patients with anorexia
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ABSTRACT: Abstract. Aim: Anorexia is characterized by weight loss leading to a body weight of at least 15% below the normal. The aim of this study was to analyze the spectrum weighted frequency- fb (brain rate) as an indicator of general mental arousal in anorectics and to compare the results with healthy preadolescents of the same age and gender. Methods: The diagnosis was made according to two statistic manuals (DMS-IV-R and ICD-10), medical history, neuropsychological assessment, biochemical analysis and quantitative electroencephalography. Results from spectra power for four conditions (eyes closed, eyes open, visual continuous performance test – VCPT and auditory continuous performance test – ACPT) were exported to brain rate software. Results and Discussion: Using factorial ANOVA we found that there is a strong statistical significance between results of brain rate for control group of healthy subjects vs. observed anorectic group (p<0.001). The post hoc Bonferroni test (summary of significant difference of groups) showed that only the fb values for central region are statistically significant. The post hoc analysis regarding condition found a significant difference in fb values for EC vs. EO and EC vs. ACPT for posterior region and for EC vs. VCPT for frontal region (all p<0.05). Conclusions: Brain rate – fb is a good indicator for general mental activity but, further investigations are needed in order to add fb as an indicator of mental arousal in assessment of mental diseases in childhood.medicina fluminensis 2011. 01/2011; Vol. 47:p. 287-293. -
Article: Qeeg, Brain Rate, Executive Functions and Neurofeedback Training in Patients with Traumatic Brain Injury
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ABSTRACT: SUMMARY Traumatic brain injury (TBI) is a serious and growing problem, and long-term consequences become more widely acknowledged recently. A group of six patients with traumatic brain injury have been acceptedfor neurofeedback training. All of them have been injured by ar accident. Mild motor impairment was apparent in all patients; however, cognitive difficulties were the main problem. Preliminary qEEG assessment showed generally predominance of slow brain waves in fronto-parietal regions. This finding indicated the type of applied training protocols. We organized 20 sessions of neurofeedback, two times a week, each 40 minute duration. Subjective assessment concerning mood, quality of sleep, ever day’s activity and cognitive abilities, as well as the changes of qEEG findings promised good outcome. All patients, except one, continued normal education as well as normal life. It is the first application of neurofeedback for treatment TBI in our region.Acta informatica medica. 01/2011; vol 19 no 1 MARCH 2011:23-27. -
Article: Congenital erythropoietic porphyria with two mutations of the uroporphyrinogen III synthase gene (Cys73Arg, Thr228Met).
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ABSTRACT: Congenital erythropoietic porphyria (CEP) is an autosomal recessive inborn error of metabolism that results from the markedly deficient activity of uroporphyrinogen III synthase (UROS). We describe a 14-year-old girl with red urine since infancy, progressive blistering and scarring of the skin, and moderate hemolytic anemia. After years of skin damage, her face is mutilated; she has a bald patch on the scalp, hypertrichosis of the neck, areas of skin darkening, and limited joint movements of the hands. Total urine excretion and fecal total porphyrin were both markedly raised above normal levels. Sequencing of the UROS gene identified two mutations causing CEP (Cys73Arg, Thr228Met). The patient lesions are progressing. Bone marrow transplantation and/or gene therapy are proposed as the next steps in her treatment. In brief, we describe a CEP with confirmed two pathogenic mutations, severe phenotype and discuss the various treatment options available.Indian Journal of Human Genetics 01/2011; 17(2):104-7. -
Article: QEEG characteristics and spectrum weighted frequency for children diagnosed as autistic spectrum disorder.
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ABSTRACT: Autistic spectrum disorders are a group of neurological and developmental disorders associated with social, communication, sensory, behavioral and cognitive impairments, as well as restricted, repetitive patterns of behavior, activities, or interests.The aim of this study was a) to analyze QEEG findings of autistic patients and to compare the results with data base; and b) to introduce the calculation of spectrum weighted frequency (brain rate) as an indicator of general mental arousal in these patients. Results for Q-EEG shows generally increased delta-theta activity in frontal region of the brain. Changes in QEEG pattern appeared to be in a non-linear correlation with maturational processes.Brain rate measured in CZ shows slow brain activity (5. 86) which is significantly lower than normal and corresponds to low general mental arousal.Recent research has shown that autistic disorders have as their basis disturbances of neural connectivity. Neurofeedback seems capable of remediating such disturbances when these data are considered as part of treatment planning. Prognosis of this pervasive disorder depends on the intellectual abilities: the better intellectual functioning, the possibilities for life adaptation are higherQEEG shows generally increased delta-theta activity in frontal region of the brain which is related to poor cognitive abilities.Brain rate measured in CZ shows slow brain activity related to under arousal.Pharmacotherapy combined with behavior therapy, social support and especially neurofeedback technique promise slight improvements.Nonlinear Biomedical Physics 09/2010; 4(1):4. -
Article: McCune-Albright syndrome (MAS): early and extensive bone fibrous dysplasia involvement and "mistaken identity" oophorectomy.
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ABSTRACT: McCune-Albright syndrome (MAS) is a triad of gonadotropin-independent precocious puberty (GIPP), café-au-lait spots (CALS) and fibrous dysplasia (FD) of bone. The extent of the abnormalities is variable. We report a 3 year old girl with CALS since infancy, FD diagnosed at age of 2.5 years, and at the age of 3 years vaginal bleeding. The ultrasound revealed a cystic mass of the ovary, surgical pathology found ovarian cyst. LHRH stimulation demonstrated GIPP (LH 9.8 mIU/ml and FSH 8.9 mIU/ml; normal LH 1.8-10, FSH 9-26 mIU/ml). Radiographs and bone scans demonstrated FD in multiple bones. Peripheral leucocytes and the ovary were negative for GNAS gene mutations. Treatment with Letrasole interrupted the pubertal development. We conclude that the clinical signs of MAS are telling and that timely MAS diagnosis prevents unnecessary oophorectomy. A close follow up is recommended regarding development of endocrine disorders and spreading of FD.Journal of pediatric endocrinology & metabolism: JPEM 08/2010; 23(8):837-42. · 0.88 Impact Factor -
Article: Autosomal dominant spondylocostal dysostosis in three generations of a Macedonian family: Negative mutation analysis of DLL3, MESP2, HES7, and LFNG.
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ABSTRACT: The spondylocostal dysostoses (SCDs) are a heterogeneous group of axial skeletal disorders characterized by multiple segmentation defects of the vertebrae (SDV) and abnormality of the thoracic cage with mal-aligned ribs and often a reduction in rib number. The four known monogenic forms of SCD follow autosomal recessive inheritance, have generalized SDV, a broadly symmetrical thoracic cage, and result from mutations in Notch signaling pathway genes-DLL3, MESP2, LFNG, and HES7. Autosomal dominant (AD) SCD has been reported less often, is very variable, and molecular genetic mechanisms remain elusive. Here, we report a three-generation, non-consanguineous family with four affected individuals demonstrating multiple or generalized SDV. Scoliosis was present and the trunk shortened but the ribs were relatively mildly affected. There were no other significant organ abnormalities, no obvious dysmorphic features, neurodevelopment was normal, and all investigations, including mutation analysis of DLL3, MESP2, LFNG, and HES7, were normal. A non-pathogenic variant was detected in LFNG but it did not segregate with the phenotype. This Macedonian kindred adds to knowledge of AD SCD and to our knowledge is the first to be tested for the four Notch pathway genes known to be associated with SCD.American Journal of Medical Genetics Part A 06/2010; 152A(6):1378-82. · 2.39 Impact Factor -
Article: Game-based peripheral biofeedback for stress assessment in children.
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ABSTRACT: Peripheral biofeedback is considered to be an efficient method for assessment and stress mitigation in children. The aim of the present study was to assess the levels of stress and stress mitigation in healthy school children (HSC), in children with cystic fibrosis (CF), general anxiety (GA) and attention-deficit-hyperactivity disorder (ADHD). Each investigated group (HSC, CF, GA, ADHD) consisted of 30 school-aged children from both sexes. Psychological characteristics were evaluated on Eysenck Personality Questionnaire (EPQ). The lie scale was used to determine participant honesty. Four biofeedback games using a pulls detector were applied for assessment of the stress levels as well as to evaluate ability to relax. EPQ found more psychopathological traits (P < 0.001) and less extroversion (P < 0.001) in children with GA and ADHD. In addition, high neurotic tendencies were found in children with CF (P < 0.01) and GA (P < 0.01). Unexpectedly, the lie scale was lower in ADHD children (P < 0.01) than in all other groups (HSC, CF, GA). The Magic blocks score was significantly different in relaxation levels between control and CF children (P < 0.05). Speed in the game Canal was significantly different in relaxation levels between healthy controls and all other groups, but no changes in pulls, as a relaxation measure, were found during the game. The CF group had much more commissions stemming from impulsivity (t= 5.71, P < 0.01), while the GA and ADHD children had more inattention omissions (P < 0.05). Strong negative correlation between age and pulls (r= 0.49, P= 0.003) and strong negative correlation between age and omissions (r=-0.86, P= 0.029) were found among all groups analyzed. The ability to learn stress mediation is correlated with age. All three groups of children had significantly lower relaxation levels when compared to healthy controls. Relaxation was more difficult for children with GA or ADHD, and easier for children with CF.Pediatrics International 10/2009; 52(3):428-31. · 0.63 Impact Factor -
Article: Biofeedback application for somatoform disorders and attention deficit hyperactivity disorder (ADHD) in children
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ABSTRACT: Biofeedback is a modern computer-related technique used mainly for assessment and therapy of psychophysiological disorders. The influx of about 800 patients per year with stress related disorders is the cause of extensive clinical use of biofeedback in our Department. In this article some results obtained with electrodermal (EDR) and electroencephalography (EEG) biofeedback in the assessment and therapy of children with two most common disorders somatoform and Attention Deficit Hyperactivity Disorder in the period of fifteen years are presented and discussed. The two groups of patients comprised 243 children with somatoform problems (age 10.31 ± ± ± ± 2.75 years) and 50 children with Attention Deficit Hyperactivity Disorder (age 11.11 ± ± ± ± 4.51 years). Before application of individually adapted biofeedback modalities, interviews with parents and children, large scale of psychometric tests, as well as evaluations with Quantitative EEG (Mitzar, Russia) were performed. For EDR biofeedback relax plus and Inner Tunner Professional, Ultramind, UK, while for EEG biofeedback Biograph ProComp, Thought Technology LTD, Canada were applied. For somatoform problems 10 -15 sessions of EDR biofeedback were sufficient, while for Attention Deficit Hyperactivity Disorder the number of needed sessions was 20 -40, twice a week. Our experiences with these non-pharmacologic methods in the assessment and therapy of somatoform problems and Attention Deficit Hyperactivity Disorder are quite positive, providing that biofeedback is combined with psychological support and cognitive-behavioral psychotherapy. The results showed that the EDR biofeedback is more effective in the case of somatoform disorders, and the EEG biofeedback (neurofeedback) in the case of Attention Deficit Hyperactivity Disorder. Still, EDR biofeedback appeared to be more preferable method by young children than EEG biofeedback, either as a unique treatment or as a first step preceding the neurofeedback therapy.International Journal of Medicine and Medical Sciences. 03/2009; 1:17-22. -
Article: Friedreich's ataxia (FA) associated with diabetes mellitus type 1 and hypertrophic cardiomyopathy: analysis of a FA family.
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ABSTRACT: Progressive signs of ataxia in a eight year old girl with hypo-active knee and ankle jerks, prompted the analysis of the frataxin gene (FXN; 606829). The most common molecular abnormality--GAA trinucleotide repeat expansion in intron 1--was found with +300 GAA repeats (1490 bp) (normal individuals have 5 to 30 GAA repeats expansions, whereas affected individuals have from 70 to more than 1000 GAA triplets). Additionally she had unstable gait with incoordination of limb movements, impairment of position and vibratory senses, dysarthria, pes cavus, positive Babinski sign and scoliosis. At the age of fourteen the girl was referred in a comatose condition, in severe diabetic ketoacidosis. Insulin dependent diabetes mellitus was since treated with insulin preparations. Electrocardiogram showed diffuse T wave inversion with sinus bradycardia, while ultrasound revealed concentric, symmetric hypertrophy of the left ventricle leading to the diagnosis of hypertrophic cardiomyopathy. At the age of 14, she is bound to the wheelchair, unable to walk. Her brother started to show ataxia at the age of 8 years and subsequent analysis also showed hypertrophic cardiomyopathy. His mutational analysis revealed the same frataxin abnormality with +300 GAA repeats. So far, no signs of diabetes occurred. The parental DNA was not available for analysis.Medical Archives 02/2009; 63(2):110-1. -
Article: Signatures of depression in non-stationary biometric time series.
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ABSTRACT: This paper is based on a discussion that was held during a special session on models of mental disorders, at the NeuroMath meeting in Stockholm, Sweden, in September 2008. At this occasion, scientists from different countries and different fields of research presented their research and discussed open questions with regard to analyses and models of mental disorders, in particular depression. The content of this paper emerged from these discussions and in the presentation we briefly link biomarkers (hormones), bio-signals (EEG) and biomaps (brain-maps via EEG) to depression and its treatments, via linear statistical models as well as nonlinear dynamic models. Some examples involving EEG-data are presented.Computational Intelligence and Neuroscience 02/2009; -
Article: Signatures of Depression in Non-Stationary Biometric Time Series.
Comp. Int. and Neurosc. 01/2009; 2009. -
Article: Arthrogryposis multiplex congenital (AMC) in a three year old boy: differential diagnosis with distal arthrogryposis: a case report.
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ABSTRACT: Arthrogryposis multiplex congenital (AMC) is characterized by contractions of multiple joints present at birth. The involved muscles are partially or totally replaced by fat or fibrous tissue. Talipes equinovarus and scoliosis are also frequently reported. This 2 year was born after uneventful pregnancy, with normal birth weight and length. The parents are unrelated, young and healthy. No malformations or mental retardation have been reported in the family. Since his birth a specific posture was noted: internal rotation at the shoulders, extension at the elbows, and flexion at the wrists. In addition, the child has a severe equinovarus deformity of the feet. Syndactily between II and III finger was also noted. His face is round with a frontal midline capillary hemangioma, while his jaw appears to be small. Mental development is normal. The karyotype is: 46, XY. About 150 syndromes have arthrogryphosis as a presenting sign. AMC is a distinct entity and distinction with the distal forms of arthrogryphosis can be difficult, since there is a considerable clinical and genetic heterogeneity. A comprehensive musculoskeletal evaluation and genetic consultation is necessary.Cases Journal 01/2009; 2:9403. -
Article: Neurophysical substrates of arousal and attention.
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ABSTRACT: The study of arousal and attention could be of prominent importance for elucidating both fundamental and practical aspects of the mind-brain puzzle. Defined as "general activation of mind" (Kahnemann in Attention and effort. Prentice-Hall, New Jersey, 1973), or "general operation of consciousness" (Thacher and John in Functional neuroscience: foundations of cognitive processing. Erlbaum, Hillsdale, 1977), arousal can be considered as a starting point of fundamental research on consciousness. Similar role could be assigned to attention, which can be defined by substituting the attributes "general" with "focused". Concerning the practical applications, the empirically established correlation between neuronal oscillations and arousal/attention levels is widely used in research and clinics, including neurofeedback, brain-computer communication, etc. However, the neurophysical mechanism underlying this correlation is still not clear enough. In this paper, after reviewing some present classical and quantum approaches, a transition probability concept of arousal based on field-dipole quantum interactions and information entropy is elaborated. The obtained analytical expressions and numerical values correspond to classical empirical results for arousal and attention, including the characteristic frequency dependence and intervals. Simultaneously, the fundamental (substrate) role of EEG spectrum has been enlightened, whereby the attention appears to be a bridge between arousal and the content of consciousness. Finally, some clinical implications, including the brain-rate parameter as an indicator of arousal and attention levels, are provided.Cognitive Processing 11/2008; 10 Suppl 1:S71-9. · 1.57 Impact Factor -
Article: Congenital lipomatous overgrowth, vascular malformations, and epidermal nevi (CLOVE) syndrome: CNS malformations and seizures may be a component of this disorder.
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ABSTRACT: A newborn girl was found to have a massive lymphatic truncal vascular malformation with overlying cutaneous venous anomaly associated with overgrown feet and splayed toes. These manifestations comprise the recently described CLOVE syndrome. She also had cranial asymmetry and developed generalized seizures, which were treated with anticonvulsants. Cranial CT showed encephalomalacia, widening of the ventricles and the sulci, hemimegalencephaly (predominantly white matter) and partial agenesis of corpus callosum. Review of the literature identified several other patients with CLOVE syndrome, some of whom were misdiagnosed as having Proteus syndrome, with strikingly similar manifestations. We conclude that CNS manifestations including hemimegalencephaly, dysgenesis of the corpus callosum, neuronal migration defects, and the consequent seizures, may be an rarely recognized manifestation of CLOVE syndrome.American Journal of Medical Genetics Part A 10/2008; 146A(20):2688-90. · 2.39 Impact Factor -
Article: Spectrum-weighted EEG frequency ("brain-rate") as a quantitative indicator of mental arousal.
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ABSTRACT: A concept of brain-rate is introduced, defining it as the weighted mean frequency of the EEG spectrum. In analogue to the blood pressure, heart-rate and temperature, used as standard preliminary indicators of corresponding general bodily activations, it is proposed to use the brain-rate as a preliminary indicator of general mental activation (mental arousal) level. In addition, along with the more specific few-band biofeedback parameters (theta-beta ratio, relative beta ratio, etc.), the brain-rate could be effectively used as a general multiband biofeedback parameter.Prilozi / Makedonska akademija na naukite i umetnostite, Oddelenie za biološki i medicinski nauki = Contributions / Macedonian Academy of Sciences and Arts, Section of Biological and Medical Sciences 01/2006; 26(2):35-42. -
Article: Psychosocial effects of community noise: cross sectional study of school children in urban center of Skopje, Macedonia.
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ABSTRACT: To assess noise exposure in school children in urban center in different residential areas and to examine psychosocial effects of chronic noise exposure in school children, taking into account their socioeconomic status. We measured community noise on specific measurement points in residential-administrative-market area and suburban residential area. We determined the average energy-equivalent sound level for 8 hours (LAeq, 8 h) or 16 hours (LAeq, 16 h) and compared measured noise levels with World Health Organization (WHO) guidelines. Psychological effects were examined in two groups of children: children exposed to noise level LAeq, 8 h >55 dBA (n=266) and children exposed to noise level LAeq, 8 h <55 dBA (n=263). The examinees were schoolchildren of 10-11 years of age. We used a self-reported questionnaire for each child - Anxiety test (General Anxiety Scale) and Attention Deficit Disorder Questionnaire intended for teachers to rate children's behavior. We used Mann Whitney U test and multiple regression for identifying the significance of differences between the two study groups. School children who lived and studied in the residential-administrative-market area were exposed to noise levels above WHO guidelines (55 dBA), and school children who lived and studied in the suburban residential area were exposed to noise levels below WHO guidelines. Children exposed to LAeq, 8 h >55 dBA had significantly decreased attention (Z=-2.16; p=0.031), decreased social adaptability (Z =-2.16; p=0.029), and increased opposing behavior in their relations to other people (Z=-3; p=0.001). We did not find any correlation between socioeconomic characteristics and development of psychosocial effects. School children exposed to elevated noise level had significantly decreased attention, and social adaptability, and increased opposing behavior in comparison with school children who were not exposed to elevated noise levels. Chronic noise exposure is associated with psychosocial effects in school children and should be taken as an important factor in assessing the psychological welfare of the children.Croatian Medical Journal 09/2004; 45(4):473-6. · 1.80 Impact Factor
Top co-authors
Top Journals
Institutions
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2008–2011
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Macedonian Academy of Sciences and Arts
Skopje, Opstina Karpos, Macedonia
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2004
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Institute of Public Health of the Republic of Macedonia
Skopje, Opstina Karpos, Macedonia
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1970
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University American College Skopje
Skopje, Opstina Karpos, Macedonia
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