M Djordjevic

University of Belgrade, Belgrade, SE, Serbia

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Publications (19)40.34 Total impact

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    ABSTRACT: INTRODUCTION:Rett syndrome (RTT) is a severe neurodevelopmental disorder. Bone manifestations of RTT include osteopenia and fractures. Studies addressing serum vitamin D levels in RTT patients are scarce.GOALS:1. To determine prevalence of vitamin D deficiency in RTT patients, 2. To compare serum vitamin D levels between patients with RTT and other neurological diseases, 3. To explore correlation between demographic and clinical characteristics of RTT patients and vitamin D levels.METHODS:Demographic and clinical characteristics included age, BMI z-score, mutation status, Clinical Severity Score, presence of epilepsy, number of antiepileptic drugs (AEDs), history of fractures, scoliosis and ambulation ability. Laboratory parameters included serum 25(OH)D, PTH, calcium and alkaline phosphatase.RESULTS:The study included 35 RTT patients and 35 age-matched females with other neurological diseases. The median serum 25(OH)D in RTT group was 26.25 nmol/L, with values below 75 nmol/L in all participants. Severe deficiency (<25 nmol/L) was detected in 17/35 (48.6%) patients. Median 25(OH)D concentration was significantly lower in RTT patients than in controls. The risk for fracture by 12 years of age in RTT patients was 35.3%. Inverse correlation of 25(OH)D level to age and PTH level was detected. Patients receiving antiepileptic polytherapy had 3.3 times greater chance for severe vitamin D deficiency than patients with monotherapy.CONCLUSION:Prevalence of vitamin D deficiency in RTT patients is higher than in patients with other neurological diseases. High risk for vitamin D deficiency should be accounted for in the strategy of antiepileptic treatment in RTT, especially when polytherapy is considered.
    The Journal of clinical endocrinology and metabolism 10/2013; · 6.50 Impact Factor
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    ABSTRACT: In Serbia, infection with Trichinella spp. has been recognized as a human health and animal husbandry problem for almost a century. The rate of swine infection gradually decreased from 0.14% to 0.02% between 2001 and 2010. For the past 5 years, Trichinella infections among swine were detected at levels higher than 0.05% in 3 districts of Serbia while prevalence persisted at lower levels for the rest of the country. During this 10-year period, there were 2257 cases of human trichinellosis, including 3 deaths; however, a significant decrease in the number of cases was reported during the last 5 years (fewer than 200 cases per year). The fact that prevalence data presented here are similar to prevalence data from 1990 indicates that this period of 10 years was needed to overcome the re-emergence of Trichinella infection in swine and humans that occurred during the last decade of the previous century.
    Veterinary Parasitology 02/2013; · 2.38 Impact Factor
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    ABSTRACT: Phenylketonuria (PKU) is caused by mutations in the gene encoding phenylalanine hydroxylase (PAH) enzyme. Here, we report the updated spectrum of PAH mutations in 61 Serbian PKU patients. By using both DGGE/DNA sequencing and PCR-RFLP, we identified 26 disease-causing mutations (detection rate 99%). The most frequent ones were p.L48S (31%), p.R408W (16.4%), p.P281L (6%), p.E390G (5.2%), and p.I306V (5.2%). Homozygosity value indicated high heterogeneity of Serbian population.To overcome possible pitfalls of patients' phenotypic classification, we used two parameters: pretreatment/maximal phenylalanine blood concentration and Phe tolerance. The two phenotypes did not match only for patients with p.L48S. Therefore, we used Mann-Whitney statistical test to compare pretreatment/maximal blood Phe concentration and Phe tolerance detected in patients with p.[L48S];[null] and p.[missense];[null] genotypes. For patients with p.L48S, our results implied that Phe tolerance is a better parameter for phenotypic classification. Also, Fisher's exact test was used to compare p.L48S effect on phenotype of homozygous and functionally hemizygous patients. Our findings showed that effect of p.L48S was altered in functional hemizygotes. Moreover, phenotypic inconsistency found in homozygotes suggested that interallelic complementation and/or additional factors play a role in genotype-phenotype correlation.Since BH4-supplementation therapy is not available in Serbia, we made the first estimation of its potential benefit based on patients' genotypes. In the analyzed cohort, the total frequency of BH4-responsive mutations was 52.6%. Furthermore, we found a significant number of genotypes (26.2% BH4-responsive and 51% probably BH4-responsive) that may respond to BH4 therapy. This led us to a conclusion that BH4-supplementation therapy could bring benefit to Serbian PKU patients.
    JIMD reports. 01/2013; 9:49-58.
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    ABSTRACT: INTRODUCTION: We evaluated a novel approach for investigation of lymphocyte dysregulation in Gaucher patients by including determination of IgH and TCR gene rearrangements together with levels of immunoglobulins, natural autoantibodies as well as presence of monoclonal protein. MATERIALS AND METHODS: Measurement of serum immunoglobulins, monoclonal immunoglobulins, selected autoantibodies, as well as analysis of immunoglobulin heavy chain and T cell receptor gene rearrangements. RESULTS: Immunoglobulin disorder was detected in 29.6% patients, 40.7% demonstrated presence of B cell clonality and 44.4% demonstrated presence of autoantibodies. In five patients in our series, the presence of IgH gene rearrangement was the only detectable indicator of B cell dysfunction. TCR gene rearrangements were not found in any of the patients. CONCLUSION: Based on our results, we propose IgH gene rearrangements as a new biomarker for investigation of B cell dysfunction occurring as a complication of Gaucher disease.
    Blood Cells Molecules and Diseases 12/2012; · 2.26 Impact Factor
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    ABSTRACT: The objective of the study was to evaluate etiology, clinical characteristics and outcome in children with epilepsia partialis continua (EPC). The investigation included 51 children with EPC aged 0.2-18 years treated in the period 1993-2009. The median period from the onset of underlying disorder to EPC was 6 months (0-72 months). EPC was caused by different pathologies: inflammatory and immune-mediated (52%), metabolic (13.7%), structural brain abnormalities (11.8%), cryptogenic (7.8%), vascular (5.9%), dual (5.9%), postoperative (2%). Median duration of EPC was 15 days (1-200 days). EPC involved more frequently the right side of the body comparing to the left one. The outcome was assessed at the end of the follow up period (mean 6.5 years, ranged 0.2-16 years). Unchanged neurological status was observed in 10 (19.6%) children, neurological consequences in 33 (64.7%) children and lethal outcome in 8 (15.7%) children. The most frequent etiology in our cohort was inflammatory and immune-mediated disease of central nerve system including Rasmussen's encephalitis. The duration of EPC was prolonged, most frequently involving the right upper limb. The outcome of EPC in children was unfavorable.
    Epilepsy research 10/2012; · 2.48 Impact Factor
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    ABSTRACT: Since bone pathology is a major concern in type 1 Gaucher disease (GD1), we evaluated bone mineral density (BMD) in adults receiving velaglucerase alfa in the seminal Phase I/II and extension trial. Ten treatment-naïve symptomatic patients with GD1 (four men, six women; median age 35years, range 18-62years) were included; of these, four patients were receiving bisphosphonates at enrollment. Using WHO criteria to classify the lumbar spine (LS) and femoral neck (FN) BMD T-scores, respectively, one (10%) and four (40%) patients had osteoporosis; eight (80%) and five (50%) had osteopenia; and one each (10%) was in the normal range, at baseline. By Month 69, two LS and one FN osteopenic patients normalized and one FN osteoporotic patient became osteopenic; change was seen only in patients not receiving bisphosphonates. Significant improvements in BMD Z-scores were seen at the LS by Month 24 and at the FN by Month 33 and were continuous thereafter. In linear mixed models, Z-scores were significantly lower than the reference population at baseline and improved significantly with treatment (LS and FN both P<0.01); analysis of the subgroup of patients not receiving bisphosphonates showed similar results. In conclusion, in this small cohort, velaglucerase alfa was associated with clinically meaningful and statistically significant LS and FN BMD improvements as early as Month 24 (LS) and 33 (FN), despite dose reduction and significant baseline skeletal pathology. These results suggest that velaglucerase alfa may hold promise in the management of skeletal pathology associated with GD1.
    Blood Cells Molecules and Diseases 06/2011; 47(1):56-61. · 2.26 Impact Factor
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    ABSTRACT: Therapeutic goals have been described to monitor achievement, maintenance and continuity of therapeutic response in patients with type 1 Gaucher disease receiving enzyme replacement therapy. To benchmark the impact of velaglucerase alfa treatment against therapeutic goals for 5 key clinical parameters of type 1 Gaucher disease (anemia, thrombocytopenia, hepatomegaly, splenomegaly and skeletal pathology). In an open-label Phase I/II study, twelve adults with symptomatic type 1 Gaucher disease and intact spleens received velaglucerase alfa for 9 months (60 U/kg infusion every other week [EOW]). Eleven patients completed the study and 10 enrolled in a long-term extension. After 1 year, patients who achieved ≥ 2 hematological or organ goals began step-wise dose reduction from 60 to 45 then 30 U/kg EOW. Data for anemia, thrombocytopenia, hepatomegaly, splenomegaly and skeletal pathology at baseline and 4 years are available for 8 patients (3 male, 5 female). The proportion of patients at goal for anemia, thrombocytopenia, hepatomegaly and splenomegaly at baseline was compared with the proportion achieving each goal at 4 years. The proportion achieving the skeletal pathology goal was determined on the basis of Z-score improvement from baseline to 4 years. The proportion of patients who achieved all 5 goals at 4 years was compared with the proportion at goal for all 5 parameters at baseline. At baseline, no patient was at goal for all clinical parameters. After 1 year of treatment, all patients maintained goals present at baseline, and all achieved ≥ 2 goals. All 8 patients began step-wise dose reduction from 60 to 30 U/kg EOW between 15 and 18 months. By year 4 of treatment, all patients met goals for all 5 clinical parameters; therefore 100% achievement was seen for each of the 5 long-term, therapeutic goals. In this velaglucerase alfa Phase I/II and extension study, clinically meaningful achievement of each long-term, therapeutic goal was observed for each patient, despite dose reduction after 1 year. This is the first report of a cohort where all patients receiving ERT for type 1 Gaucher disease achieved all 5 of these long-term, therapeutic goals within 4 years of starting treatment and after ≥ 2years dose reduction.
    Blood Cells Molecules and Diseases 01/2011; 46(1):119-23. · 2.26 Impact Factor
  • Journal of Inherited Metabolic Disease 03/2010; 33(3):301-2. · 4.07 Impact Factor
  • Balkan Journal of Medical Genetics - BALK J MED GEN. 01/2008; 11(1):65-68.
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    ABSTRACT: X-linked adrenoleukodistrophy is a severe neurodegenerative disorder with impaired very long chain fatty acid metabolism. The disease associated ABCD1 gene encodes a peroxisomal membrane protein which belongs to the superfamily of ATP-binding cassette transporters. We investigated eight male X-ALD patients diagnosed among 142 suspected patients referred for investigation. Plasma levels of very long chain fatty acids were measured at our laboratory using capillary gas chromatography. Eight cases of childhood X-ALD were diagnosed. This is the first published series of Serbian patients with X-ALD. In addition, diagnosis identifies carriers, which could be benefit for genetic counselling and prenatal diagnosis.
    Indian Journal of Clinical Biochemistry 09/2007; 22(2):118-22.
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    ABSTRACT: Phenylketonuria (PKU) is the most common inborn error of amino acid metabolism in Caucasians. PKU is caused by mutations in the gene encoding phenylalanine hydroxylase (PAH) enzyme. Here, we report the spectrum and the frequency of mutations in the PAH gene and discuss genotype-phenotype correlation in 34 unrelated patients with PKU from Serbia and Montenegro. Using both polymerase chain reaction-restriction fragment length polymorphism and 'broad-range' denaturing-gradient gel electrophoresis/DNA sequencing analysis, 19 disease-causing mutations were identified, corresponding to mutation detection rate of 97%. The most frequent ones were L48S (21%), R408W (18%), P281L (9%), E390G (7%) and R261Q (6%), accounting for 60% of all mutant alleles. The genotype-phenotype correlation was studied in homozygous and functionally hemizygous patients. We found that the most frequent mutation, L48S, was exclusively associated with the classical (severe) PKU phenotype. The mutation E390G gave rise to mild PKU. For the mutation R261Q, patients had been recorded in two phenotype categories. Considering allele frequencies, PKU in Serbia and Montenegro is heterogeneous, reflecting numerous migrations over the Balkan Peninsula.
    Clinical Genetics 09/2006; 70(2):151-5. · 3.94 Impact Factor
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    ABSTRACT: In the Balkan countries, where trichinellosis is a re-emerging zoonosis, it is of great importance to determine Trichinella infection prevalence among the major hosts, including horses. One method for monitoring prevalence is serological surveillance; however, the validity of serological methods in horses is not well understood. The dynamics of anti-Trichinella IgG production and circulating excretory/secretory (ES) antigens were investigated in three horses experimentally-infected with Trichinella spiralis. Horses were slaughtered at 32 week post infection (p.i.). Low worm burdens were found in all three animals. Anti-Trichinella IgG was detected up to 32 weeks p.i. by an indirect immunofluorescence assay (IFA) and by Western blot (Wb), but not by ELISA. The ELISA test detected antibodies for only a short period of time (up to 18 weeks p.i. using ES antigen or up to 20 weeks p.i. using tyvelose-BSA antigen). The presence of circulating muscle larvae ES antigen in sera of infected horses was observed by dot blot from the 4th week p.i. up to the 32nd week p.i.
    Veterinary Parasitology 10/2005; 132(1-2):107-11. · 2.38 Impact Factor
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    M Djordjevic, K Cuperlovic, M Savic, S Pavlovic
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    ABSTRACT: Implementation of methods to control inspection for Trichinella in meat recommended by International Commission on Trichinellosis (ICT), particularly the introduction of the quality assurance standards and proficiency panels for certified analysts is extremely important in Serbia and other countries where Trichinellosis is endemic. In spite of existing regulations, including the inspection of 0.5 g samples of diaphragm by the compression method or by artificial digestion of 1g samples, in Serbia 280 people were diagnosed with clinical trichinellosis after consumption of inspected meat during the period 2001--2002. These outbreaks, which occurred in the municipalities of Kumane, Surcin and Bogatic, were a consequence of inadequate application of inspection methods and insufficient education of some veterinary inspectors. The problem of inadequate veterinary inspection in Serbia can be overcome by strict application of the ICT recommendations for the control of Trichinella with specific emphasis on implementing the quality assurance system (QAS) and proficiency sampling (PS/--PP/panel).
    Veterinary Parasitology 10/2005; 132(1-2):185-8. · 2.38 Impact Factor
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    K Cuperlovic, M Djordjevic, S Pavlovic
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    ABSTRACT: The countries of southeastern Europe including the Balkan region and bordering countries - Albania, Bulgaria, Bosnia and Herzegovina, Croatia, Greece, Hungary, Macedonia, Romania, Serbia and Montenegro, Slovenia, and the European part of Turkey - occupy a very important strategic position and represent a land bridge between Europe and Asia. In the majority of southeastern European countries, cases of trichinellosis among the human and animal populations were described in the late 19th or early 20th centuries. Trichinella infections among wildlife were also described in the aforementioned countries. Today, the prevalence of trichinellosis is different between the Balkans and bordering countries. A high prevalence of trichinellosis in domestic animals and humans has been reported in Bulgaria, Serbia and Montenegro, Romania and Croatia. A moderate prevalence was found in Bosnia and Herzegovina. In Hungary, human trichinellosis has not been present for a long period of time. However, sporadic cases were recorded in swine over the last 2 years. Trichinellosis has not been found among domestic animals and humans in Greece and Macedonia in recent years while in Turkey and Slovenia human trichinellosis is sporadic. The re-emergence of trichinellosis is connected with the changes in the social and political systems in Bulgaria and Romania. In Serbia and Montenegro as well in Croatia, however, a re-emergence of trichinellosis was due not only to political and social changes but also to wars that took place in these countries during the last years of the 20th century. Social, economic and political factors responsible for the re-emergence of trichinellosis in southeast European countries are discussed in this communication.
    Veterinary Parasitology 10/2005; 132(1-2):159-66. · 2.38 Impact Factor
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    ABSTRACT: A discovery in 2002 of a Trichinella spiralis-infected horse in Serbia offered an opportunity to conduct needed epidemiological studies on how horses, considered herbivores, acquire a meat-borne parasite. This enigma has persisted since the first human outbreaks from infected horse meat occurred in then 1970s. The trace back of the infected horse to a farm owner was carried out. Interviews and investigations on the farm led to the conclusion that the owner had fed the horse food waste in order to condition the horse prior to sale. Further investigations were then carried out to determine the frequency of such practices among horse owners. Based on interviews of horse producers at local horse markets, it was revealed that the feeding of animal products to horses was a common practice. Further, it was alleged that many horses, particularly those in poor nutritional condition would readily consume meat. A subsequent series of trials involving the experimental feeding of 219 horses demonstrated that 32% would consume meat patties. To confirm that horses would eat infected meat under normal farm conditions, three horses were offered infected ground pork balls containing 1100 larvae. All three became infected, and at necropsy at 32 weeks later, were still positive by indirect IFA testing, but not by ELISA using an excretory-secretory (ES) antigen. This result indicates that further study is needed on the nature of the antigen(s) used for potential serological monitoring and surveillance of horse trichinellosis, especially the importance of antigenic diversity. The experimentally-infected horses also had very low infection levels (larvae per gram of muscle) at 32 weeks of infection, and although the public health consequences are unknown, the question of whether current recommended inspection procedures based on pepsin digestion of selected muscle samples require sufficient quantities of muscle should be addressed. It is concluded that horses are more willing to consume meat than realized and that the intentional feeding of animal products and kitchen waste is a common occurrence among horse owners in Serbia (and elsewhere?). This is a high risk practice which demands closer scrutiny by veterinary and food safety authorities, including the implementation of rules and procedures to ensure that such feeds are rendered safe for horses, as is now required for feeding to swine.
    Veterinary Parasitology 10/2004; 123(3-4):223-33. · 2.38 Impact Factor
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    ABSTRACT: Over the past decade, eastern Europe has experienced a resurgence of trichinellosis. A recent outbreak in Serbia, Yugoslavia, from December 2001 to January 2002, involving 309 people, revealed many of the causes for this reemergence. Epidemiological investigations indicate that the immediate cause of the recent outbreak was the consumption of smoked sausages produced by a small slaughterhouse or meat processor. However, failure of in-house meat inspection procedures and quality assurance as well as oversight by official veterinary control were also responsible. Further analysis of this breakdown in the food safety net revealed additional general factors that have yielded a seriously deficient veterinary control system, and these are factors that are relevant to the problems experienced throughout eastern Europe and other regions. The recent civil war that led to the breakup of the former Federation of Yugoslavia resulted in severe economic and demographic changes, including high inflation and external economic sanctions. This led to (1) the loss of large numbers of experienced veterinary control officers and their replacement with inexperienced personnel, (2) a change in the swine industry with reduction in the number of large establishments with in-house inspection and replacement with more than 1,000 small abattoirs, too small to afford full-time in-house inspection, and (3) an increase in smallholder pig farming with reduced government oversight to ensure high standards in pig-rearing practices (infection risk management). The consequences of these events have been a 300% increase in Serbian pig infection and a concomittant large increase in human outbreaks. Before 1990, swine trichinellosis in Serbia was confined to 4 small districts, but today about one third of the Republic is considered endemic for trichinellosis. The reemergence of trichinellosis in Serbia illustrates the ability of this zoonosis to "leak" through a poorly maintained food safety barrier and the vulnerability of effective veterinary control to national and international events.
    Journal of Parasitology 05/2003; 89(2):226-31. · 1.32 Impact Factor
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    ABSTRACT: Trichinellosis was recognized almost one century ago as a health and animal husbandry problem in Serbia. In the last 10 years, trichinellosis has been expanding from three endemic regions (Srem, Macva and Negotinska Krajina) to neighbouring regions. The infection rate detected by veterinary inspection in 1999 year was 0.17% in slaughtered swines. Simultaneously, the number of infected humans increased three-five times in comparison with the period 1980-1990. For instance, 555 individuals were registered in 1999 as infected after the consummation of non-inspected pork from domestic swine or wild boar. Prevalence of trichinellosis in wild animals was examined more than a 20 years ago. The trichinellosis in horses has not been detected in the country, but infected horses imported from Serbia were detected in France and Italy.
    Parasite (Paris, France) 07/2001; 8(2 Suppl):S95-7. · 1.12 Impact Factor
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    ABSTRACT: Time of survival and infectivity of Trichinella spiralis larvae in pig muscle tissue, buried at various depths in the ground were assessed. In the pork pieces the number of infective larvae was 250 ML/g. Meat originated from pig halves was divided in 39 equal pieces, 0.7 kg each, disposed in three groups of 13, and buried in depths of 30, 50, and 100 centimeters respectively. The pork was dug up at 13 intervals, approximately every week, until 91st day of the experiment. After each time interval, infectivity of larvae was assessed by bioassay on rats. The artificially infected rats were sacrificed on 42nd day after the infection and meat was examined by the following methods--artificial digestion and trichinoscopy. It was found that the larvae during all 90 days preserved infectivity in each depth.
    Parasite (Paris, France) 07/2001; 8(2 Suppl):S213-5. · 1.12 Impact Factor
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    ABSTRACT: A novel lateral flow card (TS-Card pork) test was developed for the serological detection of Trichinella infected pigs. Based on extensive studies performed in Romania during 1999-2000 this test proved to be highly specific sensitive, rapid (3-12 minutes) and easy to use (no need for laboratory facilities). It can be used both for the detection of Trichinella infection in carcasses and for epizooliological studies using a variety of samples including whole or dried blood, serum, or tissue fluids. The TS-Card pork test, used as a screening test, can be the foundation of an on-farm or field based inspection system to significantly improve food safety in countries with a high prevalence of Trichinella in pigs or other food animal species. The results presented are also promising for application of the test in an on-line laboratory based inspection system since the speed of the test allows sufficient time to rail out suspected hog carcasses during the slaughter process.
    Parasite (Paris, France) 07/2001; 8(2 Suppl):S240-2. · 1.12 Impact Factor

Publication Stats

132 Citations
40.34 Total Impact Points

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  • 2013
    • University of Belgrade
      • School of Medicine
      Belgrade, SE, Serbia
  • 2012–2013
    • Institute for Health Protection of Mother and Child of Serbia
      Beograd, Central Serbia, Serbia
  • 2010–2011
    • Institut za zdravstvenu zaštitu majke i deteta Srbije Dr Vukan Čupić
      Beograd, Central Serbia, Serbia
  • 2006
    • Institute for Educational Research, Belgrade, Serbia
      Beograd, Central Serbia, Serbia