Faculty of Medical Sciences, Kragujevac
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Item Oxidative stress in fetal distress: Potential prospects for diagnosis(2010) Raicevic, Sasa; Čubrilo D.; Arsenijevic, Slobodan; Gordana V.; Zivkovic, Vladimir; Vuletic, Milena; Jeremic, Nevena; Anđelković, Nebojša; Antonovic O.; Jakovljevic, VladimirOur aim was to investigate the relation between fetal distress and oxidative stress. Fetal distress was associated with increased concentration of superoxide in the fetal blood and with significant increase of the level of H2O2 in both maternal and fetal blood. The activity of superoxide dismutase was increased roughly sixfold (p < 0.01) in the maternal [7330 ± 2240 U/g of hemoglobin in controls (C) and 36811 ± 16862 U/g in fetal distress (FD)] and fetal blood (C: 5930 ± 2641 U/g; FD: 41912 ± 17133 U/g). In contrast, fetal distress was related to a considerable decrease of catalase activity in both maternal (C: 26011 ± 8811 U/g; FD: 7212 ± 1270 U/g) and fetal blood (C: 37194 ± 9191 U/g; FD: 6173 ± 1965 U/g). From this we concluded that in fetal distress, the maternal and fetal bloods are exposed to superoxide- and H 2O2-mediated oxidative stress, which could be initiated by hypoxic conditions in the fetal blood and placenta. A tremendous increase/decrease of the activities of superoxide dismutase/catalase in the blood of women bearing a distressed fetus in comparison to healthy subjects implies that the assessment of superoxide dismutase/catalase activity could be of use for establishing a timely and accurate ante- or intrapartum diagnosis of fetal distress. © 2010 Landes Bioscience.Item Von Willebrand factor and oxidative stress parameters in acute coronary syndromes(2011) Jakovljevic, Vladimir; Koprivica Z.; Djordjevic, Dusica; Vuletic, Milena; Zivkovic, Vladimir; Barudzic N.; Anđelković, Nebojša; Djuric, Dragan M.; Iric Cupic, Violeta; Krkeljic J.Considering the role of von Willebrand factor (vWf) in hemostasis, and the role of oxidative stress in the development of endothelial dysfunction and atherosclerotic disease, the aim of our study was to investigate the relationship between vWf, parameters of oxidative stress and different types of acute coronary syndromes (ACS). Levels of vWf activity (vWfAct), vWf antigen (vWfAg), nitric oxide (estimated through nitrites-NO 2-), superoxide anion radical (O 2-), hydrogen peroxide (H 2O 2), index of lipid peroxidation (estimated through thiobarbituric acid reactive substances-TBARS), superoxide dismutase (SOD) and catalase (CAT) activity of 115 patients were compared with those of 40 healthy controls. ACS patients had significantly higher vWfAct and vWfAg levels, as well as TBARS levels, while their levels of NO 2-, H 2O 2, SOD and CAT activities were lower than controls'. vWfAg showed high specificity and sensitivity as a test to reveal healthy or diseased subjects. Multivariant logistic regression marked only vWfAg and TBARS as parameters that were under independent effect of ACS type. The results of our study support the implementation of vWf in clinical rutine and into therapeutic targets, and suggest that ACS patients are in need of antioxidant supplementation to improve their impaired antioxidant defence. © 2011 Zoran Koprivica et al.Item Nitroglycerine effects on portal vein mechanics and oxidative stress in portal hypertension(2012) Vujanac A.; Jakovljevic, Vladimir; Djordjevic, Dusica; Zivkovic, Vladimir; Stojković M.; Celikovic D.; Anđelković, Nebojša; Jurisic Skevin, Aleksandra; Djuric, Dragan M.AIM: To examine the effects of nitroglycerine on portal vein haemodynamics and oxidative stress in patients with portal hypertension. METHODS: Thirty healthy controls and 39 patients with clinically verified portal hypertension and increased vascular resistance participated in the study. Liver diameters, portal diameters and portal flow velocities were recorded using color flow imaging/pulsed Doppler detection. Cross-section area, portal flow and index of vascular resistance were calculated. In collected blood samples, superoxide anion radical (O2-), hydrogen peroxide (H2O2), index of lipid peroxidation (measured as TBARS) and nitric oxide (NO) as a marker of endothelial response (measured as nitrite-NO2-) were determined. Time-dependent analysis was performed at basal state and in 10th and 15th min after nitroglycerine (sublingual 0.5 mg) administration. RESULTS: Oxidative stress parameters changed significantly during the study. H2O2 decreased at the end of study, probably via O2- mediated disassembling in Haber Weiss and Fenton reaction; O2-increased significantly probably due to increased diameter and tension and decreased shear rate level. Consequently O2- and H2O2 degradation products, like hydroxyl radical, initiated lipid peroxidation. Increased blood flow was to some extent lower in patients than in controls due to double paradoxes, flow velocity decreased, shear rate decreased significantly indicating non Newtonian characteristics of portal blood flow. CONCLUSION: This pilot study could be a starting point for further investigation and possible implementation of some antioxidants in the treatment of portal hypertension. © 2012 Baishideng. All rights reserved.Item Presentation of an infant with nutritional deficiency dermatitis as the initial manifestation of cystic fibrosis(2013) Stojkovic Andjelkovic, Andjelka; Radlovic N.; Vuletic, Biljana; Nestorović B.; Leković Z.; Obradovic, Slobodan; Vujic, AnaIntroduction Cystic fibrosis (CF) is a multisystemic autosomal recessive disease most frequently recognized by characteristic respiratory and/or digestive manifestations. Exceptionally rare, as is the case with the infant we are presenting, the initial sign of the disease can be nutritional deficiency dermatitis (NDD). Case Outline A three-month-old male infant of young and healthy non-consanguineous parents, born at term after the first uneventful pregnancy, was hospitalized due to atopic dermatitis (AD)-like skin changes, failure to thrive and normochromic anemia (Hb 60 g/L). As exclusively breast-fed, failure to thrive was attributed to hypogalactia and skin changes to nutritional allergy, so that, besides exclusion of cow's milk protein and other highly allergenic foods in mother's diet, hypoallergenic milk formula was added to the child's diet. However, dietetic measures were without effect, and the child was re-hospitalized at age 4.5 months, this time in the condition of severe malnutrition with hypoproteinemic edemas, extensive dermatitis, moderate hepatosplenomegaly and recurrent normochromic anemia (Hb 57 g/L). After plasma-free erythrocyte transfusion, correction of hypoalbuminemia and two-week parenteral and semi-elementary nutrition resulted in gradual recovery of the child, also including the resolution of skin changes. Having in mind the clinical course of the disease, as well as the response to applied therapeutic measures, CF was suspected as the cause of the child's problems, which was also confirmed by a high level of sweat chlorine (92 mmol/L) and DNA analysis (ΔF508/ΔF508). Conclusion Our experience indicates that NDD, as the initial manifestation of CF, should be also kept in mind in differential diagnosis of the infant's AD-like changes.Item An unusual case of aneurysmal tibial nerve compression detected in ED(2013) Toncev, Slavco; Sretenovic Z.; Mitrovic, Slobodanka; Toncev, GordanaItem Plasma homocysteine concentrations in patients with Rheumatoid arthritis(2015) Vasiljevic, Dragan; Tomic Lucic, Aleksandra; Živanović, Sandra; Milosavljevic, Milica; Radovanovic, Snezana; Anđelković, Nebojša; Djuric, Dragan M.; Veselinovic, MirjanaIn this study, we investigated the concentration of serum homocysteine (Hcy) in patients with rheumatoid arthritis (RA) compared with the control group and the connection between homocysteine and parameters of inflammation and disease activity. Sixty RA patients and 20 healthy controls were included in the study, and clinical examination and investigation were performed during which disease activity was assessed. Peripheral blood samples were used for all of the assays. Levels of Hcy were 33% higher in the RA patients than in the control subjects (mean +/- SD 11.79±3.72 μmol/L versus 8.90±1.38 μmol/L; p< 0.01). A significant correlation was found between parameters of inflammation (C-reactive protein) and homocysteine in patients (r=0.322, p=0.012). Patients with high disease activity had a significantly greater increase in homocysteine (p<0.05). An increase in plasma homocysteine in RA patients is related to the parameters of inflammation and disease activity. Elevated Hcy levels occur commonly in patients with RA and may explain some of the increased cardiovascular mortality seen in RA patients.Item Budget Impact of Publicly Reimbursed Prescription Medicines in the Republic of Srpska(2015) Petrusic I.; Jakovljevic, MihajloItem Improvements in Neonatal and Childhood Medical Care – Perspective from the Balkans(2015) Veličković V.; Simovic, Aleksandra; Lazarevic G.; Lazarevic M.; Jakovljevic, MihajloItem Health Spending Follows Pace of Population Aging: Challenges Lying Ahead of the Largest Western Balkan Market(2015) Stojković M.; Milovanovic, OliveraItem Can a single lactate value predict adverse outcome in critically ill newborn?(2015) Simovic, Aleksandra; Stojkovic Andjelkovic, Andjelka; Savic, Dragana; Milovanovic, DraganOBJECTIVES: The aim of this study was to investigate the role of the lactic acidosis, as an early predictor of significant consequences and/or a fatal outcome in term neonates after a perinatal asphyxia. BACKGROUND: Severe perinatal asphyxia can generate multiple organ dysfunction and neonatal mortality. METHODS: In routine clinical practice, after an admission to the Intensive Care Unit, lactate concentration was determined in capillary blood samples during the first one to six hours after birth in 55 term newborns with the post-asphyxial hypoxic-ischemic encephalopathy. The control group consisted of 36 healthy term neonates randomly selected in the maternity ward at the Gynecology and Obstetrics Clinic. RESULTS: Significantly higher concentrations of lactate (p < 0.0005) were observed in term neonates with post asphyctic syndrome (8.63±4.43 mmol/L) if compared to the control group subjects (1.04±0.36 mmol/L). The increase in lactate level >8.7mmol/L with 80 % sensitivity and 82 % specificity indicated the development of the hypoxic-ischemic encephalopathy stage II/III, while the lactate level >9.95 mmol/L was a predictor of death, with 75 % sensitivity and 74.4 % specificity. CONCLUSION: Determination of lactate concentrations in serum of term newborns associated with risk factors for the perinatal asphyxia is a useful tool in diagnosing metabolic disorders and ischemic damage, particularly severe clinical forms.Item BRIC’s Growing Share of Global Health Spending and Their Diverging Pathways(2015) Jakovljevic, MihajloItem Growing Burden of Non-Communicable Diseases in the Emerging Health Markets: The Case of BRICS(2015) Jakovljevic, Mihajlo; Milovanovic, OliveraItem Dental Services Funding and Affordability in Serbia – Decade-Long Perspective(2015) Kanjevac, TatjanaItem Is it Possible to Predict Mortality in Preterm Neonates, Based on a Single Troponin I Value at 24 h?(2016) Simovic, Aleksandra; Stojkovic Andjelkovic, Andjelka; Dejan J.; Savic, DraganaItem Clinical trial / experimental study (consort compliant): Optimal time period to achieve the effects on synbiotic-controlled wheezing and respiratory infections in young children(2016) Stojkovic Andjelkovic, Andjelka; Simovic, Aleksandra; Bogdanović Z.; Banković, Dragić; Poskurica, MinaIntroduction Urban life is often followed by immune dysfunction and loss of immune tolerance in the youngest children. Objective The study aimed to determine optimal time efficiency of a synbiotic (5×109 Lactobacillus acidophilus Rosell-52, Bifidobacterium infantis Rosell-33, Bifidobacterium bifidum Rosell-71) in controlling respiratory infections and wheezing disease. Methods We randomly selected a group of children younger than five years, hospitalized earlier, and classified them into three groups. Results The incidence of respiratory infection before the study was once a month, while after a threemonth supplementation with the synbiotic children rarely suffered from respiratory infections, and the state was maintained after six-month and nine-month supplementations with the synbiotic. The decreased incidence of respiratory infections was followed by a falling incidence of concomitant wheezing. A significant increase in tIgA serum was observed in all groups for only three months, the increase being the highest in children with recurrent respiratory infections accompanied by wheezing. After a ninemonth administration of the synbiotic, total IgE serum was lower in all groups of patients. Conclusion The optimal duration of administration of the synbiotic containing three probiotic cultures to provide effective control of the frequency of respiratory infections was three months, and six months were required to establish control of the frequency of wheezing. This synbiotic is useful for immunomodulation in children and is well-tolerated in young children.Item Editorial: Health Care Financing and Affordability in the Emerging Global Markets(2016) Jakovljevic, Mihajlo; Groot W.; Souliotis K.Item Allogeneic fetal stem cell transplantation to child with psychomotor retardation – A case report(2016) Dajic K.; Veličković V.; Djurdjevic, Predrag; Simovic, Aleksandra; Stojkovic Andjelkovic, AndjelkaIntroduction The consequences of autologous and allogeneic stem cell transplantation (stem cells of hematopoiesis), applied in adults and children suffering from leukemia or some other malignant disease, are well-known and sufficiently recognizable in pediatric clinical practice regardless of the indication for the treatment. However, the efficacy of fetal stem cell transplantation is unrecognizable when the indications are psychomotor retardation and epilepsy. Case Outline With the exception of neurological psychiatric problems, a boy aged 9.5 years was in good general health before transplantation with allogeneic fetal stem cells. The main aim of allogeneic fetal stem cell transplantation was treatment of psychomotor retardation and epilepsy. After 13 months of treatment, he was admitted to hospital in a very serious, life-threatening condition due to sepsis and severe pleuropneumonia. The humoral immunity in the boy was adequate, unlike cellular immunity. The immune imbalance in terms of predominance of T-suppressor lymphocytes contributes to delayed and late development of sepsis and severe pleuropneumonia. The boy still shows the same severity of psychomotor retardation, dyslalia, epilepsy, strabismus and amblyopia. Conclusion Implementation of fetal stem cell therapy for unconfirmed indications abuses the therapeutic approach, harms patients, misleads parents, and brings financial harm to the healthcare system of any country, including Serbia.Item Capitation-Based Financing Hampers the Provision of Preventive Services in Primary Health Care(2016) Sandor J.; Kósa, Karolina; Papp M.; Furjes G.; Korosi L.; Jakovljevic, Mihajlo; Ádany R.Mortality caused by non-communicable diseases has been extremely high in Hungary, which can largely be attributed to not performed preventive examinations (PEs) at the level of primary health care (PHC). Both structures and financial incentives are lacking, which could support the provision of legally defined PEs. A Model Programme was launched in Hungary in 2012 to adapt the recommendations for PHC of the World Health Organization. A baseline survey was carried out to describe the occurrence of not performed PEs. A sample of 4320 adults representative for Hungary by age and gender was surveyed. Twelve PEs to be performed in PHC as specified by a governmental decree were investigated and quantified. Not performed PEs per person per year with 95% confidence intervals were computed for age, gender, and education strata. The number of not performed PEs for the entire adult population of Hungary was estimated and converted into expenses according to the official reimbursement costs of the National Health Insurance Fund. The rate of service use varied between 16.7 and 70.2%. There was no correlation between the unit price of examinations and service use (r = 0.356; p = 0.267). The rate of not performed PEs was not related to gender, but older age and lower education proved to be risk factors. The total number of not performed PEs was over 17 million in the country. Of the 31 million euros saved by not paying for PEs, the largest share was not spent on those in the lowest educational category. New preventive services offered in the reoriented PHC model program include systematic and scheduled health examination health promotion programs at community settings, risk assessment followed by individual or group care, and/or referral and chronic care. The Model Programme has created a pressure for collaborative work, consultation, and engagement at each level, from the GPs and health mediators up to the decision-making level. It channeled the population into preventive health services shown by the fact that more than 80% of the population in the intervention area has already participated in the health status assessment.Item Review of Diagnosis-Related Group-Based Financing of Hospital Care(2016) Mihailović N.; Kocic, Sanja; Jakovljevic, MihajloSince the 1990s, diagnosis-related group (DRG)-based payment systems were gradually introduced in many countries. The main design characteristics of a DRG-based payment system are an exhaustive patient case classification system (ie, the system of diagnosis-related groupings) and the payment formula, which is based on the base rate multiplied by a relative cost weight specific for each DRG. Cases within the same DRG code group are expected to undergo similar clinical evolution. Consecutively, they should incur the costs of diagnostics and treatment within a predefined scale. Such predictability was proven in a number of cost-of-illness studies conducted on major prosperity diseases alongside clinical trials on efficiency. This was the case with risky pregnancies, chronic obstructive pulmonary disease, diabetes, depression, alcohol addiction, hepatitis, and cancer. This article presents experience of introduced DRG-based payments in countries of western and eastern Europe, Scandinavia, United States, Canada, and Australia. This article presents the results of few selected reviews and systematic reviews of the following evidence: published reports on health system reforms by World Health Organization, World Bank, Organization for Economic Co-operation and Development, Canadian Institute for Health Information, Canadian Health Services Research Foundation, and Centre for Health Economics University of York. Diverse payment systems have different strengths and weaknesses in relation to the various objectives. The advantages of the DRG payment system are reflected in the increased efficiency and transparency and reduced average length of stay. The disadvantage of DRG is creating financial incentives toward earlier hospital discharges. Occasionally, such polices are not in full accordance with the clinical benefit priorities.Item Collodion baby - Presentation of a rare form of familial lamellar ichthyosis(2016) Stanojević M.; Stojković, Dragan; Savic, Dragana; Vuletic, Biljana; Stojkovic Andjelkovic, Andjelka; Medović, Raša; Simovic, AleksandraWe present the case of a male infant who was born at 38th gestational week and who was the product of nonconsanguineous marriage and vaginal delivery. There was no family history of skin diseases in the parents, but the older sister also had lamellar ichthyosis. The mother received regular prenatal care. Spontaneous rupture of membranes occurred approximately 2 hours prior to the delivery. Apgar scores were 7/7 at 1st and 5th minute. The baby’s weight was 3410 grams, body length was 54 cm and head circumference was 35 cm. Upon the initial physical examination, the patient was presented with a thin collodion membrane that was found over the majority of his skin surface. The skin was dry, shining with yellow-brownish membrane and cracks in the neck region and on the skin ridges. There was also a severe outer distortion of both eyes (ectropia) and lips (eclabium), and ear lobes were small and poorly modelled. Laboratory аnd biochemistry analyses were appropriate for the patient’s age. Serological diagnosis was established by increased IgG antibody titer for Rubella and Citomegalovirus. Other serologic tests were negative. With swab of the skin we were able to extract Enterococcus species, Klebsiela-Enterobacter and Pseudomonas species. Pathohistological finding of skin biopsy showed lamellar type hyperkeratosis, thickened granular layer with elongated epidermal rungs toothed type. In the upper dermis, immature hair follicles and low level perivascular lymphocytic infiltrate were observed. Cytogenetic analysis of peripheral blood lymphocytes showed a normal male karyotype.