Off label use of human approved drugs in treatment of dogs in the Republic of Serbia.

Since drug companies are driven by the need to produce profit they are unwilling to make large investments in the development of new drugs if there is no market large enough to justify such investment. For this reason, veterinarians face a major obstacle - the veterinary drug market is not very profitable, which sometimes leads to not having a licensed drug available for treatment in veterinary practice. In this case, the cascade procedure allows veterinarians to, under certain circumstances, prescribe human approved drugs. The aim of our study was to analyze the pattern of human approved drugs prescription for 150 medical records of dogs participating in the survey. The results show that antimicrobial agents were the most commonly prescribed drugs for animals (50%) of all human approved drugs, and beta-lactams (38.6%) were the most widely used antibiotic classes. The most common general conditions for therapeutic use of antimicrobials in this study were digestive, skin and respiratory disorders. Our study shows that the frequency of bacterial culture, susceptibility testing and cytology was very low. Even though the off-label use of human approved drugs in animal practice is regulated by law, the results of this study indicate the need for more specific strategies and guidelines for such use. This may represent a potential for improvement by raising veterinarians' awareness toward more prudent use of human drugs.

Biological variations of hematologic and biochemical parameters in cows during early lactation.

The aim of the study was to determine biologic variations of the main parameters in cows in early lactation and to compare intra-individual variations of parameters in cows and other species. 50 cows were included in the experiment. Blood samples were taken at the moment of calving, then on 1st, 7th, 14th and 28th day after calving. CVi had the following values: 1.9-5% for MCV, MCH, MCHC, GLU, TProt, ALB, UREA, Ca, P and Mg; 5.1-10% for RBC, Hgb, Hct, WBC, NEU, LYM, BHB, ALT, CHOL, TGC and >10% for PLT, NEFA, TBil, AST and GGT. For RBC, Hgb, Hct, MCV, MCH subject-based reference values or the reference change value should be used. For all other parameters except AST, population-based reference intervals should be used with caution. For LYM, NEU, PLT, GLU, TProt, ALB, CHOL and TGC index of individuality was close to 0.6 which means that subject-based reference values can be much more adequate to use then population-based reference intervals. For AST population-based intervals should be used. There is little effect of parity (increase CVi with parity) and no effect of milk production. CVi values obtained in cows in early lactation are specific because they deviate from the CVi values of other animal species and human. Calculated RCVs varied from 5.5% for MCHC to 41% for AST. High individuality index for many metabolic parameters opens possibility for development of model for longitudinal monitoring of metabolic status of individual animals during lactation. That requires further research.

Effect of postpartum administration of ketoprofen on proinflammatory cytokine concentration and their correlation with lipogenesis and ketogenesis in Holstein dairy cows.

Early lactation period in dairy cows could be harmful to their health since it is challenging and demanding. Proinflammatory cytokine concentrations are increased in the early phase of the inflammatory response and during the early lactation period in cows. The aim of this study was to determine if ketoprofen treatment in the first days following parturition would decrease proinflammatory cytokine concentration and their correlation between lipid mobilization, ketogenesis and metabolic parameters in cows. The study was conducted on 30 cows divided into two groups of 15 cows each. The experimental group was treated with 3 mg × kg.bw.-1 ketoprofen for three consecutive days after parturition. The blood samples were collected on the first day of treatment and in the first and second week postpartum and they were analyzed for biochemical parameters such as non-esterified fatty acids (NEFA), beta-hydroxybutyrate (BHBA), glucose, cholesterol and total bilirubine and inflammatory parameters such as tumour necrosis factor-α (TNF-α), interleukin-1α (IL-1α) and interferon-γ (IFN-γ). The results suggested that ketoprofen- treated cows had a significantly lower concentration of TNF-α, IL-1α, IFN-γ, NEFA and BHBA in the first and second postpartum week compared to the control group. Ketoprofen administration increased glucose levels (the first week, p⟨0.05), increased cholesterol levels (the second week, p⟨0.01) and decreased serum total bilirubin levels (second week, p⟨0.01) compared to the control group of cows. A positive correlation was found between TNF-α and NEFA and total bilirubin, significantly more expressed in the control than in experimental group of cows (p⟨0.01) and it was also found between IL-1α and NEFA (p⟨0.01). A negative correlation was found between TNF-α and glucose and cholesterol, significantly more expressed in the control than in experimental group of cows (p⟨0.01). A positive correlation was also found between IL-1α and glucose (p⟨0.01). Ketoprofen given parenterally to Holstein cows immediately after calving could reduce inflammation and decrease the relation between inflammatory response and lipogenesis and ketogenesis in postpartum cows.

Association of metabolic and inflammatory markers with milk yield in postpartum dairy cows treated with ketoprofen.

Inflammation together with lipolysis and ketogenesis in early lactation can cause low productivity and may be harmful to the cow health. The objective of the study was to determine if ketoprofen treatment in the first days following parturition would positively affect the milk production and whether it was associated with the metabolic and inflammatory response. The study was conducted on 30 cows divided into two groups of 15 cows each. The experimental group was treated with 3 mg × kg. bw. -1 ketoprofen for three consecutive days after parturition. The blood samples were collected on the first day of treatment and in the first and second week postpartum and they were analyzed for non-esterified fatty acids (NEFA), beta-hydroxybutyrate (BHB), tumour necrosis factor-a(TNF-a) and haptoglobin. The results suggested that ketoprofen-treated cows with a higher milk production had a significantly lower concentration of NEFA, BHB, TNF-a and haptoglobin in the first and second week postpartum. No differences were found in the control group in metabolic status regardless of the achieved level of milk production. Ketoprofen administration in postpartum cows can enhance the milk yield. The higher milk yield in the experimental group might be associated with a lower degree of lipolysis, ketogenesis and reduced inflammatory response in the first two weeks postpartum.

Beta-hydroxybutyrate in milk as screening test for subclinical ketosis in dairy cows.

Ketosis is a very frequent metabolic disease in dairy cows, resulting in lower milk production, impaired fertility and increased frequency of other diseases. The course of the disease is often subclinical, so early detection is very important. The aim of the study was to investigate the relation between the concentration of beta-hydroxybutyrate in blood and milk and to determine the cut-off value in milk for detection of subclinical ketosis. The study included 94 cows, which were in the first third of lactation. Beta-hydroxybutyrate (BHB) concentrations were measured in blood and milk serum using a biochemical analyser. The average concentration of BHB in the blood serum samples was 1.14 mmol/L while in the milk it was about ten times lower at 0.117 mmol/L. A statistically significant positive correlation between the concentration of BHB in blood and milk (r=0.705, p<0.001) was found. In cows with BHB in blood below 2.0 mmol/L a stronger correlation between blood and milk BHB was established (r=0.658, p<0.001) than in cows with blood BHB above 2.0 mmol/L (r=-0.292, p=0.206). Therefore, BHB in milk is a very suitable indicator in the diagnosis of subclinical ketosis as there is a good correlation between BHB in the blood and milk of cows with subclinical ketosis. The cut-off concentration of BHB in milk set at ≥0.080 mmol/L (AUC=0.91±0.03; p<0.001) is a significant indicator for subclinical ketosis in dairy cows. The sensitivity of the test was 94% and specificity 74%. Beta-hydroxybutyrate in milk is a good indicator of subclinical ketosis in dairy cows and can be measured accurately with a biochemical analyser.

Demographic characteristics of patients with laryngeal cancer and their socioeconomic status.

PURPOSE: To define demographic characteristics of patients with laryngeal cancer in central Serbia, and to investigate possible relationships between their socioeconomical status and the appearance of laryngeal cancer. METHODS: 100 patients (cases) with histologically verified laryngeal cancer were investigated. The control group consisted of 100 patients (controls) having no cancer. A questionnaire was filled in by both cases and controls and comparison between the groups was carried out by individual matching of demographic characteristics and socioeconomical status. RESULTS: 91% of the cases and controls were male (mean age 60 years). Most of the cases had lower educational level and poorer socioeconomical status compared to controls, whilst no difference was found between the 2 groups concerning their living in urban or rural environment. CONCLUSION: It was not possible to correlate urban environment (air pollution) as risk factor. People of lower educational level and poor socioeconomical status had increased risk of getting laryngeal cancer.

[Orbital complications of rhinosinusitis].

INTRODUCTION: Orbital complications were observed in 53 patients (1.35%, n=53/3912 of all treated patients; 11.04%, n= 53/480 of hospitalized patients). Complications in the orbit can occur in 3-5% of adults with the inflammatory condition of sinuses, while the percentage in children ranges from 0.5-8%. OBJECTIVE: The objective of our work was to determine the frequency of the occurence of orbital complications of the rhinosinal inflammatory origin in a group of adults and children. METHOD: The retrospective analysis of patients treated of rhinosinusitis in the period 1992 to 2007, in the Clinical Center in Kragujevac. RESULTS: In the period of 15 years, a total number of 3912 patients were treated for inflamatory conditions of paranasal cavities. Orbital complications were found in 53 patients (1.35%, n=53/3912 of all treated patients). The number of children showing orbital complications caused by rhinosinusitis was 0.79%, while the number of adults was 1,88%. Acute rhinosinusitis in children was manifested as orbital complication in 14 patients (n=14/15, 93.33%), while 33 adults (n=33/38, 86.84%) had the exarcerbation of the chronic rhinosinusitis at the time of diagnosis of orbital complication. 80% of examined children had the maxillary and ethmoid sinus infected (n=12/15), while the adults most often had polysinusitis (n=22/38, 57.89%). In the juvenile age the most frequent complication was the cellulitis of the orbite (n=7/15, 46.66%), while in the adults it was the subperiostal absces (n=14/38, 36.84%). The adults were mostly treated surgically (n=31/38, 81.58%), while the children were treated by using conservative treatment (n=13/15, 86.67%). There were no cases of mortality. CONCLUSION: The prevention of complications is based on the adequate and timely treatment of acute sinusitis in children, as well as the curative treatment of chronical processes in adults.

[A-mode ultrasonography and roentgenography in diagnosing chronic nonpolypoid maxillary rhinosinusitis].

OBJECTIVES: The aim is to demonstrate diagnostic alternatives for A-mode ultrasonography in examining chronic nonpolypoid rhinosinusitis, its implementation, as well as its advantages and disadvantages in regards to roentgenography. METHOD: The prospective research conducted included patients with chronic nonpolypoid rhinosinusitis, at 79 maxillary sinuses. Chronic diseases are classified into two separate categories depending on the clinical entity. Comparative analysis of the ultrasound and roentgenography findings was conducted for both, while the status of the maxillary sinuses obtained by sunusoscopy provided the gold standard. RESULTS: Generally speaking, the reliability of the A-mode ultrasonography in diagnosing chronic nonpolypoid diseases in maxillary sinuses was of a somewhat greater degree in comparison to roentgenography, amounting to 72.15% in relation to 60.76%. There is no statistically significant divergence in relation to the foregoing methods. A-mode ultrasonography is more helpful in the process of identifying liquid contents, and can be less utilized in identifying hypertrophic mucous membrane. CONCLUSION: Ultrasonography is efficient, economical and quite simple for the implementation. Its chief advantage is to be perceived in the fact that both the patient and the examiner avoid being exposed to ionized radiation. Ultrasonography and roentgenography suggest lesser degree of utility and represent a triage method in detecting chronic nonpolypoid pathological conditions.

[The HLA antigen system in married couples with recurrent spontaneous abortions]. / Ispitivanje antigena HLA sistema u bracnih parova sa rekurentnim spontanim abortusima.

INTRODUCTION: Investigations of factors responsible for the disturbance of fetomaternal tolerance during pathological pregnancies and causes of recurrent spontaneous abortions are pointing that HLA antigens play a key role in their development. Rejection of semiallogeneic allograft in this pregnancy disorder is a consequence of interaction between genetic and immunologic phenomena. MATERIAL AND METHODS: This article reports results of an investigation of human lymphocyte antigens in 130 couples with recurrent spontaneous abortions and in control group of 57 healthy couples. In both investigated groups the first class of human lymphocyte antigens was detected using microlymphocytotoxicity test by Terasaki. The phenotypic frequencies in the group with recurrent spontaneous abortions were compared with the corresponding results in the control group. We investigated the relative risk for development of this disorder and statistically significant difference of human lympocyte antigen frequencies between both investigated groups. RESULTS: The results of investigation showed that in the group of couples with recurrent spontaneous abortions the relative risk is hihger than 1 for the following human lymphocyte antigens: A2 = (1.53), A9 = (1.149), A10 = (1.07), A29 = (1.70), B18 = (2.24), B40 = (3.31). A significant difference in human lymphocyte antigen frequencies was established for HLA A2, HLA B18 and HLA B40, in comparison with the results of control group. Couples with recurrent spontaneous abortions had a statistically significantly higher rate of identical human lymphocyte antigens among spouses in comparison with the control group, at the level of significance p < 0.05 = 6.32. CONCLUSION: The results of this investigation showed that human lymphocyte antigens play an etiopathogenic role in development of recurrent spontaneous abortions and that some of these antigens are increasing susceptibility to pregnancy disorders.

[Association between HLA antigens and leukemia in the population of Vojvodina]. / Ispitivanje asocijacije HLA antigena i leukemija u populaciji Vojvodine.

INTRODUCTION: One of the most fascinating areas of research within the field of histocompatibility at present time concerns an observation that a major human histocompatibility system, HLA, is deeply involved in development of a great number of diseases. MATERIALS AND METHODS: HLA class I antigens were investigated in 225 cases with various kinds of leukemia: 112 patients with acute myeloblastic leukemia (AML), 31 with acute lymphoblastic leukemia (ALL), 44 with chronic myelocytic leukemia (CML) and 38 with chronic lymphocytic leukemia (CLL). Applying method of microlymphocytotoxicity, 13, 19 and 8 antisera were used for A, B and C loci respectively. Control group comprised 300 unrelated persons, whose phenotypic frequencies were used to calculate the relative risk (RR), while for values of RR greater than 1, we calculated etiologic fraction (EF), and for negative RR values we calculated preventive fraction (PF). RESULTS: Results of investigation showed that RR in AML was: for A2 = 1.144, for A3 = 1.038, for A29 = 1.814, for A34 = 2.69, for B7 = 1.06, for B14 = 1.74, for B17 = 1.65 and for B21 = 2.49 and B35 = 1.77 with value of chi 2 test of 4.62 and 4.63; that RR in ALL was: for A1 = 1.61, for A2 = 1.1, for A10 = 1.23, for A11 = 1.57, for A30 = 1.4, for A32 = 2.2, for B7 = 2.81 with value of chi 2 test 4.39; that RR in CML was: for A2 = 1.21, for A32 = 1.89, for B7 = 1.52, for B12 = 1.2 and for B15 = 3.28 with value of chi 2 test of 5.89; and that RR in CLL was: for A1 = 1.35 with value of chi 2 test of 3.973, RR for A2 = 1.02, for A28 = 1.97, for A32 = 1.25, for B5 = 1.44, for B8 = 1.27, for B13 = 1.91 without statistically significant differences of frequencies except for A1. Investigation of differences between haplotype frequencies among controls and patients showed statistically significant difference of A10 B40 haplotype in CML with RR value 7.24, while there were no statistically significant differences between controls and other leukemias. DISCUSSION: Our results of investigation showed statistically significant differences between HLA frequencies in the control group and investigated diseases, and that the relative risk is under 1, and values of chi 2 test under borderline values for B21 and B35 in AML, for B7 in ALL, for B15 in CML and for A1 in CLL. CONCLUSION: Results of this investigation point to an association between HLA system and leukemias. This association is of great importance because it provides a new tool for investigation of genetics and etiology of abovementioned diseases.

[Distribution of HLA class II antigens and allele linkage disequilibrium in the population of Vojvodina]. / Distribucija HLA antigena II klase i neravnoteza vezivanja alela u populaciji Vojvodine.

INTRODUCTION: Polymorphism of human leucocyte antigens (HLA) is important in transplantation medicine, anthropological studies and paternity testing. MATERIAL AND METHODS: We investigated polymorphisms of HLA class II in population of Vojvodina by means of serologic typing using microlymphocitotoxicity test. We calculated the HLA-DR and HLA-DQ gene frequencies in 174 subjects. Haplotype frequencies, coefficient of linkage disequilibrium (delta values) and their statistical significant levels, were analyzed on the basis of these data. RESULTS: The most frequent HLA-DR and HLA-DQ alleles were: DR5(11) (gene frequency 0.138), DR4 (gene frequency 0.083), DR1 (gene frequency 0.077), DQ1 (gene frequency 0.388), DQ3 (gene frequency 0.197), and DQ2 (gene frequency 0.09). The highest positive values of coefficient of linkage disequilibrium (delta) were calculated for the following haplotypes: DR1DQ1 (delta value 0.07308708), DR2DQ1 (delta value 0.059846528), DR3DQ2 (delta value 0.06193263), DR2(15)DQ1 (delta value 0.039186022), DR5(11)DQ3(7) (delta value 0.04969439), DR7DQ2 (delta value 0.057985517). Significant differences between observed vs. expected haplotype frequencies were also considered for these haplotypes. CONCLUSION: This study indicates distinctiveness and specificity of the population of Vojvodina and highlights the importance of determining HLA frequencies in endogamic groups of Serbia.

[Implementation of a quality control system in transfusion practice]. / Implementacija sistema kontrole kvaliteta u transfuzioloskoj praksi.

Quality assurance and improving systems, standardization of all transfusion procedures as well as quality control and standardization of prepared blood products are necessary elements for work of transfusion centers in the future. Requirements for blood and/or blood products for therapy are: safety, adequate concentration of all active components needed, and treatment efficacy. To satisfy these requirements, we decided to adjust the work process of transfusion service to requirements of ISO 9001 standard series. To achieve this aim, quality control system documentation is created. Creation of quality control system documentation is one of the most difficult and most comprehensive parts the quality control system implementation process. The quality policy is adopted, whereas the basic procedures for blood products quality control, which are the subject of this paper, are created.

[Complications in the use of blood transfusions--alloimmunization in polytransfused patients]. / Komplikacija primanja transfuzija krvi--aloimunizacija politransfundovanih bolesnika.

INTRODUCTION: The objective of this paper was to examine the frequency of red blood cell (RBC) alloantibodies in polytransfused hematologic patients. MATERIAL AND METHODS: Blood samples of 2669 polytransfused hematologic patients were examined on clinical significant alloantibodies using antibody screening and identification according to Standards of AABB Technical Manual (1). Available medical charts were reviewed for sex, age and medical history and total number of given transfusions. RESULTS: During a three year period blood samples of 2669 polytransfused hematologic patients were examined for RBC alloantibodies. Alloantibodies were detected in 48 cases with the incidence of 1.79%. 36 patients (1.35%) developed single antibody while in 12 patients (0.45%) multiple antibodies were detected. Antibodies were registered more frequently in females than in males (37:17). In patients with single antibody next specificity was detected: anti-D (38.89%), anti-K (22.22%), antibodies to antigens MNSs system (22.22%), while anti-Le, anti-Fy and anti-P specificity was detected in 13.89%. Patients with multiple antibodies had specificity to Rhesus, Kell, Duffy, MNSs, Lewis and P blood group systems. All patients received more than 10 RBC transfusions. CONCLUSION: The incidence of alloimmunization was 1.79%. Sensibilization occurred more frequently in females than in males. Usually, the discovered alloantibodies were clinically significant and made problems in pretransfusion testings and required special efforts in blood selection for transfusion. For patients with the risk of frequent transfusions we suggest to include blood transfusion charts with complete phenotyping against antigens in Rhesus, Kell, Kidd and MNSs blood group systems and the data of all received transfusions.

[Transfusion aspects of viral hepatitis C]. / Transfuzioloski aspekti virusnog hepatitisa C.

The investigation comprised 83 patients with acute non-A, non-B hepatitis who were treated at the Clinic of Infectious and Dermatovenerology Diseases in Novi Sad in the period 1986-1991. They were receiving blood transfusions and/or blood products from blood donors who had not been previously tested for presence of hepatitis C virus (HCV). In order to establish diagnosis anti-HCV ELISA screening tests from various producers were used. Out of 83 blood screening assays 17 patients (20.48%) were found to be anti-HCV seropositive. Out of these 17 seropositive patients 3 patients were intravenous drug-addicts (IVDA), while 14 patients (16.68%) previously received blood transfusions, whereas out of these 7 patients underwent open heart surgery. Only 2 blood donors, out of 48 whose blood was used for therapeutical purposes, were found to have anti-HCV antibodies after blood screening assays. The blood with detected anti-HCV antibodies caused acute post transfusion hepatitis C in 6 blood recipients. The obtained results show that comprehensive and thorough blood screening assays should be performed in all blood donors in order to prevent incidence of post transfusion C hepatitis. The Blood Transfusion Center in Novi Sad introduced compulsory viral screening assays for all blood donors on November 15, 1994, and since then 15019 blood donors have been tested. Only 38 (0.25%) were found to be anti-HCV seropositive, and were excluded from further blood donation and are under constant control. Now it is impossible to transmit HCV to patients who receive blood transfusion and/or blood products, and at the same time anti-HCV seropositive donors are prevented to develop chronic hepatitis and adverse complications due to HCV presence.