The effect of the octenidine-based oral antiseptic on the structure of microbial communities and periodontal status in patients with fixed orthodontic treatments.

OBJECTIVE: To evaluate the effect of an octenidine (OCT)-based antiseptic on the gingival inflammation and microbial composition of subgingival dental plaque in patients with fixed orthodontic appliances. PATIENTS AND METHODS: Thirty-three orthodontic patients were randomized into 2 groups. The control group patients were given standard oral hygiene and dietary advice, while the experimental group patients used an OCT-based antiseptic together with standard oral hygiene and dietary recommendations. The periodontal status was evaluated using the following indices: the plaque index (PI), the gingival index (GI), the papilla bleeding index (PBI) and the probing pocket depth (PD). Next Generation Sequencing of the 16S rRNA amplicons was performed in order to assess the subgingival microbiome. RESULTS: The PD values obtained were significantly lower in the experimental group after one month, as well as PBI. The microbiological analysis showed a significant increase in the occurrence of the genus Prevotella in the control group, while the number of other periodontopathogens remained stable in both groups. The changes in the abundance of the bacteria not directly associated with periodontal disease were also observed. CONCLUSIONS: The use of an OCT-based antiseptic has a positive effect on the prevention of gingival inflammation. Additionally, it also prevents a likely increase in numbers of periodontopathogens of the subgingival dental plaque in the first three months of fixed orthodontic treatment.

Seroepidemiology of varicella zoster virus infection in Vojvodina, Serbia.

The present cross-sectional serosurvey constitutes the first effort to describe the varicella zoster virus (VZV) seroepidemiology in Serbia. An age-stratified serum bank of 3570 residual samples collected between 2015 and 2016 in each of the seven districts of the Vojvodina Province was tested for IgG anti-VZV antibodies with an enzyme immunoassay. Results were standardised into common units according to the European Sero-Epidemiology Network (ESEN2) methodology. Univariable and multivariable analyses were used to examine the relationships between standardised anti-VZV positivity or logarithmically transformed antibody titres and demographic features of study subjects. Seropositivity (85% overall) increased with age, in parallel with geometric mean titres. By the time of school entry, 68% of children were immune. The slower subsequent acquisition of immunity leaves epidemiologically relevant proportions of adolescents (7%), young adults (6%) and especially females of reproductive age (6%) prone to more severe forms of varicella. In the ongoing pre-vaccine era, natural infection provides a high level of collective immunity, with the highest VZV transmission in children of preschool age. The detected gaps in VZV immunity of the Serbian population support the adoption of the official recommendations for varicella immunisation of non-immune adolescents and young adults, including non-pregnant women of childbearing age.

Proton Chemical Shift Imaging Study of the Combined Antiretroviral Therapy Impact on Neurometabolic Parameters in Chronic HIV Infection.

BACKGROUND AND PURPOSE: The introduction of combination antiretroviral therapy has failed to reduce the high prevalence of mild forms of HIV-associated neurocognitive disorders. The aim of this study was to test the effect of combined antiretroviral therapy on brain metabolite ratios in chronic HIV infection by using proton chemical shift imaging. MATERIALS AND METHODS: We performed 2D chemical shift imaging in 91 subjects (31 HIV+ patients with chronic infection on combination antiretroviral therapy, 19 combination antiretroviral therapy-naïve HIV+ subjects with chronic infection, and 41 healthy controls), covering frontal and parietal subcortical white and cingulate gyrus gray matter, analyzing ratios of NAA/Cr and Cho/Cr on long-TE and mIns/Cr on short-TE MR spectroscopy. We correlated neurometabolic parameters with immunologic, clinical, data and combined antiretroviral therapy efficacy scores. RESULTS: There was a significant decrease in NAA/Cr (P < .05) in HIV-positive patients on and without combined antiretroviral therapy, compared with healthy controls in all locations. There were significant differences in Cho/Cr (P < .05) and mIns/Cr (P < .05) ratios between HIV+ patients on and without therapy, compared with healthy controls, but these differed in distribution. There were no significant differences in brain metabolite ratios between the 2 groups of chronically HIV-infected patients. The CNS penetration efficacy score showed weak positive correlations only with Cho/Cr ratios in some locations. CONCLUSIONS: The impact of combined antiretroviral therapy on the process of neuronal loss and dysfunction in chronic HIV infection appears to be suboptimal in successful peripheral suppression of viral replication. Spectroscopic imaging might be a useful tool for monitoring the effects of different combined antiretroviral therapy regimens on brain metabolite ratios.

Ethanol concentration changes in blood samples during medium-term refrigerated storage.

OBJECTIVE: Stability of blood alcohol concentration (BAC) in laboratory samples is of great importance when it is necessary to perform repeated analyses. MATERIALS AND METHODS: We have analyzed the stability of BAC in 50 samples, which were taken from apprehended drivers, kept at -18ºC, without preserving agents. Quantitative analyses were performed using headspace sampling gas chromatography (HS-GC) with flame ionizing detection (FID). Samples were analyzed immediately after collection (C1), and after 60 (C60), 120 (C120) and 180 (C180) days. A group of 50 samples, which were kept closed for 180 days at -18ºC, was utilized as a control. RESULTS: We found a significant decrease in BAC between C1 and C180 (= 0.224; SD= 0.144; t = 10.98; p<0.001), and between C1 and C60, C60 and C120, C120 and C180. There was a significant positive correlation (r=0.8) between starting concentration C1, and the value of BAC changes (ΔC). Linear regression analysis (R2=0.64) implies the degree of validity to the proposed model of ΔC change regarding initial BAC. There were significant changes in ΔC between the two groups. CONCLUSIONS: These data underline the significance of air chamber percent (CA%) and ethanol evaporation due to ventilation between liquid and gas phase as a mechanism of ethanol decay.

Treatment of Periodontal Disease with an Octenidine-based Antiseptic in HIV-positive Patients.

OBJECTIVE: To evaluate the effects of a periodontal therapy with subsequent application of an octenidine (OCT)-based antiseptic in HIV-positive patients receiving highly active antiretroviral therapy. METHODS: HIV-positive patients with a clinically diagnosed periodontal disease were randomly divided into two groups (n = 30/group). Both groups initially received a periodontal therapy. Patients in the OCT group additionally used an OCT-based mouthwash. Subgingival plaque samples and periodontal indices were analysed prior to treatment onset as well as one and 3 months post-treatment. RESULTS: Periodontal therapy has resulted in a significant decrease in the values of all periodontal indices one and 3 months following the therapy completion (P = 0.000). The effects of the two applied therapeutic protocols differed significantly in terms of the variation in the PBI (F = 4.617; P = 0.017) and the PD (F = 3.203; P = 0.044) value. In the patients in the OCT group, a more pronounced decrease in the PBI and PD was noted at 1-month follow-up as well as a greater increase in the PD value 3 months upon treatment completion. In the OCT group, no more atypical microorganisms were detectable 1 month post-treatment, while in the control group they were found in 34.5% of patients. CONCLUSIONS: The periodontal therapy bears good results in HIV-positive patients. Additional administration of OCT contributes to the significant decline in the PBI and DS values and eliminates atypical microorganisms within 1 month post-treatment. However, more favourable results were not noted in the OCT group at the 3-month assessment.

Influence of graded exercise therapy on anxiety levels and health-related quality of life in chronic fatigue syndrome.

AIM: The purpose of the present study was twofold: 1) to determine to what extent graded exercise therapy (GET) improves health-related quality of life (HRQOL) and anxiety levels in patients with chronic fatigue syndrome (CFS); and 2) to correlate scores of HRQOL and anxiety levels in CFS patients. METHODS: Anxiety and HRQOL were assessed in 26 CFS patients before and after 12 weeks of GET. Anxiety was measured using the State-Trait Anxiety Inventory questionnaire (STAI) and HRQOL using the Medical Outcomes Study Short-Form questionnaire (SF-36). RESULTS: GET significantly decreased trait anxiety (STAI-T) levels in patients with CFS. Patients' scores on SF-36 following GET showed higher levels of functioning, but only the "vitality" subscale scores showed a statistically significant difference. A negative correlation was present between all eight subscales of SF-36 and anxiety levels. The strongest negative correlation for both state and trait anxiety scores (STAI-S and STAI-T) was found with the scores on the "Limitations due to emotional problems" subscale of SF-36 (r=-0.69 and r=-0.55, respectively), while the weakest negative correlation was with the "Physical functioning" subscale scores (r=-0.30 and r=-0.31, respectively). CONCLUSION: Graded exercise therapy has a positive effect on both physical and psychological state of CFS patients. GET can decrease anxiety and improve quality of life of CFS patients. CFS patients with higher state and trait anxiety levels have lower quality of life, and vice versa.

Mid-pregnancy interleukins levels in serum and amniotic fluid as predictors of preterm delivery.

Abstract Objectives: To find out if determination of IL-4, IL-13 and IL-6 in amniotic fluid (AF) and serum in mid-pregnancy can be used as predictors of preterm delivery. Material and methods: The research has comprised 88 pregnant women at 16-24 weeks of gestation, who were subjected to early amniocentesis. Levels of interleukins were determined by ELISA tests. Pregnant women had been monitored untill termination of pregnancy and divided in two groups: 68 term and 20 preterm deliveries. Results: IL-13 was not detectable at all in serum and amniotic fluid samples. IL-4 was not detectable in serum samples of both groups of women and it was detectable only in small number (20 % - 27 %) of AF samples. There was no statistically significant difference (p=0.665) in the mean values of AF IL-4 levels between the examined groups of women. Detectability for IL-6 was very low in serum specimens, while in AF it was detectable in 100% of cases and its levels was significantly higher (p<0.001) in preterm delivery group. Conclusions: The results obtained in this study suggest that the AF mid-pregnancy levels of IL-6 higher than 132 pg/ml may indicate preterm delivery.

Science ethics education: effects of a short lecture on plagiarism on the knowledge of young medical researchers.

PURPOSE: Plagiarism is the most common form of scientific fraud. It is agreed that the best preventive measure is education of young scientists on basic principles of responsible conduct of research and writing. The purpose of this article was to contribute to the students' knowledge and adoption of the rules of scientific writing. METHODS: A 45 min lecture was delivered to 98 attendees during 3 courses on science ethics. Before and after the course the attendees fulfilled an especially designed questionnaire with 13 questions, specifically related to the definition and various types of plagiarism and self-plagiarism. RESULTS: Although considering themselves as insufficiently educated in science ethics, the majority of the attendees responded correctly to almost all questions even before the course, with percentages of correct responses to the specific question varying from 45.9-85.7%. After completion of the course, these percentages were significantly (p<0.01) higher, ranging from 66.3-98.8%. The percentage of improvement of the knowledge about plagiarism ranged from 9.18- 42.86%. The percentage of impairment ranged from 1.02- 16.33%, the latter being related to the question on correct citing unpublished materials of other people; only for this question the percentage of impairment (16.33%) was greater than the percentage of improvement (11.22%). CONCLUSION: Even a short lecture focused on plagiarism contributed to the students' awareness that there are many forms of plagiarism, and that plagiarism is a serious violation of science ethics. This result confirms the largely accepted opinion that education is the best means in preventing plagiarism.

Science ethics education part II: changes in attitude toward scientific fraud among medical researchers after a short course in science ethics.

PURPOSE: To determine the impact of the short science ethics courses on the knowledge of basic principles of responsible conduct of research (RCR), and on the attitude toward scientific fraud among young biomedical researchers. METHODS: A total of 361 attendees of the course on science ethics answered a specially designed anonymous multiple- choice questionnaire before and after a one-day course in science ethics. The educational course consisted of 10 lectures: 1) Good scientific practice - basic principles; 2) Publication ethics; 3) Scientific fraud - fabrication, falsification, plagiarism; 4) Conflict of interests; 5) Underpublishing; 6) Mentorship; 7) Authorship; 8) Coauthorship; 9) False authorship; 10) Good scientific practice - ethical codex of science. RESULTS: In comparison to their answers before the course, a significantly higher (p<0.001) number of students qualified their knowledge of science ethics as sufficient after the course was completed. That the wrongdoers deserve severe punishment for all types of scientific fraud, including false authorship, thought significantly (p<0.001) more attendees than before the course, while notably fewer attendees (p<0.001) would give or accept undeserved authorship CONCLUSION: Even a short course in science ethics had a great impact on the attendees, enlarging their knowledge of responsible conduct of research and changing their previous, somewhat opportunistic, behavior regarding the reluctance to react publicly and punish the wrongdoers.

Science ethics education part I. Perception and attitude toward scientific fraud among medical researchers.

PURPOSE: To assess the knowledge of basic principles of responsible conduct of research and attitude toward the violations of good scientific practice among graduate biomedical students. METHODS: A total of 361 subjects entered the study. The study group consisted mainly of graduate students of Medicine (85%), and other biomedical sciences (15%). Most participants were on PhD training or on postdoctoral training. A specially designed anonymous voluntary multiple-choice questionnaire was distributed to them. The questionnaire consisted of 43 questions divided in 7 parts, each aimed to assess the participants' previous knowledge and attitudes toward ethical principles of science and the main types of scientific fraud, falsification, fabrication of data, plagiarism, and false authorship. RESULTS: Although they considered themselves as insufficiently educated on science ethics, almost all participants recognized all types of scientific fraud, qualified these issues as highly unethical, and expressed strong negative attitude toward them. Despite that, only about half of the participants thought that superiors-violators of high ethical standards of science deserve severe punishment, and even fewer declared that they would whistle blow. These percentages were much greater in cases when the students had personally been plagiarized. CONCLUSION: Our participants recognized all types of scientific fraud as violation of ethical standards of science, expressed strong negative attitude against fraud, and believed that they would never commit fraud, thus indicating their own high moral sense. However, the unwillingness to whistle blow and to punish adequately the violators might be characterized as opportunistic behavior.

The impact of biomedical literature published in the province of Vojvodina on researchers in the world and in Yugoslavia.

This study uses bibliometric analysis to evaluate scientific biomedical literature published on the territory of Vojvodina and its impact on researchers in Yugoslavia and in the world. The study sample comprised 6.979 publications from the territory of Vojvodina published in the period 1986-1997. The following parameters were determined: productivity of authors and institutions where they were employed and some other bibliometric parameters. The impact of these publications on other researches was analyzed for the same period, by citation analysis of papers published in 3 most eminent medical journals in Yugoslavia (3.440 articles, 58.484 references) and in Science Citation Index. Results of the study revealed that production of biomedical literature on the territory of Vojvodina was at high level. Medical research presented in journals of Vojvodina, which are the carriers of current information and accomplishments in science, technique, and practice in biomedicine, was satisfactory. Biomedical articles published in Vojvodina showed a tendency towards increase in number of authors, whereas the greater number of publications were written by a small number of extremely productive authors and institutions. Biomedical researches in Yugoslavia usually cite only foreign literature, while domestic references are mostly self-citations or citations of older literature. The impact of publications published in Vojvodina on other researchers in Yugoslavia is evident, but it is greatest on the territory where they are published. In regard to biomedical journals from Vojvodina "Medical review" is the most cited journal in Yugoslavia and in SCI. Most of the cited references belong to a small number of authors. Thus, according to bibliometric criteria the impact of medical science and professional practice in Vojvodina on international scientific streems is negligible, as well as the impact of papers published in Vojvodina on researchers in the world. Only 0.4 works published in Vojvodina, 0.87% papers from journals published in Vojvodina and written by 0.59% authors were cited in SCI.

[Salmonella bacteremia]. / Salmonela bakteriemije.

INTRODUCTION: Non-typhi salmonellae are invasive bacteria, which can, in certain conditions, get into the blood stream, and course bacteriemia or localized infections in different organ systems. Incidence of salmonella bacteriemia varied in different studies between 5.2-13.7%. The incidence is higher in patients younger than 1 year and the elderly. Among different serotypes, the most invasive are Salmonella typhimurium, Salmonella choleraesuis and Salmonella Virchow. The aim of our study was to determine the incidence of salmonella bacteriemia among patients hospitalized at the Clinic of Infectious Diseases Novi Sad during 1991-1998, and to point to certain risk factors for salmonella bacteriemia. RESULTS: During 1991-1998, 1309 patients were hospitalized with the diagnosis of Salmonella gastroenteritis. 12 patients (0.99%) had positive blood culture. The average age of salmonella bacteriemia patients was 17 (1-54 year), but 50% of them were younger than 10. 4/12 patients (33.33%) had positive stool and blood culture, but in 8/12 (66.66%) only positive blood culture had been established. The main serotype was Salmonella enteritidis (83.33%) and after that Salmonella Virchow (16.66%). In more than 50% of patients there was at least one risk factor responsible for dissemination: sideropenic anemia (25%), cerebral palsy (8.33%) and chronic cardiac disease (8.33%). Average duration of fever was 13.16 days and diarrhea 8.83. All patients presented with hepatosplenomegaly. One patient had a localized salmonella infection (periappendicular abscess) and she had undergone successful surgery. All our patients had been under cephalosporins of the third generation for 2 weeks and they recovered completely without sequelae. CONCLUSIONS: A relatively low incidence of salmonella bacteriemia (0.99%) in our patients can be explained with small number of children younger than 1 year and patients older than 70 years of age in whom bacteriemia is most common. Positive blood culture doesn't mean obligatory positive stool culture. Routine laboratory analyses are relatively nonspecific for the diagnosis of generalized infection. Cephalosporins of the third generation are considered to be the drug of choice in treatment of salmonella bacteriemia.

[Clinico-epidemiologic characteristics of Lyme disease treated at the Infectious Disease in Novy Sad 1993-1998]. / Klinicko-epidemioloske karakteristike lajmske bolesti lecenih na Klinici za infektivne bolesti u Novom Sadu u periodu 1993-1998. godine.

INTRODUCTION: Borrelia burgdorferi, the etiological agent of Lyme disease, is transmitted by the bite of Ixodes ricinus, registered in all parts of Yugoslavia. Vectors are very active in spring and early summer and the disease has a seasonal distribution. Generally speaking, there are three defined stages of the disease, but some of them can be misdiagnosed or really absent. Serological analysis of Lyme disease is very difficult to interpret, especially in later stages, so confirmation by immunoblot assays is recommended. The aim of this study was to present some epidemiologic and clinical characteristics of Lyme disease in Vojvodina in the period from 1993-1998. Throughout this period, 1.659 persons with tick bite were registered, whereas 560 with diagnosed Lyme disease have been treated at the Clinic for Infectious Diseases in Novi Sad. RESULTS: In 511 patients (91.25%) we registered the first stage of the disease, in 42 (7.50%) the second stage and in 7 (1.25%) the third stage of the disease. The mean age of patients with erythema migranes was 38.67 years, mean incubation period was 9.37 days, and tick was removed from the skin after 2.29 days on average. Most of the identified tick bites originated from suburban areas (50.29%), they predominantly occurred in May and June (63.01%), and most of the ticks were removed improperly (57.67%). Dominant clinical manifestations of the second stage were acute meningitis (9.52%), Bannwarth's syndrome (9.52%), arthralgia and arthritis (50%), skin lesions (14.28%), cardiac disorders (11.90%) and mild liver lesions (2.38%) and generalized lymphadenopathy (2.38%). Chronic neuroborreliosis (42.85%), acrodermatitis chronica atrophicans (28.57%) and chronic arthritis were dominant clinical manifestations of the third stage. Up to 81.63% of patients with late stage of disease had a history of previous tick bite. One third of patients were asymptomatic in the first stage of the disease. Improper treatment of the first stage resulted in development of late stage disease in 57.14% of patients. CONCLUSIONS: Morbidity of Lyme disease in Vojvodina is about 1.98-9.8 cases on 100.000 inhabitants, and it belongs to regions with low incidence. Majority of bites are registered during summer months arround cities. Longer persistence of vector on the skin is a risk factor for manifested diseases. Inappropriately treated or completely untreated persons have higher risk for disseminated infection. In our country, most common manifestations of the second stage are neurological and articular manifestations as in the third stage. Leading symptoms and epidemiology aren't enough for diagnosis of Lyme disease, and more specific and sensitive serologic assays are necessary.

[Reactivation of herpes zoster infection by varicella-zoster virus]. / Reaktivacija herpes zoster infekcije varicela-zoster virusom.

HISTORY: There has been considerable interest in varicella-zoster virus in the middle of the twentieth century. Virus isolation in 1958 had made it possible to find out the complete DNA sequence of the varicella-zoster virus. Molecular identify of the causative agents of varicella and shingles had been proved. ETIOPATHOGENESIS AND HISTOPATHOLOGY: Varicella-zoster virus is a member of the Herpesviridae family. After primary infection which results in varicella, the virus becomes latent in the cerebral or posterior root ganglia. Some of these individuals develop shingles after several decades because of virus reactivation. It is caused by decline of cellular immune response. Circumstances such as old age, hard work, using of steroids or malignancies contribute to the appearance of shingles. Histopathological findings include degenerative changes of epithelial cells such as ballooning, multinucleated giant cells and eosinophilic intranuclear inclusions. EPIDEMIOLOGY: Shingles occur sporadically, mainly among the elderly who have had varicella. There is no seasonal appearance of shingles. Individuals suffering from shingles may be sometimes contagious for susceptible children because of enormous amount of virus particles in vesicle fluid. CLINICAL FEATURES: Clinically, shingles is characterized at first by pain or discomfort in involved dermatome, usually without constitutional symptoms. Local edema and erythema appear before developing of rash. Maculopapular and vesicular rash evolves into crusts. The most commonly involved ganglia are: lumbar, thoracic, sacral posterior root ganglia, then geniculate ganglion of the VIIth cranial nerve and the trigeminal ganglion. The most common complication, postherpetic neuralgia, may last for as long as two or three weeks, sometimes even one year or more. Other complications that may be seen in shingles, but more rarely, are ocular (keratitis, iridocyclitis, secondary glaucoma, loss of sight), neurological (various motor neuropathies, encephalitis, Guillain-Barre syndrome), secondary bacterial infection of vesicles. Immunocompromised patients often develop more severe disease lasting up to two weeks, skin lesions are more numerous and often with hemorrhagic base and there is a high possibility for cutaneous dissemination and visceral involvement including viral pneumonia, encephalitis and hepatitis. Chronic shingles may also be found in immunocompromised hosts, particularly in those with a diagnosis of HIV infection. In patients with HIV infection, shingles is often characterised by radicular pain and itching several days before appearance of skin lesions. Those patients may have two or more dermatomes involved and recurrences of shingles cannot be quite infrequent in those patients. But visceral involvement is rarer than in other immunocompromised patients. Shingles may occur in the second half of pregnancy and usually have a mild course. However, congenital abnormalities has been described in few cases. DIAGNOSIS: The diagnosis of shingles is usually made by history and physical examination. Exceptionally, for example in zoster sine herpete and atypical forms of shingles, virus isolation and serological tests must be used. DIFFERENTIAL DIAGNOSIS: Some other diseases may cause similar skin lesions and rash (varicella, erysipelas, impetigo, enteroviral infections, herpes simplex infections). These diseases are excluded by using detailed history taking and physical examination, laboratory findings, virus isolation and commercially available serological tests. THERAPY: The vast majority of immunocompetent persons with shingles should be treated only by symptomatic therapy. Predominantly it is directed toward reduction of fever and avoiding secondary bacterial skin infection in immunocompetent hosts. Acute neuritis and post-herpetic neuralgia require administration of various analgesics, even like amitriptyline hydrochloride and fluphenazine hydrochloride. Acyclovir therapy is limited to ophthal

[Meningoencephalitis as the only manifestation of Epstein-Barr virus infection]. / Meningoencefalitis kao jedina manifestacija infekcije Epstein-Barrovim virusom.

INTRODUCTION: Epstein-Barr virus (EBV) infection is most often manifested as infective mononucleosis, which exhibits fever, tonsillopharyngitis, lymphadenopathy and hepatospleenomegaly, and presence of leucocytosis with lymphocytosis in the complete blood count. Neurological manifestations are rarely seen during EBV infection, in less than 1% of the diseased, most often under the features of serous meningitis, encephalitis, encephalomyelitis, transversal myelitis, neuritis, polyradiculoneuritis, convulsions etc. PATIENTS AND METHODS: The aim of the study was to investigate the frequency and clinical features of neurological manifestations in EBV infected patients treated at the Clinic for Infectious Diseases. Clinical Centre Novi Sad, during 1997. Etiologic diagnosis was confirmed by establishing presence of the viral capsid antigen specific antibodies--EBV VCA, IgM and IgG class, in the blood and cerebro-spinal fluid, as well as according to the dynamics of their titre. RESULTS: Most patients (94.64%), had the classic features exhibited by fever, angina, polylymphadenopathy and hepatospleenomegaly, while 5.36% of patients had neurological symptoms, that is meningoencephalitis as the only manifestation of EBV infection. Besides antibodies in sera, EBV antibodies in the cerebro-spinal fluid had been proved in these patients. In all patients, other viral etiology of meningoencephalitis had been excluded by serologic blood examination. Bacterial findings in the cerebro-spinal fluid had been negative as well. The outcome of the illness was favourable in all patients.

[Agranulocytosis as a complication of acute infectious mononucleosis]. / Agranulocitoza kao komplikacija akutne infektivne mononukleoze.

INTRODUCTION: Acute infections mononucleosis is the most common clinical manifestation of primary Epstein-Barr virus (EBV) infection occurring during adolescence. It is a benign lymphoproliferative, usually self-limiting disease. Complications are relatively rare, but they may occur, especially hematological. Most common are autoimmune hematolytic anemia and thrombocytopenia, and they respond to corticoid therapy. Deuteration of white blood cells is rather rare, whereas mild neutropenia is a normal finding during the course of acute disease. On the other hand, agranulocytosis is extremely rate, and almost every case has been reported in the literature. Filgrastim--the recombinant human granulocyte colony-stimulating factor (G-CSF) stimulates the activation, proliferation and maturation of progenitor granulocyte cells. This drug is usually applied in treatment of iatrogenic neutropenia, during chemotherapy of malignancies and in some idiopathic and cyclic neutopenias. CASE REPORT: A female patient, 18 years of age, has been hospitalized at the Clinic of Infectious Diseases in Novi Sad on two occasions. First because of severe acute infectious mononucleosis with acute hepatitis and jaundice 10 days after onset of symptoms. Physical examination revealed severe intoxication, dehydration, icteric skin, mucosis and massive hepatosplenomegaly. The diagnosis was confirmed by ELISA IgM, EBV VCA positive and ELISA IgG EBV VCA and IgG EBVNA negative results. The patient was discharged from hospital after 24 days without complaints and with normal physical and laboratory findings. For several days she felt well, but gradually severe fatigue and malaise occurred and she became febrile again. That was the reason why she was hospitalized again, two weeks later. This time she was febrile, extremely intoxicated with general lymphadenopathy, catarrhal gingivostomatitis and massive splenomegaly. The first laboratory findings showed severe neutropenia (absolute count of granulocytes was 0.156 x 10/l, with only 12% segmented neutrophils). Mild anemia--3.05 x 10/l was also registered, while the platelet count was normal. Other biochemical analyses were normal, the Coombs' test negative, while the serological response was also normal. Bone marrow puncture was performed and normocellular bone marrow was registered, somewhere hypercellular due to hyperplasia of granulocyte progenitor cells from promyelocytes to normal maturated cells. Anemia showed megaloblastoid proliferation, while megakaryocytes were normal. High doses of corticosteroids were applied (dexamethasone 160 mg daily) and filgrastim 5 micrograms every other day. From the very beginning of therapy the patient felt better, whereas granulocytes responded with elevation as soon as 48 hours after initiation of therapy. On the sixth day the treatment was stopped because the level of granulocytes was normal and the patient has completely recovered. She was discharged from hospital 4 weeks later with mild meteorism, but normal physical and laboratory findings and mild splenomegaly registered only by ultrasonography. DISCUSSION: During the last 10 years only several cases of severe leukopenia with acute infectious mononucleosis had been reported in literature. In all cases it was associated with some other hematological complications and it occurred in young adults without previously registered immunodeficiency. We have no knowledge about application of filgrastim in treatment of EBV-induced agranulocytosis, but the International Association for Studying Agranulocytosis and Aplastic Anemia reported that in 4% of patients Epstein-Barr virus can cause agranulocytosis even a year after the occurrence of acute disease.

[Primary infection with varicella-zoster virus in risk groups]. / Primoinfekcija virusom varicele zoster kod rizicnih grupa.

INTRODUCTION: Chickenpox represents the primary form of Varicella-zoster virus (VZV) infection and appears most commonly in preschool and school children. The clinical course of chickenpox in immunocompetent children is mainly mild and complications are rare (1-5). Adults and immunocompromised patients are considered to be risk groups for development of serious and even life-threatening complications. The most frequent bacterial complications include secondary bacterial skin infections, angina, sinusitis, otitis and bronchopneumonia. Central nervous system complications, visceral dissemination, pneumonitis and myocarditis are the major viral complications (6,7). Acyclovir is approved for treatment of chickenpox in risk groups to reduce the frequency of viral complications and to treat those ones which have already appeared (7,8). The treatment of bacterial complications is based on the examination results of the bacterial sensitivity to antibiotics. MATERIAL AND METHODS: In our study patients with the diagnosis of chickenpox based on the history of disease, clinical features and clinical course and data on intimate contact with individuals suffering from chickenpox, were clinically followed-up. Sedimentation rate, blood count and urine samples were analyzed. A unique questionnaire was designed to follow-up the following data: sex, age, course of the disease, occurrence of complications in immunocompetent patients and those belonging to risk groups and effects of acyclovir therapy. RESULTS: During a three-year period 48 patients with chickenpox treated at the Clinic of Infectious and Dermatovenereology Diseases have been observed. 64.6% of them were males and 35.4% were females. 29.2% were infants under 1 year of age, 29.2% were 2-13 years of age and 41.6% were 14-50 years of age. According to the clinical course, patients were divided into two groups: the first one included patients who developed complications of chickenpox (54.1%), the second one consisted of those without complications (45.1%). 72.7% of all complications occurred in patients belonging to risk group (14-50 years of age). Among viral complications in risk groups the most common were pneumonia (44.4%) and haemorrhagic rash (44.4%), only one patient (11.1%) developed a mild, viral meningitis. Bacterial complications were also present in risk group as secondary bacterial skin infections (71.4%) and otitis media (28.6%). Viral complications were treated successfully by 750 mg intravenous acyclovir given 3 times a day, or by 800 mg oral acyclovir given 5 times a day during 7-10 days. Adequate antibiotics were used in the treatment of bacterial complications. A case of chickenpox associated with the meningitis caused by Haemophilus influenzae was also reviewed. DISCUSSION: In this study the majority of observed patients had a mild, clinical form of chickenpox that is in accordance with the other available clinical data (1-4). Complications developed more frequently in the adults and usually were of viral etiology. All patients were on time treated with acyclovir and visceral dissemination did not occur in any of them. Complications had a favourable evolution and VZV meningitis was healed without sequelae. Many authors have written about successful use of acyclovir in the treatment of chickenpox. However, acyclovir is not recommended to immunocompetent persons without chickenpox viral complications who do not belong to risk groups (1,3,4,9-11). CONCLUSION: Our findings lead to the conclusion that chickenpox in adults may have an uncertain outcome because of a more severe clinical course and susceptibility to complications. In our study application of acyclovir in that age group provided good results as for prevention and treatment of complications of chickenpox if already manifested.

[Genital herpes with special emphasis on perinatal herpes simplex virus infection]. / Genitalni herpes s posebnim osvrtom na perinatalnu infekciju virusom herpes simpleksa.

INTRODUCTION: The incidence of genital herpes is increasing worldwide and at present herpes simplex virus type 2 is the most common cause of genital ulceration all over the world. CLASSIFICATION: The International Herpes Management Forum (IHMF) was established in 1993, suggesting a new classification of genital herpes: primary genital herpes, non-primary genital herpes, recurrent genital herpes, first episode genital herpes, atypical genital herpes and asymptomatic HSV (herpes simplex virus) infection. DIAGNOSIS: Clinical diagnosis of genital herpes should be confirmed by laboratory techniques, whereas a positive HSV culture is the best test for confirming the clinical diagnosis. Serological testing, including Western blot assay, is not the method of choice for diagnosis genital herpes. THERAPY: Management of patients with genital herpes must include various antiviral drugs (acyclovir, valacyclovir, famiclovir), but also must take into consideration the patients' clinical and emotional issues. Patients with few recurrences are best managed with episodic antiviral therapy, but those with more frequent recurrences may find a long term suppressive therapy more beneficial. Herpes simplex virus is acquired during labor in about 90% of neonatal herpes virus cases with direct contact with infected maternal genital secretions, in 5% of cases in utero (ascending infection or transplacentary) and in another 5% of cases HSV is acquired post partum. Herpes simplex virus infection includes skin infection, eye and mouth manifestations, CNS diseases and disseminated disease with multiorgan involvement. CONCLUSION: In order to reduce the risk of HSV transmission to the infant IHMF has suggested management of pregnant women with primary genital herpes: delivery by Caesarean section between 34th week and term. Acyclovir treatment may reduce the viral load at delivery, but before this can generally be recommended, more data are still required.

[Herpes zoster--treatment with acyclovir]. / Herpes zoster--lecenje aciklovirom.

We investigated the effect of acyclovir to the evolution of cutaneous changes and acute herpetic neuralgia at the time of herpes zoster infection. The examined group of 47 patients predominantly consisted of women in older ages, with anamnestic data usually referring to the chronic disease or stress as a provoking factor. In case of 19 patients the therapy was initiated in the phase of maculopapular changes, in 24 patients it was in the phase of vesicular changes and in 4 patients in the phase of encrustation. The evolution of cutaneous changes was accelerated under the acyclovir therapy regardless of the phase in which it was initiated. The intensity and duration of acute herpetic neuralgia directly depended on the time of therapy initiation. The patients who were given the therapy in time (not later than 6 days after the disease onset) reported the pain of lower intensity which completely ceased at the time of hospital discharge.

[Viruses and malignant diseases]. / Virusi i maligna oboljenja.

Although we live in the age of fast scientific progress, what causes malignant diseases in humans is still unknown. The idea of viral etiology of malignant diseases is 80 years old, but during the last years this connection has been undoubtedly proved in some viral infections. There are numerous diseases of viral etiology possibly connected with malignomas in humans. However, literature data point to the fact that this connection has not been proved for certain. Fast development of antiviral therapy and reliable proofs about oncogenic effects of certain viruses should open possibilities for adequate therapeutic approaches to diseases most often lethal.