Influenza vaccination in autoimmune rheumatic disease patients.

Patients suffering from autoimmune rheumatic diseases have significantly higher risk of developing various infections compared to the healthy population. Our study included patients suffering from systemic lupus erythematosus (n = 30), rheumatoid arthritis (n = 37) or Sjögren's syndrome (n = 32), with stable underlying diseases status. In November 2010, 47 patients, including 35 subjects vaccinated annually during 2006-2010, received immunization against influenza with trivalent inactivated split vaccine, whereas 52 patients did not accept proposed vaccination in that period. The presence of viral (primarily influenza) and bacterial infections, parameters of disease activity (from the date of vaccination until April 2011), and titers of antibodies against A H1N1 were then monitored in vaccinated and unvaccinated patients. We have identified the importance of predisposing factors for influenza occurrence (i.e. previous respiratory infections and vaccinations in last five years, age, sex, type of disease and duration, medications, smoking) in those groups of patients. The incidence of influenza or bacterial complications (bronchitis) among vaccinated patients was significantly lower, compared to the non-vaccinated group. Importantly, there was no case of exacerbation of the underlying disease. The last vaccination in 2010 reduced the risk of influenza by 87%, but previous bacterial infections (bronchitis and pneumonia) increased influenza risk significantly. In the present study, we have shown the efficiency, sufficient immunogenicity and safety of modern influenza vaccine application in patients suffering from systemic lupus erythematosus, rheumatoid arthritis or Sjögren's syndrome.

[Therapeutic approach to actinomycosis--experience gained at the department of infectious and tropical diseases].

INTRODUCTION: Actinomycosis is a chronic infectious disease caused by anaerobic, gram-positive microorganisms from the order of Actinomyce or Propionobacterium. The disease manifests iself mostly in cervicofacial form and less frequently in thoracic and abdominal form. The study was aimed at reviewing clinical manifestations and therapeutic approaches in treatment of patients with Actinomycosis. MATERIAL AND METHODS: The study sample consisted of four patients with different clinical manifestations of Actinomycosis, who had been treated at the Institute for Infectious and Tropical Diseases in Belgrade in 2002, 2003, 2006 and 2008. RESULTS: Four patients with Actinomycosis were treated during the above mentioned periods of time. One patient had kidney Actinomycosis, which developed into generalized Actinomycosis. Two patients had the most common cervical form, while the forth one had abdominal form; all patients received Penicillin G followed by Ampicillin, during the period of four weeks to up to a year. CONCLUSION: Actinomycosis is a rare disease, which imposes great diagnostic dilemmas. The treatment of this disease requires long term use of antibiotics.

Characteristics of patients dying from acute viral hepatitis in Serbia.

BACKGROUND/AIMS: Acute viral hepatitis is complicated rarely with severe liver failure due to many factors associated with the etiology, patient age, and time of development of hepatic encephalopathy, etc. The aim of this study was to identify some of the clinical and laboratory features associated with a fatal outcome in patients dying from acute viral hepatitis in Serbia. METHODS: Clinical and laboratory data from 47 patients hospitalized from January 1989 December 2006 were reviewed retrospectively. Serological tests for hepatitis A, B, C, D, and E viruses, herpes simplex viruses, cytomegalovirus, and Epstein-Barr virus were done. Histological features were assessed from 35 liver tissues. The electronic base, SPSS for Windows (version 11.0), was used for statistical analysis. RESULTS: The majority of the patients had alanine aminotransferase (ALT) >20x the normal value, serum bilirubin >300 µmol/L, prothrombin time >25 seconds (s), and white blood cell count >12 x 10(9)/L. Regression analysis revealed activity of alanine aminotransferase >20x the normal value to be associated with fulminant (p=0.015) and serum bilirubin concentration with subfulminant hepatitis (p=0.008). Hepatitis B virus was the most commonly detected virus (70%). Massive hepatocyte necrosis vs. sub-massive with bridging necrosis were found to be independent of clinical presentation. CONCLUSIONS: Hepatitis B virus infection, severe impairment of liver function tests, and confluent hepatocyte necrosis and infection characterize patients dying from acute viral hepatitis in Serbia. High activity of alanine aminotransferase reflects rapid and extensive acute viral liver injury, while deep jaundice is more common in a protracted course of the disease.

Expression of Bcl-2 and Bax proteins in thyroid glands of rats in experimental thyroiditis.

In the recent years, iodine was associated to the development of apoptosis in thyroid diseases. The aim of the present study is to determine the expression of pro-apoptotic and anti-apoptotic proteins, Bax and Bcl-2, in a Wistar rat experimental model of thyroiditis induced by administration of different doses of potassium iodide. Immunohistochemical staining was done with chromogen diaminobenzidine on avidin-biotin peroxidase using the Animal Research Kit (ARK), stained with antibodies to Bcl-2 and Bax proteins. The intensity and distribution of positive staining were evaluated by light microscopy on a scale of 0 to 4. Bax protein was expressed in the area of regenerating follicular cells in high percent in potassium iodide treated rats, but was not expressed in thyrocytes from control rats. Bcl-2 expression was constantly observed in thyrocytes of the control group and in the mantle-zone of lymphoid follicular infiltrates. Our results show that Bax expression is significantly higher in the Wistar rat experimental model of thyroiditis than in the control group. These data suggest that the increased expression of Bax may contribute to the role of apoptosis in the pathogenesis of experimental thyroiditis.

[Chlamydia trachomatis and urogenital mycoplasms in nonconococcal urethritis in men].

INTRODUCTION: Nongonococcal urethritis is the most common sexually transmitted infection in men, with vast majority of the etiological agents such as Chlamydia trachomatis, followed by urogenital mycoplasmas. The aim of this study was to determine the prevalence of Chlamydia trachomatis, Ureaplasma urealyticum and Mycoplasma hominis in nongonococcal urethritis in men, and to examine infections associated with these agents. Material and methods 299 sexually active, heterosexual men with nongonococcal urethritis were included into the study. Urethral samples were taken with a dacron swab placed into the urethra up to 2-3 cm. The Direct immunofluorescence technique was performed for identification of Chlamydia trachomatis. Ureaplasma urealyticum and Mycoplasma hominis were detected with Mycoplasma IST assay. RESULTS: Chlamydia trachomatis was detected in 22.75%, Uraeplasma urealyticum in 21.08% and Mycoplasma hominis in 8.02% cases. We found no significant differences in prevalence between Chlamydia trachomatis and Ureaplasma urealyticym (p > 0.05). Monoinfections were found in 51.85% with significantly higher rate (p < 0.01) than associated infections (11.70%). Among associated infections, coinfection of Chlamydia trahomatis and Ureaplasma urealyticum was predominant. Association of Chlamydia trachomatis with urogenital mycoplasmas was significantly higher (p < 0.05) than the one between Ureaplasma urealyticum and Mycoplasma hominis. In 36.45% patients no patogenic microorganisms were detected. CONCLUSION: These results confirmed the etiological role of Chlamydia trachomatis and urogenital mycoplasmas in nongonococcal urethritis with prevalence of 51.85% in monoinfections and 11.70% in associated infections. In 36.45% of cases the etiology of urethritis was not elucidated. These results suggest that more sensitive diagnostic tool should be applied when searching for the derailed etiology of nongonococcal urethritis.

[Varicella complications: is it time to consider a routine varicella vaccination?].

BACKGROUND/AIM: Varicella is a common and benign disease of childhood. Complications are rare, but in some patients, even without risk factors, severe, life treathening complications could be seen. The aim of this study was to establish the type and frequency of varicella complications among hospitalised patients over an 8-year period. METHODS: This retrospective analysis included medical charts of the patients hospitalised in the Infectious Disease Clinic, Belgrade, Serbia, from 2001-2008 (4.85% of all registered patients with varicella in Belgrade, 2001-2008). Among hospitalised patients dermografic characteristics were analysed: hospitalisation lenght, presence and type of complications, presence of immunocompromising conditions and outcome of the disease. The diagnosis of varicella was made on clinical grounds, and in persons >40 years, with negative epidemiological data of contacts, serological confirmation (ELISA VZV IgM/IgG BioRad) and avidity of IgG antibodies were done to exclude the possibility of disseminated herpes zoster. RESULTS: A total of 474 patient were hospitalised over an 8-year period. The age of patients was from 5 months to 75 years (mean 22.4 +/- 16.1, median 23.5 years). The majority of patients were adults (n=279; 58.9%) and 195 (41.1%) patients were < or =15 years old. Complications were found in 321/474 (67.7%) patients. The registered complications were: varicella pneumonia (n=198; 41.38%), bacterial skin infections (n=40; 8.4%), cerebelitis (n=28; 5.9%), bacterial respiratory infection (n=21; 4.4%), viral meningitis (n=10; 2.31%), encephalitis (n=9; 1.9%), thrombocytopenia (n=2; 0.4%); 11 (2.3%) patients had more than one complication, among them were sepsis, myopericarditis and retinal hemorrhages. When complications were analysed according to the age, there were no statistical significance, but when type of complication was analysed statistical significance was found (p < 0.05). In adults, pneumonia was the most common complication: 173/279 (62%), followed by skin infections (2.9%), bacterial respiratory infections (2.2%), and more than one complication (2.3%). Pneumonia was more common in adults than in children (7:1). In children skin infections were the most common complications (16.4%), followed by cerebelitis (13.3%), viral pneumonia (12.8%), bacterial respiratory infections (7.7%), encephalitis (3.6%), and more than one complication (4.1%). Neuroinfections were more common in children than in adults (6:1), as well as bacterial skin infections (4:1). Two patients died (0.4%). CONCLUSION: There was no difference in the incidence of varicella complication in children and adults, but the type of complication differed. In children the most common complications were skin and neurological infections, while in adults it was varicella pneumonia. These data provide a baseline for estimating the burden of varicella in Belgrade and support the inclusion of varicella vaccine in childhood immunisation program in Serbia.

Systemic manifestations in the course of meningococcal disease.

BACKGROUND/AIM: Meningococcal disease most often manifests itself as meningitis or sepsis. During the course of these diseases, other clinical events sometimes develop such as pneumonia, pericarditis, arthritis, and they are referred to as extrameningeal or systemic manifestations of the meningococcal disease. The aim of this study was to investigate the type and the incidence of particular extrameningeal/systemic manifestations among patients with meningococcal meningitis and sepsis, including time of their onset and the influence on the disease outcome. METHODS: The retrospective study of the medical records of 246 patients treated for meningococcal disease over the 25-year period in the Institute for Infectious and Tropical Diseases, Belgrade was conducted. The patients, aged 3 months to 82 years both sexes, were divided into two groups. RESULTS: Out of 246 patients extrameningeal/systemic manifestations were found in 42 (17.1%) patients: 35 (14.2%) occurred during meningitis, and seven (2.8%) during sepsis. Pulmonary manifestations (mostly pneumonia) were the most prevalent, found in 12 (4.9%) patients, followed by heart involvement in nine (3.6%) patients (mostly pericarditis, in seven or 2.8% patients). Various ophthalmic manifestations occurred in seven (2.8%), arthritis in 4 (1.6%) and sinusitis in six (2.4%) patients. Otitis, multiple renal embolisms with hematuria, osteomyelitis and thrombophlebitis were evidenced in one patient, each. Most of the systemic manifestations (30 patients or 71.4%), developed within the initial three days of the disease (p < 0.01), suggesting direct pathogenic mechanism induced by meningococci per se, while only three (7.1%) developed after seven days, when immune-mediated disease was more likely. Even though these manifestations complicate and prolong treatment of the meningococcal disease, they had no major influence on the disease outcome. Lethal outcome occurred in 2 (4.76%) patients, both with the meningococcal type of the disease. CONCLUSION: Extrameningeal or systemic manifestations are uncommon complications during the course of both meningococcal meningitis and sepsis. The onset of pneumonia, pericarditis, eye involvement, and arthritis, within the initial seven days of the disease, were most prevalent in the course of meningitis. They had no major influence on the disease outcome.

Reduced quality of life in patients with chronic viral liver disease as assessed by SF12 questionnaire.

BACKGROUND & AIM: Quality of life may be reduced in patients with chronic liver diseases. The purpose of this study was to assess the impact of chronic viral liver disease on health-related quality of life (HRQOL). PATIENTS AND METHODS: Quality of life was prospectively investigated in 227 patients with chronic viral liver disease and 75 controls. The generic Short Form 12 questionnaire was applied to measure the HRQOL: Mental and physical component scores were expressed as numeric and categorical values (presence/absence of disability). The electronic database (SPSS for Windows) was used for statistical analysis with 95% confidence intervals. RESULTS: Mental and physical numeric and categorical scores for the absence of disability were significantly worse in patients compared with controls. Patients were a negative predictive factor for the absence of disability on both mental and physical components while the physical component was the significant factor in multivariate regression analysis (p =0.000). There was no difference in HRQOL scores among patients with hepatitis C or B virus infection. Mental and physical numeric scores were lower in patients with cirrhosis. Liver cirrhosis predicted lower components of the absence of disability in comparison to chronic hepatitis more influencing the physical component (p =0.003). CONCLUSIONS: Chronic viral liver disease reduces and predicts a lower quality of life in comparison to a healthy population impairing more the physical component. Hepatitis viruses do not influence differently the quality of life. Liver cirrhosis has a higher negative impact on the quality of life than chronic hepatitis, especially relating to a physical component.

Bilateral pulmonary shadows and incapsulated mediastinal effusion in a patient with respiratory blastoschizomycosis.

INTRODUCTION: Invasive blastoschizomycosis is an emerging and fatal infection of severely immunocompromised patients. Pneumonia caused by this fungus has been reported as a post mortem diagnosis in a patient with haematologic malignancy. CASE REPORT: A 46-year-old unemployed Caucasian man, smoker, was admitted on emergency in a serious condition, with bilateral pulmonary infiltrates (chest x-ray) and incapsulated mediastinal pleural effusions (computed tomography scans). Blastoschizomyces capitatus (Trichosporon capitatum) has been isolated from two sputum samples and bronchial secretion aspirate obtained by bronchoscopy. CONCLUSION: Pneumonia caused by Blastoschizomyces capitatus can develop in subjects without underlying malignancy but with history of heavy alcohol intake, tobacco smoking and malnutrition and may have favorable disease outcome.

Immunohistochemical analysis of gamma catenin in Wilms' tumors.

The aim of our study was to investigate the expression of gamma-catenin in normal kidney and in Wilms' tumor by immunohistochemistry and to correlate the results with tumor stage, histological type, and prognostic group. We investigated 28 cases of Wilms' tumor, 2 Wilms' tumor metastases in lungs, and 1 specimen of normal renal tissue. Expression of gamma-catenin was detected in 14 cases. There was a weak inverse relationship between gamma-catenin expression and tumor stage. Expression of gamma-catenin was detected in various histologic types of Wilms' tumor, but there was no statistically significant correlation, except in cases with diffuse anaplasia that were negative. In 2 metastatic cases and in the case of bilateral Wilms' tumor gamma-catenin immunostaining was not observed Our findings suggest an absence of strong correlation between the loss of gamma-catenin and unfavorable outcome.

[Erysipelas today].

INTRODUCTION: Erysipelas is a form of cellulitis and a bacterial infection affecting the most superficial layers of the skin which is caused by group A--hemolytic Streptococcus. The symptoms of erysipelas usually arise quite suddenly and they are often accompanied by fever, chill and shivering. The affected skin is distinguished from other forms of cellulitis by well-defined, raised edge. The affected skin is red, swollen and may be finely dimpled (like an orange skin). TREATMENT OF ERYSIPELAS: Uncomplicated erysipelas can be treated on an outpatient basis. Indications for hospitalization include a severe clinical picture and socioeconomics factors. Most patients suffering from erysipelas in Belgrade are treated at the Institute of Infectious and Tropical Diseases, and the aim of this study was to analyze patients treated during 2002 and 2003, in order to determine characteristics of erysipelas at the beginning of the XXI century. MATERIAL AND METHODS: During the studied period, we treated 60 patients (26.7%) of all registrated erysipelas cases in Belgrade. The male/female ratio was 1:1.6. DISCUSSION AND CONCLUSION: Prevalence was higher during the summer months. In most cases, the severity and the need for hospitalization were recognized at the beginning; therefore, 74% of patients were hospitalized during the first five days from the onset of nonspecific signs of illness. Laboratory tests showed mild leukocytosis (med 12.05 x 10/9/l), with predominant neutrophils (74.8%) and increased fibrinogen (med 5.4 g/l). Predisposing factors were present in 83.3% of cases; of them, in 35% of cases this was not the first episode of this illness. In 85% of cases erysipelas of the leg was established, and it was the most frequent localization of all.

[Influenza: a current medical problem].

INTRODUCTION: Acute respiratory infections are the most common infections in the human population. Among them, virus infections, especially those caused by influenza viruses, have an important place. TYPE A INFLUENZA: Type A influeza virus caused three epidemics during the last century. A high percetage of deceased in pandemics of 1918, and 1919 were young, healthy persons, with many of the deaths due to an unusually severe, hemorrhagic pneumonia. At the end of 2003, and the beginning of 2004, an epidemic emerged in South East Asia of poultry influenza caused by animal (avian) virus. Later it spread to the human populaton, with a high death rate of 73% and with a possibility of interhuman transmission. This review article provides an overview of the clinical manifestations, laboratory findings and chest radiographs. Apart from the symptomatic and supportive therapy, there are antiviral drugs and corticosteriods. CONCLUSION: The use of vaccine containing subtypes of virus hemagglutinins and neuraminidase from an influenza virus currently infecting the population has a great importance.

Hepatitis C virus genotypes in Serbia and Montenegro: the prevalence and clinical significance.

AIM: To investigate the prevalence of hepatitis C virus (HCV) genotypes in Serbia and Montenegro and their influence on some clinical characteristics in patients with chronic HCV infection. METHODS: A total of 164 patients was investigated. Complete history, route of infection, assessment of alcohol consumption, an abdominal ultrasound, standard biochemical tests and liver biopsy were done. Gene sequencing of 5' NTR type-specific PCR or commercial kits was performed for HCV genotyping and subtyping. The SPSS for Windows (version 10.0) was used for univariate regression analysis with further multivariate analysis. RESULTS: The genotypes 1, 2, 3, 4, 1b3a and 1b4 were present in 57.9%, 3.7%, 23.2%, 6.7%, 6.7% and 1.8% of the patients, respectively. The genotype 1 (mainly the subtype 1b) was found to be independent of age in subjects older than 40 years, high viral load, more severe necro-inflammatory activity, advanced stage of fibrosis, and absence of intravenous drug abuse. The genotype 3a was associated with intravenous drug abuse and the age below 40. Multivariate analysis demonstrated age over 40 and intravenous drug abuse as the positive predictive factors for the genotypes 1b and 3a, respectively. CONCLUSION: In Serbia and Montenegro, the genotypes 1b and 3a predominate in patients with chronic HCV infection. The subtype 1b is characteristic of older patients, while the genotype 3a is common in drug abusers. Association of the subtype 1b with advanced liver disease, higher viral load and histological activity suggests earlier infection with this genotype and eventually its increased pathogenicity.

Older age at the time of liver biopsy is the important risk factor for advanced fibrosis in patients with chronic hepatitis C.

BACKGROUND/AIMS: Progression of chronic hepatitis C depends on the host and viral characteristics, duration of infection, co-infection with other viruses, etc. In this study, some of demographic, epidemiological and viral data as risk factors for a degree of liver fibrosis were evaluated. METHODOLOGY: A total of 144 patients was investigated (89 males, ages from 16-65 years) classified into two groups, with fibrosis scores 0-3 and 4-6, using the Ishak scoring system. Significant variables were entered into univariate logistic regression model and further multivariate analysis was performed. RESULTS: There were 64% and 36% of patients with fibrosis scores 0-3 and 4-6, respectively. Gender, moderate to heavy alcohol abuse and high viral RNA were equally distributed between both groups. In univariate analysis, the age older than 40, history of intravenous drug abuse, and the genotype 1b were independently associated with different fibrosis scores. Multivariate regression analysis revealed ages older than 40 as the positive (p < 0.001), and younger than 40 as the negative predictive factors for fibrosis scores 4-6 and 0-3 (p < 0.001), respectively. CONCLUSIONS: Our results indicate the age over 40 at the time of liver biopsy as the important risk factor for advanced liver disease in chronic hepatitis C according to fibrosis scores.