[Immunomodulatory actions of antibiotics]. / Imunomodulatorna delovanja antibiotika.

INTRODUCTION: Antimicrob drugs and immune system interaction has been studied since the pioneer works of Metchnikoff. After the introduction of antibiotics in clinical practice this area has attracted little attention of investigators, because of the lack of standards. This is the reason that the studying of the influence of antibiotics on immune system is still at its beginning. AIM: To point out the immunomodulatory action of some antibiotics on certain components of immune system. METHODS AND RESULTS: The literature findings show that antibiotics express immunomodulatory action on some components of immune system such as fagocytes (polymorphonucleary, macrophages, monocytes), cytokines, immunoglobulines, and on cellular immunity. The principles of antibiotics action on phagocyte are the inhibition of chemotaxis and oxidants production. Macrolides applied for a short time enhance the phagocytic functions while their long use leads to immunosupression. Some cephalosporines and rifampicin in therapeutic doses inhibit the oxydative metabolism, of macrophages. Tetracyclines, clindamycines, chloramphenicol and tobramycin inhibit the synthesis of superoxyd anione. The action of some antibiotics on cytokine and specific antibodies is also important. Cellular immunity can be affected as well. After administration of certain antibiotics it takes 1-2 weeks to reestablish normal cellular immunity, and for other even more. CONCLUSION: There is still no clear standing on real effects of antibiotics on the immune system. Clinicians should search for more information from this new-old field of investigation in order to give more adequate therapy to patients.

[Diseases caused by bacteria and rickettsia in biological warfare and bioterrorism].

INTRODUCTION: Until recently, the use of biological weapons was considered more from an academic than practical point of view. The list of agents and/or toxins that can be used as biological weapons is long. Some of them are highly lethal, while others cause morbidity and disability. BIOLOGICAL WEAPONS: Bacteria, rickettsia, viruses, fungi, protozoa and toxins can all be used as biological weapons. The infection may be acquired by inhalation of aerosols, ingestion of contaminated water or food or direct contact with infectious agents. Early recognition, diagnosis and treatment of these patients is of utmost importance. Special attention must be given to the use of genetically modified microorganisms. Medical protection from biological weapons is very important as well as continuous education. CONCLUSION: This article describes the main clinical characteristics of anthrax, cholera, plague, Q fever, tularemia, brucellosis, and glanders, as biological weapons, their diagnostics, treatment and basic prevention measures.

[Diseases caused by viruses and toxins in biological warfare and bioterrorism].

INTRODUCTION: Viruses and toxins, as well as bacteria and rickettsia can potentially be used as biological weapons in conflicts or in bioterrorism. USE OF BIOLOGICAL WEAPONS: The infection can be acquired by inhalation of aerosols, ingestion of contaminated food or water, or direct contact with the skin or mucosa. Special attention must be given to the possible use of genetically modified agents. CONCLUSION: This paper describes the clinical features of diseases caused hbi viruses (smallpox, hemorrhagic Jever and encephalitis) and toxins (botulinum, staphylococcal enterotoxin B, ricinus toxin and mycotoxins) their diagnosis, treatment, as well as basic preventive measures.

[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.

[Treatment options for chronic hepatitis C virus infection].

INTRODUCTION: The incidence of chronic hepatitis C virus (HCV) infection is rather high. Its most frequent consequences are chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. TREATMENT OF CHRONIC HCV INFECTION: In treatment of chronic HCV infection, interferons have antiviral, anriproliferative, and immunoregulatory action. Within the cell, they induce protein synthesis, inhibiting viral replication. The most important among them are RNA dependent protein kinase, and eukaryotic initiation factor. However, viral proteins prevent their phosphorylation and activation. In order to overcome this problem, treatment is prolonged, higher doses of lFN are used, as well as induction therapy. The optimal period for viral response is 52 weeks, while induction therapy has shown controversial results.

[Effects of interferons on hepatitis C virus infection].

INTRODUCTION: The consequences of hepatitis C virus infections (chronic hepatitis, liver cirrhosis and hepatocellular carcinoma) are one of the major problems in clinical medicine. The persistence of infection in spite of high specific antibody titre suggests that the virus has the abillity to "escape" the immunological response. INTERFERON THERAPY: Interferons are important components of the early host response to infection. They have antiviral, antiproliferative, and immunomodulatory activities. Many viruses have developed the ability to "annul" or alleviate the action of interferon by preventing its synthesis or by interfering with signaling pathways in the cells. During acute infection some of the non-structural proteins of HCV block regulatory factors that are responsible for the synthesis of endogenous infection. Within a cell, interferon induces a number of genes to produce proteins that prevent virus replication. Among them, the most important are RNA-dependent protein kinase and the eukaryotic initiation factor. However, viral proteins, especially viral envelope proteins and nonstructural protein 5A, prevent their phosphorylation and activation which enhance virus replication. These are the facts that have to be considered when using IFN in chronic hepatitis C patients.

[Abnormal ultrasonographic findings of the kidneys obtained with a portable echosonographic device in the patients with infectious diseases--a five-year study].

BACKGROUND/AIM: Ultrasonographic kidney changes might be a part of the clinical picture, or consequence of the various infections diseases. The aim of this study was to establish ultrasonographic findings obtained by portable devices, the frequency of abnormal findings of the kidneys in the non-selected group of the patients with infections diseases. METHODS: Over a five-year period (January 1, 2000-December 31, 2004), the kidneys were examined by ultrasonography in 2,718 patients, 1,452 males and 1,266 females, mean age 47.52 +/- 17 years, (16-92 years). The examination included the measurement of the size of the kidneys, evaluation of the condition of parenchyma and pyelo-calix, detection of simple cysts, calculi and tumor. The conventional portable ultrasonographic devices ALOKA SSD-500 and SSD-1000 (B-mode) with a convex 3.5 and 5 MHz sonde were used. RESULTS: The size of kidneys was normal in 95% of the patients, while they were enlarged in 1.3% and reduced in 1.5% of the patients. A normal ultrasonographic recording was noted in 68.9% of the patients, double pelvis in 0.1%, while hydronephrosis was revealed in 0.9% of the patients. A reduced renal parenchyma was observed in 16.1% of the patients. Nephrolithiasis was found in 10.9% of the patients, and simple cysts of kidneys in 8.9% of the patients. The finding of polycystic kidneys was seen in 0.5% of the patients. An ultrasonographic recording of angiomyolipoma was noted in 0.4% of the patients, and the finding of other tumors in 0.1% of the patients. Adrenal tumors were found in 0.1% of the patients. CONCLUSION: Portable ultrasonographic units may be highly useful for the standard morphological diagnostics of renal changes during infections, as well as in clinical-epidemiological studies and screening of hereditary and the acquired diseases of this organ.

[Role of various virus genotypes in progression of chronic hepatitis C]. / Uloga razlicitih genotipova virusa u progresiji hronicnog hepatitisa C.

The relation between HCV genotypes and the progression of chronic hepatitis is still unknown. Some studies implied more pathogenic effect of genotype 1b for the severity of liver inflammation. However, other studies did not show the association between HCV genotype 1b and the severe outcome of HCV infection. The aim of this study was to determine the most frequent genotypes in this environment and their influence on hepatitis C severity. The investigation included 34 patients with histologically confirmed chronic hepatitis C, aged 20-65 (mean 35.0 years). On the basis of pathohistological findings, applying the modern classification, the disease activity was graded as: minimal (A1) moderate (A2) and severe (A3). The extent of fibrosis was marked as: absent (F0), mild (F1), moderate (F2) and severe (F3). Genotyping was performed by nested PCR with type-specific primers and LIPA test and verified by sequencing. The most prevailing genotype in our group of patients was 1b (44.1%), followed by genotype 3a (26.4%), genotype 1a (11.7%) and 2a (2.8%). Five patients had mixed genotypes (four 3a/1b, and one 1a/1b). The severity of liver cell necrosis, measured by alanintransferase (ALT) levels in serum was not related to any of HCV genotypes. There was no statistically significant difference between histological disease activity in relation to HCV genotypes. Stage of the disease was not significantly related to the HCV genotypes. There was a strong association between the degree of fibrosis and the age of patients (p < 0.01). These results could indicate that the determination of HCV genotypes was not useful in the estimation of disease severity and that liver biopsy was the most important for the prognosis of the disease.

[Kikuchi-Fujimoto disease]. / Kikuchi-Fujimotova bolest.

Kikuchi-Fujimoto disease (KFD), also know as histiocytic necrotizing lymphadenitis, is a benign disorder characterized histologically by necrotic foci surrounded by histiocytic aggregates, and with the absence of neutrophils. KFD was recognized in Japan, where it was first described in 1972. The disease is most commonly affecting young women. The cause of the disease is unknown, and its exact pathogenesis has not yet been clarified. Many investigators have postulated viral etiology of KFD, connecting it with Epstein Barr virus, human herpes simplex virus 6 parvo B 19, but also with toxoplasmic infection. Kikuchi-Fujimoto disease is usually manifested with lymphadenopathy and high fever, and is associated with lymphopenia, splenomegaly, and hepatomegaly with abnormal liver function tests, arthralgia, and weight loss. The disease has the tendency of spontaneous remission, with mean duration of three months. Single recurrent episodes of KFD have been reported with many years' pauses between the episodes. Kikuchi-Fujimoto disease may reflect systemic lupus erythematosus (SLE), and self-limited SLE-like conditions. Final diagnosis could only be established on the basis of typical morphological changes in the lymph node, and lymph node biopsy is needed for establishing the diagnosis. Lymphadenopathy in a patient with fever of the unknown origin could provide a clue to the diagnosis of lymphoma, tuberculosis, metastatic carcinoma, toxoplasmosis and infectious mononucleosis. As KFD does not have any classical clinical features and laboratory characteristics, it may lead to diagnostic confusion and erroneous treatment. We described a case of KFD, and suggested that this disease should be considered as a possible cause of fever of the unknown origin with lymphadenopathy.

[First documented case of enterocolitis in Yugoslavia caused by enterohemorrhagic Escherichia coli O157]. / Prvi dokazani slucaj enterokolitisa u Jugoslaviji uzrokovan enterohemoragijskom eserihijom koli O157.

A 'new' group of pathogenic agents, enterohemorrhagic Escherichia coli (EHEC) (particularly the strains of O157 serogroup), emerged in the last 20 years, causing an increased number of sporadic and epidemic diarrhoeal diseases with hemorrhagic enterocolitis as a most common clinical manifestation of the infection. As a consequence of the absorption and cytotoxic effect of the main virulence factor of these bacteria--verotoxin (shiga-toxin), in about 10% of the affected persons extraintestinal complications, most frequently hemolytic-uremic syndrome (HUS), occurred 7-14 days after an episode of diarrhoeal disease. The first case of hemorrhagic enterocolitis with the documented EHEC O157 infection in Yugoslavia is presented in this paper. Considering the existing expansion trend of these carriers, practitioners should be aware of them in case of the occurrence of diarrhoeal disease, (particularly hemorrhagic enterocolitis), and keep these patients under control during the reconvalescence period because of potential development of extraintestinal complications, such as HUS.

[Multiorgan tuberculosis]. / Multiorganska tuberkuloza.

Tuberculosis is an unusual infectious disease because of the latent period between the infection and the appearance of the disease may be prolonged for many weeks, months, or years as it is in case of the secondary tuberculosis. Tuberculosis in organs other than the lung has been observed for many years but has not always been recognized as tuberculosis, and it has been given many names. Extrapulmonary tuberculosis gained new importance, because it represented a progressively greater proportion of new cases. Multiple extrapulmonary sites were reported rarely except for one anatomical site, which was reported frequently. Extrapulmonary rates increase with age, so there are marked differences in age in specific rate patterns among the sites. Extrapulmonary tuberculosis occurred in respiratory organs other than lung, such as lymphatic, urogenital, and central nervous system, abdominal, osteoarticular, as well as tuberculosis of other organs such as skin, pericardium and endocrine glands. This case was reported to analyse clinical, morphologic and laboratory characteristics, method of diagnosis and the outcome in patients with multiorgan tuberculosis in order to explore the factors which might contribute to the decision making, concerning these forms of tuberculosis. Recent knowledge of pathogenesis was summarized as well as clinical presentation and the effects of cytokines produced by T lymphocytes and cellular population on antimycobacterial immune defences, and also susceptibility to tuberculosis. Mortality remains high and the treatment should start as soon as tuberculosis is suspected.

[Necrotizing fasciitis caused by group A streptococcus]. / Nekrotizujuci fasciitis uzrokovan streptokokom grupe A.

The first case of the confirmed necrotizing fasciitis caused by Group A Streptococcus in Yugoslavia was presented. Male patient, aged 28, in good health, suddenly developed symptoms and signs of severe infective syndrome and intensive pain in the axillary region. Parenteral antibiotic, substitutional and supportive therapy was conducted along with the radical surgical excision of the necrotizing tissue. The patient did not develop streptococcal toxic shock syndrome thanks to the early established diagnosis and timely applied aggressive treatment. He was released from the hospital as completely cured two months after the admission.