[Autologous stem cell transplantation in the treatment of multiple myeloma--single center experience].

BACKGROUND/AIM: In comparison to standard therapy autologous stem cell transplant (ASCT) with high doses mel-phalane has improved treatment of multiple myeloma (MM) patients. The aim of this study was to evaluate the results of treatment of MM patients in our center with ASCTconditioning with melphalane or combining busulphane, cyclophosphamide and melphalane. METHODS: We performed 62 ASCT procedures in 47 patients from 1998 till 2008. Single ASCT were performed in 32 patients (68%), after 3-6 cycles of (26% patients. RESULTS: Median engraftment was on 12th day. In a 50-month follow-up period 64% patients were alive. The overall response rate (ORR), wich was reached in 38 (80%) patients, was better in the group of patients treated in the early phase of MM. Totally 25 (53%) patients were without progression in a 25-month follow-up period. Twenty patients met criteria for CR + VGPR (very good partial remission), that was 5 patients more than in the period before ASCT. Fourteen (30%) patients died and median time till death was 17 months. CONCLUSION: The ASCT perfomed in early phase of MM after V A D induction had a significant influence onthe treatment of MM patients. Reaching CR + VGPR before and after the ASCT is predictive factor for overall survival (OS) or prolongation of period till recidive appears, progression, therapy withdrowal or death.

Monitoring of cytomegalovirus infection after allogeneic stem cell transplantation.

BACKGROUND/AIM: More than 90% of worldwide population is infected with human cytomegalovirus (CMV), one of the most common agents which complicate immunocompromised patients. Viral infections, in particular CMV ones are still a major cause of moratality and morbidity after stem cell transplantation (SCT). Monitoring is performed by detecting CMV-Ag or virus DNA in peripheral blood. Risk factors are donor/recipient CMV status, type of transplant and acute graft versus host disease. The aim of the study was to determine the extent of validity of CMV infection monitoring after transplantation as a reliable parameter of further CMV replication course in patients with hematopoietic stem cell transplantation. METHODS: A total of 49 patients with stem cell transplantation were studied prospectively during a 2-year period after transplantation for the presence of CMV DNA. Polymerase chain reaction (PCR) CMV DNA was performed on 222 full blood samples using Cobas Amplicor assay. RESULTS: Activation of CMV was detected in 10/49 (20.48%) of the patients. The median posttransplantation time for the first positive PCR result was 6 weeks for the stem cell transplant patients. Viremia became negative in all the cases after the antiviral therapy with ganciclovir. CONCLUSION: Our data show that the level of CMV-DNA load at the time of initial CMV detection after transplantation could be a possible predictor for further course of CMV replication in patients receiving hematopoietic stem cell.

[Therapy of chronic hepatitis C--virologic response monitoring].

BACKGROUND/AIM: Virological testing is considered to be essential in the management of hepatitis C virus (HCV) infection in order to diagnose infection, and, most importantly, as a guide for treatment decisions and assess the virological response to antiviral therapy. The aim of this study was to determine the rate of a sustained virological response (SVR) and various factors associated with response rates in chronic hepatitis C infected patients treated with peg interferon alpha (PEG-INF) and ribavirin (RBV) combination therapy. METHODS: A total of 34 patients, treated with PEG-IFN and RBV were studied. Serum HCV-RNA was measured before the treatment, 12 weeks following the start of the therapy and 6 weeks after the treatment cessation. SVR was defined as undetectable serum HCV-RNA 6 months of post-treatment follow-up, virologic relapse (VR) as relapse of HCV-RNA during the posttreatment follow-up. Serum HCV-RNA was measured with the Cobas Amplicor test. RESULTS: At the end of post-treatment follow-up 19 (55.8%) patients demonstrated a SVR. The majority of the patients were genotype 1 (27), and the other were genotype 3 (5 patients) and genotype 4 (2 patients). There was VR in 6 patients 6 months after the therapy. In 9 patients HCV-RNA was positive after 12 weeks. CONCLUSION: We demonstrated that patients with chronic HCV infection can be successfully treated with combination of PEG-INF and RBV. This result emphasizes also that post-treatment follow-up to identify patients with SVR or VR could be important.

Empirical antimicrobial therapy of acute dentoalveolar abscess.

BACKGROUND/AIM: The most common cause of acute dental infections are oral streptococci and anaerobe bacteria. Acute dentoalveolar infections are usually treated surgically in combination with antibiotics. Empirical therapy in such infections usually requires the use of penicillin-based antibiotics. The aim of this study was to investigate the clinical efficiency of amoxicillin and cefalexin in the empirical treatment of acute odontogenic abscess and to assess the antimicrobial susceptibility of the isolated bacteria in early phases of its development. METHODS: This study included 90 patients with acute odontogenic abscess who received surgical treatment (extraction of a teeth and/or abscess incision) and were divided into three groups: two surgical-antibiotic groups (amoxicillin, cefalexin) and the surgical group. In order to evaluate the effects of the applied therapy following clinical symptoms were monitored: inflammatory swelling, trismus, regional lymphadenitis and febrility. In all the patients before the beginning of antibiotic treatment suppuration was suched out of the abscess and antibiotic susceptibility of isolated bacteria was tested by using the disk diffusion method. RESULTS: The infection signs and symptoms lasted on the average 4.47 days, 4.67 days, and 6.17 days in the amoxicillin, cefalexin, and surgically only treated group, respectively. A total of 111 bacterial strains were isolated from 90 patients. Mostly, the bacteria were Gram-positive facultative anaerobs (81.1%). The most common bacteria isolated were Viridans streptococci (68/111). Antibiotic susceptibility of isolated bacteria to amoxicillin was 76.6% and cefalexin 89.2%. CONCLUSION: Empirical, peroral use of amoxicillin or cefalexin after surgical treatment in early phase of development of dentoalveolar abscess significantly reduced the time of clinical symptoms duration in the acute odontogenic infections in comparison to surgical treatment only. Bacterial strains isolated in early stages of dentoalveolar abscess showed high sensitivity to amoxicillin and cefalexin.

[Impact of vaginal and cervical colonisation/infection on preterm delivery].

BACKGROUND/AIM: Preterm delivery together with insufficient body weight and death cases in newborns is the main issue in obstetrics. About 40% of preterm delivery is caused by infections. The aim of this study was to investigate whether and which bacterial infections of genital tract can be associated with preterm delivery, and depending on when diagnosis was made. METHOD: The study involved 216 pregnant women. According to pregnancy outcome, two groups were formed. The study group involved 29 pregnant women who had preterm delivery out of which nine were examined in I trimester, eight in II trimester and 12 in III trimester. The control group involved 187 pregnant women out of which 47 were examined in I trimester, 73 in II trimester and 67 in III trimester. Bacteriological examination of vaginal and cervical swabs was done in all pregnant women. Infection was diagnosed by finding bacterial antigen in cervical swabs or positive cultures of vaginal and/or cervical swabs followed by the presence of the increased number of polymorphonuclears in direct microscopic preparation. RESULTS: The results showed that in III trimester of pregnancy vaginal bacterial infection was statistically more common (p = 0.021) in women who had preterm delivery (66.7%) in relation to women who delivered in term (29.9%). In this period of gestation the increased number of polymorphonuclears in DMP of vaginal swabs is more common in the women of the study group (75%) than in the women of the control group (43.3%). Preterm delivery was registered in 16.1% women whose microbiological analyses were done in I trimester, 9.9% women in whom microbiological analyses were done in II trimester and in 15.2% pregnant women microbiologically tested in III trimester. CONCLUSION: Based on the obtained results it could be concluded that bacterial infections of genital tract and period of gestation when infection is diagnosed have influence on reducing perinatal morbidity and mortality caused by preterm delivery.

[Oncogenic viruses and their role in tumour formation].

Oncogenic viruses trigger persistent infections, which can stimulate uncontrolled cell growth by inducing cell transformation. Different oncogenic viruses use different mechanisms for infecting cells. Most oncogenic DNA viruses integrate transforming sets of genes into the host chromosome and encode proteins that bind and inactivate cell growth regulatory proteins, such as p53 and retinoblastoma gene product. Tumourous RNA viruses use different oncogenic mechanisms. Some of them encode oncogenic proteins that are almost identical to the cellular proteins involved in the control of cellular growth. The overproduction or altered function of these oncogenic materials stimulates cell growth. These RNA viruses can cause tumours rapidly. The second group of oncoviruses integrates their promoter sequences and viral enhancers near to the cellular growth-stimulating gene, initiating the transformation of the cell. The third group of RNA tumour viruses encodes a protein tax that transactivates the expression of cellular genes. Virus-induced malignant transformation of the cell represents the first step in the complex process of oncogenesis.

[SARS corona virus--a new dilemma].

In late 2002, cases of life-threatening respiratory disease with no identifiable cause were reported from Guangdong Province, China, and they were followed by reports from other countries. The syndrome was designated "severe acute respiratory syndrome" (SARS). Investigators used a combination of traditional methods and molecular techniques to identitify the unknown pathogen. Researches showed that SARS is caused by a new coronavirus, never detected before and which is not related to any of the known coronaviruses.

[Smallpox--in the past or not?]. / Variola--proslost ili ne?

Smallpox is a potentially deadly illness caused by the variola virus, an orthopoxvirus. Severe illness followed by blister-like body rash is the sign of smallpox. Smallpox symptoms develop about 12 days after exposure. V. variole can spread very readily by aerosol, which may lead to explosive epidemics. For centuries, smallpox has been a worldwide cause of death, killing about 30% of the infected people. In 1972, the epidemic of smallpox in ex-Yugoslavia was the largest postwar smallpox epidemic in Europe. The total number of the affected was 175, out of whom 35 with fatal outcome, accounting for 20% of mortality. However, after a decade-long vaccination effort, the last natural case of smallpox occurred in 1977. The only way to prevent smallpox epidemic is by vaccination and patients' isolation. The possibility of future bioterrorism attacks, which may cause a new outbreak of smallpox and return variola, is very serious. World population is not immune, because of lack of vaccination. In 1980, the World Health Organization (WHO) declared the disease fully eradicated.

[Early diagnosis of cytomegalovirus infections in organ recipients]. / Rana dijagnoza citomegalovirusne infekcije kod primalaca organa.

INTRODUCTION: Cytomegalovirus (CMV) infections and acute rejection of organs are the commonest complications in the early posttransplantation period. Clinical picture of CMV reactivation in organ recipients may have a dramatic course, occasionally even with a fatal outcome. DIAGNOSIS OF CMV: In order to prevent acute rejection of organs in the posttransplantation period, patients are subjected to immunosuppressive therapy, which sustains reactivation of CMV. Thus, early diagnosis of CMV infections before clinical assay of CMV, is of crucial importance. Early diagnosis allows preventive antiviral therapy. Conventional and contemporary diagnostic tests are presented, with particular review on their interpretation and significance in prevention of CMV infections. Present serologic tests are positive a few weeks after infection, which is late for organ recipients. Cytopathogenic effects characteristic for CMV occur several weeks later. Antigenemia assay is a fast, quantitative test for detection of early CMV antigen pp65. Methods of molecular biology represent the latest innovation in the laboratory diagnosis of posttransplantation CMV infections. However, they have been in use only lately, and therefore their use and significance are still not sufficiently experienced. Standardization is thus required, in order to provide comparison between various diagnostic centres.

[Emerging diseases. Crimean-Congo hemorrhagic fever]. / Pretece zaraze-krimsko-kongoanska hemoragijska groznica.

INTRODUCTION: Recognized for many years in central Asia and Eastern Europe, Crimean-Congo hemorrhagic fever (CCHF) is a severe zoonotic disease which affects people coming into contact with livestock or ticks. The range of the CCHF virus is now known to extend form central Asia to India, Pakistan, Afghanistan, Iran, Iraq, the Middle East, Eastern Europe, and to most of Saharan and sub-Saharan Africa. ETIOLOGY: CCHF virus is a member of the Bunyavirus family, and is classified as a Nairovirus. CLINICAL FEATURES: After an incubation period of approximately 3 to 6 days the abrupt onset of acute febrile illness occurs. The first symptoms are similar to severe influenza and include fever, headache, severe back and abdominal pain. The hemorrhagic fever manifestations occur after several days of illnesses and include petechial rash, ecchymoses, hematemmesis, and melenna. Cases typically present with some form of hepatitis. The mortality rate is 10-50% in different outbreaks with deaths typically occurring during the second week of illness. EPIDEMIOLOGY: The genus Hyalomma of ixodid ticks is the most important vector of the CCHF virus. Vertebrates including birds and small animals provide excellent amplifier hosts of both the virus and the tick. The virus can be transmitted to humans by direct contact with infected animals and from person to person. DIAGNOSIS: Early diagnosis is possible in special laboratories using antigen detection by imunofluorescence or ELISA tests or molecular methods as PCR and antibody detection. CONTROL: Tick control measures need to be emphasized and utilized to prevent CCHF. This includes spraying camp sites, clothing and danger areas with acaricides or repellent. Strict isolation of patients with CCHF and a focus on barrier nursing would help to prevent nosocomial spread. Presently the vaccine is a dangerous mouse brain-derived version. Future development of a vaccine would help to prevent human infection.

Isolation of Chlamydia trachomatis or Ureaplasma urealyticum from the synovial fluid of patients with Reiter's syndrome.

BACKGROUND: The aim of this study was to contribute to the insight of the role of the infectious agent in ethiopathogenesis of the Reiter's syndrome development, which could directly influence the choice of treatment of these patients. METHODS: Eighteen patients with urogenital form of the Reiter's syndrome and 16 controls (6 with rheumatoid arthritis and 10 with pigmented villonodular synovitis) were included in the study. In all patients standard laboratory analyses of the blood, urine and stool were made; antibody titer to Chlamydia trachomatis and Ureaplasma urealyticum was determined in synovial fluid and serum; isolation of Chlamydia trachomatis and Ureaplasma urealyticum in urethral, cervical and conjunctival swabs, as well as in prostatic and synovial fluid, was also made. HLA typing was done, too. Chlamydia was isolated in the McCoy cell culture treated with cycloheximide, while Ureaplasma was identified according to its biochemical properties grown on cell-free liquid medium. RESULTS: Chlamydia trachomatis was isolated from the synovial fluid of 4 patients with Reiter's syndrome (22.2%), while Ureaplasma urealyticum was isolated in 7 of them (38.9%). These microorganisms were not found in any synovial fluid of the control group patients. CONCLUSION: Presence of these bacteria in the inflamed joint might be an important factor in etiopathogenesis of this disease, and it supports the hypothesis that arthritis in Reiter's syndrome is probably of the infectious origin.