Occupational and non-occupational risk factors correlating with the severity of clinical manifestations of carpal tunnel syndrome and related work disability among workers who work with a computer.

The contribution of certain occupational and personal factors to the development of carpal tunnel syndrome (CTS) is still uncertain. We investigated which specific occupational and non-occupational factors correlate with the level of clinical manifestations and work disability related to CTS. The study included 190 workers who work with a computer and have diagnosed CTS (100 men, 90 women, aged 20-65 years). Subjective experience of CTS-related impairments was assessed with the Symptom Severity Scale (SSS) and the Functional Status Scale (FSS) of the Boston Carpal Tunnel Syndrome Questionnaire (BCTQ). The objective, neural impairments were tested with electrodiagnostics (EDX), whereas CTS-related work disability data were collected from medical records. We found a high inter-correlation between BCTQ, EDX, and work disability data. These also showed high correlations with certain occupational factors (duration of computer-working in months and hours spent daily in computer-working, certain ergonomic, microclimatic, and other occupational conditions) and non-occupational factors (demographic and lifestyle factors: nutritional status, diet, smoking, alcohol consumption, and physical activity). Despite its limitations, our study has identified occupational and non-occupational risk factors that can aggravate CTS and work disability, but which can also be improved with workplace and lifestyle preventive and corrective measures. More research is needed, though, to establish the possible causal relationships and the independent influence of each of those risk factors.

The relationship between occupational stress, health status, and temporary and permanent work disability among security guards in Serbia.

Purpose. This study aimed to examine the influence of occupational stress on health status and work disability among security guards in Serbia. Methods. Three hundred and ninty nine male security guards (aged 25-65 years) were examined during regular medical preventive check-ups at the Institute of Occupational Health. Data on their health status and permanent and temporary work disability were obtained, and correlations with the levels of occupational stress (measured by occupational stress index [OSI] questionnaire) were analysed. Results. A high prevalence of health impairments, including diabetes (38.8%), dyslipidaemia (82.7%), hypertension (69.9%) and metabolic syndrome (77.7%), was found. Highly significant correlations were shown between reported levels of total stress at work (total OSI score) and measured values of glucose, lipids, blood pressure, heart rate, Framingham cardiovascular risk scale, occurrence of diabetes and impaired fasting glucose, dyslipidaemia, hypertension, metabolic syndrome, coronary heart disease, cerebrovascular insults, degenerative eye-fundus changes, and temporary and permanent work disability. All of these correlations remained significant even after adjustments for age, body mass index and smoking status. Regression analysis confirmed the independent effect of occupational stress on the analysed parameters. Conclusions. There is a significant independent impact of occupational stress on development of health impairments and work disability among security guards.

Evaluation of genotoxic potential of tert-butylquinone and its derivatives in prokaryotic and eukaryotic test models.

Tert-butylquinone (TBQ) and its alkylamino and aralkylamino derivatives are of high interest as a potential antitumor agent. Therefore, it was necessary to investigate if the compounds exert undesirable activities such as interaction with DNA molecule which could result in negative side effects in the case of their use in the diseases treatment. The major aim of this study was to investigate genotoxic potential of TBQ and selected derivatives in an acellular model by using plasmid DNA, in the prokaryotic model by the SOS/umuC assay in Salmonella typhimurium TA1535/pSK1002 and in eukaryotic models by using comet assay in human fetal lung cell line (MRC-5) and human liver cancer cell line (HepG2). Results indicated that in the acellular model TBQ and its derivatives do not interact with plasmid pUC19. In the prokaryotic model, only TBQ exerted weak genotoxic potential and only at highly cytotoxic concentrations. In eukaryotic models, genotoxic potential was detected mainly at the highest concentrations of the tested substances but the effect was lower in both cell lines in comparison with benzo[a]pyrene and etoposide which were used as positive controls. Weak genotoxic potential of tested compounds recommends them as good candidates for further testing in development of new antitumor agents.

Evaluation of genotoxic potential in the Velika Morava River Basin in vitro and in situ.

The Velika Morava River is the greatest national Serbian river and the significant tributary of the Danube River. The major problems in the Velika Morava River Basin (VMRB) represent untreated industrial and municipal wastewaters. In this study, the level of genotoxic potential at the sites along the VMRB was evaluated by parallel in vitro and in situ approach. Within in vitro testing, genotoxicity of native water samples collected from the sites in VMRB was evaluated by SOS/umuC test on Salmonella typhimurium TA1535/pSK1002 and by the comet assay on HepG2 cells. DNA damage in situ was assessed in bleak (Alburnus alburnus) erythrocytes by the comet (alkaline and Fpg-modified comet) and micronucleus assays. Additionally, the concentration of heavy metals in fish tissue was measured and this data, compiled with the data of the physico-chemical parameters measured in water, was used as a measure of the pollution pressure at the sites. Results showed that applied in vitro tests with native water samples are less sensitive in comparison with in situ tests and should be taken with precaution when making predictions on the status of the ecosystem. Within applied battery of in situ assays differential sensitivity of assays was observed where alkaline comet assay showed the highest potential in differentiation of the sites based on genotoxic potential. Integrated biomarker response showed that usage of the battery of bioassays provides better insight in a genotoxic effects in animals, and consequently, that the holistic approach is more suitable for this type of study.

Tumor phosphatidylinositol-3-kinase signaling and development of metastatic disease in locally advanced rectal cancer.

BACKGROUND: Recognizing EGFR as key orchestrator of the metastatic process in colorectal cancer, but also the substantial heterogeneity of responses to anti-EGFR therapy, we examined the pattern of composite tumor kinase activities governed by EGFR-mediated signaling that might be implicated in development of metastatic disease. PATIENTS AND METHODS: Point mutations in KRAS, BRAF, and PIK3CA and ERBB2 amplification were determined in primary tumors from 63 patients with locally advanced rectal cancer scheduled for radical treatment. Using peptide arrays with tyrosine kinase substrates, ex vivo phosphopeptide profiles were generated from the same baseline tumor samples and correlated to metastasis-free survival. RESULTS: Unsupervised clustering analysis of the resulting phosphorylation of 102 array substrates defined two tumor classes, both consisting of cases with and without KRAS/BRAF mutations. The smaller cluster group of patients, with tumors generating high ex vivo phosphorylation of phosphatidylinositol-3-kinase-related substrates, had a particularly aggressive disease course, with almost a half of patients developing metastatic disease within one year of follow-up. CONCLUSION: High phosphatidylinositol-3-kinase-mediated signaling activity of the primary tumor, rather than KRAS/BRAF mutation status, was identified as a hallmark of poor metastasis-free survival in patients with locally advanced rectal cancer undergoing radical treatment of the pelvic cavity.

The epigenetics of breast cancer.

Epigenetic changes can be defined as stable molecular alterations of a cellular phenotype such as the gene expression profile of a cell that are heritable during somatic cell divisions (and sometimes germ line transmissions) but do not involve changes of the DNA sequence itself. Epigenetic phenomena are mediated by several molecular mechanisms comprising histone modifications, polycomb/trithorax protein complexes, small non-coding or antisense RNAs and DNA methylation. These different modifications are closely interconnected. Epigenetic regulation is critical in normal growth and development and closely conditions the transcriptional potential of genes. Epigenetic mechanisms convey genomic adaption to an environment thereby ultimately contributing towards given phenotype. In this review we will describe the various aspects of epigenetics and in particular DNA methylation in breast carcinogenesis and their potential application for diagnosis, prognosis and treatment decision.

Frequent aberrant DNA methylation of ABCB1, FOXC1, PPP2R2B and PTEN in ductal carcinoma in situ and early invasive breast cancer.

INTRODUCTION: Ductal carcinoma in situ (DCIS) is a non-invasive lesion of the breast that is frequently detected by mammography and subsequently removed by surgery. However, it is estimated that about half of the detected lesions would never have progressed into invasive cancer. Identifying DCIS and invasive cancer specific epigenetic lesions and understanding how these epigenetic changes are involved in triggering tumour progression is important for a better understanding of which lesions are at risk of becoming invasive. METHODS: Quantitative DNA methylation analysis of ABCB1, CDKN2A/p16INK4a, ESR1, FOXC1, GSTP1, IGF2, MGMT, MLH1, PPP2R2B, PTEN and RASSF1A was performed by pyrosequencing in a series of 27 pure DCIS, 28 small invasive ductal carcinomas (IDCs), 34 IDCs with a DCIS component and 5 normal breast tissue samples. FOXC1, ABCB1, PPP2R2B and PTEN were analyzed in 23 additional normal breast tissue samples. Real-Time PCR expression analysis was performed for FOXC1. RESULTS: Aberrant DNA methylation was observed in all three diagnosis groups for the following genes: ABCB1, FOXC1, GSTP1, MGMT, MLH1, PPP2R2B, PTEN and RASSF1A. For most of these genes, methylation was already present at the DCIS level with the same frequency as within IDCs. For FOXC1 significant differences in methylation levels were observed between normal breast tissue and invasive tumours (P < 0.001). The average DNA methylation levels were significantly higher in the pure IDCs and IDCs with DCIS compared to pure DCIS (P = 0.007 and P = 0.001, respectively). Real-time PCR analysis of FOXC1 expression from 25 DCIS, 23 IDCs and 28 normal tissue samples showed lower gene expression levels of FOXC1 in both methylated and unmethylated tumours compared to normal tissue (P < 0.001). DNA methylation levels of FOXC1, GSTP1, ABCB1 and RASSF1A were higher in oestrogen receptor (ER) positive vs. ER negative tumours; whereas methylation levels of FOXC1, ABCB1, PPP2R2B and PTEN were lower in tumours with a TP53 mutation. CONCLUSIONS: Quantitative methylation analysis identified ABCB1, FOXC1, PPP2R2B and PTEN as novel genes to be methylated in DCIS. In particular, FOXC1 showed a significant increase in the methylation frequency in invasive tumours. Low FOXC1 gene expression in both methylated and unmethylated DCIS and IDCs indicates that the loss of its expression is an early event during breast cancer progression.

[Chronic infectious mononucleosis]. / Hronicna infektivna mononukleoza.

INTRODUCTION: Chronic infectious mononucleosis is a clinical entity recognized 15 years ago with clearly defined serological criteria: high titres of IgG Epstein-Barr virus (EBV) virus capsid antigen (VCA), IgG EBV early antigen without IgG Epstein-Barr nuclear antigen (EBNA) antibodies. MATERIAL AND METHODS: This follow-up study lasted for 2 years and included 100 acute infectious mononucleosis patients who were investigated every 6 months. Apart from physical examination we evaluated history, complete blood count and liver function together with 5 commercial ELISA tests: IgM EBV VCA, IgG EBV VCA, IgG EB NA, IgG EBV EA and IgA EBV EA. RESULTS: Although malaise and fatigue with cervical lymphoadenopathy were the most frequent symptoms, their statistical significance was most established. All laboratory analyses were completely normal during the follow-up period, but there were four patients with acute hepatitis due to hepatitis A virus and adenoviruses. After 6 months of acute illness, two patients without IgG EB NA antibodies who were candidates for chronic disease, presented no other serological findings for chronic disease. It was confirmed that they had delayed serological response due to EBV infection, because one year later they had a completely normal immune status on EBV infection. CONCLUSION: Chronic infectious mononucleosis seems to be an extraordinary event after acute disease. This conclusion corresponds with literature reports of sporadic cases of this disease.

Serologic profile of Epstein-Barr virus infection in acute infectious mononucleosis.

The aim of our study was to determine classes of antibodies in different clinical forms of Epstein-Barr Virus (EBV) primary infections. The investigation included 100 patients with acute mononucleosis who were hospitalized at the Clinic for Infectious Diseases in Novi Sad during 1995-1997. Apart from clinical and laboratory parameters, 5 different ELISA assays were performed: IgM EBVVCA, IgG EBVVCA, IgG EBNA, IgA EBVEA and IgG EBVEA. All patients were IgM EBVVCA positive, only 42% IgG EBVVCA positive and 6% IgG EBNA positive. Antibodies due to EBVEA IgA were established in 58% of patients and IgG class in 41%. Serologic profile of early EBV primary infection was established in 25%, acute EBV primary infection in 69% and late EBV primary infection in 6%. A statistically significant difference regarding absolute lymphocyte count and serologic response to early antigens of EBV infection was established in patients with positive findings. Clinical findings in the throat correlated with serologic response to early EBV proteins. We didn't find any correlation due to duration of illness, fever, clinical forms of EBV primary infection and liver damage. Paul Bunnell test was positive only in 42% of our patients, with significantly higher number of negative results in groups of early and late EBV primary infections.

[Clinical importance of adenoviral infections]. / Klinicki znacaj adenovirusnih infekcija.

INTRODUCTION: The aim of this article was to point to ubiquitous adenoviral infections and to give a literature overview. Adenoviral infections present with a variety of clinical manifestations, causing many differential diagnosis problems. DIAGNOSIS AND EPIDEMIOLOGY: In our country diagnosis is made using the complement fixation test (CFT), which detects antibodies due to soluble group specific antigen. In acute infections, we need two sera samples given in 2 weeks period with 4-fold rise or fall in titers. Due to many asymptomatic infections which can given increased titer by CFT, many physicians think that patients have a persistent infection. Persistent adenoviral infections need not be accompanied by any special clinical symptomatology. However, adenoviral infections still play an important role in acute respiratory infections. The most severe respiratory infection is pneumonia which can be associated with acute respiratory distress syndrome and death. Disseminated adenoviral diseases appear in 2.5% of all adenoviral infections with the same percentage between immunocompetent and immunocompromised persons. In immunocompromised persons adenoviral infections manifest as haemorrhagic cystitis, fulminant or acute hepatitis or meningoencephalitis. THERAPY AND CONCLUSION: We still don't have a special treatment for these kinds of infections. Variety of antiviral drugs with controversial effects have been reported in management of adenoviral infections in immunocompromised persons. In USA adenoviral vaccine has been excluded from vaccine schedules among military personnel, but morbidity and the first two deaths due to these infections in the last 30 years reported by MMWR in 2000, may change this policy.