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E. Jusufovic, M. Košnik, J. Nurkić, N. Arifhodzic, M. Al‐Ahmad, L. Bulat-Kardum, M. Bećarević, M. Osmić et al.

Despite multistep efforts many asthma patients remain symptomatic. Anti-inflammatory activities of curcumin were shown. Aim was to analyse the add-on therapy with curcumin on inflammatory parameters, lung function, disease control and quality of life in asthma patients. 150 non-smokers with moderate partially controlled asthma were treated during 3 months with stable moderate dose of inhaled glucocorticoids and divided into three groups (n=50): curcumin group (receiving curcumin 500 mg per os twice daily), placebo and control group. Before study, sputum eosinophils (sEo), blood eosinophils (bEo), high sensitive C-reactive protein (hsCRP), predicted forced expiratory volume in first second (FEV1%), Asthma Control Test (ACT) and Asthma Quality of Life Questionnaire (AQLQ) were similar between groups. After study, FEV1%, ACT and AQLQ were improved in all groups, but these improvements were more prominent in curcumin group than in placebo and control. Additionally curcumin group only showed improvement in sEo, bEo and hsCRP. Furthermore, curcumin group showed also more frequent clinically significant improvement in ACT score (change>3) and in AQLQ score (change≥0.5) when compared to placebo and control. However, placebo and control showed similar distribution in FEV1%, ACT, AQLQ, hsCRP, sEo and bEo after study. This is the first placebo controlled and single-blind study to suggest that add-on therapy with curcumin could improve lung function, disease control and quality of life in moderate partially controlled asthma. Future studies may benefit from a larger sample size, longer study duration, double blind design, different dose of curcumin and/or improvements in oral bioavailability.

E. Jusufovic, M. Košnik, J. Nurkić, N. Arifhodzic, M. Al‐Ahmad, L. B. Kardum, M. Bećarević, M. Osmić et al.

Sputum eosinophils might predict response to inhaled corticosteroids (ICS) in patients with advanced chronic obstructive pulmonary disease (COPD). Induction of sputum requires expertise and may not always be successful. Aim was to investigate correlation and predictive relationship between peripheral blood eosinophils (bEo) and sputum eosinophils (sEo), and impact of peripheral blood eosinophilia on outcome of COPD exacerbation. 120 current smokers with COPD (GOLD group C) (57.4 ± 0.92 years, M/F ratio 1.4), with no blood (≥7% or >0.43x109/L) nor sputum (≥3%) eosinophilia, were treated with moderate dose of ICS and long-acting bronchodilatator during stable disease, but systemic corticosteroids and antibiotics during exacerbation. According to sputum eosinophilia (≥4%) during exacerbation, patients were divided into eosinophilic (n=45) and non-eosinophilic group (n=75). In stable disease, bEo and sEo were similar in both groups (p>0.05). During exacerbation, bEo and sEo were significantly higher in eosinophilic group (eosinophilic vs. non-eosinophilic: blood: 1.42 ± 0.39 x109/l vs. 0.23 ± 0.02 x109/l, p<0.001; sputum: 8% (4, 19) vs. 1% (0, 3), p<0.0001), but bEo correlated with sEo in both groups (eosinophilic: r=0.52, p<0.001; non-eosinophilic: r=0.25, p<0.05). Relative bEo predicted sputum eosinophilia (area under the curve=0.71, standard error=0.05; 95% confidence interval [CI] =0.61-0.81; p<0.001) and enabled identification of the presence or absence of sputum eosinophilia in 82% of the cases at a threshold of ≥4% (specificity=83.56%, sensitivity=93.83%, positive likelihood ratio=3.67). Eosinophilic group during exacerbation showed less frequent hospitalisations and shorter exacerbation (eosinophilic vs. non-eosinophilic: hospitalisations: 26.7% vs. 60.0%, p<0.001; duration of exacerbation (days): 8.1±0.35 vs. 10.13±0.31, p<0.0001). In COPD exacerbation, relative peripheral blood eosinophils ≥4% might identify sputum eosinophilia. Blood eosinophilia indicate better outcome of COPD exacerbation. Further investigations are needed to predict eosinophilic exacerbation in COPD patients, with prior absence of sputum or blood eosinophilia.

E. Jusufovic, M. Košnik, Azra Jusufovic, M. Bećarević, M. Al‐Ahmad, J. Nurkić, M. Osmić, Alma Nadarević et al.

Despite intensive treatment, considerable proportion of patients with asthma remains symptomatic. Anti-inflammatory activity of curcumin has been shown. Aim: analyse the impact of add-on therapy with curcumin in asthma patients on inflammatory parameters, lung function and asthma control. During 2 months, 100 non-smokers (46.8±12.4 years, F/M ratio 1.04) with moderate, partially controlled asthma were treated with moderate dose of inhaled glucocorticoids (IGK) with no changes in dose. Patients were divided into two groups (n=50): curcumin group receiving curcumin 500 mg per os twice daily and control group. Before study, sputum and blood eosinophils (Eo), blood neutrophils, high sensitive C-reactive protein (hsCRP), predicted forced expiratory volume in first second (FEV1%), Asthma Control Test (ACT) and Asthma Quality of Life Questionnaire (AQLQ) were similar between groups. After study, in curcumin group blood Eo count and hsCRP decreased, and FEV1, ACT and AQLQ increased significantly (before vs. after study: Eo: 5.9±0.6 vs. 4.1±0.4; hsCRP: 4.2±0.3 vs. 3.4±0.2; FEV1%: 77.7±0.8 vs. 83.9±0.5; ACT: 14.5 (6,19) vs. 18 (14,21); AQLQ: 3.4±0.2 vs. 4.1±0.2). There was no change in the control group. Compared to control curcumin group showed significantly lower blood Eo and hsCRP and higher FEV1% (curcumin vs. control: Eo: 4.1±0.4 vs. 5.4±0.5; hsCRP: 3.4±0.2 vs. 4.0±0.3; FEV1%: 83.9±0.5 vs. 78.3± 0.8), and improved ACT and AQLQ (ACT change>3: 72% vs. 28%; AQLQ change>0.5: 54% vs. 32%) after study. Add-on therapy with curcumin in patients with moderate partially controlled asthma seems to improve response to IGK regarding lung function, asthma control and quality of life. Further placebo controlled trials are needed.

Š. Umihanić, Fuad Brkić, M. Osmić, Šefika Umihanić, Suad Imamovic, S. Kamenjaković, Samir Hodžić

Introduction: Surgical and medical treatments of nasal obstruction are a common parts of otolaryngologist practice. The definitive treatment of deviated nasal septum is septoplasty. Aim: In this study was to evaluate the values of subjective parameters, and active anterior rhinomanometry parameters prior and three months after the septoplasty. Patients and Methods: We analyzed the subjective parameters (“NOSE” scale), the active anterior rhinomanometry parameters according to International Committee on Standardization of Rhinomanometry, on 40 patients. Thirty healthy adult volunteers participated belonged to the control group. None of the patients or healthy volunteers had previous history of nasal surgery or active rhinological disease. Results: The post-operative improvement in symptoms of nasal obstruction obtained in 92,5% patients and improvement parameters of the active anterior rhinomanometry in 42,5% patients. Conclusion: The correlation between the findings with rhinomanometry and subjective sensation of nasal patency remains uncertain. There still seems to be only a limited argument for the use of rhinomanometry for quantifying surgical results. Three months postoperative findings are very early results to interpret the permanent effects.

Growing body of evidence suggests that molecular markers are an important prognostic marker for non-small lung cancer (NSCLC). Using targeted therapy based on these markers leads to improved outcomes in lung adenocarcinoma. However, progress of targeted therapy in squamous lung cancer is still modest. p16(ink) protein acts as tumor suppressor and vascular endothelial growth factor (VEGF) promotes tumor angiogenesis. Purpose of this study was to evaluate the difference in p16(ink4) and VEGF expression between squamous and adenocarcinoma of the lung; to evaluate the relationship of p16(ink4) and VEGF expression to survival outcomes in NSCLC patients, and the difference of their prognostic values between squamous and adenocarcinoma subtypes. 100 NSCLC patients (50 squamous and 50 adenocarcinoma) and 80 healthy individuals were included. p16(ink4) and VEGF proteins were immunohistochemicaly detected on formalin-fixed tissues. One- and 2-year progression-free survival (PFS) and overall survival (OS) were observed. p16(ink4) expression was significantly lower in squamous type compared to adenocarcinoma. In both squamous and adenocarcinoma, high VEGF expression correlated with worse 1-year PFS and OS, but only with worse 2-year PFS. Low p16(ink4) expression correlated with worse 1- and 2-year PFS, as well as OS, in both NSCLC subtypes. In squamous lung cancer p16(ink4) expression was an independent negative prognostic marker. Our study confirms the difference of p16(ink4) protein expression in squamous and adenocarcinoma of the lung. Besides anti-VEGF therapy, the regulation of p16(ink4) expression could have a therapeutic potential in NSCLC, especially in squamous lung cancer.

ABSTRACT Introduction: Lung cancer is most common cause of cancer-related mortality worldwide. Non-small-cell lung carcinoma (NSCLC) is disease with very low 5-year relative survival rate. For patients with non-small cell lung cancer, roles of current treatments are to prolong survival time and to improve quality of life. Aim: The aim of the work was to compare values of Glasgow Prognostic Score (GPS) before application of the chemotherapy medication with response to chemotherapy and toxic side effects associated with chemotherapy in patients treated with cisplatin-etopozid (PE) and cisplatin-gemcitabin (PG) in stages IIIb and IV of NSCLC. Testing role of Glasgow Prognostic Score as a possible predictor of response to therapy and toxic side effects of chemotherapeutic protocol was another aim of this work. Patients and methods: This prospective study included 60 patients in stages IIIb or IV of NSCLC, with ECOG ≤ 2. The patients were divided in two groups. First group contained 30 patients treated with chemotherapeutic protocol using cisplatin-etopozid (PE), and the same number of patients in the second group were treated with cisplatin-gemcitabin (PG). Results: Glasgow Prognostic Score (GPS) evaluation before the chemotherapy inclusion showed values of 1 (43.30:53.30), then 2 (40.00:36.70) and the lowest 0 (16.70:10.00) which supports the pathological values of GPS in developed lung cancer, i.e. most patients had pathological GPS value in both protocols (83.30:90.00). Monitoring of toxic side effects and response to chemotherapy was done after each cycle of treatment. Discussion: Results of this study revealed importance of GPS in selection of patients for treatment with chemotherapy. Patients with lower values of GPS treated using PE chemotherapeutic protocol had weaker response to therapy. Conclusion: Coefficient of correlation for therapy response in both chemotherapeutic protocol, compared with values of GPS before treatment, were not statistically significant, therefore GPS cannot be considered as a predictor of therapeutic on chemotherapy.

A. Ustamujić, H. Zutić, Z. Dizdarević, V. Čukić, Irma Sladic, J. Maglajlic, M. Osmić, Jasmina Abazovic

Multidrug-resistant tuberculosis (MDR-TB) defined as TB caused by strains of Mycobacterium tuberculosis that are resistant to at least isoniazid and rifampicin. The aim of this paper was to describe the resistance patterns of MDR-TB in FBH previously treated 121) in 2000;1184 (1054;129) in 2001; 1036 (936;100) in 2002; 1042 (951;91) in 2003; 1125 (1048; 77) in 2004; 769 (692;77) in 2005; 908 (827;81) in 2006; 951 (847;104) in 2007; 518 (471;47) in 2008; 581 (529;52) in 2009. MDR-TB among never-treated cases: 1 (0.11%) in 2000; 2 (0.19%) in 2001; 4 (0.42%) in 2002; 1 (0.10%) in 2003; 4 (0.38%) in 2004; 4 (0.57%) in 2005; 2 (0.24%) in 2006; 7 (0.82%) in 2007; 3 (0.63%) in 2008; 0 (0.0%) in 2009. MDR-TB among previously-treated cases: 2 (1.65%) in 2000; 7 (5.42%) in 2001; 9 (9.0%) in 2002; 1 (1.09%) in 2003; 6 (7.79%) in 2004; 5 (6.49%) in 2005; 3 (3.70%) in 2006; 10 (9.61%) in 2007; 9 (19.14%) in 2008; 1 (1.92%) in 2009. Conclusion: Data from FB&H show relatively low prevalences of MDR-TB during ten years.The prevalence of MDR-TB remains low at 0.57% - 0.82% among newly detected cases and 9.61% - 19.14% among previously detected cases.Recent data also indicate a further desrease in MDR-TB. This decrease may likely be the result of well implemented DOTS.Establishing reference laboratory facilities with adequate capacity to supervise DST and surveillance activities in the country is a critical step in MDR-TB control and care.

Fejzo Džafić, A. Čustović, Sead Jamakosmanovic, Damir Sabitović, Indira Sejranic, M. Osmić, Suad Dedic, Kemija Prohic et al.

Introduction: Asthma is a chronic inflammatory airway disease, with more present allergic component who cause disease. Pacient and Metods: In this study was included 35 patients who had been bronchial asthma whom was made total IgE determined by nefelometric metod and skin test by Prick metod. Subjects which had increased values of IgE, had been tested for fecal parasites . Subjects wich was positiv for scin allergens was tested for specific IgE on Hytec 288 instrument with ELISA metod. Results: Folowing resaults was obtained: 57.14% (20) of subjects had increased values of total IgE, while 42.86% (15) had normal total IgE. All patients with increased values of total IgE were tested negative for fecal parazites. Percent conform Prick tests and specific IgE was for house dust 54.55%, ragweed 53.85%, grass pollen 45.45%, Dermato-phagoides Pteronyssinus 43.75%, Pollen trees 25.00%. Conclusion and Discussion: Allergic bronchial asthma capture big percent in patients with bronchial asthma. The most frequent allergen was house dust.

M. Nurkić, A. Imamovic, F. Numanović, M. Gegić, M. Osmić, Selma Hadzihafizbegović

Aim of this research was to investigate diagnostic value of discovering of antibody on A60 antigen in patients who were tested for presents of Mycobacterium tuberculosis in there biological samples. We tested a samples of sputum, gastric juice, urine, cerebrospinal fluid and punctate from group of 353 patients who were suspected for tuberculosis. In all patients we were looking for antibodies classes A60 antigen. We used immune chromatographic "Hexagon TB" test, Germane company "Human Geselschaft fur Biochemica und Diagnostica". From 353 patients we found 58 (16.43%) patients with positive BK, 79/22,38%) patients with positive Lowenstein culture and 122 (34,55%) patients with antibody in sera on A60 antigen. Patients who were BK and Lowenstein positive, have had antibody in 94,23% cases, Patients who were BK negative and Lowenstein positive have had antibodies in 70,37% cases and patients who were BK negative and Lowenstein negative have had antibody in 19,03% cases. Patients with BK positive and Lowenstein negative results have had antibody in 50,00% cases. Difference between results is significant (p<0,01). From 122 patients with positive antibodies, 52 were BK positive and 68 have had positive Lowenstein cultures. From 231 patients with no antibody, just 6 were BK positive and 11 Lowenstein positive. In 62 patients with positive antibodies, were BK and Lowenstein negative. We confirmed that antibody on A60 antigen in microbiological positive patients are more often then in microbiological negative patients (p<0,001).

M. Nurkić, A. Imamovic, F. Numanović, M. Gegić, M. Osmić, Selma Hadzihafizbegović

Aim of this work is to show the level of prevalence of patients infected with resistant strains Mycobacterium tuberculosis in Canton Tuzla. In the period of 1996-2003 year we tested 87,408 samples of different materials on existence of Mycobacterium tuberculosis. Among all samples there were 66,128 sputum, 14,599 urines, 3,817 gastric juice, 1,174 materials from broncholavage and 547 other samples. Microscopically it was found 4,380 smear-positive samples and 6,365 samples were positive on Loewenstein medium. Positive sputum had 1,917 patients, and positive culture had 3,018 patients. Resistance test was done on streptomycin, isoniazid, rifampicin and ethambutol with standard proportional method for 2,662 patients. Totally sensibile were 2,570 or 96.54%, and restant were 92 or 3.46% patients. Patients infected with mono-drug resistant strains Mycobacterium tuberculosis were 71 or 2.67%, and poli-drugs resitant 21 or 0.78%. There were 16 patients or 0.60% infected with multi-drugs resistant strains. Time of bacteriological negativization for the patients infected with resistant strains was in the average 8.19 months, for the patients infected with mono-drug resistant strains was 2.75 months and for infected with multi-drugs resistant strains was 32 months. It is concluded that region of Canton Tuzla has high level of bacteriological prevalence but low level of prevalence of patients infected with resistant strains Mycobacterium tuberculosis in the this period of time, and it is significantly lower then earlier periods, thanks to national tuberculosis control program and system of directly observed treatment.

Our objective was to establish if mother's age affects the anthropometric properties their 11 and 16 years old sons, and if the boys' BMI is satisfactory. Cross-sections, questionnaires, and statistics were used for data processing BMI (kg/m2) was presented according to the scale Quetelet's index nutritional status. Twelve anthropometric properties were researched. It was established that mother's age affects anthropometric properties in adolescent boys. The younger mothers' boys come to puberty with significantly higher mean values for most anthropometric parameters. In the course of adolescent jump, older mothers' boys have significantly higher anthropometric measures in comparison to their age boys delivered by younger mothers. After the completion of their intensive growth and development anthropometric measures in both category boys are equal or insignificantly higher in younger mothers' sons. Mother's age affects their sons' anthropometric properties of growth and development, particularly in prepuberty and puberty. After puberty that effect is not significant. According to BMI, the boys coming from the researched region make the group of underfed children. That is probably the outcome of bad living conditions, irregular and insufficient diet, stress, etc. in the course of four year aggression on Bosnia and Herzegovina.

J. Hadžihalilović, R. Hadziselimovic, R. Terzić, E. Hasković, A. Ahmić, Amir H Halilović, M. Osmić, Šaćira Mešalić et al.

Dynamics of growth of male children and youths from the Region of Tuzla influenced by some exogenous factors was researched by a corresponding analysis of the sample which included 751 tested individuals, aged from 11 to 17 years. The analysis performed is primarily based on the scientific elaboration of the registered state in two time-points (1996 and 1999) in the tested part of broader population. This research involved the period of four-year aggression on Bosnia and Herzegovina, taking into consideration the fact that the tested persons spent one period of their growth and development in extremely bad wartime living conditions. By quasicanonic correlative analysis it was established that the next factors participated in connection of variables of both sets (initial and final measurements): mother's standard, total mother's and father's standard of living, mother's age and sequence of births participated to some less extent in connection of both sets of variables. Anthropometric variables that had most significant impact of both sets of variables are: length parameters, body mass, width parameters, circumferences had somewhat less impact, while indexes of head and sitting height had the least impact on this connection.

J. Hadžihalilović, A. Redžić, R. Terzić, Fatima Jusupović, Amir Hadzihalilović, M. Osmić

Birth order and its effect on growth and development of children and youths have rarely been studied so far. The objective of this research was an analysis of the birth order effects on some anthropometric properties of the boys 11-16 years old. The sample consisted of 748 boys from the Tuzla region. As the sample included very few boys born as the third, forth, or fifth child, we decided to consider only the differences in the mean values for some anthropometric parameters between the groups of the first- and the second-born. Measurements were taken according to IBP and the following parameters were investigated: body height, body mass, chest circumference, upper arm circumference, upper leg circumference, sitting height, arm length, leg length, pelvis width, shoulders width, length and width of head. We established that in most generations the firstborn boys have larger mean values for most anthropometric variables in comparison to the second-born.

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