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EDITORIAL BOARD Editor Mensura Kudumovic Secretaries Dzenana Jusupovic Azra Kudumovic Technical editor Eldin Huremovic Lectors Mirnes Avdic Adisa Spahic Members Borut Poljsak (Ljubljana) Josip Vincelj (Zagreb) Budimka Novakovic (Novi Sad) Dragana Stoisavljevic (Banja Luka) Bakir Mehic (Sarajevo) Mirsada Hukic (Sarajevo) Slavica Ibrulj (Sarajevo) Farid Ljuca (Tuzla) Emina Nakas-Icindic (Sarajevo) Fatima Jusupovic (Sarajevo) Amira Duric (Sarajevo) Aida Hasanovic (Sarajevo) Dijana Avdic (Sarajevo) Ago Omerbasic (Sarajevo) Address of the Sarajevo, Bolnicka BB Editorial Board phone/fax 00387 33 640 407 [email protected] Published by DRUNPP, Sarajevo Volume 2 Number 4, 2008 ISSN 1840-2291 EBSCO Publishing (EP) USA http://www.epnet.com Health MED Volume 2 / Number 4 / 2008 Journal of Society for development of teaching and business processes in new net environment in B&H Sadržaj / Table of Contents Estimation of exhumed male persons’ stature based on bayesian analysis Procjenjivanje visine ekshumiranih osoba muškog spola na osnovu bayes-ove analize ................................... 187-191 Anisa Masovic, Nermin Sarajlic * * * Liver function in patients with diabetes mellitus type 2 and hyperlipidemia Funkcija jetre u oboljelih od dijabetes melitusa tip 2 i hiper- lipidemijom .......................................................... 192-197 Farid Ljuca, Esad Alibasic, Sabina Nuhbegovic * * * Dietary factors as protectors or predictors for lung cancer: survey control study Faktori ishrane kao zaštitni faktori ili faktori rizika za karci- nom pluća: pregledno kontrolno istraživanje ..... 198-205 Suvad Dedic, Nurka Pranjic * * * Socio-Demographic and Health Characteristics of Fre- quent Attender in Family Practice Sociodemografske i zdravstvene karakteristike čestih kori- snika u porodičnoj medicini .............................. 206-213 Zaim Jatic, Dzanana Jatic * * * Basal cell carcinoma of orbital region Bazocelularni karcinom orbitalne regije .............. 214-218 Adi Rifatbegovic, Ermina Iljazovic, Nedret Mujkanovic, Azra Pasic, Emir Halilbasic, Mufid Burgic * * * Effects of Specific Forms of Extramedullary Fixation in Treatment of Diaphyseal Small Bone Fractures Efekti specifičnih oblika ekstramedularne stabilizacije na sanaciju prijeloma dijafiza malih kostiju ......... 219-224 Zoran Hadziahmetovic, Narcisa Vavra – Hadziahmetovic * * * Adipokines and Acute Coronary Syndrome Adipokini i Akutni Koronarni Sindrom ............. 225-233 Emina Nakas-Icindic, Amina Valjevac, Asija Zaciragic * * * Relation of disseased towards feding aditions vitamins and minerals Odnos bolesnika prema prehrambenim dodacima vitamina i minerala ............................................................ 234-238 Fatima Jusupovic, Arzija Pasalic, Jasmina Mahmutovic, Dijana Avdic, Azra Kudumovic
Transcript
Page 1: Health Journal

EDITORIAL BOARD

Editor Mensura Kudumovic Secretaries Dzenana Jusupovic Azra Kudumovic Technical editor Eldin Huremovic Lectors Mirnes Avdic

Adisa Spahic Members Borut Poljsak (Ljubljana) Josip Vincelj (Zagreb) Budimka Novakovic (Novi Sad) Dragana Stoisavljevic (Banja Luka) Bakir Mehic (Sarajevo) Mirsada Hukic (Sarajevo) Slavica Ibrulj (Sarajevo) Farid Ljuca (Tuzla) Emina Nakas-Icindic

(Sarajevo) Fatima Jusupovic (Sarajevo) Amira Duric

(Sarajevo) Aida Hasanovic (Sarajevo) Dijana Avdic (Sarajevo) Ago Omerbasic (Sarajevo)

Address of the Sarajevo, Bolnicka BB Editorial Board phone/fax 00387 33 640 407

[email protected] Published by DRUNPP, Sarajevo Volume 2 Number 4, 2008 ISSN 1840-2291

EBSCO Publishing (EP) USAhttp://www.epnet.com

HealthMEDVolume 2 / Number 4 / 2008

Journal of Society for development of teaching and business processes in new net environment in B&H

Sadržaj / Table of Contents

Estimation of exhumed male persons’ stature based on bayesian analysisProcjenjivanje visine ekshumiranih osoba muškog spola na osnovu bayes-ove analize ................................... 187-191Anisa Masovic, Nermin Sarajlic

* * *Liver function in patients with diabetes mellitus type 2 and hyperlipidemiaFunkcija jetre u oboljelih od dijabetes melitusa tip 2 i hiper-lipidemijom .......................................................... 192-197Farid Ljuca, Esad Alibasic, Sabina Nuhbegovic

* * *Dietary factors as protectors or predictors for lung cancer: survey control studyFaktori ishrane kao zaštitni faktori ili faktori rizika za karci-nom pluća: pregledno kontrolno istraživanje ..... 198-205Suvad Dedic, Nurka Pranjic

* * *Socio-Demographic and Health Characteristics of Fre-quent Attender in Family PracticeSociodemografske i zdravstvene karakteristike čestih kori-snika u porodičnoj medicini .............................. 206-213Zaim Jatic, Dzanana Jatic

* * *Basal cell carcinoma of orbital regionBazocelularni karcinom orbitalne regije ..............214-218 Adi Rifatbegovic, Ermina Iljazovic, Nedret Mujkanovic, Azra Pasic, Emir Halilbasic, Mufid Burgic

* * *Effects of Specific Forms of Extramedullary Fixation inTreatment of Diaphyseal Small Bone FracturesEfekti specifičnih oblika ekstramedularne stabilizacije nasanaciju prijeloma dijafiza malih kostiju ......... 219-224Zoran Hadziahmetovic, Narcisa Vavra – Hadziahmetovic

* * *Adipokines and Acute Coronary SyndromeAdipokini i Akutni Koronarni Sindrom ............. 225-233Emina Nakas-Icindic, Amina Valjevac, Asija Zaciragic

* * *Relation of disseased towards feding aditions vitamins and minerals Odnos bolesnika prema prehrambenim dodacima vitamina i minerala ............................................................ 234-238Fatima Jusupovic, Arzija Pasalic, Jasmina Mahmutovic, Dijana Avdic, Azra Kudumovic

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HealthMEDSadržaj / Table of Contents

Volume 2 / Number 4 / 2008

Journal of Society for development of teaching and business processes in new net environment in B&H

Does serum C-reactive protein concentration correlate with blood pressure values in patients with probable Alzheimer’s disease?Da li koncentracija C-reaktivnog proteina u serumu korelira sa vrijednostima krvnog pritiska kod pacijenatasa mogućom Alzheimerovom bolesti? ............... 239-245Asija Zaciragic, Amina Valjevac, Orhan Lepara,Azra Alajbegovic

* * *The effects of spirulina platensis on biohumoral markers of renal function in gentamicin-induced acute tubular ne-crosis in ratsEfekti spiruline platensis na biohumoralne markere bubrežne funkcije kod gentamicinom-uzrokovane akutne tubularne ne-kroze kod štakora ....................................................... 246-252Nesina Avdagic, Esad Cosovic, Emina Nakas-Icindic, Zakira Mornjakovic, Asija Zaciragic, Almira Hadzovic-Dzuvo

* * *Anthropometric values for boys aged 14 – 15 years who actively train basketball in comparison to boys of the same age who do not train any sportsAntropometrijske vrijednosti kod dječaka uzrasta 14 – 15 godina koji aktivno treniraju košarku u odnosu na dječake iste dobi koji nemaju sportskih aktivnosti .......... 253-264Dijana Avdic, Fatima Jusupovic, Mensura Kudumovic

* * *Methods of removing infectious and laboratory’s waste in clinic centersMetode uklanjanja infektivnog i laboratorijskog otpada u kliničkim centrima .............................................. 265-272Aida Vilic-Svraka, Zlatko Vucina,Aida Filipovic-Hadziomeragic, Mirsada Mulaomerovic

* * *Repulsing of harmful rodents in specific environmentalconditions of pharmaceutical factorySuzbijanje štetnih glodavaca u specifičnim uvjetima na po-dručju farmaceutske tvrtke ................................. 273-282Suad Habes, Sandra Mramor-Muzevic, Sefkija Muzaferovic

* * *The relationship between myocardial viability and col-lateral circulationOdnos vijabilnosti miokarda ikolateralne cirkulacije ........................................ 283-287Aida Hasanovic

Application of cognitive behavior therapeutic techniques for prevention of psychological disorders in police officersPrimjena kognitivno-bihevioralnih psihoterapijskihtehnika u prevenciji psihičkih poremećajakod policajaca .................................................... 288-292Sibila Sijaric-Voloder, Dzejna Capin

CASE REPORTTrisomy 18 – Edwards’ syndromeTrisomija 18 – Edwardsov sindrom ..................... 293-297Izeta Aganovic-Musinovic, Mirela Djurovic, Zimka Seremet

PROFESSIONAL PAPERSInfluence of malignant disease on physical and mental he-alth in patients with oncology diseaseUticaj malignog oboljenja na tjelesno i duševno zdravljeonkoloških bolesnika ................................................. 298-304Amela Dzubur, Dragana Niksic, Esad Pepic,Amna Pleho Kapic

PREVIEW PAPERSOsteophorosis, how prevent and how treat itOsteoporoza, kako spriječiti, kako liječiti ....... 305-306Dijana Avdic, Edin Buljugic

* * *

Instructions for the autors ............................... 307-308

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Estimation of exhumed male persons’ stature based on bayesian analysisPROCJENJIVANJE VISINE EKSHUMIRANIH OSOBA MUŠKOG SPOLA NA OSNOVU BAYES-OVE ANALIZEAnisa Masovic, Nermin Sarajlic

Institut of Forensic Medicine, Medical School, University of Sarajevo, Bosnia and Herzegovina

Summary

The basis in the process of identifying ex-humed skeletal remains is the identification of abiological profile and, within it, stature estimationas one of the most important parameters. Since 1996, the estimation of war victims’ stature in the territory of Bosnia and Herzegovina has been carried out based on formulae obtained through research on American population. In this study, stature estimation was carried out by applying a Bayesian analysis on 105 exhumed and identifiedmale persons from the territory of the northwest Bosnia, namely of 78 left humeri, 105 left femurs, 96 left tibia and 80 left fibulas. 369 persons fromthe Sarajlić’s study were used as a reference sam-ple. Stature estimation formulae were developed by applying the Bayesian analysis and were com-pared with the formulae obtained by Ross and Konigsberg and Sarajlić and associates. Results show that the formulae developed in this study are more precise for the estimation of exhumed per-sons’ stature than the models compared, except for the formula for tibia, where the Sarajlić’s formula proved to be more accurate.

Key words: Forensic anthropology, stature es-timation, Bosnian population, Bayesian analysis.

Sažetak

U procesu identifikacije ekshumiranih posmr-tnih ostataka osnovu predstavlja određivanje bio-loškog profila, u sklopu kojeg je i procjenjivanjevisine kao jedan od najvažnijih parametara. Od 1996 godine na području Bosne i Hercegovine procjenjivanje visine ekshumiranih žrtava rata, vr-šeno je na osnovu formula dobijenih ispitivanjem na američkoj populaciji. U ovoj studiji procjenji-vanje visine je izvršeno primjenom Bayes-ove analize na 105 ekshumiranih i identificiranih oso-ba muškog spola sa područja sjevero-zapadne Bo-sne, i to 78 lijevih humerusa, 105 lijevih femura, 96 lijevih tibija i 80 lijevih fibula. Kao referentniuzorak korišteno je 369 osoba iz Sarajlićeve stu-dije. Primjenom Bayes-ove analize su razvijene formule za procjenjivanje visine, koje su kom-parirane sa formulama dobijenim po Ross-ovoj i Konigsberg-u, te Sarajliću i suradnicima. Rezulta-ti su pokazali da formule razvijene u ovoj studiji preciznije procjenjuju visinu ekshumiranih osoba u odnosu na komparirane modele, izuzev formu-le za tibiju, gdje se Sarajlićeva formula pokazala tačnijom.

Ključne riječi: forenzička antropologija, pro-cjena visine, bosanska populacija, Bayes-ova ana-liza

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Introduction

In the course of the recent war in Bosnia and Herzegovina (1992-1995), more than 30,000 per-sons went missing and the search for more than 10,000 persons is still going on.

In addition to DNA analysis, identification alsoimplies the designing of a biological profile, whichimplies the determining of sex and the estimati-on of age and stature. Even today identificationis greatly hampered by a large number of mixed skeletal remains exhumed from mass graves and especially from secondary and tertiary mass gra-ves (1,2). Stature estimation is one of the most im-portant procedures in the forensic-anthropologist analyses of skeletal remains.

Since 1996, the Trotter and Gleser’s formulae (3) developed from American Whites have been used to estimate the stature of the Bosnia and Her-zegovina population, although the authors them-selves warned about the injudicious use of popu-lation specific formulae on other populations, aswell as about the obligatory taking into account a secular trend in the development of a population (4).

The development of a sceleton is influenced bymany factors which make differences in the pro-portion of bones in different geographical areas and it is these features that provide for a possi-bility to establish differences among populations, groups and individuals (5).

Stature estimation formulae developed from the Bosnia and Herzegovina population were be-ing obtained by a regressive analysis method (6), which is considered to give more distinctive vari-ations as the distance from the mean value is gre-ater, thereby contributing to more imprecise esti-mation of the stature of small and tall persons. In addition to the aforementioned, the length of long limb bones were being obtained through readings of x-ray photographs of cadavers, which also co-uld have influence on obtaining of precise results(6). Therefore, a need arose for the development of formulae that would give smaller deviations and more precise data. In 2002, Ross and Konigs-berg presented new formulae for estimation of the stature of people from the Balkans by applying a Bayesian analysis and using bones of unidentifi-ed Bosnians and Croats, victims of the recent war.

In their study, they used samples from 545 whi-te persons from World War II, using these data as reference samples, as well as from 177 exhumed men killed during war operations in the territory of Bosnia and Herzegovina and Croatia (7). As they did not have data on the stature of the exhu-med persons while still alive, they were using data from literature (8).

Everything mentioned thus far indicates to the necessity of developing models for estimating ex-humed male persons’ stature based on a Bayesian analysis and their correlation with the formulae obtained by Sarajlić and associates (6) and Ross and Konigsberg (7), which was the main objective of this study.

Materials and methods

The research included 105 exhumed and identi-fied male persons from the territory of the northw-est Bosnia at the age ranging from 19 to 65 years. Since not all the persons had all the bones, the fol-lowing was used for research: 78 left humeri, 105 left femurs, 96 left tibia, 80 left fibulas. Maximumlengths of all four bones were measured (9).

Due to an insignificant difference in the lengthof the left and right side of the skeleton, the left side was arbitrarily taken for the research. The stature of persons while still alive was obtained based on antemortem data collected from their fa-milies.

Data on the length of bones and the stature of 369 exhumed and identified persons from the Sa-rajlić and associates’ study were taken as a refe-rence sample (10).

The data were processed by applying descri-ptive statistics, regressive-correlative analysis and models as per Bayes’ Theorem, based on which formulae for stature estimation were developed on the basis of the length of long limb bones.

The prediction based on the Bayesian analysis from this study was compared with the models presented by Ross and Konigsberg (7) and Sa-rajlić and associates (10), through calculation of non-explained variability. A lower non-explained variability meant the prediction model was more reliable and more accurate.

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Results

The formula, which, as per Bayes’ Theorem, is applied for stature estimation based on the length of long bones, is as follows (7)

where:α and β – are coefficients of a simple linear

regressive model with stature as an independent variable and the length of bones as a dependant variable in a reference sample

- is mean stature in an analysed sample

- is a stature variant in an analysed (target) sample

- is a stature variant in a reference sampler - is a coefficient of a simple linear

correlation between the stature and the length of a bone for a reference sample

lb - actual value of the length of a bone for an observed case

Based on the above presented application of the Bayes’ Theorem, formulae for predicting stat-ure were developed based on the length of long bones (in centimetres) for humerus (LH), femur (LF), tibia (LT) and fibula (Lfib), with the indica-tion of standard error in estimation (+/-):

ŝ = 55.77 + 3.59 LH +/- 4.52ŝ = 55.75 + 2.663 LF +/- 3.62ŝ = 70.66+2.744 LT +/- 3.58ŝ = 61.58 + 3.018 Lfib +/- 3.94

Deviations of performed estimations from original measurings from the sample are graphi-cally presented by dispersion clouds.

LH: left humerusGraph 1. Comparison of original data with esti-mation for humerus

LF: left femurGraph 2. Comparison of original data with esti-mation for femur

LT: left tibiaGraph 3. Comparison of original data with esti-mation for tibia

Lfib: left fibulaGraph 4. Comparison of original data with esti-mation for fibula

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In order to numerically test whether the predicti-on based on the Bayesian analysis from this study gives more reliable (more precise) data compared to the models presented by Ross and Konigsbergu (7) and Sarajlić (10), a non-explained variability or mean square deviation (MQD) was calculated as per the following model:

non-explained variability = ∑ (soriginal – ŝobtained through estimation)2

number of actual measurings

The obtained expression for the non-explained variability is in direct relationship with the devia-tion in estimation from the original measuring. A lower non-explained variability means the predi-ction model is more reliable and more accurate.

Predictions based on humerus gave the follow-ing results in terms of non-explained variability: ac-cording to the prediction from this study – 231.621, and according to Ross and Konigsberg 451.569.

Predictions based on femur gave the following results in terms of non-explained variability: ac-cording to the prediction from this study – 1662.7, according to Ross and Konigsberg – 2088.19, and according to Sarajlić – 1885.18.

Predictions by tibia gave the following results in terms of non-explained variability: according to the prediction from this study – 275.506, ac-cording to Ross and Konigsberg – 563.394, and according to Sarajlić – 196.558.

Predictions based on fibula gave the followingresults in terms of non-explained variability: ac-cording to the prediction from this study – 114.5-24, and according to Sarajlić 117.302.

Discussion

In this research, estimation of exhumed male persons’ stature was carried out based on the length of long bones of both extremities. The male sex was included as the largest number of missing per-sons in Bosnia and Herzegovina is of male sex.

This way, formulae for stature prediction were obtained based on a Bayesian analysis. When ap-plying formulae on samples used in this study, the standard error was: for humerus (4.53), femur (3.62), tibia (3.58), fibula (3.94). It follows fromthe aforementioned that the smallest standard er-

ror was obtained when applying the formula using the tibia length, which means that the use of tibia gives most precise results in stature estimation. The greatest standard error and, consequently, the least precise stature estimation was obtained when applying the formula using the humerus length for stature estimation, which is in compliance with to-dates researches (3, 7) indicating that stature esti-mation is more precise when the length of long limb bones is used.

In order to test whether the prediction based on the Bayesian analysis and resulting from this stu-dy gives more precise data on stature estimation compared to other prediction models, a non-ex-plained variability was calculated.

When prediction based on humerus was con-cerned, the comparison of the model from this study with the Ross and Konigsberg’s model sho-wed that the non-explained variability is smaller when stature estimation is carried out based on the model from this study and it amounts 231,621 compared to the Ross and Konigsberg’s model in which it amounts 451,569. The comparison with the Sarajlić and associates’ model was not possi-ble, because they did not present formulae for hu-merus. Although Ross and Konigsberg used a Ba-yesian analysis in their study, deviations are evi-dent when compared with this study in which the same model was used. The difference in results is probably the consequence of parameters they used in their study. They made a study on the Balkan population and had at their disposal the length of the bones of exhumed persons from Bosnia and Herzegovina and Croatia. However, they did not have data on the actual height of the exhumed per-sons for whom they had data on the length of the bones and used data from literature (8) instead. They used data on American Whites from World War II as a reference sample. Differences among populations, secular trend in the development of a population and, consequently, probable non-re-levance of data they applied as reference samples are possible reasons for greater deviations in the application of their formulae compared to the re-sults in this study.

Identical results were obtained when predicting stature based on the femur length. The non-explai-ned variability as calculated as per the model from this study was 1662.7, as per the Sarajlić and asso-

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ciates’ model - 1885.18, and as per Ross and Ko-nigsberg’s model - 2088.19.

Predictions based on tibia, when comparing models from this study with the models developed by Ross and Konigsberg and Sarajlić and associa-tes, show that the lowest values of non-explained variability were obtained by using the Sarajlić and associates’ model, they were followed by those based on this study and the greatest were those using the Ross and Konigsberg model. A possible explanation for the obtained results of comparison for tibia, where the formula developed by Sarajlić and associates proved to be the most precise one, perhaps lies in the fact that tibia is a bone that is most difficult to measure. X-ray measurings of thetibia length, which were used by Sarajlić and as-sociates, could have been more precise than the measuring of the tibia length carried out on an osteometric table and used in this study.

The comparison of results for fibula was possi-ble only with the formulae developed by Sarajlić and associates, as Ross and Konigsberg did not use this bone. The lowest values of non-explained variability and, consequently, the most precise re-sults in stature estimation were obtained when ap-plying the formulae developed in this study.

The obtained results confirm that the formulaeobtained by applying a Bayesian analysis on Bo-snia and Herzegovina population give statistically more precise results in the estimation of the stature of exhumed male persons in Bosnia and Herzego-vina than the previously derived Ross and Konigs-berg’s models on the Balkan population (7) and Sarajlić’s models, with the utilization of regressi-on analysis (10).

Conclusion

The results of research show that stature esti-mation based on the length of humerus, femur and fibula by applying Bayes’ Theorem is more preci-se compared to the models developed by Sarajlić and associates, with the utilization of the regressi-on analysis. Only stature estimation based on the length of tibia and utilizing regressive analysis gi-ves more precise results than this research.

All formulae developed in this study give more precise estimation of exhumed persons’ stature

compared to the formulae developed by Ross and Konigsberg on the Balkan population, which indi-cates to the necessity of developing adequate mo-dels specific for a population.

Literature

1. Zečević D. i suradnici. Sudska medicina i deontolo-gija, 4. obnovljeno i dopunjeno izdanje (Zečević D and Associates. Forensic Medicine and Deontolo-gy, 4th reprinted and supplemented edition), Zagreb, 2004; p 189-191.

2. Sigel J, Knupfer G, Saukko P. Encyclopedia of Fo-rensic Sciences, Three- Volume Set, 1-3, 1 edition, Hardbound: Academic Press, 2000; p 252-284.

3. Trotter M, Gleser GC. A reevaluation of stature based on measurements of stature taken during life and of long bones after death. Am J Phys Anthrop, 1958; 16:79-123.

4. Trotter M, Gleser GC. The effect of ageing on statu-re. Am J Phys Anthrop., 1951; 9: 311-324.

5. William G, Eckert. Introduction to forensic scien-ces, New York, CRC press, 1997.

6. Sarajlić N, Cihlarž Z, Klonowski EE, Selak I. Stature estimation for Bosnian male population. Bosn. J Basic Med Sci, 2006; 6(1): 62-67.

7. Ross AH, Konigsberg LW. New formulae for esti-mating stature in the Balkans. J Forensic Sci, 2002; 47(1): 165–167.

8. Tomazo-Ravnik T. Secular trend in growth of scho-olchildren in Yugoslavia, Coll Anthropol, 1988; 12:121–33.

9. Moore-Jansen PH, Ousley SD, Janty RL. Data col-lection procedures for forensic skeletal material, Report of investigations no. 48, The University of Tennessee, Knoxville, 1994.

10. Sarajlić N, Cihlarž Z, Klonowski EE, Selak I. Stature estimation for Bosnian male population. Bosn. J. Basic Med Sci, 2006; 6(1): 62-67.

11. Bralić I. Paediatr Croat, Sekularne promjene rasta i razvoja (Secular Changes in Growth and Develop-ment), 2008; 52 (1): 25-35.

12. Trotter M, Gleser GC. Estimation of stature from long bones of American Whites and Negroes. Am J Phys Anthrop, 1952; 10: 463-514.

Corresponding author: Anisa Masovic Institut of Forensic Medicine, Medical School, University of Sarajevo Bosnia and Herzegovina e-mail: [email protected]

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Summary

Introduction: Liver plays an important role in metabolism of glucose and lipids. There is a mu-tual relation between liver disease and diabetes. Lipid and glucose metabolism abnormalities may be a consequence of liver disease and reverse. Aim of this research was to analyze the liver function in patients with diabetes mellitus type 2 and hy-perlipidemia.

Patients and methods: This research has been retrospective-prospective study in which 120 pati-ents have been analyzed divided into 2 groups: 1) patients with diabetes mellitus type 2 and hyper-lipidemia (n=60), 2) patients with diabetes melli-tus type 2 and with normal lipid status (n=60). In this study only patients who had diabetes mellitus type 2 diagnosed more than two years were inclu-ded. To analyze liver function we have measured following parameters: bilirubin (total, conjugated and unconjugated), aspartate-amino transferase (AST), alanine-amino transferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpepti-dase (GGT), albumin, prothrombin time, HbsAg, antiHbsAg, antiHCV. Data have been analyzed by Student t, Chi square or Fischer’s test

Results: This study has shown that liver functi-on in patients with diabetes mellitus type 2 and hy-perlipidemia was more injured than in those with normal lipid status.

Conclusion: Poorly regulated glucose homeo-stasis and hyperlipidemia may contribute to liver injury. It is necessary to make, from time to time, screening of liver function and lipid profile in pa-tients with diabetes mellitus type 2.

Key words: diabetes mellitus type 2, liver function, hyperlipidemia

Sažetak

Uvod: Jetra igra važnu ulogu u metabolizmu glukoze i masti. Postoji uzajamni odnos između bolest jetre i dijabetesa. Abnormalnosti metabo-lizma masti, glukoze mogu biti posledica bolesti jetre i obrnuto. Cilj ovog istraživanja je bio anali-zirati funkciju jetre u oboljelih od dijabetesa tipa 2 sa hiperlipidemijom.

Pacijenti i metode: Ovo istraživanje je retro-spektivno-prospektivna studija u kojoj je analizi-rano 120 pacijenata koji su podijeljeni u 2 grupe: 1) oboljeli od dijabetesa tipa 2 sa hiperlipidemijom (n=60), 2) oboljelih od dijabetesa tipa 2 sa nor-malnim lipidnim statusom (n=60). U ovu studiju su uključeni samo oni oboljeli od dijabetesa tipa 2 koji su na terapiji više od dvije godine. Za pro-cjenu stanja funkcije jetre u svim grupama pacije-nata urađena je analiza slijedećih funkcionalnih parametara: bilirubini (ukupni, konjugovani i ne-konjugovani), aspartat-amino transferaza (AST),

Liver function in patients with diabetes mellitus type 2 and hyperlipidemiaFUNKCIJA JETRE U OBOLJELIH OD DIJABETES MELITUSA TIP 2 I HIPERLIPIDEMIJOMFarid Ljuca1, Esad Alibasic2, Sabina Nuhbegovic1

1 Department of physiology, Medical faculty, University of Tuzla, Bosnia and Herzegovina2 Family medicine department, Dom zdravlja Kalesija, Bosnia and Herzegovina

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alanin-amino transferaza (ALT), alkalna fosfataza (ALP), gama-glutamil transpeptidaza (GGT), al-bumin, protrombinsko vrijeme, HbsAg, antiHb-sAg, antiHCV. Usporedba između ispitivanih gru-pa pacijenata je napravljena pomoću Studentovog t testa za kontinuirane varijable i Hi kvadrat ili Fi-sher-ovog testa za kategoričke varijable.

Rezultati: Ovo istraživanje je pokazalo da je funkcija jetre u oboljelih od dijabetesa tipa 2 sa hiperlipidemijom je više oštećena nego u onih sa normalnim lipidnim statusom

Zaključak: Loše regulirana glikemija i hiperli-pidemija mogu dovesti do oštećenja funkcije jetre. Potrebno je napraviti povremeni skrining funkci-je jetre i lipidnog statusa u oboljelih od dijabetesa tipa 2.

Ključne riječi: dijabetes melitus tip 2, funkcija jetre, hiperlipidemija

Introduction

Liver plays an important role in metabolism of glucose and lipids. There is a mutual relation between liver disease and diabetes. Lipid and glu-cose metabolism abnormalities may be a consequ-ence of liver disease and reverse. Diabetic patients develop macrovascular complications such as: co-ronary artery disease, cerebrovascular disease and peripheral vessels disease (1) and microvascular complications such as: retinopathy, nephropathy, neuropathy and foot problems (2).

Glycogen accumulation in the liver has been observed in 80% diabetic patients. Glycogen synt-hesis in the liver of diabetic patients at the onset of disease is insufficient due to abnormal activationof glycogen sinthase. In patients with chronic di-abetes Glycogen accumulation in the liver is pre-sent, but mechanism is that long-term of lacking of insulin facilitates glycogen synthase activity. In addition to that gluconeogenesis increased lead to glycogen accumulation (3).

Glycogen accumulation in the liver is well-known complication in diabetes is observed in 40–70% cases. Lipids are accumulated in trigly-ceride form and it might be duo to increased lipid intake lipids in the liver, lipid synthesis increased and lower level of oxidation and decreased lipid outtake from the liver. Steatosis can be microvesi-

cular and macrovesicular and it may progress into fibrosis and cirrhosis. Level of glycemia controlcorrelates with lipid accumulation (4). The most frequent clinical symptom is hepatomegalia, and the most patients have normal or mild abnormal transaminase level and normal serum bilirubin le-vel. Liver biopsy is obviously the best method for detection of lipid accumulation in the liver (5).

Non-alcoholic steatohepatitis (NASH) is a va-riant of liver steatosis in that beside lipid accumu-lation in hepatocites there is lobular inflammationand steatonecrosis. In diabetic patients having ste-atohepatitis, Mallory bodies similar to those seen in alcoholic liver disease. NASH is most frequent in obese diabetic patients. There is high prevalen-ce prevalence of NASH in patients with diabetes mellitus type 2 treated by insulin (6). Spectra of clinical symptoms in patients with liver steatosis and steatohepatitis vary from asymptomatic incre-ase of liver enzymes to severe liver disease with fibrosis and nodular regeneration. Patients withNASH may develop progressive liver disease and complication such severe that liver transplantati-on is needed (7). NASH should be considered as a cause of chronic increase of liver enzymes in asymptomatic diabetic patients especially in those who are obese and with hyperlipidemia. In pati-ents with diabetes mellitus type 2 with or without obese, 30% of them have liver steatosis and in-flammation, 25% fibrosis and 1–8% cirrhosis (8).

Incidence of cirrhosis in diabetic patients is in-creased, and 80% patients with cirrhosis have glu-cose intolerance (9). Diabetes mellitus increases risk for steatohepatitis that can progresses in cirr-hosis (10, 11). Aim of this research was to analyze the liver function in patients with diabetes mellitus type 2 and hyperlipidemia.

Patients and methodsPatients

This research has been retrospective-prospecti-ve study in which 120 patients have been analyzed divided into 2 groups: 1) patients with diabetes mel-litus type 2 and hyperlipidemia (n=60), 2) patients with diabetes mellitus type 2 and with normal lipid status (n=60). In this study only patients who had diabetes mellitus type 2 diagnosed more than two

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years were included. To analyze liver function we have measured following parameters: bilirubin (to-tal, conjugated and unconjugated), aspartate-ami-no transferase (AST), alanine-amino transferase (ALT), alkaline phosphatase (ALP), gamma-gluta-myl transpeptidase (GGT), albumin, prothrombin time, HbsAg, antiHbsAg, antiHCV. Data have been analyzed by Student t, Chi square or Fischer’s test.

All tests have been measured routine methods on AR and Dimension RxL devices at UKC Tu-zla. Ultrasonography has been done to determine presence of steatohepatitis. It has been done at De-partment Radiology, UKC Tuzla. To all diabetic patients blood glucose level (fasting and 2 hours postprandial) and HbA1c have been measured.

Results

Serum concentration of aspartat aminotransfe-rase (AST) was higher in patients with DM 2 ha-ving increased level of lipid status parameters than in those with normal ones (p<0,001).

Figure 1. Serum AST level in patients with DM 2 and increased serum lipid parameters

Serum level of ALT was statistically higher in patients with DM 2 and increased serum lipid para-meters than in those with normal ones (p<0,0001).

Figure 2. Serum level of ALT in patients with DM 2 and increased serum lipid parameters

There was no difference between serum levels GGT and ALP in patients with DM 2 and increa-sed serum lipid parameters and in those with nor-mal ones.

Figure 3. Serum GGT level in patients with DM 2 and increased serum lipid parameters

Figure 4. Serum ALP level in patients with DM 2 and increased serum lipid parameters

Platelets counts in serum in patients with DM 2 and increased serum lipid parameters and in those with normal ones have not been statistically dif-ferent.

Figure 5. Platelet count in patient with DM 2 and increased serum lipid parameters

Prothrombine time was in referent range and had no difference among values in patients with DM 2 and increased serum lipid parameters and in those with normal ones.

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Figure 6. Prothrombin time in patients with DM 2 and increased serum lipid parameters

Serum bilirubin level in patients with DM 2 and increased serum lipid parameters was statistically higher than in those with normal ones, however in all patients level was in referent range.

Figure 7. Serum total bilirubin level in patients with DM 2 and increased serum lipid parameters

There were no statistically significant differen-ce between serum unconjugated bilirubin levels in patients with DM 2 and increased and normal serum lipid parameters.

Figure 8. Serum unconjugated bilirubin level in patients with DM 2

Serum conjugated bilirubin level in patients with DM 2 and increased serum lipid parameters was statistically higher than in those with normal serum lipid parameters (p<0,001).

Figure 9. Serum conjugated bilirubin level in pa-tients with DM 2

There was no difference among serum protein and albumin levels in patients with DM 2 and in-creased serum lipid parameters and in those with normal ones.

Figure 10. Serum protein level in patients with DM 2

There was no difference among negative and positive HbsAg, anti HbsAg and anti HCV cases in patients with DM 2 and increased serum lipid parameters and in those with normal ones.

Figure 11. Serum albuminlevel in patients with DM 2

There was positive correlation among Hb1c, serum LDL, triglycerides and cholesterol level and serum AST, ALT and conjugated bilirubin le-

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vels. The strongest level of correlation was among Hb1c, LDL and conjugated bilirubin (table 1).

There was negative correlation among Hb1c, HDL and liver functional parameters (AST, ALT and conjugated bilirubin). The strongest level of correlation was among Hb1c, HDL and conjuga-ted bilirubin (table 1).

Other liver functional parameters did not cor-relate with Hb1c and serum lipid parameters in patients with DM 2.

Discussion

Diabetes mellitus (DM) is one of the most freq-uent metabolic disease causing micro- and macro-vasculcar complications (12). Patients with DM develop macrovascular complications such as: co-ronary artery disease, cerebrovascular disease and peripheral vessels disease (1) and microvascular complications such as: retinopathy, nephropathy, neuropathy and foot problems (2). All complica-tions develop faster and they are more severe if patients with DM have hyperlipidemia.

Due to additional risk of hyperglycemia and hyperlipidemia for cardiovascular and other dise-ases, metabolism abnormalities and their influen-ce to function of different organs, they should be tested in DM (13). This study has shown that liver function in patients with diabetes mellitus type 2 and hyperlipidemia was more injured than in those with normal lipid status. Serum concentration of AST, ALT and conjugated bilirubin were higher in patients with DM 2 having increased level of lipid status parameters than in those with normal ones

There was positive correlation among Hb1c, serum LDL, triglycerides and cholesterol level and serum AST, ALT and conjugated bilirubin le-

vels. The strongest level of correlation was among Hb1c, LDL and conjugated bilirubin. Our results have shown negative correlation among Hb1c, HDL and liver functional parameters (AST, ALT and conjugated bilirubin). The strongest level of correlation was among Hb1c, HDL and conjuga-ted bilirubin.

Several research studies have shown similar re-sults about additional harmful effect of abnormal lipid metabolism on the function of different or-gans in patients with DM (14, 15,16, 17).

Conclusion

Poorly regulated glucose homeostasis and hy-perlipidemia may contribute to liver injury. It is necessary to make, from time to time, screening of liver function and lipid profile in patients withdiabetes mellitus type 2.

Table 1. Correlation among Hb1c, serum lipid parameters and liver functional parameters in patients with DM 2

Liver functional parameter Hb1c

LDL HDL Triglycerides Cholesterol

AST 0,72 -0,60 0,52 0,57

ALT 0,86 -0,69 0,58 0,64

Conjugated bilirubin 0,91 -0,75 0,73 0,71

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Literature

1. Beckman JA (2002) Diabetes and atherosclerosis. JAMA 287: 2570-2581.

2. Kernan WN, Inzucchi SE (2004) Type 2 Diabetes Mellitus and Insulin Resistance: Stroke Prevention and Management. Curr Treat Options Neurol 6: 443-450.

3. Ferrannini E, Lanfranchi A, Rohner-Jeanrenaud F, Manfredini G, VandeWerve G (1990) Influence oflong-term diabetes on liver glycogen metabolism in the rat. Metabol 39: 1082-1088.

4. Silverman JF, O’Brien KF, Long S, Leggett N, Kha-zanie PG, Pories WJ, Norris JR, Caro JF (1990) Liver pathology in morbidly obese patients with and without diabetes. Am J Gastroenterol 85:1349-1355.

5. O’Connor BJF, Katbamna B, Tavill AS (1997) No-nalcoholic fatty liver (NASH syndrome). Gastroen-terol 5: 316-329.

6. Bacon BR, Farahvash MJ, Janney CG, Neuschw-ander-Tetri BA (1994) Nonalcoholic steatohepati-tis: an expanded clinical entity. Gastroenterol 107: 1103-1109.

7. Zein NN, Abdulkarim AS, Wiesner RH, Egan KS, Persing DH (2000) Prevalence of diabetes mellitus in patients with end-stage liver cirrhosis due to he-patitis C, alcohol, or cholestatic disease. J Hepatol 32(2): 209-17.

8. Lebovitz HE, Kreider M, Freed MI (2002) Evalua-tion of Liver Function in Type 2 Diabetic Patients During Clinical Trials. Diebet Care 25: 815-821.

9. Baig NA, Herrine SK, Rubin R (2001) Liver disease and diabetes mellitus. Clin Lab Med 21(1): 193-207.

10. Anonymous (2003) The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus.Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. DiabetCare 26(suppl 1): S5-S20.

11. Amarapurkar D, Das HS (2002) Chronic liver disease in diabetes mellitus. Trop Gastroenterol 23(1): 3-5.

12. Afkhami-Ardekani M, Shojaoddiny-Ardekani A. Effect of vitamin C on blood glucose, serum lipids & serum insulin in type 2 diabetes patients. Indian J Med Res. 2007;126(5):471-4.

13. Koshiyama H. Lipid management--treatment goal and strategy. Nippon Rinsho. 2006; 64(11):2102-6.

14. Lund SS, Petersen M, Frandsen M, Smidt UM, Parving HH, Vaag AA, Jensen T. Sustained post-prandial decrease in plasma levels of LDL cho-lesterol in patients with type-2 diabetes mellitus. Scand J Clin Lab Invest. 2008; 16:1-14.

15. Khan SR, Ayub N, Nawab S, Shamsi TS. Trigly-ceride profile in dyslipidaemia of type 2 diabetesmellitus. J Coll Physicians Surg Pak. 2008;18(5):270-3.

16. Chapman MJ. Metabolic syndrome and type 2 diabetes: lipid and physiological consequences. Diab Vasc Dis Res. 2007; 4 Suppl 3:S5-8.

17. Gadi R, Samaha FF. Dyslipidemia in type 2 diabe-tes mellitus. Curr Diab Rep. 2007;7(3):228-34.

Corresponding author: Farid Ljuca Zavod za fiziologiju Medicinski fakultet Bosna i Hercegovina e-mail: [email protected]

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Summary

Introduction: It is estimated that one third of the lung cancers is due to the nutritional factors. The research is conducted with the aim of identi-fying risk, as well as protective factors in alimen-tation. Those are related to the occurrence of lung cancer at Tuzla Canton interviewees.

Methodology: Interviewees were two hundred patients of the Tuzla Lung Diseases Clinics. Ex-perimental group were hundred patients with lung cancer disease. Control group were hundred pa-tients who did not have lung cancer disease. There were no significant differences between experi-mental and control groups by age and sex. The data was collected by using anonymous question-naire. It contains social - demographic, and ques-tions related to the consumption of specific nutri-tive are alimentation. Time span for the consump-tion of nutritive was a day, week, month and year, and amount of consumption of them.

Results: Incidence of lung cancer was signifi-cantly higher among interviewees living in rural areas in comparison to the ones living in urban ar-eas (63% vs.30%, P =0.001). There is a significantdifference among different social statuses, so that ones with worse social status were lung cancer patients (Z=-4.916, P=0.001). Among nutritional factors, the one serving as predictor for develop-

ment of lung carcinoma was deficiency of olives(OR=1.26), grapefruit (OR=1.47), fish (OR=1.45)and garlic luk (OR=1.38).

Conclusion: Lung cancer can be prevented by consumption of adequate alimentation rich with protective factors. Those are especially beans’ fibers, grapefruit, garlic, olives etc. It seems thatthe greatest obstacle at choice of nutritive which would act as protective factors for the develop-ment of lung cancer is low social status, as well as differences between environments one lives in, city vs. village.

Key words: nutritive factors, alimentation, lung cancer.

Sažetak

Uvod: Procijenjeno je da su faktori ishrane odgovorni za nastanak jedne trećine karcinoma pluća. Istraživanje je provedeno s ciljem da se ot-kriju faktori rizika, kao i zaštitni faktori u ishrani, a koji su u vezi sa nastankom karcinoma pluća u ispitanika Tuzlanskog kantona.

Metode: Ispitanike je činilo 200 pacijenata Klinike za plućne bolesti Tuzla. Eksperimentalnu skupinu činilo je 100 pacijenata kojima je dijagno-sticiran karcinom pluća, a kontrolnu skupinu 100 pacijenata kojima nije dijagnosticiran karcinom

Dietary factors as protectors or predictors for lung cancer: survey control studyFAKTORI ISHRANE KAO ZAŠTITNI FAKTORI ILI FAKTORI RIZIKA ZA KARCINOM PLUĆA: PREGLEDNO KONTROLNO ISTRAŽIVANJESuvad Dedic¹, Nurka Pranjic²

¹ Clinic of lung disorders and tuberculosis, University Clinic Centre Tuzla, Bosnia and Herzegovina² Department of Occupational Medicine, Medical school University of Tuzla, Bosnia and Herzegovina

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pluća. Između kontrolne i eksperimentalne sku-pine nisu postojale signifikantne razlike po dobii spolu. Podaci su prikupljeni upotrebom anonim-nog upitnika, koji sadrži socio- demografska pi-tanja, pitanja u vezi sa unosom pojedinačnih nu-tritijenata u ishrani, a prema dnevnoj, sedmičnoj, mjesečnoj i godišnjoj učestalosti unosa i količini istih.

Rezultati: Značajno veća učestalost karcino-ma pluća bila je zastupljena u ispitanika koji su živjeli na selu u odnosu na one koji su živjeli u gradu (63% vs. 30%, P =0.001). Pacijenti koji su imali lošiji imovinski status imali su signifikantnoveću učestalost oboljevanja od karcinoma pluća u odnosu na one sa boljim imovinskim statusom (Z=-4,916, P=0.001). Prediktori za razvoj karci-noma pluća među faktorima ishrane su smanjen unos zaštitnih faktora u ishrani: masline (OR=-1.26), grejpfrut (OR=1.47), riba (OR=1.45) i bije-li luk (OR=1.38).

Zaključak: Kacinom pluća se može spriječiti odgovarajućim unosom zaštitnih faktora u ishrani naročito vlakana u grahu, buraniji, grašku zatim grejfruta, bijelog luka, maslina i drugih. Čini se da najveći problem u odabiru namirnica koje bi bile protektivni faktor za razvoj karcinoma pluća čini loš imovinski status stanovništva, kao i razlike u odnosu na mjesto življenja selo- grad.

Ključne riječi: faktori ishrane, ishrana, karci-nom pluća

Introduction

Epidemiological studies indicate the strong re-lation between the nutritious factors and the oc-currence of the particular types of cancer, so it is estimated that the nutritious factors are responsi-ble for the one third of the cancer occurrence (1-3). Big part of different types of cancers is poten-tially related to the nutrition habits and factors. It is assumed that 30 % of cancer mortality could be evaded by the modification of the eating ha-bits through one’s life. Considering the different cultural nutrition habits in different countries we can talk about the international risks as well as the protective factors of cancer (2).

The mechanism of the nutrition effect to the development of the carcinogenesis has not been

illuminated yet, but it can be rightfully said that nutritional factors can modify its process. The plant fibers are shortening the exposition time ofthe potential carcinogens decreasing the time of the food passing through the intestinal tract (3). Broccoli contains three active protective substan-ces that inactivate carcinogen compounds: sulpho-raph, beta-carotene and indol - carabinol. Spinach contains glutathione, tomato - licopen, citrus fruit bioflavonoid and vitamin C, carrot retinol and betacarotene, and the onion - alicin. Pickled vegetables, alcohol, salty, greasy and fried food represent the risk factors for the occurrence of the cancer of the abdominal organs, but not the lungs (4). Potential protective vitamins characteristics are at the cen-tre of the investigation at present, especially the A, C, D and E vitamin. Protective characteristics of the vitamins can be explained by the anti- oxidant effects and by the degradation of the free radicals that contributes to the decreasing of the substan-ces that are the potential causes of the cancer in the human body. Selene compounds have anti-oxidant characteristics and the important role in the metabolism of the glutathione-peroxidaze, the enzyme that has the protective characteristic aga-inst the oxidative damage of the tissue. (1) Selene present in the food decreases the occurrence of the chemical induced tumors on few locations. (1-2) Specific micro nutrition such as retinol, all caro-tenoids and Vitamin C are considered the protecti-ve factors in the development of the lung cancer (4-7). Theoretically, they have stronger protective role when continuously consumed, and the prote-ction depends on the doses/ amount of the intake of those protectors (4-5). Fruits and vegetables re-present protective factors in the development of the lung cancer because of the contents of the use-ful ingredients (carotenoids, vitamins A, E, C and minerals.) Because of the insufficient intake of thefruit and vegetable the risk of getting the cancer of many organs, as well as the lung is increasing (5). Vitamin A controls the growth and the diffe-rentiation of the cells (decreases the risk of the de-velopment of the gastrointestinal and respiratory cancer). Vitamin C inactivates O2 radicals at the cell level, increases the produce of the collagen, whereby obstructs the penetration of the mali-gnant cell in the environment. Vitamin E, calcium, selenium block the process of the carcinogenesis,

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by the decreasing of the excretion of the tertiary galls and fatty acids (6-7). Micro- nutritionist such as retinol, total carotenoids, B- carotene and Vi-tamin C protect the cells from the oxidant DNA damages, and in that way protect from the cancer (4, 8-10). Diet enriched by the fibers (bean, peas,lentil, fruit and vegetables) help in elimination of the toxins in the body.

Habits, cultural characteristics and the assets influence the eating habits and the choice of thenutrition’s. In Bosnia and Herzegovina, the conti-nuing increase of the incidence and the death rate of the lung cancer are noted. (11) The aim is to identify the nutrition risk factors for the occurren-ce of the lung cancer and to estimate the relation of the protective nutrition factors and the lung can-cer diseased in Tuzla Canton.

Subjects and methods

Control study involved 200 patients who are cured at the Clinic for the lung diseases and tuber-culosis University - clinical centre of Tuzla since the 1st January 2007 to the 31st December 2007. Experimental group was formed of the incidence diagnosed with the lung cancer. Control group was formed of 100 examinees that are not diagno-sed with the lung cancer, or any other malignant disease. Research has been done by the method of the poll, and the instrument of the poll was the qu-estionnaire which has been designed specially for this research. The first part of the questions wasmade of the questions containing: demographic information (gender, age, education, working sta-tus, location, asset, satisfaction with the financialsituation), family history of the lung cancer. The other part of the questions referred to the evalua-tion of the food. Supplements to the diet are every active substance that is taken orally for the sake of diet enrichment, and contains one of the next components: vitamins, minerals, herbs, or medical plants, their concentrates or extracts or their mixtu-re (with the premises that is not the medicament). Through the answers to the questions the intake of the fruit and vegetables, meat, milk, has been estimated, onion, fish, preparations ( intake freq-uency: 1-3 x monthly, 1 x weekly, 2-4 x weekly, 5- 6 x weekly and daily), vitamins in supplements

( how often: never, 2x yearly, 1-3 x yearly, 5-6 x yearly, 1 x monthly, 2 x monthly, daily), intake: intake half of plate –fresh, fried or boiled carrot, half of plate – grapefruit, banana, apple, half of plate- blueberry, blackberry, raspberry, half of pla-te –broccoli, spinach, bulb, egg plant, lettuce, pep-per, green salad, ( regular consumption frequency- never, 1-3x monthly, 1x weekly, 2-4 x weekly, 5-6x weekly, and daily), intake of one plate of beans, lentil, or peas(contain fibers), 1-2 dcl natural fruitjuice-lemon, orange, tomato or carrot ( regular consumption frequency - never, 1-3x monthly, 1x weekly, 2-4 x weekly, 5-6x weekly, and daily), 2-5 olives (regular consumption frequency - ne-ver, 1-3x monthly, 1x weekly, 2-4 x weekly, 5-6 x weekly, and daily).

Therefore, answers about the regular menu of the 13- types of nutritionist or micro nutritionist were created in accordance to the questionnaires done before for the conducted research (3-10). Re-liability of the questionnaire is tested by the Cron-bach alpha coefficient of the consistency and inthe total sample is sufficient >70% and the sum isα = 0.76.

Statistical analysis

During the statistical analysis of the results standards method of descriptive statistics were used (central tendency and dispersion measures). We used Mann- Whitney non parametric test to assess the differences between experimental and control group subjects. Multivariate analysis of variance (ANOVA; multivariate regression analy-sis) was performed to test the relationship betw-een predictive variables (13- types of nutritionist or micro nutritionist). The results were presented as regression coefficient β (R), adjusted odds ratio(OR) with 95% confidence intervals (CI). Stati-stical hypothesis were tested on the significancelevel of Alfa = 0.05.

Results

Lung cancer is the disease which in Tuzla Can-ton has 9 fold higher incidences at male when compared to female population, ages 50-79 (77%).

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Lung cancer patients in a statistically significantmanner belong to the pensioned group of intervi-ewees when compared to the group which didn’t have lung cancer disease (28% vs. 7%, P=0.001). They also in a statistically significant manner be-long less to the group of employed when compared to the group which didn’t have lung cancer disease (29% vs.11%, P= 0.001, z= 4.819).

The interviewees suffering from the lung can-cer disease have statistically significant lowereducational level when compared to the healthy (Mann- Whitney test; Z= -6.174, P= 0.001). Signi-ficantly greater incidence of lung cancer patientslives in villages when compared to the patients living in the cities (63% vs.43%, P= 0.001) only 10 % of lung cancer patients is well off, that is,

better than majority, 59% estimates to be as wealt-hy as others, and 31% practically lives in poverty. There is significant difference in social status atpatients’ group when compared to healthy group. Lung cancer patients have worse social status (z= -4.916, P= 0.001). Poverty is important determi-nant at becoming sick of lung cancer. In the total sample majority has declared that there is no fa-mily history of lung cancer (82%), 86% at control group and 78% at patients group. Significant diffe-rence for family predisposition to becoming ill of lung cancer was not noticed in experimental when compared to control group (z= -1.273, P= 0.203). There was significantly higher number of smokersin experimental when compared to control group. (P=0.001).

Table 1 Distribution of the interviewees (N=200) according to the demographic characteristics and the groups

Demographic characteristics of examiners Control groupN (%)

Experiment groupN (%) P

Educational levelUncompleted primary school 11 (11) 29 (29)Completed primary school 5 ( 5) 18 (18)*High school 38 (38) 46 (46)*Completed High school 24 (24)* 2 ( 2)Academy 7 ( 7)* 2 ( 2)Faculty 15 (15)* 3 ( 3) 0.001Location Town 45 (45) 30 (30)Country 43 (43) 63 (63)Near the industrial facilities 12 (12) 7 ( 7) 0.001Financial situation compared with otherMuch better than the others 6 ( 6) 1 ( 1)Better then the majority 29 (29) 9 ( 9)Similar to the majority 54 (54) 59 (59)Somehow less then the majority 8 ( 8) 17 (17)Much less than the majority 3 ( 3) 10 (10)Much less than the rest 0 ( 0) 4 ( 4) 0.001Family predisposition for the lung cancerNo, no one 86 (86) 78 (78)One of the parents 6 ( 6) 15 (15)*Brother or sister 1 ( 1) 4 ( 4)Uncles/aunts 1 ( 1) 1 ( 1)Grandfather or his brother or sisters 2 ( 2) 0 ( 0)Other relatives 4 ( 4) 2 ( 2) 0.203Smoking statusI have never smoked 36 (36) 9 ( 9)I quit this year 7 ( 7) 1 ( 1)I quit 2 years ago 2 ( 2) 5 ( 5)I smoked less than 10 years 17 (17) 4 ( 4)I smoked more than 20 years 18 (18) 16 (16)I smoked more than 30 years 13 (13) 29 (29)I have been smoking more than 40 years 7 ( 7) 36 (36) 0.001

* Mann Whitney non parametric test

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Culture and eating habits of our interviewees have the next characteristics: >80 % of all intervi-ewees consume the right amount of fruit and ve-getable, but the less of half eat the right amount of carrot weekly. Among the lung cancer patients 87 % are of those who have the habit of consuming the fruit and vegetable 2- 4 x weekly to daily. As for this habit, there is almost no difference in ta-king the fruit and vegetable among the lung cancer patients and in the control group. Among the 60 %

of the interviewees there is drinking habit of con-suming the natural fruit juice in their diet. There is enough consuming of vegetables that have active substances such as broccoli, bulb, egg plant, let-tuce, spinach, green salad and pepper (75 % the right amount). The deficiency of our kitchen isin the shortage of the intake of: vegetables with fibers (beans, peas, and lentil), olive, blueberry,blackberry, raspberry, and fish and increased/oftenintake of meat and meat products, milk and dai-

Table 2 Distribution of the nutrition and micro- nutrition input and in the interviewees diet (N=200) according to the frequency and the group

Nutrition and micro- nutrition in a diet according to the frequency

Control groupN (%)

Experimental groupN (%) P

Fruit and vegetable* Rarely 16 (16) 13 ( 13)Often 84 ( 84) 87 ( 87) 0.070Half of plate of carrotRarely 55 (55) 66 (66)Often 45 (45) 34 (34) 0.0911-2 dcL natural juice of citrus fruitRarely 31 (31) 40 (40)Often 69 (69) 60 (60) 0.300Half of plate of broccoli, spinach, lettuce, egg plant, green salad, bulbs, pepperRarely 21 ( 21) 25 (25)Often 79 (79) 75 ( 75) 0.508Plate of beans, green beans, lentil, peasRarely 45 (45) 81 (81)Often 55 (55) 19 (19) 0.0012-5 olivesRarely 75 (75) 94 (94)Often 25( 25) 6 ( 6) 0.001Half of portion blueberry, blackberry, raspberryRarely 75 (75) 90 (90)Often 25 (25) 10 (10) 0.001Half of plate of grapefruit, banana, apple Rarely 48 (48) 29 (29)Often 52 (52) 71 (71) 0.001GarlicRarely 33 (33) 18 (18)Often 67 (67) 82 (82) 0.001FishRarely 98 (98) 80 (80)Often 2 (02) 20 (20) 0.001Intake of the vitamins A, C and E in a supplement±Very rarely 87 (87) 96 (96)often 13 (13) 4 ( 4) 0.001Intake of meat and meat productsRarely 10 ( 10) 5 ( 5)Often 90 (90) 97 (97) 0.040Intake of milk and dairy productsRarely 13 ( 13) 5 ( 5)Often 87 (87) 95 (95) 0. 002

Mann Whitney non parametric test* (dichotomized often and rarely): often: 2-4 x weekly, 5-6 x weekly; daily: 1x weekly, 1-3 x monthly and never;± (dichotomized often and rarely): often: 1x monthly; 2x monthly and daily; very rarely: 5-6 x yearly, 1-3 x yearly and never;

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ry products. There is no regular consumption of the vitamins A, C and E in the supplement. There is statistically significant difference of the con-sumption frequency of the meat, milk and their

products among the lung cancer patients and the control group (P= 0,040), as for the frequent milk and dairy products consumption (87% vs. 95%; P=0.002)

Table 3 Predictors of the lung cancer due to the decreased intake (rare) or often intake of the significantnutrition’s and micro nutrition’s in a diet of the interviewees of the experimental and the control group.

Intake of the nutrition or micro- nutrition a dietLung Cancer

PModel 1β0*

Model 1β2±

Often intake of fruit and vegetable 0. 657 0.993 0.884Decreased intake of the fresh, fried or boiled carrot 0.852 0.926 0.113Often intake 1-2 dcL natural fruit juices 0.687 0.952 0.303Often intake of broccoli spinach, egg plant, bulbs... 0.619 0.965 0.407Decreased intake of green beans, beans peas and lentil 0.817 0.835 0.001Decreased olive intake 0.986 0.986 0.519Decreased intake of blueberries, raspberry and blackberry 0.946 0.993 0.811Often intake of grapefruit, banana, apples 1.190 0.187 0.006Decreased intake of fish 0.959 0.913 0.033Decreased consumption of preparations vitamins A, C, E in a supplement 0.624 1.117 0.023

Often intake of garlic 0.678 0.913 0.033Often consumption of meat and meat products 0.514 0.986 0.177Often consumption of milk and dairy products 0.503 1.000 1.000

Logistic regression analysis*β0- for the diseased group±β2- for the control group

Table 4 Estimation of the relative risk for the lung cancer due to the decreased intake of the nutrition and micro- nutrition in the total sample

Decreased intake of nutrition and micro- nutrition’s OR ( 95% CI) P

Fruit and vegetable 1.044 (0.587- 1.857) 0.060Fresh, fried or boiled carrot 1.588 (0.897- 2.812) 0.001Natural fruit juice 1.359 (0.760- 2.430) 0.002Broccoli, lettuce, egg plant, bulbs... 1.322 (0.685-2.459) 0.001Beans, green beans, peas, lentil 3.488 (1.846- 6.590) 0.001Olive 1.532 (0.419- 5.613) 0.001Blueberry, raspberry, blackberry 1.123 (0.436- 2.895) 0.001Grapefruit, banana, apple 2.260 (1.261. 4.051) 0.001Fish 2.006 (1.044- 3.854) 0.001Vitamins A, C, E in a supplement 0.519 (0.295- 0.915) 0.001Garlic 2.047 (1.054- 3.973) 0.001

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Predictors for the development of the lung can-cer among the nutrition factors are the deficiencyof the fibers intake in the diet of the beans, peasand lentils (P=0.001), decreased consumption of the fish (P=0,033) and decreased consumption ofthe vitamins A, C and E in the supplement (P= 0.0-23). Protective factors for the development of the lung cancer in our interviewees’ diet are: increased intake of grapefruit, banana and apple (P=0.006), frequent garlic intake (P=0.033).

Lung cancer can be prevented by the adequate intake of the protective factors in diet especially fibers in beans, peas and lentil, enough amount ofthe carrot, fish, garlic, blueberry, raspberry, grape-fruit, banana and apple, olive and others.

Results of the logistic regression analysis indi-cate that the significant protective factors amongthe smokers for the development of the lung can-cer are only the decreased intake of milk and dairy products (β= 1.001; P=0.002) and the consumption of the sufficient amount of grapefruit, banana andapple (β= -0.133; P= 0.025; data was not shown).

Discussion and conclusion

Last years in the world many researchers have been done which involve risky population gro-ups with the main aim to identify the risk factors that are significant for the development of thelung cancer (6, 12). According to the regression analysis statistically significant predictors for thedevelopment of the lung cancer among the nu-trition factors are: deficit of the fibers intake ina diet enriched by them such as beans, peas, len-til, then grapefruit, fish, vitamin preparations ina supplement and garlic. The same groceries are the protective factors from the emergence of the lung cancer. Statistically significant risk factor forthe lung cancer exists in the decreased intake of the protective factors in a diet: olive (OR=1.26), grapefruit (OR=1.47), fish (OR=1.45) and garlic(OR=1.38). According to the results non-consum-ption or decreased consumption of the vitamins in a supplement represents the protective factor (re-gression linear analysis of the risk factors). In the control group the risk factor is increased due to the continuing intake of the vitamin in the supplement (OR=1.39). Diseased significantly less consume

fish, once a week when compared to the controlgroup (P=0.04).

Many studies about the diet and lung cancer have been focused to the hypothesis that the diet rich with antioxidants can protect from the oxida-tive damage of DNA and considering that protect from the carcinoma (9). At the researches it has been noted that diet enriched by fruit had clear protective role in a development of the lung can-cer, in 4 studies (5, 10, 13, and 2). In 2 studies it has been supposed that fruit has the protective role (14-15).

Traditionally, in Bosnia and Herzegovina diet fruit and vegetable intake is represented in the suf-ficient amount. We have not noted significant dif-ferences among the lung cancer patients and in the control group for this habit, so we couldn’t note their clear significant protective role. Consequen-tly our results are in accordance with the results of the others studies, and it’s not the protective factor in two studies (16-17). That doesn’t mean that we have to stop this good habit in our diet. Decrea-sed daily intake of the fresh, fried or boiled carrot in our research presents significant relative riskfor the lung cancer (OR= 1.588, 95% CI 0.897- 2.812). Evidences related to the diet richen with retinol are combined with the decrease risk of the lung cancer noted in many studies (8, 18-19), and protective role of the diet rich with beta carotene in results of the next studies (2, 15, 20). Smoking is strongly connected to the bad life style, so it is hard to reveal which nutrition factor except the smoking represent the cancerous risk (4, 21). We have revealed that the adequate intake of grape-fruit, banana and apple can decrease the cancerous risk as the decreased intake of milk and dairy pro-ducts in a smokers’ diet. In our circumstances that is especially related to the rural population.

Lung cancer can be prevented by the intake of the right amount of the protective factors in a diet especially fibers in beans, pulse, peas, then grape-fruit, garlic, olive and others.

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Literature

1. Pranjić N. Bolesti modernog doba i ishrana (Dise-ases of modern time). U: Pranjić N (ur) Zdravstve-na ekologija (Environmental health). Medicinski fakultet Univerziteta u Tuzli 2006; pp 111-120.

2. Shibata A, Paganini-Hill A, Ross RK, et al. Intake of vegetables, fruits, beta-carotene, vitamin C and vitamin supplements and cancer incidence among the elderly: a prospective study. Br J Cancer 1992; 66:673-79.

3. Niki E. Interaction of ascorbate and Alpha tocophe-rol. In: Third Conference on vitamin C. Burns J. J. Rivers J.M. Machlin JL (eds). The N. York Academy of sciences. N. York 1997, pp 123-31.

4. Margetts BM, Jackson AA. The determinants of pla-sma beta- carotene: interaction between smoking and other lifestyle factors. Eur J Clin Nutr 1996; 50:236-38.

5. Axelsson G, Liljeqvist T, Andersson L, et al. Dietary factors and lung cancer among men in west Swe-den. Int J Epidemiol 1996; 25:32-39.

6. Bandera EV, Freudenheim JL, Marshall JR, et al. Diet and alcohol consumption and lung cancer risk in the New York State Cohort (United States). Can-cer Causes Control 1997; 8:828-40.

7. Darby SC, Whitley E, Doll R, et al. Diet, smoking and lung cancer: a case-control study of 1000 ca-ses and 1500 controls in South-West England. Br J Cancer 2001; 84:728-35.

8. Bjelke E. Dietary vitamin A and human lung can-cer. Int J Cancer 1975; 15: 561-65.

9. Peto R, Doll R, Buckley JD, et al. Can diatary beta- carotene materially reduce human cancer rates? Nature 1981; 290: 201- 208.

10. Fontham ET, Pickle LW, Hienszel W, et al. Dietary vitamins A, and C, and lung cancer among men in west Sweden. Int J Epidemiol 1996; 25: 32-39.

11. Ferković V. Registar malignih neoplazmi Tuzlan-skog kantona 2001/ 2002 (Register of malign di-seases in Tuzla Canton 2001/ 2002). Tuzla, Print-Com 2004.

12. Carol L, David J, Charles L, George D, Graham M, Victo H. Social class differences in lung cancer mortality: risk factor explanations two Scotish co-hort studies. International J Epidemiol 2001; 30: 268- 74.

13. Gao CM, Tajima K, Duroishi T, et al. Protective effects of raw vegetables and fruit against lung cancer among smokers and ex- smokers: a case- control study in the Tokai area of Japan. J Cancer Res 1993; 84: 594-00.

14. Fraser GE, Beeson WL, Philips RL. Diet and lung cancer in California seventh day adventists. Am J Epidemiol 1991; 133: 683-93.

15. Steinmetz KA, Potter JD, Folsom AR.Vegetables, fruit and lung cancer in Iowa women’s health stu-dy 1993; 53: 536-43.

16. Feskanich D, Ziegler RG, Michaud DS, et al. Pro-spective study of fruit and vegetable consumption and risk of lung cancer among men and women. J Natl Cancer Inst 2000; 92: 1812-23.

17. Kromhout D. Essential micro-nutritients in rela-tion to carcinogenesis. Am J Clin Nutr 1987; 45: 1361-67.

18. Churg A. Lung cancer cell type and occupational exposure. In: Samet JM (ed) Epidemiology of lung cancer. Marcel Dekker New York, Ny 1994; pp 413-36.

19. Mayne ST, Janerich DT, Greenwald P. Et al. Di-etary beta- carotene and lung cancer risk in US non- smokers. J Natl Cancer Inst 1994; 86: 33-38.

20. Voorrips LE, Goldbohm RA, Verhoeven DT, et al. Vegetable and fruit consumption and lung cancer risk in the Netherlands cohort study on diet and cancer. Cancer Causes Control 2000; 11: 101-15.

21. Boffetta P, Agudo A, Ahrens W, et al. Multi canter case- control study of exposure to environmental tobacco smoke and lung cancer in Europe. J Nat Cancer Inst 1998; 90:1440-50.

Corresponding author: Suvad Dedic Clinic of lung disorders and tuberculosis, University Clinic Centre Tuzla, Bosnia and Herzegovina email: [email protected]

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Summary

Aim: to estimate the prevalence of frequent at-tenders (FA), comparing to their socio-demograph-ic characteristics, health indicators and health care service usage indicators.

Methods: Retrospective and longitudinal medical charts review of patients registrated in four family medicine offices. Medical charts of434 randomly chosen patients were screened for socio-economic data, health status indicators and health care system usage indicators.

Results: Prevalence of FA is 23,3%. Significantcorrelation has been found between frequent visits and elderly people (t=2,1, df=432, P<0,05), retired and unemployed people (r=0,104, P<0,05), and people living in rural and suburban areas.(r=0,123, P<0,01) FAs had more chronic diseases. (F=51,6; P<0,01) The most associated diseases found in FA are neoplasms (OR=2,86;95%CI:1,42,5,80), dia-betes mellitus (OR= 2,16;95%CI:1,53,3,04) and mood disorders (OR=2,03; 95%CI:1,13,3,63). FA significantly use more health care services to oth-ers (P<0,001).

Discussion: FAs use significantly more healthcare system services. Notably, high percentages of the referrals, hospital days, sick leave days and home visits were observed.

Conclusion: FAs are usually characterized as older people with a bad socio-economic back-ground, living in the rural or suburb areas with a poor physical and mental health. It is crucial for the family medicine team to develope a strategy how to deal with the FA.

Key words: frequent attendees, office visits,Family medicine, general practice, primary health care, health indicators, socio-demographic charac-teristics,

Sažetak

Cilj: Procjena prevalencije čestih korisnika (FA) i poređenje njihovih socio-demografskih ka-rakteristika, indikatora zdravlja i indikatora upo-trebe zdravstvenog sistema.

Metod: Retrospektivno, longitudinalno ispiti-vanje zdravstvenih kartona pacijenata registrira-nih u timovima porodične medicine. Pregledani su socio-ekonomski podaci, indikatori zdravlja i indikatori upotrebe zdravstvenog sistema u 434 slučajno izabrana kartnona.

Rezultati: Prevalencija čestih korisnika je 23,3%. Nađena je signifikantna povezanost izme-đu čestih korisnika i starije dobi (t=2,1, df=432, P<0,05), penzionisanih i nezaposlenih (r=0,104,

Socio-Demographic and Health Characteristics of Frequent Attender in Family PracticeSOCIODEMOGRAFSKE I ZDRAVSTVENE KARAKTERISTIKE ČESTIH KORISNIKA U PORODIČNOJ MEDICINIZaim Jatic1,2, Dzanana Jatic1

1 Public Institution Medical Centre of the Sarajevo Canton, Bosnia and Herzegovina2 Medical Faculty of Sarajevo University, Department for Family Medicine, Bosnia and Herzegovina

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P<0,05) i osoba koje žive na selu i predgrađu.(-r=0,123, P<0,01) Česti korisnici imaju prosječno više hroničnih bolesti. (F=51,6; P<0,01) Najčešće udružene bolesti kod ovih pacijenata su neopla-zme (OR=2,86;95%CI:1,42,5,80), diabetes mel-litus (OR= 2,16;95%CI:1,53,3,04) i poremećaji raspoloženja (OR=2,03; 95%CI:1,13,3,63). Oni i signifikantno više koriste usluge zdravstvenog si-stema od drugih pacijenata.(P<0,001).

Diskusija: Česti korisnici znatno više koriste zdravstveni sistem. Posebno su visoki procenti upućivanja specijalistima, bolničkih dana, dana bolovanja i kućnih posjeta.

Zaključak: Česte korisnike karaterizira starija dob, loši socio-ekonomski uslovi, stanovanje na selu i predgrađu, loše fizičko i mentalno zdravlje.Bitno je da timovi porodične medicine razviju strategiju rada sa čestim korisnicima

Key words: česti korisnici, ljekarski pregle-di, porodična medicina, opšta praksa, primarna zdravstvena zaštita indikatori zdravlja, socio-de-mografske karakteristike,

Introduction

Researches dating back from the second half of the 20th century point out that the small percentage of patients were responsible for the majority of the visits paid to the family physician (1). Since then, a significant number of researches regarding thecauses and reasons why people frequently use the services of family medicine have been conducted. These patients are called frequent attenders (FA), constant attenders, high users or high utilizers.

Patients that frequently visit family doctors significantly use more resources of health caresystem. Researches conducted in countries with different health systems show similar results. A group of 4 to10% of patients called frequent at-tendees make up about 21to 60% of all visits. (2, 3) It has also been proven that FAs have more mental and physical illnesses, social and econo-mic problems and that they are under increasing emotional stress. (4, 5)

Frequent visits lead to the consumption of limi-ted health resources, cause an overload of medical professionals and spread frustration among the members of Family Medicine team. This Research

has shown that the female sex- that is divorced fe-males, widows and women above 65- is a domi-nant sex when the socio-demographic features of these patients are taken into consideration. (2, 3, 4, 6, 7, 8) FAs are the perfect choice for the ‘’super-ficial examination’’ and for the referrals to specia-lists. (9) They have lower educational status, more often choose experienced doctors and doctors who does not use the appointment system, and they are more satisfied with health services. (10) FA, also, often have elements of low quality health care, they have a notion that the physicians don’t under-stand complexity of their problems which is a ca-use to a dysfunctional relationship between doctor and patient. (11, 12, 13)

There are various definitions of FAs: those whovisit family doctors more than 5 times (14), more than 9 times (2), more than 10 times (3) more than 12 times annually (3, 8, 15, patients who have a number of visits above 75th percentile per year (16, 17) or above of 90th percentile for age and sex gro-up. (7, 9, 18) Some FAs are defined as patients whovisit the family medicine offices more than averagepeople from their age and sex group. (19, 20) So-metimes FA is defined as a person who has twice ormore consultation than an average patient from the same age and sex group. (21) Weight of patient’s medical record greater than 100 g is a turning po-int which separates FAs from other patients.(22) It must not be forgotten that the term FA sometimes in the medical jargon has a derogatory meaning for people who cause “an unnecessary and unwelcome workload’’ and “Thick-file case”. (12, 13, 23) Thereare other numerous, mostly pejorative names, used by health professionals for these patients. (25)

In the survey FAs are defined as persons whohad more visits than 75th percentile (Q3) for his/her sex group in the year of 2006.

A visit is defined as encounter between a pati-ent and a doctor ‘’face to face’’.

Aims

1. Estimation of the prevalence of frequent attenders (FA);

2. Estimation and comparison of socio-demo-graphic characteristics of frequent attenders and non-frequent attenders (NFA);

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3. Determination of the health features of frequent attenders and comparison to not-frequent attenders;

4. Comparison of the health care services between FA and NFA.

Methods

Retrospective, longitudinal study based on data obtained from 434 randomly selected medical charts belonging to patients from four family me-dicine offices (1 urban, 2 suburban and 1 rural) inCanton of Sarajevo. There are twelve doctors in these family medicine offices and 10253 registe-red patients. Medical charts of patients who had only one visit in 2006 are not included in the sur-vey.

The medical sheet for a period of one year (2006) has been analyzed according to three main parameters:

a) Socio-demographic features: age, sex, marital status, household members, place of residence;

b) Health indicators: smoking status, number of chronic diagnosis, the leading diseases;

c) Indicators for use of health care resources: the number of visits during a year of 2006, the number of prescribed drugs, the number of referrals to specialists, the number of hospital days, number of days of sick leave, the number of home visits.

Continuous data is presented through out a de-scriptive statistics, ie mean and standard deviation (SD). Pearson’s correlation coefficient was usedfor measuring correlation between FA and NFA, as well as demographic data and presence of chronic diseases. Mann-Whitney Test was used for testing means of health service usage indicators because data hadn’t been regularly distributed. Odds ratio and 95% confidence interval were calculated to measure the strength of the association between the presence of disease and the occurrence of fre-quent visits.

All analyses above were calculated using the statistical package SPSS for Windows release (15.0.).

Results

434 medical charts out of 10253 registered pa-tients, belonging to above mentioned four FM of-fices have been analyzed. The sample was consist-ed of 273 female (62.9%) and 161 men (37,1%). The average age was 59.27 years (SD = 17.46, min = 7, max = 97). Patients from the sample had 5706 visits in the year of 2006. The Q3 value was 19 for men and 16 for women regarding the visits. The number of FAs with more visits than Q3 was 101 (23.3% of all analyzed medical charts). Table 1. Statistics of patients’ visits

Results Female Male TotalNumber of patients 273 161 434Number of visits 3439 2267 5706Mean 12,6 14,0 13,15Median 11 13 12Std. Deviation 7,7 8,9 8,17Minimum 2 2 2Maximum 47 64 64Percentiles 25 7 8 8 50 10 13 12 75 16 19 17

Socio-Demographic Characteristics

There were no significant differences betweenthe numbers of visits of female and male patients. Female sex representatives do not use the frequent visits services as much. (r=0,035, P>0,05). How-ever, significant differences were found betweenage groups.(r=0,105, P<0,05). The number of FA grows linearly with increasing of the age. Mean age of FAs (M=62,5, SD 14,3) is significantly hig-her than mean age of NFA. (M=58, 3, SD 18,2) (t=2, 1, df=432, P<0,05) Work status of the pati-ents also has a significant impact on the numberof frequent visits. (r=0,104, P<0, 05) The largest percent of the FA is in the group of pensioners (M of age=68,5, SD=10,8), and a group of adults wit-hout regular jobs (M of age=44,9, SD=10,2).

Small and non-significant differences werefound between groups of different marital status. (r=0,048, P>0,05). There were not significant dif-ferences between groups of type of households (r=0,036, P>0,05)

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The highest percentage of FAs live in a rural parts (29,7%), suburbs (26,0%) and the smallest percentage (17,3%) in the urban parts of Canton of Sarajevo. (r=0,123, P<0,01)

Health Indicators

Smoking prevalence among FAs is 23,0%. There were not significant differences withsmoking prevalence of NFAs (23,6%). (r=0,048, P>0,05) All patients had an average of 2,66 (SD 1,5) of chronic diseases. FAs had significantlymore chronic diseases (M=3,48, SD 1,67) than NFAs (M=2,34, SD 1,31). (F=51,6; P<0,01)

These are top ten diseases or disease groups followed with ICD-10 cods, total percentage, odds ratio (OR) and 95% confidence interval (95%CI).

1. Essential hypertension [I10] (58,3%, OR= 1,39, 95%CI: 1,19, 1,62) ,

2. Diabetes mellitus [E10-E11] (22,1%, OR= 2,16, 95%CI: 1,53, 3,04),

3. Other forms of heart disease [I30-I52] (19,4%; OR= 1,83; 95%CI: 1,24, 2,70),

4. Diseases of oesophagus, stomach and duodenum [K20-K29] (15,7%; OR= 1,05; 95%CI:0,90, 1,23),

5. Dorsopathies [M40-M54] (13,8%; OR= 1,1; 95%CI: 0,64, 1,89),

6. Ischemic heart diseases [I20-I25] (12,9%, OR= 1,44; 95%CI:0,85, 2,43),

7. Mood disorders [F30-F39] (9,7%, OR= 2,03, 95%CI:1,13, 3,63),

8. COPD [J44] (8,3%; OR= 1,27; 95%CI: 0,63, 2,54),

9. Neoplasms [C00-D48] (6,5%; OR= 2,86; 95%CI: 1,42, 5,80),

10. Disorders of lipoprotein metabolism and other lipdaemias [E70] (5,1%; OR=0,97; 95%CI: 0,37, 2,56),

Table 3 shows diseases significantly associatedwith frequent visits.

Table 2 Socio-demographic characteristicsFA NFA Total

Female 66 (24,2%) 207 (75,8%) 273 (62,9%)Male 35 (21,4%) 126 (78,6%) 161 (37,1%)Age groups - ≤19 1 (5,6%) 17 (94,4%) 18 (4,1%) - 20-39 5 (13,9%) 31 (86,1%) 36 (8,3%) - 40-59 33 (23,7%) 106 (76,3%) 139 (32,0%) - 60-79 52 (25,2%) 154 (74,8%) 206 (47,5%) - ≥80 10 (28,6%) 25 (71,4%) 35 (8,1%)Working status - Pensioner 73 (26,2%) 206 (73,8%) 279 (64,3%) - Employed 15 (16,8%) 63 (47,5%) 78 (18,0%) - Biro 12 (20,3%) 47 (79,7%) 59 (13,6%) - Student 0 (0%) 3 (100%) 3 0,7%) - Disciple 1 (6,7%) 14 (93,3%) 15 (3,5%)Marital status - Married 65 (24,3%) 202 (75,7%) 267 (61,5%) - Widow/er 2 (11,8%) 15 (88,2%) 17 (3,9%) - Divorced 28 (28,9%) 69 (71,1%) 97 (22,4%) - Never married 6 (11,3%) 47 (88,7%) 53 (12,2%)Household - Family (spouse and/or children) 81 (24,5%) 250 (75,5%) 331 (76,3%) - Single 14 (17,9%) 64 (82,1%) 78 (18,05) - Other 6 (24,0%) 19 (76,0%) 25 (5,8%)

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Health service usage indicators

FAs (23,3%) used among 33,9% to 54,1% ser-vices out of 7 health service usage indicators. Significant differences on the level P< 0,01 werefound between FAs and NFAs

Discussion

The Research of the prevalence of FAs can in-clude population of registered patients in the med-ical clinics (2, 5, 7, 8, 14, 18) or less frequently, the general population. (9, 25) The first type of stud-ies have considerably greater prevalence than the second type (5-26%vs.3-4,7%). FAs prevalence in this study is very similar to results of studies conducted in neighboring Croatia (total FAs prev-

alence 22%) (16) and Slovenia (24%) (10). How-ever, our patients had a much higher mean of visits to those in Croatia and Slovenia.

Most results of the research link FAs with old-er age and female sex. (7, 15, 21, 22, 26, 27, 28) Non-significant differences were fond between sexgroups in this study.

Working status had significant impact on num-ber of visits. Pensioners were more in number to those in other groups. This could be explained by the fact that pensioners are elderly people and prob-ably have less income. Also, unemployed patients have more visits per year than others. Both these results match the researches conducted in different countries. (2, 3, 7, 8, 15, 21, 26, 27, 29)

Many of researches highlighted the importance of the influence of marital status on the number ofvisits. (2, 3, 7, 15, 26) In this research marital sta-

Table 3 Most common diseases of FADisease FA NFA Total

1 Essential hypertension (I10)** 75 (74,3%) 178 (53,5%) 253 (58,3%)

2 Diabetes mellitus (E10-E11)** 38 (37,6%) 58 (17,4%) 96 (22,1%)

3 Other forms of heart disease (I30-I52)** 30 (29,7%) 54 (16,2%) 84 (19,4%)

4 Mood disorders (F30-F39)* 16 (15,8%) 26 (7,8%) 42 (9,7%)

5 Neoplasms (C00-D48)** 13 (12,9%) 15 (4,5%) 28 (6,5%) * P<0,05 ** P<0,01

Table 4. Health service usage indicators (data for year 2006)

Indicator*FA NFA Total

N % M SD N % M SD N M SD

Office Visits 2489,0 43,6 24,6 7,4 3217,0 56,4 9,7 4,3 5706,0 13,1 8,2

Medications 527,0 34,5 5,2 2,8 999,0 65,5 3,0 1,9 1526,0 3,5 2,3

Specialists Referrals/ consultation 876,0 45,0 8,7 13,4 1072,0 55,0 3,2 3,1 1948,0 4,5 7,3

Referrals in the laboratory 184,0 33,9 1,8 1,4 358,0 66,1 1,1 1,0 542,0 1,2 1,2

Days spent in hospital 627,0 50,5 6,2 13,0 614,0 49,5 1,8 7,6 1241,0 2,9 9,3

Sick leave days** 1193,0 53,4 79,5 106,0 1042,0 46,6 16,5 40,4 2235,0 29,5 28,9

Home visits 40,0 54,1 0,4 1,0 34,0 45,9 0,1 0,4 74,0 0,2 0,6*P<0,01 for all indicators** Counted for the group of patients with regular jobs

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tus correlated non-significantly with the numberof visits, although the divorced group had largest percentage FA (28,9%).

Significantly greater percentage of FAs in therural and suburban group could be explained by the influence of low education level, health illit-eracy, as well as low socio-economic status.

There is a vast amount of evidence that FAs have more chronic physical and psychiatric is-sues. (2, 3, 7, 8, 9, 11, 15, 16, 18, 25, 26, 30) The results of this study are similar to others. It has been shown that FAs had more diseases, especial-ly essential hypertension, diabetes mellitus, other forms of heart disease, mood disorders and neo-plasms. Smoking is not connected with frequent visits as results of other researchs.(17)

Smaller group of patients, the FAs used signifi-cantly more health care system services then more numerous groups of NFAs. Such results match with other researches.(9, 26) Especially there were high percentages of the referrals to other special-ists, hospital days, sick leave days and home vis-its.

Conclusion

In all health systems, there is a certain percent-age of patients who can be identified as FAs. Theseare the people mostly defined as elderly men andwomen with a bad socio-economic background, coming form the rural and suburban parts of the country, and most importantly with a poor physi-cal and mental health. FAs have significantly morechronic diseases and are frequent consumers of the services and resources of the health system, espe-cially, patients with specific chronic illnesses suchas hypertension, diabetes mellitus, and other forms of heart disease, mood disorders and neoplasms. Other researches also emphasize the specificity of hypertension and diabetes (31) The fact that they feel the need for frequent doctor visits, reflectstheir need and vulnerability (17), which requires special care for this group of patients.

In addition, it is a common thing to have FAs who have unrecognized and unsolved medical problems. (19, 32)

A higher percentage of Fas in family medicine office may be indicator of low quality level of he-

alth care and an improper use of health systems.(-28, 33) It is often an indication of undiagnosed problems, especially hidden depression.(19)

It is very important that family medicine team members to develop a strategy how to deal with the FA, especially with those who have a very lar-ge number of visits.(16, 27)

The first step is the identification of FAs andtheir health and other problems. It is possible to divide these patients into the following subgroups: “(1) patients with entirely physical illnesses; (2) patients with clear psychiatric illnesses; (3) crisis patients; (4) chronically somatizing patients; and (5) patients with multiple problems.’’(31) An ana-lysis of families and communities capabilities to help patient is needed. Most of them really have a serious chronic illnesses, which implicate the sec-ond step- thoroughly planning and management of those chronic diseases. The third step is to resolve social and other problems, if possible, with the en-gagement of all available resources.

Continuous monitoring of those diseases through out a longer period of time is the next step which needs to be ensured for these patients. There is a need to assess and heal a so called “iatrogenic factor’’ that is common in FAs. Iatrogenic factor is characterized with a lack of information for pa-tients, polypharmacy, excessive and unnecessary tests and treatments. (28, 34, 35, 36)

There are other possible causes for such a high percentage of FAs estimated in this study such as: poor health of our residents in comparison to other countries, the poor work organization FM teams, a low level of quality of management of chronic diseases (especially hypertension, diabetes, heart diseases, depression and malignant diseases), obstacles associated with the regulation of drugs prescription, the lack of healthcare information systems and poor and ineffective cooperation with other health levels.

Limitation to this study is a relatively small number of analyzed medical charts, only 4 FM of-fices in Canton of Sarajevo, a limited level of in-formation about patients in medical charts (a lack of essential parameters about of income, specificeducation and detailed information about patients’ jobs, family cycles and family relations, the level of stress, somatoform disorders) Level of patients satisfaction is not explored.

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Future researches in our region should involve a greater number of patients in more FM officesand secondary health care. They have to focus on finding ways for easier FAs identification, effec-tive preservation and continuity of health care and finding efficient management methods of healthand other FAs problems.

Literature

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2. Browne GB, Humphrey B, Pallister R, et al. Preva-lence and characteristics of frequent attenders in a prepaid Canadian family practice. J Fam Pract 1982; 14: 12

3. Karlsson H, Lehtinen V, Joukamaa M. Frequent Attenders of Finnish Public Primary Health Care: Sociodemographic Characteristics and Physical Morbidity. Fam. Pract. 11:424-430, 1994.

4. Gill D, Sharpe M. Frequent consulters in general practice: a systematic review of studies of preva-lence, associations and outcome. J Psychosom Res. 1999;47:115–130.

5. Vedsted P, Fink P, Olesen F, Munk-Jřrgensen P.Psychological distress as a predictor of frequent attendance in family practice: a cohort study.Psyc-hosomatics. 2001 Sep-Oct;42(5):416-22.

6. Carney TA, Guy S, Jeffrey G. Frequent attenders in general practice: a retrospective 20-year follow-up study. Br J Gen Pract. 2001 Jul;51(468):567-9.

7. Westhead JN.Frequent attenders in general practi-ce: medical, psychological and social characteri-stics.J R Coll Gen Pract. 1985 Jul;35(276):337-40.

8. McArdle C, Alexander WD, Murray Boyle C. Freq-uent attenders at a health centre. Practitioner 1974; 213:696-702

9. Svab I, Zaletel-Kragelj L. Frequent attenders in ge-neral practice: a study from Slovenia. Scand J Prim Health Care. 1993;11:38-43.

10. Kersnik J, Svab I, Vegnuti M. Frequent attenders in general practice: quality of life, patient satisfa-ction, use of medical services and GP characteri-stics. Scand J Prim Health Care. 2001 Sep;19(3):174-7

11. Scaife B, Gill P, Heywood P, Neal R. Socio-eco-nomic characteristics of adult frequent attenders in general practice: secondary analysis of data. Fam. Pract. 2000; 17(4): 298 - 304.

12. Hodgson P, Smith P, Brown T, Dowrick C. Stories from Frequent Attenders: A Qualitative Study in Primary Care. Ann. Fam. Med, 2005; 3(4): 318 - 323.

13. Jackson JL, Kroenke K. Difficult patient encoun-ters in the ambulatory clinic: clinical predictors and outcomes. Arch Intern Med. 1999;159:1069–1075.

14. Andersson SO, Mattsson B & Lynoe N (1995) Pa-tients frequently consulting general practitioners at a primary health care centre in Sweden -a com-parative study. Scand J Soc Med 23: 251-257.

15. Larivaara P, Väisänen E & Wynne LC () Develo-ping a family systems approach to rural healthca-re: dealing with the “heavy-user” problem. Fami-lies, Systems & Health. 1996 ;14: 291-302.

16. Vrca Botica M, Kovacić L, Kujundzić Tiljak M, Katić M, Botica I, Rapić M, Novaković D, Lovasić S.Frequent attenders in family practice in Croa-tia: retrospective study.Croat Med J. 2004;45(5):620-4.

17. Savageau JA, McLoughlin M, Ursan A, Bai Y, Collins M, Cashman SB.Characteristics of freq-uent attenders at a community health center.J Am Board Fam Med. 2006 May-Jun;19(3):265-75.

18. Von Korff M, Ormel J, Katon W, et al. Disabili-ty and depression among high utilizers of health care. Arch Gen Psych 1992; 49: 91-100.

19. Smits FT, Mohrs JJ, Beem EE, Bindels PJ, van Weert HC.Defining frequent attendance in generalpractice.BMC Fam Pract. 2008 Apr 15;9:21.

20. Howe A, Parry G, Pickvance D, Hockley B. De-fining frequent attendance: evidence for routineage and sex correction in studies from primary care settings. Br J Gen Pract. 2002;52:561–562.

21. Dowrick CF, Bellon JA, Gomez MJ. GP frequent attendance in Liverpool and Granada: the impact of depressive symptoms. Br J Gen Pract. 2000;50: 361-365.

22. Goodridge DMG An analysis of fat folders. J R Coll Gen Pract.1982;32: 239-241.

23. Mathers N, Jones N, Hannay D. Heartsink pati-ents: a study of their general practitioners. Br J Gen Pract. 1995;45:293-296.

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24. Gill D, Dawes M, Sharpe M, Mayou R. GP fre-quent consulters: their prevalence, natural histo-ry, and contribution to rising workload. Br JGen Pract. 1998;48:1856-1857

25. Jyväsjärvi S. Frequent attenders in primary health care A cross-sectional study of frequent attenders’ psychosocial and family factors, chronic disea-ses and reasons for encounter in a Finnish health centre , Doktorska disertacija, University of Oulu, 2001; 24-25

26. Heywood PL, Blackie GC, Cameron IH & Dowell AC (1998) An assessment of the attributes of freq-uent attenders to general practice. Fam Pract 15: 198-204.

27. Neal RD, Heywood PL, Morley S, Clayden AD, Dowell AC. Frequency of patients’ consulting in general practice and workload generated by fre-quent attenders: comparisons between practices. Br J Gen Pract.1998; 48: 895-898.

28. Reid S, Wessely S, Crayford T, Hotopf M. Medical-ly unexplained symptoms in frequent attenders of secondary health care: retrospective cohort study. BMJ 2001; 322; 767-771

29. Báez K, Aiarzaguena JM, Grandes G, Pedrero E, Aranguren J & Retolaza A. (1998) Understanding patient-initiated frequent attendance in primary care: a case-control study. Br J Gen Pract 48: 1824-1827.

30. Leung KWM, Tsui WSW, Chu DWS. Survey on fre-quent attenders - a study to analyze the associati-ons between frequency of attendance and chronic illness and socio-economic factors in an outpati-ent clinic. HK Pract 2007;29:189-198

31. Foster A, Jordan K, Croft P. Is frequent attendan-ce in primary care disease-specific? Fam. Pract.2006;23:444-452,

32. Karlsson H, Joukamaa M, Lahti I, Lehtinen V, Kokki-Saarinen T: Frequent attender profiles: dif-ferent clinical subgroups among frequent attender patients in primary care. J Psychosom Res. 1997, 42:157-166.

33. Stewart P, O’Dowd T: Clinically inexplicable frequent attenders in general practice. Br J Gen Pract 2002, 52:1000-1001.

34. Kouyanou K, Pither C, Wessely S. Iatrogenic fa-ctors and chronic pain. Psychosom Med 1997;59:597-604.

35. Kouyanou K, Pither CE, Rabe-Hesketh S,Wessely S. A comparative study of iatrogenesis, medication abuse, and psychiatric morbidity in chronic pain patients with and without medically unexplained symptoms. Pain. 1998;76:417-26.

36. Wilkie A, Wessely S. Patients with medically une-xplained symptoms. Br J Hosp Med 1994; 51:4-21-7.

Corresponding author: Zaim Jatic Public Institution Medical Centre of the Sarajevo Canton, Bosnia and Herzegovina e-mail: [email protected]

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Summary

Basal cell carcinoma is slow growing malignant skin tumor characterized by uncontrolled growth of the basal skin layer. It represents very common type of tumor that rarely yields in metastases. It usually found in craniofacial region, in locations that make rather simple surgical procedures ap-pear complex, such as orbital and nasal regions. The most effective treatment of this tumor is radi-cal surgical excision, sometimes in cases of well progressed tumor invasion it also includes and/or radiotherapy, rarely even chemotherapy. The goal of this retrospective study was to determine the prevalence of this tumor in different parts of crani-ofacial region, its distribution in terms of patient’s gender and age, as well as clinical stage in time of the diagnosis. In statistical analysis of acqui-red data the methods of descriptive statistics were used, and for the proper level of results significan-ce p was made to be <0,001.

The basal cell carcinoma represents the most common epithelial non-melanocytic tumor in this region. 127 cases of basal cell carcinoma located in craniofacial region were analyzed through data obtained during the 5-year period (2004. – 2000.). Data was obtained from different aspects of me-dical history records, clinical findings, diagnosticprocedure used, and through surgical treatment of choice. 11% of all diagnosed basal cell carcinoma found in craniofacial region were those localized in orbital subregion. Gender distribution showed female dominance in male to female ratio of 1:1,5. There was no significant difference between ages

for men and women diagnosed with this tumor, and in 80% of cases the clinical stage at which ba-sal cell carcinoma was diagnosed was I.

Key words: basal cell carcinoma, orbital re-gion

Sažetak

Bazocelularni karcinom je maligni tumor kože, sporog rasta koji nastaje nekontroliranim buja-njem temeljnog (bazalnog) sloja kože. Predstavlja vrlo čest, tumor koji rijetko metastazira. Najčešće se pojavljuje na kraniofacijalnim regijama i to vrlo često na lokalizacijama koje su vrlo kompleksne za hirurški rad, kao što su orbitalna regija i nos. Najefikasnija terapija tumora ove regije je radikal-na hirurška ekscizija a kod veoma uznapredova-lih stadija hirurška i/ili radio terapija a nekada i hemioterapija. Cilj rada je da se utvrdi učestalost ovog karcinoma u odnosu na druge dijelove kra-niofacijalne regije. Njegova polana i starosna di-stribucija i klinički stadij u kojem je bolest dija-gnostikovana. Ovaj rad predstavlja retrospektivnu studiju. U statističkoj obradi dobijenih podataka koristit će se metode deskriptivne statistike sa izračunavanjem srednje vrijednosti i standardne devijacije, a za utvrđivanje značajnosti razlika ko-ristit će se χ2 test uz prihvatanje signifikantnostina nivou p<0,001.

Ovaj tumor predstavlja najčešći maligni epi-telni nemelanositni tumor u ovoj regiji. U ovom radu anlaizirali smo 127 dijagnostikovanih bazo-celularnih karcinoma u petogodisšnjem vremen-

Basal cell carcinoma of orbital regionBAZOCELULARNI KARCINOM ORBITALNE REGIJEAdi Rifatbegovic1*, Ermina Iljazovic2, Nedret Mujkanovic1, Azra Pasic1, Emir Halilbasic1, Mufid Burgic1

1 Department of plastic and reconstructive surgery, Surgery clinic, University clinical center of Tuzla, Bosnia and Herzegovina2 Department of pathology, Policlinic for laboratory diagnostics, University clinical center of Tuzla, Bosnia and Herzegovina

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skom periodu (2000-2004). Rad predstavlja re-trospektivnu studiju u kojoj smo iz istorija bolesti sagledali: anamnestičke podatke, klinički nalaz, dijagnostičke procedure i primjenjenu hirurško-te-rapijsku mjeru. U odnosu na sve dijagnostikovane bazocelularne karcinome kraniofacijalne regije na orbitalnoj regiji dijagnostikovan je u 11% slučaje-va. Polna distribucija muškarci u odnosu na žene nalazi se u omjeru 1:1,5. Prosječna starosna dob je skoro identična a u 80% slučajeva karcinom je dijagnostikovan u kliničkom stadiju I.

Ključne riječi: Bazocelularni karcinom, orbi-talna regija

Introduction

Basal cell carcinoma (BCC) is slow growing malignant skin tumor characterized by uncon-trolled growth of the basal skin layer. It represents very common type of tumor that rarely yields in metastases. BCC has a tendency to occur in skin regions that are chronically exposed to sun, and in people with pale-looking skin (Hurt i Santa Cruz, 2003; Rosai, 2004). Radiation with 20-50 year latency period and long-term contact exposure to arsenic, as well as UV radiation are all considered to be important risk factors in development of BCC. It has a very good prognosis, if treatment is adequate, but on the other hand untreated lesions locally do invade deeper tissue structures. Dur-ing a large study which involved 900.000 people (550.000 men and 350.000 women) it was found that BCC incidence for men was 475 and 250 for women which then translated in to 33-39% risk for Caucasian men, and 23-38% for Caucasian women (Ramsey, 2004). This skin tumor most commonly occur in the regions of head and neck (91,5%) (Tiftikcioglu i sar., 2006) usually local-ized in places that are much complex for surgi-cal treatment such as eyelids and nose, although they also occur in different bare parts of the body such as hands, and very rarely on the parts of the body that are usually cover with clothes. It can be exulcerated in late stages of the disease. BCC me-tastases occur in 0,0028 to 0,1% of cases (Patel, Thigpen, Vance, Elkins i Guo, 1999). Fatal out-come is very rare in case of basal cell carcinoma. Frequency of occurrence for men and women is

2:3. BCC in head and neck regions can invade deeper structures and can have endo- and peri-neural spread which can additionally complicate the course of the disease and proper treatment. Orbital region presents a bilateral facial subregion that is further divided into four distinct parts: me-dial and lateral angle of eye, and upper and lower eyelid. This type of subregional distinction is made because of easer orientation, detailed localization of pathological process and different surgical ap-proach. Tumors of this region are very common in clinical practice. The most effective treatment of tumors in this region is radical surgical exci-sion, and for those diagnosed in late stages surgi-cal and/or radiotherapy, followed by chemothera-py when needed. The most common localizations are as follows: lower eyelid 48,9%, medial angle of eye 27,6%, upper eyelid and lateral angle of eye 23,5% (Cook i Bartley, 1999). Postoperative defects are often very complex for proper closure since the radical excision is absolute priority and since reconstruction must be functionally impec-cable as well as aesthetically flawless (Picture 1, 2.and 3.) BCC is most common epithelial non-me-lanocytic tumor of this region. It is often necessary to clinically determine if the suspicious lesion is in fact tumor or some local inflammatory reactionsince in some cases the appearance is very simi-lar. Eyelid tumors are relatively frequent findingin clinical practice.

Picture 1. BCC of lower eyelid

Picture 2. Radically excised BCC with recon-structive procedure planned

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Picture 3. Postoperative result

Aim

The aim of this study was to determine the prev-alence of basal cell carcinoma (BCC) occurring in orbital region diagnosed in University Clinical Center of Tuzla during 5-year period (01.01.2000. – 31.12.2004.), its distribution in terms of patient’s gender and age, as well as its clinical stage in time of the diagnosis. The study included 127 cases of BCC localized in orbital region during the 5-year time period. It is a retrospective study during which patient medical history was used for acquir-ing general data, as well as data on clinical find-ing, diagnostic procedures and surgical treatment. Following variables were analyzed: general patient data, age, gender; clinical finding: characteristics ofsuspected lesion (anatomical localization and size). Proper diagnosis was based on adequate biopsy and pathohistological verification of tumor. Biopsy ofsuspected lesion can be done by curettage, deep layer aspiration, incision and excision. Excision bi-opsy stands for complete removal of tumor tissue together with “clean” (tumor-free) margin, and thus is of great diagnostic and treatment value. Incision biopsy stands for surgical removal of only a small part of tumor tissue, usually when tumor is too large and has complex location which makes the subse-quent total removal impossible. Surgical excision presents very effective way in treatment of all kinds of skin tumor in many different locations. The size

of “tumor-free” margin varies depending on patho-histological type of tumor, as well as on size and tumor localization, but 3-5 mm margin usually suf-fice. When large defect is present after the removalof tumor, a reconstructive surgical treatment is nec-essary. Histomorphologic analysis of excised lesion and resection margins was done using standard 5µm thick paraffin cut slices, dyed using standard H&Emethod. Imunohistochemical analysis was done for a certain number of undifferentiated malignant pri-mary and secondary lesions using three-step imuno-peroxidase method with streptavidine. In statistical analysis of acquired data the methods of descriptive statistics were used including χ2 test used in diffe-rence determination, and for the proper level of re-sults significance p was made to be <0,001.

Results

During 5-year period (01.01.2000. – 31.12.2004.) in University clinical center of Tuzla, 881 basal cell carcinoma (BCC) occurring in craniofacial region was diagnosed. 127 of them were localized in or-bital region (11%), 51 of which were diagnosed in men, and 76 in women. Mean age for both male and female was about the same (Table 1.).

This study showed that BCC was usually veri-fied in clinical stage I (Graph 1.)

Graph 1. Prevalence of different clinical stages for BCC

Table 1. Mean age of patients diagnosed with BCC in orbital region in respect to gender Orbital region

Type of skin tumorMean age

Min. i max. ageM FŽ

M F Min. Max. Min. Max.Basal cell carcinoma 66 65 39 89 33 86

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Discussion

One of the most important characteristics of skin as an organ lays in its sensory function to communicate with surroundings, but it is also the largest organ of the human body that provides protection from all potentially harmful external influences. All of the frequently exposed parts ofskin such are those in the regions of face, neck and hands, that are often under constant influenceof multiple external factors such as UV radia-tion, weather and climate conditions, diet, nico-tine and alcohol with time accumulate effects of such destructive impact. Different world studies conclude increase in skin cancer incidence, espe-cially in past few decades (Corona, 1996; Collins at all., 2004). In USA alone every year it is ex-pected about 1 million newly diagnosed cases of skin cancer, mostly basal (BCC) and sqamuos cell carcinoma (SCC), while in Holland, in accordance with national cancer registry, predictive calcula-tions about increase in incidence for these tumors surge up to 80%. 20 654 patients with skin cancer were newly diagnosed in the year 2000., and it is expected that the number of those patients for the year 2015. will be 37 342 (de Vries at all., 2005). Various epidemiological studies showed that pa-tients who are diagnosed with BCC and SCC have greater risk of developing some other malignant disease, although the exact assessment of such risk is not yet known (Karagas at all., 1998). Orbital region is very specific and very complex regionfor surgical interventions that often necessitates team work form both plastic and ophthalmolog-ic surgeon. That is why the frequency, size and the type of tumor occurring in this region are of much interest. During our study, 127 skin tumors were verified in this region, which is completelyin accordance to data obtained from different rel-evant literature. It was found that these types of skin tumors are somewhat more often diagnosed in women (60%), which also coincide to data in available world literature. It was found that BCC is more often diagnosed (95%) than SCC, mostly in women, while SCC is much more rarely veri-fied with equal distribution in both genders. Manydifferent studies throughout the world also present similar results (Szepietowski, 2004; Salomon at all., 2004; Rubin at all., 2005). During the gen-

der and age distribution analysis it was shown that diagnosed tumors occur in both male and females mostly between third and ninth decade. In men there is a peak in incidence somewhere between sixth and eighth decade, while in women such peak occurs in seventh and eighth decade. The highest number of diagnosed skin tumors in both genders was in clinical stage I (80%), and clini-cal stage II (17%), which is in accordance to data obtained during a study that was done in Izmir, Turky, where 78% of skin tumors was verified inclinical stage I, with maximal diameter measuring 20 mm (Ceylan at all., 2003). Tumors with sizes 2-5cm in diameter (T2) are large tumors where ex-cision almost always results in large tissue defects. Such defects in this region present exceptional problem in terms of its reconstruction. It is often necessary to excise, in variation to its localization, whole eyelid or at least large part of both upper and lower eyelid including medial or lateral angle of eye. Reconstruction of such defect in delicate orbital subregion often presents complex surgical problem. If surgical excision requires resection all of the eyelid structures, then it is necessary to reconstruct complete eyelid ad integrum. Smaller defects are usually closed via direct suturing or using full thickness skin graft from an adequate donor site, while larger defects are reconstructed via local skin flaps in combination with conjunc-tiva free flaps from the opposite side or buccalmucosa and auricular cartilage, or with cartilage from nasal septum. Excision radicality should be pathohistologically verified during operative pro-cedure, which means prior immediate reconstruc-tion. Because of the region’s specificity and itsdeep structures, it is clear that any mistake made during the operative procedure may result in very grave consequence for the patient.

Conclusion

Out of all diagnosed BCC in craniofacial re-gion, 11% was localized in orbital subregion. Male to female distribution ratio was 1:1,5. Aver-age age in both genders was almost identical, and BCC was in 80% of the cases diagnosed in clinical stage I. When diagnosed in clinical stage I, BCC does not require complicated surgical approach.

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BCC with large diameters are sometimes associ-ated with excessive surgical procedures, and ra-diotherapy with or without chemotherapy follows. Every BCC classified as T1 have good prognosisfollowing surgical treatment.

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11. Salomon J., Bieniek A., Baran E., Szepietowski JC (2004) Basal cell carcinoma on the Eyelids: Own Experience. Dermatol Surg 30:257-263.

12. Szepietowski JC (2004) Basal cell carcinoma on the eyelids: Own experience. Dermatol. Surg. 30:257-263.

13. Rubin P, Mykula R, Griffiths R.W. (2005) Ectropi-on following excision of lower ejelid tumours and full thickness skin graft repair. Britis Journal of Plastic surgery 58:353-360.

14. Ceylan C., Ozturk G., Alper S (2003) Non-Mela-noma skin cancers between the years of 1990 and 1999 in Izmir, Turkey: demographic and clinico-pathological characteristics. J Dermatol. 30(2):1-23-131.

15. Meads SB., Greenway HT (2006) Basal Cell Car-cinoma Associated with Orbital Invasion: Clinical Features and Treatment Options. Dermatol. Surg. 32:442-446.

Corresponding author: Adi Rifatbegovic, Department of plastic and reconstructive surgery,

Surgery clinic, University clinical center of Tuzla, Bosnia and Herzegovina e-mail: [email protected]

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Summary

In the article according to the previously set parameters is correlated efficacy of two forms ofextramedullary ostheosynthesis in case of diaphy-seal small hand and foot bones fractures.

Research goal is to determine definite func-tional and radiography parameters after fractures and bone changes (24 fractures. 6 bone tumors/cysts) after implementation of the Extramedul-lary Fixation with Kirschner wires and Cerclage – EFIKS ostheosynthesis and use of technique with plates and screw.

Material and methodology; Two groups of 15 ostheosynthesis among 26 patients were selected. Fist injury was present in 22, and foot in 4 cases. In case of 2 patients there were open fractures (Gustilo I/II).

Results; after the end of the treatment all im-plants were identified in the primary set posi-tion. Complete healing of the fractures was in 25 (83.3%) ostheosynthesis. Reduction of movement in neighboring joints was in ratio + 50 - 100 . In the EFIKS group of ostheosynthesis complications

were noted in 2 (6.6%) ostheosynthesis; break of the cerclage wire (1), angulations at the point of fracture (1). In case of ostheosynthesis with use of plate and screws complications were noticed in 3 (10%) ostheosynthesis; slower bone healing (1), loosening of the screws and plate (1), plate bend-ing (1).

Conclusion; Extramedullary stabilization of fracture and bone changes within the tested sample and the two specific group of patients with differ-ent forms of extramedullary ostheosynthesis did not show statistically significant differences in thefinal radiology and functioning results accordingto the set parameters of research (p>0.05). EFIKS ostheosynthesis have the possibility for wider ap-plication in surgery and it is complete acceptable alternative to those who does not have the plates and screws. Opposite to this extramedullary fixa-tion of fractures with the use of screws and plates is still leading and irreplaceable as the method in case of joint and metaphyseal fractures.

Key words; extramedullary ostheosynthesis, bone healing

Effects of Specific Forms ofExtramedullary Fixation in Treatment of Diaphyseal Small Bone FracturesEFEKTI SPECIFIČNIH OBLIKA EKSTRAMEDULARNE STABILIZACIJE NA SANACIJU PRIJELOMA DIJAFIZA MALIH KOSTIJUZoran Hadziahmetovic1, Narcisa Vavra – Hadziahmetovic2

1 Clinic for emergency medicine, Clinical Center of Sarajevo University, Bosnia and Herzegovina2 Institute for physical medicine and rehabilitation, Clinical Center of Sarajevo University, Bosnia and Herzegovina

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Sažetak

U radu se prema zadanim parametrima kore-lira efikasnost dva oblika ekstramedularne osteo-sinteze kod prijeloma dijafiza malih kostiju šake istopala.

Cilj istraživanja je utvrđivanje definitivnihfunkcionalnih i radiografskih parametara poslije prijeloma i koštanih promjena (24 prijeloma. 6 koštanih tumora/cista) nakon provođenja Ekstra-medularne FIksacije Kirschner iglama i Serklažom – EFIKS osteosinteze i tehnike korištenjem pločica sa vijkom.

Materijal i metode; Selektirane su dvije grupe od po 15 osteosinteza kod 26 pacijenata. Povreda šake je bila kod 22, a stopala kod 4 ispitanika. Kod 2 pacijenta prijelomi su bili otvoreni (Gustilo I/II).

Rezultati; Po završenom liječenju svi implan-tati su bili identificirani u primarno postavljenojpoziciji. Potpuna sanacija prijeloma je bila kod 25 (83,3%) osteosinteza. Redukcija kretnji na susjed-nim zglobovima je bila u omjeru + 50 - 100. U gru-pi EFIKS osteosinteza komplikacije su zabilježe-ne kod 2 (6,6%) osteosinteze; pucanje serklažne žice (1), angulacija na mjestu prijeloma (1). Kod osteosinteze sa pločicom i vijcima komplikacije su evidentirane kod 3 (10%) osteosinteze; uspo-reno koštano cijeljenje (1), razlabavljenje vijaka i ploče (1), savijanje ploče (1).

Zaključak; Ekstramedularna stabilizacija pri-jeloma i koštanih promjena u ispitivanom uzorku i dvije specifične grupe ispitanika sa različitim ob-licima ekstramedularnih osteosinteza nija pokaza-la signifikantne razlike u konačnim radiografskimi funkcionalnim rezultatima prema zadanim para-metrima istraživanja (p>0,05). EFIKS osteosinte-za ima mogućnost šire praktične hirurške primje-ne i potpuno je prihvatljiva alternativa za one koji ne raspolažu pločicama i vijcima. Nasuprot tome ekstramedularna fiksacija prijeloma sa vijcimai pločicama još uvijek je suverena i nezamjenjiva kao metoda u situacijama zglobnih i metafizarnihprijeloma

Ključne riječi; ekstramedularna osteosinteza, koštano cijeljenje

Introduction

When discussing about the ostheosynthesis of the small bones still today there is an always pre-sent problem of ostheosintetic material selection as well as adequate fixation of the fractures, espe-cially when it is a case of unstable fracture of fistand foot. Majority of authors as only or alternati-ve solution see in preference for Kirschner wires or screws positioned intramedullary (adaptation ostheosynthesis), even in situation when there are complex fractures of one or multiple bones (se-rial fractures of metacarpal/tarsal bones). What is actually in use in these situations is the use of generally mini plates of 2.7 mm according to AO authors(1,2). Regardless of the fixation type used(tension band, wire loop, plates, screws, external fixator) the main goal is to achieve positive fixati-on effect trough dynamic compression where with mobility and muscle activity compressive to the point of fracture will increase. What is also impor-tant is the limited contact between the implant and the bone („low contact plate/ no contact plate“) with which principles of the „biological fixation”of the fracture are achieved. With this preserved are elements of moderate elasticity, rigidness, better biological tolerance as well as presence of the sufficient compression between fragments (3,4). What is the crucial problem in case of isolated intramedullary adaptation ostheosynthesis is the control over the bone axis disorder such as: tor-sion, angulations or contraction of the fragments, and which are caused by bending or fracture of the ostheosintetic material after the fragments are kept in bad (“mal”) position. This often escalates to the lack of healing, poor healing with the consequen-tial deformities and biomechanical disorders (5,6).

Today in use is the large number of fixation tec-hniques for the diaphyseal fractures small bones fractures. That is usually stabile extramedullary or instable intramedullary fixations which are lin-ked to the especially adapted instruments as well as implants of various sizes and shapes (7). When eventually thinking of external fixation in caseof small diaphyseal fractures of foot and fist thatit is very inappropriate in case of load or muscle activity, which leads to loosening of the complex screw - external fixator, as well as movement ofthe fracture, so it is reserved exclusively for the

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larger defects of the soft tissue and the bone as temporary procedure.

Voluminous implants which are implanted in proclaimed surgical procedures often leads to huge surgical and post-surgical hazard; soft tissue destruction, increase of periosteal necrosis in large segmented bone fields (endangered local vascula-rization), reduced elasticity of the bone and others. This have as a consequence progression of prima-ry state and occurrence of above mentioned com-plications (8). Due to this large number of authors modified their implantation techniques giving pri-ority to the minimally invasive surgical procedu-res, without open presentation of the fracture site and with fluoroscopic guidance of the fragmentuntil reduction and fixation of the fracture. Amongother complications we should mention migration of alanthesis which can have extensive consequ-ences (9,10).

Research goal

Previous experimental and clinical researches indicated that the radiography and functional trea-tment results of the small bone diaphyseal fractu-

res with specific, original model of extramedullaryfixation of the fractures (Extramedullary Fixation with Kirschner Wires and Cerclage - EFIKS) in comparison to intramedullary ostheosynthesis much better with less complications (7,11). This initiated further research in terms of determining definite functional results after conducted EFIKSostheosynthesis and other extramedullary ostheo-synthesis under same conditions of traumatic sub-strate which will give an answer about:

• process of bone healing in case of fractures and bone fusions (arthrodesis) by use of elastic and non elastic (rigid) extramedullary ostheosynthesis of the small diaphyseal fractures

• surgical applicability of these two forms of ostheosynthesis

Matherial and research methods

At the Clinical Center of Sarajevo University within Clinics for Emergency Medicine as well as Plastic and Reconstructive Surgery in a time pe-riod from January 1st 2006 until December 31st

Table 1 Indications for implantation of the ostheosintetic material in certain fractures types

Tension band (Zuggurtung)

Screw / Kirsch. wire

intramedullary, cerclage (8)

Tension screw (8) Plate with screws (8)

Extramedullary fixationwith Kirschner wires

and cerclage

1.joint destructions - arthrodesis

1.transfersal fractures, stable fractures

1.unstable long and skew or spiral diaphyseal fracture

2. joints fractures

1. Multiple MTC fractures

2. periaticular and multiple fractures of the joints

3. multi-fragmented fractures with shortening and rotation

4. fractures with segment bone loss

5. open fractures

6. joint destructions - arthrodesis

1. multi-fragmented fractures with shortening and rotation

2. fractures with segment bone loss

3. open fractures

4. Multiple MTC fractures

5. unstable long and skew or spiral diaphyseal fracture

6. transversal stable fractures

7. joint destructions - arthrodesis

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2007 we have treated 26 patients (24 fractures and 6 bone tumors/cysts). Selection of ostheosintetic material or type of the surgical procedure was wit-hin indication field presented at the Table 1. Weused two forms of extramedullary ostheosynthe-sis at feet and hands as follows: 14 patients with 15 EFIKS ostheosynthesis (11 diaphyseal, 1 bone tumor, 3 cysts) and 12 patients which have im-planted 15 plates 2.7/3.5 mm with screws - AO (13 fractures, 1 bone tumor, 1 cyst) of phalanges and metacarpal/metatarsal bones. Fractures and bone changes on hands were present among 22 patients and among 4 patients on foot. Ratio between men and women was 21: 5. Average age of the respon-dents was 33.4 years (ranging between 12 and 53 years). Under general anesthesia we surgically treated 22 patients while 4 patients had regional anesthesia. Average duration of hospitalization was 8 days. The shortest follow up time (functio-nal and radiography finding) was after 3, and lon-gest after 6 months. 7 patients had open fractures (Gustilo I/II) within the EFIKS group in 4 cases.

Surgical technique

Surgical treatment approach to all fractures was in terms of classic surgical procedures which were conducted immediately after the injury, and not later than 48 hours, while in case of all bone changes (tumors/cysts) previously were condu-cted adequate diagnostic procedures (CT, MRI, angiography ..).

In all cases drainage of the wounds was done with one drain. Antibiotics were prescribed as prophy-laxis. Removal of the drainage was done after 48-72 hours. Neither one patient was immobilized. In one case there was double fixation with the EFIKSostheosynthesis at the same hand, and in case of 1 patient (serial fractures) we used plates and screws on 3 metacarpal bones (Figure 2) and also in one patient on metacarpal and proximal phalange. Pati-ents were stimulated to perform movements early. In case of foot fractures walking and partial load was recommended to all patients after 3 months.

Clinical, functioning and radiography testing of ostheosynthesis effectiveness was performed in all cases immediately after the surgery, and than after 1, 3, and 6 months.

A

B

C

Figure 1 (♂ 1962) Amputation of II and III hand finger with complete loss of proximal phalangesof IV and V finger and sub capital fracture of theV metacarpal bone – adaptation fixation intrame-dullary with Kirschner wires (A). EFIKS osthe-osynthesis, osteoplastic replacement of proximal phalanges of IV and V finger with II metacarpalbone and double arthrodesis PIP and MTCP joints on IV and V finger. Fixation of sub capitalfracture of the V metacarpal bone (B). Healing of the V metacarpal bone with complete fusion at position of arthrodesis after 5 months. Satisfacto-ry functioning effect (C).

The followed parameters were: radiography healing of the fractures, fixation of the implant inrelation to the bone and soft tissues, development of infection, deformities occurrence, grip in case

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of fist fractures, movements in neighboring joints,as well as baropodometric evaluation of plantar foot pressure distribution and supportive walk analysis.

A

B

Figure 2 (♂ 1950) Spiral fractures of II, III and V metacarpal bone (A). Repositioning and fixationwith plates 2.7 mm and free screws (B)

Results

In all cases early functional mobility is achie-ved. All movements in the neighboring joints of the hand and foot were minimally reduced + 50 -

100. Fist grip was satisfactory, except in two cases where is was difficult to achieve for one patient inEFIKS ostheosynthesis group (amputation injury) and one with arthrodesis II MTCP joint with plate and screws.

By radiography all implants are identified inthe primary set position. Verification of full bonehealing in case of fractures or fusion in case of arthrodesis is noticed in 25 (83.3%) ostheosynt-hesis. In 3 (10%) cases with implanted plate and screws: slower healing of metacarpal fracture is noticed – 1 which required additional bone stimu-lation, loosening of the screws and plate without

migration of the spiral metacarpal fracture to, but with healed fracture – 1, bending of the plate with poor position of the fragments in case of metatar-sal fracture – 1, without need for additional corre-ction. In 2 (6,6%) cases with EFIKS ostheosynt-hesis noticed is the break of one of the cerclage wires inn case of transversal diaphyseal fracture of the metacarpal bone – 1, without consequences on final healing. angulations at the point of fracturewith defect of the primary base on the V metatar-sal bone – 1, with normal bone healing. Baropo-dometric evaluation of walk and posture in 4 cases of patients with ostheosynthesis of the foot was adequate (analysis 5 months after surgery) without need for correction.

Two patients had signs of local inflammationwithout involvement of the bone or ostheosynthe-sis. After 2 and 4 weeks inflammation is coupledwith the targeted antibiotic therapy.

Discussion

What EFIKS ostheosynthesis definitely sho-wed, first in experimental research, and than bycomparison of its effects with the intramedullary forms of adaptation ostheosynthesis, and even compared to the rigid ostheosynthesis with plates and screws is without any doubt, one new choice for all diaphyseal fractures of the fist and foot assituations of very quality bridging of the bone de-fects with its ostheoplastic replacement (7, 11).

Good functional results is conditioned by the graduate induced movements and dosage of the load during the post surgery period. It is for sure that locus minoris resistentiae of EFIKS ostheo-synthesis is the possibility that the lever effect can occur, and which must be prevented that the fra-cture is the medium locus of the dyaphisis. This can lead to loosening of the basic components, pri-marily cerclage wire, which happened in one case and it is also confirmed during the experimentalresearch (11). By forming the successful bone basis. Selection of adequate thickness of the Kirschner wires and number of the cerclage wires at the risk segments of the bone this complication can be successfully avoided. But within research done by Burge identical secondary movements of the fra-gments were noticed also when using plates and

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screws, when bending of the plate and loosening of the screws occurred (8). Also in our research, ho-nestly in only 2 cases (at each group one patient) there were these complications.

Elasticity of the EFIKS ostheosynthesis is addi-tional factor which leads to avoidance of the large rigid diaphyseal segments which for sure adds ad-ditional stimulating effects to the healing which is the advantage of the biological fragments fixation.This have great importance in indicated fusions (arthrodesis) where we can expect even resorption of the bone ends and where rigid ostheosynthesis done with plates prevents additional activity of the dynamic-compressive link of muscle-ligament-tendons apparatus.

Although we did not evaluated fractures of the joints it is certain that within selection of alenthe-sis is leading decision for plates and screws.

Conclusion

Extramedullary stabilization of the fractures and bone changes within the tested sample and two specific groups of respondents with use of diffe-rence forms of extramedullary ostheosynthesis did not show statistically significant differences in thefinal radiography and functional results accordingto the set parameters of the research (p>0.05).

Both methods showed sufficient achievementof stabilization and have full support in treatment of simple and complex diaphyseal fractures of short and medium bones as well as arthrodesis of the IP and MTP/MCP joints.

Because of the simple implants (Kirschner wire and wire for bone cerclage) as well as necessary instruments EFIKS ostheosynthesis have possibi-lity for wider practical application in surgery and it is cost acceptable for those institutions which lack plates and screws. Opposite to this extramedulla-ry fixation of fractures with the use of screws andplates is still leading and irreplaceable as the met-hod in case of joint and metaphyseal fractures.

Literature

1. Muller ME, Allgower M, Schneider R, Willenegger H. Manual of internal fixation. Third edition, Sprin-ger – Verlag, Berlin, Heidelberg, New York, Lon-don, Paris, Tokyo, Hong Kong, Barcelona, 2000.

2. Ruedi TP, Murphy WM. AO principles of fracture management. Thieme, Stuttgart – New York, 2000.

3. Baumgart F, Wahl D, Owen G. et al. The post–ma-nufacture manipulation of implants. Dialoge, 2001; 2: 13–4.

4. Gooship AE, Kenwright J. The influence of inducedMicromovement Upon the healing of Experimental. JBJS, 1985, 76 – B – 650 – 5.

5. Kirchwehm WW, Figura MA, Binning TA. et al. Fractures of internal metatarsals. In; Scurran BL, Foot and Ankle Trauma, Churchill Livingstone, 1989: 345–62.

6. Boyes JH. The Hand, 7 ed., Lippincott comp., Phi-ladelphia – Toronto, 1995.

7. Hadžiahmetović Z. Početna klinička iskustva u lije-čenju dijafizarnih prijeloma malih kostiju tehnikomoriginalne ekstramedularne osteosinteze, Med Arh 2006 ; 60 (6, supl. 1) 9 - 12

8. Burge P. Internal fixation of the metacarpals andphalanges,Riv Chir Mano, 2006, :(3), 301 - 543

9. Foster GT. et al. Hemoptysis due to migration of a fractured Kirschner Wire. Chest, 2001; 119: 1285–6.

10. Anic D, Brida V, Jelić I, Orlić D. The cardiac mi-gration of a Kirschner wire a case report. Tex He-art Inst J, 1997 ; 24(4): 359–61.

11. Hadžiahmetović Z, Krasni J. Osteosinteza tehni-kom ekstramedularne fiksacije prijeloma Kirsc-hner iglama i serklažom (EFIKS). Tr Glas, 2006; 4 (3): 27-30.

Corresponding author: Zoran Hadziahmetovic Clinic for emergency medicine, Clinical Center of Sarajevo University, Bosnia and Herzegovina e-mail: [email protected]

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Summary

Adipose tissue has traditionally been conside-red as a tissue devoted mainly to energy storage. Now it is recognized as a multifunctional organ involved in the production of hormones, growth factors and cytokines named adipokines.

In obese subject the production of adipokines is impaired. In obesity high level of leptin, resistin, and low level of adiponectin have been observed and implicated in insulin resistance, atherosclero-sis and metabolic syndrome.

In patients with established coronary atheros-clerosis increased body weight is an independent predictor of an acute coronary syndrome. The ex-act mechanism of obesity induced coronary heart disease is not fully elucidated. Current research is aimed to determine links between adipokines and coronary heart disease.

Leptin, adiponectin and resistin are adipokines that are implicated in coronary endothelial dysfun-ction, trombogenesis and inflammation. Theseprocesses are known to precipitate atherosclerotic plaque rupture and acute coronary syndrome.

Recent studies demonstrated that high plasma leptin and low adiponectin levels as observed in obese subjects impair coronary acetylcholine-me-diated vasodilatation in vitro and in vivo. Resistin also impair coronary vasodilatation but via brady-kinin pathway.

Leptin and resistin show proinflammatory ef-fects upregulating cytokine production in ma-crophages and might lead to destabilization of coronary atherosclerotic plaque. Leptin has been observed to stimulate angiogenesis, platelet aggre-

gation, and atherothrombosis in obese human. In obese subject the production of adiponectin, which has protective effects on coronary blood vessels is suppressed.

This paper summarizes the role of three adi-pokines: leptin, resistin and adiponectin in acute coronary syndrome and implicates theirs possible appliance in clinical practice.

Key words: Adipokines, leptin, adiponectin, resistin, acute coronary syndrome

Sažetak

Donedavno se smatralo da je jedna od osno-vnih fiziološka uloga masnog tkiva da pohranjujeenergiju. Sada se zna da je masno tkivo multifun-kcionalni organ koji proizvodi hormone, faktore rasta i citokine koji se jednim imenom zovu adi-pokini. Kod gojaznih osoba produkcija adipoki-na je poremećena te je uočen visok nivo leptina i resistina i nizak nivo adiponektina. Poremećen odnos adipokina je povezan sa inzulinskom re-zistencijom, aterosklerozom i metaboličkim sin-dromom.

Kod pacijenata sa razvijenom koronarnom aterosklerozom, povećana tjelesna masa je ne-zavistan prediktor nastanka akutnog koronarnog sindroma. Mehanizmi kojima gojaznost dovodi do koronarne bolesti nisu u potpunosti rasvijetlje-ni. Istraživanja su usmjerena u cilju razjašnjenja povezanosti adipokina i bolesti koronarnih krvnih sudova. Leptin, adiponektin i resistin su adipokini koji dovode do koronarne endotelne disfunkcije, trombogeneze i inflamacije, procesa za koje se zna

Adipokines and Acute Coronary SyndromeADIPOKINI I AKUTNI KORONARNI SINDROMEmina Nakas-Icindic1, Amina Valjevac1, Asija Zaciragic1

1 Institute of physiology and biochemistry, Medical Faculty, University of Sarajevo, Bosnia and Herzegovina

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da potiču ruturu aterosklerotskog plaka i nastanak akutnog koronarnog sindroma.

Nedavno objavljene studije su pokazale da vi-sok nivo leptina i nizak nivo adipokina, uočen kod gojaznih osoba, inhibira vazodilataciju koronarnih krvnih sudova preko acetilholina in vitro i in vivo. Resistin također inhibira koronarnu vazodilataciju ali preko bradikinina.

Leptin i resistin djeluju proinflamatorno dovo-deći do povećane ekspresije citokina u makrofazi-ma, procesa koji može biti okidač destabilizacije koronarnog aterosklerotskog plaka. Uočeno je da leptin stimulira angiogenezu, agregaciju trombo-cita i aterotrombozu kod gojaznih osoba. Istovre-meno višak masnog tkiva dovodi do smanjenog stvaranja adiponektina, koji djeluje protektivno na koronarne krvne sudove.

Ovaj članak ima za cilj da sumira ulogu nave-dena tri adipokina: leptina, resistina i adiponektina u akutnom koronarnom sindromu kao i da implici-ra njihovu moguću primjenu u kliničkoj praksi.

Ključne riječi: Adipokini, leptin, adiponektin, resistin, akutni koronarni sindrom

Introduction

Adipose tissue has traditionally been conside-red as a tissue devoted mainly to energy storage. Adipose tissue is now recognized as a multifuncti-onal organ producing proteins and peptides named adipokines. Adipokines are hormones, growth fa-ctors and cytokines acting via endocrine, paracrine and autocrine modes (1).

Leptin was one of the first adipocyte-derivedhormon which signals the status of energy stores and its secretion can reduce appetite and increase energy expenditure (2). Since the initial identifi-cation of leptin, numerous adipocyte-derived pro-teins and peptides have been discovered. Besides leptin, adiponectin and resistin have been given much attention in research lately.

Adipokines are known to contribute to the chronic low grade inflammation state observed inobese patients. In the same time they participate in the development of obesity-related comorbiditi-es, such as insulin resistance, metabolic syndrome and atherogenesis (1)

Circulating adipokine levels are elevated in obese and insulin-resistant states in animals and humans. Weight loss is associated with a decrease

in the serum levels of most of these adipokines, with the exception of adiponectin, which is in-creased (3).

Obesity is an independent risk factor for de-velopment of atherosclerosis. In patients with es-tablished coronary atherosclerosis increased body weight is an independent predictor of an acute cor-onary syndrome (ACS) (4). The exact mechanism by which increased body weight leads to coronary artery disease is not fully understood.

The term acute coronary syndrome refers to a range of acute myocardial ischemic states. It en-compasses unstable angina, non-ST and ST seg-ment elevation myocardial infarction and sudden ischemic death. Underlying mechanism precipi-tating acute coronary syndrome in a majority of cases, is coronary atherosclerotic plaque rupture and consequent thrombus formation. The vulner-ability of a plaque to disruption appears to be de-termined by the presence of a large lipid-rich core, a thin fibrous cap, and an inflammatory cellularinfiltrate. Endothelial dysfunction is present in pa-tients with atherosclerosis, even in the early stages of disease. Dysfunctional endothelium encoura-ges the recruitment of leukocytes into the arterial wall and thereby predisposes to inflammation andplaque disruption. In addition to plaque disruption and thrombosis, characteristic feature of coronary artery disease is enhanced coronary vasoconstric-tion (5).

Adipokines might play an important role in ini-tiation and progression of atherosclerotic plaque rupture enhancing endothelial dysfunction, im-mune response and thrombogenesis but the find-ings regarding exact mechanism of their action are contradictory and inconclusive.

Aim of this paper is to summarize current find-ings regarding the role of adipokines in acute cor-onary syndrome and possible appliance of adipo-kines blocking and boosting agents in clinical setting. Clinical significance of adipokines mea-surement during acute coronary syndrome is also discussed.

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Leptin

Leptin is a 16 kDa protein predominantly ex-pressed and secreted in adipose tissue, but also produced by other tissues including the heart (6). Plasma leptin concentrations reported in normal, healthy humans are 3–5 ng/mL and in morbidly obese humans leptin concentrations are elevated and range from 90–95 ng/mL (7).

Leptin exerts its effect by binding to its recep-tors which are expressed abundantly in many dif-

ferent cells including cardiomyocites and coronary arteries. Leptin receptors are classified as short(ObR a,c, d, f), secreted (ObRe) and long (ObRb). ObRb receptor is present in coronary arteries and considered to be involved in full cellular signaling process (8). Its intracellular domain belongs to the Janus kinase signal transduction and translation system (Jak2/STAT3)(7).

The production of cardiomyocyte derived leptin is increased by both endothelin-1 and angiotensin II suggesting a paracrine or autocrine role of leptin

Table 1. Main adipokines outline: most important physiological functions and involvment in diseases.Adipokines Physiological function Related diseases

Leptin

Energy and glucose homeostasis ↑2

Trombogenesis ↑ 18

Immunity ↑ 1

Haematopoesis ↑ 17

Obesity ↑ 11

Atherosclerosis ↑ 12

Adiponectin

Insulin sensitivity ↑ 31

Energy expenditure ↑ 31

Fatty acid oxidation ↑ 31

Vasodilatation ↑ 25

No production ↑ 25

Inflammation ↓ 1

Cell proliferation ↓ 22

Tissue remodeling ↓ 22

Obesity ↓23

Dislipidemia ↓ 23

Atherosclerosis ↓ 23

Nonalcoholic fatty liver disease ↓40

Nonalcoholic steatohepatitis ↓40

Diabetes mellitus type 2 ↓ 23

Cancer ↓1

Resistin Glucose production ↑ 34

Inflammation ↑ 40

Obesity ↑ 34

Insuline resistance ↑ 34

Atherosclerosis ↑ 36

Vistatin Insulin sensitvity ↑ 44 Obesity ↑ 44

Diabetes mellitus type 2 ↑ 44

Adipsin Complement activation ↑ 43 Obesity ↑43

IL-6

Acute phase protein synthesis ↑ 1

Hypothalamic–pituitary axis ↑1

activation↑ 1

Thermogenesis ↑1

Coagulation ↑1

Obesity ↑ 3

Acute and chronic inflamatory diseases ↑3

Atherotrombosis ↑6

TNF-αInflammation ↑ 1

Cellular proliferation ↑1

Cellular differentiation ↑1

Chronic inflammation ↑1

Malignancy ↑1

Obesity ↑ 3

Anorexia ↑3

Insuline resistance ↑3

Coronary heart disease ↑6

PAI-1 Trombogenesis ↑ 6Obesity ↑1

Hyperglicemia ↑1

Hyperlipidemia ↑6

Atherotrombosis ↑6

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in the regulation of cardiac functions particularly under pathological conditions (9). The primary cardiac response to leptin in terms of physiologi-cal function appears to be a negative inotropic re-sponse which has been shown primarily in cardio-myocytes and which is mediated by endogenously produced nitric oxide (NO) (10).

High circulating plasma leptin levels in obesity are thought to play a role in the hastened develop-ment of coronary artery disease (11). Again, se-veral clinical, epidemiologic studies have shown a strong association between hyperleptinemia and risk for coronary artery disease (12, 13). There are still numerous unresolved issues regarding the ex-act nature of leptin’s effects on coronary arteries and during acute coronary syndrome. Plasma le-ptin levels were found to be significantly higher inpatients presenting with acute coronary syndrome compared to the patients with stable angina and healthy subjects (14). Leptin correlated positively

with interleukin-6 and high-sensitivity C-reactive protein in patients with acute coronary syndrome suggesting its possible role in systemic inflamati-on and in asssesing the risk for developing acute coronary syndrome.

Earlier studies have demonstrated that leptin is vasoactive in noncoronary vascular beds (2,15), but the coronary vascular effects of leptin are largely uncharacterized. However, few studies to date have examined the effects of leptin on the co-ronary circulation. Several studies suggested that leptin affects coronary vascular resistance but the findings are inconclusive. Matsuda et al. (16) werefirst to report that leptin increases coronary bloodflow approximately 40% in patients undergoingcardiac catheterization and that this vasodilata-tion is independent of nitric oxide (NO) synthase. On the contrary, Knudson et al. (17) demonstrated that high pharmacologic concentrations of leptin induce nitric oxide–dependent vasodilatation of coronary arterioles in animal models. But, leptin-mediated coronary vasodilatation in the studies was only observed at extremely high leptin con-centrations (160 ng/mL) which are rarely seen in obese subjects. Knudson et al. (8) recently dem-onstrated that increasing plasma leptin concentra-tions to levels similar to those observed in obese subjects (10–90 ng/mL) significantly impairedacetylcholine-mediated vasodilatation in vitro and

in vivo. In contrast, normal concentrations of leptin (4 ng/mL) do not affect vasodilatation to acetyl-choline. Therefore, concentrations of leptin found in obese subject appear to have deleterious effects on coronary endothelial function and myocardial blood flow acutely.

Leptin has been linked to all processes under-ling acute coronary syndrome. Leptin leads to T-cell proliferation, phagocytosis and upregulation of cytokine production in macrophages. On endo-thelial cells leptin has been shown to upregulate endothelin-1 and NO synthase, and at the same time it induces oxidative stress (18).

In addition, leptin has been observed to stimu-late angiogenesis, platelet aggregation, and ath-erothrombosis in human obesity (1).

Dubey et al. (19) analized angiographically simple and complex lesions on coronary arteries in patients presenting with unstable angina pecto-ris and found leptin to be an independent predictor of complex lesion suggesting its potential role as useful biomarker for risk stratification in patientswith unstable angina.

Damaging effect of leptin on acutely ischemic myocardial tissue might be inhibited with novel pharmacological tools targeting leptin receptors. Therefore, with the development of specific ObRantagonists a clear and consistent consensus will be reached regarding the role of leptin on isch-emic myocardial tissue. Leptin receptors antago-nists called muteins could promiuse as a possible therapy in patients with coronary atherosclerotic disease and acute coronary syndrome (20).

Adiponectin

Adiponectin is 30 kDa protein mostly secret-ed by adipose tissue. Adiponectin concentration ranges from 1.9–17.0 mg/dL in normal healthy subjects (1).

Adiponectin expression and release from adi-pocytes are stimulated by activation of peroxi-some proliferator-activated receptor PPAR-γ, a key transcriptional factor involved in adipocyte differentiation (21). Adiponectine can function as full length proteine which binds to AdipoR1 (adi-ponectin receptor 1) or smaller globular fragment

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binding to AdipoR2 (adiponectin receptor 2). In myocardial tissue, AdipoR1 is expressed in sub-stantially greater abundance compared to AdipoR2 (22).

Plasma adiponectin levels correlate inversely with body fat content and in obese subjects low plasma adiponectin level is an independent pre-dictor of all-cause mortality, cardiac mortality, and myocardial infarction in patients presenting with chest pain (23). Also, decreased circulating adiponectin levels in obesity are associated with an increased risk of coronary artery disease and myocardial infarction (24).

Wolk et al. (25) found that patients with acute coronary syndrome (ACS) had significantly loweradiponectin levels than those without ACS, inde-pendent of a variety of cardiovascular risk fac-tors.

Within the last year a few studies examining the role of adiponectin in coronary vasomotor func-tion have been published. Epicardial adipose tis-sue produces adiponectin. Furthermore, in humans with coronary artery disease, there is a reduction in local epicardial adiponectin production (26). A study by Date et al. (27) observed a significantcorrelation between coronary flow reserve and thetranscardiac adiponectin gradient (i.e., great car-diac vein concentration minus left coronary artery concentration) in 22 nondiabetic, healthy subjects with angiographically normal coronary arteries. Those subjects with higher transcardiac adiponec-tin gradients exhibited higher coronary flow re-serves. Another recent study by Takano et al. (28), found a positive correlation between transcardiac adiponectin gradient and acetylcholine-induced increases in coronary artery diameter. The authors concluded that adiponectin plays a role in coro-nary endothelial function (as assessed by acetyl-choline-mediated coronary vasodilation).

Adiponectin is associated with induction of antiinflammatory cytokine production (IL-10 andIL-1) (29). It has also been shown that adiponectin plays a role in endogenous antithrombosis (30).

Promising results obtained from numerous ani-mal experiments and human epidemiological stu-dies support the role of adiponectin as a potential drug target in treating obesity-related chronic low grade inflamatory diseases. Direct supplementati-on of recombinant adiponectin in human subjects

would be extremely expensive. An alternative ap-proach is to use pharmacological or dietary inter-vention to increase the suppressed endogenous adi-ponectin production in obesity, or to enhance adipo-nectin actions in its target tissues. In this respect, it is interesting to note that the PPAR-γ agonists thiazo-lidinediones (TZDs), such as rosiglitazone and pio-glitazone, which increase adiponectin production in both humans and rodents, demonstrate many of the therapeutic effects of adiponectin, such as insulin-sensitizing, vasoprotective, and anti-inflammatoryproperties (31). Whether the therapeutic effects of the PPAR-γ agonists are mediated via induction of adiponectin remains to be investigated. In addition, metformin, another commonly used antidiabetic drug, as well as beta-blocking drugs which are used during myocardial infarction have been shown to mimic the action of adiponectin (32).

Resistin

Resistin is 12 kDa protein named after the ob-servation that it leads to insulin resistance. Alt-hough it was detected in adipose tissue of obese subjects, resistin levels are substantially higher in human inflammatory cells (33). Plasma resistinconcentration is in the range of 3–13 ng/ml in he-althy subjects with levels approaching 40 ng/mL in obese individuals (34). Although resistin cell receptors are yet to be identified, direct action ofresistin in the heart and specifically on cardiomy-ocytes has been described. Mouse adult cardio-myocytes treated with resistin show a reduction in insulin-stimulated glucose uptake (35).

Studies by Kougias et al. (36) and Dick et al. (37) demonstrated that resistin alters coronary va-somotor responses in vivo and in vitro imparing coronary vasorelaxation to bradykinin in both por-cine and canine coronary circulations.

Studies regarding resistin effect on ischemic myocardium are scarce and conflicting. In onestudy resistin depressed functional recovery from ischemia in isolated perfused rat hearts, an effect which appeared to be dependent on NF-kB activi-ty (38). In contrast, resistin reduced infarct size in mice subjected to coronary artery occlusion and reperfusion (39). The obvious discrepancy requi-res further research.

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Qiao at al. (40) reported increased serum re-sistin levels in patients with acute coronary syn-drome and in patients with stable angina pectoris (SAP) compared with the healthy subjects. The highest serum resistin values were found in acu-te myocardial infarction (AMI), followed by un-stable angina pectoris (UAP) and SAP. Serum resistin levels positively correlated with CKmax, CK-MBmax, cTnImax, WBC and hsCRP. Lubos et al. (41) reported that resistin levels were elevated in patients presenting with unstable angina, non-ST-elevation myocardial infarction and ST-elevation myocardial infarction.

Resistin might reflect an inflammatory proces-ses occurring in mononuclear cells during acute coronary syndrome. Because of diverse myocar-dial ischemia and ischemic impairment in AMI\UAP\SAP patients, the inflammatory factorsmight be released in different degrees. Serum resi-stin levels increased with the severity of myocar-dial impairment and therefore might play a role as a diagnostic marker.

Discussion

Increased adipose tissue in obese subject pro-duces more adipokines such as leptin and resistin which have recently been implicated in the pat-hogenesis of acute coronary syndrome affecting coronary vasculature, inflammatory processes andthrombogenesis and thus predisposing the ruptu-re of coronary atherosclerotic plaque. On the ot-her hand, increased adipose tissue suppresses the production of an adipose tissue hormone, adipo-nectin, which has protective effects on coronary vasculature.

Disruption of physiologic adipokine plasma le-vels and perturbations in adipokine signaling wit-hin the coronary vascular wall culminates in co-ronary endothelial dysfunction. Thus, alterations in adipokine biology may be a major precipitating factor in the initiation of coronary artery disease in individuals with metabolic disease.

Plasma concentration of leptin and resistin is associated with the extent of coronary occlusion during acute coronary syndrome while plasma concentration of adiponectin correlates inversely with the degree of myocardial ischemia. Average

plasma leptin concentration in patients with myo-cardial infarction is in the lower obese range and significantly higher compared to the patients withunstable angina. Leptin concentration in obese range (10-90 ng/mL) was found to impair acetylc-holine mediated coronary relaxation and could be attributable to prolonged myocardial ischemia (8). It remains to be assessed whether the predetermi-ned ranges of plasma adipokines concentration co-uld be used as a useful biomarker for stratificationof patients with coronary heart disease. It has not been assessed whether elevated concentrations of adipokines during myocardial ischemia changes during and after acute coronary syndrome. Du-ring myocardial infarction, increased sympathetic activity causes release of renin and elevation of plasma leptin concentration could be due to incre-ased plasma angiotensin II levels, which is known to stimulate leptin release.

There are numerous challenges facing investi-gators in this field. Important among these is thefundamental question of precisely how leptin, adiponectin, and other adipokines affect cardiac pathology. This task will undoubtedly be facilita-ted and expedited with the eventual development of new pharmacological tools targeting specificadipokine systems. A second major challenge is to understand how the various adipokines inte-ract with each other since numerous adipokines with diverse biological properties can be released simultaneously and, as such, the net effect of in-creased adipokine production may not reflect theactions of a single individual substance. This re-mains a challenge for future investigations which are important not only to fully understand the role of adipokines in cardiac regulation but in terms of potential for the development of novel cardiac the-rapeutic targets.

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Conclusion

Adipokines are involved in all stages of acu-te coronary syndrome initiation and progression. With the use of drugs affecting adipokines plasma level in future research; a more clear insight will be gained regarding their exact role in acute coro-nary syndrome.

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15. Zabeau L, Lavens D, Peelman F, Eyckerman S, Vandekerckhove J, and Tavernier J. The ins and outs of leptin receptor activation. FEBS Lett 546: 45–50, 2003.

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17. Knudson JD, Dincer UD, Dick GM, Shibata H, Akahane R, Saito M, et al. Leptin resistance ex-tends to the coronary vasculature in prediabetic dogs and provides a protective adaptation against endothelial dysfunction. Am J Physiol Heart Circ Physiol; 289:H1038–46, 2005.

18. Corsonello A, Perticone F, Malara A, De Dome-nico D, Loddo S, Buemi M, Ientile R, Corica F. Leptin-dependent platelet aggregation in healthy, overweight and obese subjects. Int J Obes Relat Metab Disord 27:566–573, 2003.

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19. Dubeya L. Zenga H., Hashimb S., Hongjiea W., Taoa H. Association of plasma leptin levels and complexity of the culprit lesion in patients with unstable angina. International Journal of Cardi-ology. Article in press.

20. Gertler A.Development of leptin antagonists and their potential use in experimental biology and medicine. Trends in endocrinology and metabo-lism 17, 372-378, 2006.

21. Maeda N, Takahashi M, Funahashi T, Kihara S, Nishizawa H, Kishida K et al. PPARg ligands in-crease expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabete-s;50:2094–2099, 2001.

22. Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Natu-re;423:762–769, 2003.

23. Cavusoglu E, Ruwende C, Chopra V, Yanamada-la S, Eng C, Clark LT, Pinsky DJ, Marmur JD. Adiponectin is an independent predictor of allca-use mortality, cardiac mortality, and myocardial infarction in patients presenting with chest pain. Eur Heart J 27:2300–2309, 2006.

24. Sattar N, Wannamethee G, Sarwar N, Tcherno-va J, Cherry L, Wallace AM, Danesh J, Whincup PH. Adiponectin and coronary heart disease: a prospective study and meta-analysis. Circulation 114:623–629, 2006.

25. Wolk R, Berger P, Lennon RJ, Brilakis ES, Davi-son DE, Somers VK. Association between plasma adiponectin levels and unstable coronary syndro-mes. Eur Heart J 28:292–298, 2007.

26. Iacobellis G, Pistilli D, Gucciardo M, Leonetti F, Miraldi F, Brancaccio G, Gallo P, di Gioia CR. Adiponectin expression in human epicardial adi-pose tissue in vivo is lower in patients with coro-nary artery disease. Cytokine 29:251–255, 2005.

27. Date H, Imamura T, Ideguchi T, Kawagoe J, Sumi T, Masuyama H,Onitsuka H, Ishikawa T, Nagoshi T, Eto T. Adiponectin produced in coronary circu-lation regulates coronary flow reserve in nondia-betic patients with angiographically normal coro-nary arteries. Clin Cardiol 29:211–214, 2006.

28. Takano H, Kodama Y, Kitta Y, Nakamura T, Obata JE, Mende A, Kawabata KI, Saito Y, Fujioka D, Kobayashi T, Hasebe H, Kugiyama K. Transcar-diac adiponectin gradient is independently related to endothelial vasomotor function in large and re-sistance coronary arteries in humans. Am J Physi-ol Heart Circ Physiol 291:H2641–H2646, 2006.

29. Wolf AM, Wolf D, Rumpold H, Enrich B, Tilg H. Adiponectin induces the anti-inflammatory cytoki-nes IL-10 and IL-1RA in human leukocytes. Bioc-hem Biophys Res Commun 323:630–635, 2004.

30. Kato H, Kashiwagi H, Shiraga M, Tadokoro S, Kamae T, et al. Adiponectin acts as an endoge-nous antithrombotic factor. Arterioscler Thromb Vasc Biol 26:224–230, 2006.

31. Chaldakov GN., Stankulov I.S., Hristova M., Ghe-nev P.I. Adipobiology of disease: Adipokines and adipokine-targeted pharmacology. Current Phar-maceutical Design, 9,1023-1031, 2003.

32. Delporte ML, Funahashi T, Takahashi M, Matsu-zawa Y, Brichard SM. Pre- and post-translational negative effect of beta-adrenoceptor agonists on adiponectin secretion: in vitro and in vivo studies.Biochem J 367:677-685, 2002.

33. Yang RZ, Huang Q, Xu A, McLenithan JC, Eisen JA, Shuldiner AR, Alkan S, Gong DW. Compara-tive studies of resistin expression and phylogeno-mics in human and mouse. Biochem Biophys Res Commun. 2003;310(3):927–935.

34. Pfutzner A, Langenfeld M, Kunt T, Lobig M, Forst T. Evaluation of human resistin assays with serum from patients with type 2 diabetes and different de-grees of insulin resistance. Clin Lab 49:571–576, 2003.

35. Graveleau C, Zaha VG, Mohajer A, Banerjee RR, Dudley-Rucker N, Steppan CM et al. Mouse and human resistins impair glucose transport in pri-mary mouse cardiomyocytes, and oligomerization is required for this biological action. J Biol Chem 2005;280:31679–31685.

36. Kougias P, Chai H, Lin PH, Lumsden AB, Yao Q, Chen C. Adipocyte derived cytokine resistin cau-ses endothelial dysfunction of porcine coronary arteries. J Vasc Surg 41:691–698, 2005.

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37. Dick GM, Katz PS, Farias M, III, Morris M, Ja-mes J, Knudson JD, Tune JD. Resistin impairs en-dothelium-dependent dilation to bradykinin, but not acetylcholine, in the coronary circulation. Am J Physiol Heart Circ Physiol 291:H2997–H3002, 2006.

38. Rothwell SE, Richards AM, Pemberton CJ. Resi-stin worsens cardiac ischaemia-reperfusion inju-ry. Biochem Biophys Res Commun 2006;349: 400–407.

39. Gao J, Chang CC, Chen Z, Wang H, Xu X, Hamdy C et al. Resistin, an adipocytokine, offers protecti-on against acute myocardial infarction. J Mol Cell Cardiol 2007;43:601–609.

40. Xiao-zhi Qiao, Yun-mei Yang, Zhe-rong Xu, Li-ai Yang. Relationship between resistin level in serum and acute coronary syndrome or stable angina pe-ctoris. J Zhejiang Univ Sci B. 2007; 8(12): 875–880

41. Lubos E, Messow C, Schnabel R, Rupprecht H, Espinola-Klein C, Bickel C, Peetz D, Post F, Lac-kner K, Tiret L. Resistin, acute coronary syndrome and prognosis results from the AtheroGene study. Athero-sclerosis. 2007;193(1):121–128. ž

42. Ma H, Gomez V, Lu L, Yang X, Wu X, Xiao SY.Ex-pression of adiponectin and its receptors in livers of morbidly obese patients with non-alcoholic fatty liver disease. J Gastroenterol Hepatol. 2008 Epub ahead of print

43. Fain JN, Nesbit AS, Sudlow FF, Cheema P, Pe-eples JM, Madan AK, Tichansky DS. Release in vitro of adipsin, vascular cell adhesion molecule 1, angiotensin 1-converting enzyme, and soluble tumor necrosis factor receptor 2 by human omen-tal adipose tissue as well as by the nonfat cells and adipocytes. Metabolism: 56(11):1583-90, 2007.

44. Adeghate E.Visfatin: structure, function and rela-tion to diabetes mellitus and other dysfunctions.Curr Med Chem., 15(18):1851-62, 2008.

Corresponding author: Emina Nakas-Icindic Institut of physiology and biochemistry, Medical faculty University of Sarajevo, Bosnia and Herzegovina e-mail: [email protected]

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Summary

The term, feeding additions stands for indivi-dual forms or mixtures of feeding materies that serves as feeding additions in order to complete it or they are taken directly in concentrated form (vitamins, mineral materies, proteins, aminoa-cids, lipids). Vitamins and minerals can be taken into organism in two ways: by taking of food or by taking of mineral and vitamin additions. The products with vitamin additions aren’t that useful as evidential usage of fruits and vegetables. The aim was to analyze the situation and practice of patients and their attitude towards vitamins and minerals and evaluate the taking of fruits and ve-getables in everyday feeding.

Key words: feeding additions, vitamins, mine-raly

Sažetak

Pod prehrambenim dodacima podrazumijevaju se pojedinačni oblici ili mješavine hranjivih mate-rija, koje služe kao dodaci prehrani u smislu nje-zinog obogaćivanja ili se uzimaju direktno u kon-centriranom obliku (vitamini, mineralne materije, bjelančevine, aminokiseline, masne kiseline). Vi-tamini i minerali mogu u organizam doći dvojako, ili sa hranom ili putem prehrambenih dodataka. Proizvodi sa vitaminskim dodacima nisu tako ko-

risni, kao što su dokazi o korisnom učinku voća i povrća. Cilj je bio analizirati znanje i praksu bole-snika prema prehrambenim dodacima vitamina i minerala, te dati ocjenu korištenja voća i povrća u ishrani ispitanika.

Ključne riječi: Prehrambeni dodaci, vitamini, minerali.

Introduction

The term feeding additions, stands for the single forms or mixtures of feeding materies that serves as additions to food as its’ complement, or these are taken directly in concentrated form (vitamins, mi-neral matheries, proteins, aminoacids, lipids), (1)

Feeding is basic human need for existence. In process of feeding, the basic nutrition materies which can be divided in two groups:macronutriti-ens – the primar source of energy (proteins , carbs, lipids) and mikronutrtients- protective materies (vitamines and minerals). In process of planing of feeding it is taken care of that daily meal plan includes various groceries in order to secure nee-ded intake of all anutritive and protecive materies (2). Vitamins and minerals can enter in organism in two ways, with food or as additions. Products with vitamine additions aren’t so usefull as evi-denton usefull meaning of fruits and vegetables intake.(3).

Relation of disseased towards feding aditions vitamins and minerals ODNOS BOLESNIKA PREMA PREHRAMBENIM DODACIMA VITAMINA I MINERALAFatima Jusupovic1, Arzija Pasalic1, Jasmina Mahmutovic1, Dijana Avdic2, Azra Kudumovic2

1 Faculty of Health, University of Sarajevo, Bosnia and Herzegovina2 Faculty of Medicine, University of Sarajevo, Bosnia and Herzegovina

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The aims of the work

Analasys of knowledge and practice of patient towards feeding additions vitamins and minerals

Give evaluation of fruit and vegetables using in patients' feeding

Material and methods

The used method of work is questionaire consi-sting 30 questions. Questioning is divided in four parts: status of qustioned persons, fruit and vege-tablesin feeeding of qustioned ones, artifitial pre-parats of vitamins and minerals in their feeding, their attitudes on the way of feding.

There were 297 patients of different age, disseases and hospitalised in several clinics of Clinical centre University of Sarajevo, by method of random cause.the questioning was realised in decembre 2007.

Results and discussion There were totaly 297 patients, out of which

162 males and 135 females in different age gro-up. According to educationanal level, the most of them are with finished high school (65,55 %),university and two-year higher educational level 18,18 % , while others are with finished primaryschool. More than a half live in urban area, in su-burban area live 26,26 %, and others 22,55 % live in the country

As for employment, there was the largest num-ber of employed (44,10 %), retired 22,22 %, stu-dents 4,71 %, whilie others were unemployed.

Feeding additions of vitamins and minerals in feeding of qustioned patients.

Graphic 1. Frequency of using of feeding additi-ons, minerals and vitamins by the patients treated in UKC Sarajevo

Vitamins and mineral additions, only in extreme situations, use 30,30 % of questioned (ex. In case of dissease ), several times a day 9,09 %,and there are those who don’t use them at all, 15,48%.

The reasons why the patients don’t use artifici-al preparats of vitamins and minerals or use them rarely are in the largest percentage (22,89 %, at-titude that during intake of various food in orga-nism isn’t necessary to take other supplements. It is very signifficant to point out that quite numberof patients are affraid of side effects of these ad-ditions. The most of users didn’t answer at all or mentioned any reason.

Graphic 2. The most often used feeding additions of minerals and vitamins by the patients treated in UKC Sarajevo

Patients hospitalised in KC Univerzity of Sa-rajevo, use multivitamin additions ( 26,26 % ), the second place belongs to A + C + E (23,56%), and the least used are multimineral additions 3,36 %.

Multivitamin additions, 35,01 % of questioned patients use after meal, 27,60 %, during meal and even number consume before meal.

Graphic 3. The usual place of getting of feeding additions and minerals by patients treated in UKC Sarajevo

Feeding additions of minerals and vitamins are ussualy bought in pharmacies, 61,61 %,but signif-ficant percentage belongs to common shops (19,19%). According to research, most of the questioned patients follow the instructions of producer about recomended daily doses (68,68 %), and less (49,-83 %) advisess doctor or pharmacist.

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About medical action of these suplements, the largest number of users recieved the information from the media (47,47%), doctora (22,89 %), and 10,77% cases from the pharmacist.

Fruits and vegetables are irreplaceble part of qu-ality and balanced feeding becouse provide many important vitamins and minerals and it important to overlook the intake of fruit and vegetables what can be seen in the following graphic (graphic 5.).

Graphic 4. The source of information about fe-eding additions of minerals and vitamins by the patients treated in UKC Sarajevo

Graphic 5. Fruits and vegetables in feeding The great number of questioned patients (40,40

%) consumes fruits and vegetables only several times a week what leaves the organism without important nutritiens. In recomendations of SZO in daily intake of fruits and vegetables. 5,05 % of users take it.

Interesting information would be that very small number 13,18 %, eats fruits and vegetables which they have produced themselves, while most of them provides it on the market what is shown in thwe folowing graphic.

Graphic 6. Attitude on consuming of ruits and ve-getables apart from using feeding additions.

More than a half of questioned patients consi-der that it is neccessary to take additions with re-

gular intake of fruit and vegetables while 46,12 % of them dissagree.

Out of total number of questioned patients 85,-52 %, thinks that taking of additional vitamins and minerals as supplements, doesn’t have good effect on organism without intake of fruits and vegeta-bles.

With attitude that bought groceries lose the necessary vitamins and minerals by modern pro-cessing, one third of them partialy agrees 8,75 % disagrees , while others fully agree.

Confirmative answer on claim that inappropri-ate preparation of grocerries decreases the content of vitamins has given 92,92 % of questioned pati-ents, others dissagree with this. Obviously, most of them think that vitamins are instabile connections sensitive on heat, light and storage and the way of food preparation.

Evaluation of influence of vitamins and mine-rals, regardless their origin, on health improvement of patients evaluation n1-5 has given the following results: mark 1 gave 3,7 % of questioned patients, mark 2-18,18 % , mark 3-41,07 %, mark 4-20,53 % and mark 5-16, 49 % of questioned patients.

Various feeding is one of the main marks of helthy feeding and most of our patients, 88,21 % remarks that their feeding is as such. Others claim that their feeding isn’t as it should be ant they are consuming 2 and less meals a day. There are those who try to have 4-5 meals but the average is 3 me-als per day in 53,53 %. Approximately, the same number questioned patients 57, 91 % , thinks that they do give enough attention to healthy lifestile.

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Discusion

There are totaly 297 patients, out of which 162 males and 135 females in different age group. Ac-cording to educationanal level, the most of them are with finished high school (65,55 %), univer-sity and two-year higher educational level 18,18 % , while others are with finished primary school.More than a half live in urban area, in suburban area live 26,26 %, and others 22,55 % live in the country.

Speaking in terms of education, the most of them are employed (44,10 %), retired 22,22 %, students 4,71 %, while others are unemployed.

Vitamine and mineral food addititives use se-veral times a day, 9,09 % patients. If we exclu-de those who use them only in exceptional cases (30,30 % patients – for ex. In case of illness), and those who don’t use them at all (15,48 %), 54% of them use vitamin and mineral additions to food what is significantly lower than in other authors’research. Research conducted in USA 2000 had shown that 33,9 % take artificcial additions of vi-tamins and minerals, which is 23,2 % higher than in 1987. (3).

In question ‘why do they use vitamin and mi-neral additions’?, they answered in first place(36,48 %), increasing of immunity, than impro-vement of apetite, overcomming of pyisical wea-kness, preventing of cardiovascular illnesses.

The reasons why some don’t use mineral and vitamin additions in ther food or use them rarely are (22,89 %) are becouse of the attitude that du-ring food taking such addittions aren’ t neccessary. Many of them are affraid of sideeffects and most of them didn’t answered at all.

Patients hospitalised in KC University of Sa-rajevo, who are in this questionaire processing, mostly use multivitamin additions (26,26 %), after this, the second place belongs to A + C + E, and the least taken are multimineral additions 3,36 %. The largest usage of multivitamin additions, ac-cording to research is in America (5).

Multivitamin additions in 35,01 % are con-sumed after meal , 27,60 %, during the meal, and the number of those who take before meal is even. Todays’ lifestile brings high changes for creation of subclinical lack of vitamins and mi-nerals and expert advise is implementation of

optimal feeding after which comes selection of quality addition to food.

Fruits and vegetables are irreplacable part of quality and balanced feeding, becouse they se-cure many of important vitamins and minerals. Unfortunately, the large number of them 40,40 % consumes fruit and vegetables only several times a week what excludes important nutrities to orga-nism. In recomendations of SZO about daily in-take of fruits and vegetables , only 5,05 % follow this recomendation.

Interesting information would be that very small number13,18 %, eats fruits and vegetables which they have produced themselves, while mot of them provides it on the market..

In Slovenia, where similar research was taken, the largest number of questioned eats homemade fruits and vegetables ( 6).

Popularisation of food additions has grown so much that redesigned oiramid of proper feeding, which includes daily multivitamin and mineral ad-dition to feeding as usefull prevention of potential feeding gaps.(7).

There are totaly 297 patients, out of which 162 males and 135 females in different age group. Ac-cording to educationanal level, the most of them are with finished high school (65,55 %), univer-sity and two-year higher educational level 18,18 % , while others are with finished primary school.More than a half live in urban area, in suburban area live 26,26 %, and others 22,55 % live in the country.

Such attitude san be be evaluated as excellent becouse nuritients from food are the best selecti-on, zhey are ‘wrapped’ in their natural complexes which are best apsorbed and used in the organism. (8).

As leading risk-factor in creation of illness, the questioned persons consider smoking, stress exposure at home and at work, increased blood preasure and than in the same number of opini-ons overweight, disorganised feedeing, the lack of body activity and alcohol consuming.

For most of them, the most important meal is certainly breakfast (56,90 %). There are those who thimk that the main meal is lunch and supper all in one.

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Conclusions

Participation of feeding aditions vitamins and minerals in feeding of patient is significant(54%).

Feeding aditions are taken randomly, without previous evaluation of nutritive status by the experts in this area of expertise and the most used are multivitamin preparts (26,26%).

The great role in popularisation of feeding additions have the media with constant advertising

Vegetables and fruits on the menu, as natural source of vitamins and minerals in feeding of questioned patients isn’t sattisfying. Consuming of fruits and vegetables several times a week (40, 40%) is a habit that needs to be changed in future

Education level of our population about healthy and balanced feeding is minimal becouse there is no quality source of information.

The area of nutricionism is still without a place that is deserved in a sense of promotion of healthy way of life.

Literature

1. Službene Novine Federacije, broj 7/2004.

2. Kocijančić R., Pecelj-Gec M.,Higijena, Značaj ish-rane, XX; Zavod za udžbenike i nastavna sredstva; Beograd;2002;334-339

3. Anonimous, najboljša je pestra prehrana. Zdravje 1999; 228: 31.

4. Shaw GM,etal.,Journal of the American Medical Assotiation;2000;54-55

5. Millen A.E., Dodd K.W., Subar A.F. Use of Vitamin, Mineral, Nonvitamin, and Nonmineral Supplements in the United States: The 1987, 1992, and 2000 Na-tional Health Interview Survey Results: Jurnal of The American Dietetic Association 2004; 104; 943-944.

6. Erjavec M , Vitaminski i mineralni pripravki u pre-hrani Slovencev, Diplomska naloga, Univerza v Ljubljani, 2005; 6-28.

7. J.M.Kinney,Challenges to rebuilding the US food pyramid.Curr Opin Clin Nutr Metab Care 8; 2005; 1-7

8. Moore K. L., Saddam A. M. Dietary suplement use among undergraduate college students. Journal of the American Dietetic Association: 1999

Corresponding author: Fatima Jusupovic Faculty of Health, University of Sarajevo, Bosnia and Herzegovina e-mail: [email protected]

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Summary

Background: Alzheimer’s disease (AD) repre-sents a progressive dementia. Known risk factors for the development of AD include: age, genetic susceptibility, family history of dementia and fe-male gender. Atherosclerosis, dyslipidemia, hy-pertension and inflammation are considered to bepossible vascular risk factors for AD. C-reactive protein (CRP) is an important marker and media-tor of low-grade inflammation. Its possible role inthe development and the progression of AD is still not fully understood. Results of numerous studies conducted with the purpose to elucidate the role of CRP in AD are conflicting. Association of CRPand systolic and diastolic blood pressure in AD patients has not been extensively investigated.

Methodology: AD group consisted of fifteeninstitutionalized patients, aged 65 and over, with

clinically diagnosed probable Alzheimer’s disea-se by NINCDS-ADRDA criteria. All patients had mini mental state examination (MMSE) score < 23 and a Hachinski ischemic score 4 or bellow. Fifteen community dwelling, age-matched, appa-rently healthy, subjects without dementia served as the control group. All subjects in this group had a MMSE score > 28. Subjects included in the study underwent history, clinical examination and mini mental state examination. Serum CRP concentra-tion was measured by means of particle enhanced immunonephelometry. Systolic and diastolic blo-od pressure was measured with the use of mercury sphygmomanometer on the right arm after at least a 5-min rest.

Results: Age, systolic and diastolic blood pres-sure did not differ significantly between the twogroups. In AD group we found negative correlati-on between serum CRP concentration and systolic

Does serum C-reactive protein concentration correlate with blood pressure values in patients with probable Alzheimer’s disease?DA LI KONCENTRACIJA C-REAKTIVNOG PROTEINA U SERUMU KORELIRA SA VRIJEDNOSTIMA KRVNOG PRITISKA KOD PACIJENATA SA MOGUĆOM ALZHEIMEROVOM BOLESTI? Asija Zaciragic1*, Amina Valjevac1, Orhan Lepara1, Azra Alajbegovic2 1 The Institute of Physiology and Biochemistry, University of Sarajevo, Bosnia and Herzegovina 2 Clinic of Neurology, Clinical Centre University of Sarajevo, Bosnia and Herzegovina

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blood pressure (r=-0.43) but this correlation was not statistically significant. Likewise, negative alt-hough not significant correlation was found betw-een serum CRP concentration and diastolic blood pressure (r=-0.35) in AD group.

Conclusions: Our results have shown that ne-gative correlation between serum CRP concen-tration and systolic and diastolic blood pressure exists in patients with AD but this correlation is not statistically significant. Obtained results dosupport the notion that low-grade inflammationhas no impact on blood pressure values in patients with AD. Larger prospective studies are required to investigate these findings further.

Key words: Alzheimer’s disease, C-reactive protein, systolic blood pressure, diastolic blood pressure

Sažetak

Uvod: Alzheimerova bolest (AB) predstavlja progresivnu demenciju. Poznati riziko faktori za nastanak AB uključuju: dob, genetsku predodre-đenost, porodični istoriju demencije i ženski spol. Ateroskleroza, dislipidemija, hipertenzija i infla-macija se smatraju mogućim vaskularnim riziko faktorima za AB. C-reaktivni protein (CRP) je va-žan marker i medijator inflamacije niskog stepena.Njegova moguća uloga u nastanku i progresiji AB još uvijek nije u potpunosti rasvjetljena. Rezultati brojnih studija sprovedenih sa ciljem pojašnjenja uloge CRP kod AB su oprečna. Povezanost CRP i sistolnog i dijastolnog krvnog pritiska kod pacije-nata oboljelih od AB nije opsežno istraživana.

Metodologija: AB grupa se sastojala od petna-est institucionaliziranih pacijenata, starijih od 65 godina, sa klinički dijagnosticiranom mogućom Alzheimerovom bolesti prema NINCDS-ADRDA kriterijima. Svi pacijenti su imali mini mental sta-te examination (MMSE) skor < 23 i Hachinskijev ishemični skor 4 ili manje. Petnaest, dobno odgo-varajućih, zdravih pacijenata bez demecije služili su kao kontrolna grupa. Svi ispitanici u ovoj grupi imali su MMSE skor > 28. Ispitanici uključeni u istraživanje bili su podvrgnuti uzimanju anamne-ze, kliničkom pregledu i ispitivanju kognitivne funkcije primjenom mini mental state examinati-on testa. Koncentracija CRP u serumu određena

je laser nefelometrijom. Sistolni i dijastolni krvni pritisak izmjeren je upotrebom živinog sfingoma-nometra na desnoj ruci nakon najmanje 5 minuta odmora.

Rezultati: Dob, sistolni i dijastolni krvni pri-tisak nisu signifikantno bili različiti između dvijegrupe. U AB grupi utvrdili smo negativnu korela-ciju između koncentracije CRP u serumu i sistol-nog krvnog pritiska (r=-0.43) ali ova korelacija nije bila statistički signifikantna. Također, negati-vna mada ne i signifikantna korelacija utvrđena jeizmeđu koncentracije CRP u serumu i dijastolnog krvnog pritiska (r=-0.35) u AD grupi.

Zaključci: Naši rezultati su pokazali da postoji negativna korelacija između koncentracije CRP u serumu i sistolnog i dijastolnog krvnog pritiska kod pacijenata sa AB ali ova korelacija nije stati-stički signifikantna. Dobijeni rezultati ukazuju dainflamacija niskog stepena nema uticaja na vrije-dnosti krvnog pritiska kod pacijenta sa AB. Veće prospektivne studije su potrebne da bi se ovi nala-zi opsežnije istražili.

Ključne riječi: Alzheimerova bolest, C-reakti-vni protein, sistolni krvni pritisak, dijastolni krvni pritisak

Introduction

Alzheimer’s disease (AD) represents a pro-gressive dementia neuropathologically characteri-zed by widespread ß amyloid deposits (plaques) in cerebral arterial walls, development of neuro-fibrillary tangles in brain tissue and neuronal loss.Primary symptom of AD is decline in cognition and memory, with changes in personality. These changes can be one of the first symptoms of the di-sease, followed with behavioral impairment inclu-ding delusions, hallucinations and agitation. All of the above symptoms ultimately lead to impaired daily functioning and patients with AD in later and more sever stages of disease require total care (1).

The etiology and pathophysiology of AD is still not fully understood. In diagnostics of AD stan-dard clinical diagnostic criteria designed by Nati-onal Institute of Neurological and Communicative Disorders and Stroke and Alzheimer’s disease are used. Based on these criteria, diagnosis of AD can be definite, probable and possible. The diagnosis

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of definite AD requires histopathological confir-mation by postmortem examination (2).

Based on experimental and neuropathologic studies, inflammation is postulated to play a cen-tral role in processes leading to neurodegeneration as well as vascular injury (3). Neuroinflammationincludes an innate immune system reaction which results in an attack on host neurons.

C-reactive protein (CRP) is an acute phase pro-tein and is thought to be a link between innate and acquired immune system. CRP is not only extre-mely sensitive marker but as well a mediator of inflammation and tissue damage. Possible role ofCRP in the development and the progression of AD is still not fully understood. Results of nume-rous studies conducted with the purpose to eluci-date the role of CRP in AD are conflicting.

Study conducted by Yasojima and al. (4) has demonstrated that CRP is concentrated in pyrami-dal neurons and is upregulated in affected areas of AD brain. According to these findings controllingCRP production at tissue level could be significantfactor in reducing inflammatory damage in AD.On the other hand, Dik et al. (5) have demonstrated that serum concentration of CRP is not associated with cognitive decline in older persons. We have previously reported that serum CRP concentration was significantly higher in patients with probableAD compared to age-matched controls (6).

Evidences suggest that hypertension and hy-percholesterolaemia may increase the risk of de-mentia by inducing atherosclerosis and impairing blood flow, but they can also directly induce neu-rodegeneration of Alzheimer’s disease. Since the neurodegenerative processes in AD may begin in midlife it is important to identify early risk factors for the development of AD. Studies have shown that mean systolic and diastolic blood pressure has a tendency for an increase up to the age of 75 but that it decreases afterwards. Important role in blood pressure regulation has the brain but it still remains to be elucidated whether neuronal dege-neration that occurs with aging contributes to the decline in blood pressure in elderly (7).

The relationship between blood pressure and dementia is complicated because it has been re-ported that hypertension in midlife is a risk factor for Alzheimer’s disease but on the other hand the-re are studies that have shown that low blood pres-

sure predisposes the development of Alzheimer’s disease (8,9). Thus, the influence of dementia pro-cess on blood pressure remains inconclusive.

The aim of the present study was to examine the association between blood pressure values and serum C-reactive protein concentration in patients with probable AD.

Materials and methods

Two groups of subjects were enrolled in the present study: Fifteen patients, aged 65 and over, with clinically diagnosed probable Alzheimer`s disease by NINCDS-ADRDA criteria. All patients had mini mental state examination (MMSE) score < 23 (10). Patients had a Hachinski ischemic score 4 or bellow (11). We included all patients curren-tly institutionalized at specialized unit for patients with dementia within Health-Care Hospice for persons with disabilities and other persons in Sa-rajevo, Bosnia and Herzegovina. Fifteen commu-nity dwelling, age-matched, apparently healthy, asymptomatic subjects without dementia served as the controls. All subjects in this group had a MMSE score > 28. For both groups of subject, the exclusion criteria were positive history of cardio-vascular or thyroid disease, chronic inflammatorydisease (asthma and rheumatoid arthritis), hepatic or renal insufficiency and cancer. Subjects withself-reported common cold were also not included in the study. All procedures on human subjects were performed in the accord with Helsinki De-claration of 1975. Informed consent was obtained from all subjects and/or their caregivers. Subjects underwent history, clinical examination and mini mental state examination.

Blood pressure was measured manually in a standardized manner using a sphyngomanometer, with the patient in sitting position after five minu-tes of rest. Values were based on a single measure-ment. Hypertension was defined as a systolic blo-od pressure of >140 mm Hg or a diastolic blood pressure of >90 mm Hg or both, with or without the use of blood pressure lowering medications. Pulse pressure was calculated as the difference be-tween systolic and diastolic blood pressure. It is related to arterial stiffness and as such represents a measure of atherosclerosis (12)

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Non-fasting blood samples were drawn from antecubital vein into siliconized tubes. Samples were centrifuged at 4000 r.p.m. for 10 minutes to separate serum and were immediately used for the measurement of serum CRP concentration.

Serum CRP concentration was determined by means of particle enhanced immunonephelome-try with the use of BN II analyzer at the Institute of Clinical Chemistry and Biochemistry, Clinical Centre of the University of Sarajevo. CardioPha-se high-sensitivity CRP (DADE BEHRING) was used as a diagnostic reagent. CardioPhase hsCRP consists of a suspension of polystyrene particles coated with mouse monoclonal antibodies to CRP. Reference interval for CRP with the use of this method is from 0 to 5 mg/l.

Data are reported as mean ± SEM. Since CRP is highly skewed and the study sample is small, data were analysed with Mann-Whitney U Test which is the nonparametric alternative for the un-paired t test. Associations between continuous variables were tested with Spearman`s rank cor-relation analysis. Two-tailed p values <0.05 were considered statistically significant. Statistical ana-lyses were performed using SPSS 12.0 statistical software system.

Results

The baseline characteristics of the two groups enrolled in the study are reported in Table 1. No difference emerged in age, body mass index and

waist/hip ratio between the groups. MMSE score was significantly lower in subjects with AD com-pared to controls (p<0.0001). Subjects with AD had statistically significantly higher pulse pressurevalues compared to the control group (p<0.05).

Data are presented as mean ±SEM.MMSE score: Mini Mental State Examination

score; BMI: Body Mass Index; WHR: waist/hip ratio; PP: Pulse Pressure; Alzheimer’s disease (AD) group

As shown in Figure 1, no statistically signifi-cant difference was observed in systolic and dia-stolic blood pressure between control group and patients with probable Alzheimer’s disease.

Figure 1. Mean values of systolic blood pressure (SBP) and diastolic blood pressure (DBP) in the control group and Alzheimer’s disease (AD) group.

As presented in Table 2, negative although not significant correlation between systolic bloodpressure and CRP in patients with AD was obser-ved (r =-0.43). Likewise, there was a negative cor-

Table 1. Baseline characteristics of control subjects and patients with probable Alzheimer’s disease.

Variables Control group(n=15)

AD group(n=15) p<

Age(year) 69.93±2.57 73.46±2.57 NS

MMSEscore 28.4±0.34 9.07±1.17 p<0.0001

BMI(kg/m2) 25.86±0.98 27.62±1.68 NS

WHR 0.90±0.05 0.97±0.03 NS

PP(mmHg) 49.33±2.00 56.67±3.57 p<0.05

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relation between diastolic blood pressure and CRP in patients with AD but it was not statistically si-gnificant (r =-0.35). Statistically positive correlati-on was observed between systolic blood pressure and MMSE score in AD group (r=0.58, p< 0.05). Positive correlation between diastolic blood pres-sure and MMSE score was determined but it was not statistically significant (r=0.50). Table 2. Spearman correlation analysis (unadju-sted) of systolic and diastolic blood pressure with C-reactive protein and Mini mental state exami-nation (MMSE) score in patients with probable Alzheimer disease.

SBP DBP

C-reactive protein r =- 0.43 r =- 0.35MMSE score r = 0.58* r = 0.50‡

*p< 0.05‡p=0.057

Discussion

Numerous findings from clinical, epidemiolo-gical and pharmacological studies suggest that va-scular factors play fundamental role in the patho-genesis of AD (13). Still, the mechanisms linking vascular risk factors to AD remain unclear.

It has been shown that disruption of cerebral blood vessels and reduced blood flow can havesevere consequences on neural activity. Hypo-perfusion is thought to have important role in the development of AD by triggering mitochondrial dysfunction and increased oxidative stress. Cli-nical observations have shown that episodes of hypotension may result in cerebral hypoperfusion, which may play a causative role in the develop-ment of dementia. Decreased cerebral blood flowis known to occur in AD, and the degree of redu-ction generally correlates with the severity of de-mentia. It seems possible that low blood pressure may accelerate the process of dementia by low-ering cerebral blood flow. Zhu and al. (14) havedemonstrated that oxidative stress represents one of the earliest changes in AD affected brain and plays a vital role in the vascular abnormalities un-derlying metabolic defects in AD.

It has been proposed that high blood pressu-re may increase risk of Alzheimer disease (15).

Among persons with high blood pressure decre-ased cognitive performance has been reported as well as greater cognitive decline with age (16). On the contrary, Morris and al. (17) have shown that high blood pressure was not associated with an increased risk of AD in logistic regression mo-dels adjusted for age, sex, and level of education. Interestingly, findings of Skoog et al. (8) suggestthat before disease onset in subjects with demen-tia blood pressure begins to decline which might implicate that disease process may decrease blood pressure values.

In a large epidemiologic study, Wu et al. (18) have identified high blood pressure as a risk factorfor AD. On the other hand, low diastolic blood pressure (≤65 mm Hg) was also associated with the increased risk of AD (19). A study by Kivi-pelto et al. (20) found that elevated systolic blood pressure and high cholesterol, and in particular combination of these risks in midlife, increases the risk of AD in later life, whereas diastolic blood pressure in midlife has no significant effect on therisk of AD.

According to numerous reports blood pressure declines in the years preceding dementia onset and further declines during the course of AD. Even thought it is believed that the low blood pressure in subjects with dementia and neuronal degeneration are secondary to the brain lesions, the possibility that low blood pressure causes brain damage sho-uld not be excluded. A study conducted by Hanon et al. (21) found a significant decrease of bloodpressure in patients with Alzheimer’s disease after one year of follow up which was independent of age, gender, BMI and antihypertensive therapy. Patients with the most severe impairment in de-mentia at baseline had largest decrease in blood pressure. Some authors speculate that blood pres-sure decrease might be an early manifestation of the dementing process. However, it is possible that clinically unrecognized vascular lesions in the bra-in or atherosclerosis may be responsible for both blood pressure decrease and cognitive decline in patients with AD (22).

In our study there was no statistically signifi-cant difference in mean systolic and diastolic blo-od pressure between patients with probable AD and apparently healthy controls. Conversely, Ra-zay et al. (23) found lower mean systolic blood

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pressure in patients with probable AD compared with controls. According to these authors it still re-mains unclear whether low systolic blood pressure predisposes the development of AD and contribu-tes to its etiology or is the result of neurodegene-ration.

Recent studies suggest that specific inflamma-tory mechanisms contribute to neurodegeneration. Evidences have shown that there is a local upre-gulation of inflammatory cytokines, acute phaseproteins such as CRP, activation of the comple-ment cascade and accumulation of microglia in damaged areas of AD brain (24). Our results have shown that there is a negative although not signi-ficant correlation between systolic blood pressureand CRP in patients with AD. Likewise, a nega-tive correlation between diastolic blood pressure and CRP in patients with AD was determined but it was not statistically significant. Even though wefailed to find significant association between blo-od pressure values and serum C-reactive protein concentration in patients with probable AD further investigations, especially large population studies, are necessary to explore these findings more pro-foundly.

Fischer et al. (25) evaluated numerous vascular risk factors including blood pressure and CRP and correlated these risk factors with overall cognition in a community-based cohort of 75-year-old in-dividuals. Authors did not find an association be-tween Mini-Mental State Examination score and blood pressure or CRP.

We found a statistically significant associationbetween systolic blood pressure and MMSE score in patients with probable AD. On the other hand, in the same group of patients correlation between diastolic blood pressure and MMSE score was also observed but it was not statistically significant.Our results are partly in the accordance with those of Guo et al. (26) who have reported that both sy-stolic and diastolic blood pressure were positively and significantly related to baseline MMSE scorein the very old individuals. Conversely, Scherr et al. (27) found no correlation between blood pres-sure values and cognitive performance in the el-derly. Multidisciplinary studies are needed to cla-rify possible causal relation between blood pressu-re and cognitive function in elderly population.

Conclusions

Our results have shown that negative correlati-on between serum CRP concentration and systolic and diastolic blood pressure exists in patients with AD but this correlation is not statistically signifi-cant. Obtained results do support the notion that low-grade inflammation has no impact on bloodpressure values in patients with AD. Larger pro-spective studies are required to investigate these findings further.

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15. Skoog I. Vascular aspects in Alzheimer’s disease. J Neural Transm Suppl. 2000; 49:37-43.

16. Launer LJ, Masaki K, Petrovitch H, Foley D, Ha-vlik RJ. The association between midlife blood pressure levels and late-life cognitive function: the Honolulu-Asia Aging Study. JAMA. 1995; 274:1-846-1851.

17. Morris MC, Scherr PA, Hebert LE, Glynn RJ, Bennett DA, Evans DA. Association of incident Alzheimer disease and blood pressure measured from 13 years before to 2 years after diagnosis in a large community study. Arch Neurol. 2001; 58:1640-1646.

18. Wu C, Zhou D, Wen C, Zhang L, Como P, Qiao Y. Relationship between blood pressure and Alzhei-mer’s disease in Linyian County, China. Life Sci 2003;72(10):1125-1123.

19. Qiu C, von Strauss E, Fastbom J, Winblad B, Fra-tiglioni L. Low blood pressure and risk of demen-tia in the Kungsholmen Project. A 6-year follow-up study. Arch Neurol 2003; 60:223-228.

20. Kivipelto M, Helkala EL, Laakso MP, HanninenT, Hallikainen M, Alhainen K, Soininen H, Tuomile-hto J, Nissien A. Midlife vascular risk factors and Alzheimer’s disease in later life: longitudinal, po-pulation based study. BMJ 2001; 322:1147-1451.

21. Hanon O, Latour F, Seux ML, Lenoir H, Forette F, Rigaud AS. Evolution of blood pressure in patients with Alzheimer’s disease: a one year survey of a French Cohort (REAL.FR). J Nutr Health Aging. 2005; 9(2):106-111.

22. Moretti R, Torre P, Antonello RM, Manganaro D, Vilotti C, Pizzolato G. Risk factors for vascular dementia: hypotension as a key point. Vasc Health Risk Manag. 2008;4(2):395-402.

23. Razay G, Vreugdenhil A, Wilcock G. The metabo-lic syndrome and Alzheimer disease. Arch Neurol. 2007;64:93-96.

24. Czlonkowska A, Kurkowska-Jastrzebska I. The role of inflammatory reaction in Alzheimer’s di-sease and neurodegenerative processes. Neurol Neurochir Pol. 2002;36(1):15-23.

25. Fischer P, Zehetmayer S, Bauer K, Huber K, Jung-wirth S, Tragl KH. Realation between vascular risk factors and cognition at age 75. Acta Neurol Scand. 2006;114(2):84-90.

26. Guo Z, Fratiglioni L, Winblad B, Viitanen M. Blo-od pressure and performance on the Mini-Mental State Examination in the very old. Am J Epidemi-ol. 1997;145(12):1106-1113.

27. Scherr PA, Hebert Le, Smith LA. Relation of blood pressure to cognitive function in the elderly. Am J Epidemiol. 1991;134:1303-1315.

Corresponding author: Asija Zaciragic Institute of Physiology and Biochemistry, University of Sarajevo, Bosnia and Herzegovina e-mail: [email protected]

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Summary

The aim of this study was to assess possible protective effects of Spirulina platensis on gen-tamicin-induced renal dysfunction in rats. Adult Wistar rats (n=18), both sexes, were divided into three equal groups. First, control group, was trea-ted with 0,9% sodium chloride, intraperitoneally for 7 consecutive days. Second, gentamicin group was treated with gentamicin (80 mg/kg per day), intraperitoneally also for 7days. Third, gentamici-n+spirulina group was pretreated for two days with water solution of Spirulina platensis (1000mg/kg in 2 ml of water) per os. Next 7 days was treated concomitantly with Spirulina platensis per os and gentamicin intraperitoneally in the same volume as animals in previous groups. Renal function was assessed by measuring serum urea and creatinine concentrations. The light microscopic histological analysis confirmed the acute tubular necrosis ingentamicin and gentamicin+spirilina group. Gen-tamicin induced renal failure due to acute tubular

necrosis in both experimental groups. The most significant increase of serum biohumoral markersof renal function was in gentamicin group (urea; gentamicin group (X=27,47±2,15mmol/L) versus control group (X=7,08±0,09mmol/L) and creati-nine: gentamicin group (X=192,5±23,68 mmol/L) versus control group (X=56±1,24 mmol/L) (p=0-,002). Spirulina platensis decreased the serum le-vel of biohumoral markers of renal function (urea; gentamicin+spirulina group (X=11,53±1,66mmol/L) versus gentamicin group (X=27,47±2,15mmol/L);(p=0,002) and creatinine; gentamicin+spiruli-na group (X=107,33±20,14mmol/L) versus genta-micin group (X=192,5±23,68 mmol/L) (p=0,026) and attenuated the gentamicin induced acute tu-bular necrosis. Our results indicate that Spirulina platensis diminished toxic renal effects of genta-micin and preserve renal function in gentamicin induced acute tubular necrosis in rats.

Key words: spirulina platensis, urea, creatini-ne, acute tubular necrosis, gentamicin, nephroto-xicity

The effects of spirulina platensis on biohumoral markers of renal function in gentamicin-induced acute tubular necrosis in ratsEFEKTI SPIRULINE PLATENSIS NA BIOHUMORALNE MARKERE BUBREŽNE FUNKCIJE KOD GENTAMICINOM-UZROKOVANE AKUTNE TUBULARNE NEKROZE KOD ŠTAKORANesina Avdagic1*, Esad Cosovic2, Emina Nakas-Icindic1, Zakira Mornjakovic2, Asija Zaciragic1, Almira Hadzovic-Dzuvo1

1 Institute of Physiology and Biochemistry, Faculty of Medicine, University of Sarajevo, Bosnia and Herzegovina2 Institute of Histology and Embryology, Faculty of Medicine, University of Sarajevo, Bosnia and Herzegovina

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Sažetak

Cilj ove studije je bio da procjeni moguće pro-tektivne efekte Spiruline platensis kod gentamici-nom-uzrokovane renalne disfunkcije kod štakora. Odrasli Wistar štakori (n=18), oba pola, podjeljeni su u tri jednake grupe. Prva, kontrolna grupa, je primala 0,9% natrium hlorid, intraperitonealno 7 uzastopnih dana. Druga, gentamicin grupa, je pri-mala gentamicin (80 mg/kg dnevno), intraperito-nealno također 7 dana. Treća, gentamicin+spiru-lina grupa, je dva dana prije tretirana sa vodenim rastvorom Spiruline platensis (1000mg/kg u 2 ml vode) per os. Sljedećih 7 dana je istovremeno tre-tirana sa Spirulinom platensis per os i gentami-cinom intraperitonealno u jednakoj količini kao i životinje iz prethodne grupe. Renalna funkcija je procjenjivana mjerenjem koncentracije uree i kreatinina u serumu. Histološkom analizom koja je rađena svjetlosnim mikroskopom potvrđena je akutna tubularna nekroza kod gentamicin i gen-tamicin+spirilina grupe. Gentamicin je uzrokovao renalno zatajenje zbog akutne tubularne nekroze u obje eksperimentalne grupe. Najsignifikantnijepovećanje serumskih biohumoralnih markera bu-brežne funkcije je bilo u gentamicin grupi (urea; gentamicin grupa (X=27,47±2,15mmol/L) versus kontrolna grupa (X=7,08±0,09mmol/L) i kreati-nin: gentamicin grupa (X=192,5±23,68 mmol/L) versus kontrolna grupa (X=56±1,24 mmol/L) (p=-0,002). Spirulina platensis je smanjila serumski nivo biohumoralnih markera bubrežne funkcije (urea; gentamicin+spirulina grupa (X=11,53±1,-66mmol/L) versus gentamicin grupa (X=27,47±-2,15mmol/L);(p=0,002) i kreatinin; gentamicin+-spirulina grupa (X=107,33±20,14mmol/L) versus gentamicin grupa (X=192,5±23,68 mmol/L) (p=0-,026 ) i umanjila efekte gentamicinom uzrokovane akutne tubularne nekroze. Naši rezultati ukazuju da Spirulina platensis umanjuje renalne toksične efekte gentamicina i štiti renalnu funkciju kod gentamicinom uzrokovane akutne tubularne ne-kroze kod štakora.

Ključne riječi: Spirulina platensis, urea, kre-atinin, akutna tubularna nekroza, gentamicin, ne-frotoksičnost

Introduction

Aminoglycoside antibiotics (gentamicin) are widely used in clinical medicine because of their favorable antimicrobial efficacy against Gram-ne-gative infections. Unfortunately, the clinical use of aminoglycoside is limited by their potential oto-toxicity and nephrotoxicity (1). The pathophysi-ology of aminoglycoside nephrotoxicity has not been completely elucidated. Several mechanisms could be involved in gentamicin induced renal dy-sfunction. These include binding of gentamicin to phospholipids and inhibiting the activity of phos-pholipase A and C which alters the function and structure of cellular and intracellular membrane (2,3). Gentamicin may also cause mitochondrial damage or direct inhibition of mitochondrial oxi-dative phosphorylation (4). Reactive oxygen spe-cies (ROS) may participate in the pathogenesis of gentamicin-induced renal dysfunctions (5). In previous studies some synthetic and natural anti-oxidants have been used to attenuate gentamicin-induced oxidative stress and renal dysfunctions (6,7).

Spirulina platensis, blue green algae, has a long history of use as food supplement. It is rich of proteins, essential amino and fatty acids, vi-tamins, especially vitamin B12 and provitamin A (β-carotene), and some vital elements like zinc, magnesium, selenium (8,9). Spirulina platensis has immunomodulatory (10), anticancer (11,12), antioxidant (13,14), antihyperlipidemic (15), an-tidiabetic effects (16) and prevents lead toxicity (13,17).

The aim of the present study was to assess whet-her treatment with Spirulina platensis may prevent or ameliorate renal dysfunction and injury in gen-tamicin-induced acute tubular necrosis in rats.

Materials and methods

Animals

The experiment was performed in adult Wistar rats (n=18) weighing 200 to 300g in accordance with the approval of local Ethic Committee. Befo-re the experiments all animals were housed under

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standard laboratory conditions and were allowed one week of adaptation period. Standard rat chow and tap water were given ad libitum. Animals were divided into three groups, consisting of six rats each: control, gentamicin and gentamicin+-spirulina group.

Drugs

Gentamicin was purchased, injection solute (under the trade name Bosnalijek). Spirulina pla-tensis was obtained commercially as a dark blue-green dry powder (from Nutrex Hawaii M.D. For-mulas™ ).

Experimental protocol

Control group was treated with 0,9% sodium chloride, intraperitoneally for 7 consecutive days. Gentamicin group was treated with gentamicin (80 mg/kg per day), intraperitoneally also for 7 days. Gentamicin+spirulina group was pretrea-ted for two days with water solution of Spirulina platensis (1000mg/kg in 2 mL of water) per os, followed by administration of Spirulina (1000mg/kg in 2 mL of water) per os, and gentamicin (80 mg/kg per day) intraperitoneally for 7 days. The injections were given between 9.00 and 9.30 a.m. to minimize the circadian variation seen in genta-micin-induced nephrotoxicity (18).

At the end of the experiment, 24 hours after the last gentamicin, gentamicin+spirulina and nor-mal saline injection, and rats were sacrificed un-der deep ether anesthesia and the front wall of the abdominal cavity was opened. Blood was drawn from the abdominal aorta for the measurement of serum urea and creatinine concentrations. Kidne-ys were immediately removed, vertically divided into two sections and fixed in 10% formalin andthen embedded in paraffin wax for histologicalanalyisis.

Biohumoral markers of renal functions

Urea

Serum urea concentration was determined by enzymatic method. Absorbance was measured at 340 nm. The results were expressed as mmol/L.

Creatinin

Jaffe’s reaction was used for determination of serum creatinine concentration. Absorbance was measured at 500-520 nm. The results were expres-sed as mmol/L.

Histology

For microscopic evaluation kidneys were fixedin 10% formalin and then embedded in paraffinwax. Tissue sections of 5μm were stained with hematoxylin-eosin (HE) and Periodic acid-Schiff (PAS). A minimum of 10 fields by light microsco-py for each kidney sections were examined and assigned for severity of changes according to Ho-ughton et al. (17).

Statistical analysis

Statistical analyses were performed using SPSS software, version 12. Results were expressed as mean ± SEM. The difference in values of tested parameters was assessed by Kruskal-Wallis test. Afterwards, Mann-Whitney test was used to test the significance of mean values differences betw-een the two groups. Association between serum urea concentrations and histological injury score was tested with Spearman’s rank correlation ana-lysis. The same test was used to investigate asso-ciation between serum creatinine concentrations and histological injury score in total experimental sample. The statistical significance was conside-red at p<0,05.

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Results

Biohumoral markersUrea

The significant differences in serum urea con-centrations were observed between the groups (p<0,001). The highest value was in gentamicin group (X=27,47±2,15mmol/L). In gentamicin+-spirulina group value was higher (X=11,53±1,66 mmol/L, p=0,002) than in control group(X=7,08± 0,09 mmol/L) but significantely lower than in gen-tamicin group (p=0,002). (Figure 1)

Figure 1. Serum urea concentrations (mmol/L) in control, gentamicin+spirulina and gentamicin group of rats. Values are expressed mean ± SEM. *p= 0,002 compared with control; **p= 0,002 compared with control and gentamicin;

Creatinine

Gentamicin markedly increased the serum cre-atinine concentrations, and the difference between groups was statistically significant (p=0,002). Thehighest value was in gentamicin group (X=192,-5±23,68 mmol/L). Spirulina platensis significan-tly decreased the serum creatinine concentration (X=107,33 ±20,14 mmol/L) (p=0,002), but it was still higher than in the control group(X=56±1,24 mmol/L) (p=0,026). (Figure 2).

The standard light microscopy has been used for histological analysis. In the control group there were no any changes in structure of renal tissue. The renal tissue of rats treated with gentamicin showed necrotic areas in the superficial cortex,desquamated epithelial cells debris in the lumen of proximal tubules and interstitial edema. Brush-

border membranes of almost all cells were disru-pted. Spirulina platensis partially reduced these changes.

Figure 2. Serum creatinine concentrations (mmol/L) in control, gentamicin+spirulina and gentamicin group of rats. Values are expressed mean ± SEM *p= 0,002 compared with control; **p= 0,026 compared with control and gentamicin;

Renal histology

Using Spearman’s rank correlation analysis a positive, statistically significant, correlation wasfound between histopathological injury score and serum urea concentration in total experiment sam-ple (r= 0,74; p<0,01) (Figure 3).

Figure 3. Mean serum urea concentration (mmol/L) and kidney histological injury score within control and experimental groups

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In total experimental sample a positive, statisti-cally significant, correlation between histologicalinjury score and serum creatinine concentration also was found (r= 0,62; p<0,01) (Figure 4).

Figure 4. Mean serum creatinine concentration (mmol/L) and kidney histological injury score within control and experimental groups

Discussion

Acute tubular necrosis (ATN) is most frequen-tly caused by constriction of blood vessels, but it can be also caused by cisplatin, heavy metals, radi-ological contrasts, as well as other compounds of lesser importance (20, 21). Gentamicin and other aminoglycoside antibiotics caused acute tubular necrosis and renal dysfunction in rats (22, 23).

The protective effects of Spirulina platensis were investigated in present study in animal mo-del of ATN caused by gentamicin. The renal dy-sfunction due to gentamicin induced acute tubular necrosis (ATN) has been conformed by increased of biohumoral markers of renal function, serum urea and creatinine concentration especially in animals treated only with gentamicin. Spirulina diminished this increase.

These results are in accordance with the results of Kuhad et al. (9) who used higher dose of gen-tamicin (100mg/kg) and three different doses of Spirulina (500, 1000, 1500mg/kg). Their results have showed that use of Spirulina lowers serum

urea and creatinine concentration in ATN caused by gentamicin. These results, as well as the results of our study, indicate that Spirulina platensis can ameliorate gentamicin-induced renal dysfunction in rats.

Kuhad et al. (24) and Mohan et al. (25) tested protective effects of Spirulina in ATN caused by cisplastin, where as Khan M. et al. (26) also te-sted protective effects of Spirulina in ATN caused by ciclosporin. Results of these studies confirmedthat Spirulina platensis has renoprotective effect and decreased the serum urea and creatinine con-centration and significantly prevents nephrotoxici-ty due to its antioxidant actions.

The renoprotective effects of Spirulina have been confirmed in experiments in which ATN wascaused by mercury chloride (HgCl2) (27). Humo-ral markers of renal function, serum urea and cre-atinine concentration were significantly lower inanimals that concomitantly with mercury chloride received Spirulina.

Results of light microscopic analysis in our study showed various level of reanl injury (ATN) in animals both treated with gentamicin and genta-micin+spirulina concomitantly. In the gentamicin group marked necrosis of cortical tubules, intersti-tial edema and tubular brush border loss were ob-served. Desquamated epithelial cells debris in the proximal tubular lumen was also observed widely in these necrotic areas. Treatment with Spirulina platensis reduced these changes.

Morphological changes in kidney specimens in our study were similar to those observed by Kuhad et al. (9) who also investigate protective effects of Spirulina in gentamicin-induced acute tubular ne-crosis in rats. In this study use of Spirulina platen-sis also decreased level of kidney damage.

Results of our study are also in the accordan-ce with results of Sharma et al. (27) who induced ATN with mercury chloride. The results from their study suggest that Spirulina can significantly mo-dify the renal damage in mercury chloride induced toxicity.

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Conclusion

In summary, the results of our study indicate that pretreatment with Spirulina followed by si-multaneous Spirulina and gentamicin treatment preserve the renal function and ameliorates the severity of renal tubular necrosis in gentamicin in-duced acute tubular necrosis.

Literature

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2. Laurent G, Carlier M.B., Rollman B., et al. Mecha-nism of aminoglycoside-induced lysosomal phos-pholipidosis: in vitro and in vivo studies with gen-tamicin and amikacin. Biochem. Pharmacol. 1982; 31: 3861-3870.

3. Kirschbaum B.B. Interactions between renal brush border membranes and polyamines. J. Pharmacol. Exp. Ther. 1984; 229(2): 409-16.

4. Weinberg J.M., Harding P.G., Humes H.D. Mecha-nisms of gentamicin-induced dysfunction of renal cortical mitochondria. II. Effects on mitochondrial monovalent cation transport. Arch. Biochem. Bio-phys. 1980; 205(1): 232-9.

5. Baliga R., Ueda N., Walker P.D., Shah SV. Oxidant mechanisms in toxic acute renal failure. Drug Me-tab. Rev. 1999; 31(4): 971-97.

6. Morales A.I., Buitrago J.M., Santiago J.M. et al. Protective effects of trans-resveratrol on gentami-cin induced nephrotoxicity. Antioxid. Redox. Signal. 2002; 4: 893-898.

7. Maldonado P.D., Barrera D., Medina-Campoa O.N. et al. Aged garlic extract attenuates gentami-cin induced renal damage and oxidative stress in rats. Life Sci. 2003; 73: 2543-2556.

8. Belay A. The potential application of Spirulina (Arthrospora) as a nutritional and therapeutic sup-plement in health management. The Jour of the Am Nut Asso (JANA). 2002; 5: 27-48.

9. Kuhad A., Tirkey N., Pilkhwal S., Chopra K. Effects of Spirulina, a blue green algae, on gentamicin-in-duced oxidative stress and renal dysfunction in rats. Fund and Clin. Pharmacol. 2006; 20: 121-128.

10. Mao T., Water J.V.D., Gershwin M. Effect of Spi-rulina on the secretion of cytokines from periphe-ral blood mononuclear cells. J. Med. Food.2000; 3: 135-140.

11. Dasguptat T., Baneejee S., Yadav P.K., Rao A.R. Chemomodulation of carcinogen metabolising enzymes, antioxidant profiles and skin and fore-stomach papillomagenesis by Spirulina platensis. Mol. Cell. Boichem. 2001; 226: 27-38.

12. Zhang H.Q., Lin A.P., Sun Y., Deng Y.M. Chemo- and radio-protective effects of polysaccharide of Spirulina platensis on hemopoetic system of mice and dogs. Acta Pharmacol. Sin. 2001; 22: 1121-1124.

13. Upasani C.D., Balaraman R. Protective effect of Spirulina on lead induced deleterious changes in the lipid peroxidation and endogenous antioxi-dants in rats. Phytother. Res. 2003; 17: 330-334.

14. Upasani C.D., Khera A., Balaraman R. Effect of lead with vitamin E, C or Spirulina on malondial-dehyde, conjugated dienes and hydroperoxides in rats. Indian. J. Exp. Biol. 2001; 39: 70-74.

15. Gonzalez de Rivera C., Miranda-Zamora R., Diaz-Zagoya J.C., Juarez- Oropeza M.A. Preven-tive effect of Spirulina maxima on the fatty liver induced by a fructose-rich diet in the rat, a preli-minary report. Life Sci. 1993; 53: 57-61.

16. Parikh P., Mani U., Iyer U. Role of Spirulina in the control of glycemia and lipidemia in type 2 di-abetes mellitus. Dig. Dis. Sci. 2001; 4:193-199.

17. Shastri D., Kumar M., Kumar A. Modulation of lead toxicity by Spirulina fusiformis. Phytother. Res. 1999; 13: 258-260.

18. Pariat C., Courtois P., Cambar J. et al. Circadi-an variation in the renal toxicity of gentamicin in rats. Toxicol. Lett. 1988; 40: 175-182.

19. Houghton D.C., Plamp C.E., DeFehr J.M. et al. Gentamicin and tobramycin nephrotoxicity: a morphologic and functional comparison in the rat. Am. J. Pathol. 1978; 93: 137-151.

20. Rumboldt Z. Akutno zatajenje bubrega izazvano lijekovima. In: Akutno zatajenje bubrega. Ed, Lju-tić D., Rumboldt Z. E: Slobodna Dalmacija, Split, 1995: 103-121.

21. Einn W. F. Diagnosis and management of acute tubular necrosis. Medical Clinics of North Ameri-ca. 1990; 74(4): 873-891

22. Kopple J.D., Ding H., Letoha A. et al. L-carnitine

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ameliorates gentamicin-induced renal injury in rats. Nephrol. Dial. Transplant. 2002; 17: 2122-2131

23. Avdagic N., Nakas-Icindic E., Rasic S., Hadzo-vic-Dzuvo A., Zaciragic A., Valjevac A. The effects of inducible nitric oxide synthase inhibitor L-N6-(1-iminoethyl) lysine in gentamicn-induced acute tubular necrosis in rats. Bosnian Journal of Basic Med. Sci. 2007; 7(4): 322-327.

24. Kuhad A., Tirkey N., Pilkhwal S., Chopra K. Reno-protective effect of Spirulina fusiformis on cispla-tin-induced oxidative stress and renal dysfunction in rats. Ren. Fail. 2006; 28(3):247-254.

25. Mohan I.K., Khan M., Shobha J.C. et al. Prote-ction against cisplatin-induced nephrotoxicity by Spirulina in rats. Cancer Chemother. Pharmacol. 2006; 58(6): 802-808.

26. Khan M, Shobha JC, Mohan IK, et al. Spirulina attenuates cyclosporine- induced nephrotoxicity in rats. Journal of Applied Toxicol. 2006; 26 (5): 444-451.

27. Sharma M.K., Sharma A., Kumar A. Kumar M. Evaluation of protective efficacy of Spirulina fu-siformis against mercury induced nephrotoxicity in Swiss albino mice. Food. Chem.Toxicol. 2007; 45(6): 879-887.

Corresponding author: Nesina Avdagic Institute of Physiology and Biochemistry School of Medicine, University of Sarajevo Bosnia and Herzegovina e-mail. [email protected]

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Summary

Humane anthropometry (man-measure, Greek) is a science which deals with the comparative measurings of the human body, the processing and studying of the gained measures. It finds a wideapplication in sport, school, military and industrial medicine, and it has touching points with all other branches of medicine. Anthropometric investi-gations are direct indexes of the morphological structure of the body, and indirect indexes of the exchange of energy and the caloric balance of the organism. The investigations are performed with certain methods and according to the standard conditions in the whole world, so the results can be compared. Anthropometric investigations serve to follow the growth and development of the hu-man organism, they encompass the measuring of

weight, height, scope of the body and skin wrin-kles.

In sport medicine it serves to objectively es-tablish the development of the body, that with the comparison of consecutive measurements notices the progress or stagnation in development, and that on the basis of certain anthropometric dimen-sions directs athletes towards sport disciplines in which one can expect optimal success.

The aims of this investigation are to investigate the anthropometric values of boys on a sample of 100 tested people, 50 who actively train basketball and 50 who do not train any sports at all, Canton Sarajevo, Body Mass Index, the distribution of fat tissue and compare the anthropometric measur-ings.

The research was performed on a chosen sam-ple of 100 boys aged 14 to 15 years, from which

Anthropometric values for boys aged 14 – 15 years who actively train basketball in comparing to boys of same age who do not train any sportsANTROPOMETRIJSKE VRIJEDNOSTI KOD DJEČAKA UZRASTA 14 – 15 GODINA KOJI AKTIVNO TRENIRAJU KOŠARKU U ODNOSU NA DJEČAKE ISTE DOBI KOJI NEMAJU SPORTSKIH AKTIVNOSTIDijana Avdic¹, Fatima Jusupovic², Mensura Kudumovic³

¹ KCU Sarajevo, Bosnia and Herzegovina,² Faculty of Health, Bosnia and Herzegovina,³ Faculty of Medicine, Bosnia and Herzegovina

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50 actively train basketball in the basketball club “Željezničar”, and 50 boys who do not train any sports.

The measurings were performed on boys who attend the following elementary schools:

Elementary school “Isak Samokovlija”, and el-ementary school “Vladislav Skaric” and on boys who attend the same school and train basketball in the basketball club “Željezničar”, the height cat-egory of a cadet.

The standards which we used are displayed on the percentage curves. We established an average body height for 90% of boys who do not train any sports. We established an average body height of 24% for basketball players. We established an av-erage body weight for 94% of boys who do not train any sports. We established an average body weight of 96% for basketball players. An average BMI was established for 100% of boys who do not train any sports. An average BMI was established for 100% for basketball players. We established an average value of DMT for 56% of boys who do not train any sports.

Our results have shown an above average height for even 76% of basketball players, so one sets the question whether intensive basketball training has any effect on the body height or do boys with an above average height more often decide to train basketball.

Children who train sports are not: obese, they do not consume alcohol, they do not smoke, they do not take any narcotics, they are less absent from their lessons, they have less chances of becoming ill from chronic diseases.

Key words: the sport medicine of anthropo-metric values, Body Mass Index,

Sažetak

Humana antropometrija (čovjek–mjera, grč.) je nauka koja se bavi komparativnim mjerenjima ljudskog tijela, obradom i proučavanjem dobi-venih mjera. Nalazi široku primjenu u sportskoj, školskoj, vojnoj i industrijskoj medicini, a ima do-dirne tačke i sa svim drugim granama medicine. Antropometrijska ispitivanja su direktni pokaza-telji morfološke građe tijela, te indirektni pokaza-telji izmjene energije i kalorijskog bilansa orga-

nizma. Ispitivanja se vrše određenim metodama i pod standardnim uslovima u cijelom svijetu, te se rezultati mogu upoređivati. Antropometrijska ispi-tivanjaj služe za praćenje rasta i razvoja čovječijih organizama, obuhvataju mjerenje težine, visine, obima tijela i kožnih nabora.

U sportskoj medicini služi da objektivno usta-novi razvoj tijela, da poređenjem uzastopnih mje-renja uoči napredak ili stagnaciju u razvoju, te da na bazi pojedinih antropometrijskih dimenzija usmjerava sportaše prema sportskim disciplinama u kojim se može očekivati optimalan uspjeh.

Ciljevi ovog istraživanja su ispitati: antropo-metrijske vrijednosti dječaka na uzorku 100 ispita-nika, 50 koji se bave aktivno košarkom i 50 koji se ne bave sportskim aktivnostima, Kanton Sarajevo, Body Mass Indeks, distribuciju masnog tkiva i uporediti antropometrijska mjerenja

Istraživanje je rađeno na odabranom uzorku od 100 dječaka starosti 14 – 15 godina, od kojih 50 ak-tivno trenira košarku u košarkaškom klubu “Želje-zničar”, i 50 dječaka koji se ne bave sportom.

Mjerenja su izvršena kod dječaka koji pohađaju osnovne škole: O.Š. “Isak Samokovlija”i O.Š “Vladislav Skarić” i kod učenika koji pohađaju istu školu a košarku treniraju u košarkaškom klu-bu “Željezničar”, uzrasne kategorije kadeta.

Standardi kojima smo se služili prikazani su u percentilnim krivuljama. Prosječnu tjelesnu visinu ustanovili smo kod 90% dječaka bez sportskih ak-tivnosti. Kod košarkaša prosječnu tjelesnu visinu ustanovili smo kod 24%. Prosječnu tjelesnu težinu ustanovili smo kod 94% dječaka bez sportskih ak-tivnosti. Kod košarkaša prosječnu tjelesnu težinu ustanovili smo kod 96%. Prosječan BMI usta-novljen je kod 100% dječaka bez sportskih akti-vnosti. Prosječan BMI ustanovljen je kod 100% košarkaša. Prosječnu vrijednost DMT ustanovili smo kod 56% dječaka bez sportskih aktivnosti.

Naši rezultati su pokazali nadprosječnu visinu kod čak 76% košarkaša, pa se postavlja pitanje da li intenzivno treniranje košarke ima uticaja na tje-lesnu visinu ili se dječaci sa nadprosječnom visi-nom češće odlučuju na treniranje košarke.

Djeca sportisti nisu: gojazni, ne piju, ne puše, ne drogiraju se, manje čak izostaju sa nastave, imaju manje rizika od obolijevanja od hroničnih bolesti.

Ključne riječi: sportska medicina antropome-trijske vrijednosti, Body Mass Indeks,

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1. Introduction

Anthropometric measurings are reliable and precise, and they are applied as well on an indivi-dual as on certain population groups. In medicine the most often used are the anthropologic chara-cteristics which in a certain period give an idea of the health condition. The main rules and principles during the anthropometric measurings are to alw-ays measure at the same time and if possible to measure with the same equipment and the same technique. The control of the measurings should be performed by the same person who performed the first measuring if possible.

One of the most important morphological cha-racteristics is the body height, which shows the growth, development, health condition and in-directly the living conditions of that person. The body height is the vertical distance from the base to the highest point on the top of the head. The body height is measured in the morning, conside-ring that the height decreases during the day, beca-use of the flattening of the intervertebral discusses.The measured person stands on an even base ba-refoot, straightens up, the hands are spread along the body, the feet straightened up to the knees, the heels together and the tops of the feet apart. An anthropometer is the most precise instrument for the measuring of height.

The body mass displays the health condition, physical development and the connection between the morphological and the phisiological characte-ristics of the person. The body mass is measured in the morning hours, after the emptying of the blad-der and the digestive tract, on an empty stomach if possible without or with a minimum of underwear. The body mass is measured with a medicinal deci-mal scale with an additional weight.

The indexes of the muscular and the body mass, the functional condition and the physical develop-ment of the organism are the body scopes. The body scopes are measured on clearly defined points, desi-rably in the morning hours. The scope of the waist is measured in the middle between the rib arc and the crest of the bone, and the scope of the hips on the widest part of the flanks. The scopes of the bodyare measured with a metal or plastic centimetre strip and never with a linen one because of the impreci-seness which arises during the stretching.

Anthropometric measurings are performed be-cause of scientific research or for practical aims.

Growth is the increase of certain dimensions or the total body mass. The speed of the growth varies during the phases of growth and develop-ment so that it is fast in the pre-natal, during the first year of life and in adolescence. The lengthof a newly-born during birth totals to almost one third of his or her adult weight, and to the second year one half of the height which it will have as an adult.

The development is an advancement of skills and complex functions. The growth and the de-velopment are independent, mutually connected processes. The growth usually lasts during the firsttwenty years of life and the development continu-es even after that. The best possible growth and development require an optimal health.

Factors which have an effect on the growth and development:

Genetic potential A finally reached height anddevelopment of the child depend on the genetic potential of the parents and there is also a good corelation between the height of brothers and si-sters.

Sex Male children are longer and heavier at birth than female children, but the differences fade out with the reaching of the first year of life. Latein puberty distinct differences appear in height, weight and the proportions of the body.

Seasonal variations The speed of the growth in height is the fastest in spring and it can be twice as fast from the speed of growth in autumn, con-trary to that the speed of the increase of body mass is the fastest in autumn.

Diet A regular and healthy diet provides a phy-sically healthy growth and development, and a highly caloric and unhealthy diet leads children to physical problems and illnesses. A chronic malnu-trition disables the child from reaching the height predicted by the genetic potential. Populations which suffer from chronic malnutrition do not only have less body weight but they also have less than average height. If a period od malnutrition did not last long the remnants can be substituted for in height with an accelerated growth. Shorter periods of malnutrition result only in the losing of weight, without an effect on the height of the child.

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Health condition Chronic diseases lead to a decrease of growth while brief infections do not have an effect on the speed of growth.

Functions of the individual endocrine glands The function of individual endocrine glands has an effect on the increase of cells, as on their gro-wth and especially on the growth of bones.

Socio-economic state of the family Socio-economic state of the family has an effect on the speed of the growth and development as on an utmost reached body height and weight.

Physical activity of the child-sports Sport ex-ercise is a mean of sport education and its effect on children is important. Physical activity is a basic human need from his or her birth to old age. For the physical activity to have a positive influence onthe development of a young organism it has to be: programmed, planned, organised, time scheduled (6 to 8 hours weekly), performed by a professi-onalist. It is considered that stimuli which cause systematic physical activity urge the young orga-nism to correct growth and development which is especially tumultuous in adolescence. Program-med physical activity – training, raises the level of some psychomotoric abilities: speed, strength, endurance and skills. Psychomotoric abilities re-present a complex readiness for the carrying out of certain movements, and in its development have a similar curve like other human characteristics, the culmination is reached with the reaching of the 25th year of life. Programmed physical activi-ty positively stimulates the function of the inner organs, especially the cardiovascular system, the respiratory system, organs which play a part in the metabolic processes and the autonomic nervous system. Besides all the positive aspects sport has on the growth and the development of the orga-nism there is a significant influence on the normalmental development. The majority of sports and especially collective sports have an effect on the creativity of the child.

Basketball is a sport which is played and tra-ined in the whole world and also one of the most trained sports between boys and girls. Active trai-ning of basketball contributes to:

• Physical development of the player• The development of cognitive functions

• The development of healthy and the adoption of new positive habits

• The development of personal and social values which are very important in the upbringing of children

• The accepting of obligations towards others• Individual and team responsibilities• Self-respect, the respecting of others and the

respecting of rules• A development of persistence, working

habits and moral responsibility through a respectful relationship towards the teammate and opponent.

The growth of body height, weight and the BMI of the centimeter curve In everyday praxis for the evaluation of physical progress of the infant first of all serves the body weight, and after the firstyear of life for the long-term supervision the body height. Body height, weight and the BMI of a cer-tain child we compare with the corresponding me-asures of a group of healthy children. The curves of the growth of height, weight and the BMI are made on the basis of statistically processed data of a big number of healthy children in the coordinate system in which the abscissa tells the age of the child and on the ordinate the reached weight, he-ight or BMI for that age. The percentages on those graphs represent average child height, weight and BMI. The centimeter curves are in a span of P = 3 – 97. Children with the parameters below 3, that is, above 97 in a considerable measure step away from the biggest number of children of that same age.

Picture 1. The centimeter curve of height (boys)

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Body Mass Index – BMI

The most frequent method for the establishing of nutrition which is used today in epidemiologic research but more and more often in daily practi-ce is the establishing of the index of body mass (BMI). The BMI is calculated on the basis os the relationship between the body mass and the body height squared, which can be presented as:

• BMI = Body weight/body height (m)²;• The calculation of the relationship of the body

mass and the height show the measure of the level of nutrition, but not the constitution;

• BMI changes for children with age and it is highly dependent on the BMI of the biological parents;

• The risk of developing obesity exists for children if their BMI is above the 85th percentage, and they are obese if the BMI is bigger than the 95th percentage;

• A person who follows the growth and development of a certain child is compared to the BMI with the values on the percentage curve and can early notice the threats to developing obesity or malnutrition.

The distribution of fat tissue – DMT Beside the level of obesity one needs to pay attention to the distribution of fat tissue, because the central distribution with the accumulation of fat on the trunk and abdomen are united with a big number of breakdowns. For children up to puberty there is no difference in the distribution of fat tissue accor-ding to the sexes. Only in puberty as a consequen-ce of the producing of sex hormones, they develop differences characteristic for the male or female sex. Through the relationship of the scope of the waist and hips one determines the distribution of fat tissue (DMT). Men are under a risk if the relati-onship of the scope of the waist/hips is bigger than 0,95cm and women if it is bigger than 0,85cm.

2. The aims of research

2.1. To examine the anthropometric values for boys on a model of a 100 tested people, 50 who actively train basketball and

50 who do not train any sports, Canton Sarajevo.

2.2 Examine the Body Mass Index2.3. Examine the distribution of fat tisssue2.4. Compare the anthropometric measurings.

3. The examiners and the methods of work3.1 Examiners

• The research was performed on a chosen model of 100 boys aged 14 – 15 years, from which 50 actively train basketball in the basketball club “Realway”, and 50 boys who do not train any sports.

• The measurings were performed on boys who attend the following elementary schools:

Elementary school “Isak Samokovlija” and elementary school “Vladislav Skaric” and on stu-dents who attend the same school but train basket-ball in the basketball club “Realway”, becoming category of cadets.

3.2 Methods of research

In this research the following anthropometric methods were used which include the measuring of:

- body height- body weight- scope of the waist- scope of the hips

• The data was incorporated in the appropriate form (example 1). The anthropometric measu-rings were carried out according to standard methods by which the anthropometric protocol was respected with the instructions on the procedure of measuring.

Anthropometric measurings

• During the measurings the boys had on them only the underwear and they were measured in the morning hours, before breakfast and after the carrying out of the physiological needs.

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• Before the measurings the instruments were checked in order for the measurings to be as precise as possible and mutually comparable, they were carried out by the same team, with the same apparatus and method at the same time.

Body height (cm)

• The body height was measured with an anthropometer which consists of one vertical metal rod with a scale, on which there is a mobile horizontal leg.

• The tested people were measured by standing on an even base barefoot with their heels together and a little separated toes, their body and the top of their head resting on the measuring scale. With the mobile leg of the anthropometer we touch the top of the head and we note down the height.

Body weight (kg)

• The body weight was measured with a medicinal decimal scale with a supporting weight.

• The tested people were measured by standing on the scale, they do not move during the measuring and the noting down of the body weight.

Body circumference (cm)

• Body circumference is measured with a plastic centimeter strip.

• The waist circumference is measured in the level of the umbilicus, between the rib arc and the crest bone, and the hips circumference on the widest part of the flanks.

Anthropometric indexes

• Anthropometric indexes represent certain relations of the anthropometric measurings mutually, that is, the calculating of certain proportions.

• For the comparison of the somatic growth of children many countries have set their standards, the so-called curves of growth and development of children. For international comparings and for countries which do not have such curves, such as Bosnia and Herzegovina, curves of growth are applied which have been accepted by the World Health Organisation.

5. The results of research

Table 1. The display of the tested people accor-ding to age and sport activities

Age Sport inactive boys

Basketball players K.K. “Željezničar”

14 - 15Number of boys % Number

of boys %

50 50 % 50 50 %Total 100

% 100 %

Table 2. Body height, body weight and their middle values of the total sampleAge 14 - 15

Body height and weight Number of boys % Body height

(cm) X Body weight (kg) X

Sport inactive boys 50 100% 158-187 cm 167,2 cm 45-90kg 59,2 kg

Basketball playersK.K. “Željezničar” 50 100% 165-196cm 184,5 cm 52-86kg. 71 kg

Total 100

% 100%

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In the table there is a display of the tested peopl aged 14 – 15 years devided according to the sport activities, from which 50 boys do not train sports and 50 boys who actively train basketball in the ba-sketball club “Željezničar”, and all are students of two elementary schools in the Municipality center.

In the totally expressed sample the middle value of the body height of boys without sport activities amounts to 167,2 cm, the middle value for weight is 59,2 kg. For basketball players the middle value of body height is 184,5 cm, the middle value for weight is 71 kg.

The middle value of the BMI for boys who do not train sports is 17,9 and the middle value of the DMT is 0,88 cm.

For basketball players the middle value of the BMI is 18,8, and the middle value of the DMT amounts to 0,85 cm.

The middle values for body height, weight, BMI and DMT for boys who are sport inactive show the standard values. For basketball players the middle value of the body height deviates from the standard one for this age concerning the abo-ve average, while the BMI and the DMT are also standard.

In the representative sample the measuring of body height was performed and the gained results show distinct differences in body height for these two groups of tested people.

Table 3. Body mass index, the distribution of fat tissue and their middle valuesAge 14 - 15

BMI and DMT Number of boys % BMI X DMT XSport inactive boys 50 100 13,9 – 25,4 17,9 0,79 – 0,94 0.88Basketball players K.K. “Željezničar” 50 100 15,4 – 21,9 18,8 0,67 – 0,89 0.85Total 100% 100%

Table 4. Body height, weight, BMI, DMT and their middle valuesAge 14 - 15

Anthropometric measurings Body height Body weight BMI DMT

Anthropometric values Span (cm) X Span

(kg) X Span(cm) X Span

(cm) X

Sport inactive boys 158-187 167,2 45 - 90 59,2 13,9-25,4 17,9 0,79-0,94 0,88

Basketball players K.K. “Željezničar” 165-196 184,5 52 - 86 71 15,4-21,9 18,7 0,67-0,89 0.85

Total 100% 100%

Table 5. Body weight shown in percentagesAge 14 - 15

Percentages 3 - 25 26 -75 76 - 97 >97 Number of boys %

Body height (cm) 150-162cm 163-177cm 174-181cm >182cm

Sport inactive boys 6 12% 26 52% 13 26% 5 10% 50 100%

Basketball players K.K. “Željezničar” 0 0 5 10% 7 14% 38 76% 50 100%

Total 100% %

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Graph 1. Body height

Sport inactive boys with the standard body he-ight of 150-181cm, that is, between 3-97 P we have 90% and while the above average body height of > 97 P or >182 cm is present in 10% of boys.

Basketball players with a standard body height of 150 – 181 cm, that is, 3-97 P we have 24% whi-le distinctly high > 97 P, that is, >182 cm there is present in 76% of basketball players.

In the body weight of these two groups there are distinct differences but not the same ones as for the body height.

Graph 2. Body weight

In the total sample the standard body weight between 39-81 kg, that is, from 3-97 P is present in 94% and an above average weight of >82kg, that is, of >97 P is present in 6% of sport inactive boys.

The standard weight of 39 – 81 kg, that is, from 3-97 P is present in 96% of basketball players, while an above average body weight of >82 kg is present in 4% of basketball players.

Table 6. Body height shown in percentagesAge 14 - 15

Centimeters 3 - 25 26 - 75 76 - 97 >97 Number of boys %

Body weight (kg) 39 – 49 kg 50 – 63 kg 64 – 81 kg >82 kg

Sport inactive boys 7 14% 27 54% 13 26% 3 6% 50 100%

Basketball playersK.K. “Željezničar” 0 0 13 26% 35 70% 2 4% 50 100%

Total 100

% 100%

Table 7. The BMI of boys presented in percentagesAge 14 - 15

Percentages 3 - 25 26 - 75 76 - 97 >97 Number of boys %

BMI 16 - 18 18,1 – 21,5 21,6 - 27 >27

Sport inactive boys 33 66% 12 24% 5 10% - - 50 100%

Basketball playersK.K. “Željezničar” 15 30% 31 62% 4 8% - - 50 100%

Total 100

% 100%

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Malnutrition and obesity have significant here-ditary predispositions, it is believed that the genes for nutrition operate on the level of the hormonal regulation, so that some people from the same “raw material” produce more fats than others. That leads to an increase of the total mass and to a change of body dimensions, proportions and the shape.

Graph 3. BMI

The values of the BMI on the graph show a meek malnutrition in 66% of sport inactive boys and 30% of basketball players, the normal nutriti-

on is present in 24% of sport inactive and 62% of basketball players, a moderate pre-obesity is pre-sent in 10% of sport inactive and 8% of basketball players, while there are no obese people in either of the groups.

The DMT is a measure for the determining of the type of obesity, and an important indicator of the risks for health. For boys in adolescence there is an increase in the number of muscular cells, and the amount of fats slowly decreases, so that the weight for boys increases on account of the mu-scular tissue, and if they are even sport active they can have the ideal anthropometric measures.

Graph number 4. DTM

Table 8. The DMT of boys of the total sample displayed in the following tableAge 14 - 15

DMT (cm) 0,70 – 0,79 0,80 – 0,89 0,90 – 0,94 >0,95 Number of boys %Sport inactive boys 2 4% 26 52% 18 36% 4 8% 50 100%Basketball players K.K. “Željezničar” 5 10% 42 84% 3 6% - - 50 100%

Total 100% 100%

Table 9. The relations of the tested values: body height, weight, BMI and DMTAge 14 - 15

Anthropometric measurings Body height Body weight BMI DMT

Percentages <3 3-97 >97 <3 3-97 >97 <3 3-97 >97 <3 3-97 >97Sport inactive boys - 45 5 - 47 3 - 50 - - 46 4Basketball players K.K. “Željezničar” - 12 38 - 48 2 - 50 - - 50 -

Total - 57 43 - 95 5 - 100 - - 96 4% - 57 43 - 95 5 - 100 - - 96 4

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Compared to the normal values, we have 4% of boys who are sport inactive, 10% of basketball players with a decreased value of the DMT, 52% of sport inactive boys and 84% of basketball players with the ideal values of the DMT, the maximum values are present in 36% of sport inactive boys and 6% of basketball players, and 8% of sport ina-ctive boys have the abdominal type of obesity, and there are no basketball players in this group.

The gained results show that we have distinct deviations in body height for sport inactive boys and basketball players and the standard values for body weight, BMI and DMT for both of them.

The body height of 3 – 97 percentages (150 – 181 cm) is present in 90% of sport inactive boys and 24% of basketball players, while over 97 per-centages (>182 cm) there is present in 10% of boys who are sport inactive and 76% of basketball players.

The body weight between 3 – 97 percentages (39 – 81kg) there is present in 94% of boys who are sport inactive and 96% of basketball players, over 97 percentages (> 81 kg) there is present in 6% of boys who are sport inactive and 4% of ba-sketball players.

The BMI of the total sample is between 3 – 97 percentages (16 – 27).

The DMT of 3 – 97 percentages there is pre-sent in 100% of basketball players, while for sport inactive boys 92% is between the 3 – 97 percenta-ges and 8% have an increased DMT, that is, risky.

5. Discussion

A right growth and development are one of the fundamental conditions for a later harmonious and healthy way of living. The body height and weight are factors which tell us about growth and deve-lopment, considering that in comparison to height the weight is a vague indicator and criterium for the evaluation of physical development. The BMI is the most precious indicator of the nutritive con-dition. The DMT is a useful indicator of the type of the type of obesity. The research was conducted on a sample of 100 tested people of the male sex aged 14-15 years in the municipality Center, Can-ton Sarajevo. The measuring of the anthropome-tric parameters was performed with the standard

methods and that of height, weight, waist circum-ference and hips and the recalculating of the BMI and the DMT. After that the analysis was perfor-med and the tabeling of the data and after that the comparison of the gained results. The results of the analysis of the fout most important physical indicators (body height and weight, waist circum-ference and the hips) together with the recalcula-ted BMI and DMT enable the defining of the rightgrowth and development as well as the following of the effect of sports on the same. In our research the boys from the sample belong to a group of tall boys because the average body height of sport ina-ctive boys amounts to 167,2 cm and for basketball players it is 184,5 cm. The average body weight for sport inactive boys amounts to 59,2 kg and for basketball players it is 71 kg. In our research an in-creased BMI was present in 10% of sport inactive boys and 8% of basketball players, the others were in the framework of the standard. The DMT for 100% of basketball players was in the framework of the standard. The maximum DMT was present in even 36% of sport inactive boys and 8% of an increased DMT.

Sports as movement in general, represents a stimulans to growth and development of the or-ganism. For the sport activity to give its positive stimuli to growth and development, it is not eno-ugh for it to be just exhaustive, but also frequent enough, systematic and so used that it makes up for the rest and insufficient movement to whichchildren and youth are forced to during the day.

6. Conclusion and recommendations

This research had the aim of examining the anthropometric values for boys who actively train basketball and those who do not train any sports on a sample of Canton Sarajevo. Also to examine the Body Mass Index, the distribution of fat tis-sue, and compare the anthropometric measurings. The narrow aim of the research was to examine the average body height and weight of boys in the Sarajevo Canton and the deviations from the standard values. To the deviations in growth and development which arise during puberty, in a big measure physical activity can have an effect or inactivity. Standards which we used are displa-

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yed in the percentage curves. The average body height was established for 90% of boys without sport activities. For basketball players the average body height was established for 24%. The avera-ge body weight was established for 94% of boys without sport activities. For basketball players the average body height was established for 96%. The average BMI was established for 100% of basket-ball players. The average values of the DMT was established for 56% of boys without sport activi-ties. For basketball players the average DMT was present in 94% of them. The deviations in body height was established for 10% of boys without sport activities, and deviations in body height was established for 76% of basketball players. The de-viations in body weight was established for 6% of boys without sport activities, and deviations in body weight were established for 4% of basketball players. The deviations in relation to the BMI are neither present in boys without sport activities nor in basketball players, and deviations in relation to the DMT were established for 44% of boys wit-hout sport activities. The deviations in relation to the DMT were established for 6% of basketball players. Our results have shown an above avera-ge height for even 76% of basketball players, so one sets the question whether intensive training of basketball has an effect on the body height or do the boys with an above average height more often decide to train basketball. In the group of boys without sport activities we had 10% of an above average height. There is only one more distinct in-dicator in the deviations and that is the DMT for boys without sport activities, 44% of them has an increased or risky DMT. For the DMT we are sure that basketball has a positive effect because the majority of basketball players had an ideal relation of waist and hips.

Recommendations

To promote natural diet of newly-borns and he-althy ways of living in the family. Perform syste-matic and especially periodic check-ups if school children and youth because of an early detection and prevention in the deviations of growth and development. Perform health enlightenment of school children and youth, professors and educa-tors and parents. Children in pre-school age sho-uld be introduced to organized programs of sports (children playhouses), which enables an individu-al development of intelligence and physical abili-ties with play and socialising. Recommend speci-al sport activities to children encompassed in the sport clubs.

Advantages and use from training sportsfor children

A haromonious growth and development of all organic systems and especially the cardiovascular system, the respiratory system and the muscular – bone system. A positive effect on the psychic functions especially on the reduction of stress, the strengthening of self-confidence, one learns per-sistence, the acquiring of working habits, moral responsibility is developed through a respectful and correct relationship towards the teammate and opponent. Children athletes are not: obese, they do not consume alcohol, they do not smoke, they do not take drugs, they are even less absent from their lessons, they have fewer risks of falling ill from chronic diseases.

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6. Ogden C, Flegal K, Carroll M, Johnson C. Preva-lence and trends in overweights among US children and adolescents, 1999-2000. JAMA 2002; 288 (14): 1728-32.

7. Kafatas A, Codrington CA. “Eurodiet”. Nutrition and diet for healthy lifestyles in Europe.European Commission, 2001.

8. Kolacek S, Kapetanovic T, Luzar V. Early determi-nants of cardiovascular risk factors in adults. B: Blood pressure. Acta Paediatr 1993;82:377-82.

9. Tuvemo T, Cnattingius S, Jonsson B. Prediction of male adult stature using anthropometric data at birth: a nationwide population-based study. Ped Res 1999;46:491-5.

10. Apostolidis N, Nassis GP, Bolatoglou T, Geladas ND. Physiological and technical characteristics of elite young basketball players. J Sports Med Phys Fitness. 2004 Jun;44(2):157-63.

11. Fett C, Fett W Fabbro A, Marchini J. Dietary Re-education, Exercise Program, Performance and Body Indexes Associated with Risk Factors in Overweight/Obese Women. J Int Soc Sports Nutr. 2005 Dec 9;2:45-53.

12. Drinkwater EJ, Hopkins WG, McKenna MJ, Hunt PH, Pyne DB. Modelling age and secular diffe-rences in fitness between basketball players: a 10-year-period investigation. Br J Sports Med. 2008 Jan;42(1):25-30. Epub 2007 May 25.

13. Jusupovic F, Pokorn D, Kudumovi A, Hadzihali-lovic J, Kudumovic M, Stoisavljevic D. Skin folds under the chin for scholage children, HealthMED 20071(1):.9-12

Corresponding author: Dijana Avdic KCU Sarajevo, Bosnia and Herzegovina, e-mail: [email protected]

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Summary

Introduction: Health facilities are big produ-cers of infectious and laboratory’s material waste which present the most dangerous sorts of medical waste because of high degree of infectious, hur-ting and poisoning. Carrying of this material wa-ste becomes big problem for all health facilities and it declares in increasing its quantity. That way danger of spreading infectious illness is increa-sing and it is necessary to respect strict criteria of evidence and supervision from place of approving this material waste to place it is finally carrying.

Target: Research had aim to interrogate the way of storaging, transportation, carrying and control of infectious and laboratorys’ material wa-ste in three the biggest clinical centers in area of Federation of Bosnia and Herzegovina.

Methodology: Sample includes Clinical cen-ters in Sarajevo, and Tuzla, and Clinical hospi-tal in Mostar. In order to get informations about producer of infectious and laboratorys’ material waste, its sort, structure, collection, transportation and carrying, we used questionnaire as instrument of research. Research questionnaire is sketched on the base of directives which is recommended by CDC from Atlanta. For treatment and review of information’s we used descriptions statistics (per-centual perception) in analysis of correlations of

some variations and calculating hi-square of test for comparable some variations.

Results: Research have shown that in three the biggest Clinical centers in area of Federation of Bosnia and Herzegovina, 60% of infectious and laboratory’s waste is taking away together with communal waste.

Conclusion: Results of research have shown that methods of taking away infectious and labo-ratory’s waste from three the biggest Clinical cen-ters in area of Federation Bosnia and Herzegovina are not safe, in fact, big part of this waste is taking away in deponia with communal waste. That way, this sort of waste presents big epidemiologic risk. For establishing of complete of infectious waste system in Bosnia and Herzegovina, Federation, Canton and health facilities, it is necessary, first ofall, to create regulative law and regulations which would regulate system of institutions correctly for command of medical waste. It is necessary to crea-te three or five year plan of carrying infectious andthe other medical waste and also to create detail instructions about principles of operate this sort of waste in all levels of health protection.

Methods of removing infectious and laboratorys’ waste in clinic centersMETODE UKLANJANJA INFEKTIVNOG I LABORATORIJSKOG OTPADA U KLINIČKIM CENTRIMA Aida Vilic-Svraka1, Zlatko Vucina1, Aida Filipovic-Hadziomeragic1, Mirsada Mulaomerovic1

1 Institute for public-health of Federation of Bosnia and Herzegovina

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Sažetak

Uvod: Zdravstvene ustanove su veliki proizvo-đači infektivnog i laboratorijskog otpada, koji zbog visokog stepena rizika od infekcija, ranjavanja i trovanja predstavljaju najopasnije vrste medicin-skog otpada. Zbrinjavanje ovog otpada postaje ve-liki problem svih zdravstvenih ustanova, a očituje se u povećavanju njegove količine. Na taj način se povećava i opasnost od širenja infektivnih bolesti, pa je neophodno poštovati stroge kriterije eviden-cije i nadzora, od mjesta nastanka ovog otpada, do mjesta njegovog konačnog zbrinjavanja.

Cilj: Istraživanje je imalo za cilj da ispita na-čin skladištenja, transporta, zbrinjavanja i kontrole infektivnog i laboratorijskog otpada u tri najveća klinička centra na području Federacije Bosne i Hercegovine.

Metodologija: Uzorak je obuhvatio Kliničke centre u Sarajevu i Tuzli, te Kliničku bolnicu u Mostaru. Da bi se dobili podaci o proizvođaču infektivnog i laboratorijskog otpada, njegovoj vr-sti, strukturi, sakupljanju, prevozu i zbrinjavanju, služilo se anketnim upitnikom, kao instrumentom istraživanja. Istraživački anketni upitnik je konci-piran na osnovu smijernica koje preporučuje CDC iz Atlante. Za obradu i prikaz podataka koristila se deskriptivna statistika (procentualno učešće) u analizi korelacija pojedinih varijabli, kao i izraču-navanje hi-kvadrat testa za uporedni prikaz poje-dinih varijabli.

Rezultati: Istraživanje je pokazalo da se u tri naj-veća klinička centra na području Federacije Bosne i Hercegovine 60% infektivnog i laboratorijskog otpa-da odlaže zajedno sa komunalnim. Najveći problemi su vezani za skladištenje i tretman ove vrste medi-cinskog otpada. Potvrđeno je postojanje statističkih razlika između pojedinih kliničkih centara. Najne-povoljnija situacija jeu Kliničkoj bolnici u Mosta-ru, jer se kompletan čvrsti infektivni i laboratorijski otpad odlaže zajedno sa komunalnim. Postrojenja za obradu infektivnog otpada u Kliničkom centru u Sarajevu, prerađuju 1/3 nastalog infektivnog otpa-da, a situacija je najpovoljnija u Kliničkom centru u Tuzli, gdje se svega 13,33% neobrađenog infe-ktivnog i laboratorijskog otpada odlaže zajedno sa komunalnim.

Zaključak: Rezultati istraživanja su pokazali da metode odlaganja infektivnog i laboratorijskog

otpada iz u tri najveća klinička centra na području Federacije Bosne i Hercegovine nisu sigurne, ta-čnije, veliki dio ovog otpada se odlaže na deponije zajedno sa komunalnim otpadom. Na taj način ova vrsta otpada predstavlja veliki epidemiološki rizik. Za uspostavljanje cjelovitog sistema upravljanja medicinskim otpadom na nivou BiH, Federacije, Kantona i samih zdravstvenih ustanova, potrebno je najprije stvoriti zakonsku regulativu i propise koji bi tačno regulisali sistem upravljanja medicinskim otpadom. Neophodna je izrada tro- ili petogodi-šnjeg plana zbrinjavanja infektivnog i ostalog me-dicinskog otpada, kao i izrada i primjena detaljnih uputa o principima rukovanja ovom vrstom otpada na svim nivoima zdravstvene zaštite.

1. Introduction

During giving health services (diagnosis, treat-ment of patient) there are huge amount of infec-tious and laboratory’s waste left, which can en-danger health of people and environment. In total pollution this sort of waste has a big part (5-12%), but it consists of waste matters which were creat-ed to protect health of people and animals’ health and/or similar research, it is necessary to care it according to fast requests.

Infectious waste often contains pathogen bio-logical agens which make illness in people who are under that influence because of its type, con-centration and number, and means: culture and tools from microbiology laboratory, parts of equip-ment, material and tools which come in touch with blood or secrets of illness people or it is used for surgical operations (needle, lancets, syringes, scal-pels) bandage a wounds (bandages, tampons) and abductions and waste materials from department for isolation patients and department for dialysis, systems for infusions and transfusion, gloves and other tools for one way use, clothes of staff, and material which is in contact with experimental animals which are injected with of infectious ma-terial. Pathological waste – parts of human body, amputated parts, tissues, organs which are remo-ved during surgical interventions, tissues taken in diagnostic purpose, lancets, and fetuses and so on, are special sort of potential infectious waste. Path-ological waste has ethic meaning. (1,2,3)

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In clinical-chemistry laboratory and X-ray labo-ratories ussualy appears medical chemistry liquid waste. It contains of chemicals which have dan-gerous substances (laboratory reagenses liquides for disinfection based on phenol or perohloretilen, waste with great concentration of hard metal, dif-ferent chemicals and radioactive waste material). Denatured alcohol, calciumcarbid, halogen organ, dissolvers, radio-active and other dangerous waste matters mustn’t be in canalization system.

Nonmedical chemical liquid waste consists of means for cleaning of rooms and sanitary equip-ment for example different sorts of detergent and other means for washing, salt acid, hydrogen and different disinfects. This sort of chemical liquid waste is mainly removed by releasing it in sewage system, but type and quantity of that material must be limited.

In clinical laboratory either hard chemistry waste appears (which can consist a lot of toxic and infectious substances) and radioactive waste. Waste which consists of hard metals is presented under category of dangerous waste which is very toxic. For example, waste of mercury appears dropping during break of medical equipment but waste of sodium appears of expending battery.

Special category is radioactive waste which has specific way of elimination and carrying. (4,5)

Waste water from hospitals contains many pat-hogenic bacteria that cause intestinal diseases. This water often contains Koch’s bacilli, enteroviruses (include Coxsackie viruses, rhinoviruses, polioviru-ses) and Hepatitis A viruses. Pollution by drinking water with hospital waste may cause epidemics. As viruses are more resistant to physical and chemical inactivation than bacteria, proper treatment of wa-ste water is necessary. Discharge of liquid medical waste out of sewage system is allowed only if pro-per treatment has been applied.(6)

When we talk about solid infectious waste, the main problem is taking away of sharp objects: scalpels, needles, lancets, used in interventions. On city depo, it is often possible to see needles, bandages and other material waste which is poten-tial source of infection. Pipettes, lancets and blood needles for hematology research, are often trans-mitters of virus hepatitis B (VHB) and virus hepa-titis C (VHC). Causes of infection are staying lon-ger in needles, so if someone accidentally comes

in touch with it, one can be infected easily. Risk from scalpel, lancet or some other sharp object is less than risk from needle bit, probably because there is more blood left in needle. Virus hepatitis B is really resisted and can live one week or even longer out of body. On 30 °C this virus can keep infection till 6 months, and on 60 °C – four hours. It is similar with virus hepatitis C. Virus of human immunodeficiency (HIV), is also transmittingwith infected blood, blood products, contaminated needles, sprayers and other instruments. However, this virus is less resisted (it can live 3-7 days on room temperature). (7, 8, 9)

Chemicals used in hospitals are potential so-urce of pollution, mostly through water, by sew-age system. Small amounts of dangerous chemical waste can cause poisoning and chemical burns.

Taking care of infectious and laboratory waste is becoming great problem of health institutions. Proper handling with infectious material waste is important measure in preventing hospital infec-tions. One of the general measures is environmen-tal protection and classifying, collecting, storag-ing and treatment, in fact disinfection of infectious material waste. Interesting information is that rich countries are not necessarily had to take care of material waste. It is necessary to set aside 0, 5% of bruto national income per inhabitant. That means that countries with low bruto national income should set aside between 0,18 and 6 dollars per inhabitant per year.(10,11,12).

2. Methodology of research

Sample encircled tertiary level of health prote-ction – three the biggest Clinical centers on the area of Federation Bosnia and Herzegovina (hospital de-partments and laboratories). Research has been done due to protocol of research, by standard phases:

1. Production of situation analyze based on existing data and research:

2. Production of suggestions of research;3. Production of action and financially plan;4. Implementation of research (preparement

of research questionnaire, data collecting, entering data base, statistic processing of data);

5. Evaluation and producing the report;

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Research encircled next variable:

1. Sharp objects (needles with syrers, lancets, scalpels, and tweezers)

2. Bandage materials (tampons, bandages, gazes, absorbent cotton)

3. Systems for infusion and transfusion of blood

4. Supplies for one way use (gloves …)5. Other infectious material waste6. Cultures and supplies from laboratory7. Chemicals containing other dangerous

substances (laboratory reagents, means for disinfection based on phenol or perochloretilen, acids, bases, waste with great concentration of hard metals…)

8. Other chemicals

In process of data treatment SZO and CDC, EPI info 2000 with SAAS/SUDAN software packet has been used, with aim to calculate the sample, values of factors in data base, to calculate standard mistakes and coefficient of variation. Statisticaldifferences in range from 95% interval of correc-tness’s were defined. For showing data, we useddescriptive statistics (percent inclusion) in analysis of correlation of some variables, as well as getting hi-square test for compare view of some variables, where according to analyze of data some hypothe-ses were seen important for statistic differences in relation on acting of some variables.

3. Results

Clinical center in Sarajevo doesn’t have three year or five year plan for taking care of medicalmaterial waste, while 60% of analyzed units have documentation about this sort of waste. Person in charge for organization and indoor supervision don’t have 40% of analyzed units, and person in charge for taking care of data base about medical waste, making and delivering monthly report to person in charge for organization and indoor su-pervision don’t have 86, 67% of analyzed units.

Partly selection of infectious and laboratory’s waste on place where they happened make 80% of analyzed units. For packaging infectious material waste, plastic bags are being used in 40% of ana-

lyzed units, in 40% is intended plastic wrapping material, and in 20% carton boxes are being used. For packaging of laboratory’s waste in 46,67% of analyzed units, plastic wrapping material is being used, in 26,67% plastic bags are being used, and in 20% carton boxes are being used. One third of analyzed units (33,33%) keep sharp objects in in-tended, solid covered dishes which are safe from penetration and opening.

Wrapping material for infectious and laborato-ry waste, which is waterproofed and insured from spilling of the content, have 40% of analyzed units, while 33,33% of analyzed units have wrapping material marked with proper color (red or oran-ge for infectious, yellow for chemical waste). In 66,67% of analyzed units wrapping material with infectious and laboratory’s waste can not be open without authority.

Special storage for infectious and laboratory waste, which is covered, marked and intended only for that purpose have 33,33% of analyzed units. Storaging of untilled infectious laboratory waste lasts till 24 hours, and longer than 24 hours for la-boratory waste which is being collected for taking away with authorized companies with whom the contract has been signed. Treatment of infectious material waste with disinfection and sterilization, in fact, taking it away with authorized companies, is being done in 33,33% of analyzed units. Until-led infectious and laboratory waste is being taken away together with communal waste in 66,67% of analyzed units. In all analyzed units, human tissu-es are being burried on cemetery. Liquid infectious and laboratory waste is not processing before re-leasing it into sewege system in 60% of analyzed units. Other liquid infectious and laboratory waste is being treated with disinfection, in fact it is being taken away with authorized companies.

In Clinical center in Sarajevo, 46,67% of staff working on classifying and processing of infecti-ous and laboratory waste material, is educated for that kind of job, 73,33% of staff have full protective clothes. In most of analyzed units, final treatmentof infectious and laboratory waste is huge problem. Next problem is storaging, classifying and transpor-ting infectious and laboratory waste materials.

Clinical center in Mostar doesn’t have 3 year or 5 year plan for taking care of medical material waste, as well as documentation about this sort of

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material waste. None of the analyzed units don’t have person in charge for organization and indoor control for medical material waste, as well as per-son in charge for taking care of data about medical waste who makes monthly report and deliver it to person in charge for organization and indoor su-pervision.

All analyzed units are doing partial selection of infectious and laboratory waste on place whe-re they happened. Simple plastic bags and carton boxes are being used for packaging infectious and laboratory waste. Intended plastic wrapping ma-terial is being used for laboratory waste in 20% of analyzed units. In 13,33% of analyzed units, sharp objects are being stored in intended, solid, closed dishes which are insured from penetrati-on and opening. None of the analyzed units don’t have wrapping material for waste which is water-proofed and marked with proper color. Wrapping material with infectious and laboratory material waste can not be open without authority.

There is no specific storehouse for infectiousand laboratory waste which is covered, marked and predicted only for that purpose. In most of the analyzed units, storaging of untilled laboratory waste lasts 3-12 hours. Storaging of untilled labo-ratory waste last 24 hours, and releases into a sew-erage system without previous processing.

Transportation of infectious and laboratory wa-ste is exclusively done by communal service vehi-cles without any time planning.

Solid infectious and laboratory waste treatment is not part of any analyzed unit; in fact it has been put aside together with communal waste. In all analyzed units, only human tissues are being bur-ried in cemetery. Liquid infectious and laboratory waste is processed before releasing into a sewera-ge system in 6,67% of analyzed units. Other liquid infectious and laboratory waste releases into a se-werage system without previous processing.

In Clinical hospital in Mostar, 26,67% of staff that works on classifying and processing of infe-ctious and laboratory waste, is educated for that kind of job, and 66,67% of staff have full pro-tective clothes. In most of analyzed units, finaltreatment of infectious and laboratory waste is a huge problem. Next problem is storaging, classi-fying and transportation of infectious and labora-tory waste.

Clinical center in Tuzla has 5 year plan for ke-eping of medical waste and all analyzed units have documentation about this sort of waste, as well as person in charge for organization and indoor supervi-sion who makes and deliver monthly report to person in charge for indoor supervision. All analyzed units make full selection of infectious and laboratory wa-ste on place where they happened. Intended plastic bags are being used for packaging infectious and la-boratory waste in 40% of analyzed units, and in 60% of them, plastic wrapping material is being used.

All analyzed units keep sharp objects in inten-ded, solid and covered dishes which are insured from penetration and opening. All analyzed units have wrapping material for infectious and labo-ratory waste which is waterproofed and insured from dropping or spilling the content and which is marked with proper color (red or orange for infe-ctious, yellow for chemical waste). This wrapping material couldn’t be opened without authority.

There is storehouse for infectious and labora-tory waste which is covered marked and predicted only for that purpose. Storaging of untilled infe-ctious waste in most of analyzed units lasts from 1 to 12 hours. Storaging of untilled laboratory waste lasts up to 12 hours (it is collecting for taking it away by authorized company with whom the con-tract has been signed, with residence in Tuzla). All analyzed units with human tissues as infectious waste are using freezers for their storaging. Stora-ging of human tissues lasts from 3 to 12 hours. For 86,67% of analyzed unites transportation of infe-ctious and laboratory waste is done with vehicles made only for that purpose, and vehicles are easy to clean and disinfect, and in those units there is time planed for transportation of this sort of waste material.

Infectious and laboratory waste treatment with disinfection and sterilization, in fact taking labo-ratory waste away is part of 86,67% of analyzed units. Both, communal and untilled infectious and laboratory waste are being taken away by 13,33% of analyzed units. In all of analyzed units, human tissues are being burried in cemetery. In 13,33% of analyzed units, liquid infectious and laboratory waste are not processed before releasing into a se-werage system. Other liquid infectious and labora-tory waste is processed by disinfection, in fact it is taken away by authorized companies.

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In Clinical center in Tuzla 99,33% of staff wor-king on classifying and processing infectious and laboratory waste, is educated for that kind of job and 93,33% of them have full protective clothes – those who are working with infectious and labo-ratory material waste. In most of analyzed units, final treatment of infectious and laboratory wasteis huge problem, since 86,67% of this waste is be-ing burned in places predicted for that, and it is not due to hygiene standards (connected to a boiler room chimney, without filters and without controlof outlet gas emission).

This research has shown that there is statistical important difference between clinical centers in Sarajevo, Mostar and Tuzla, in relation with met-hod insurance. The best evidenced situation is in Clinical center in Tuzla, and the worst evidenced situation is in Mostar (high average appraisal of methods which are being used in Clinical center in Tuzla, exists of epidemiology-hygiene Sector for supervision, where specialists for hygiene and epidemiology are taking seriously this issue.)

Observing full sample with average appraisal of 10,91 (maximum appraisal is 23), conclusion is that methods for removing infectious and labora-tory waste in clinical centers in the area of Fede-ration of Bosnia and Herzegovina are not insured because 60% of this sort of waste is taking away together with communal. It is a great risk for me-dical staff health, and health of patients and all pe-ople.

In order to give appraisal in clinical centers in Sarajevo, Mostar, and Tuzla, and also to compare those appraisals, there is appraisal created for each unit from the sample according to answers on re-levant questions from question mark. The biggest possible appraisal is 23, and the lowest is 0. Ac-cording to statistical processing of those given ap-praisals for three clinical centers, the results are:

Graph 1: Average appraisal of insure method of infectious and laboratory waste in clinical cen-ters (comparison according to clinical centers)

In order to check if there is statistical important difference according to average appraisal between clinical centers in Sarajevo, Mostar, and Tuzla, va-riance analyze have been done (ANOVA) and the results are in table 1.

Since F empirical > F theoretical, in fact p value is less then 0,05 = that means that difference in ave-rage appraisal is very important. According to re-moving method of infectious and laboratory waste

Table 1Anova: Single Factor

SUMMARY

Groups Count Sum Average Variance

KC Sarajevo 15 140 9,33 67,45

KC Mostar 15 46,5 3,10 2,26

KC Tuzla 15 318 20,86 2,89

ANOVA

Source of Variation SS df MS Fempirical p-value Theoretical

Between Groups 2536,41 2,00 1268,21 52,41 0,00 3,22

Within Groups 1016,33 42,00 24,20

Total 3552,74 44,00

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in Clinical centers in Tuzla, Sarajevo and Mostar, the best evidenced situation is in Clinical center in Tuzla, and the worst is in Clinical hospital in Mo-star. Since average appraisal for complete sample is 10,91, and the maximum appraisal is 23, it is relative small share (less than 50%), conclusion is that removing methods of infectious and laborato-ry waste in clinical centers are not insured, which presents risk for medical staff health, as well as risk for patients and all people’s health.

4. Discussion and conclusions

Infectious and laboratory waste is the most dan-gerous and the biggest part of medical waste and it should be treated due to management principles which are part of EU and developed countries of the world. In Europe and in the world, there are clearly defined regulations for taking away medical wasteand according to them there are obligations and responsibilities for law and physical subjects how to treat material waste. In that way, Institutions for health commit themselves to take care of their infe-ctious waste on ecological accepted way. (13,14)

Legislative-regulatory frame existing in our re-gion is not in conformity with EU countries which has influence on quality of medical interventionsand appearing epidemiology risks (15).

Results of this research have shown that three of the biggest clinical centers in Federation Bosnia and Herzegovina, 60% of untilled infectious and laboratory waste take it away together with com-munal waste. When we talk about taking care of infectious and laboratory waste in clinical centers, the best evidenced situation is in Clinical center in Tuzla, and the worst is in Clinical hospital in Mostar. High average appraisal for Clinical center in Tuzla can be explained by existing hygiene-epi-demiology Sector for supervision, where employ-ed doctors – hygiene and epidemiology specialists are seriously do their job. However, methods for taking care of infectious and laboratory waste do not completely satisfy hygiene principles. Incine-rator, where 86, 67% of infectious and laboratory waste is destroying, is old-fashioned method and partly satisfy hygiene standards. It is connected to a chimney of existing boiler room. There is no su-pervision of air pollution emission what represents

risk for medical staff health as well as for patients and all people’s health.

At the same time, Clinical center in Sarajevo, 33,33% of infectious waste refine in special instru-ments for sterilization through the microwaves. It is a method that gives complete sterilized materi-al, and sharp objects are crushing with special cru-shers. This is ecological completely safe and good method for destroying infectious waste material, because what’s given from the method can be taken away together with communal waste material.

Non existing systems for taking care of infe-ctious and laboratory waste, lack of information about health risks, lack of material and human re-sources, and bad control for taking care of, are the most common problems connected with this sort of waste materials. The most important is to clear-ly define responsibilities for correct handling withthis waste and it is finally provided:

- System establishing for handling with infectious and other medical waste, it is necessary to make legislative regulative and regulations for exact handling with this sort of waste. Based on legislative regulations, obligations and responsibilities for law and physic subjects should be defined. So, evena health institutions – producers of this dangerous waste, should be obligated to take care of waste on ecology accepted way.

- Development of system for handling and final taking care of waste which includesdefining responsibilities and providingmeans for using it. It is a long-term process.

- Rising up level of consciousness in public, education about risks connected with infectious waste and taking care of it safely.

- Choosing safe environmental solutions, so people could be protected from danger during collecting, handling, classifying, transporta-tion, treatment or final taking care of infectiousand other medical material waste (16,17).

Most economic measures for treatment of infe-ctious/medical waste in transitional period are ste-rilization with high temperatures, with chemical means, ionization radiation (gamma and UV rays) and nonionizational radiation (new technology – micro and radio waves) which is most accepta-ble method. Open container for keeping infectious

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waste materials must be replaced with solid, impe-netrable covered dishes, and transportation should be done with intended vehicles.

It is necessary to reduce number of disorganized depo-places, and to increase number of depos which will satisfy minimum of sanitary conditions, and cleaning city waste water before releasing it into a water current (mechanical and chemical treatment). The best solution would be construction of Regio-nal factory – modern incinerator for destroying of this waste which is case in EU. Those incinerators are placed in centers of big towns (for example, in Vienna), because energy produced by combustion of waste is using for heating the apartments. They have great capacity and medical waste from all regi-ons can be processed in them. They are constructed due to ecology principles, because whole emission in the air is water steam and carbon dioxide. Con-struction of factory like this is very expensive, so we can think about it only in future period.

Incineration large amount of halogen solvents (which contains chloral or flour) shouldn’t beendone if machines don’t have proper equipment for cleaning gases.

Any waste material that couldn’t been efficien-tly burned, should be given to organization or com-pany authorized for handling with dangerous waste. Those organizations can eliminate waste in rotation furnace, treat it chemically or storage it on places for dangerous chemicals. Other possibility for taking away dangerous chemical waste materials includes its return to producer. This waste can be exported to countries which have staff and machines for safe treatment of this dangerous waste. Deliveries like this should satisfy international agreements such as Basel convention. (18, 19, 20).

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9. Zvizdić, Š., Bešlagić, E., Kapić, E., Mikrobiologija sa parazitologijom – dijagnostika i terapija, Uni-verzitet u Sarajevu, Farmaceutski fakultet, Katedra za mikrobiologiju, Sarajevo, 2006.

10. WHO Regional guidelines for health care waste management in developing countries (draft), Ku-ala Lumpur: World Health Organization, Western Pacific Regional Environmental Centre; 1994.

11. Upravljanje i minimizacija zdravstvenog otpada, IWM, UK; 2000, ISBN 0

12. Priručnik o “Sigurnom upravljanju otpadom od aktivnosti zdravstvene zaštite”, WHO 1990 ISBN 92 4 154525

13. Marković, D., Đarmati, Š., Gržetić, I., Veselinović, D., Fizičko-hemijski osnovi zaštite životne sredi-ne, II knjiga, 1996, Beograd

14. Ilić, M., Miletić, S., Upravljanje zaštitom životne sredine prema Evropskom zakonodavstvu, Zbor-nik radova, XX kongres JUDIMK, Beograd, 18-19. novembar, (1999), 245-250.

15. Zakon o upravljanju otpadom, Službene novine Federacije Bosne i Hercegovine, br.01-335/03

16. Ilić, M., Miletić, C, Osnovi upravljanja čvrstim otpadom, Institut za ispitivanje materijala, 1998, Beograd, ISBN 86-82081-11-3

17. Ćatović, S., Kendić, S., Ćatović, A., Higijena, Uni-verzitet u Bihaću, Bihać, 2004.

18. Leder, K., Infectious Diseases Epidemiology Unit, Department of Epidemiology and Preventive Medi-cine, Monash University, Victoria 3181, Australia

19. R.Jerome, K., Department of Laboratory Medici-ne, University of Washington Program in Infecti-ous Diseases, Fred Hutchinson Research Center, Seattle, WA 98109.

20. World Health Organization (2004): Policy Brief: Provision of sterile injecting Equipment to reduce HIV transmission, WHO/HIV/ 2004.03.

Corresponding author: Aida Vilic-Svraka Institute for public-health Bosnia and Herzegovina e-mail: [email protected]

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Summary

In practice, the term deratization is used to des-cribe all types of measures and actions that are un-dertaken to repulse populations of harmful rodent species (mice, rats, mouse like rodents- voles, fi-eld mice and wood mice). The term deratization comes from word de-rat which means “get rid of rats”. Repulsing of harmful rodent species was carried out inside pharmaceutical company in city of Zagreb in area which size is 80. 000m2. For the implementation of deratization, the rodenticides Brodilion paraffin blocks from 30, 100 and 200gas well as Brodifakum paraffin blocks from 25 to210g were used. The rodents are important pests for humans because they carry out a quite number of contagious diseases. Especially, they represent a great danger when their population is increasing rapidly in the areas of the factories that produce food and medical supplies for humans. The most important pests to humans are Rattus norvegicus-gray rat, Rattus rattus-black rat, and Mus muscu-lus-house mouse. These species contaminate gro-ceries, water and surfaces with their urine, feces, saliva, bite and with their ectoparasytes. Also, they are the carriers of many harmful diseases like ba-cterial diseases (salmonella, plague, and brucel-losis) and rickettsial and viral diseases (typhus, encephalitis). The act of deratization was prefor-

med four times during 2006. Before performing every act of deratization, it would be wise to detect which rodent species live in the area that we want to get rid of of the rodents. For the hunting of a co-uple of rodents we used so called “sticky decoys“. Also, precaution has been taken that a percentage of abundance of each species should be known be-forehand. The assessment has shown that rodent population is rapidly increasing up to 500-1,000 individuals during the spring and autumn months, but during summer and winter population estimate is about 100-500 individuals.

Sažetak

U praksi deratizacijom se nazivaju sve mjere i postupci koji se provode s ciljem suzbijanja odno-sno smanjenja populacije štetnih glodavaca (miše-vi, štakori, mišoliki glodavci – voluharice, poljski i šumski miševi). Sam naziv deratizacija dolazi od riječi de-rat što zapravo znači «osloboditi od štakora». Suzbijanje štetnih glodavaca je vršeno unutar jedne farmaceutske tvrtke u Zagrebu čija je povrsina 80. 000m2. Za deratizaciju su korišteni Brodilion parafinski blokovi od 30, 100 i 200g., teBrodifakum parafinski blokovi od 25 i 210g. Glo-davci predstavljaju velike štetočine i prenosioce zaraznih bolesti. Posebnu opasnost predstavljaju

Repulsing of harmful rodents in specific environmental conditionsof pharmaceutical factorySUZBIJANJE ŠTETNIH GLODAVACA U SPECIFIČNIM UVJETIMA NA PODRUČJU FARMACEUTSKE TVRTKESuad Habes1, Sandra Mramor-Muzevic1, Sefkija Muzaferovic2

1 Fakultet zdravstvenih studija Sarajevo2 Prirodno-matematicki fakultet Sarajevo

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kada se namnože unutar postrojenja koje prave hranu i lijekove za potrebe čovjeka. Najveće šte-točine predstavljene su sljedećim vrstama; Rattus norvegicus-sivi štakor, Rattus rattus-crni štakor te vrsta Mus musculus-kućni miš. Ove vrste oneči-šćuju namirnice, vodu i površine urinom , fece-som, slinom, ugrizom, te preko ektoparazita. Ta-kođe, prenose brojna bakterijska (kuga, bruceloza, salmoneloza) i virusna oboljenja (tifus, bjesnilo, šap, slinavka). Deratizacija je vršena u četiri na-vrata tokom 2006. god. Prije svake deratizacije treba prvo pristupiti identifikaciji vrsta glodavacakoji obitavaju na području koje treba biti deratizi-rano. Za izlov uzoraka upotrebljavani su tzv. lje-pljivi mamci u koje se uhvatilo nekoliko primje-raka od svake vrste. Također proveden je i stupanj infestacije kojim je konstatovano da je u proljeće i jesen populacija glodavaca procjenjena na 500-1000 jedinki, dok je tokom zimskih i ljetnih mje-seci populacija glodavaca procjenjena na 100-500 jedinki.

Deratizacijom su obuhvaćena 54 slivna šahta i 16 revizionih otvora. Tokom zime i ljeta na otvo-rima šahtova i na revizionim otvorima se stavljao po jedan Brodilion parafinski blok ili Brodifakumparafinski blok, dok je tokom proljeća i jeseni naotvorima šahtova stavljana dva Brodilion parafin-ska bloka ili Brodifakum parafinska bloka, dok jena revizionim otvorima stavljan po jedan blok. Svi blokovi su fiksirani žicom da ih kojim slučajemglodavci nebi prenijeli na druga mjesta.

Oba otrova su probavni otrovi koji se mješa-ju sa hranom koju glodari rado konzumiraju. Po-sebno velika konzumacija hrane zabilježena je u proljeće i jesen kada nastupa i sezona razmnoža-vanja. Otrovi su mješani sa sljedečom hranom; meso, riba, sir, voće i povrće. Ovi otrovi su bio-loški veoma učinkoviti i glodavci ugibaju nakon samo jedne uzete doze (single doze).

20 dana nakon deratizacije napravljena je pro-cjena infestacije koja je pokazala da glodavci više nisu prisutni unutar kompanije.

Introduction

Rodents can be found in every corner of the world. They have followed mankind in its histo-rical development, becoming the most prevalent

mammal on the planet. There are approx. 5,000 species of mammals on Earth, with as many as 2,-000 rodent types (1). For the last 50 million years, the rodents have evolved and easily adapted to the climatic changes conditions.

It is not without reason that rodents are claimed to be the most intelligent and destructive mammals on the planet, having survived to this day primarily thanks to their phenomenal ability to adapt and their fast breeding capabilities. For us, the most impor-tant species are commensal rodents, which live in the vicinity of the humans and feed on human food, while causing significant damage and causing a se-rious health problem since they are a natural carri-ers of many infectious and parasite diseases of both humans and livestock. (8) The most important com-mensal rodents in the world, including Croatia, are the gray rat (Rattus norvegicus), black rat (Rattus rattus) and the household mouse (Mus musculus). (7) At the end of the 19th century, when the functi-on of the rats in the spreading of diseases, namely the plague, was discovered, the humans have come to realize that rodents are a serious enemy and have taken more care in their containment (2).

In 1397, the Dubrovnik Senate Council has become the first city in the world to introducemandatory 40-day quarantine for all travelers and goods in order to prevent the spreading of plague. In 1805, the same Council ruled that all ships ente-ring the Gruz port of Dubrovnik must exterminate rats by burning coal. This is the first written docu-ment concerning the mandatory destruction of rats (3). The named procedure mainly indicates the eradication of rats and mice that cause significanthealth and economical damage.

Economical damage stems from rodents con-suming, damaging or spoiling large quantities of food, raw goods and other items used by humans. It is almost impossible to quantify the amount of financial loss caused by rodent infestation. It isestimated that rodents damage 10 times more food than they need and that they consume up to a third of their body volume daily.

The World Health Organization (WHO) esti-mates that rodents destroy approx. 30 million tons of food annually and devour or damage approx. 5 billion dollars worth of goods. It is also estimated that they cause a 5% damage in consumer goods production, roughly sufficient for 130 million pe-

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ople (1,2) According to estimates by experts in So-uth East Asia, rodents destroy 15% of rice growths (food for 12 million people) during the vegetative period. In Congo, rodents destroy up to 40% of ta-pioca plants. They also attack sugarcane, sesame, coconut, cacao, and potato plantations.

In European warehouses, they damage wheat, rye, corn, fruit, beans, and root vegetables. Thro-ughout a year, a single gray rat can deposit up to 7 liters of urine (droplets) and 18 kg of feces (turds), causing infected food to be declared unusable for humans. Much of the damage is also caused by ‘nibbling for the sake of nibbling’. This way, ho-use infrastructure, sewer lines, gas lines, heating lines, and telephone and electric cables are dama-ged, resulting in shortcuts and fires (4).

Rodents also damage art works and documents in libraries, museums and archives. The aesthetic aspect of the rodent extermination must also be ta-ken into account, since they cause fear, revulsion and even panic. This is of particular importance for tourism sites, like camps, hotels and similar sites, where the very presence of rodents may cause eco-nomical damage. It is almost impossible to over-emphasize the importance of rodent suppression.

Concerning health aspects, rodents are one the primary carriers of infectious diseases for both hu-mans and livestock. Since they are always present in the vicinity of humans, the chance for transmis-sion is very high. Rodents usually spread diseases in the following manners:

- Pollution of water sources, goods and surfaces by urine, feces, mucus, secretion from the smell gland (near tail), and by biting (mucus, teeth)

- Via ecto-parasites (lice, fleas, ticks, mosqu-itoes)

Diseases that rodents can transmit can be divi-ded into several categories:

Bacterial - Leptospirosis, salmonellosis, tula-remia, plague, brucellosis;

Rickettsial and viral - Foot - and - mouth disease, rabies, hemorrhagic fever, typhus, viral encephalitis;

Parasitic - Trichinellosis, leishmaniasis;Protozoal – Toxoplasmosis, amebiasis;Fungal – Dermatomycoses.

Additionally, it is not uncommon to encoun-ter cases of physical attack against children and household pets (3). It is for these reasons that the number of rodents should be reduced, i. e. kept at the biological minimum, which is at the number of units that will ensure the survival of the species while being acceptable to the humans (10).

To achieve this, measures of sustained extermi-nation need to be enforced in all spaces occupied by humans. The above practice includes all met-hods that result in the reduction of the population of rodents (mice, rats, mouse like rodents like vo-les, field mice and forest mice) although the root ofthe word deratization means de-rat, ‘to be free off rats”. The successful extermination requires the use of biological, mechanical, physical, and che-mical measures followed by the sanitization of the environment. Unfortunately, mostly chemical me-asures are used today, causing the extermination to be treated merely as setting up poisoned traps, which is incorrect.

Chemical measures include the use of pestici-des that will cause poisoning or sterilization of the rodents. These pesticides are known by a collecti-ve name of raticides or rodenticides and can be used in different combinations.

The choice of the combination, the method and the application of precautionary measures are de-pendent on the type of the rodent against which they are used, namely the biological conditions, the size of the population and location of certain construction (11). Humidity plays an important part when performing deratization since not all ro-denticides can be used in humid conditions.

The deployment of scattered baits, whether it is in the form of grains or pellets, is not suitable for humid environment due to degradation of said ba-its. In humid conditions, mold often forms on the baits, making them inadequate for the use. Mo-dern methods of extermination in wet conditions, like cellars, sewers or brooks, is based on solid paraffin baits, created by mixing 40-45% paraffin(melting point 80ºC) with rat food. Such baits are very attractive to rats, which often carry them to their dens. Due to their resistance to environment conditions (because of paraffin), they remain acti-ve for a longer period.

In addition to the composition of the bait, the active ingredient is also important, namely the po-

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ison that will kill the rodent. It must be mixed well into the bait, because otherwise, the rodents will not notice it and will not indigest it.

Today, most used rodenticides are anticoagu-lants (1).

Aims of the Study

- To describe the suppression of rodents in specific conditions in the area of apharmaceutical company in 2006

- To show results of suppression after deployment of suppression measures

- To estimate effectiveness of executed measures

Material and Methods

The eradication of harmful rodents (deratizati-on) in wet environment conditions has been done within the property area of a pharmaceutical com-pany in Zagreb. The size of entire area is 80 000 m² whereas the green and traffic areas, on whichan external eradication linked to wet conditions was performed, have about 20 000 m² in size. The horizontal sewerage system which serves for the drainage of the part of the industrial water as well as precipitations has its drainpipe connected to filtering system. The length of the system pipenetwork is about 8 000 m in conjunction with the network of 16 metallic control channels (revisi-on apertures) and 54 drain manholes which are covered with iron bars for collecting precipitati-ons. Also, the channel-like watercourse, 400 m in length, passes through the area and both the pede-strian and traffic bridge span over it. The emban-kments on both stream sides are arranged and well maintained.

For the deratization of external areas Brodilon paraffin blocks (30 g, 100 g, and 200 g) as well asBrodifakum paraffin blocks (25 g and 210 g) wereused. Accordingly, the following chemical com-pounds were used during eradication procedure:

a) Brodilon paraffin blocks contain hydroxy coumarin derivative bromadiolone, second generation anticoagulant rodenticide. Both

the bait block traps and pellets contain bromadiolone. According to the law regulating the poisonous substances (NN 27/1999) and the register of permissible poisons (NN 7/2001) bromadiolone is listed the group III poison at concentration of 0. 005%. Brodilon rodenticide paraffin blockis a very efficacious tool for the eradicationof gray and black rats and household mice in the communal hygiene and public health setting.

b) Brodifakum paraffin blocks contain 0. 005 % brodifacoum as the active compound which belongs to group II poisons. Brodifakum paraffin blocks weighing 25 gare suitable for the use in open areas. When the rats are targeted for the eradication, two brodifakum blocks should be applied. Conversely, one block is applied in the case of mice eradication. The brodifakum paraffin blocks of 210 g weight connectedto the wire are also available and they can be hanged for the use in the drainage system apertures.

For the purpose of investigation which included an estimation of the size of rodents’ population oc-cupying the area of a pharmaceutical company in Zagreb, the method of Gunderson was used and the following criteria were applied:

- If the rodents cannot be seen but the damage attributed to their presence is observable, the size of rodent population is between 1 and 100,

- If the rodents can occasionally be seen at the sunset and during the night, population size is between 100 and 500,

- If the rodents are regularly seen during the night as well as occasionally on the daytime, population size is between 500 and 1,000,

- If the rodents are regularly seen both during the night and in broad daylight, population size is estimated to be between 1,000 and 5,000.

In addition, the assessment of the level of infe-station of investigated area is based on informati-on obtained by quizzical of the company working

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staff and by our direct observations throughout period of the research conduct in the designated area which, amongst other, include finding rodentfeces and other trails, damages done by their pre-sence and by the discovery of systems of tunnels and active holes which the rodents built on the cer-tain locality.

Eradication procedure

The eradication procedure was performed in the accordance with the Guidelines describing the exact means by which obligatory disinfection, de-sinsection, and deratization are carried out.

a) Deratization within the area of pharmaceutical company

Having in mind specific and sensitive nature ofthe working activities within the pharmaceutical corporation, an enormous emphasize is given to proper sanitation of all the factory buildings and structures and their environs. Along these lines, it is particularly important to perform a proper dera-tization within the structures and spaces of sewe-rage system due to following reasons:

- The drainage network is unlimited source of constant food supply to rodents,

- The drainage network and its microclimate offer favorable conditions for rodent growth and reproduction,

- The drainage network is simplest but yet the best way for rats to communicate.

Given that our investigation was focused on performing deratization procedure in wet conditi-ons, we shall describe those deratization activities which were done on the external green and trafficareas of the pharmaceutical company and its dra-inage system.

The network of metallic corrective control channels of the sewerage system consists of 16 shafts on designated area. Each shaft has 0. 65 m x 0. 65m dimension. Previous to setting of any bait within the shafts, it is necessary to carefully check after opening of shaft for the presence of explosive

gases such as methane or hydrogen sulfide (H2S) or any other potentially explosive gas by using Dräger’s detector which is equipped with special tubes for detection of explosive gases. Afterward, deratization was done by using Brodilon 200 g pa-raffin blocks as well as 210 g Brodifacum paraffinblocks equipped with wire noose which impro-ves the accessibility to certain places. Also, wire noose increasingly prevents rats of taking away and relocating paraffin blocks to more convenientplace for them. Additionally, wire noose has been shown a reliable tool in the fixing paraffin blockwithin a specific control place of the drain systemwhich thus prevents paraffin blocks to be carriedaway by water stream. Accordingly, one paraffinblock equipped with wire noose was placed into each shaft and was fixed to the metal frame of thecontrol channel in a way that the paraffin blockwas put down to the level of the branching of the drainage network tubes. When put properly, the lure is hanging in the air above the embankment which serves as a place of rest for the rats and thus presents an ideal place for luring tired rats to stop and have a rest and frequently consume the bait.

As mentioned before, there are also 54 manho-le shafts 0. 47 x 0. 47 m in the diameter which are covered with iron bars for collecting precipitati-ons. For deratization purpose, in each collecting shaft at least one light-green 100 g Brodilon wire noose-equipped paraffin block (5 x 5 x 4 cm) wasinserted as described previously.

For deratization of the channel-like watercour-se in its entire length (400 m) and the green areas (20. 000 m2) Brodilon paraffin blocks of 30 g masswere used, covered by plastics. Additionally, 25 g Brodifakum paraffin blocks were put in differentquantities which were depending on the asses-sment of the level of infestation.

Five days after performing external deratizati-on, control checking was done and the damaged and consumed lures were replenished. The dera-tization procedure was done during 2006 and was repeated four times within three month time inter-vals. The assessment of infestation was done prior to and after performing deratization procedure and the efficacy of eradication procedure in wet condi-tions was evaluated accordingly.

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Results and Discussion

First step in our approach was to determine the level of infestation of investigated area by using the method of Gunderson. By using the method criteria, we have found that the population size was between 500 and 1,000 during spring and au-tumn. Conversely, we have found that the level of infestation was lower during summer and winter and that population size was between 100 and 500 rodents.

Table 1. presents a summary data for the pa-raffin blocks consumption during the execution offour acts of deratization of the sewerage system (drain manholes and revision apertures) performed in 2006. Since the level of infestation was lower during summer and winter sessions, one Brodilon and Brodifakum paraffin block each were used inthat period. The consumption of paraffin blockshas increased during spring and autumn due to in-crease in rodent population. Accordingly, an incre-ased amount of paraffin blocks of different weight(100 g, 200 g, and 210 g) was applied. It can be seen from the table that the consumption of a pa-raffin blocks stand at 15,760 during spring as wellas autumn actions and that 10,800 g of Brodilon 100 g blocks as well as 1,600 g of Brodilon 200 g and 3. 360 g Brodifakum 210 g blocks were used. On the other hand, 8,680 g of different blocks were consumed during summer and winter actions, re-

spectively. Brodilon 100 g blocks were consumed in the amount of 5,400g, 200 g blocks in the amo-unt of 1,600g, whereas 3,360 g of Brodifakum 210 g blocks were consumed concomitantly. Overall, 48,880 g of different blocks was consumed in four sessions during 2006.

Table 2. illustrates a summary data for the Bro-dilon paraffin 30 g and Brodifakum 25 g blocks re-spective consumptions during the execution of four acts of deratization in 2006 which was performed on the outdoor 20. 000 m2 big green surface area and streams (canals) at their entire 400 m length. As expected, overall consumption of paraffin blockswas in accordance with the level of infestation; du-ring spring and autumn periods, when infestation was higher, the deratization was done by placing alternately two Brodilon and one Brodifakum block at 10m distance intervals (2:1 ratio) on designated areas whereas during the summer and winter peri-ods, when infestation decreased, the baits were put at 20 m intervals and at 1:1 ratio. Consequently, during spring and autumn sessions of deratization total of 8,500 g of paraffin blocks was consumed ineach period and included the consumption of 6,000 g Brodilon 30 g blocks and 2,500 g Brodifakum 25 g blocks, respectively. An overall paraffin blocksconsumption during summer and winter period was 1,730 g of blocks in each period and included consuming 930 g Brodilon and 800 g Brodifakum paraffin blocks, respectively.

Table 1. Consumption of the 100 g and 200 g Brodilon and Brodifakum paraffin 210 g blocks used forderatization of the sewerage system (drain manholes and revision apertures).

Time of deratization Brodilonparaffin block 100 g

Brodilonparaffin block 200 g

Brodifakumparaffin block 210 g Total

Spring 10. 800 g 1. 600 g 3. 360 g 15. 760 gSummer 5. 400 g 1. 600 g 1. 680 g 8. 680 gAutumn 10. 800 g 1. 600 g 3. 360 g 15. 760 gWinter 5. 400 g 1. 600 g 1. 680 g 8. 680 gTotal 32. 400 g 6. 400 g 10. 080 g 48. 880 g

Table 2. Consumption of the Brodilion 30 g and Brodifakum 25 g paraffin blocks used for deratizationof outdoor green surface areas and streams (canals).

Time of deratization Brodilonparaffin block 30 g

BrodifakumParaffin block 25 g Total

Spring 6. 000 g 2. 500 g 8. 500 gSummer 930 g 800 g 1. 730 gAutumn 6. 000 g 2. 500 g 8. 500 gWinter 930 g 800 g 1. 730 gTotal 13. 860 g 6. 600 g 20. 460 g

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Overall, 20,460 g of different paraffin blockswas consumed in four sessions of deratization of green area and water stream systems during 2006.

In addition, we would like to emphasize that we have created ‘eradication map’ before perfor-ming act of deratization. The map was showing all the places at which the baits were to be located. Additionally, the baits were placed into the rodent active holes and hidden places and rodent paths, were afterward carefully masked and covered by the layers of earth to prevent any accidental ex-posure of humans and animals to these poisonous traps. Also, the protective gloves were used during the placing of baits which prevented the possibili-ty that human sweat could come in contact with the baits and repulse rats of taking it.

Table 3. summarizes the consumption of Bro-dilon and Brodifakum paraffin blocks during timeof the inspection and the replenishment of deco-ys which was done five days after deratization ofexternal areas. The biggest quantity of paraffinblocks was consumed after autumn session (1,950 g) whereas somewhat lesser amount (1,490 g) of paraffin blocks was consumed after spring sessi-on of deratization. The consumption of the blocks during summer and winter acts of deratization was

similar and averaged 650 g of consumed blocks in each of two periods. It was reasonable to expect the difference between data having in mind hig-her level of infestation during spring and autumn periods. Overall, we have verified throughout in-spection and decoy replenishment that 4,740 g of paraffin blocks were consumed during four sessi-ons of external deratization in 2006.

Table 4. reviews total consumption of Brodilon and Brodifakum paraffin blocks that were spenton deratization of the sewerage system and outdo-or surface areas of pharmaceutical factory area du-ring four sessions of deratization in 2006. The use of Brodilon paraffin blocks amounted to 55,600gwhereas Brodifakum paraffin blocks were used at18,480 g quantity. Thus, total yearly consumption of both Brodilon and Brodifakum baits used for the deratization in wet conditions was 74,080 g. Also, we have observed that the rodents did not discriminate between Brodilon and Brodifakum blocks and they consumed both types of baits eq-ually well. This finding testifies that both types ofdecoys were equally attractive and well prepared.

It has previously been stated that rodenticides are digestive poisons and thus they should be in-gested to get in touch with rodent organism. Sin-ce the poison active compound is not attracting

Table 3. Consumption of the Brodilon 30 g and Brodifakum 25 g paraffin blocks during the inspectionand supplementation of the decoys, carried out five days after deratization of the outdoor surface area.

Time of deratization Brodilonparaffin block 30 g

Brodifakumparaffin block 25 g Total

Spring 990 g 500 g 1. 490 gSummer 300 g 250 g 550 gAutumn 1. 200 g 750 g 1. 950 gWinter 450 g 300 g 750 gTotal 2. 940 g 1. 800 g 4. 740 g

Table 4. The review of total consumption of Brodiion and Braodifakum paraffin blocks utilized for de-ratization of sewerage system and outdoor surface in pharmaceutical factory area during 2006.

Location Brodilonparaffin blocks

BrodifakumParaffin blocks Total

Sewerage system 38. 800 g 10. 080 g 48. 880 gOutdoor green areas 13. 860 g 6. 600 g 20. 460 gDecoy supplement 2. 940 g 1. 800 g 4. 740 gTotal 55. 600 g 18. 480 g 74. 080 g

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rodents, it should be mixed with a kind of food which rodents prefer. Such mixture of the poison and attractive food is called ‘mamak’. Mamak, ir-respective of its way of manufacturing, should be of highest quality because overdosing it may deter rodents of taking it whilst the sub dosing of the poison may result in the development of resistance to the poison. In addition, mamak’s organoleptic features should be well manufactured to attract ro-dents.

Graph 1. illustrates the overall consumption of all types of Brodilon and Brodifakum paraffinblock rodenticides that were used for deratization of sewerage system and outdoor surface in phar-maceutical company area during 2006.

Graph 1. Total consumption of all types of Bro-dilon and Brodifakum paraffin blocks used forderatization of the sewerage system and outdoor surface area in pharmaceutical company during 2006.

Currently, there are different decoy nouris-hment preparations present on the market called the carriers. They use different types of attractive food stuff such as meat, fish, cheese, fruits and ve-getables, as well as different types of grains. On the other hand, fresh decoys should be prepared just prior to use to prevent spoil of the ingredients. Also, cooking oil is added to ensure better mixing of the poison and food compound. On the other hand, liquid rodenticides, which dissolve in wa-ter, are seldom used. In addition, decoy powdered forms are used to cover active holes and rodent communication paths. However, solid paraffin de-coys are only forms of decoys which are stable in wet conditions.

In order to attract rodents the decoys also con-tain a moderate amount of different smelly and ta-sty attractants such as anis, smoked meat, cheese, sugar, salt, etc. Today, it is generally recognized that rodenticides of choice for the eradication of rodents in wet conditions are solid forms of the se-cond generation anticoagulants whose active com-pound is based on bromadiolon and brodifakum. The main characteristic of the second generation of anticoagulants is that they are highly efficacio-us at single dose. On the other hand, first generati-on of the anticoagulant rodenticieds is efficaciousonly after five to six days of constant consumptionby rodent.

In Table 5. presented are the LD50 values for the first and second generation of anticoagulantrodenticides obtained on brown rat.

Table 5. LD50 values of anticoagulant rodenticides of the first and second generation for the brownrat.

Antikoagulants -first generation

LD50 mg/kg brown rat

Antikoagulants -second generation LD50 mg/kg brown rat

Kumatetralil 16. 5 Brodifakum 0. 3

Difacinon 3. 0 Flokumafen 0. 4

Warfarin 58. 0 Bromadiolon 1. 3

Pival 50. 0 Difenakum 1. 6

Klorfacinon 20. 5

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Conclusions

1. Efficacious eradication of rodents is basedon the comprehension of their biological, etiological, and ecological distinctiveness. The act of deratization is a complex and responsible action requesting methodical preparatory and organizational activities and requests skilled staff to execute it properly.

2. Deratization in wet conditions is a unique activity which asks for additional organizational efforts, particularly the determining the most efficaciousformulationand suitable form of decoys which will be used.

3. For the purpose of the eradication of rodents in wet environments, specificallythe deratizations of the open green areas and sewerage system of the pharmaceutical factory, the manufactured paraffin blocks ofdifferent weight and dimensions containing anticoagulants of the second generations (Brodilon and Brodifakum), were used.

4. During four sessions of deratization in 2006 the amount of 55,600 g Brodilon paraffinblocks as well as 18,480 g Brodifakum was spend.

5. Generally, full amount of spent paraffinblocks which were chosen for deratization in wet conditions in 2006 was 74,080 g. The degree of infestation was assessed by using method of Gunderson.

6. The level of infestation and the size of rodent population in designated area was calculated to be between 500 and 1,000 during spring and autumn whereas population size was estimated to be between 100 and 500 during the summer and winter time.

7. Three weeks after performing of deratization additional evaluation of the level of infestation was done; it has been concluded that population size has been reduced bellow 100 rodents.

8. Based on overall data, it has been concluded that the measures which have been undertaken during 2006 were successful and that the choice of paraffin decoys wasappropriate for the act of deratization in wet conditions in the open green areas and sewerage system of the pharmaceutical factory in Zagreb.

Literature

1. Capak K. : Javnozdravstvena važnost deratizaci-je, Zbornik predavanja, Glodavci i ptice, Zagreb, 2002: 1

2. Capak K. , Korunić Z. : Javnozdravstvena i gospo-darska važnost štetnika uskladištenih poljoprivre-dnih proizvoda i hrane, Zbornik predavanja, Štetni-ci hrane, uskladištenih poljoprivrednih proizvoda i predmeta opće uporabe te muzejski štetnici, Zagreb, 2005 : 3

3. Krajcar D. : Dezinfekcija, dezinsekcija, deratizacija, Zagreb: Zavod za javno zdravstvo grada Zagreba, 2001, 167-198

4. Bakić J. : Naši sinantropni mišoliki glodavci, Zbor-nik predavanja, Glodavci i ptice, Zagreb, 2002: 1

5. Pravilnik o načinu obavljanja obvezatne dezinfekci-je, dezinsekcije i deratizacije (NN 38/98)

6. Krajcar D. : Praktična provedba deratizacije, Zbor-nik predavanja, Glodavci i ptice, Zagreb, 2002: 43

7. Zidar R. , Poljak V. : HACCP-teorija i praksa s po-sebnim osvrtom na kontrolu štetočina, Zbornik pre-davanja, Dezinfekcija, dezinsekcija i deratizacija u HACCP sustavu, Zagreb, 2004: 11-23

8. Molek K. : Analiza rizičnih kontrolnih mjesta za sprovođenje djelotvorne deratizacije (HACCP), DDD i ZUPP 2001, Novine u djelatnosti dezinfe-kcije, dezinsekcije, deratizacije i zaštite uskladište-nih poljoprivrednih proizvoda, Poreč, 2001:226

9. Milinković Lj. : Suzbijanje glodavaca, DDD i ZUPP 2001, Novine u djelatnosti dezinfekcije, dezinsekci-je, deratizacije i zaštite uskladištenih poljoprivre-dnih proizvoda, Poreč, 2001: 216

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10. Lukić I. , Veledar H. : Preventivna sustavna de-ratizacija kanalizacijske mreže-nova saznanja , 5. znanstveno stručni skup iz DDD-a s međunaro-dnim sudjelovanjem, Pouzdan put do zdravlja ži-votinja, ljudi i njihova okoliša, Mali Lošinj, 2004: 380

11. Bakić J. : Način provedbe obvezatne dezinsekcije i deratizacije, Zbornik predavanja, Oživotvorenje Pravilnika o uvjetima i načinu provođenja obve-zatnih DDD mjera-provedba u praksi, Zagreb, 2006: 31,32

12. Bakić, J. : Prednosti krutih raticidnih meka s djela-tnim sastavcima I i II generacije antikoagulanata u sustavnoj deratizaciji razorenih naselja. Zbor-nik 2. znanstveno stručnog skupa s međunarodnim sudjelovanjem DDD u zaštiti zdravlja životnja i očuvanju okoliša, Umag, 1995: 267-273

Corresponding author: Suad Habes Fakultet zdravstvenih studija Sarajevo Bosna i Hercegovina e-mail: [email protected]

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Summary

The present study evaluated the relationship between the presence of viable myocardium and the develompment of collateral circulation to the infarct area in patients with total coronary occlu-sion.

The study group consisted of 80 patients with occlusion of at least one major coronary artery.

The patients were categorized in two groups depending on the extent of their collateral circu-lation: group 1 (n =45) - patients with well-deve-loped coronary collaterals to the infarct-related coronary artery; group 2 (n =35) - patients with poor coronary collateral development or without significant collateral circulation. In the first groupwe established the presence of viabile myocardi-um in the perfusion territory of the infarct-related artery.

The perfusion defects in the group with good collateras were predominantly reversible, sugge-sting that coronary collaterals preserved myocar-dial viability in the regions subtended by a total coronary occlusion. A significant correlation be-tween good collaterals with complete protection and poor collaterals with no protection was noted.

These results suggest that the existance of well-developed coronary collaterals may contribute to minimizing the infarct area and to prediction of the presence of viable myocardium.

Key words: myocardial viability, collateral cir-culation, coronary occlusion

Sažetak

Studija evaluira odnos postojeće vijabilnosti miokarda i razvoja kolateralne cirkulacije u infar-ciranom području kod pacijenata sa totalnom ko-ronarnom okluzijom.

Studija je obuhvatila 80 pacijenata sa okluzi-jom najmanje jedne veće koronarne arterije.

Pacijenti su kategorizirani u dvije grupe na osnovu veličine kolateralne cirkulacije: grupu 1 (n=45) su činili pacijenti sa dobro razvijenom kolateralnom cirkulacijom, dok je druga grupa (n =35) obuhvatila pacijente sa neadekvatnom kola-teralnom cirkulacijom. U prvoj grupi smo ustano-vili postojanje vijabilnog miokarda u perfuzionom području infarktom zahvaćene arterije.

Perfuzioni defekti u grupi sa dobrom kolateral-nom cirkulacijom su bili pretežno reverzibilni, što ukazuje da koronarne kolaterale štite mikardnu vi-jabilnost u području sa totalnom koronarnom oklu-zijom. Uočena je signifikantna korelacija izmeđudobrih kolaterala i kompletne zaštite i loših kola-terala bez zaštite miokardne vijabilnosti.

Ovi rezultati ukazuju da dobro razvijena ko-lateralna cirkulacija može dovesti do smanjenja infarciranog područja i da predviđa postojanje vi-jabilnog miokarda.

Ključne riječi: miokardna vijabilnost, kolate-ralna cirkulacija, koronarna okluzija

The relationship between myocardial viability and collateral circulationODNOS VIJABILNOSTI MIOKARDA I KOLATERALNE CIRKULACIJEAida Hasanovic

Institute of Anatomy, University of Sarajevo, School of Medicine, Bosnia and Herzegovina

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Introduction

The relationship between the presence of viable myocardium and the extent of coronary collateral circulation to the infarct area during occlusion of coronary arteries was evaluated by authors (1, 2, 3, 4).

Although coronary arteriography provides cle-ar definition of significant coronary artery diseaseit is less satisfactory in the delineation of coronary collateral vessels for it reveals only epicardial ana-stomoses of a size no smaller than 100-200 ų and not the deeper connections which exist within the myocardium (5,6,7).

Angiography is used for measuring coronary artery lumen norrowing; however, it is not the ide-al method for determining its physiologic signifi-cance (8).

Myocardial imaging using thallium-201 (201Tl) is a non–invasive technique which is valuable in the analysis of regional myocardial perfusion. Re-gions of ischemia caused by severe coronary dise-ase appear as functional defects of tracer accumu-lation in the myocardial scintigram (9,10).

The most widely available method for iden-tification of viable myocardium is single photonemission computed tomographic (SPECT) ima-ging with thallium-201 (Tl-201).

Thallium 201 enters myocytes primarily by active transport, which means that regional my-ocardial concentration of Tl-201 is dependent on regional blood flow, extraction and clearance. Ne-crotic myocardium, without an intact cell mem-brane, is unable to retain Tl-201. In viable myo-cardium, Tl-201 is continuously exchanged betw-een the myocardium and the blood stream, with the rate of exchange in proportion to the difference in Tl-201 concentration between the myocardium and the blood stream. Therefore, after the admini-stration of Tl-201, the myocardium concentration is greatest in those areas of myocardium with the highest blood flow. Over time, a tendency towardequilibrium of Tl-201 concentration in viable my-ocardium. This phenomenon is termed „redistri-bution“. Therefore, a Tl-201 perfusion defect that is reversible is considered indicative of ischemic but viable myocardium (11).

Using 201Tl imaging, we have analysed the in-fluence of well-developed coronary collateral cir-

culation angiographically documented on myocar-dial viability in patients with coronary occlusion.

Patients and methods

Eighty patients with angiographically docu-mented coronary artery disease at the Department of Nuclear Medicine were investigated by (201Tl) myocardial scintigraphy, shortly after coronary artery disease had been demonstrated by contrast arteriography.

All patients selected for myocardial imaging had severe stenosis or total occlusion of at least one major coronary artery. The majority of pati-ents had complete occlusion of at least one vessel. A significant coronary stenosis was defined as re-duction of the coronary lumen by more than 50 per cent, and severe stenosis as a reduction in dia-metar greater than 80 per cent.

Patients with hypertension, valvular heart dise-ase, or primary myocardial disease were excluded from this study.

The study was approved by the local ethical commitee and conducted in accordance with the Helsinki declaration.

Coronary Angiography

Selective coronary angiography was perfor-med in multiple projection using the Judkins tec-hnique. All coronary arteriograms were reviewed independently by two observes in ignorance of the scintigraphic analysis, and note was made of the site and number of complete coronary occlusions and severe coronary stenoses together with any as-sociated coronary collateral channels.

We determinated a maximal lumen constriction of the coronary artery (right coronary artery-RCA, left anterior descending artery-LAD, and circum-flex artery –Cx) and the existence, origin and thedirection of collateras.

On the angiograms we analyzed collaterals as “adequate” (average calibar greater than 1,0 mm) and “inadequate” (average calibar -1mm and less).

For all patients we applied left ventriculogra-phy for the evaluation of its function, ejective fra-

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ction and kinetics. Left ventriculography was per-formed in the right anterior oblique projectin.

Thallium-201 Myocardial Scintigraphy

Studies of regional myocardial perfusion were performed at rest and during pressure (a maximal exercise test on a bicycle ergometer). All patients had a complite physical examination, resting 12 lead electrocardiogram, and an electrocardiogram recorded during a maximal exercise test on a Mo-nark bicycle ergometer with lead V5 monitoring.

During the exercise test each patients received 1,5 mCi of 201Tl through an indwelling intraveno-us canila at the onset of angina pectoris or limiting dispnoea.

The exercise end-point was maintained for one and a half to two minutes so that there was maxi-mal myocardial uptake of circulating tracer in the presence of symptoms.

After a 10–minute recovery period, myocardial imagining was performed with subjects in the su-pine positions using a gamma camera and a high-sensitivity parallel-holed collimator.

Anterior, left anterior oblique 45º and 70º were routinely acquired in every patients (each positi-on-five minuts) after exercise and redistributionafter 3 hours. A 20 % symmetric energy window centered on the 72 keV peak was used.

All projections images were stored on ma-gneto-optic disks in a 64x64 matrix. The digital images were displayed on a TV monitoring. After computer treatment a digital scintigraphic images were described by one interpreter.

Localisation of perfusion defects in relation with corresponding blood vessel determinated visual on each image divided into five segments.Each defect was further classified as moderate orsevere according to the degree of tracer deficitseen in that region.

The result was considered “positive“ when a re-versible defect was allocated to the perfusion territo-ry of the coronary artery of interest. Defects located in the anterior wall and septal region were allocated to the left anterior descending artery, defects in the lateral wall were allocated to the left circumflex co-ronary artery, and defects in the inferior wall were allocated to the right coronary artery.

Statistical comparison of data was perfomed using the Chi-square test. Using Chi-square test, the differences between the groups were signifi-cant (P<0.001).

Results

The study included 80 patients with chronic total occlusion who underwent rest-stress myo-cardial perfusion scintigraphy and coronary angi-ography.

Patients were divided into two groups accor-ding to the presence (group 1, n =45) or absence (group 2, n =35) of viable myocardium in the per-fusion territory of the infarct-related artery.

In the first group we established well-develop-ment coronary collateral vessels and predominan-tly normal or hypokinetic left ventricular function. In the group with poor collaterals in the vast majo-rity cases demonstrated akinesia or dyskinesia of the corresponding myocardial segment.

The difference between the two groups was si-gnificant at the 0.001 level. An ejection fraction in the group with well-developed coronary collateral vessels and good left ventricular function was > 50%; in the group with inadequate collateral cir-culation was 35%.

The viability of myocardial tissue was assessed by exercise thallium-201 myocardial scintigraphy.

Our patients with chronic total occlusion had severe and extensive stress-induced myocardial perfusion defects regardless of the grade of angi-ographic coronary collaterals. The perfusion de-fects in the group with good collateras were pre-dominantly reversible (Figure 1), suggesting that well-developed coronary collaterals preserved myocardial viability in the regions subtended by a total coronary occlusion. In the group with poor coronary collateral development the perfusion de-fects were predominantly ireversible.

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Figure 1. Single-photon emission tomography of the heart with 201tallium was performed accor-ding to standard stress (planar projection -45 º); Analysis of perfusion scintigrams in patients with angiographically documented collaterals referen-ce to reversible defect of infero-lateral segment, and ischemia of this region

The relation between the degree of coronary collateral development assessed angiographicaly and the severity of 201 Tl uptake defects seen in the myocardial scintigram showed a highly significantassociation between well-developed coronary col-lateral vessels and accompanying preservation of myocardial 201 Tl uptake. Similary, poor or absent coronary collateral development was usually as-sociated with severe deficit of tracer in correspon-ding regions of the scintigram.

Angiographically invisible collaterals were ne-ver associated with complete scintigraphic prote-ction and usually conferred no protective benefit.Similary, vessel ghosting was always accompanied by severe scintigraphic uptake defects. Bridging collaterals also offered inadequate protection from myocadial ischemia during exercise.

Discussion

In patients with a chronic total occlusion, our study investigated the relationship between the an-giographic development of collateral circulation and myocardial viability in patients with coronary occlusion. Patients with chronic total occlusion had severe and extensive stress-induced myocar-

dial perfusion defects regardless of the grade of angiographic coronary collaterals.

Several studies have suggested that coronary collaterals preserve resting myocardial flow butare inadequate to protect againist reduced blood flow during hyperemic stress (6,7). In contrast,several studies with planar 201 scintigraphy sugge-sted that coronary collaterals also prevent stress-induced ischemia (1,2,3, 8,11).

Our study showed that the perfusion defects in the group with good collateras were predominan-tly reversible, suggesting that well-developed co-ronary collaterals preserved myocardial viability in the regions subtended by a total coronary oc-clusion. In the group with poor coronary collateral development the perfusion defects were predomi-nantly ireversible. In this group the absence of vi-able myocardium in the perfusion territory of the infarct-related artery was established.

The relation between the degree of coronary collateral development assessed angiographicaly and the severity of 201 Tl uptake defects seen in the myocardial scintigram in our patients showed a association between well-developed coronary col-lateral vessels and accompanying preservation of myocardial 201 Tl uptake.

Using 201Tl myocardial scintigraphy many pa-tients with total occlusive disease of a dominant right coronary artery are seen to have adequate collateral vessels providing complete protection from ischemia in the distribution of this artery du-ring dynamic exercise. Patients with left anterior descending disease, however, were not protected from the appearance of ischaemic uptake defects (4,5).

Although the mechanism for this protection is not clear the normal pressure gradient that exists between left and right ventricles may be increased during dynamic exercise, particulary during dia-stole in an ischaemic left ventricle, so that collate-ral flow is maintained or increased in the directionof the low pressure right ventricular myocardium. This effect probably accounts for the preservation of tracer uptake in the inferior wall of the left ven-tricle as seen in 201Tl scintigrams (9,10).

However, one relevant limitation of 201TI ima-ging is that relative regional myocardial ischaemia is reflected in the scintigram rather than in termsof absolute perfusion. Thus, it is possible that even

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the right coronary artery territory is ischemic du-ring exercise, though better perfused than the left coronary artery.

Conclusions

1. The clear correlation between the angio-graphic grade of collaterals and corresponding areas of protection seen in the scintigram gives the angiographer reasonable reassurance that there is functional relevance in a detail description of these important channels.

2. Reversible perfusion defects on stress thallium imaging in the group with adequate collateral circulation suggesting that well-developed coronary collaterals preserved myocardial viability in the regions subtended by a total coronary occlusion.

3. These findings indicate that the presenceof ischemic but viable myocardium is intimately related to the development of collateral circulation in patients with myocardial infarction, and the existence of well-developed collateral channels predicts the presence of viable myocardium in the infarct area.

Literature

1. Fujita M, Ohno A, Wada O, Miwa K, Nozawa T, Yamanishi K, Sasayama S. Collateral circulation as a marker of the presence of viable myocardium in patients with recent myocardial infarction. Am Heart J. 1991;122(2):409-14.

2. Fukai M, Li M, Nakakoji T, Kawakatsu M, Nariy-ama J, Yokota N, Negoro N, Kojima S, Ohkubo T, Hoshiga M, Nakajima O, Ishihara T. Angiographi-cally demonstrated coronary collaterals predict re-sidual viable myocardium in patients with chronic myocardial infarction: a regional metabolic study.J Cardiol. 2000;35(2):103-11.

3. Aboul-Enein F, Kar S, Hayes SW, Sciammarella M, Abidov A, Makkar R, Friedman JD et all. Influenceof angiographic collateral circulation on myocardi-al perfusion in patients with chronic total occlusion of a single coronary artery and no prior myocardial infarction. J Nucl Med. 2004;45(6):950-5.

4. Sand NP, Rehling M, Bagger JP, Thuesen L, Flo C, Nielsen TT. Functional significance of recruitablecollaterals during temporary coronary occlusion evaluated by 99mTc-sestamibi single-photon emis-sion computerized tomography. J Am Coll Cardi-ol.2000;35:624-632.

5. Wainwright RJ, Maisey MN, Edwards AC, Sowton E. Functional significance of collateral circulationduring dynamic exercise evaluated by thallium-201 myocardial scintigraphy.Br Heart J 1980:47-55.

6. Werner GS, Ferrari M, Betge S, Gastmann O, Ric-hartz BM, Figulla HR. Collateral function in chro-nic total coronary occlusions is related to regional myocardial function and duration of occlusion. Cir-culation.2001;104:2784-90.

7. Tajfl D, Kamenica S, Spaić R, Milošević A, Oda-vić M. Uticaj kolateralnog srčanog krvotoka na rezultate scintigrafije srčanog mišića u bolesnikasa ishemijskom bolešću srca. Vojnosanit Pregled. 1987 44 (2): 128-131.

8. Hasanović A, Kulenović A, Šišić F. The role of col-lateral circulation in preserving myocardial functi-on. Bosn J Basic Med Sci. 2006;6(4):29-31.

9. Hasanović A, Jurić I, Fazlibegović E. Perfuziona scintigrafija miokarda i ehokardiografija kod pa-cijenata sa koronarnim kolateralama.Medic. Žurn. 2002; 8 (1):12-17.

10. Hasanović A. Angiogenesis of ischemic myocardi-um. HealthMED. 2007; 3(1): 89-93.

11. E Skoufis, AI McGhie. Radionuclide techniques forthe assessment of myocardial viability. Tex Heart Inst J. 1998; 25 (4): 272-279.

Corresponding author:

Aida Hasanovic Institute of Anatomy, University of Sarajevo, School of Medicine, Bosnia and Herzegovina, email: [email protected]

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Summary

Introduction: Police work has been recogni-zed as high risk for stress. Police officers are expo-sed on daily basis to stressful and traumatic events, that is, the events outside usual human experience (e.g. serious threat to one’s life and body integrity, witnessing violent acts or severe physical harm or death of another).

Consequences and symptoms of stress include physical and psychosomatic illnesses, behavior changes, emotional and cognitive problems. Once the reaction to traumatic experience, judged by its intensity and duration, exceeds one’s “subjective coping threshold” we talk about pathologic reacti-on to trauma which can cause various psychologi-cal disorders.

Objectives: Objective of our work was to de-velop a structured stress management program based on cognitive behavior therapy principles for persons in high risk professions such as police officers. Another objective was to evaluate the ef-fects of structured stress management program on police officers by measuring their anxiety levelsbefore and after the treatment.

Materials and methods: The subjects were police officers, aged from 30 to 45 years, divided

into two groups, each consisting of 20 persons. One group received structured stress management program and another did not. All members of both groups completed BAI and ASI tests ahead and after the treatment, as well as three months after the treatment.

Outcomes: Statistical data analyzes revealed that the subjects who had received stress mana-gement program displayed a statistically signifi-cant anxiety sensitivity reduction, developed more active and planned coping strategies for stressful situations, had less somatic reactions to stress and have thus also achieved improved performance at work and in private life. The subjects were also significantly more likely to request medical adviceafter completing psychotherapeutic program.

Conclusions: - The group of police officers who had received

the structured stress management program regi-stered statistically significant anxiety sensitivityreduction compared to the test group.

- The subjects who had completed the program were significantly more likely than the subjectsfrom control group to request medical advice in crisis situations.

Key words: cognitive-behavior psychothera-py, stress management, anxiety.

Application of cognitive behavior therapeutic techniques for prevention of psychological disorders in police officersPRIMJENA KOGNITIVNO-BIHEVIORALNIH PSIHOTERAPIJSKIH TEHNIKA U PREVENCIJI PSIHIČKIH POREMEĆAJA KOD POLICAJACASibila Sijaric-Voloder1, Dzejna Capin1

1 Association for psychological assessment, help and consulting ‘’DOMINO’’

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Sažetak

Uvod: Posao policajca spada u grupu visokori-zičnih zanimanja po pitanju stresa. Svakodnevna je izloženost policajaca stresnim i traumatskim do-gađajima, odnosno događajima koji su izvan gra-nica uobičajenog ljudskog iskustva (npr. ozbiljna prijetnja životu ili tjelesnom integritetu, pogled na drugu osobu koja je ozbiljno povrijeđena ili ubije-na u nesreći, odnosno nasilnom činu te prisustvo takvim događajima).

Posljedice ili simptomi stresa su tjelesni-psi-hosomatske bolesti, promjene u ponašanju, emo-cionalne posljedice te kognitivne smetnje. Kada reakcije na traumatsko iskustvo pređu određenu mjeru po „subjektivnoj nepodnošljivosti“, po obi-mu i trajanju govorimo o tzv. patološkom obliku reakcije na traumu koje može biti uzrok razvoja različitih psihijatrijskih poremećaja.

Cilj rada: Cilj rada je bio strukturirati stres menadžment po principima kognitivno-bihevio-ralne psihoterapije za lica koja obavljaju visoko rizične poslove kao što su policajci.

Također, cilj rada je bio evaluirati efekte stru-kturiranog stres menađmenta za pripadnike poli-cijskih snaga utvrđivanjem stepena anksioznosti prije i nakon tretmana.

Materijal i metode: Ispitanici su policajci, starosne dobi od 30-45 godina života podjeljeni u dvije grupe od po 20 članova. Jedna grupa je pro-šle strukturirani stres menađment dok druga nije. Svi su tri puta popunili BAI i IOA; na početku tretmana, nakon završenog tretmana i tri mjeseca nakon toga.

Rezultati rada: Statistička obrada podataka je pokazala da je kod grupe koja je prošla strukturira-ni stres menađment došlo do statistički značajnog sniženja anksiozne osjetljivosti, povečanja načina za aktivno i plansko suočavanje sa stresnim situ-acijama, smanjenja somatizacijskih reakcija a sa-mim tim i do poboljšanja njihovog funkcionisanja u radnoj i privatnoj sredini. Nakon završenog psi-hoterapijskog programa njihova spremnost da se obrate za stručnu pomoć se izrazito povečala.

Zaključci: - Grupa policajaca koji su bili uključeni u stru-

kturirani stres menađment je imala statistički zna-čajno smanjenje anksiozne osjetljivosti u odnosu na kontrolnu grupu.

- Spremnost da se obrate za stručnu pomoć u kriznim situacijama je kod ispitanika značajno po-rasla dok kod kontrolne grupe nije došlo do pro-mjena.

Ključne riječi: kognitivno-bihevioralna psiho-terapija, stres menađment, anksioznost.

Introduction

Police work has been recognized as high risk for stress. Police officers are exposed on daily basisto stressful and traumatic events, that is, the events outside usual human experience (e.g. serious threat to one’s life and body integrity, witnessing violent acts or severe physical harm or death of another).

Consequences and symptoms of stress include physical and psychosomatic illnesses (hart and co-ronary artery diseases, digestive problems, asthma, dermatologic diseases, spinal problems etc.), be-havior changes (abuse of alcohol and some medi-cines – anxiolitics or social withdrawal, increased consumption of coffee, alcohol, food, excessive to-bacco smoking, sleeping disorders, short temper), emotional problems (anxiety, rage, restlessness, irritability, guilt, mood swings, sadness) and co-gnitive problems (memory problems, inability to concentrate, trouble thinking clearly, indecisive-ness, changing opinions, fearful anticipation…). Once the reaction to traumatic experience, judged by its intensity and duration, exceeds one’s “subje-ctive coping threshold” we talk about pathologic reaction to trauma which can cause various psyc-hological disorders.

As a result of his research, Blackmore (1) has ranked police work among the top 17 occupations (out of 130) related to increased risk of health pro-blems. Jacobi (1) studied health-related workers’ compensation claims to discover that police offi-cers were seven times more likely than other pro-fessionals to submit such claims, as well as that 30% of police officers’claims were related to backpain and another 50% to hypertension.

Richard and Fell (2) conducted a research on the sample of 23 976 workers from Tennessee in-cluding 168 police officers. They discovered thatpolice officers experienced many more health pro-blems than other professionals, particularly dige-stive and blood circulation problems.

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Unfortunately, most police officers request me-dical assistance at the point when stress at work had already caused long-term consequences on their health and professional efficiency. They rare-ly require psychiatric or psychological assistance out of fear of stigmatization, but also fear that they will be judged as incapable of police work. They are little or not at all educated about the concept of stress and trauma, normal and pathological reacti-on to stress and traumatic experience. In addition to psychological and physical health consequen-ces, the above can also jeopardize their professi-onal safety.

Coping with stress is different to simple and automatic adaptive reaction to a new situation because it includes cognitive efforts to adjust to a new situation which exceeds one’s capacities at the point when possibility of automatic adaptation is excluded.

It cannot be valued as good or bad because it is defined as investing efforts into overcomingspecific obstacles. There are two primary functi-ons of stress coping: regulating emotions resulting from stressful situations and attempting to solve the problem. This sets the basis for the basic clas-sification of stress coping styles as: problem-ori-ented coping and emotion-oriented coping, also known as active and evasive coping. However, such a broad definition of coping styles was pro-ven to be imprecise, because they both include different distinct strategies. Problem-oriented sty-les include planning actions, active confrontation, suppressing competing activities, direct action, problem solving, negotiation, information seeking etc, while emotion-based coping styles include de-nial, self-blame, suppression, imaginary thinking, wishful thinking, turning to religion, using humor, positive thinking, reappraisal, passivity, holding-back emotions etc.

There is also the difference between cognitive and behavioral coping strategies. Behavioral stra-tegies can include visible action taken to reduce the effects of stress, while cognitive coping strate-gies include attempts to re-interpret the situation.

However, despite the above distinction, diffe-rent coping strategies do not exclude one another. It is common for a person to use different coping strategies in similar situations, depending on per-sonality, as well as characteristics and cognitive

appraisal of the situation, in that, all coping styles have their own function.

Results of evaluation of cognitive-behavior stress management used on different groups of cli-ents point to positive outcomes of programs used (3), (4), (5). Several studies show that the use of cognitive-behavior stress management leads to normalization of some physiological parameters such as blood pressure (6), while studies of blood parameters are contradictory (7), (8).

Most previous studies (9), (10) conclude that stress management programs have positive effects. Despite numerous positive consequences of the modern lifestyle, it also affects human organism in the way of producing various psychological and somatic changes. Such effects of modern lifestyle are further intensified in transitional, post-war co-untries such as Bosnia and Herzegovina.

Research objectives

Objective of our work was to develop a structu-red stress management program based on cogniti-ve behavior therapy principles for persons in high risk professions such as police officers. Anotherobjective of our work was to evaluate the effects of structured stress management program on poli-ce officers by measuring their anxiety levels befo-re and after the treatment.

Subjects (material) and research methodology

a) SubjectsOur subjects are police officers. Experimental

group consisted of 20 randomly selected police officers serving with the Interior Ministry of theSarajevo Canton, aged from 30 to 45 years.

b) Control groupControl group consisted of 20 randomly sele-

cted police officers serving with the Interior Mi-nistry of the Sarajevo Canton, aged from 30 to 45 years.

c) Procedure (organization of research)- In cooperation with the Ministry of Interior,

two groups of 10 people were formed. The

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groups received educational-therapeutic program of structured cognitive-behavior stress management.

- Group treatment was organized once a week over a period of one month. At the start of the treatment all members of therapeutic groups completed objective psychological measurement tests which were also used at the end and three months after the treatment in order to evaluate effects. In the therapeutic part of the program we used cognitive-behavior therapeutic techniques, while educational part of the program focused on the issues related to stress and trauma.

- The control group completed the same psychological tests at the same time as the experimental group but no member of this group has taken part in the program during that period.

- Stress management was structured in such way to cover the following issues:

1. Concept of Stress2. Coping strategies, normal and

pathological reactions to stress 3. Results, consequences of stressful

events (short-term and long-term)4. Trauma; Post-Traumatic Stress disorder5. Relaxation techniques (breathing

techniques, progressive muscular relaxation)

6. Problem-solving technique7. Communication skills

d) Research instruments 1. Beck Anxiety Inventory (BAI); (Osman,

Kooper, Barrios, Osman & Wade 1997)2. Anxiety Sensitivity Index (ASI)

Results

The following diagrams show mean BAI and ASI scores of the two samples, during specificmeasurement periods.

Statistical data analyses were conducted using ANOVA (variance analyses), in that, it was sin-gle-factor analyses (participation in stress mana-gement program). The analyses proved that BAI and ASI scores of the subjects who received stress management program have fallen and that the dif-ference between their and the control group’s sco-res on the two scales was statistically significant.

Results of this research show that the subjects continued to use newly-acquired techniques after receiving structured stress management program based on cognitive-behavior therapy, which has resulted in further decline in the above-mentioned parameters.

Discussion

High risk occupations, such as policing job, place persons at risk of being in situations which are outside usual human experience. Members of police experience a different kind of work stress compared to other professions. This kind of stress is called burst stress. Burst stress means there is not always a steady stressor, but at times, there is an immediate “burst” from low stress to a high stress state. In usual stressful situations, most indi-viduals develop their own ways to reduce or adapt to stress and attempt to control their behavior in various ways. However that is not the case among

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police officers because their stress does not deve-lop gradually but comes in a burst, like an explosi-on. Police work is reactive and not proactive. It is very difficult for police officers to deal with stress.Due to cumulative effects of exhaustion and stress police officers become prone to making mistakesat work, which is often intolerable and very dan-gerous. Besides, cumulative effects of exhaustion and stress negatively impact police officers’ fami-ly and social life, placing them in an even more difficult situation.

This paper studied the effects of structured stress management on police officers.

Results have shown that the stress management has helped persons in a high risk profession to de-velop new ways for coping with stressful situati-ons and to further improve already existing coping skills. Also, reduced anxiety sensitivity has lead to their improved psychosocial functioning which had a direct impact on their interpersonal commu-nication.

Increased readiness to seek medical advice when experiencing psychological problems wo-uld be of enormous significance, because it wouldenable taking appropriate measures early after pat-hological reactions occur.

Conclusions

- The scores on BAI scale of the subjects who received stress management program have fallen and the difference between their and the control group’s scores was statistically significant.

- The experimental group also registered a significant fall in the scores on ASI scalecompared to control group.

- After stress management program was completed, the experimental group continued to register statistically significant fall in BAIand ASI scores compared to control group.

Literature

1. Moro, Lj. (1994). Što su stres i psihotrauma i kako ih prevladati? TIP, A.G. Matoš, Samobor.

2. Milovanović, R (1998). Policijska psihologija. Po-licijska akademija, Beograd.

3. Jane Sims (1997). The evaluation of stress mana-gement strategies in general practice: an evidence-led approach; British Journal of General Practice, 47, 577-582.

4. Frank M. Perna, Michael H. Antoni, Andrew Bra-um, Paul Gordon, Neil Schneiderman (2003). Co-gnitive Behavioral Stress Management Effekts on Injury and Illiness Among Competetive Athletes: A Randomized Clinical Trial; Ann Behav Med, 25(1): 66-73

5. Kathryn A Mannix, Ivy Marie Blackburn, Anne Garland, Jannifer Gracie, Stirling Moorey, Barba-ra Reid, Sally Standard, Jan Scott (2006). Effekti-veness of brief training in cognitive behaviour the-rapy techniques for palliative care practitioners; Palliaiative Medicine; 20: 579-584.

6. Silja Vocks, Margit Ockenfels, Ralf Jurgensen, Lutz Mussgaz and Heinz Ruddel (2004). Blood Pressure Reactivity Can Reduced by a Cognitive Behavioral Stress Management Program; International Jour-nal of Behavioral Medicine; Vol.11.No. 2, 63-70.

7. Jens Granath, Sara Ingvarsson, Ulrica von Thiele and Ulf Lundberg (2006). Stress Management: A Randomized Study of Cognitive Behavioural The-rapy and Yoga; Cognitive Behavioural Therapy; Vol 35, No1, pp. 3-10.

8. M. Claesson, L.S. Birgander, J.H. Jansson, B. Lin-dahl, G.Burell, K. Asplund and C. Mattson (2006). Cognitive-behavioural stress management does not improve biological cardiovascular risk indicators in women with ischaemic heart disease: a randomi-zed-controlled trial; Journal of Internal Medicine; 260:320-331.

9. Vicki R. LeBlanc, Cheryl Regehr, R. Blake Jelly and Irene Barath (2008). The Relationship Between Co-ping Styles, Performance, and Responses to Stres-sful Scenarios in Police Recruits. International Jo-urnal of Stress Management, Vol. 15, No.1, 70-93.

10. Sima Zach, Shula Raviv, Reuven Inbar (2007). The Benefits of Graduated Training Program for Secu-rity Officers on Physical Performance in StressfulSituations; International Journal of Stress Mana-gement, Vol. 14, No.4, 350-369.

Corresponding author: Sibila Sijarić-Voloder Association for psychological assessment, help

and consulting ‘’DOMINO’’ e-mail: [email protected]

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Summary

People with trisomy 18 have additional DNA from chromosome 18 in some or all of their cells. The extra material disrupts the normal course of development, causing the characteristic features of trisomy 18. It can appear like three forms: comple-te trisomy 18, mosaic trisomy 18 and as a translo-cation type (partial trisomy for chromosome 18).

Genetic testing by amniocentesis before birth or blood test after birth can confirm the diagnosis.

Most of the children with trisomy 18 die within the first year of life. Middle life span is less thantwo months in 50% of these children, 95% die wit-hin the first year.

Key words: Trisomy 18 (types), cytogenetic findings, short life span

Sažetak

Osobe sa trisomijom 18 imaju višak DNA koji potiče od hromosoma 18 u nekim ili svim njiho-vim stanicama. Ovaj višak materijala dovodi do ometanja normalnog razvoja, uzrokujući karakte-ristične simptome za trisomiju 18. Javlja se u tri oblika: kompletna trisomija 18, mozaični oblik i translokacijski oblik.

Genetičko testiranje koristeći amnocentezu pri-je rođenja ili citogenetska analiza poslije rođenja može potvrditi dijagnozu.

Većina djece sa trisomijom 18 umre unutar prve godine života. Prosječan životni vijek je manji od

dva mjeseca za 50% ove djece, a 95% umre unutar prve godine.

Ključne riječi: trisomija 18 (tipovi), citogene-tička analiza, kratak životni vijek

Introduction

The patient with trisomy 18 was first describedby Edwards (1960). Physical abnormalities may point to Edwards’ syndrome, but definitive dia-gnosis relies on karyotyping – cytogenetic testing. Trisomy 18 affects about 1 : 5000-8000 newborn, or 1:3000, regarding different references. (3, 11). Girls are affected more often than boys. (1)

Humans normally have 23 pairs of chromo-somes. Chromosomes are numbers 1-22, and the 23rd pair is composed of the sex chromosomes, X and Y. A person inherits one set of 23 chromo-somes from each parent. Occasionally, a genetic error occurs during egg or sperm cell formation. A child conceived with such an egg or sperm cell may inherit an incorrect number of chromosomes. (1, 4)

Clinical report

In last ten years, in our Center for human gene-tics, there have been registrated three cases of Sy Edwards, two boys and a girl. Boys had complete trisomy 18, while a girl had mosaic type of triso-my 18 – all died within first two months of life.

Trisomy 18 – Edwards’ syndromeTRISOMIJA 18 – EDWARDSOV SINDROMIzeta Aganovic-Musinovic, Mirela Djurovic, Zimka Seremet

Center for human genetics, Medical colleage of University of Sarajevo, Bosnia and Herzegovina

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Cytogenetics

Definitive diagnosis relies on karyotyping,which involves cytogenetic microscopic examina-tion of the chromosomes, using special stains for standard G-band examination.

Picture 1. Kariotype of child with trisomy 18

Picture 2. Normal kariotype

Basic symptoms of clinical report

Trisomy 18 severely affects all organ systems of the body. Symptoms may include:

1. Nervous system and brain – mental retarda-tion and delayed development (100% of individuals), high muscle tone, seizures, and physical malformations such as brain defects.

2. Head and face – small head (microcephaly), small eyes, epicanthal folds, small lower jaw.

3. Heart – congenital heart defects (90% of individuals) such as ventricular heart defect and valve defects.

4. Bones – severe growth retardation, clenched hands with 2nd and 5th fingers on top of theothers, and other defects of the hands and feet.

5. Malformations of the digestive tract, the urinary tract and genitals. (2)

Picture 3. Reviles typical pes equinovarus

Picture 4. Typical position of hand fingers (2.overlaps 3. and 5. overlaps 4.)

Picture 5. Low set position and unmodulated ears

In table are shown characteristic symptoms of trisomy 18, whereas can be seen the presence of symptoms at complete trisomy 18 and mosaic type of trisomy. Based upon shown data, it can be stated that in both cases are present anomalies in-compatible with life, but some symptoms more or less are not present in mosaic type of trisomy 18.

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Discussion

People with trisomy 18 have additional DNA from chromosome 18 in some or all of their cells. The extra material disrupts the normal course of development, causing the characteristic features of trisomy 18. (4)

Trisomy 18 results when each cell in the body has three copies of chromosome 18 instead of the usual two copies. A small percentage of cases oc-cur when only some of the body’s cells have an extra copy of chromosome 18, resulting in a mix-ed population of cells with a differing number of chromosomes. Such cases are sometimes called mosaic trisomy 18.

Table 1.

Symptoms Patient 1 (Trisomy 18)

Patient 2 (Trisomy 18)

Patient 3 (mosaic type 46 XX/47 xx*18)

Head:Dolichocephalism * - +

Microcephaly * - -Hypoplastic orbits - - -Microphtalmy * + -Corneal opacities - - -Insert nose base * + -Small mouth - - +Narrow, high palate * - -Microghnaty * + -Irregular formed ears * + +Extremities:-Typical position of hand (2. over 3., and 5. over 4. finger)

* + +

Hipoplasic nails * - - Born with * - +Prominent heels * - -Foot thumb in dosoflexy position - - -Syndactily * + -Other: Heart malformations (95%) * + +

Malformations of GIS * + -Kidney malformations * - - CNS malformations - + -Chryptorchysam * + -Hypoplastic large labia with hypertrophy of clitoris - - +

Short sternum * -Weakness and fragileness * + +Mental retardation * + +Partial hemi vertebra * * -

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Very rarely, a piece of chromosome 18 beco-mes attached to another chromosome (transloca-ted) before or after conception. Affected people have two copies of chromosome 18, plus extra material from chromosome 18 attached to another chromosome. With a translocation, the person has a partial trisomy for chromosome 18 and often the physical signs of the syndrome differ from those typically seen in trisomy 18. (3, 9)

Most cases of trisomy 18 are not inherited, but occur as random events during the formation of re-productive cells (eggs and sperm). An error in cell division called nondisjunction results in reprodu-ctive cells with an abnormal number of chromo-somes. If one of these atypical reproductive cells contributes to the genetic makeup of the child, the child will have an extra chromosome 18 in each cell of the body. (9)

Mosaic trisomy 18 is also not inherited. It oc-curs as a random error during cell division early in fetal development. As a result, some of the body’s cells have the usual two copies of chromosome 18, and other cells have three copies of the chro-mosome.

Translocation trisomy 18 can be inherited. An unaffected person can carry a rearrangement of genetic material between chromosome 18 and another chromosome. This rearrangement is cal-led a balanced translocation because there is no extra material from chromosome 18. People who carry this type of balanced translocation are at an increased risk of having children with the condi-tion. (2)

Before birth, ultrasound can detect abnormali-ties in the fetus. (7) Genetic testing by amniocen-tesis before birth or blood testing after birth can confirm the diagnosis. (10)

Conclusion

Since trisomy 18 babies frequently have major physical abnormalities, doctors and parents face difficult choices regarding treatment. Abnormali-ties can be treated to a certain degree with surgery, but extreme invasive procedures may not be in the best interests of an infant whose lifespan is measu-red in days or weeks, so is questionable their use. (5). Medical therapy is basically supportive care with the goal of making infant comfortable, rather than prolonged life.

Most children born with trisomy 18 die within their first year of life. The average lifespan is lessthan two months for 50% of the children, and 90-95% dies before their first birthday. 5% of the chil-dren who survive their first year are severely men-tally retarded. (10) They need support to walk, and learning is limited. Verbal communication is also limited, but they can learn to recognize and inte-ract with others. (1, 8)

Without questioning ethical, population, euge-nic and disgenetic discussions, we would conclu-de that genetic information is equal part of child medical care and protection.

The way of improvement and protection of hu-man health is antenatal reveal of inherited disea-ses. Modern medicine is using several methods to achieve this. These methods are: physical (exami-nation of pregnant women, ultrasound, fetoscopy or amniscopy and amniocentesis. Close related to these are physico-chemical methods. Cytogenetic methods have special place and significant impor-tance as a base for genetic consulting and infor-ming in this field.

The main cause for this kind of information is not just to prevent having the affected child or to prevent having the infant with inherited mal-formations, but to make possible to all parents, especially those from families with risk, to have healthy child.

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Literature

1. Julia Barrett, Gale Encyclopedia of Medicine, De-cember 2002, (updated 14. 08. 2006.)

2. Chen, H, (2004). Trisomy 18. eMedicine, accessed at http://www.emedicine.com/ped/topic 652.htm (updated may 2, 2004.)

3. Cassidy, Suzanne B; Allanson, Judit E; Manage-ment of genetic syndromes; 2nd ed; Hooboken, N.J.: John Wiley & Sons, c2005. NLM Catalog.

4. Chen CP, Chern SR, Tsai FJ, Lin CY, Lin YH, Wang W. A comparation of maternal age, sex ratio and associated major anomalies among fetal trisomy 18 cases among different cell divison of error. Prenat Diagn. 2005 Apr; 25 (4):327-30. PubMed citation.

5. Graham EM, Bradley SM, Shirali GS, Hills CB, Atz AM; Pediatric cardiac Care Consortium. Effecti-veness of cardiac surgery in trisomies 13 and 18 (from the Pediatric Cardiac Care Consortium). Am J Cardiol. 2004 Mar 15;93(6):801-3. PubMed cita-tion.

6. Huether CA, Martin RL, Stoppelman SM, D’Souza S, Bishop JK, Torfs CP, Lorey F., et al. Sex ratios in fetuses and liveborn infants with autosomal aneu-ploidy. Am J Med Genet. 1996 Jun 14;63(3):492-500. PubMed citation.

7. Moyano D, Huggon IC, Akkab KD. Fetal echocar-diography in trisomy 18. Arch Dis Child Fetal Neo-natal Ed. 2005 Nov; 90(6);F520-2. Epub 2005 May 24. PubMed citation.

8. Petek E, Pertl B, Tschernigg M, Bauer M, Mayr J, Wagner K, Kroisel PM. Characterisation of a 19-year old «long-term survivor» with Edwards syn-drome. Genet Couns. 2003,14(2);239-44. PubMed citation.

9. Ramesh KH, Verma RS. Parental origin of the extra chromosome 18 in Edwards syndrome. Ann Genet. 1996;39(2):110-2. PubMed citation.

10. Rasmussen SA, Wong LY, Yang Q, May KM, Frie-dman JM. Population-based analyses of mortali-ty in trisomy 13 and trisomy 18. Pediatrics. 2003 Apr;111(4 Pt 1):777-84. PubMed citation.

Corresponding author: Izeta Aganovic-Musinovic Center for human genetics, Medical colleage of University of Sarajevo, Bosnia and Herzegovina e-mail: [email protected]

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Summary

Increased incidence of chronic mass noninfecti-ous diseases such as hypertensive disease, diabetes mellitus and malignant neoplasms has been obser-ved during the last five years in Canton of Sarajevo.Malignant diseases in 2004 accounted for 23,7% of all death causes among Canton of Sarajevo popu-lation. Aim of the study was to investigate the type and duration of malignant disease and the influenceof malignant disease on physical and mental health in patients with malignant disease in terminal sta-ge of the disease. This prospective, study has been conducted in one population group in Canton of Sa-rajevo area during the period from 2005-2006. This study included 400 subjects, age 18-65, in terminal stage of a malignant disease. This study showed that the most frequent neoplasms are respiratory and intrathoracic organs malignant neoplasms and digestive organs. Least present was malignant neo-plasms of bone and articular cartilage. Patients in terminal phase of malignant disease are not able to perform regular activities and most of the patients are not mobile. It can be concluded that patients with malignant disease are completely dependant on care from other persons and require efficient andeffective palliative care service which can be help-ful in relieving psychological disorders in terminal stage of the disease.

Key words: oncology patients, physical health, mental health

Sažetak

Na području Kantona Sarajevo se u posljednjih pet godina bilježi porast hroničnih masovnih ne-zaraznih oboljenja kao što su hipertenzivna obo-ljenja, dijabetes i maligne neoplazme. Maligne neoplazme su u 2004 činile 23,7% svih uzroka smrti stanovništva u Kantonu Sarajevo. Cilj rada je bio ispitati vrstu i dužinu trajanja malignog oboljenja, kao i uticaj malignog oboljenja na tje-lesno i duševno zdravlje onkoloških bolesnika u terminalnom stadiju bolesti Studija je prospekti-vna, populaciona sa jednom grupom ispitanika. U studiju je uključeno 400 ispitanika u dobi od 18 do 65 godina koji boluju od maligne neoplazme u terminalnom stadiju bolesti Istraživanje je sprove-deno na području kantona Sarajevo u 2005 i 2006 godini putem anketnog upitnika za ispitivanje pa-lijativne njege. U ovoj studiji je utvrđeno da su najzastupljenije maligne neoplazme respiratornog trakta i digestivnog trakta. Najmanje oboljelih je bilo sa malignim neoplazmama kostiju i zglobne hrskavice.

Onkološki bolesnici u terminalnoj fazi bolesti nisu u mogućnosti da obavljaju umjerene kućne aktivnosti i velika većina onkoloških bolesnika nije pokretna. Možemo zaključiti da su onkološki bolesnici u terminalnoj fazi bolesti potpuno ovi-sni o njezi drugih lica. Takvi bolesnici zahtijevaju i njegu palijativne službe koja svojom efektivno-šću i efikasnosću uveliko može da ublaži psiho-

Influence of malignant diseaseon physical and mental health in patients with oncology diseaseUTICAJ MALIGNOG OBOLJENJA NA TJELESNO I DUŠEVNO ZDRAVLJE ONKOLOŠKIH BOLESNIKAAmela Dzubur1, Dragana Niksic1, Esad Pepic2, Amna Pleho Kapic2

1 Department of social medicine, Medical Faculty, University of Sarajevo, Bosnia and Herzegovina2 Department of pathophysiology, Medical Faculty, University of Sarajevo, Bosnia and Herzegovina

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loške potrebe onkoloških bolesnika u terminalnoj fazi bolesti.

Ključne riječi: Onkološki bolesnici, fizičkozdravlje, mentalno zdravlje

Introduction

Increased incidence of chronic mass noninfe-ctious diseases such as hypertensive disease, dia-betes mellitus and malignant neoplasms has been observed during the last five years in Canton of Sa-rajevo. Malignant diseases in 2004 accounted for 23,7% of all death causes among Sarajevo Kan-ton population. Incidence of death caused by ma-lignant disease was 2,1‰ , while there were 846 deaths caused by malignant disease (1).

Patients with oncology disease, especially in the terminal stage of the disease, usually experi-ence psychological disorders and not just physical disorders related to presence of the tumor.

Physical disorders in patients with malignant disease can be caused by the presence of the tumor, related to the treatment and/or invalidity caused by the tumor and other disorders, among which usually are pain, nausea, insomnia, vomiting and others. Many patients together with their family members are faced with problems of psychologi-cal origin. Most common psychological disorders are worry, sadness, nervousness, sleep disorders, irritability and lack of concentration (2, 3, 4, 5).

Aim of the study

Aim of the study was to investigate the type and duration of malignant disease and the influ-ence of malignant disease on physical and mental health in patients with malignant disease in termi-nal stage of the disease.

Subjects and work method

This prospective, population study has been conducted in Canton of Sarajevo area during the period from 2005-2006. This study included 400 subjects, age 18-65, in terminal stage of a mali-gnant disease. Subjects were selected randomly

with insight in evidence of patients with oncology disease receiving palliative care in ambulance for palliative care “Jablanička” in Canton of Sarajevo. International questionnaire for palliative care, de-signed in accord with World Health organization methodology, was used. All patients gave formal consent for participating in the study.

Results

This study included 400 patients, 194 females (48,5%) and 206 males (51,5%). Average age was 65,1 years (SD =11.9566; M=67,000). Most pati-ents (54,14%) belonged to age group older than 65 years (females 65,16%; males 53,17%), while 24,31% of patients belonged to age group 55-65 years (female 25,5%, male 23,4%). There was a decrease in incidence of malignant disease as the age decreased so in the age group 45-54 years be-longed 15,7% of patients (females 13%; males 17%), in age group 35-44 years 4,7% patients (fe-males 4%; males 5%), in age group 25-34 years there were 0,75% of patients (females 3; male 0), and in the age group 18-24 years there were 0,25% patients (female 0; male 1)(Graph 1). There was no statistically significant difference in sex betw-een the age groups, but significant difference wasfound in age groups incidence (p<0,05).Average income in a family was 1014,68 KM (SD=704,5; M=800,00KM). Patients spent in average 337,7 KM for the treatment (SD=398,6; M=312,5).

Graph 1. Age structure of oncology patients

Investigating the type of malignant disease it was found that 32% of patients had malignant ne-oplasms of respiratory and intrathoracic organs and 30% of patients had malignancy of digestive organs (Table1).

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It was found that incidence of malignant disea-se is greatest after the age of 45 years. Decrease in malignant neoplasm incidence related to older age

group has been observed in case of pharynx, oral and lymphoid tissue malignancy. Increased inci-dence of other malignancy types was associated

Table 1. Patient with different types of malignant disease grouped by International malignant disease classification No=number of patients

International disease

classificationNo %

1. Malignant neoplasms of lip, oral cavity and pharynx2. Malignant neoplasms of digestive organs3. Malignant neoplasms of respiratory and intrathoracic

organs 4. Malignant neoplasms of bone and articular cartilage 5. Melanomas and other skin neoplsms 6. Malignant neoplasms of mesothelial and soft tissue 7. Breast malignant neoplasms 8. Malignant neoplasms of female genital organs9. Malignant neoplasms of male genital organs10. Malignant neoplasms of urinary tract11. Malignant neoplasms of eye, brain and other parts of

central nervous system 12. Malignant neoplasms of thyroid and other endocrine

glands 13. Malignant neoplasms of ill-defined, secondary and

unspecified sites14. Malignant neoplasms, stated or presumed to be primary, of

lymphoid, haematopoietic and related tissue 15. Malignant neoplasms of independent (primary) multiple

sites

1 13 3,32 120 30,03 130 32,04 8 2,05 4 1,07 25 6,38 28 7,09 11 2,810 26 6,511 19 4,812 7 1,813 8 2,014 2 0,5Σ 400 100,0

Table 2. Malignant disease type in accord with Interantional malignant disease classification (IMCD)in relationship with the disease duration (No=number of patients)

IMDC Up to 6 months 6-12 months 1-2 years 2-5 years 5 years and more

No % No % No % No % No %1 0 0 7 5,47 5 4,95 1 1,06 0 02 7 21,21 38 29,69 36 35,65 30 31,92 9 20,933 17 51,52 37 28,90 29 28,71 31 32,98 14 32,554 0 0 5 3,91 3 2,97 0 0 0 05 0 0 1 0,78 0 0 2 2,13 1 2,337 1 3,03 13 10,16 4 3,96 5 5,32 2 4,658 1 3,03 8 6,25 5 4,95 9 9,58 5 11,639 2 6,06 7 5,47 1 0,99 1 1,06 0 010 2 6,06 6 4,69 9 8,91 5 5,32 4 9,3011 1 3,03 3 2,34 5 4,95 3 3,19 7 16,2812 1 3,03 2 1,56 1 0,99 3 3,19 0 013 1 3,03 1 0,78 3 2,97 3 3,19 0 014 0 0 0 0 0 0 1 1,06 1 2,33Σ 33 10,7 128 32 101 25,2 94 8,5 43 10,7

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with older age group. Most common malignant neoplasm in female patients was in digestive or-gans (36,7%), followed by malignant neoplasm of respiratory and intrathoracic organs (21,7%), and breast (11,9%). Most common malignant ne-oplasm in male patients was malignant neoplasms of respiratory and intrathoracic organs (41,7%), followed by malignant neoplasm of digestive or-gans (24,7%) and malignancies of urinary tract (10,2%). Most patients reported that the time span from fist symptoms appearance to the examinationday was 6-12 months (32%), and only 8,5% of pa-tients reported time span of 2-5 years (Table 2).

Investigating the influence of malignant diseaseon physical health, a statistically significant num-ber of patients (80%) reported that malignant dise-ase was restricting them in doing everyday activi-ties such as home chores, kneeling etc. (p<0,05). Statistically significant number of patients (73%)

reported that malignant disease restricted mobili-ty (p<0,01) and 52% of patients reported that the disease enabled them to bath and dress alone (p<-0,05), many (42%) reported on impossibility to sit alone (p<0,05), and 47% of patients reported that the disease disallowed feeding by the patients alone (p<0,05), and significant number of patients(52,7%) were not able to go to the bathroom alone (p<0,05) (Table 3).

Malignant disease was cause of psychological disorders in many patients It was found that among numerous psychological disorders, most common were fear of death and pain found in 75,3% of pa-tients, followed by worry and anxiety reported by 65% of patients, depressive mood was found in 52,7% of patients while least reported psychologi-cal disorder was aggressive behavior found in just 7,0%of patients (Table 4).

Table 3. influence of malignant disease on physical health of oncology patients (No=number of patients)

ActivityYes, very restricting Yes, partly Not restricting

No % No % No %

Moderate activity (cleaning, vacuum-cleaning)

320 80, 0 71 17,7 9 2,2

mobility around the house 291 73,7 81 20,2 28 7,0

bathing, dressing 211 52,7 180 45,0 9 2,2

sitting 170 42,5 163 40,7 67 16,7

Self feeding 190 47,5 99 24,7 111 27,7

Bathroom habits 211 52,7 164 41 25 6,2

Table 4. Influence of malignant disease on psychological reaction presence in oncology patients;(No=number of patients)

Psychological reactionsvery often sometimes seldom never

No % No % No % No %

Very moody, sad, blue 215 52,7 65 16,2 53 13,2 71 17,7

Worried, anxious 260 65,0 96 24,0 32 8,0 12 3,0

Fear of pain, death 301 75,3 32 8,0 61 15,2 6 1,5

Guilt 56 14,3 151 37,7 121 30,0 72 18,0

Aggressive, angry 28 7,0 37 9,2 201 50,3 134 33,5

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Investigating the influence of malignant diseaseon invalidity it was found although not significantthat 35% of patients reported invalidity. No signi-ficant difference was found between the sexes. Si-gnificant number of patients 50,7% reported sleepdisorders (p<0,05). Most common cause of sleep disorder was pain (85,7%) and difficulty in breat-hing (12,1%). Analyzing psychological reactions, 64 (16,1%) patients reported experiencing rage or anger during the disease, while wish to talk was reported by 177 (44%) patients. All patients who belonged to age groups 18-24 years and 25-34 years experienced both range and anger and also wish to talk. Out of patients who expressed anger during the disease, 46% belonged to age group 46-54 years. Greatest percentage of patients who ex-pressed whish to talk belonged to age group older than 65 years.

Using the regression coefficient it was found asignificant positive correlation between psycholo-gical reactions such as anger and rage and the time waited for home visit by a nurse or a doctor (r=-0,21, p<0,05). A significant negative correlationwas found between psychological reactions such as anger and rage and satisfaction with palliative care (r=-0,166, p>0,05), and between psychologi-cal reactions such as anger and rage and improve-ment in general state upon palliative care arrival (r=-1,98, p<0,05) (Table 5).

Analyzing the association between calls to the palliative care for patients physical disorders and symptoms relive no correlation was found using regression analysis between patients physical needs such as pain, difficulties in breathing, badappetite and decrease in symptoms of the disease upon the palliative care arrival (Table 6).

Table 5. Regression analysis coefficient between observed parameters in palliative care service andpsychological reaction such as anger and rage in patients with malignant disease

Coefficient t P

Waiting for home visit by doctor or nurse 0.210 2.717 0.007

Satisfaction with palliative care service -0.166 -2.112 0.036

Improvement in general state upon palliative care arrival -0.198 -2.666 0.008

Symptoms relieve 0.002 0.034 0.973

Table 6. Regression analysis coefficients between physical needs parameters and symptoms ease in patientswith malignant disease

Coefficient t P

Pain 0.042 0.660 0.510

Breathing difficulties 0.008 0.135 0.893

Bad appetite -0.074 -1.379 0.169

Elimination of feces and urine -0.042 -0.742 0.458

Maintains of hygiene 0.005 0.095 0.924

Sleep difficulties -0.017 -0.263 0.793

vomiting -0.072 -1.014 0.311

bleeding 0.062 0.903 0.367

restlessness 0.034 0.547 0.585

immobility -0.023 -0.405 0.685

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Discussion

According to the data from World Health Or-ganization, average life duration has increased, in Europe and other developed countries in the world, with more people living longer than 65 years (6). There are constantly more persons who die in old-er age from chronical diseases such as malignant neoplasms, causing large array of physical, psy-chological and social problems. Health care sys-tems need to be able to satisfy the needs of those patients easing the pain and giving the support to their families (7, 8, 9, 10).

In this study it was found that the great num-ber of patients (32%) is suffering from malignant neoplasms of respiratory and intrathoracic organs, and less percentage (30%) of patients are having malignant neoplasms of digestive organs. This study found that the most patients with malignant disease in terminal stage of the disease are experi-encing great restriction in physical activities caus-ing psychological disorders. In many patients ma-lignant disease enabled them to do house chores, kneel, independent movement, bathing and dress-ing, feeding. Among leading psychological reac-tions are fear of pain and death, worry, anxiety, depressive moods and sleep disturbances.

Similar psychological reactions were found by Wong et al. and other researchers, where most common psychological disorder were worry in 72% of patients, sadness in 67%, nervousness in 62%, sleep disturbances in 53%, irritability in 47%, and lack of concentration in 40% of patients (2, 3, 4, 5). Previous studies of palliative care have mostly been concentrated on patients with mali-gnant disease. Most attention was dedicated to the need for communication inside the family, and the help which health professionals can offer in order to overcome pain, anxiety and depression.

Pain is one of the symptoms causing the pa-tients and their family members to call a palliative care service. Other common symptoms are breath-ing difficulties, personal hygiene, depression, apa-thy, guilt or aggressiveness. Similar results found researchers in Great Britain, USA and Canada (11,12). Family members and fosters usually call for help and support in taking care of the patient and for overcoming anxiety and depression.

Our study showed that the efficiency of pallia-tive care was associated with psychological reac-tions such as anger and rage in patients with malig-nant disease. It is observed that the anger and rage were less frequent if the waiting time for nursing is less, if the patients are more satisfied with pal-liative care and if the patient’s general state is im-proved upon the palliative care arrival. Our study did not find any association between symptomsrelive and physical needs such as pain, breathing difficulties, lack of appetite and others for whichthe palliative care was called.

Conclusion

This study showed that the most frequent are respiratory and intrathoracic organs malignant neo-plasms and digestive organs. Least present was ma-lignant neoplasms of bone and articular cartilage.

Patients in terminal phase of malignant disease are not able to perform regular activities and most of the patients are not mobile. It can be concluded that patients with malignant disease are complete-ly dependant on care from other persons and re-quire efficient and effective palliative care servicewhich can be helpful in relieving psychological disorders in terminal stage of the disease.

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Literature

1. Zavod za javno zdravstvo Kantona Sarajevo, Stra-tegija razvoja zdravstva na Kantonu Sarajevo 2006-2015. Sarajevo, Novembar 2005.

2. Wong RKS, Franssen E, Szumacher E, Connolly R, Evans M, Page B, et al. What do patients living with advanced cancer and their carers want to know? A needs assessment. Support Care Cancer 2002;10: 408-15.

3. Glaser BG, Strauss AL. The discovery of grounded theory: strategies for qualitative research. New York: Adline Press, 1967.

4. Lincoln YS, Guba EG. Naturalistic inquiry. Beverly Hills: Sage, 1985.

5. Altheide DL, Johnson JM. Criterion for assessing interpretive validity in qualitative research. In: Denzin N, Lincoln Y, eds. Handbook of qualitative research. London: Sage Publishers, 1994: 485-99.

6. Paliative care- the solid facts.Copenhagen, WHO regional Office for Europe, 2004.

7. Why paliative care for older people is a public health priority. WHO regional Office for Europe,2004; 9-10

8. Higginson IJ. Public Health and palliative care. Geriatric Medicine, 2005;21(1): 45-55

9. Hinton J. A comparation of places and policies for terminal care. Lancet, 1979;29-32.

10. Sepulveda C et al. Palliative care: The World He-alth Organisations global perspective. Journal of Pain and Symptom Management, 2002; 24:91-96.

11. Aitken LH. Evaluation research and public policy: Lessons from the national hospice study. Journal of Chronic Desease, 1986;39:1-4.

12. Mc Carthy M, Lay M, Addington- Hall JM. Dying from Cancer disease. Journal of the Royal Colle-ge of Physicians, 1996;30:325-328.

Corresponding author: Amela Dzubur Department of social medicine, Medical Faculty, University of Sarajevo, Bosnia and Herzegovina e-mail: [email protected]

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About a book

Osteophorosis has been defined as a diseasecharacterized by low bone mass and micro archi-tectural deterioration of bone tissue leading to en-hanced bone fragility and a consequent increase in fracture risk. Many clinical, social and economic consequence are coming from those facts. Oste-ophorosis’ treatmants takes a lot of money inclu-ding expences for fractures treatment. Modern and adequate diagnosis helps in discovering disease on time, before fracture happens, which means make as less as possible of its costs. There is a good ways of a pre-vention of Ostephorosis like a good diagnosis and succeeds in treatmant of it. Therefore, it is a very important to raise a medical and public consciences about si-gnificance of Osteophorosis, sowe can reduce clinical, social and economic consequences.

A book, has been wrote in a monography style. With all in-clusive detials this book very successfuly presenting Osteo-phorosis as a disease for a con-temporary human and a society in general. Authors have been choosen for all relevant facts abo-ut Osteophorosis including a dia-

Book preview

Osteophorosis, how prevent and how treat itOSTEOPOROZA, KAKO SPRIJEČITI, KAKO LIJEČITIDijana Avdic, Edin Buljugic

KCU Sarajevo, Bosnia and Herzegovina

gnosis. They paid a special attention to measures of prevetion and its treatment. Book has been written using a very simple and understandable language, so it is easy to read for everyone. Besides essence facts, authors are using theirs own experinces in ex-plaining things. They believed that the most impor-tant part in all way of procedure of a disease lie in identification of a “risk” group because it helps verymuch in prevention. Text has been illustarted by ta-bles and pictures, which are so clear and original made. This book containes precious informations for the good of the service for doctors from general

practitioner and family me-dicals and others specialists to students of medicine, sto-matology, pharmacology as much as to a people who are willing to take care of theirs health by preventing a dise-ase also called “a quite thief of the bones”.

The book will take place in a medical library of a do-mestic authors, which is in our country kind of an em-pty place. Readers will findinformations on a questions given in an ordinary life and in a medical practice, as well.

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O knjizi

Osteoporoza je najčešće metaboličko oboljenje koštanog tkiva karakterizirano poremećenom gu-stoćom kosti i povećanim rizikom za prelom kosti, a iz čega proizilaze kliničke, socijalne i ekonom-ske posljedice osteoporoze. Troškovi tretmana osteoporoze i osteoporotskih preloma su znatni. Savremena dijagnostika omogućava pravovre-meno otkrivanje bolesti, prije nastanka preloma, a time i intervenciju koja zahtjeva znatno manje materijalne troškove. Osteoporoza je bolest koju je danas moguće prevenirati, dijagnosticirati i uspješno liječiti. Stoga je važno podići svijest me-dicinskih profesionalaca i javnosti o značaju ove bolesti kako bi se umanjile njene kliničke, soci-jalne i ekonomske posljedice, a time direktni i in-direktni troškovi nastali tokom zbrinjavanja ovih bolesnika.

Knjiga, u vidu monografije, je uspjela da sve-obuhvatno prezentira osteoporozu kao bolest zna-čajnu za savremenog čovjeka i društvo u cjelini. Autori su odabrali sve relevantne podatke o oste-oporozi, dijagnostici oboljenja, a posebno su po-svetili pažnju mjerama prevencije i liječenja. Sva poglavlja su obrađena iscrpno i kompetentno, na vrlo jednostavan i razumljiv način, tako da knjigu mogu čitati svi. Pri tome se autori služe relevan-tnim podacima iz literature, ali i vlastitim iskustvi-ma. Najveću nadu polažu u identifikaciji “rizične”grupe, jer će se na taj način moći poduzeti mjere prevencije. Tekst je ilustriran tabelama i slikama koje su vrlo pregledne i originalne.

Ova knjiga sadrži dragocjene informacije po-trebne ljekarima, kako opšte i porodične medicine, tako i onima različitih usmjerenja i specijalnosti, studentima medicine, stomatologije, farmacije, osobama koje žele sačuvati svoje zdravlje preve-nirajući oboljenje, pacijentima koji već imaju ovo oboljenje i drugim zainteresiranima. Knjiga će po-puniti literaturu o osteoporozi, koja je kod nas više nego skromna, a čitaoci će naći u njoj informacije i odgovore na pitanja koja se postavljaju u svako-dnevnom životu i medicinskoj praksi.

Corresponding author: Dijana Avdic KCU Sarajevo, Bosnia and Herzegovina, e-mail: [email protected]

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Every sent magazine gets its number, and author(s) will be notified if their paper is accepted and what is thenumber of paper. Every corresponedence will use that number. The paper has to be typed on a standard size pa-per (format A4), leaving left margins to be at least 3 cm. Ali materials, including tables and references, have to be typed double-spaced, so one page has no more than 2000 alphanumerical characters (30 lines). Sent paper needs to be in the form of triplicate, considering that original one enclosure of the material can be photocopied. Presenting paper depends on its content, but usually it consists of a page title, summary, text references, legends for pictures and pictures. Type your paper in MS Word and send if on a diskette or a CD-ROM.

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Svaki upućeni časopis dobija svoj broj i autor(i) se obavještavaju o prijemu rada i njegovom broju. Taj broj koristit će se u svakoj korespondenciji. Rukopis tre-ba otipkati na standardnoj veličini papira (format A4), ostavljajući s lijeve strane marginu od najmanje 3 cm. Sav materijal, uključujući tabele i reference, mora biti otipkan dvostrukim proredom, tako da na jednoj strani nema više od 2.000 alfanumeričkih karaktera (30 linija). Rad treba slati u triplikatu, s tim da original jedan pri-log materijala može biti i fotokopija. Način prezentacije rada ovisi o prirodi materijala, a (uobičajeno) treba da se sastoji od naslovne stranice, sažetka, teksta, referenci, tabela, legendi za slike i slika. Svoj rad otipkajte u MS Wordu i dostavite na disketi ili kompakt disku Redakcij-skom odboru, čime će te olakšati redakciju vašeg rada.

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