Medicinski arhiv ДЌ a s o p i s l jekara/lijeДЌnika bih • Godina 2009 • volumen 63 • broj 3 • Medical Archives journal of physicians of BiH • Year 2009 • Volume 63 • No 3 • ДЊasopis je indeksiran u bazama medline (www.pubmed.gov), ebsco (www.ebscohost.com) Nepoznati autor: Zimski pejsaЕѕ. i index copernicus (www.indexcopernicus.com) ISSN 0350-199 X Instructions for the Authors of the Journals “medical Archives” EDITORIAL BOARD Editor-In-Chief Izet Masic Secretary Alma Zejnilovic Technical editor Mirza Hamzic Lector Lejla Masic English lector Dubravko Vanicek MEMBERS OF EDITORIAL BOARD Sebija Izetbegovic (Sarajevo), Zdenka Krivokuca (Banja Luka), Sahib Muminagic (Zenica), Ljerka Ostojic (Mostar), Haris Pandza (Sarajevo), Enra SuljicMehmedika (Sarajevo), Selim Toromanovic (Bihac), Narcisa Vavra-Hadziahmetovic (Sarajevo), Muharem Zildzic (Tuzla) ADDRESS OF EDITORIAL BOARD Sarajevo, Cekalusa 90, Tel: 033 444 714, e-mail: avicena@lol.ba imasic@lol.ba www.avicenapublisher. org PUBLISHED BY Avicena d.o.o., Sarajevo, Zaima Sarca 43 Transakcijski racun: UNION banka Sarajevo, br.: 1020500000020077 SWIFT Code UBKSBA22, Deutsche Bank AG, Franfurt am Main (DEUTDEFF), Account No. 9365073 10 (EUR) Journal is indexed in MEDLINE (www.pubmed.gov) and EBSCO (www.ebscohost.com) All papers need to be sent electronically by web page: www.avicenapublisher.org : Print version and signed copyright form need to be sent by post to the Editorial board of journal Med Arh. 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UU Medical Archives Journal of BiH Physicians CONTENTS original papers 124Contact Network and Satisfaction with Contacts in Children Whose Parents Have Post Traumatic Stress Disorder Zihnet Selimbasic, Osman Sinanovic, Esmina Avdibegovic, Nemina Kravic 128EtioloЕЎke karakteristike akutnih infekcija mokraД‡nog sistema steДЌenih u zajednici kod odraslih hospitaliziranih bolesnika EDITORIAL BOARD Editor-In-Chief Izet Masic Secretary Alma Zejnilovic Technical editor Mirza Hamzic Lectors: Lejla Masic, Dubravko Vanicek MEMBERS OF THE BOARD Sebija Izetbegovic (Sarajevo, BiH), Izet Hozo (Split, Croatia), Zlatko Hrgovic (Franfurt, Germany), Zdenka Krivokuca (Banja Luka,BiH), Dragica Milinkic (Sydney, Australia), Sahib Muminagic (Zenica, BiH), Ljerka Ostojic (Mostar, BiH), Haris Pandza (Sarajevo,BiH), Enra SuljicMehmedika (Sarajevo,BiH), Selim Toromanovic (Bihac,BiH), Narcisa Vavra-Hadziahmetovic (Sarajevo,BiH), Muharem Zildzic (Tuzla,BiH), Adnan Zubovic (Oxford, UK) ADDRESS OF THE BOARD Sarajevo, Cekalusa 90, Tel: +387 33 444 714, e-mail: avicena@lol.ba www.avicenapublisher.org PUBLISHED BY Avicena d.o.o., Sarajevo, Zaima Sarca 43 Bank account: UNION banka Sarajevo, br.: 1020500000020077 SWIFT Code UBKSBA22, Deutsche Bank AG, Franfurt am Main (DEUTDEFF), Account No. 9365073 10 (EUR). IBAN BA 39 1020500000020077. Medical Archive journal is published five to six times per year (Feb, Apr, Jun, Oct, Dec). Subscription for individuals is 50 euros, for institutions 100 euros, and includes VAT and postal services. Journal is indexed in MEDLINE, EBSCO and INDEX COPERNICUS - ICV for 2008 is 5,22 Etiological Factors of Community Acquired Urinary Tract Infections in Hospitalized Patients Dilista PiljiД‡, Sead AhmetagiД‡, Dragan PiljiД‡, Muharem ZildЕѕiД‡, Humera PorobiД‡ 133Mikroalbuminurija i ultrazvuДЌne karakteristike bubrega u djece i adolescenata sa Dijabetes melitusom tip 1 Microalbuminuria and Ultrasound Characteristics of Kidneys in Children and Adolescents with Diabetes Mellitus Type 1 Evlijana HasanoviД‡, Denijal TulumoviД‡, Goran ImamoviД‡, Senaid TrnaДЌeviД‡ 137Colposcopic Changes Based on Number of Sexual Partners, Births, and Contraceptives Use Myrvete PaГ§arada, Shefqet Lulaj, Gyltene Kongjeli, Niltene Kongjeli, Hana Qavdarbasha, Bujar ObГ«rtinca 141Diagnostic Value of CEA in Pleural Fluid for Differential Diagnosis of Benign and Malign Pleural Effusion Tatjana Radjenovic-Petkovic, Tatjana Pejcic, Desa NastasijeviД‡-Borovac, Milan Rancic, Danijela Radojkovic, Milan Radojkovic, Ivanka Djordjevic 143Effects of Extracorporeal Shockwave Lithotripsy on Renal Vasculature and Renal Resistive Index (RI) Mustafa Hiros, Mirsad Selimovic, Hajrudin Spahovic, Sabina Sadovic 146AerozagaД‘enje i trend hospitalizacije djece zbog bronhoopstrukcije na podruДЌju Tuzlanskog kantona Air Pollution and Hospital Admission Trends of Children with Bronchial Obstruction in Tuzla Canton Devleta HadЕѕiД‡, Nada Mladina, Farid Ljuca, Mustafa BazardЕѕanoviД‡ 152Uticaj statina na postoperativni tretman pacijenata operiranih radi ugradnje aortokoronarnih premoЕЎtenja Effects of Statins on Postoperative Treatment of Patients After Aortocoronary Bypass Grafting Mehmed KuliД‡, Mirza DiliД‡, Vjekoslav Gerc, BeД‡ir HeljiД‡ 157Effectiveness of Diabetes Flow Sheet in Controlling Blood Pressure: Should Family Medicine Teams in Zenica Use Recommended Guidelines? Larisa Gavran, Olivera Batic-Mujanovic, Selmira Brkic, Sabina Nuhbegovic 160Collective Immunity of the Population from Endemic Zones of Hemorrhagic Fever with Renal Syndrome in Kosovo Sefedin MuГ§aj, Serbeze Kabashi, Salih Ahmeti, Isuf Dedushaj, Naser Ramadani, Tatjana Avsic-Zupanc professional papers 163LijeДЌenje Hallux valgusa osteotomijom prve kosti metatarzusa po Krameru The Kramer Osteotomy in the Treatment of Hallux Valgus Sahib MuminagiД‡, Sanja DrljeviД‡, Amela GraniД‡, Tarik KapidЕѕiД‡, Mehmed KovaДЌeviД‡, Faruk HodЕѕiД‡ reviews 166Perkutane koronarne intervencije bez „on-site“ kardiohirurЕЎke potpore Percutaneous Coronary Interventions Without On-Site Cardiac Surgical Backup Zoran StajiД‡, Zdravko M. MijailoviД‡ 171Pineal Region Tumors – Neurosurgical Review Ivan Radovanovic, Kemal Dizdarevic, Nicolas de Tribolet, Tarik Masic, Sahib Muminagic case reports 174Management of a Comatose Patient with Multiple Intracranial Aneurysms Lessons Learned Kemal Dizdarevic, Vino Apok, Ibrahim Omerhodzic, Tarik Masic books review 177Medical Informatics In A United And Healthy Europe Contact Network and Satisfaction with Contacts in Children Whose Parents Have Post Traumatic Stress Disorder Contact Network and Satisfaction with Contacts in Children Whose Parents Have Post Traumatic Stress Disorder Zihnet Selimbasic1,3, Osman Sinanovic2,3, Esmina Avdibegovic1,3, Nemina Kravic1,3 Clinic for Psychiatry, University Clinical Center Tuzla, Bosnia and Herzegovina1 Clinic for Neurology, University Clinical Center Tuzla, Bosnia and Herzegovina2 Faculty of Medicine, University of Tuzla, Bosnia and Herzegovina3 Original paper SUMMARY Aim: The aim was to analyse contacts network and satisfaction with contacts among children of parents with post traumatic stress disorder (PTSD). Subject and methods: The sample consisted of 100 pupils (age 10 to 15) from two randomly chosen schools. Children were selected from general population, lived with both parents who have had war traumatic experiences. They agreed to participate in psychometric research. We divided them in two groups: observed (O) group of children (N=50) whose parents were showing symptoms of post traumatic stress disorder (PTSD) and control (C) group of children (N=50) whose parents did not show symptoms of PTSD (evaluated by Harvard trauma questionnaire – BiH version). Contact network was examined by a Map of Contact Network which includes contact and satisfaction with persons in close environment. In relation to gender representatives of fathers and mothers, sample was homogenous. Results: The most important persons in children whose parents are showing symptoms of PTSD were schoolmates (88,0%), home mate (86,0%), mother (72,0%), and father (2,0%). At children whose parents did not show symptoms of PTSD, most important persons were schoolmate (94,0%), mother (80,0%), brother (6,0%), grandfather (8,0%), and father (14, 0%). The most distinct disappointment in contacts in children with parents with PTSD symptoms were family, relatives and friends, in school and formal contacts (p<0,001). Conclusion: Children of parents who have had symptoms of post traumatic stress disorder (PTSD), the most important persons that they communicate were schoolmates and they had problem in communicating with fathers and males. According to satisfaction children whose parents suffered from PTSD were showing distinction in contacts with their families, relatives, schoolmates and formal contacts. Keywords: contact network, contact satisfaction, children, parents, post traumatic stress disorder 1. Introduction War and post war period brings many problems inside family, illness, lower standard rate disruption in family contacts etc. There are different circumstances that could disrupt traditional relationships and create confusion inside family. The development of individual in social environment is made of mutual interaction where external influence makes important factor in changes of development and it emphasized unity between individual and environment (1,2,3,4). Environmental factors and individual factors influence on relationships network through the life span (5). Parents, especially war veterans are usually overwhelmed by PTSD, what makes them difficult to recognize as well as to satisfy all family needs. The family represents basic spot and certain communication field which offer to any family member aid in confrontation, built of self esteem and self respect in facing with critical moments (6). Preoccupied with their war traumas, fears, anxiety and guilty feelings parents with PTSD became distant of family and for that 124 distance they accuse their family. Children are feeling unnoticed, detached with adults, especially fathers. Parents’ usually sacrifice their authentic contact with children and transfer it on appearance and clichГ© level rather to be floated with unpleasant feelings (7). With traumatization, interactions between parents and children is destroyed (8,9). 2. aim The aim of this study is to examine contact network and satisfaction with it in children whose parent’s show PTSD symptoms. 3. Methods In our examination we took 100 school age children (from 10 to 15 years old) from two randomly chosen elementary schools from Tuzla Canton area. The research was approved from Pedagogy and School Council of Tuzla Canton, and school boards confirmed testing approach. The research was done among children from 5. to 8. grade. Based on social map of school we took 150 children who have lived in complete family. From that number MED ARH 2009; 63(3) • ORIGINALNI ДЊLANCI / ORIGINAL PAPERS we include 120 children whose parents subscribe written approval for participating testing and fulfilled Harvard Trauma Questionnaire. Among 120 of children we discovered 50 whose parents have shown positive result in PTSD in HTQ scale (> 2.5) and we have chosen 50 children whose parents have not shown PTSD symptoms in HTQ scale (< 2.5). Conditions for parents to participate in research were: general population, previous traumatic experiences, show symptoms of posttraumatic stress disorder, no other psychical disturbances. Conditions for children to participate in research were: complete family, equal number of male and female participants, elementary school age (5-8 grade). Harvard Trauma Manual, BosniaHerzegovina Version (HTQ) HTQ-Version for Bosnia and Herzegovina, consisted of four parts: possible traumatic event, declaration for possible traumatic events, description of the most traumatic event, questions about head injuries, and questions about psychosocial disturbances caused by trauma. Results for PTSD and/or total score >2.5 is counted as „positive“for PTSD. Total score value represent intensity of PTSD and that result represent symptoms and functional status. Network contact map (10) is concerned to contact with persons who surround child and his/her satisfaction with those contacts. It measured contacts with the most important, important and les important persons, as well as important persons with weak contacts and their satisfaction with those contacts. Contacts are done in 1.) family, 2.) friends and neighbors, 3.) relatives, 4.) school, 5.) formal contacts. For significance testing we have used descriptive statistics. For performing of statistical evidences in research we have used program SPSS 10.0 for Windows. 4. Results In total sample, participants age 11-13 represent 86.0% and there were 46.0% girls and 40.0% boys. (ME=12.06, SDE=0.91 ), (MK=12.10, SDK=1.23) . According to number of family members the most of them live in family with 4-5 members and there is no statistically significant difference between groups (X2=6.27, df=4, p>0.05). Regarding number of siblings children Contact Network and Satisfaction with Contacts in Children Whose Parents Have Post Traumatic Stress Disorder The most important persons in contacts Groups in sample Children of parents Children of parents with PTSD without PTSD N % N % 44 88.0 47 94.0 43 86.0 43 86.0 36 72.0 40 80.0 30 60.0 33 66.0 21 42.0 29 58.0 7 14.0 4 8.0 6 12.0 3 6.0 5 10.0 4 8.0 1 2.0 7 14.0 2 4.0 6 12.0 Total p N% School mate 91 91.0 0.940 Domicile friend 86 86.0 1.000 Mother 76 76.0 0.745 Doctor 63 63.0 0.789 Grandmother from mother 50 50.0 0.165 Aunt 11 11.0 0.518 Brother 9 9.0 0.473 Grandfather 9 9.0 0.813 Father 8 8.0 0.105 Grandmother from father 8 8.0 0.310 * Contacts network map. Table 1. Distribution of participants according to contacts with the most important person and groups in sample on Contact Nework Map. Less important person in contacts Sister Teacher of mother language Brother Family friend Friend’s parents Uncle Principal Aunt Psychologist- pedagogue Policeman Groups in sample Children of parents Children of parents with PTSD without PTSD N % N % 17 34.0 23 46.0 13 26.0 14 28.0 15 30.0 11 2.0 15 30.0 10 20.0 11 22.0 14 28.0 13 26.0 9 18.0 14 28.0 8 16.0 10 20.0 11 22.0 8 16.0 11 22.0 11 22.0 8 16.0 Total N% 40 40.0 27 27.0 26 26.0 25 25.0 25 25.0 22 22.0 22 22.0 21 22.0 19 19.0 19 19.0 P 0.501 0.891 0.578 0.477 0.670 0.544 0.361 0.877 0.625 0.625 Table 2. Distribution of participants concerning contacts with less important persons and groups in sample of parents who shows symptoms of PTSD live in family with more siblings (X2=8.43, df=3, p<0.05) (p<0.05). According to contacts with the most important persons in total sample of children for 91.0% of them the most important person is school mate, domicile friend 86%, 76% mother, and only 8.0% children in total sample declare father as the most important person in their lives (Table 1). Important persons in contacts are: teacher (72.0%), father (70.0%), domicile friend (42.0%), nurse (38.0%) and friend’s parents (30.0%). In group of children whose parents did not show symptoms of PTSD important persons are teacher (74.0%), father (72.0%), nurse (42.0%), grandfather (40.0%) and friend’s parents (38.0%). Results shows that in group of children whose parents show symptoms of PTSD less important persons in contacts are sister (34.0%), brother (30.0%), neighbor family friend (30.0%), school principal (28.0%) and uncle (26.0%). In group of children whose parents did not show symptoms of PTSD les important persons is sister (46.0%), teacher of mother language (28.0%), friend’s parents (28.0%), aunt (22.0%) and psychologist- pedagogue Important persons, but with weak contacts Children of parents with PTSD N % 36 72.0 16 32.0 5 10.0 5 10.0 4 8.0 5 10.0 4 8.0 2 4.0 3 6.0 (22.0%). There was no statistically significant difference between children from group whose parents show symptoms of PTSD and those whose parents do not show symptoms of PTSD (Table 2). Important persons with weak contacts are relatives (32.0%), aunts (10.0%), school keeper (10.0%), family friend, displaced persons (10.0%), father (8.0%) and 72.0% of children have no answer. In group of children whose parents do not show symptoms of PTSD important persons with weak contacts were relatives (24.0%), aunts (18.0%), school keeper (16.0%), uncle (14.0%) and 84.0% of children have no answer. Among children of parents with PTSD symptoms and those children whose parents did not show symptoms of PTSD there was no statistically significant difference between groups (p>0.05). Important persons with weak contacts were relatives (28.0%), aunt (14.0%), school keeper (13.0%), family friend, displaced persons (8.0%), father (5.0%) and 72.0% have no answer (Table 3). Regarding satisfaction with contacts which make children of parents with PTSD symptoms were more unsatisfied with contacts which make with family, relatives, school as well as formal contacts (p<0.001) (Table 4). 5. Discussion Family system has significant influence on manifestation of PTSD symptoms and a person who suffers from PTSD shows inappropriate emotional reactions, withdrawal, social isolation from other family members (Williams and Williams, 1987; Sipprelle, 1994; Grupe u uzorku Children of parens without PTSD N % 42 84.0 12 24.0 9 18.0 8 16.0 7 14.0 2 4.0 1 2.0 3 6.0 / / Total P N% 78 78.0 28 28.0 14 14.0 13 13.0 11 11.0 7 7.0 5 5.0 5 5.0 3 3.0 No answer 0.630 Relatives 0.592 Aunt 0.445 School keeper 0.553 Uncle 0.518 Family friend 0.411 Father 0.320 School principal 0.750 Medical doctor 0.157 Stepbrother/ 3 6.0 / / 3 3.0 0.157 stepssister Table 3. Distribution of participants concerning contacts with important persons, but with weak contacts and groups in sample. MED ARH 2009; 63(3) • ORIGINALNI ДЊLANCI / ORIGINAL PAPERS 125 Contact Network and Satisfaction with Contacts in Children Whose Parents Have Post Traumatic Stress Disorder Groups in sample Children of parents with Children of parents Satisfaction with contacts PTSD without PTSD N % N % 35 70.0 50 100.0 Family s 15 30.0 / / 35 70.0 50 100.0 Relatives s 15 30.0 / / 38 76.0 48 96.0 Friends/neighbours s 12 24.0 2 4.0 35 70.0 49 98.0 School s 15 30.0 1 2.0 26 52.0 48 96.0 Formal contacts s 24 48.0 2 4.0 N=total number of children in group, s=satisfied, u=unsatisfied. P 0.001 0.001 cording to satisfaction with contacts they have, showed more unsatisfied in contacts they made in family, relatives, school, formal contacts. REFERENCES 1. 0.001 0.001 0.001 2. Table 4. Distribution of participants regarding satisfaction with contacts and groups in sample Daud et al, 2008). Our study has shown that in children whose parents suffer from PTSD symptoms groups of school friends, domicile peers and mother represented the most important persons and those were appropriate with developmental stage (2,15,16,17,18,19). Mother is still the most important family member. Very significant place presented mothers parents- grandmother and grandfather, what could be a part of cultural milieu and relationships. Some i mpor t a nt person s a re teacher, father, medical professionals, relatives and friends, but less important persons are siblings. Boys from traumatized families had more difficulties in communications with brothers and male persons in family (p<0.05). There was big percentage (78.0%) without any answer what could mean that children mostly communicate with persons in their nearest surrounding. Very weak contact was established with father as family member and we explain it with weak resonance and weak capacity for communication because of father’s traumatic experiences in which made him emotionally “stuck”, isolated and distanced, so children look confidence in communication with those persons who were capable to do that. This point up that relations and roles inside the family have been changed, but it could also be consequence of specific developmental ageearly adolescence. Our results are compliant with previous researches (14,20,21,22,23) that the most important persons in the age of latency and early adolescence are peers, parents, 126 school friends, teachers, siblings, cousins and close friends. It could be an “important social capital” for normal development and growing up. There were no significant difference between two groups in choosing the most important, important and less important persons with weak contacts (p>0.05), but children whose parents do not show PTSD symptoms had more frequency in contacts with the most important persons. Our study has shown that children whose parents had PTSD symptoms significantly more unsatisfied with contacts inside the family, relatives, school, friends/ neighbors and formal contacts comparing with children whose parents did not have PTSD symptoms (p<0.001). Our results are compatible with previous researches (7,9) which showed that relationship between parents and children were destroyed and that traumatised parents show up too little resonance for children. Many PTSD symptoms in parents are connected with interpersonal relationships like less interest for people and things around them, weak emotional expression and irritability (20,24,25). 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Filozofski fakultet, Univerzitet u Sarajevu, 2000. 20. Lauterbach D, Koch E, Porter K.The relationship between childhood support and later emergence of PTSD. Journal of Traumatic Stress, 2007;20(5):857-67. 21. NikoliД‡ S.ZaЕЎtita mentalnog zdravlja mladih.Medicinska naklada. Zagreb, 1993. 22. TadiД‡ N, Kraigher A. NeurotiДЌna reagovanja djece i omladine. Institut za mentalno zdravlje. IstraЕѕivaДЌki projekat. Medicinski fakultet, Beograd, 1988. 23. TadiД‡ N. Psihijatrija detinjstva i mladosti. NauДЌna KMD, Beograd, 2006. Instructions for the authors of the journal Medical Archives has to contain a list of 3 to 4 keywords Central part of the article Authentic papers contain these parts: introduction, goal, methods, results, discussion and conclusion. Introduction is brief and clear review of problem. Methods are shown so that interested reader is able to repeat described research. Known methods don’t need to be identified, it is cited (referenced). 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MED ARH 2009; 63(3) • ORIGINALNI ДЊLANCI / ORIGINAL PAPERS 127 EtioloЕЎke karakteristike akutnih infekcija mokraД‡nog sistema steДЌenih u zajednici kod odraslih hospitaliziranih bolesnika EtioloЕЎke karakteristike akutnih infekcija mokraД‡nog sistema steДЌenih u zajednici kod odraslih hospitaliziranih bolesnika Etiological Factors of Community Acquired Urinary Tract Infections in Hospitalized Patients Dilista PiljiД‡В№, Sead AhmetagiД‡В№, Dragan PiljiД‡ВІ, Muharem ZildЕѕiД‡Ві,Humera PorobiД‡В№ Klinika za infektivne bolesti, Univerzitetski kliniДЌki centar Tuzla, Bosna i Hercegovina1 Klinika za kardiovaskularne bolesti, Univerzitetski kliniДЌki centar Tuzla, Bosna i Hercegovina2 Medicinski fakultet Univerziteta u Tuzli, Bosna i Hercegovina3 Originalni ДЌlanak SAЕЅETAK EtioloЕЎki faktori infekcija mokraД‡nog sistema (IMS) steДЌenih u zajednici specifiДЌni su za Еѕivotnu dob, spol, sezonu, kompliciranost i kategoriju infekcije, a njihova prevalenca i osjetljivost na antimikrobne lijekove pokazuju geografsku varijabilnost i varijabilnost u vremenu. UzimajuД‡i u obzir ove ДЌinjenice provedeno je istraЕѕivanje kod 200 odraslih bolesnika sa akutnim IMS steДЌenim u zajednici, koji su zbog teЕѕine kliniДЌke slike i neuspjeЕЎnog ambulantnog lijeДЌenja hospitalizirani u Klinici za infektivne bolesti Tuzla, u dvogodiЕЎnjem periodu (2006. i 2007. godina). Dominantni etioloЕЎki faktori ovih infekcija su: E. coli (73,5%), Klebsiella spp. (8,5%), Proteus mirabilis (5,5%), Pseudomonas aeruginosa (4%) i Enterococcus faecalis (3%). E. coli je znaДЌajno ДЌeЕЎД‡i etioloЕЎki faktor IMS kod Еѕena, kompliciranog i nekompliciranog pijelonefritisa i cistouretritisa (P<0.0001). Nije naД‘ena statistiДЌki znaДЌajna razlika u uДЌestalosti izmeД‘u etioloЕЎkih faktora IMS u odnosu na dobne skupine bolesnika, godiЕЎnje doba i prostatitis (P>0.05). E. coli je senzitivna na Cefalosporine III generacije, Gentamycin, Nitrofurantoin, Norfloxacin, Ciprofloxacin i Pipemidinsku kiselinu (senzitivnost iznad 88,7%), Klebsiella spp. na Imipenem i Meropenem (senzitivnost 100%), Proteus mirabilis na Imipenem i Meropenem (senzitivnost 100%) i relativno na Amikacin (senzitivnost 81,8%), Pseudomonas aeruginosa na Imipenem (senzitivnost 100%) i Meropenem (senzitivnost 87,5%) i Enterococcus faecalis na Vancomycin (senzitivnost 100%) i relativno na Ampicillin, Amoxicillin, Ciprofloksacin, Doxyciclin i Nitrofurantoin (senzitivnost 83,4%). KljuДЌne rijeДЌi: EtioloЕЎke karakteristike, IMS, osjetljivost. Original paper SUMMARY Introduction: Etiological factors of community-acquired urinary tract infections (UTI) are specific for age, gender, season, complication of UTI and type of UTI. Their prevalence and susceptibility to antimicrobial agents shows geographic and time variability. Purpose: To evaluate etiological characteristics of acute communityacquired UTI in hospitalised patients. Patients and methods: This retrospective-prospective study included 200 adult patients with community-acquired UTI who were, in view of the serious clinical picture and unsuccessful ambulatory treatment, hospitalised in the Clinic for Infectious Diseases in Tuzla, for a period of two years (2006 and 2007). The data concerning the age, gender, season, complication of UTI and type of UTI were collected from the patient’s records. Urine analysis was done following standard microbiological methods, and the antibiogram was done following standard disc-diffusion method on the MГјeller-Hinton agar. Work results: The dominant etiological factors of UTI were: E. coli (73.5%), Klebsiella spp. (8.5%), Proteus mirabilis (5.5%), Pseudomonas aeruginosa (4.5%) and Enterococcus faecalis (3%). The predominant etiological factor of this UTI was E. coli (P<0.0001). E. coli was significantly more frequent etiological factor of UTI in females (P<0.0001). There was no significant difference in the frequency between etiological factors of UTI for different age groups of patients (P=0.173), or for different seasons (P>0.05). All etiological factors are significantly more frequent during warmer periods of the year (P<0.05). E. coli is a significantly more frequent etiological factor in complicated and non-complicated pyelonephrytis and cystourethritis (P<0.05), but there was no significant difference of frequency between etiological factors of prostatitis (P=0.7163). By analyzing the susceptibility for antimicrobials, we found that E. coli has good susceptibility for Cephalosporins of the third generation, for Gentamycin, Nitrofurantoin, Norfloxacin, Ciprofloxacin and Pipemidin acid (susceptibility higher than 88.7%), Klebsiella spp. for Imipenem and Meropenem (susceptibility 100%), Proteus mirabilis for Imipenem (susceptibility 100%) and relatively for Amikacin (susceptibility 81.8%), Pseudomonas aeruginosa for Imipenem (susceptibility 100%) and for Meropenem (susceptibility 87.5%) and Enterococcus faecalis for Vancomycin (susceptibility 100%) and relatively for Ampicillin, Amoxicillin, Ciprofloxacin, Doxicyclin and Nitrofurantoin (susceptibility 83.4%). Conclusion: Etiological characteristics of UTI are specific for different regions. Evaluation of these characteristics in our region is the basis for empirical antimicrobial therapy of UTI, which is necessary for a timely and successful treatment of UTI. Keywords: etiological characteristics, UTI, susceptibility 128 MED ARH 2009; 63(3) • ORIGINALNI ДЊLANCI / ORIGINAL PAPERS 1. UVOD EtioloЕЎki faktori infekcija mokraД‡nog sistema (IMS) steДЌenih u zajednici najДЌeЕЎД‡e su G-negativne bakterije iz porodice Enterobacteriaceae koje ДЌine fizioloЕЎku floru crijeva, a dobro rastu u mokraД‡i. Escherichia coli (E. coli) je etioloЕЎki faktor 70-80% ovih infekcija (1). Kod nekompliciranih IMS, E. coli je etioloЕЎki faktor 5090% ovih infekcija (2,3), dok je kod kompliciranih IMS, E coli je, takoД‘er, vaЕѕan etioloЕЎki faktor, ali se sa veД‡om uДЌestaloЕЎД‡u javljaju i druge G-bakterije: Proteus spp., Klebsiella spp., Enterobacter spp., Pseudomonas spp., Morganella spp., Citrobacter spp. i Acinetobacter spp. (2,4). Od G+bakterija faktora, Staphylococcus saprophyticus izaziva 5-15%, a u periodu kasnog ljeta i rane jeseni i do 40% nekompliciranih IMS donjeg dijela mokraД‡nog sistema kod mladih seksualno aktivnih Еѕena (2,5) i vodeД‡i je etioloЕЎki faktor ovih infekcija u SAD, Kanadi i skandinavskim zemljama, dok je u nekim zemljama rijedak, samo 0,9% (6). Staphylococcus aureus je najДЌeЕЎД‡i uzroДЌnik intrarenalnog i perinefritiДЌkog apscesa (7), dok izolacija Staphylococcus epidermidis u mokraД‡i najДЌeЕЎД‡e predstavlja kontaminaciju mokraД‡e, a samo rijetko moЕѕe znaДЌiti IMS vezanu za mokraД‡ni katater. Enterococcus faecalis je ДЌeЕЎД‡e povezan sa kompliciranim IMS, dok Streptococcus agalactiae ДЌesto kolonizira genitalno podruДЌje i kontaminira mokraД‡u, a rijetko uzrokuje IMS (8). Candida albicans je najДЌeЕЎД‡i etioloЕЎki faktor gljiviДЌnih IMS kod bolesnika sa kamencima u mokraД‡nom sistemu, kod kateteriziranih bolesnika u jedinicama intenzivne njege i kod pacijenata koji su dugo tretirani antimikrobnim lijekovima (9). Adenovirusi su ДЌesti etioloЕЎki faktori hemoragiДЌnog cistitisa kod djece i primalaca alogenog transplantata (7). DosadaЕЎnji rezultati istraЕѕivanja pokazuju da je prevalencija dominantnih etioloЕЎkih faktora IMS razliДЌita u odnosu na spol i dob bolesnika, sezonu, kompliciranost i kategoriju IMS. Mikrobna osjetljivost uzroДЌnika IMS je smanjena zbog poveД‡ane i ДЌesto neracionalne upotrebe i poveД‡anja antimikrobne rezistencije. EtioloЕЎki faktori IMS u odnosu na navedene parametre pokazuju geografsku varijabilnost i varijabilnost u vremenu, te autori istiДЌu potrebu kontinuirane evaluacije ovih faktora (3,10). EtioloЕЎke karakteristike akutnih infekcija mokraД‡nog sistema steДЌenih u zajednici kod odraslih hospitaliziranih bolesnika rentnim IMS i bolesnici kod kojih nije uraД‘en antibiogram. Analizirana je uДЌestalost etioloЕЎkih faktora IMS kod ovih bolesnika u odnosu na spol, Еѕivotnu dob, godiЕЎnje doba, kompliciranost 3. PACIJENTI I METODE RADA IMS i kategoriju IMS. Retrospektivno-prospektivnim istra- Analizirana je osjetljiЕѕivanjem obuhvaД‡eno je 200 odraslih bo- vost dominantnih etilesnika sa akutnim IMS steДЌenim u za- oloЕЎkih faktora IMS na jednici, koji su zbog teЕѕine kliniДЌke slike i antimikrobne lijekove. GRAFIKON 1. Dominantni etioloЕЎki faktori akutnih infekcija mokraД‡nog sistema steДЌenih u zajednici kod hospitaliziranih bolesnika neuspjeЕЎnog ambulantnog lijeДЌenja hos- Svi podaci prikupljani pitalizirani u Klinici za infektivne bole- su iz dostupnih historija sti Tuzla u dvogodiЕЎnjem periodu (2006. bolesti. Urinokultura je raД‘ena standar- 4. REZULTATI i 2007. godina). Svim bolesnicima je po- dnim mikrobioloЕЎkim metodama, a anE. coli kao etioloЕЎki faktor akutnih tvrД‘ena IMS na osnovu kliniДЌke slike, tibiogram standardnom disk-difuzio- IMS steДЌenih u zajednici registrirana je laboratorijskih, radioloЕЎkih, sonograf- nom metodom na MГјeller-Hinton agaru kod 147 (73,5%) hospitaliziranih boleskih i endoskopskih pretraga, kod svih u Zavodu za mikrobiologiju UKC Tuzla. snika. Ne-E. coli etioloЕЎki faktori su reKoriЕЎten je program za statistiДЌku gistrirani kod 53 (26,5%) hospitalizirana je dokazana signifikantna bakteriurija (prema uputama Evropskog udruЕѕenja obradu podataka Arcus Quickstat Bio- bolesnika. E. coli je statistiДЌki znaДЌajno urologa iz 2006. godine) ambulantno ili medical, Addison Wesley Longman Ltd, ДЌeЕЎД‡i etioloЕЎki faktor IMS u odnosu na do 48 sati od hospitalizacije i kod svih je 1997. Za testiranje statistiДЌke znaДЌajno- ne-E. coli etioloЕЎke faktore (P<0,0001). uraД‘en antibiogram. Iz istraЕѕivanja su sti razlike kvalitativnih podataka kori- Od ne-E. coli etioloЕЎkih faktora, po uДЌeiskljuДЌeni bolesnici koji su uz IMS imali ЕЎten je test proporcija. Pri testiranju hi- stalosti su sljedeД‡i: Klebsiella spp. 17 neku drugu akutnu infekciju, bolesnici sa poteza u svim proraДЌunima je konzi- (8,5%), Proteus mirabilis 11 (5,5%), Pseintrahospitalno-steДЌenim IMS, bolesnici stentno pretpostavljen nivo znaДЌajnosti udomonas aeruginosa 8 (4%), Enterocosa genitalnim infekcijama, bolesnici sa od 5% (P=0.05). ccus faecalis 6 (3%), Staphylococcus auasimptomatskom bakteriurijom i rekureus 3 (1,5%), Candida albicans i Salmonella enteritidis 2 (1%) i Streptococcus Spol agalactiae, Acinetobacter spp., EnteroЕЅenski spor MuЕЎki spol Ukupno EtioloЕЎki faktori bacter spp. i Mycobacterium tuberculon % n % n % sis 1 (0,5%) IMS. RaДЌunajuД‡i 95% interEscherichia coli 131 65,5 16 8,0 147 73,5 val povjerenja za proporciju oboljelih od Klebsiella species 14 7,0 3 1,5 17 8,5 E. coli IMS (95%CI: 0.72-0.74), utvrД‘eno Proteus mirabilis 9 4,5 2 1,0 11 5,5 je da je znaДЌajno veД‡i broj bolesnika sa Pseudomonas aeruginosa 4 2,0 4 2,0 8 4,0 E. coli IMS u odnosu na bolesnike sa neEnterococcus faecalis 3 1,5 3 1,5 6 3,0 E. coli IMS (P<0.0001). Dominantni etiOstali 10 5,0 1 0,5 11 5,5 oloЕЎki faktori ovih IMS prikazani su na Ukupno 171 85,5 29 14,5 200 100,0 Grafikonu 1. U odnosu na ukupan broj bolesnika TABELA 1. UДЌestalost dominantnih etioloЕЎkih faktora akutnih infekcija mokraД‡nog sistema steДЌenih u 200 (100%), registrirano je 131 (65,5%) zajednici u odnosu na spol hospitaliziranih bolesnika Еѕena i 16 (8%) muЕЎkaraca sa E. coli IMS, dok su infekcije sa ne-E. coli etioloЕЎkim Dob (godine) EtioloЕЎki faktorima u znatno manjem broju: 14 15-24 25-34 35-44 45-54 55-64 ≤65 Ukupno faktori (7%) Еѕena i 3 (1,5%) muЕЎkarca sa IMS (IMS) n % n % n % n % n % n % n % uzrokovanim Klebsiellom spp., zatim 9 Escherichia 35 17,5 8 4,0 21 10,5 24 12,0 22 11,0 37 18,5 147 100,0 (4,5%) Еѕena i 2 (1%) muЕЎkarca sa IMS coli uzrokovanim Proteus mirabilisom i daKlebsiella 4 2,0 2 1,0 1 0,5 3 1,5 3 1,5 4 2,0 17 8,5 lje 4 (2%) Еѕene i muЕЎkarca sa IMS uzrospecies kovanim Pseudomonas aeruginosom i 3 Proteus 2 1,0 1 0,5 0 0,0 2 1,0 0 0,0 6 3,0 11 5,5 mirabilis (1,5%) muЕЎkarca i Еѕene sa IMS uzrokovaPseudomonas 1 0,5 0 0,0 2 1,0 0 0,0 4 2,0 1 0,5 8 4,0 nim Enterococcus faecalisom. E. coli izaaeruginosa ziva ДЌeЕЎД‡e IMS kod Еѕena uz znaДЌajnost Enterococcus 1 0,5 0 0,0 1 0,5 0 0,0 2 1,0 2 1,0 6 3,0 razlike od P<0.0001. RaДЌunajuД‡i 95% infaecalis terval povjerenja za proporciju Еѕena sa E. Ostali 2 1,0 0 0,0 2 1,0 2 1,0 2 1,0 3 1,5 11 5,5 coli IMS (95%CI: 0.72-0.74), utvrД‘eno je Ukupno 45 22,5 11 5,5 27 13,5 31 15,5 33 16,5 53 26,5 200 100,0 da je u naЕЎem uzorku znaДЌajno veД‡i broj TABELA 2. UДЌestalost dominantnih etioloЕЎkih faktora akutnih infekcija mokraД‡nog sistema steДЌenih u Еѕena sa E. coli IMS P<0.0001. ДЊeЕЎД‡e su zajednici po dobnim skupinama hospitaliziranih bolesnika Еѕene sa Klebsiella spp. i Proteus mirabi2. CILJ ISTRAЕЅIVANJA Cilj istraЕѕivanja je evaluacija etioloЕЎkih karakteristika akutnih IMS steДЌenih u zajednici kod bolesnika hospitaliziranih u Klinici za infektivne bolesti Tuzla u dvogodiЕЎnjem periodu (2006. i 2007. godina). MED ARH 2009; 63(3) • ORIGINALNI ДЊLANCI / ORIGINAL PAPERS 129 EtioloЕЎke karakteristike akutnih infekcija mokraД‡nog sistema steДЌenih u zajednici kod odraslih hospitaliziranih bolesnika lis IMS, ali statistiДЌku razliku nismo dokazivali zbog malog broja bolesnika sa ovim infekcijama (tabela 1.). E. coli kao etioloЕЎki faktor IMS registrirana je u najveД‡em broju u dobnoj skupini 65 i viЕЎe godina kod 37 (18,5%) bolesnika, zatim u dobnoj skupini od 15-24 godine kod 35 (17,5%) bolesnika, u dobnoj skupini 45-54 godine kod 24 (12%) bolesnika, u dobnoj skupini od 55-64 godine kod 22 (11%) bolesnika, u dobnoj skupini od 35-44 godine kod 21 (10,5%) bolesnika i najmanje u dobnoj skupini od 25-34 godine, kod 8 (4%) bolesnika. Ne-E. coli etioloЕЎki faktori IMS u najveД‡em broju su registrirani u dobnoj skupini 65 i viЕЎe godina kod 16 (8%) bolesnika, zatim u dobnoj skupini od 5564 godine kod 11 (5,5%) bolesnika, u dobnoj skupini 15-24 godine kod 10 (5%) bolesnika, u dobnoj skupini 45-54 godine kod 7 (3,5%) bolesnika, u dobnoj skupini od 35-44 godine kod 6 (3%) bolesnika i najmanje u dobnoj skupini od 25-34 godine kod 3 (1,5%) bolesnika. Ne postoji statistiДЌki znaДЌajna razlika u uДЌestalosti izmeД‘u E. coli i ne-E. coli etioloЕЎkih faktora IMS u navedenim dobnim skupinama bolesnika (P=0.173) (tabela 2.). Rezultati istraЕѕivanja pokazuju da je E. coli kao etioloЕЎki faktor IMS u najveД‡em broju registrirana u proljeД‡e kod 56 (28%) bolesnika i ljeto kod 52 (26%) bolesnika, zatim u jesen kod 23 (11,5%) bolesnika i najmanje u zimskom periodu kod 16 (8%) bolesnika. UДЌestalost E. coli kao etioloЕЎkog faktora IMS u periodu proljeД‡e-ljeto kod 108 (54%) bolesnika je statistiДЌki znaДЌajno veД‡a od uДЌestalosti u periodu jesen-zima kada je registrirana kod 39 (19,5%) bolesnika (P<0.0001). Ne-E. coli etioloЕЎki faktori IMS, registrirani su u proljeД‡e kod 16 (8%) bolesnika, u ljeto kod 18 (9%) bolesnika, u jesen kod EtioloЕЎki faktori (IMS) Escherichia coli Klebsiella species Proteus mirabilis Pseudomonas aeruginosa Enterococcus faecalis Ostali Ukupno Komplicirane IMS Pyelonefritis Cistouretritis n % n % ProljeД‡e Ljeto Jesen Zima Ukupno EtioloЕЎki faktori (IMS) n % n % n % n % n % Escherichia 56 28,0 52 26,0 23 11,5 16 8,0 147 73,5 coli Klebsiella 5 2,5 10 5,0 2 1,0 0 0,0 17 8,5 species Proteus 2 1,0 3 1,5 4 2,0 2 1,0 11 5,5 mirabilis Pseudomonas 2 1,0 2 1,0 4 2,0 0 0,0 8 4,0 aeruginosa Enterococcus 2 1,0 1 0,5 2 1,0 1 0,5 6 3,0 faecalis Ostali 5 2,5 2 1,0 4 2,0 0 0,0 11 5,5 Ukupno 72 36,5 70 35,0 39 19,5 19 9,5 200 100,0 TABELA 3. UДЌestalost dominantnih etioloЕЎkih faktora akutnih infekcija mokraД‡nog sistema steДЌenih u zajednici kod hospitaliziranih bolesnika po godiЕЎnjim dobima Komplicirane IMS Nekomplicirane IMS n % n % 103 51,5 44 22,0 11 5,5 6 3,0 7 3,5 4 2,0 8 4,0 0 0,0 5 2,5 1 0,5 8 4,0 3 1,5 142 71,0 58 29,0 EtioloЕЎki faktori (IMS) Escherichia coli Klebsiella species Proteus mirabilis Pseudomonas aeruginosa Enterococcu faecalis Ostali Ukupno Ukupno % 73,5 8,5 5,5 4,0 3,0 5,5 100,0 TABELA 4. UДЌestalost dominantnih etioloЕЎkih faktora kompliciranih i nekompliciranih akutnih infekcija mokraД‡nog sistema steДЌenih u zajednici kod hospitaliziranih bolesnika 16 (8%) bolesnika, dok su u zimskom periodu registrirani samo kod 3 (1,5%) bolesnika. UДЌestalost ne-E. coli etioloЕЎkih faktora IMS u periodu proljeД‡e-ljeto kod 34 (17%) bolesnika je statistiДЌki znaДЌajno veД‡a od uДЌestalosti u periodu jesen-zima kada su registrirani kod 19 (9,5%) bolesnika (P=0.033) (tabela 3). U odnosu na ukupan broj bolesnika sa IMS, registrirano je 103 (51,5%) bolesnika sa kompliciranim IMS uzrokovanim E. coli, a 39 (19,5%) bolesnika sa kompliciranim IMS uzrokovanim ne-E. coli etioloЕЎkim faktorima. Registrirano je 44 (22%) bolesnika sa nekompliciranim Nekomplicirane IMS Prostatitis Pyelonephritis Cistouretritis n % n % n % Ukupno 59 29,5 35 17,5 9 4,5 12 6,0 32 16,0 147 73,5 5 2,5 4 2,0 2 1,0 1 0,5 5 2,5 17 8,5 3 1,5 3 1,5 1 0,5 1 0,5 3 1,5 11 5,5 2 1,0 4 2,0 2 1,0 0 0,0 0 0,0 8 4,0 3 1,5 0 0,0 2 1,0 0 0,0 1 0,5 6 3,0 5 77 2,5 38,5 3 49 1,5 24,5 0 16 0,0 8,0 2 16 1,0 8,0 1 42 0,5 21,0 11 5,5 200 100,0 TABELA 5. UДЌestalost dominantnih etioloЕЎkih faktora akutnih infekcija mokraД‡nog sistema steДЌenih u zajednici prema kategoriji infekcije kod hospitaliziranih bolesnika 130 n 147 17 11 8 6 11 200 MED ARH 2009; 63(3) • ORIGINALNI ДЊLANCI / ORIGINAL PAPERS IMS uzrokovanim E. coli, a 14 (7%) bolesnika sa nekompliciranim IMS uzrokovanim ne-E. coli uzroДЌnicima. Ne-E. coli etioloЕЎki faktori kompliciranih IMS su: Klebsiella spp. kod 11 (5,5%), Pseudomonas aeruginosa kod 8 (4%), Proteus mirabilis kod 7 (3,5%), Enterococcus faecalis kod 5 (2,5%) i ostali kod 8 (4%) bolesnika. Ne-E. coli etioloЕЎki faktori u nekompliciranim IMS su: Klebsiella spp. kod 6 (3%), Proteus mirabilis kod 4 (2%), Enterococcus faecalis kod 1 (0,5%) i ostali kod 3 (1,5%) bolesnika. RaДЌunajuД‡i 95% interval povjerenja za proporciju kompliciranih IMS (95%CI: 0.71-0.73) i nekompliciranih IMS (95%CI: 0.71-0.77) izazvanih E. coli, utvrД‘eno je da su proporcije ovih IMS znaДЌajno ДЌeЕЎД‡e nego proporcije istih IMS izazvanih ne-E. coli etioloЕЎkim faktorima. U svim sluДЌajevima proraДЌuna je P<0.05 (tabela 4). U odnosu na ukupan broj bolesnika sa IMS, E. coli je etioloЕЎki faktor kompliciranog pijelonefritisa kod 59 (29,5%) bolesnika, kompliciranog cistouretritisa kod 35 (17,5%) bolesnika, prostatitisa kod 9 (4,5%) bolesnika, nekompliciranog pijelonefritisa kod 12 (6%) bolesnika i nekompliciranog cistouretritisa kod 32 (16%) bolesnika, a ne-E. coli etioloЕЎki faktori kompliciranog pijelonefritisa kod 18 (9%) bolesnika, komplicira- EtioloЕЎke karakteristike akutnih infekcija mokraД‡nog sistema steДЌenih u zajednici kod odraslih hospitaliziranih bolesnika nog cistouretitisa kod 14 (7%) bolesnika, prostatitisa kod 7 (3,5%) bolesnika, nekompliciranog pijelonefritisa kod 4 (2%) bolesnika i nekompliciranog cistouretritisa kod 10 (5%) bolesnika. Proporcija sluДЌajeva kompliciranog i nekompliciranog pijelonefritisa i cistouretritisa izazvanim E. coli znaДЌajno je veД‡a od proporcije sluДЌajeva istih izazvanim ne-E. coli etioloЕЎkim faktorima. U svim sluДЌajevima proraДЌuna je P<0.05. Ne postoji statistiДЌki znaДЌajna razlika proporcija sluДЌajeva prostatitisa izazvanog E. coli i ne-E. coli etioloЕЎkim faktorima (P=0.7163) (tabela 5.). Analizom senzitivnosti dominantnih etioloЕЎkih faktora IMS na antimikrobna sredstva evidentno je da je E. coli dobro osjetljiva na Cefalosporine III generacije, Gentamycin, Nitrofurantoin, Norfloxacin, Ciprofloxacin i Pipemidinsku kiselinu (senzitivnost iznad 88,7%). Klebsiella spp. je dobro osjetljiva na Imipenem i Meropenem (senzitivnost 100%), Proteus mirabilis na Imipenem i Meropenem (senzitivnost 100%) i relativno na Amikacin (81,8%), Pseudomonas aeruginosa na Imipenem (senzitivnost 100%) i Meropenem (87,5%) i Enterococcus faecalis na Vancomycin (senzitivnost 100%) i relativno na Ampicillin, Amoxicillin, Ciprofloksacin, Doxyciclin i Nitrofurantoin (senzitivnost 83,4 %) (tabela 6.). 5. DISKUSIJA Od ukupno 200 hospitaliziranih bolesnika sa akutnim IMS steДЌenim u zajednici, 73,5% bolesnika imalo je E. coli-IMS ЕЎto je ДЌini predominantnim etioloЕЎkim faktorom IMS (P<0.0001). SljedeД‡i etioloЕЎki faktori po uДЌestalosti su: Klebsiella spp., Proteus mirabilis, Pseudomonas aeruginosa i Enterococcus faecalis, ЕЎto je saglasno sa rezultatima istraЕѕivanja drugih istraЕѕivaДЌa (3). E. coli znaДЌajno ДЌeЕЎД‡e uzrokuje IMS kod Еѕena, 131 (65,5%) u odnosu na muЕЎkarce, 16 (8%), (P<0.0001). Prema podacima iz dostupne literature kod muЕЎkaraca su akutne IMS, naroДЌito akutni prostatitis najДЌeЕЎД‡e uzrokovane E. coli, a zatim slijede Klebsiella pneumoniae, Morganella spp. i Enterococcus spp. (11). U odnosu na Еѕivotnu dob bolesnika ne postoji znaДЌajna razlika u uДЌestalosti E. coli i ne-E. coli etioloЕЎkih faktora IMS (P=0.173). Svi uzroДЌnici su znaДЌajno ДЌeЕЎД‡i u starijoj Еѕivotnoj dobi, 65 i viЕЎe godina (P<0.05). Prema Petersonu, kod bolesnika starije Еѕivotne dobi koji boluju od hroniДЌnih i degenerativnih bolesti i kod Antimikrobni lijek Ampicillin Amoxicillin Amoxiclav Piperacillin Norfloxacin Ciprofloxacin Imipenem Meropenem Vancomycin Cefotaxim Ceftriaxon Ceftazidim Erythromycin Doxycyclin Gentamycin Amikacin Tmp-Smx Nitrofurantoin Pipemid. kis. Escherichia coli Klebsiella species %S 43,3 46,5 43,4 * 92,4 88,7 * * * 95,5 95,2 95,9 * * 94,6 * 66,5 92,5 90,5 %S 21,8 35,3 35,3 * 41,2 * 100,0 100,0 * * 64,7 53,0 * * 41,2 64,7 47,0 17,7 17,7 Proteus Pseudomonas mirabilis aeruginosa %S 18,2 45,5 45,5 * 54,5 45,5 100,0 100,0 * * 36,4 27,3 * * 54,5 81,8 * 18,2 27,3 Enterococcus faecalis %S * * * 74,1 25,0 37,5 100,0 87,5 * * 12,5 * * * 25,0 37,5 * * * %S 83,4 83,4 66,7 * 66,7 83,4 * * 100,0 * * * 66,7 83,4 66,7 * 33,3 83,4 * TABELA 6. Osjetljivost na antimikrobne lijekove dominantnih etioloЕЎkih faktora akutnih infekcija mokraД‡nog sistema steДЌenih u zajednici kod hospitaliziranih bolesnika. S–senzitivan, *–nije raД‘en antibiogram, Tpm-Smx–trimetoprim-sulphametoxasol, Pipemid. kis.–pipemidinska kiselina kojih su ДЌesto primijenjene agresivne terapijske i dijagnostiДЌke procedure na mokraД‡nom sistemu, uzroДЌnici IMS sem E. coli su ДЌesto i druge enterobakterije ЕЎto je u skladu sa faktorima rizika i spektrom etioloЕЎkih faktora za komplicirane IMS (12), dok se Staphylococcus saprophyticus ДЌeЕЎД‡e javlja kod mladih seksualno aktivnih Еѕena (2,5). AnalizirajuД‡i uДЌestalost etioloЕЎkih faktora u odnosu na godiЕЎnje doba, dobili smo zanimljive rezultate da su i E. coli (P<0.0001) i ne-E. coli etioloЕЎki faktori (P=0.033) znaДЌajno ДЌeЕЎД‡i u toplijem dijelu godine (proljeД‡e–ljeto) ЕЎto daje IMS epitet sezonskih bolesti. DosadaЕЎnje studije pokazuju da su IMS neЕЎto ДЌeЕЎД‡e u hladnijim godiЕЎnjim dobima, dok Staphylococcus saprophyticis ДЌeЕЎД‡e uzrokuje IMS u kasno ljeto i ranu jesen 5-15%, pa ДЌak i do 40% IMS (5). E. coli je znaДЌajno ДЌeЕЎД‡e etioloЕЎki faktor kompliciranih i nekompliciranih IMS u odnosu na ne-E. coli etioloЕЎke faktore (P<0.0001), ЕЎto se takoД‘er slaЕѕe sa izvjeЕЎtajima drugih istraЕѕivaДЌa koji naglaЕЎavaju uДЌestalost E. coli u kompliciranim i nekompliciranim IMS (2,4), s tim ЕЎto su ДЌeЕЎД‡e uzroДЌnici kompliciranih IMS i druge G-bakterije (2,3,4). IstraЕѕivanje provedeno u Izraelu dalo je rezultate da je prevalenca E. coli kao uzroДЌnika IMS u padu od 70,5% u 1991. godini, na 56% u 2000. godini, ЕЎto potvrД‘uje varijabilnost prevalence etioloЕЎkih faktora (E. coli) u vremenu (3). U odnosu na kategoriju IMS E. coli je znaДЌajno ДЌeЕЎД‡i etioloЕЎki faktor kompliciranog i nekompliciranog cistouretritisa i pijelonefritisa (P<0.05), dok kod bolesnika sa prostatitisom nema znaДЌajne razlike u uДЌestalosti E. coli i ne-E. coli etioloЕЎkih faktora (P=0.7163). Alos izvjeЕЎtava da je E. coli etioloЕЎki faktor 85% nekompliciranog cistitisa, dok su Staphylococcus saprophyticus, Proteus mirabilis, Streptococcus agalactiae i Klebsiella spp. odgovorni za veД‡inu drugih sluДЌajeva (10). Colodner i sar. izvjeЕЎtavaju da je u Izraelu svega 0,9% nekompliciranih IMS uzrokovano sa Staphylococcus saprophyticus (6). 6. ZAKLJUДЊCI Dominantni etioloЕЎki faktori akutnih IMS steДЌenih u zajednici kod hospitaliziranih bolesnika su: E. coli (73,5%), Klebsiella spp. (8,5%), Proteus mirabilis (5,5%), Pseudomonas aeruginosa (4%) i Enterococcus faecalis (3%). E. coli je znaДЌajno ДЌeЕЎД‡i etioloЕЎki faktor IMS kod Еѕena, kompliciranog i nekompliciranog pijelonefritisa i cistouretritisa (P<0.0001). Nije naД‘ena znaДЌajna razlika u uДЌestalosti izmeД‘u etioloЕЎkih faktora IMS u odnosu na dobne skupine bolesnika, godiЕЎnje MED ARH 2009; 63(3) • ORIGINALNI ДЊLANCI / ORIGINAL PAPERS 131 EtioloЕЎke karakteristike akutnih infekcija mokraД‡nog sistema steДЌenih u zajednici kod odraslih hospitaliziranih bolesnika nary tract infections in Israel: diagnosis, lijeДЌniДЌki zbor, 2006. doba i prostatitis (P>0.05). pathogens and antibiotic guidelines adhe- 9. Gonzalez-Pedraza Aviles A, Luis HerE. coli je dobro osjetljiva na Cefalosrence: A prospective study. Int J Infect Dis. nandez R, Luna Avila J, Davila Mendoza porine III generacije, Gentamycin, Ni2007; 11: 245-250. R, Ortiz Zaragoza C. Urinary tract infectrofurantoin, Norfloksacin, Ciproflok- 4. Ronald A. The etiology of urinary tract tion by Candida species. Aten Primaria, infections: Traditional and emerging 2006;38 (3):147-53. sacin i Pipemidinsku kiselinu, Klebsiella pathogens. Am J Med, 2002; 113 (Suppl 10. Alos JI. Epidemiology and etiology of urispp. i Pseudomonas aeruginosa na Imi1A): 14-19. nary tract infections in the community. penem i Meropenem, Proteus mirabilis 5. Widerstrom M, Wistrom J, Ferry S et al. Antimicrobial susceptibility of the main na Imipenem, Meropenem i relativno Molecular Epidemiology of Staphylocopathogens and clinical significance of rena Amikacin, Enterococcus faecalis na ccus saprophyticus Isolated from Women sistance. Enferm Infecc Microbiol Clin, Vancomycin i relativno na Ampicillin, With Uncomlicated Commynity-Acqu2005; 23 (Suppl 4):3-8. ired Urinary Tract Infection. J Clin Mi- 11. Krieger JN. Urinary tract infections: Amoxicillin, Ciprofloksacin, Doxyciccrobiol, 2007: 1561-4. what’s new? Urol, 2002; 168: 2351-8. lin i Nitrofurantoin. 6. LITERATURA 1. 2. 3. Norrby SR. Urinary tract infections. In: Finch RG, Greenwood D, Norrby SR, Whitley RJ (eds). Antibiotic And Chemothe- 7. rapy. Edinburg: Churchill Livingstone, 2003: 764-71. Gypta K, Stamm WE. Urinary Ttract Infections. ACP Medicine, 2005; http://www. medscape.com/viewarticle/505095. 8. Nesher L, Novack V, Riesenberg K, Schlaeffer F. Regional community-acquired uri- Colodner R, Ken-Dror S, Kavenshtock B, 12. Peterson DL. Resistance in gram-negative Chazan B, Raz R. Epidemiology and Clinibacteria: Enterobacteriaceae. Am I Med, cal Characteristics of Patients with Stap2006; 119 (6 Suppl1):20-8. hylococcus saprophyticus Bacteriuria in Israel. Infection, 2006; 34 (5):278-81. Kontakt adresa autora: Prim. mr. med. sci. Sobel JD, Kaye D. Urinary tract infections. dr. Dilista PiljiД‡, Klinika za infektivne bolesti. In: Mandell GL, Bennet JE, Dolin R (eds). Univerzitetski kliniДЌki centar Tuzla, Trnovac Principles and practice of infectious diseases. New York: Churchill Livingstone, bb, 75000 Tuzla, Tel: posao: 035-303-334 (335), E-mail: dilista.piljic@ukctuzla.ba 2005: 875-901. KuДЌiЕЎec-TepeЕЎ N, Bejuk D. Empirijske upute za analizu urina. Zagreb; Hrvatski MEDICAL INFORMATICS IN A UNITED AND HEALTHY EUROPE WELCOME TO The XXII International Conference of the European Federation for Medical Informatics MIE SARAJEVO UNSA University of Sarajevo ISfTeH International Society for Telemedicine and eHealth 09 EuroRec European Institute for Health Records August 30th - September 2nd, 2009 EFMI European Federation for Medical Informatics BHSMI Society for Medical Informatics of Bosnia and Herzegovina www.mie2009.org 132 MED ARH 2009; 63(3) • ORIGINALNI ДЊLANCI / ORIGINAL PAPERS European Association of Healthcare IT Managers Mikroalbuminurija i ultrazvuДЌne karakteristike bubrega u djece i adolescenata sa Dijabetes melitusom tip 1 Mikroalbuminurija i ultrazvuДЌne karakteristike bubrega u djece i adolescenata sa Dijabetes melitusom tip 1 Microalbuminuria and Ultrasound Characteristics of Kidneys in Children and Adolescents with Diabetes Mellitus Type 1 Evlijana HasanoviД‡1, Denijal TulumoviД‡2, Goran ImamoviД‡2, Senaid TrnaДЌeviД‡2 Klinika za djeДЌije bolesti, Univerzitetski kliniДЌki centar, Tuzla, Bosna i Hercegovina1 Klinika za interne bolesti, Univerzitetski kliniДЌki centar, Tuzla, Bosna i Hercegovina2 Originalni ДЌlanak SaЕѕetak Cilj rada je bio utvrditi ultrazvuДЌnim pregledom dimenzije i volumen bubrega u djece i adolescenta sa dijabetes melitusom tip 1 (DMT1), te ih uporediti sa nalazom mikroalbuminurije, metaboliДЌkom kontrolom bolesti i vrijednostima klirens kreatinina. U 80. djece i adolescenata, koji su oboljeli od DMT1 u dobi od 2. do 16. godine Еѕivota, morfometrijski ultrazvukom mjerila su se oba bubrega. Nefelometrijskom metodom se je iz tri uzastopna uzorka urina odreД‘ivala mikroalbuminurija. OdreД‘ivan je serumski kreatinin u ispitanika sa mikroalbuminurijom. Demografski podaci su dobiveni odgovorom od roditelja i iz medicinske dokumentacije ispitanika. U odnosu na duЕѕinu trajanja bolesti svi ispitanici su podijeljeni u dvije grupe: prva grupa sa trajanjem DMT1 <10 godina i druga sa trajanjem bolesti >10 godina. U ispitanika sa trajanjem DMT1 duЕѕe od 10 godina uДЌestalost patoloЕЎkog nalaza uzduЕѕnog dijametra i volumena oba bubrega u odnosu na dob i antropometrijske standarde je statistiДЌki znaДЌajno veД‡a. TakoД‘er, isti ispitanici imali su statistiДЌki znaДЌajno veД‡u srednju vrijednost HbAlc i uДЌestalije mikroalbuminuriju. Kod ispitanika sa mikroalbuminurijom ukupna srednja vrijednost klirensa kreatinina bila je u granicama referentnih vrijednosti a statistiДЌki znaДЌajno veД‡a kod ispitanika kod kojih je bolest trajala manje od deset godina, ЕЎto govori u prilog hiperfiltracije bubrega. UltrazvuДЌno praД‡enje dimenzija i volumena bubrega uz mikroalbuminuriju, moЕѕe ukazati na postojanje ranih faza dijabetesne nefropatije (DN) i uticati na njeno spreДЌavanje i dalju progresiju. KljuДЌne rijeДЌi: dijabetes melitus, nefropatija, mikroalbuminurija, ultrazvuДЌni parametri. Original paper SUMMARY The aim of the study was to compare ultrasound findings of kidneys in children and adolescents with diabetes mellitus type 1 (DMT1), establish the association with microalbuminuria, blood pressure values and metabolic control of the disease, and creatinine clearance. In 80 children and adolescents with DMT1, in whom illness occurred in period between 2 and 16 years of age, morphometry measurements with ultrasound were performed. Nephelometric method of three consecutive samples of urine determined microalbuminuria. In patients with microalbuminuria, creatinine clearance was also measured. Demographic data were obtained from the parents and from the patients medical records. In relation to the duration of the disease, all patients were divided into two groups: the first group of patients with illness lasting for less than 10 years, and the second were those whose illness had lasted more than 10 years. In patients with duration of DMT1 of more than 10 years, the frequency of pathological findings of the longitudinal diameter and volume of both kidneys in relation to age and anthropometric standards was statistically significantly greater. Also, the finding of microalbuminuria was more frequent. In the group of patients with DMT1 lasting for more than 10 years, the mean value of HBAlc was statistically significantly higher. In patients with microalbuminuria the total mean value of creatinine clearance was within the bounds of the reference values and was statistically significantly higher in patients in whom the illness had lasted less than three years, which indicates hyperfiltration of the kidneys. Alongside microalbuminuria, monitoring of the dimension and volume of the kidneys may indicate the existence of the early phases of diabetic nephropathy and result in its prevention and prevention of illness progression. Keywords: Diabetes mellitus, nephropathy, microalbuminuria, ultrasound parameters 1. UVOD Dijabetesna nefropatija (DN) je najДЌeЕЎД‡a specifiДЌna dugoroДЌna komplikacija dijabetes melitusa tip 1 (DMT1). Kod 2080% oboljele djece i adolescenata u kasnijoj Еѕivotnoj dobi razviti Д‡e se dijabetesna nefropatija (1, 2). Progresivno propadanje funkcije bubrega u DMT1 prvi su opisali Mogensen i sar., (3). Nezavisno jedan od drugoga nekoliko je autora otkrilo da postoje tri faze DN: hipertrofijska hiperfiltracija, mikroalbuminurija i hroniДЌno zatajenje bubrega (4, 5). TeЕЎko je taДЌno odrediti kada poДЌinje proces oЕЎteД‡enja bubrega (6). BubreЕѕna disfunkcija se javlja ДЌeЕЎД‡e kada je bolest poДЌela prije 20. godine Еѕivota. Jedini prvi znak nefropatije je pojava mikroalbuminurije (7, 8, 9). Nerijetko mikroalbuminurija prelazi u makroalbuminuriju, dolazi do pada glomerularne filtracije i porasta krvnog pritiska (10). U poДЌetnim stadijima dijabetesne nefropatije u djece sa normalnom bubreЕѕnom funkcijom ultrazvuДЌni pregled moЕѕe biti od pomoД‡i pri detekciji ranih patomorfoloЕЎkih parenhimskih lezija bubrega (11). Ultrasonografija kao jedna od screening metoda, svakim danom ima sve veД‡u ulogu u praД‡enju bolesti urinarnog trakta u djece. UltrazvuДЌna aparatura je ЕЎiroko dostupna, pregled jednostavan, relativno brz i ne zahtijeva posebnu pripremu pacijenta. Za preciznu evaluaciju abnormalnosti morfologije bubrega, a indirektno za kliniДЌke manifestacije i funkciju potrebno je poznavanje normalnih sonografskih parametara bubrega djece (12). 2. CILJ RADA Obzirom da mikroalbuminurija uz praД‡enje ultrazvuДЌnim pregledom dimenzija i volumena bubrega predstavljaju znaДЌajne parametre u kliniДЌkoj procjeni nastanka DN, poduzeto je ovo istraЕѕivanje, s ciljem da se utvrdi korelacija nalaza mikroalbuminurije i ultrazvuДЌnog pregleda bubrega, kao jednostavne i rutinske metode, u djece i adolescenata sa DMT1, te da bi se moglo koristiti u blagovremenom otkrivanju, lijeДЌenju i prevenciji DN. 3. METODE I ISPITANICI Analizom je obuhvaД‡eno 80 ispitanika, oba spola, razliДЌite Еѕivotne dobi koji se redovno kontroliЕЎu u ambulanti za endokrinologiju Klinike za djeДЌije bolesti Univerzitetsko kliniДЌkog centra Tuzla (UKC Tuzla). Kriteriji ukljuДЌenja u ovu studiju su bili da je kod ispitanika DMT1 poДЌeo u uzrastu od 2. do 16. godine Еѕivota i da u terapiji primaju insulin. Dok su kriteriji iskljuДЌenja iz ove studije predstavljali pojavu akutne i hroniДЌne bolesti (centralnog, respiratornog, kardiovaskularnog, gastrointestinalnog, genitourinarnog sistema), sistemska oboljenja (lupus eritematodes, juvenilni reumatoidni artritis, dijabetes melitus tip 2), oboljenja jetre, trudnoД‡a i upotreba lijekova kao ЕЎto su kortikosteroidi duЕѕi vremenski period. U odnosu na duЕѕinu trajanja bolesti svi ispitanici su podijeljeni u dvije grupe: prvu kod kojih je bolest trajala manje od deset godina i drugu kod kojih je bolest trajala viЕЎe od deset godina. U odnosu na Еѕivotnu dob kada je poДЌeo dijabetes, ispitanici su takoД‘er podijeljeni u tri podgrupe: prvu grupu saДЌinjavali su ispitanici koji su u vrijeme oboljevanja od DMT1 imali manje od 4.9 godina, drugu grupu ispitanici od 5 do 10.9 godina i treД‡u podgrupu ispitanici stariji od 11 godina. Prije dolaska na pregled, svaki ispi- MED ARH 2009; 63(3) • ORIGINALNI ДЊLANCI / ORIGINAL PAPERS 133 Mikroalbuminurija i ultrazvuДЌne karakteristike bubrega u djece i adolescenata sa Dijabetes melitusom tip 1 tanik uzeo je u dva prethodna dana tri uzorka urina, dva u jutarnjim i jedan u poslijepodnevnim satima. Do dolaska na pregled uzorci su ДЌuvani u friЕѕideru na temperaturi izmeД‘u +2 do +8В°C (13). U nativnom urinu odreД‘ivana je mikroalbuminurija nefelometrijskom metodom sa reagensima firme Dade Behring (13). Za perzistentnu mikroalbuminuriju smatrane su vrijednosti albumina 20-200 Вµg/minuti u najmanje dva od tri uzastopna uzorka urina, a intermitentnu ako su vrijednosti albumina bile 20-200 Вµg/minuti u jednom od tri uzastopna uzorka urina (14). MetaboliДЌka kontrola bolesti procjenjivana je na osnovu prosjeДЌnih vrijednosti svih dostupnih nalaza HbAlc od poДЌetka bolesti do dana ispitivanja. DuЕѕina trajanja bolesti izraДЌunata je u decimalnim godinama na osnovu datuma poДЌetka bolesti i datuma skupljenog treД‡eg uzorka urina. Za datum poДЌetka bolesti smatrao se datum primanja prve injekcije insulina (15). Za odreД‘ivanje funkcionalnog stanja bubrega odreД‘ivan je klirens endogenog kreatinina pomoД‡u Schwartzova jednadЕѕbe a na osnovu Counahan- Barratova jednadЕѕbe izraДЌunata je i procjenivanja glomerularna filtracija (GF) (16, 17). Nije bilo moguД‡e kontrolisati GF kod zdrave djece i adolescenata. Kod svih ispitanika pomoД‡u В»RealtimeВ« ultrazvuДЌnog pregleda radila su se morfometrijska mjerenja oba bubrega. Real- time tehnikom na aparatima Toshiba Corevision 350 i Logiq 3 uz upotrebu multifrekventne konveksne sonde od 3.75 mHz, prvo u leЕѕeД‡em poloЕѕaju na leД‘ima, te u desnom i lijevom „polukosom dekubitus- poloЕѕaju“ mjerile su se dimenzije oba bubrega pojedinaДЌno, maksimalni uzduЕѕni promjer bubrega, ЕЎirina (izraЕѕene u mm), izgled parenhima (ehogenost), pratio izgled sinusa i odreД‘ivao volumen bubrega u mililitrima (ml). Analizirane su dimenzije bubrega dobivene iz maksimalnog uzduЕѕnog tzv. centralnog srednjeg najduЕѕeg dijametra bubrega. Е irina parenhima je mjerena iz prethodnog presjeka na mjestu spoja srednje i spolje treД‡ine (12, 18, 19, 20). Za ovo istraЕѕivanje dobijena je saglasnost EtiДЌkog komiteta UKC u Tuzli. StatistiДЌka obrada podataka Za testiranje statistiДЌkih znaДЌajnosti razlike meД‘u uzorcima koriЕЎteni su XВІ-test, Studentov t-test i Z-test proporcija). Razlika meД‘u uzorcima smatrala se znaДЌajnom ako je P< 0.05. U sta134 tistiДЌkoj obradi podataka je koriЕЎten Ar- perzistentnu. cus QuickStat program (21). Klirens kreatinina u ispitanika sa mikroalbuminurijom izraДЌunat na osnovu 4. REZULTATI RADA Schwartzove i Counahan Barrattove jedU Tabeli 1 prikazane su demograf- nadЕѕbe prikazan je u Tabeli 4. ske karakteristike ispitanika u odnosu Ukupna srednja vrijednost klirensa na dob poДЌetka DMT1. kreatinina kod ispitanika sa mikroalbuminurijom bila Dob poДЌetka Demografske je u granicama refeЕЎeД‡erne bolesti tip 1 (godine) Ukupno karakteristike rentnih vrijednosti <4.9 5-10.9 >11 Broj (sa MA**) 9 10 19 i iznosla je 83.9В±5.1. Broj (bez MA) 19 24 18 61 Srednja vrijednost M/ЕЅ (sa MA) 3/6 5/5 8/11 klirensa kreatinina M/ЕЅ (bez MA) 14/5 13/11 12/6 39/22 iznosila je 87.5В±5.5 Dob u vrijeme ispitivanja u 6 (31.5%) ispita(godine; В±SD) (sa MA) - 17.2В±5.1 19.5В±6.2 18.4В±5.6 nika, kod kojih je Dob u vrijeme ispitivanja 9.9В±3.8 14.1В±3.6 19.4В±4.7 14.4В±4.7 DMT1 trajao ma(godine; В±SD) (bez MA) nje od 10 godine, a Dob poДЌetka bolesti (godine; В±SD) (sa MA) 8.5В±1.9 11.9В±0.8 10.3В±2.2 u 13 (68.5%) ispitaDob poДЌetka bolesti 3.3В±1.9 8.7В±1.8 12.8В±1.3 8.3В±1.7 nika sa duЕѕim tra(godine; В±SD) (bez MA) janjem DMT1 je Trajanje dijabetesa (godine; bio 80.4В±4.5. StaВ±SD) (sa MA) 8.6В±6.7 6.5В±5.9 7.5В±6.2 Trajanje dijabetesa 6.8В±3.7 5.2В±3.6 6.7В±4.8 6.3В±1.9 tistiДЌki znaДЌajno veД‡a ukupna sred(godine; В±SD) (bez MA) nja vrijednost kliHbA1C (%; В±SD) (sa MA) 9.4В±2.9 8.9В±1.0 9.2В±2.1 HbA1C (%; В±SD) 8.2В±1.2 8.6В±1.7 8.2В±1.6 8.3В±1.3 rensa kreatinina (bez MA) bila je kod ispitaTabela 1. Demografske karakteristike ispitanika u odnosu na dob poДЌetka nika kod kojih je DMT1*, * Diabetes mellitus tip 1, ** Mikroalbuminurija bolest trajala manje od deset godina NajveД‡i broj ispitanika (41.5%) u vri- u odnosu na ispitanike kod kojih je bojeme poДЌetka bolesti bio je u dobu od lest trajala duЕѕe. MeД‘utim, nije bilo sta5 do 10.9 godina. DjeДЌaci oboljeli od tistiДЌki znaДЌajne razlike izmeД‘u vrijedDMT1 u svim dobnim skupinama bili nosti klirenska kreatinina kod ispitanika su ДЌeЕЎД‡e zastupljeni u odnosu na djevoj- sa intermitentnom i perzistentnom miДЌice. ProsjeДЌna dob poДЌetka bolesti uku- kroalbuminurijom u odnosu na duЕѕinu pno gledano iznosila je 8.6В±3.7 godina trajanja bolesti. a prosjeДЌne vrijednosti Trajanje DMT1 HbAlc za sve ispitanike Ukupno Mikroaliznosile su 8.3В±1.7%. < 10 godine >10 godine buminurija UДЌestalost intermin % n % n % tentne i perzistentne miIntermitentna 5 26.3 3 15.8 8 42.1 kroalbuminurije u odPerzistentna 6 31.6 5 26.3 11 57.9 nosu na trajanje DMT1 Ukupno 11 57.9 8 42.1 19 100. (<10 i >10 godina) prikaTabela 2. UДЌestalost intermitentne i perzistentne mikroalbuminurije u zana je u Tabeli 2. U grupi sa trajanjem odnosu na trajanje DMT1 (<10 i >10 godina) DMT1 manje od 10 godina, 11 ili 57.9% ispiKlirens kreatinina (ml/min; В±SD) Ukupno tanika imalo je mikro- Mikroal(n=19) < 10 godine >10 godine albuminuriju, a od toga buminurija (n=6) (n= 13) broja u 5 ispitanika mikroalbuminurija je bila Intermitentna 83.6В±9.6A 77.2В±15.5 80.4В±12.1 intermitentna, a u 6 per- (n= 8) zistentna. U grupi ispita- Perzistentna 91.4В±17.1B 83.5В±14.6 85.6В±14.8 nika sa trajanjem DMT1 (n=11) 87.5В±5.5C 80.4В±4.5 83.9В±5.1 duЕѕe od 10 godina 8 Ukupno (n=19) (42.1%) ispitanika imalo Tabela 4 Klirens kreatinina u ispitanika sa mikroalbuminurijom u je izraЕѕenu mikroalbu- odnosu na duЕѕinu trajanja DMT. At = 0.92; df = 17; P = 0.37, Bt = minuriju, i to 3 ispita- 1.04; df = 17; P = 0.31, Ct = 2.08 df = 17; P = 0.008 u odnosu na nika intermitentnu, a 5 ispitanike sa trajanjem DMT1 viЕЎe od 3 godine. MED ARH 2009; 63(3) • ORIGINALNI ДЊLANCI / ORIGINAL PAPERS Mikroalbuminurija i ultrazvuДЌne karakteristike bubrega u djece i adolescenata sa Dijabetes melitusom tip 1 t r aja njem DMT1 kojih je DMT1 trajao duЕѕe od 10 godina od 10 godina u od- u odnosu na ispitanike kod kojih je boDecimalna dob i nosu na decimalnu lest kraД‡e trajala. Razlozi pojave mikroantropometrijski Nalaz UZ Nalaz UZ dob t a koД‘er n ije albuminurije u naЕЎih ispitanika usko su parametri Normalan PatoloЕЎki Normalan PatoloЕЎki statistiДЌki znaДЌajna, povezani sa njihovom slabom dugogoN; (%) N; (%) N; (%) N; (%) dok u odnosu na tje- diЕЎnjom metaboliДЌkom kontrolom boDob 58 (93.4) 4 (6.6) 16 (88.8) 2 (11.2)A lesnu visinu, teЕѕinu lesti na ЕЎto ukazuju i njihove prosjeДЌne Tjelesnu visinu 57 (91.9) 5 (8.1) 14 (77.7) 4 (22.3)B i povrЕЎinu postoji srednje vrijednosti HbAlC od 9.2В±2.1%. Tjelesnu masu 56 (90) 6 (10) 14 (77.7) 4 (22.3)C statistiДЌki znaДЌajna Tome u prilog govori i nalaz HbAlc od Tjelesnu povrЕЎinu 55 (88.7) 7 (11.3) 14 (77.7) 4 (22.3)D razlika. 8.3В±1.2% u naЕЎih ispitanika bez mikroU Tabeli 7 prikaalbuminurije. Tabela 5. UДЌestalost normalnog i patoloЕЎkog nalaza uzduЕѕnog dijametra zana je, u odnosu na U naЕЎih ispitanika sa mikroalbumidesnog bubrega u odnosu na trajanje DMT1 mjerenog ultrazvukom i izraДЌunatog u odnosu na decimalnu dob i antropometrijske parametre. trajanje bolesti uДЌe- nurijom ukupna srednja vrijednost kliAZ = 0.11; 95% CI 0.013751 – 0.347121; P = 0.11, BZ = 0.22; 95% stalost normalnog rensa kreatinina bila je u granicama reCI 0.064092 – 0.476373; P = 0.02, CZ = 0.55; 95% CI 0.307572 – i patoloЕЎkog nalaza ferentnih vrijednosti i iznosila je 83.9В±5.1 0.784699; P = 0.41, DZ = 1.45; 95% CI 0.357451 – 0.827014; P = 0.01 volumena desnog ml/min. ZnaДЌajno veД‡a ukupna srednja u odnosu na ispitanike sa trajanjem DMT1 manje od 10 godina. bubrega mjerenog vrijednost klirensa kreatinina, iako u ultrazvukom i izra- granicama normalnih vrijednosti, bila UДЌestalost normalnog i patoloЕЎkog ДЌunatog u odnosu na decimalnu dob i je u ispitanika kod kojih je bolest tranalaza uzduЕѕnog dijametra desnog buantropometrijske parametre. jala manje od deset godina. Te veД‡e vribrega, mjerenog ultrazvukom i izraДЌuUДЌestalost patolonatog u odnosu na decimalnu dob i anUltrazvuДЌni nalaz uzduЕѕnog dijametra lijevog ЕЎkog nalaza volumen tropometrijske parametre a s obzirom na bubrega u odnosu na trajanje DMT1 desnog bubrega u grupi trajanje bolesti prikazana je u Tabeli 5. Decimalna dob i <10 godina (n=62) >10 godina (n=18) ispitanika sa trajanU grupi ispitanika sa trajanjem antropometrijski Nalaz UZ Nalaz UZ jem DMT1 duЕѕe od parametri DMT1 duЕѕe od 10 godina, uДЌestalost pa10 godina u odnosu Normalan PatoloЕЎki Normalan PatoloЕЎki toloЕЎkog nalaza uzduЕѕnog dijametra dena decimalnu dob i N; (%) N; (%) N; (%) N; (%) snog bubrega je statistiДЌki znaДЌajno veД‡a tjelesnu visinu stati- Dob 58 (93.5) 4 (6.5) 16 (88.8) 2 (11.2)A prema tjelesnoj visini i povrЕЎini u odnosu stiДЌki se znaДЌajno ne Tjelesnu visinu 57 (91.9) 5 (8.1) 14 (77.7) 4 (22.3)B na ispitanike sa trajanjem DMT1 manje razlikuju, dok prema Tjelesnu masu 56 (90) 6 (10) 14 (77.7) 4 (22.3)C od 10 godina. tjelesnoj teЕѕini i povTjelesnu povrЕЎinu 56 (90) 6 (10) 14 (77.7) 4 (22.3)D U Tabeli 6 prikazana je uДЌestalost rЕЎini postoji statistiДЌki normalnog i patoloЕЎkog nalaza uzduЕѕTabela 6. UДЌestalost normalnog i patoloЕЎkog nalaza uzduЕѕnog dijametra znaДЌajna razlika. nog dijametra lijevog bubrega, mjerenog lijevog bubrega u odnosu na trajanje DMT1 mjerenog ultrazvukom i UДЌestalost normalizraДЌunatog u odnosu na decimalnu dob i antropometrijske parametre. ultrazvukom i izraДЌunatog u odnosu na nog i patoloЕЎkog na- AZ = 0.33; 95% CI 0.133427 – 0.590075; P = 0.12, BZ = 2.06; 95% decimalnu dob i antropometrijske palaza volumena lijevog CI 0.260191 – 0.739809; P = 0.02, CZ = 2.06; 95% CI 0.307572 – rametre s obzirom na trajanje bolesti. bubrega mjerenog ul- 0.784699; P = 0.02, DZ = 3.74; 95% CI 0.260191 – 0.739809; P = UДЌestalost patoloЕЎkog nalaza uzduЕѕtrazvukom i izraДЌuna- 0.0002 u odnosu na ispitanike sa trajanjem DMT1 manje od 10 godina. nog dijametra lijevog bubrega u ispitatog u odnosu na decinika sa trajanjem DMT1 manje od 10 gomalnu dob i antropometrijske parame- jednosti klirensa kreatinina, moguД‡e je dina statistiДЌki se znaДЌajno ne razlikuju. tre prikazana je u Tabeli 8 a u odnosu na objasniti glomerularnom hiperfiltraIsto tako, uДЌestalost patoloЕЎkog nalaza trajanje bolesti. cijom, koja se javlja na poДЌetku dijabeovog parametra u ispitanika sa duЕѕim U odnosu na ispitanike sa trajanjem tesa. Prema istraЕѕivanju Mogenesen i DMT1 manje od 10 sar., (3) i Chiarelli i sar., (22) hiperfiltraUltrazvuДЌni nalaz volumena desnog bubrega u godina uДЌestalost pa- cija kroz glomerul je odgovorna za naodnosu na trajanje DMT1 toloЕЎkog nalaza volu- stanak nefropatije, dok Lervang i sar., Decimalna dob i <10 godina (n=62) >10 godina (n=18) mena lijevog bubrega (23) i Dramond i sar., (24) smatraju da antropometrijski Nalaz UZ Nalaz UZ se statistiДЌki znaДЌajno moguД‡i mehanizmi odgovorni za uniparametri Normalan PatoloЕЎki Normalan PatoloЕЎki razlikuje u grupi is- ЕЎtenje bubreЕѕnog tkiva joЕЎ nisu dovoljno N; (%) N; (%) N; (%) N; (%) pitanika sa trajanjem istraЕѕeni. Hiperfiltracija glomerula nije Dob 55 (88.7) 7 (11.3) 15 (83.3) 3 (16.7)A DMT1 duЕѕim od 10 jedina i dovoljna za nastanak nefropaTjelesnu visinu 54 (87) 8 (13) 12 (66.7) 6 (33.3)B godina prema deci- tije, ali udruЕѕena sa drugim metaboliДЌTjelesnu masu 56 (90) 6 (10) 12 (66.7) 6 (33.3)C malnoj dobi, tjelesnoj kim i hemodinamiДЌkim poremeД‡ajima u Tjelesnu povrЕЎinu 53 (85.4) 9 (14.5) 11 (61.2) 7 (38.8)D visini, masi i povrЕЎini. toku dijabetesa, doprinosi nastanku ove komplikacije. Tabela 7. UДЌestalost normalnog i patoloЕЎkog nalaza volumena desnog 5. DISKUSIJA VeД‡e vrijednosti klirensa kreatinina bubrega u odnosu na trajanje DMT1 mjerenog ultrazvukom i izraДЌunatog U t o k u n a ЕЎ e g ubrzo poslije dijagnostikovanja DMT1 su u odnosu na decimalnu dob i antropometrijske parametre. AZ = 0.55; 95% CI 0.307572 – 0.784699; P = 0.40, BZ = 0.78; 95% CI 0.523627 istraЕѕivanja znaДЌajno znak hiperperfuzije i hiperfiltracije glo– 0.935908; P = 0.18, CZ = 1.67; 95% CI 0.409925 – 0.866573; P = uДЌestalija mikroal- merula bubrega. DuЕѕe trajanje navede0.05, DZ = 1.57; 95% CI 0.657879 – 0.986249; P = 0.04 u odnosu na buminurija bila je u nih poremeД‡aja uz druge hemodinamispitanike sa trajanjem DMT1 manje od 10 godina. grupi ispitanika kod ske faktore i slabije kontrolisanu bolest UltrazvuДЌni nalaz uzduЕѕnog dijametra desnog bubrega u odnosu na trajanje DMT1 <10 godina (n=62) >10 godina (n=18) MED ARH 2009; 63(3) • ORIGINALNI ДЊLANCI / ORIGINAL PAPERS 135 Mikroalbuminurija i ultrazvuДЌne karakteristike bubrega u djece i adolescenata sa Dijabetes melitusom tip 1 sti istraЕѕivanja. U ovoj fazi su bubrezi uveDecimalna dob i <10 godina (n=62) >10 godina (n=18) Д‡ani zbog hiperfiltraantropometrijski cije, poveД‡anog hidroNalaz UZ Nalaz UZ parametri statskog pritiska u gloNormalan PatoloЕЎki Normalan PatoloЕЎki merulima i hipertroN; (%) N; (%) N; (%) N; (%) fije pojedinih nefrona Dob 57 (91.9) 5 (8.1) 15 (83.3) 3 (16.7)A (12, 18, 26). PoredeД‡i Tjelesnu visinu 53 (85.5) 9 (14.5) 13 (72.3) 5 (27.7)B dimenzije desnog i liTjelesnu masu 56 (90) 6 (10) 13 (72.3) 5 (27.7)C jevog bubrega evidenTjelesnu povrЕЎinu 47 (75.8) 15 (24.2) 11 (61.2) 7 (38.8)D tno je da su procesi u DMT1 obostrani, diTabela 8. UДЌestalost normalnog i patoloЕЎkog nalaza volumena lijevog fuzni i hroniДЌni. U bubrega u odnosu na trajanje DMT1 mjerenog ultrazvukom i izraДЌunatog izraЕѕenoj bubreЕѕnoj u odnosu na decimalnu dob i antropometrijske parametre. AZ = 1.67; 95% CI 0.035785 – 0.414178; P = 0.05, BZ = 2.06; 95% CI 0.096949 insuficijenciji i termi– 0.534802; P = 0.02, CZ = 2.31; 95% CI 0.172986 – 0.642549; P = nalnim stadijumima 0.01, DZ = 2.19; 95% CI 0.133427 – 0.590075; P = 0.03 u odnosu na drugih parenhimskih ispitanike sa trajanjem DMT1 manje od 10 godina. bubreЕѕnih bolesti dimenzije bubrega se dovest Д‡e do mikroalbuminurije i dalje znaДЌajno smanjuju (25, 11). Kod dijabeprogresije nefropatije. tesne nefropatije veliДЌina bubrega se ne U grupi naЕЎih ispitanika sa trajanjem smanjuje proporcionalno funkcionalDMT1 manje od 10 godina, uzduЕѕni dinom oЕЎteД‡enju (27, 18, 26). Prije su prijametar i volumen oba bubrega nisu bili sutni kliniДЌki i biohemijski parametri neznaДЌajno promijenjeni u odnosu na korifropatije, nego ЕЎto se promjena na bubreЕЎtene standarde za dob i antropometrijzima ultrazvuДЌno mogu registrovati kod ske parametre. I drugi autori u sliДЌnim oboljelih od DMT1 (19, 26). istraЕѕivanjima su imali gotovo istovjetne UДЌestalost patoloЕЎkog nalaza volurezultate (12, 25, 19, 18). Dok u ispitanika mena desnog bubrega se znaДЌajno rakod kojih DMT1 trajao duЕѕe od 10 gozlikuje u ispitanika sa trajanjem DMT1 dina, znaДЌajno je uДЌestaliji patoloЕЎki naduЕѕe od 10 godina prema tjelesnoj masi laz uzduЕѕnog dijametra i volumena oba i tjelesnopj povrЕЎini. PatoloЕЎki nalaz vobubrega u odnosu na dob i antropomelumena lijevog bubrega je bio znaДЌajno trijska mjerenja. Nije jasno utvrД‘ena pouДЌestaliji u istoj grupi ispitanika prema vezanost izmeД‘u duЕѕine trajanja bolesti, decimalnoj dobi, tjelesnoj visini, tjelekliniДЌkih manifestacija i morfoloЕЎkih, ulsnoj masi i tjelesnoj povrЕЎini. Ta razlika trazvuДЌnih promjena koje se mogu regidesnog i lijevog bubrega, s obzirom na stravati ultrazvuДЌnim pregledom. MoЕѕe obostrani parenhimski proces, ne moЕѕe se zakljuДЌiti da u ispitanika koji boluju se pouzdano objasniti (12, 18, 26). Zbog od DMT1 duЕѕe od 10 godina, a pri tome ograniДЌenja studije ove razlike se javljaju, su oboljeli u dobi od 2. do 16. godine Еѕiali su nepouzdane i malo vjerovatne. vota, postoji uveД‡anje uzduЕѕnog dijaSmatra se da u dijabetesu uveД‡anje vometra bubrega uoДЌljivo B modom ultralumena bubrega nastaje zbog zadrЕѕavazvuДЌnim pregledom. nja soli i vode, te promjena na krvnim suZapaЕѕeno je, da je kod tih ispitanika dovima (26, 18, 10, 4). UveД‡anje dimenuДЌestaliji patoloЕЎki nalaz uveД‡anog uzzija i volumena bubrega je jedna od kaduЕѕnog dijametra desnog bubrega prema rakteristika DMT1 u fazi hipertrofijske tjelesnoj visini i tjelesnoj povrЕЎini, koji hiperfiltracije (19). korelira sa uДЌestalijom mikroalbuminurijom. U istoj grupi ispitanika, sa traja6. ZAKLJUДЊAK njem DMT1 duЕѕe od 10 godina, znatno PraД‡enje mikroalbuminurije i metaje uДЌestaliji patoloЕЎki nalaz uveД‡anog uzboliДЌke kontrole bolesti uz ultrazvuДЌni duЕѕnog dijametra lijevog bubrega u odnalaz bubrega moЕѕe doprinijeti definisanosu na tjelesnu visinu, tjelesnu masu i nju optimalnog vremena za screening i tjelesnu povrЕЎinu. ZaЕЎto je uzduЕѕni dijaprevenciju nefropatije kod djece i adolemetar desnog bubrega promijenjen samo scenata sa DMT1. u odnosu prema tjelesnoj masi i tjelesnoj povrЕЎini nije jasno. Prema tjelesnoj masi LITERATURA ovaj dijametar nije promijenjen, moЕѕda, 1. Cooper ME. Pathogenesis, prevention and treatment of diabetic nephropathy. Lancet, 1998;352:213-9.. zbog nehomogenosti grupe, manjeg 2. Bogdanovic R. Diabetic nephropathy in children. Nephrology Dialysis Transplantation, 2001;16: 120-2. uzorka ispitanika ili drugih ograniДЌenoUltrazvuДЌni nalaz volumena lijevog bubrega u odnosu na trajanje DMT1 3. 136 Mogensen CE, Cristensen CK. Predicting diabetic MED ARH 2009; 63(3) • ORIGINALNI ДЊLANCI / ORIGINAL PAPERS 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. nephropathy in insulin-dependet patients. N Engl J Med, 1983;320:966-70. Viberti GC, Hill RD, Jarret RJ, Argyropoulos A, Mahmud U, Keen H. Microalbuminuria as a predictor of clinical nephropathy in insulin dependet diabetes mellitus. Lancet, 1982;1:1430-2. Mathiesen ER, Saurbrey N, Parving H-H. Prevalence of microalbuminuria in children with type diabetes melitus. Diabetologia, 1984;29:640-3. Atkinson MA, Maclaren NK. The pathogenesis of insulin- dependent diabetes mellitus. N Engl J Med, 2001;331:1428. Mogensen CE, Cristensen CK, Vittinghus E. The stages of diabetic renal disease with emphasis on the stage of incioient diabetic nephropathy. Diabetes, 1997;32 64-72. Feldt- Rasmussen B, Baker L, Deckert T. Exercise as a provocative test in early renal disease in Type 1 diabetes: albuminuria, systemic and renal haemodinamics. Diabetologia, 1999;28:389-96. Sperling MA. Diabetes Mellitus in: Sperling MA et al. Pediatric Endocrynology . W.B. Saunders Company, Philadelphia, USA, 1996;229-60. Gibb DM, Dunger D, Levin M, Shah V, Smith C, Barratt TM. Early markers of the renal complications of insulin dependent diabetes mellitus. Archives of Disease in Childhood, 1989;64:984-91. BeneЕЎ-MiriД‡ S i sar. Atlas ultrazvuДЌne dijagnostike abdomena, Univerzitet u Tuzli, PrintCom, Tuzla, 2002. Han BK, Babcock DS. Sonografic measurements and appearance of normal kidneys in children. A JR Am J Roentgenol, 1985;145:611-6. Anonymous. Evaluation of precision performance of clinical chemistry devices. Approved Guideline. NCCLS document EP5-A. Wayne, 1999. Anonymous. Variation and trends in incidence of childhood diabetes in Europe. Lancet, 2000;355: 873-6. Anonymous. Glomerulopathy in diabetes. Medforum, 2000; 14 (suppl 2): 46-7.. Schwartz GJ, Brion LP, Spitzer A. The use of plasma creatinine concentration for estimating glomerular rate in infants, children and adolescent. Pediatr Clin North Am, 1987;34:571-90. Filler G, Prim F, Lepage N. ОІ- trace protein, cystatin C, ОІ2- mikroglobulin and creatinine compared for detecting impaired glomerular filtration rate in children. Clin Chem, 2002;48:729-36. Rademacher J. Ultrasonography of kidney and the renal vessels: Normal findings, inherited and renoparenchymatous diseases. Part I. Der Internist, 2003;44:1413-29. BrkljaДЌiД‡ B. Dopler krvnih Еѕila. Medicinska naklada, Zagreb, 2000. LiДЌanin Z. Dopler Atlas of the extermitets and abdominal vessels: normal anatomy and pathologic findings. Е tamparija „Fojnica“, Fojnica, 2002. Anonymous. Evaluation of precision performance of clinical chemistry devices. Approved Guideline. NCCLS document EP5-A. Wayne 1999; 2;242-4. Chiarelli F, Verrotti A, Morgese G. Glomerular hyperfiltration increases the risk of developing microalbuminuria in diabetic children. Pediatr Nephrol, 1988;9:154-8. Lervang HH, Jensen S, Brochner Mortensen J, Ditzel J. Early glomerular hyperfiltration and the development of late nephropathy in type 1 (insulin- dependent) diabetes mellitus. Diabetologia, 1988; 31:723-9.. Drummond K. Young kidneys respond differently than adults kidneys to insulin dependent diabetes mellitus. Diabetic Nephropathy Study Group. J Am Soc Nephrol, 1990;1:307. Braun R. Pediatric Ultrasound: How, Why and When. Churchill Livingstone. British Library Cataloguing in Publication Data London, 2005. Gross IJ, Azevedo M, Suveiro S, Cananai L, Caramori ML, Zelmanovitz T. Diabetes Nephropathy: Diagnosis, Prevention and Treatman. American Diabetes Assotiation. Diabetes Care, 2005;Vol. 28 (1).. FuД‡kar ЕЅ. Sonografija urogenitalnog sistema. Partizanska knjiga. Ljubljana- Rijeka, 1998. Rudberg S, Ullman E, Dahlquist G. Relationship between early metabolic control and the development of microalbuminuria. A longitudinal Study in children with type 1 diabetes mellitus. Diabetologia, 1993; 36:1309- 14. Kontakt adresa autora: Mr. dr. sc. Evlijana HasanoviД‡, Klinika za djeДЌije bolesti, Univerzitetski kliniДЌki centar Tuzla, 75 000 Tuzla, Bosna i Hercegovina, E mail evlijanah@yahoo. com telefon 00387 61 887721. Colposcopic Changes Based on Number of Sexual Partners, Births, and Contraceptives Use Colposcopic Changes Based on Number of Sexual Partners, Births, and Contraceptives Use Myrvete PaГ§arada, Shefqet Lulaj, Gyltene Kongjeli, Niltene Kongjeli, Hana Qavdarbasha, Bujar ObГ«rtinca Gynecology/Obstetrics Clinic, University Clinical Centre of Kosova, Prishtina, Kosovo Original paper SUMMARY Objective: The aim of this study was to determine the role of colposcopy and cytodiagnosis in the early detection of pathological changes in the uterine cervix and the association between the number of birth, sexual partners and colposcopic changes and cytological atypia. Material and Methods: Colposcopic changes in the cervix in relationship to number of births, abortions, and number of sexual partners were determined based on data from examinations performed at the Obstetric-Gynecologic Clinic in Prishtina, Kosovo during 2006 and 2007. The 500 examined patients were categorised in several groups. Results: All study patients underwent colposcopy. Colposcopic atypia was observed in 70 patients (14%), and 77 (15.4%) had other abnormal findings. The amount of colposcopic atypia increased with an increasing number of sexual partners. In the group with three or more sexual partners (nВ =В 43) the rate was 62.8%. Infections were also more frequent in this group; of the 43 patients examined, 51.3% (22 patients) had infections, whereas in the group of 76 patients with only one sexual partner, 18.3% had infections and only 20.6% used contraceptives. Conclusion: Number of births, abortions, number of sexual partners, and contraceptive use directly affect colposcopic changes and cytological atypia. Keywords: colposcopy, endometrial changes. contraceptives 1. Introduction The uterine cervix is very susceptible to infections and is thus vulnerable to numerous pathological processes (1,2,3,4,5,6). In addition, injuries to the cervix incurred while giving birth or injuries incurred during an abortion or the course of other gynecologic or obstetric procedures often result in disorder of the cervix’s functional and anatomic structure (7). In women, cervical cancer is a major cause of death from malignant diseases (1). Three different groups of factors that increase the risk for this disease have been described (8): (1) infection with human papilloma virus (HPV) and the duration of viral infection; (2) conditions such as multiparity and poor nutrition that compromise the immune system; and (3) lifestyle factors such as smoking, contraceptive use, and number of sexual partners, as well as the age at menarche. The link between cervical cancer and human papilloma virus (HPV) infection is well established (4). HPV infections are more frequent in more sexually active females, and the virus is found in more that 90% of intraepithelial lesions detected in younger women (5). Although, the majority of the infections pass after several months or years, a small percentage of the virally infected cells slowly undergo malignant transfor- mation (9, 10), with invasive disease affecting mostly older women. The role of immunodeficiency virus (HIV) in the pathogenesis of cervical cancer is not clear yet, although it a has been shown that HPV is more frequently present in HIV-seropositive patients than in those who are HIV-seronegative (11). Cervical cancer can be detected and characterised with respect to the involved area, degree of differentiation, and atypia in the vagina by examination with a special binocular magnifier, the colposcope. The main function of colposcopy is the early diagnosis of pre-cancerous cells in the cervix. In the majority of patients, it enables the early detection of cancer and thus allows the use of more conservative treatment (including electrocautery, diathermy, cautery, cryotherapy, and laser) of atypical changes, thereby avoiding more aggressive conisation and gynecologic surgery. The early detection of cytological changes is further enhanced by the combined use of the cytological Papanicolau technique and colposcopy. Cytological analysis detects endocervical changes, which are not seen with colposcopy. Together, these methods result in the early and certain detection of carcinoma of the cervix in over 85% of patients. Moreover, with the advent of organised screening programs, cancer of the cer- vix has become relatively rare in young women (<25 years of age). Instead, cervical cancer mainly affects older women, especially those who have not benefited from screening (2). Despite the advent of these non-invasive methods for early detection of malignant diseases of the cervix, in Kosovo, early detection is relatively rare because of unfavourable socio-economic conditions. The aim of this research study is to obtain more accurate data on the effect of different factors in the pathology of the cervix, more specifically the role of abortions, number of births, and number of sexual partners. 2. Patients and Methods To study the relationship between colspocopic changes in the uterine cervix and number of births, abortions, and sexual partners, data from examinations performed at the Obstetric-Gynecologic Clinic in Prishtina, Kosovo during 2006 and 2007 were analysed. Vaginal smears were taken for cytological analysis, after which colposcopy was performed using a ZeissOberkochen colposcope, with a 20Г— magnification. Extended colposcopic examination consisted of swabbing the vagina and cervix with 3% acetic acid and using these samples for the Schiller test with iodine. Tissue from abnormal areas was biopsied and submitted for histopathological testing. The 500 patients in the study were classified in groups based on the numbers of births, abortions, and sexual partners. Group 1 comprised patients who had not given birth or had abortions; group 2, patients who had not given birth but possibly had a spontaneous or induced abortion; group 3, patients had given birth once and possibly a spontaneous or induced abortion; group 4, patients had given birth twice and possibly a spontaneous or induced abortion; and group 5, patients had given birth three or more times. Our research did not include pregnant women or women who had undergone any procedures involving the cervix (conisation, thermocoagulation, polypectomy, or plastic surgery of the cervix). 3. Results All women who participated in the study underwent a colposcopy examination (Table 1). Atypical colposcopic changes were detected in 70 women MED ARH 2009; 63(3) • ORIGINALNI ДЊLANCI / ORIGINAL PAPERS 137 Table 1. Atypical and abonormal colposcopic findings according to patient group Colposcopic Changes Based on Number of Sexual Partners, Births, and Contraceptives Use Atypical and abnormal Table 1. Atypical and abonormal colposcopic findings according to colposcopic patient group findings Atypical and abnormal colposcopic findings Atypical Group Changes Atypical Transformation Zone White epithelium Base of leucoplaky Mosaic Leucoplakia Atypical Vascularization Suspicion of malignancy Total number of changes Inflammatory changes True erosion Condyloma accuminata Papilloma Polyps Total number of changes 1 0 0 0 0 0 0 2 0 1 0 3 - 2 3 0 2 0 0 4 16 0 1 1 18 3 9 Group Total number of such changes was higher in Changes 1 2 3 4 5 N women having Atypical Transformation Zone intercourse 0 3 once 9 a7 week 23 42 Total White epithelium - - more than in those who reported freBase of leucoplaky - quent intercourse, and0 for0 colpitis, lac-Mosaic 2 3 13 18 N Leucoplakia % erations, and atypical colposcopic 0 2 5 3 find18 28 42 Atypical 8.4 Vascularization 0 0 significant. 3 4 23 30 ings, the differences were of malignancy 0 0 0 1 1 - Suspicion However, there may be 00other factors that number of changes 4 13 10 43 70 - Total explain these changes, as women Inflammatory changes 2 16 11 11 who 20 60 18 3.6 True erosion 0 0 0 as 1 well 5 6 did not have sexual intercourse 28 5.6 Condyloma accuminata 1 1 1 2 0 5 as widowed, divorced, and older women 30 6 Papilloma - 1 Polyps 0.2 were included in the group 0 1of women 2 0 en3 6 70 Total 14 number of changes 3 18 a 14 14 28 77 gaging in intercourse once week. 4 5 7 23 Atypical 2 3 13 5 3 18 3 4 23 0 0 1 13 10 43 Abnormal 11 11 20 60 12 0 1 5 6 1.2 1 2 0 5 1 0 2 0 3 6 1.2 14 14 28 77 15.4 4. Discussion The main causes of malignant processes in the cervix are now known. Abnormal Among these, experimental and epidemiologic research has found that the on(14.0%), and other findings were noted ceptive use, the frequency of all other set of carcinoma of the cervix is directly in 77 (15.4%). Based on the group clas- changes was significant in women who sifications, the frequency of changes in- used contracreased from the first group, in which ceptives com- Table 2. Patients based on residence and age at first sexual activity only three patients had other findings pared to those Age at first Village residents City residents Total and none had atypical changes, to the who did not. sexual % Number % Number % fifth group, in which 43 patients had L ac e r at i o n s activity, years Number atypical changes and 28 had other find- were detected ≤19 58 40.56 145 40.62 203 40.60 ings (Table 1). in 35 (34.0%) Table 2. Patients based onofresidence and ageofatthe first103 sexual Nearly half (46.8%) the women pa- activity20-24 63 44.06 171 47.9 234 46.80 inAge the at study became sexually active bet i e n t s w h o first Village residents City residents Total25+ 22 15.38 41 11.48 63 12.60 tween the ages of 20 and 24 years, and used contrasexual 40.6% reported sexual activity at age ceptives and Total % 143 100.00 357 100.00 500 100.00 % Number % Number activity, years Number 19 (Table 2). No major differences were in 66 (16.6%) 3. Marital status of the study participants noted≤19 between58women who in vil- of40.62 the 397 203 who Table40.60 40.56lived145 Table 3. Marital status of the study participants lages and those who lived in cities, except did not. Marital status Total 63 44.06 171 47.9 234i46.80 Marital status Total that a20-24 larger proportion of village women A pprox Number of Not Married Divorced Widowed Number % became sexually active at an older age mately 44% of Number marriages of married Not Married Divorced Widowed Number % 25+ 22 15.38 41 11.48 63 12.60 (>25 years) compared with city women the women in marriages married 0 62 62 12.4 (15.8% the study500 reTotal vs. 11.48%, 143 respectively). 100.00 357 100.00 100.00 0 62 62 12.4 1 387 31 5 423 84.6 The majority of the women in the p or t e d t h at 387 5 study were married (80%); 6.6%, di- they engaged 21 -10 131 11423 2.284.6 vorced; 1.0%, widowed; and 12.4%, not in sexual inter2 3+ -310 11 4 11 0.82.2 married (Table 3). course three 3 1 n (%) 62 (12.4) 400 (80) 33 (6.6) 5 (1) 5004 1000.8 The study participants were as- or more times Total,3+ signed to one of the five groups de- p e r w e e k ; Total, n (%) 62 (12.4) 400 (80) 33 (6.6) 5 (1) 500 100 scribed above. Groups 1–5 consisted of 30.4%, twice 100 women each. Of the 100 women in per week; and Table 4. Number of births and abortions group 5, 60 had 3-4 births, and 12 had 25.5%, once a and abortions of abortions Total 7 or more births. Regarding spontane- week (Table Table 4. Number of birthsNumber ous and induced abortions, nearly half 6). No conof abortions Total% Number 0 1–2Number3–4 5–6 7+ N of the women (235, 47.0%) reported no clusions could of births Number 0 1–2 3–4 5–6 7+ N % abortions; 42.2% (211), 1 or 2 abortions; be reached re0 100 91 9 200 40.0 of births 8.2%, 3-4 abortions; and 1.6%, 5-6 abor- ga rd i ng t he 10 57 38 59 -- 100 20.0 100 91 200 40.0 tions. Five patients had undergone 7 or r o l e o f t h e more abortions (Table 4). frequency 21 45 41 135 1100 20.00 57 38 100 20.0 The number of women who used con- of sexual in3-4 20 21 1113 51 3 60100 12.00 2 45 41 20.00 traceptives as a means of family plan- tercourse in 5-6 820 15 211 15 23 2860 5.60 3-4 21 12.00 ning was relatively low (103, 20.6%), but p a t h o l o g i pathological changes were observed sig- c a l ch a nge s 7+ 58 515 12 11 - 2 1228 2.40 5-6 5.60 nificantly more often in this group of pa- in the cervix. Total 235 211 411 81 550012 100.00 7+ N 5 5 2.40 tients (Table 5). Although the number of Perhaps sur42.20 8.20 1.60 1.00 100.00 infections did not correlate with contra- prisingly, the Total %N 47.00 235 211 41 8 5 500 100.00 % 138 MED ARH 2009; 63(3) • ORIGINALNI ДЊLANCI / ORIGINAL PAPERS 47.00 42.20 8.20 1.60 1.00 100.00 - % 8.4 3.6 5.6 6 0.2 14 12 1.2 1 0 1.2 15.4 Colposcopic Changes Based on Number of Sexual Partners, Births, and Contraceptives Use risk factors for questionnaire answered by the patients, the onset of the study population ranged in age from П‡ test Use of contraceptives pre-malignant 17 to 55 years, with nearly the majority Diagnosis (P value) Yes No Total and malignant between 20 and 29 years (233 women, (n = 103) (n = 397) (n = 500) cervical dis- 46.6%). Among the women in the age Colpitis, n (%) 30 (29.1) 85 (1.4) 115 (23.00) >0.01 eases: parity groups 19 years and younger and over and promiscu- 50, pathological findings were identiity (16). While fied in 13 (2.6%). Lacerations, n (%) 35 (34.0) 66 (16.6) 101 (20.20) <0.01 The cervical epithelium is very sensiincreasing parity as a risk tive and vulnerable during adolescence, Erythoplakia, n (%) 20 (19.4) 41 (10.3) 61 (12.20) <0.01 factor for cer- especially in those under the age of 19, v ica l cancer which may in part explain the associais supported tion between age at first sexual activOther atypical cervical findings, n (%) 5 (4.9) 16 (4.0) 21 (4.20) <0.01 by abundant ity and cervical cancer. Accordingly, we data and has paid special attention to this age group, long been rec- even though for many women sexual life Total, n 90 208 298 <0.01 ognized, pro- begins with marriage (16). This is parAdditional examinations of atypia miscuity is a ticularly true for women over the age of Atypical colposcopy, n (%) 39 (37.9) 73 (18.4) 112 (22.40) <0.01 relatively re- 50. However, we found that 40.6% of the cent issue, and women began an active sexual life before Papanicolau (groups III-IV), n (%) 18 (17.5) 24 (6.0) 42 (8.40) <0.01 there are sig- the age of 19, with no significant differSchiller test (positive), n (%) 30 (29.1) 61 (15.4) 91 (18.20) <0.01 nificant prob- ence between women from urban and lem s i n ob - rural areas. Atypical colposcopic findrelated to age at first sexual activity (12). taining accu- ings were detected in 12% of women who The number of atypical colposcopic rate data on the number of sexual part- became sexually active at an age younger findings increases with increasing age. ners. than 25 compared with 1.20% among Cytological changes of types III, IIIa, As determined from the results of a women who became sexually active afIIIb, IV, and V, based on the classifiTable 6. Atypical changes in the cervix as a function of the frequency of sexual cation system of Papanicolau, also inintercourse crease with age. In our study, there were Group 1 Group 2 Group 3 Group 4 Group 5 Total Frequency (n = 100) (n = 100) (n = 100) (n = 100) (n = 100) (n = 500) Diagnosis two cases (0.40%) of cytological changes of sexual Births, 0; Births, 0; Births, 1; Births, 2; Births, 3; N (%) in women 20–29 years of age, but there intercourse Ab, 0 Ab, + Ab, +/Ab, +/Ab,+/were 34 cases (6.80%) among women Colpitis 1 9 13 5 5 12 44 (8.80) 2 2 6 4 8 6 26 (5.20) >40 years old. These statistics are par3+ 7 14 9 10 5 45 (9.00) ticularly important because malignant Total 18 33 18 23 23 115 (23.0) processes in the cervix are preceded by Lacerations 1 0 0 4 10 21 35 (7.00) a prolonged period of cytological atypia, 2 0 0 3 11 22 36 (7.20) 3+ 0 0 5 9 16 30 (6.00) and the highest frequency of cervical Total 0 0 12 30 59 101 (20.20) neoplasia involves women 45–55 years Erythroplakia 1 0 1 4 4 4 13 (2.60) of age (13). 2 0 0 3 11 13 27 (5.40) In our study, the number of patients 3+ 2 5 2 5 7 21 (4.20) Total 2 6 9 20 24 61 (12.20) who used contraceptives was relatively 1 1 1 2 2 5 11 (2.20) small (103 women, 20.6%). The preferred Cervical atypia 2 0 1 1 0 4 6 (1.20) contraceptive methods were intrauterine 3+ 0 0 0 0 4 4 (0.80) devices and birth control pills. AtypiTotal 1 2 3 2 13 21 (4.20) 1 10 15 15 21 42 103 (20.60) cal colposcopic and cytological find- Total 2 2 7 11 30 45 95 (19.00) ings were significantly more apparent 3+ 9 19 16 24 32 100 (20.00) in women using contraceptives: for the N 21 41 42 75 119 298 (59.60) former, 37.9% compared with 18.4% for % 4.20 8.20 8.40 15.00 23.80 59.60 (-) non-users, and for the latter, 17.5% com- Additional pared with 6.0% for non-users. Similar diagnostic examinations results have been reported by other au- Atypical 1 1 6 8 11 17 43 (8.60) 2 1 3 6 4 16 30 (6.00) thors (14). Other atypical processes show 3+ 1 10 9 5 14 39 (7.80) a relatively similar tendency. Total 3 19 23 20 47 112 (22.40) We also determined that atypical Papanicolau 1 0 1 2 5 10 18 (3.60) colposcopic findings positively corre- (groups III-IV) 2 0 0 1 1 11 13 (2.60) 3+ 0 0 3 3 7 13 (2.60) lated with the number of births, increasTotal 0 1 6 9 28 44 (8.80) ing from three cases in the group with Schiller 1 0 5 5 7 16 33 (6.60) no births to 47 cases in the group with (positive) 2 0 2 4 2 16 24 (4.80) three or more births (15). 3+ 0 4 10 7 13 34 (6.80) Total 0 11 19 16 45 91 (18.20) Other authors have identified two Table 5. Use of contraceptives and changes in the cervix 2 MED ARH 2009; 63(3) • ORIGINALNI ДЊLANCI / ORIGINAL PAPERS 139 Colposcopic Changes Based on Number of Sexual Partners, Births, and Contraceptives Use ter the age of 25. Erythoplakia was more frequent in the former group, which had 31 cases (6.20%) versus five cases (1%) in the latter group. Due to the link between promiscuity and cervical cancer, we questioned the women regarding frequency of sexual activity. Slightly less than half the women (222, 44.4%) reported engaging in sexual intercourse more than three times per week, but we did not obtain data as to whether intercourse was always with the same partner. There were no significant differences between this group and the group that engaged in sexual activity once per week. However, colpitis was more frequent in the group with three or more sexual partners (51.2%) than in the group of women with one partner (18.3%). Both HPV and Chlamydia trachomatis have been linked to cervical changes, but their effects on the cervix are independent of each other (17). Atypical colposcopic findings tended to increase with an increasing number of partners: 17.8% in the group with one partner but 62.8% in the group with three or more partners. The association between the number of births and abortions and pre-cancerous and cancerous processes in the cervix uteri has been addressed by many authors but without a consensus (10). Erythoplakia increases with an increasing number of births. Nine cases were detected in the group of women with one birth; 20 cases, in the group with two births; and 24 cases, in the group with three births. These increases were highly statistically significant. Cervical lacerations during the birth process, particularly in women who carried past term, are related to pathological changes in the cervix and were detected in 101 of the 500 women (20.20%) who participated in the study, and in 33.67% of the women who had given birth. These figures are higher than the 11.5/36.67% reported in a previous study (2). In atypical colposcopic findings, there is a dominant atypical zone of transformation. This was not seen in the group with no births, whereas there 140 Women’s colposcopy experience and preferences: a mixed methods study. 14 January 2008. 8. Terzic B. Uloga kolposkopije u otkrivanju HPV na donjem genitalnom traktu zene. Jugoslovenska skola za patologiju cerviksa, vagine vulve i kolposkopiju, Beograd 1996:16-8. 9. Cullhed S. Carcinoma cervicis uteri stages I and IIa. Treatment–histopathologyprognosis.Acta Obstet Gynecol Scand Suppl. 1978;75:1-149. 10. Stanimirovic B. Infekcija cerviksa humanism papilloma virusima i njena uloga u onkogenezi.Patologia cerviksa. Beograd, 1996;27-9. 11. Divisions of HIV/AIDS Prevention. HIV and Its Transmission. Centers for Disease Control & Prevention. Retrieved on, 200605-23 12. Marrazzo JM, Martin DH. Management of 5. Conclusion Women With Cervicitis. Clin Infect Dis, The number of births, abortions, and 2007; (S3): S102. doi:10.1086/511423. sexual partners as well as contraceptive 13. Popovic D. Razvoj kolposkopije I njeno use directly influenced the frequency mesto u detekciji prekancerozivnih promena i ranih stadijuma carcinoma donjeg of atypical colposcopic and cytological dela genitalnog trakta zene.Jugoslovenska findings. Our results show that the numskola za patologiju cerviksa, vagine, vulve ber of births and the number of sexual i kolposkopiju.Beograd, 1996. partners are directly related to patholog- 14. Stranimirovica B. Faktori rizika u nasical changes in the cervix. Both colpostanku maligne bolesti grlica materice, copy and cytology demonstrated an inznacaj njihovog ranog otkrivanja, za profilaksu, terapiju i prognozu bolesti. Dokcrease in pathological findings with intorska disertacija, Beograd, 1988. creasing patient age. 15. Berisavac M. Nova nomlenklatura u kolposkopiji: Znacaj jedinstvenih kriterijuma REFERENCES u kolposkopskoj diagnostici. Jugoslovenska 1. Cunningham G, Leveno K, Bloom LS, skola za patologiju cerviksa, vagine, vulve Hauth CJ, Gilstrap L., Wenstrom K, Wili kolposkopiju.Beograd, 1996. liams Obstetrics, 22nd edition, 2005; 16. WorkoWski K, Berman S. Sexually trans1303-8. mitted diseases treatment guidelines, 2. Elsebeth Lynge Danish Cancer Registry, 2006. MMWR Recomm Rep, 2006;55 (RRInstitute of Cancer Epidemiology, Dan11):1–94. ish Cancer Society, Landskronagade 66, 17. Claas ECJ, Melchers WJG, Niesters HM, DK-2100 Copenhagen, Denmark. ScreenRuud van Muyden, Stolz E, Quint WGV. ing for cancer of the cervix uteri. May 16, Infections of the cervix uteri With hu2005 man papillomavirus and Chlamydia tra3. American Cancer Society. What Are the chomatis Journal of Medical Virology, Risk Factors for Cervical Cancer?. Re2005;37(1):54-7. trieved on 2008-02-21. 18. Kesic V. Normalni i patoloski kolposkop4. G r g u r e v i q M , P a v l i c Z , G r i z e l j , siki nalazi. Jugoslovenska skola za patologV; [Gynecology, 3rd ed., Croatioan]. iju Cerviksa, vagine, vulve i kolposkopiju. Zagreb:Jugoslovenska Medicinska Nak1996;107-9. lada 1987; 110-15. 19. Eckerert et al. Inflammation on Papanico5. Poevonen J, Teisal K, Heinonen P K et al. laou. Obstet Gynecol, 1995;86:360-6. Endometrititis and acute salpingitis associated with Chlamydia trachomatis and herpes simplex virus type. Wo. Am J ObCorresponding author: Myrvete PaГ§arada, stet Gynecol, 1985; 65:288-91. MD, PhD. Gynecology/Obstetrics Clinic; 6. Bukovi D. et al. Sexual Life after Cervical University Clinical Centre of Kosova, Rrethi i Carcinoma, Coll. Antropol. 2003;1: 173– Spitalit pn. 10 000 Prishtina Phone: +377 44 80. 111089, e-mail: myrvetepaqarada@hotmail.com 7. Wancutt DRS, Greenfield SM, Wilson S. were 23 cases in the group with three or more births. Poor economic conditions negatively impact health, including a general weakening of the immune system (20). Furthermore, the frequency of gynecologic examinations is an important factor in the early detection of atypical findings in the cervix. Contraceptive use may also play a role in the prevalence of pathological changes in the cervix, as seen in five women in the present study. Interestingly, this effect was also evident in women who used mechanical contraceptive devices. MED ARH 2009; 63(3) • ORIGINALNI ДЊLANCI / ORIGINAL PAPERS Diagnostic Value of CEA in Pleural Fluid for Differential Diagnosis of Benign and Malign Pleural Effusion Diagnostic Value of CEA in Pleural Fluid for Differential Diagnosis of Benign and Malign Pleural Effusion Tatjana Radjenovic-Petkovic1, Tatjana Pejcic1, Desa NastasijeviД‡-Borovac1, Milan Rancic1, Danijela Radojkovic2, Milan Radojkovic3, Ivanka Djordjevic1 Clinic for Lung Disease, Clinical Center Nis, Serbia1 Clinic for Endocrinology and Toxicology, Clinical Center Nis, Serbia2 Clinic for Surgery, Clinical Center, Nis, Serbia3 Original paper Summary The diagnostic value of tumor markers in pleural fluid is still the subject of debate. The aim of this work was to evaluate diagnostic value of carcinoembryonic antigen (CEA) in pleural fluid for differentiating malignant from non malign pleural effusion, and their additive value to cytological examination. Design: Prospective, case control study. Setting: Tertiary University hospital, Clinic for Lung Disease, Knez Selo. Patients: Eighty two patients with pleural effusion, forty one with malignant, and forty one with non malignant pleural effusion. Measurements and results: Levels of CEA in pleural fluid was measured by IRMA CEA methods, INEP Belgrade. Patients with lung cancer were found to have significantly higher CEA levels than patients with non malign pleural effusion. Using cut off values of 2.4 ng/ml, the sensitivity of marker was 78%, and specificity 95.1 % (CI 95%). The addition of CEA to cytology increase diagnostic rate from 68 to 85.3%. Conclusion: CEA may represent a helpful adjunct to cytology in order to include malignancy as probable diagnosis, thus guiding the selection of patients for more invasive procedures. Keywords: pleural effusion, CEA, cytology 2.3. Statistical analysis Non parametric analysis wes used to make group comparation. Differences between two independent groups were determinated by means of the Man Whitney U test. In an attemp to establish a sensitivity-specifity relationship, reciever-operating characteristic (ROC) curves was constructed, using values levels of CEA in patients with malignant pleural effusion, and patients with benign pleural effusion as controls. Valus of p less than 0,05 were considered as significant. 3. Results Of 82 subjects, 41 (group I) had a malignant, and 41 (group II) had non malign pleural effusion. A detailed account of the etiology is presented in table 1.Of 41 patients with malignant pleural effusion, 21 subjects (51,2%) were male, and 20 (48,8%) were female. The mean age in this group were 62,8 years (range 48-80 years). Of 41 benign cases, 29 subjects (70,8%) were male, and 12 (29%) were Effusion were conNeoplastic Non neoplastic sidered as maligetiology number % etiology number % nant if one of the 28 68,29 parapneumonic 13 31,70 following critheria Lung mesothelioma 2 4,87 empyema 8 21,95 was met: 1. DemonBreast 4 9,76 tuberculosis 9 21,95 stration of maligCongestive nant cells at cyth- Ovary 2 4,87 7 17,07 heart failure ological examina1 2,44 Liver cirhosis 2 4,88 tion 2. Demonstra- kidney Dressler tion of malignancy uterus 1 2,44 1 2,44 syndrome on pleural biopsy Connective speciement. The prostate 1 2,44 1 2,44 tissue disease critheria for non 1 2,44 Traumatic 1 2,44 malignant effusion leukemia liver 1 2,44 have been refered total 41 total: 41 elswere (5). Table 1. Ethiology of the effusions 2.2. CEA measurment Pleural fluid for female, mean age 63,1 years (range 25CEA mesurment were colected and 85 years). The histological tipes of neofrosen to -70oC. The levels of CEA were plasm are shown in table 2. measured using immunoradiometric assay, IRMA CEA (INEP, Belgarde, Serbia). n=41 % The assays is based on two monoclonal Hystological types antibodies specific for CEA, not cross re- adenocarcinoma 22 53,66 active with other CEA related moleculs, Small cell carcinoma 4 9,76 suited for use in solid phase assays. The Squamous cell carcinoma 4 9,76 assays is standardised against 1st Inter- mesothelioma 2 4,87 national Reference Preparation of CEA, lymphoproliferative 1 2,44 2. Materials and methods 73-601 (NIBC, WHO). Detection lim- others* 8 19,51 2.1. Patients its of the assays is 0,5 –l mg. Inter and We collected pleural fluid from 82 intraassay variations are less than 10%. Table 2. Malignant effusion: histological types, patients who were admited to the Clinic The bound radioactivity was measured *undifferentied n=6, hepatocarcinoma n=1, rГ©nal carcinome n=1 for lung disease due to pleural effusion. using g-counter. 1. Introduction Pleural effusion is common problem in clinical practice. The differential diagnose is diverse, but most common cases include malignancy, congestive hurt failure, tuberculous and pneumonia related effusion (1). Malignant pleural effusion can be initial presentation of the disease in 10-50% of patients (2). Cytology is standard method for the diagnosis of malignant effusion, but sensitivity of cithology is 40-80%, depending of tumor tipes (3). Altrough thoracoscopy can establish the diagnosis in aproximately 90% of patients with malignancy (4), this procedure may not be available at all facillites, or may be to invasive for patients with poor performance. Several tumor markers in pleural fluid have been evaluated to distinguih benign from malignant pleural effusion, but carcinoembrionic antigen has been studied the mostResults in literature are still contraversal. The aim of this study were to investigate role of CEA in distinguishing malignant and non malign pleural effusion, and their aditive value to cytological examination. MED ARH 2009; 63(3) • ORIGINALNI ДЊLANCI / ORIGINAL PAPERS 141 Diagnostic Value of CEA in Pleural Fluid for Differential Diagnosis of Benign and Malign Pleural Effusion CEA (ng-ml) malignant benign n 41 41 Mediana 44,50 1.200 meanВ±SD 55,76В± 57,25 1,23В±0,55 SE Max 9,05 0.113 164,00 2.400 Table 3. Pleural fluid level of CEA Sensitivity of citology 0,38 is 20-80%, 0.890 depending of tumor tipes Min adenocarcinoma (light). Therefore, value of pleural fluid CEA would be limited in the PE other than adenocarcinoma. The adition of CEA to citology increase diagnostic rate from 68 to 85,3%. We shown that CEA can imrove citology sensitiv- The median, mean and standard de(2) In aproxiviation levels for the CEA in group I sensitivity Specifity PPV NPV mately 40% of % % % % and group II are shown in table 3. The cases, citology ROC curve with cut off value, specifity 28/41 (68,2) 41/41 (100) 28/28 (100) 41/54 (75,92) does not pro- citology CEA 32/41 (78,05) 40/41 (97,56) 32/33 (96,97) 40/49 (81,63) v ide a de c iCEA+ citology 35/41 (85,36) 40/41 (97,56) 35/36 (97,22) 41/46 (89,13) sive answer to wheather pleu- Table 5. Operating caracteristics of CEA and citology in pleural fluid ral effusion is malignant or ity, but it depends from histological tipe not (7). In that cases, many autors sugof tumor. gest the evaluation of different tumor In the cases of suspicion malignant markers in pleural fluid . Therefore, we pleural effusion with negative citological evaluated the diagnostics utility of CEA the determination of CEA may be helpto differentiate malignant from benign ful as a complementary tool for the difpleural effusion. CEA is mostly used tuferential diagnosis of pleural effusion. mor marker, since its not tumor specific. Results of his usefull is contraversal. It REFERENCES is difficult to drow comparation amnog 1. Light RW. Tumor Markers in Undiagnosed Pleural Figure 1. Receiver operating curves for CEA levels such studies, since there are differences Effusions. Chest 2004, 126; 1721-22. in pleural fluid in numberof patients and etiology of ef- 2. Hwa Lee J, Chang JH. Diagnostic utility of serum and pleural fluid carcinoembryonic antigen, neufusion , as well as lack of uniformity in ron-specific enolase, and cytokeratin 19 fragments and sensititivity are shown in graf. 1. the laborathory metodology, and the in patients with effusions from primary lung canThe number of positive CEA among pacer. Chest, 2005;128:2298–303. parametar established as cutt off pointes tients with malignant pleural effusion 3. Sallach SM, Sallach JA, Vasquez E, Schultz L, Kvale to determinate specifity-sensitivity, toP. Volume of pleural fluid required for diagnosis of who have negative cithology findings is gether with the tumor tipe in in the pleural malignancy. Chest, 2002;122: 1913-17. reported in table 4. groups studied. CEA was found to be 4. Light RW. Pleural effusions related to metastatic malignancies. In: Light RW, ed. Pleural diseases. tip tumora CEA>2,4 ng/ml best single marker in pleural fluid in ac4th ed. Philadelphia, PA: Lippincott, Williams & cordance to previous reports (2). Wilkins, 2001:108-34. Lung adenocarcinoma 3/3 Altroug usually evaluated in terms of 5. Porcel JM, Vives M. Differentiating tuberculous Squamous cell carcinoma 2/3 from malignant pleural effusions: a scoring model. sensitivity, specifity and accurency, a vaMed Sci Monit, 2003;9:175–180. Small cell carcinoma 0/3 riety of criteria have been used to asses 6. Romero S, FernГЎndez C, Arriero JM, Espasa A, hepatocarcinoma 1/1 Candela A, MartГn C,. SГЎnchez-PayГЎ J. CEA, CA diagnostic value of CEA in pleural fluid. 15-3 and CYFRA 21-1 in serum and pleural fluid Adenocarcinoma uteri 1/1 Some autors used a specifity of 100% (8), of patients with pleural effusions.Eur Respir J, Mesotelioma 0/1 but with poor sensitivity. Because of that, 1996;9:17–23. 7. Porcel JM, Vives M, Esquerda A, Salud A, PГ©rez Table 4. CEA values higher than cut off threshold some groups agee to use specifity of 95% B, RodrГguez-Panadero F. Use of a panel of tumor markers (carcinoembryonic antigen, cancer antiamong malignant effusion with negative citology as the cut off pintes (9). The use of ROC gen 125, carbohydrate antigen 15-3, and cytokerresults curve helps to preserve i higher sensitivatin 19 fragments) in pleural fluid for the differential diagnosis of benign and malignant effusions. ity than when using 100% specifity as a Specifity, sensitivity, PPV and NPV 2004;126(6):1757-63. points reference, and avoides the burden 8. Chest, Villena V, Lopez-Encuentra A, Echave-Sustaeta of CEA and citology are shown in taof 5% false positive cases. Using ROC J, MartД±n-Escribano S, Ortuno-de-Solo J, Esteble 5. Diagnostic yield of citology was noz-Alfaro J. Diagnostic value of CA 549 in pleucurve, we found that pleural fluid CEA ral fluid. Comparison with CEA, CA 15.3 and CA 68,2%. The combination use of citology have high diagnostic accurancy. Our re72.4. Lung Cancer, 2003;9:289-94. and CEA increased the detection rate sults are similar with Hwa Lee (2) study 9. Salama G, Miedouge M, Rouzaud P, Mauduyt MA, of malignant pleural effusion to 85,36%. Pujazon MC, Vincent C, Carles P, Serre G. Evalu(cut off 5 ng-ml, sensitivity of 82,4%). ation of pleural CYFRA 21–1 and carcinoembryonic antigen in the diagnosis of malignant pleural Sensitivity in our study was beeter than 4. Discussion Br J Cancer, 1998;77:472-76. in Alatas et all (10) study. Better sensi- 10. effusions. AlataЕџ F, AlataЕџ O, MetintaЕџ M, Colak O, Harmanci Pleural effusion is often a clinical tivity of CEA in our study may be conE, Demir S. Diagnostic value of CEA, CA 15-3, CA problem in medical practice, as differ19-9, CYFRA 21-1, NSE and TSA assay in pleural sequence of adenocarcinoma dominaeffusions. Lung Cancer, 2000;31(1): 9-16. ential diagnosis includes awide wariety tion, and small group of small cell carof local or sistemic diseases. Any carcinoma and mesothelioma. Measurcinoma can metastase to pleura, but Corresponding author: prof Tatjana ment of CEA in pleural fluid improved the most common primary sites are the the sensitivity of citology. This fact has Radjenovic-Petkovic, MD, PhD. Clinic for lung lung, brests, and ovary (6). Histological disease, Clinical Center Nis, Serbia. been found in other studies (7,8). Pleuconfirmance of malignancy is still the ral effusion occurs with all tumor tipes, only definitive diagnosis of malignancy. but appert to be the most frequent with 142 MED ARH 2009; 63(3) • ORIGINALNI ДЊLANCI / ORIGINAL PAPERS Effects of Extracorporeal Shockwave Lithotripsy on Renal Vasculature and Renal Resistive Index (RI) Effects of Extracorporeal Shockwave Lithotripsy on Renal Vasculature and Renal Resistive Index (RI) Mustafa Hiros, Mirsad Selimovic, Hajrudin Spahovic, Sabina Sadovic Urology Clinic, Clinical Center University Sarajevo, Bosnia and Herzegovina Original paper SUMMARY Objective: It is known that ESWL can promote acute renal injuries and long–term complications of renal vasculature. Effects on renal vasculature can be evaluated by color Doppler ultrasonography measuring renal resistive index (RI). This prospective study aimed to determine the influence of number of delivered SW-s, used kV and changes in renal resistive index. Patients and Methods: Total of 60 normotensive patients, 38 males (63%) and 22 females (37%), with renal stones 6-18 mm in size were included in this study. Median age was 42.3 years (range 22-55). RI was measured at interlobar artery before, 1, 3, 5 and 30 days after treatment on treated and contra lateral non-treated kidney. Patients were divided in two groups: Group I (N=25) received 2000SWs; 0-2 units; (0,5 unit each 500SWs) Group II (N=35) received 4000SWs, 0-4 units; (0,5 unit each 500SWs). Results: In treated kidneys RI significantly increased first and second day after treatment from 0,62В±0,05 at baseline to 0,67В±0,05, p<0,001 at first and 0,66В±0,05, p<0,007 on the second day after treatment. Increase of RI seven days after treatment is not significant (0,62В±0,05). The contra lateral, non-treated kidney showed significant changes in RI only first day after treatment (0,64В±0,05), p<0,01. One month after the treatment RI is on normal values in both kidneys. Conclusions: Resistive index -RI is important parameter in evaluation of renal vasculature. Patients treated by ESWL showed a temporary increase in RI two days after the treatment and only first day in contra lateral non-treated kidney - probably caused by release of substance with vasoconstriction properties (need further investigations). Keywords: extracorporeal shock-wave lithotripsy, renal stones, color Doppler ultrasonography, renal resistive index tient was 2000 to 4000 SW-s. The mean maximum 0 to 4 units (energy steps loaded in kV, voltage was 21.6 kV (range 19–22 kV). Colour Doppler examinations were performed on a Siemens Sonoline G40 using a 3.75-MHz convex transducer. In the study group, measurements were made in the renal interlobar arteries before, first, second, seventh and thirty days after ESWL. For renal stones, measurements were made in the vicinity of the stones (nearby region), at a distance of at least 2 cm from the stones (remote region) and in the contra lateral kidney. Measurements were made when three similar waves were registered sequentially. Measurements were repeated three times for each region, and the RI value recorded for each region was the arithmetic mean of these three measurements. Vascular resistance was determined at an artery of renal parenchyma with the help of pulsed wave Doppler ultrasound. To eliminate the problem of angle correction the RI was calculated by the equation: (systolic peak velocityend diastolic peak velocity) / systolic peak velocity. The paired t-test, a parametric test, was used to compare RI values at 1,2,7 days and 30 days post-ESWL with preESWL values in the renal stones group. The paired t-test was also used to compare RI values in the nearby and remote regions with those in the contra lateral kidney for the pre-ESWL measurement and both post-ESWL measurements. 22 females(37%) with renal stones size 6-18mm, who underwent ESWL. Their ages ranged from 22 to 55 years, with mean ages of 42,3 years. Stones were diagnosed by means of i.v. urography (IVU), X-ray and ultrasonography. Patients with normal kidney function on IVU and normal parenchyma echo on ultrasonography were included in the study. Patients with diabetes melli- 3. RESULTS tus, renal parenchyma disease or uriMean blood pressure in patients with nary system infections were excluded. renal stones was 118/79 mmHg before Patients with hypertension (diastolic and 124/83 mmHg after ESWL. No sigblood pressure 90 mmHg and/or sys- nificant changes were found between tolic blood pressure 140 mmHg) and patients receiving hypertensive therapy were also excluded. A mong pat ient s with renal stones (calyceal and pelvis renal stones), those with ecstasies in the collecting system were excluded. ESWL was performed using a Siemens Multiline 2. MATERIALS AND METHODS lithotripter. The avThe study group comprised 60 nor- erage number of Figure 1. Calculation of renal resistive index (RI) A peak systolic velocity; B motensive patients 38 males(63%) and shock waves per pa- peak end diastolic velocity. RI=(A-B)/A 1. OBJECTIVES Extracorporeal shock wave lithotripsy (ESWL) hase become a routine methode for treatement of upper urinary tract stone disease. It is effective and minimal invasive treatment for the most urinary stones, but also with significant acute renal injuries and longterm complications (1,2,3). At present, extracorporeal shock-wave lithotripsy (ESWL) is used in the treatment of 90% of all renal stones . Although its reliability and efficacy have been demonstrated, there are a number of studies concerning post-ESWL complications (4,5). However, major life-threatening complications are rare in either the early or late phase. Many techniques have been used to investigate the effects of ESWL on the kidneys, one of which involves measurement of the resistive index (RI) in the renal interlobar arteries using Doppler, a non-invasive diagnostic technique (6). In this study, colour Doppler ultrasonography was used to determine whether interlobar RI values were affected in patients treated with ESWL for renal stones. MED ARH 2009; 63(3) • ORIGINALNI ДЊLANCI / ORIGINAL PAPERS 143 Effects of Extracorporeal Shockwave Lithotripsy on Renal Vasculature and Renal Resistive Index (RI) Figure 2. Changes in resistive index (RI) in treated kidney. (Data were presented by mean В±SD 0,005) pre- and post-ESWL means blood pressures. No correlation was found between mean maximum voltage or average number of shock waves and changes in RI at 1, 2,7days and 30 days post-ESWL. In patients with renal stones, RI (mean kidney before ESWL, there were, however, significant differences 1 day and 2 day after ESWL. There was also a significant difference 1 day after ESWL between RI values in the contra lateral kidney. RI was measured in all patients with 4. DISCUSSION Resistive index 0,645 0,64 0,635 0,63 Resistive index 0,625 0,62 0,615 0,61 Before ESWL 1.day 2.day 7.day 30.day Figure 3. Changes in resistive index (RI) in contra lateral-not treated kidney. (Data were presented by mean В±SD 0,005) В±SD) in the nearby region was 0.62 В± renal stones 30 days after ESWL. There 0.05 before ESWL, increasing to 0.67 were no statistically significant differВ± 0.05 at 1 day; to 0.66 В± 0.05 at 2 day ences between RI values in the nearby and to 0,62 В± 0.05 at 7 day post-ESWL. or remote regions and those in the conBoth post-ESWL values first and second tra lateral kidney either before or 30 days day were significantly different from the after ESWL. RI values in the nearby repre-ESWL values (p =0.001). RI was at gion and contra lateral kidney 1, 2 and base line 30days after ESWL 0,62 В± 0,05. 7 days after ESWL did not differ signifThere was an increase in RI after ESWL icantly from those before ESWL. Howin the contra lateral kidney. This difference was significant at first day after ESWL 0,64 В± 0,05. Di f ferences between pre- and postESWL values in the contra lateral kidney are shown in Fig.4. There were no significant differences between RI in the nearby or remote regions and Figure 4. Sequent changes in RI in ipsilateral and contra lateral kidney in the contra lateral 144 ever, values recorded in the remote region 1 week after ESWL were not significantly higher than those recorded before ESWL. There was also no statistically significant difference in the contra lateral kidney between pre-ESWL and 2,7 and 30 days post-ESWL values (p > 0.05), but there was a significant difference between pre-ESWL and 1 day post- ESWL values 0,64 В± 0,05. No significant difference in RI values was determined in the ipsilateral and contra lateral kidneys before and 2,7 days and 30 days after the ESWL procedure in patients with renal stones (p > 0.05). RI was measured in all patients with renal stones 30 days after ESWL; there was no statistically significant difference between these values and pre-ESWL values in either the ipsilateral or contra lateral kidney. MED ARH 2009; 63(3) • ORIGINALNI ДЊLANCI / ORIGINAL PAPERS The safety and efficacy of ESWL has been proved by a number of studies investigating acute renal injuries from ESWL by various techniques (7,8,9,10). ESWL has been used since the 1980s for the treatment of urolithiasis, and its efficacy and reliability have been established. A number of methods have been used to investigate post-ESWL changes in the kidney, including IVU, ultrasonography, CT, MRI, radionucleide renography and serum and urine analyses. Although complications necessitating surgery, such as hematoma, are rare, MRI studies have revealed post-ESWL change rates as high as 74%. In studies of the effects of ESWL on renal RI using Doppler ultrasonography, a non-invasive method, measurements have been made at different times post-ESWL (11,12,13). The present study demonstrated that the RI of treated kidneys significantly increased after ESWL. As result of cellular infiltration and oedema formed around the peripheral branches of renal arteries, perivascular tissue thickening may occur and vascular resistance may therefore increase (14,15). In the present study, we found increased RI values at least 2 cm from the stones at 1 day and 2 day post-ESWL on ipsilateral kidney and 1.day on contra lateral kidney. Interestingly, although there was no difference between pre-ESWL and 7 days and 30 days post-ESWL values in the nearby region and the contra lateral kidney. Effects of Extracorporeal Shockwave Lithotripsy on Renal Vasculature and Renal Resistive Index (RI) 5. CONCLUSION The RI has proved to be a sensitive tool for monitoring vascular and tubulointestinals diseases of the kidney. It is widely used to detect intrarenal oedema, which occurs transplant rejection, acute tubular necrosis and obstructive pyelocaliectasis. In all conditions RI levels greater than 0,7 are considered to indicate pathologic change. In conclusion, there is a temporary increase in RI values in the first and second day following ESWL in the ipsilateral kidneys, which is most marked in the region near the renal stones. RI in contra lateral kidney is most market first day following ESWL. RI values return to normal within 7 day and 30 day after ESWL in ipsilatreal kidney and for contra lateral kidney RI values returns to base line 2 day post ESWL. ESWL did not indicate pathological RI changes in treated and non treated kidney. REFERENCES 3. 4. 5. 6. 7. 8. 9. 1. Aoki Y, Ishitoya S, Okubo K, et al. Changes 10. in resistive index following extracorporeal shock wave lithotripsy. Int J Urol, 1999;6:483-92. 2. Villanyi KK, Szekely JG, Farkas LM, et al. Short-term changes in renal function af- 11. ter extracorporeal shock wave lithotripsy in children. J Urol, 2001;166:222-4. Karlsen SJ, Berg KJ. Acute changes in kidney function following extracorporeal shock wave lithotripsy for renal stones. Br J Urol, 1991;67:241-5. Knapp PM, Kulb TB, Lingeman JE, et al. Extracorporeal shock wave lithotripsyinduced perirenal hematomas. J Urol, 1988;139:700-3. Knapp R, Frauscher F, Helweg G, et al. Agerelated changes in resistive index following extracorporeal shock wave lithotripsy. J Urol 1995;154:955-8. Ulrich JC, York JP, Koff SA. The renal vascular response to acutely elevated intrapelvic pressure: resistive index measurements in experimental urinary obstruction. J Urol, 1995;154:1202-4. Williams CM, Kaude JV, Newman RC, et al. Extracorporeal shock-wave lithotripsy: long-term complications. AJR Am JRoentgenol, 1988;150:311-5. Webb JA. Ultrasonography and Doppler studies in the diagnosis of renal obstruction. BJU Int,2000;86(Suppl 1):25-32. Dodd GD, Kaufman PN, Bracken RB. Renal arterial duplex Doppler ultrasound in dogs with urinary obstruction. J Urol, 1991;145:644-6. Willis LR, Evan AP, Connors BA, et al. Relationship between kidney size, renal injury, and renal impairment induced by shock wave lithotripsy. J Am Soc Nephrol, 1999;10:1753-62. Beduk Y, Erden I, Gogus O, et al. Evalu- ation of renal morphology and vascular function by color flow Doppler sonography immediately after extracorporeal shock wave lithotripsy. J Endourol, 1993;7:45760. 12. Newman R, Hackett R, Senior D, et al. Pathologic effects of ESWL on canine renal tissue. Urology, 1987;29:194-200. 13. NazarogluВ H, AkayВ A. Ferruh, BГјkteВ Yasar, Sa h i nВ Hay ret t i n et a l l . S c a nd i n avian journal of urology and nephrologyВ 2003,В vol.В 37.В 408-2.В 14. Karadeniz T, Topsakal M, Eksioglu A, et al. Renal hemodynamics in patients with obstructive uropathy evaluated by color Doppler sonography. Eur Urol, 1996;29:298301. 15. Kaude JV, Williams CM, Millner MR, et al. Renal morphology and function immediately after extracorporeal shockwave lithotripsy. AJR Am J Roentgenol, 1985;145:305-13. 16. Shokeir AA, Nijman RJ, el-Azab M, et al. Partial ureteral obstruction: role of renal resistive index in stages of obstruction and release. Urology, 1997;49:528-35. Corresponding author: Ass prof Mustafa Hiros, MD, PhD. Urology clinic. Clinical center of Sarajevo University. Bolnicka 25. E-mail: m.hiros@bih.net.ba MED ARH 2009; 63(3) • ORIGINALNI ДЊLANCI / ORIGINAL PAPERS 145 AerozagaД‘enje i trend hospitalizacije djece zbog bronhoopstrukcije na podruДЌju Tuzlanskog kantona AerozagaД‘enje i trend hospitalizacije djece zbog bronhoopstrukcije na podruДЌju Tuzlanskog kantona Air Pollution and Hospital Admission Trends of Children with Bronchial Obstruction in Tuzla Canton Devleta HadЕѕiД‡В№, Nada MladinaВ№, Farid Ljuca2, Mustafa BazardЕѕanoviД‡2 Klinika za djeДЌije bolesti, Univerzitetski kliniДЌki centar Tuzla, Bosna i Hercegovina1 Zavod za fiziologiju, Medicinski fakultet Univerziteta u Tuzli, Bosna i Hercegovina2 Klinika za urologiju, Univerzitetski kliniДЌki centar Tuzla, Bosna i Hercegovina3 Originalni ДЌlanak SAЕЅETAK Prevalenca bronhoopstrukcije kod djece je u stalnom porastu u svim uzrasnim kategorijama i po globalnim podacima. Brojne studije dovode u vezu stalni porast respiratornih oboljenja i aerozagaД‘enje. Cilj ovog rada bio je da se istraЕѕi moguД‡a povezanost trenda hospitalizacije djece zbog bronhoopstrukcije i visine izmjerenih koncentracija polutanata aerozagaД‘enja na podruДЌju Tuzlanskog kantona. Rezultati istraЕѕivanja pokazali su da je distribucija bolniДЌki lijeДЌene djece zbog bronhoopstrukcije u posmatranom jednogodiЕЎnjem periodu bila razliДЌita u odnosu na mjesto stanovanja i sezonu. Prostorna distribucija pokazala je najveД‡u zastupljenost pacijenata iz Tuzle, Lukavca i ЕЅivinica. Procenat lijeДЌene djece iz ovih opД‡ina bio je znaДЌajno iznad procenta koje su ove opД‡ine zauzimale u ukupnoj populaciji. Sezonska distribucija bolniДЌki lijeДЌene djece zbog bronhoopstrukcije statistiДЌki znaДЌajno se razlikovala u dvije posmatrane grupe opД‡ina i u dva perioda sezone grijanja. Polutanti aerozagaД‘enja, sumpordioksid i taloЕѕna praЕЎina, bili su znaДЌajno viЕЎih vrijednosti u sezoni grijanja u odnosu na sezonu bez grijanja. UtvrД‘ena je povezanost izmeД‘u trenda hospitalizacije djece zbog bronhoopstrukcije i visine izmjerenih polutanata aerozagaД‘enja. KljuДЌne rijeДЌi: bronhoopstrukcija, trend hospitalizacije, aerozagaД‘enje, djeДЌija dob. Original paper SUMMARY The prevalence of bronchial obstruction in children is continuously increasing at any age. Many studies have found associations between increase of respiratory diseases and air pollution. The aim of this paper was to establish possible connection between children hospital admission trends for bronchial obstruction and levels of measured concentration of air pollution agents in Tuzla Canton area. The results of investigation demonstrated that the distribution of hospital admissions of children with bronchial obstruction was different regarding place of inhabitants and season. Spatial distribution demonstrated that the highest number of children treated for bronchial obstruction was from Tuzla, Lukavac and ЕЅivinice. The incidence of patients from these municipalities was significantly above the participation of these municipalities in total population. Seasonal distribution of hospital admissions of children with bronchial obstruction was different for single municipalities of Tuzla Canton and for different seasons. Air pollutants, sulfur oxide and dust deposition were significantly higher for heating season compared to season without heating. There is a link between frequency of hospital admission for bronchial obstruction and level of measured air pollutants. Key words: bronchial obstruction, hospital admission trends, air pollution, childhood 1. UVOD Prevalenca bronhoopstrukcije kod djece u stalnom je porastu u svim uzrasnim kategorijama i po globalnim podacima (1). Prema veД‡ini istraЕѕivanja, oko 50% djece ima barem jednu epizodu bronhoopstrukcije u prvih 6 godina Еѕivota (2). Genetska predispozicija ima neosporan znaДЌaj, a izloЕѕenost odreД‘enim okolinskim faktorima u ranom djetinjstvu moЕѕe ubrzati nastanak ranih simptoma (1, 2). Brojne studije izvjeЕЎtavaju o porastu prevalence bronhoopstrukcije kroz trend prvih hospitalizacija, od kojih i do 75% su djeca ispod 4 godine, a preko 60% djeДЌaci (3). VeД‡ina autora govori o znaДЌajnom opadanju ponovnih hospitalizacija, ЕЎto se pripisuje unapreД‘enju lijeДЌenja (4, 5). Sezonske varijacije trenda hospitalizacije djece zbog 146 bronhoopstrukcije biljeЕѕe porast broja lijeДЌenih najДЌeЕЎД‡e u jesen i zimu, a u veД‡ini studija najmanji broj lijeДЌenih biljeЕѕi se u ljetnjim mjesecima (6, 7, 8). Autori to objaЕЎnjavaju sezonskim varijacijama uvjeta okoline, kao ЕЎto su aerozagaД‘enje i sezonske virusne infekcije. Studije koje izvjeЕЎtavaju o geografskim varijacijama incidence i prevalence respiratornih oboljenja, razlike u uДЌestalosti respiratornih oboljenja za pojedina podruДЌja vezuju uz ambijentalne uvjete sredine, prije svega nivo aerozagaД‘enja (9, 10). Brojne studije dovode u vezu stalni porast respiratornih oboljenja i aerozagaД‘enje. IzloЕѕenost polutantima aerozagaД‘enja (taloЕѕna praЕЎina, sumpor dioksid, azotdioksid i ozon) i njen efekat na zdravlje bila je predmet istraЕѕivanja brojnih epidemioloЕЎkih studija (9, 10, 11, 12, MED ARH 2009; 63(3) • ORIGINALNI ДЊLANCI / ORIGINAL PAPERS 13). ZnaДЌajno veД‡a prevalenca bronhitisa i perzistentnog kaЕЎlja, posebno kod mlaД‘e djece i ДЌeЕЎД‡e kod djeДЌaka, dovodi se u pozitivnu povezanost sa izmjerenim nivoom taloЕѕne praЕЎine kao polutanta aerozagaД‘enja (14). ZnaДЌajan porast prijema u bolnicu kod djece zbog respiratornih oboljenja u svim starosnim grupama, gdje dominira pneumonija i bronhitis kod djece mlaД‘e od 4 godine, a astma kod djece u grupi 5-14 godina, dovodi se u vezu sa izmjerenim nivoom polutanata aerozagaД‘enja, taloЕѕne praЕЎine, azotdioksida i sumpordioksida (15). VeД‡ina studija istraЕѕuje aerozagaД‘enje uzrokovano saobraД‡ajem (16, 17, 18 ). Tuzlanski kanton je najveД‡i kanton u Federaciji Bosne i Hercegodine. PovrЕЎine je 2792 km2 ЕЎto ДЌini 10,6 % ukupne povrЕЎine Federacije, i ima 611 000 stanovnika ЕЎto je 26 % ukupnog stanovniЕЎtva Federacije (19). Od toga 91 491 ДЌine djeca uzrasta do 15 godina. Tuzlanski kanton ima najveД‡u gustinu naseljenosti u Bosni i Hercegovini, koja iznosi 203 stanovnika na km2, ЕЎto je dvostruko viЕЎe od presjeka Bosne i Hercegovine. Smatra se najzagaД‘enijim kantonom Bosne i Hercegovine (19). Sva toplotna i elektriДЌna energija u Tuzlanskom kantonu dobija se sagorijevanjem fosilnih goriva, i to uglavnom uglja, koji u ovom podruДЌju sadrЕѕi visok procenat sumpordioksida (19). Na podruДЌju Tuzlanskog kantona 2003. godine uspostavljen je Sistem za praД‡enje kvaliteta zraka kojim se vrЕЎi automatski monitoring koncentracije osnovnih pokazatelja kvaliteta zraka i meteoroloЕЎkih podataka. Sistem se sastoji od pet fiksnih i jedne mobilne imisione stanice, koje su opremljene mjernim ureД‘ajima za mjerenje koncentracija pet polutanata aerozagaД‘enja (sumpordioksid, azotdioksid, ozon, ugljenmonoksid i taloЕѕna praЕЎina); meteoroloЕЎkih podataka (temperatura zraka, brzina vjetra, pravac vjetra, pritisak, sunДЌevo zraДЌenje i koliДЌina padavina), te centralne jedinice (server) za prikupljanje, pohranjivanje i obradu rezultata mjerenja. VoД‘enje i odrЕѕavanje Sistema za praД‡enje kvaliteta zraka i informiranje javnosti o kvalitetu zraka je u nadleЕѕnosti Ministarstva prostornog ureД‘enja i zaЕЎtite okolice i provodi se u skladu sa Zakonom o zaЕЎtiti zraka, Pravilnikom o graniДЌnim vrijednostima kvaliteta zraka i Pravilnikom o monitoringu kvaliteta zraka Federacije Bosne i Hercegovine, te u skladu sa meД‘unarodnim ugovorima. Prema IzvjeЕЎtaju za 2006. godinu (20) Tuzla, Luka- AerozagaД‘enje i trend hospitalizacije djece zbog bronhoopstrukcije na podruДЌju Tuzlanskog kantona Ukupno 30,0 Bolesno 25,0 20,0 20,6 18,7 15,0 11,6 11,5 10,0 11,3 8,8 8,8 8,3 5,0 10,9 8,8 7,3 3,5 0,8 3,8 3,42,7 1,81,5 2,72,3 3,2 2,3 2,7 5,05,0 iД‡ i j c an no v Ba Kl ad da ДЌa st ok G ra ik ob o jI re n D el iД‡ Sr eb ДЊ a ni c ДЌa oДЌ ak G ra Te pn a ija Sa le s Ka c ni ce ЕЅi vi va zla 0,0 ka Grafikon 1. Distribucija ukupne i populacije lijeДЌene djece uzrasta do 6 godina prema opД‡ini stanovanja izloЕѕene aerozagaД‘enju, jer je pritisak na U periodu od 01. 01. 2006. do 31. kvalitet zraka u promatranom razdoblju 12. 2006. u Odjeljenju intenzivne njege uglavnom dolazio iz izvora sa podruДЌja i terapije 332 pacijenata su lijeДЌena ove tri opД‡ine; istraЕѕeni su zbirni podaci zbog bronhoopstrukcije. Od toga 208 za tri vodeД‡e opД‡ine : Tuzla, Lukavac i ЕЅisu bili djeДЌaci (63 %), a 124 djevojДЌice vinice (opД‡ine Grupe jedan) i uporeД‘eni (37%). ProsjeДЌna starosna dob iznosila sa zbirnim podacima za ostale opД‡ine je 3,06В±3,22 godine. Od 332 pacijenta Tuzlanskog kantona - opД‡ine Grupe dva. 254 (76,5 %) bilo je mlaД‘e od pet godina. Procenat lijeДЌene djece iz opД‡ina Grupe Prostorna distribucija uzorka po- jedan (Tuzla, Lukavac i ЕЅivinice) bio je kazala je najveД‡i udio pacijenata iz Tu- daleko iznad procenta koje su ove opД‡ine zle, Lukavca i ЕЅivinica. Prostorna distribucija 70,0 63,0 Ukupno Bolesno 59,5 lijeДЌene djece izraЕѕena 60,0 procentualno upore- 50,0 40,5 Д‘ena je sa prostornom 40,0 distribucijom ukupne 27,0 populacije djece Tu- 30,0 zlanskog kantona za 20,0 uzrast do 6 godina, 10,0 prema demografskim 0,0 podacima vaЕѕeД‡im za Grupa 1 Grupa 2 period istraЕѕivanja. U dobnoj skupini do 6 go- Grafikon 2. Udio ukupne i populacije lijeДЌene djece do 6 godina u dina bilo je 80 % uku- dvije posmatrane grupe opД‡ina prema stepenu aerozagaД‘enja opД‡ina pnog uzorka lijeДЌene stanovanja (p<0,0001) djece zbog bronhoop70 strukcije (grafikon 1). 60 Procenat lijeДЌene djece iz Tuzle i Lukavca 50 bio je daleko iznad procenta koje su ove opД‡ine 40 imale u ukupnoj populaciji djece do 6 godina. 30 S obzirom da se razliДЌita uДЌestalost u razli20 ДЌitim geografskim po10 druДЌjima vezuje uz ambijentalne uvjete sre0 dine, prije svega nivo 0 2 4 6 8 10 12 14 aerozagaД‘enja i s obziMjesec rom da su Tuzla, Luka- Grafikon 3.broja Korelacija Slika . Korelacija oboljelihbroja tokomlijeДЌene godine djece i sezone. Broj lijeДЌene djece P=0,009 vac i ЕЅivinice ocijenjene se znaДЌajno poveД‡ava u zimskim mjesecima (p<0,009) Broj oboljelih se znaДЌajno poveД‡ava u zimskom periodu kao opД‡ine posebno 3. REZULTATI RADA Broj oboljelih Analiza se bazirala na populaciji pacijenata lijeДЌenih zbog bronhoopstrukcije u Odjeljenju intenzivne njege Klinike za djeДЌije bolesti u Tuzli u periodu od 01. 01. 2006. do 31.12. 2006. godine. Svi odabrani pacijenti bili su sa podruДЌja Tuzlanskog kantona. Izvor podataka za ovo istraЕѕivanje bili su Protokoli prijema u Kliniku za djeДЌije bolesti i Protokol Odjeljenja intenzivne njege Klinike za djeДЌije bolesti, kao i historije bolesti lijeДЌene djece. IstraЕѕen je trend hospitalizacije djece zbog bronhoopstrukcije u odnosu na dob, spol, mjesto stanovanja i sezonu. U istraЕѕivanju je koriЕЎtena i druga baza podataka dobijena iz aktuelnog IzvjeЕЎtaja Ministarstva prostornog ureД‘enja Vlade Tuzlanskog kantona o kvalitetu zraka na podruДЌju Tuzlanskog kantona sa mjernih stanica Sistema za praД‡enje kvaliteta zraka za period koji obuhvata istraЕѕivanje (20). PraД‡ene su maksimalne, minimalne i prosjeДЌne dnevne vrijednosti pet pokazatelja kvaliteta zraka: sumpordioksida, azotdioksida, ugljenmonoksida, ozona i taloЕѕne praЕЎine sa pet fiksnih mjernih imisionih stanica i jedne mobilne imisione stanice. OpД‡ine Tuzla, Lukavac i ЕЅivinice, u ovom IzvjeЕЎtaju ocijenjene kao opД‡ine posebno izloЕѕene aerozagaД‘enju, oznaДЌene kao opД‡ine Grupe jedan. Analizirani rezultati za ove opД‡ine uporeД‘eni su sa zbirnim podacima za ostale opД‡ine Tuzlanskog kantona koje su u istraЕѕivanju oznaДЌene kao opД‡ine Grupe dva. U statistiДЌkoj obradi podataka koriЕЎtene su standardne metode deskriptivne statistike (mjere centralne tendence, mjere disperzije). Za testiranje znaДЌajnosti razlika medju uzorcima koriЕЎteni su parametarski i neparametarski testovi signifikantnosti (XВІ-test, Studentov t-test) kao i metoda linearne korelacije. StatistiДЌke hipoteze su testirane na nivou signifikantnosti od О± = 0,05, tj. razlika meД‘u uzorcima smatra se znaДЌajnom a koje p < 0,05. 32,8 Lu 2. ISPITANICI I METODE RADA 35,0 Tu vac i ЕЅivinice ocijenjene su kao opД‡ine posebno izloЕѕene aerozagaД‘enju, jer pritisak na kvalitet zraka u promatranom razdoblju uglavnom je dolazio iz izvora sa podruДЌja ove tri opД‡ine. Cilj ovog rada bio je da se istraЕѕi moguД‡a povezanost trenda hospitalizacije djece zbog bronhoopstrukcije tokom 2006. godine i visine izmjerenih koncentracija polutanata aerozagaД‘enja na podruДЌju Tuzlanskog kantona. MED ARH 2009; 63(3) • ORIGINALNI ДЊLANCI / ORIGINAL PAPERS 147 AerozagaД‘enje i trend hospitalizacije djece zbog bronhoopstrukcije na podruДЌju Tuzlanskog kantona 25,0 Grupa 1 22,8 Grupa 2 20,0 18,5 15,0 13,8 12,9 12,3 10,9 9,2 10,0 7,97,7 6,9 5,0 3,5 2,3 7,4 7,9 5,4 4,5 7,9 5,4 4,0 2,3 4,6 3,5 4,6 ba r ba r ec em D r r ov em ba N O kt o m ba pt e gu st Se Au Ju li i Ju n M aj ril Ap t M ar r br ua Fe Ja n ua r 0,0 Grafikon 4. Sezonska distribucija lijeДЌene djece u dvije grupe opД‡ina imale u ukupnoj populaciji djece do 6 godina. U opД‡inama Grupe dva (ostale opД‡ine Tuzlanskog kantona) bio je znaДЌajno manji procenat lijeДЌene djece u odnosu na procenat koji su ove opД‡ine imale u ukupnoj populaciji djece do 6 godina za podruДЌje Tuzlanskog kantona prema demografskim podacima vaЕѕeД‡im za period istraЕѕivanja. Razlika meД‘u grupama oznaДЌena je statistiДЌki znaДЌajnom sa p < 0,0001 (grafikon 2). Broj djece lijeДЌene u Odjeljenju intenzivne njege zbog bronhoopstrukcije bio je razliДЌit tokom godine i po mjesecima. NajveД‡i broj djece zabiljeЕѕen je u mjesecu decembru, a najmanji u julu i augustu. Na sljedeД‡em grafikonu prikazana je korelacija broja lijeДЌenih pacijenata i sezone. Broj lijeДЌenih se znaДЌajno poveД‡avao u zimskom periodu sa p<0,009 (grafikon 3). Sezonska distribucija hospitalizacije djece zbog bronhoopstrukcije istraЕѕena je u dvije posmatrane grupe opД‡ina Tuzlanskog kantona: Grupa jedan (Tuzla, Lukavac i ЕЅivinice) i Grupe dva (ostale opД‡ine Tuzlanskog kantona). Sezonski trend hospitalizacije bio je razliДЌit u dvije posmatrane grupe opД‡ina (grafikon 4). Broj lijeДЌene djece iz opД‡ina Grupe jedan (Tuzla, Lukavac i ЕЅivinice ) bio je veД‡i u odnosu na broj lijeДЌene djece iz opД‡ina Grupe dva (ostale opД‡ine Tuzlanskog kantona) tokom veД‡eg dijela godine. UoДЌena su dva sezonska perioda tokom kojih je bio veД‡i broj lijeДЌene djece iz opД‡ina Grupe jedan. To su bili periodi od januara do aprila, te period od oktobra do decembra. Broj lijeДЌene djece iz opД‡ina Grupe dva (ostale opД‡ine Tuzlan148 13,8 zirane djece u dvije posmatrane grupe opД‡ina. Postojale su razlike u broju lijeДЌene djece iz opД‡ina Grupe jedan u dva sezonska perioda. U sezoni grijanja bilo je znaДЌajno viЕЎe lijeДЌene djece iz opД‡ina Grupe jedan u odnosu na period bez grijanja. Razlika u broju lijeДЌene djece u dva sezonska perioda za opД‡ine Grupe jedan oznaДЌena je statistiДЌki znaДЌajnom (p<0,0001). U opД‡inama Grupe dva nije postojalo znaДЌajno odstupanje u broju hospitalizirane djece u dva sezonska perioda. U istraЕѕivanju su analizirani maksimalne, minimalne i prosjeДЌne dnevne vrijednosti pet pokazatelja kvaliteta zraka, sumpordioksida, azotdioksida, ugljenmonoksida, ozona i taloЕѕne praЕЎine na podruДЌju Tuzlanskog kantona za period koji obuhvata istraЕѕivanje. Od pet pokazatelja kvaliteta zraka prekoraДЌenje dozvoljenih vrijednosti zabiljeЕѕena su za sumpordioksid i taloЕѕnu praЕЎinu, a prekoraДЌenja dozvoljenih vrijednosti za ova dva polutanta aerozagaД‘enja zabiljeЕѕena tokom posmatranog jednogodiЕЎnjeg perioda, bila su u mjesecima koji odgovaraju sezoni grijanja. UporeД‘ene su izmjerene prekoraДЌene vrijednosti sumpordioksida i taloЕѕne praЕЎine u dva sezonska perioda: u sezoni grijanja i sezoni bez grijanja (grafikon 6). U sezoni grijanja zabiljeЕѕen je zna- skog kantona) bio je veД‡i u odnosu na broj lijeДЌene djece iz opД‡ina Grupe jedan (Tuzla, Lukavac i ЕЅivinice) tokom jednog sezonskog perioda: u periodu od maja do septembra. PrimijeД‡ena prostorna i sezonska razlika trenda hospitalizacije slagala se sa uobiДЌajenim periodima sezone grijanja. U toku uobiДЌajene sezone bez grijanja od maja do septembra, zabiljeЕѕen je veД‡i broj lijeДЌene djeca iz opД‡ina Grupe dva (ostale opД‡ine Tuzlanskog kantona). U sezoni grijanja, od oktobra do decembra i od januara do aprila zabiljeЕѕen je veД‡i broj lijeДЌene djece 160 iz opД‡ina Grupe jedan Grijanje Bez grijanja 140 (Tuzla, Lukavac i ЕЅivi120 nice) u odnosu na broj 100 lijeДЌene djece iz opД‡ina 80 Grupe dva. 60 Trend hospitaliza40 cije djece zbog bronho20 opstrukcije u odnosu 0 na grupe opД‡ina i na seGrupa 1 Grupa 2 zonu grijanja prikazan GRAFIKON 5. Broj lijeДЌene djece u dvije sezone (sa i bez grijanja) u je na grafikonu 5. U sezoni grijanja dvije posmatrane grupe opД‡ina (p<0,0001) bio je znaДЌajno veД‡i broj hospitalizirane djece iz opД‡ina Grupe jedan 60 (Tuzla, Lukavac i ЕЅivi- 50 nice) u odnosu na op40 Д‡ine Grupu dva (ostale opД‡ine Tuzlanskog kan- 30 tona). Razlika meД‘u 20 grupama oznaДЌena je statistiДЌki znaДЌajnom 10 (p<0,0001). U periodu 0 Bez grijanja bez grijanja nije posto- Grijanje jalo znaДЌajno odstupa- GRAFIKON 6. Procenat dana sa prekoraДЌenim razinama sumpor nje u broju hospitali- dioksida i taloЕѕne praЕЎine u dva sezonska perioda (p<0,0001) MED ARH 2009; 63(3) • ORIGINALNI ДЊLANCI / ORIGINAL PAPERS 134 84 75 61 53,8 SO2 PraЕЎina 16,5 2,7 0,0 AerozagaД‘enje i trend hospitalizacije djece zbog bronhoopstrukcije na podruДЌju Tuzlanskog kantona ДЌajno veД‡i procenat dana sa prekoraДЌenim vrijednostima koncentracije sumpordioksida (53,8 %) u odnosu na sezonu bez grijanja (2,7 %). Razlika izmjerenih vrijednosti u sezonama sa i bez grijanja bila je statistiДЌki znaДЌajna (p<0,0001). U sezoni grijanja zabiljeЕѕen je znaДЌajno veД‡i procenat dana sa prekoraДЌenim vrijednostima koncentracije taloЕѕne praЕЎine (16,5%) u odnosu na sezonu bez grijanja (0 %). Razlika izmjerenih vrijednosti u dva posmatrana sezonska perioda bila je statistiДЌki znaДЌajna (p<0,0001). NajveД‡i procent izmjerenih prekoraДЌenih vrijednosti polutanata aerozagaД‘enja zabiljeЕѕen je u mjesecu decembru. U istom periodu zabiljeЕѕen je najveД‡i procenat hospitalizirane djece zbog bronhoopstrukcije. Od ukupnog uzorka petina je hospitalizirana tokom mjeseca decembra, a treД‡ina od tog broja bili su pacijenti iz Tuzle. Analizirano je dnevno kretanje koncentracije polutanata aerozagaД‘enja i trend hospitalizacije zbog bronhoop- 3,5 Zagadjenost 3 2,5 2 1,5 1 0,5 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 Grafikon 7. Odnos prekomjernog aerozagaД‘enja i broja hospitalizirane djece ak godina. NeizbjeЕѕno je spomenuti Londonsku epizodu iz decembra 1952. godine (21) kada je visoko aeorozagaД‘enje imalo poguban efekat na porast mortaliteta sedmicama nakon Ima toga perioda. Ova epizoda je znaДЌajna, jer je ukazala na nedvosmislenu uzroДЌnu povezanost. PoveД‡an mortalitet nije zabiljeЕѕen u drugim podruДЌjima, niti u periodima bez aerozagaД‘enja, iako su ostali klimatski uvjeti bili gotovo isti. Mortalitet je bio poviЕЎen u fazama visokog aerozaNema 0 1 2 3 gaД‘enja i poДЌeo je opaBroj djece dati kada je aerozagaД‘eGrafikon 8. Korelacija prisustva prekomjernog aerozagaД‘enja i broja nje opadalo. DojenaДЌka hospitalizirane djece iz Tuzle ( r = -0,394 ; p = 0,046 ) smrtnost u tom periodu bila je dvostruka. strukcije djece iz Tuzle. Rezultati su priGeneralno se pacijenti djeДЌijeg uzrakazani na grafikonu 7. sta smatraju podloЕѕnijim i vulnerabilniRezultati ove analize pokazali su da jim na ЕЎtetne efekte aerozagaД‘enja (13, je nakon nekoliko uzastopnih dana sa iz14, 22). VeД‡ina studija potvrД‘uje znamjerenim prekoraДЌenim vrijednostima ДЌajnu povezanost aerozagaД‘enja i porepolutanata aerozagaД‘enja , u narednim meД‡aja pluД‡ne funkcije u djece (13, 23, danima dolazilo do znaДЌajnog porasta 24, 25). Nedavne studije izvjeЕЎtavaju da broja hospitalizirane djece zbog bronje prenatalna izloЕѕenost prevelikom aehoopstrukcije. rozagaД‘enju povezana sa ranom fetalKorelacija trenda prekomjernog aeronom smrti, prematuritetom i niЕѕom tjezagaД‘enja i trenda hospitalizirane djece lesnom masom na roД‘enju (26, 27). Tazbog bronhoopstrukcije na podruДЌju TukoД‘er postoje studije koje izvjeЕЎtavaju o zle bila je statistiДЌki znaДЌajna sa r= -0,394 povezanosti aerozagaД‘enja i porasta doi p<0,046 (grafikon 8). jenaДЌke smrtnosti (28, 29, 30). Efekti aerozagaД‘enja u djece mogu biti razliДЌiti 4. DISKUSIJA u odnosu na odrasle za iste vrijednosti Uticaj aerozagaД‘enja na zdravlje vanjskih koncentracija pojedinih polutapredmet je brojnih studija zadnjih 50nata aerozagaД‘enja (13). To se posebno Zagadjenost Broj djece odnosi na ozon, koji je produkt fotohemijske reakcije u atmosferi, tako da pokazuje jake sezonske i dnevne varijacije: PoviЕЎen je ljeti i poslijepodne, a nizak je zimi, noД‡u i rano ujutro. UnutraЕЎnji prostori, naroДЌito klimatizirani, smatraju se zaЕЎtiД‡enim. Suprotno tome, taloЕѕne ДЌestice, posebno finije, prodiru u unutraЕЎnje prostore i ne podlijeЕѕu hemijskim promjenama kao ozon ili sumpordioksid (31). Ljetnje epizode aerozagaД‘enja i efekti na zdravlje vezuju se za ozon; a u epizodama zimskog aerozagaД‘enja pogorЕЎanje kliniДЌkih simptoma i pluД‡ne funkcije u djece sa astmom vezuje se za nivo taloЕѕnih ДЌestica (13). Dnevne varijacije polutanata aerozagaД‘enja utiДЌu na trend hospitalizacije zbog respiratornih bolesti. NajviЕЎe se izvjeЕЎtava o pogorЕЎanju astme, poveД‡anoj incidenci bronhitisa i pneumonije (32, 33). U naЕЎem istraЕѕivanju 76,5% hospitalizirane djece bilo je mlaД‘e od 5 godina, a 60 % bili su djeДЌaci. Brojne studije daju sliДЌne rezultate o dobnoj i spolnoj distribuciji hospitalizirane djece zbog bronhoopstrukcije (6, 34). Razlike u uДЌestalosti respiratornih bolesti u razliДЌitim podruДЌjima uglavnom se vezuju uz ambijentalne prilike. Oyana i Rivers (9) objavili su 2005. godine rezultate istraЕѕivanja trenda hospitalizacije zbog bronhoopstrukcije pacijenata uzrasta od 0-18 godina za podruДЌje grada Bafalo i okoline. Rezultati su pokazali signifikantno veД‡i broj pacijenata iz istoДЌnih dijelova ovog podruДЌja u odnosu na zapadne dijelove ЕЎto se objaЕЎnjava postojeД‡im izvorima saobraД‡ajnog, industrijskog i ostalog aerozagaД‘enja. Eroshina i saradnici MED ARH 2009; 63(3) • ORIGINALNI ДЊLANCI / ORIGINAL PAPERS 149 AerozagaД‘enje i trend hospitalizacije djece zbog bronhoopstrukcije na podruДЌju Tuzlanskog kantona (10) objavili su 2004. godine sliДЌne rezultate za podruДЌje Moskve i okoline. U naЕЎem istraЕѕivanju znaДЌajno veД‡i broj hospitaliziranih bio je iz opД‡ina koje su evidentno bile viЕЎe izloЕѕene aerozagaД‘enju. Brojne studije provedene u Evropi, Americi i Australiji osamdesetih i devedesetih observirale su dnevni trend hospitalizacije zbog respiratornih bolesti u poreД‘enju sa dnevnim kretanjem nivoa aerozagaД‘enja i zabiljeЕѕile o porast prijema u danima visokog aerozagaД‘enja (13, 35). Pope (32) je analizirao hospitalizaciju djece zbog respiratornih bolesti u Utahu tokom 3 godine u vezi sa viЕЎemjeseДЌnim prekidom rada ДЌeliДЌane, najveД‡eg zagaД‘ivaДЌa u tom podruДЌju. Rezultati su pokazali da je za viЕЎe od 50% opao prijem djece u bolnicu zbog astme i pneumonije u periodu u kojem je ДЌeliДЌana bila zatvorena i u kojem je aerozagaД‘enje bilo niЕѕe. Narednih godina, nakon prekida ЕЎtrajka, trend hospitalizacije je ponovo porastao. Susjedna podruДЌja, gdje ДЌeliДЌana nije imala uticaja, nisu imala kolebanja nivoa aerozagaД‘enja niti trenda hospitalizacije. U naЕЎem istraЕѕivanju analiza dnevnih kolebanja pet glavnih pokazatelja aerozagaД‘enja zabiljeЕѕila je prekoraДЌenje dozvoljenih vrijednosti za sumpordioksid i taloЕѕnu praЕЎinu. Ova prekoraДЌenja uglavnom su bila u mjesecima koji odgovaraju sezoni grijanja. Trend hospitalizacije pacijenata slagao se sa stepenom izloЕѕenosti aerozagaД‘enju. Glavni zagaД‘ivaДЌi na ovom podruДЌju su izvori toplotne i elektriДЌne energija koja u Tuzlanskom kantonu potiДЌe od sagorijevanja fosilnih goriva, uglavnom uglja, koji sadrЕѕi visok procenat sumpordioksida. SliДЌno istraЕѕivanje proveli su Barnet i saradnici (15) tokom tri godine u pet velikih gradova Australije i Novog Zelanda, ЕЎto ДЌini preko 50 % ukupne populacije ovog regiona. Analizirana je povezanost aerozagaД‘enja i trenda hospitalizacije djece zbog respiratornih oboljenja. Signifikantan porast hospitalizacije djece zbog pneumonije i akutnog bronhitisa zabiljeЕѕen je u dobnoj skupini od 0–5 godina; te astme u dobnoj skupini od 5–14 godina. Ovaj porast bio je signifikantno povezan sa nivoom taloЕѕne praЕЎine, azotdioksida i sumpordioksida. Postoje dokazi da reduciranje aerozagaД‘enja ima povoljan efekat na zdravlje, reducira se broj hospitalizacija, broj pogorЕЎanja astme i drugih respiratornih bolesti, te popravlja pluД‡na funkcija ispitanika (32, 36, 37, 38). Osim spomenute 150 studije iz Utaha, postoji i novija studija provedena u Atlanti tokom olimpijskih igara, zbog kojih je saobraД‡aj u tom periodu bio planski reduciran. Rezultati su pokazali opadanje epizoda pogorЕЎanja astme u periodu reduciranog saobraД‡aja i aerozagaД‘enja (36). Nedavna studija u IstoДЌnoj NjemaДЌkoj pokazala je da redukcija aerozagaД‘enja dovodi do smanjenja respiratornih bolesti i simptoma u djece (37). PoboljЕЎanje praД‡ene pluД‡ne funkcije evidentirano je u djece koja su promijenila mjesto boravka i napustila podruДЌja visokog aerozagaД‘enja (38). Sve ove studije imaju veliki znaДЌaj zbog evidentnog dokaza da intrvencija u pravcu popravljanja ambijentalnih uvjeta ima povoljne efekte na zdravlje. 7. 8. 9. 10. 5. ZAKLJUДЊCI Trend hospitalizacije djece zbog bronhoopstrukcije u Tuzlanskom kantonu imao je razliДЌitu sezonsku i prostornu distribuciju. Dominirala su djeca uzrasta do 5 godina uz prednost djeДЌaka. Broj lijeДЌenih bio je statistiДЌki znaДЌajno veД‡i u zimskim mjesecima. Sezonski trend hospitalizacije bio je razliДЌit za pojedine opД‡ine Tuzlanskog kantona i zavisno od sezone grijanja. Polutanti aerozagaД‘enja, sumpordioksid i taloЕѕna praЕЎina, bili su znaДЌajno viЕЎih vrijednosti u sezoni grijanja u odnosu na sezonu bez grijanja. UtvrД‘ena je povezanost trenda hospitalizacije djece zbog bronhoopstrukcije i dnevnih varijacija polutanata aerozagaД‘enja. LITERATURA 1. 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Kontakt adresa autora: Dr. Devleta HadЕѕiД‡, Univerzitetski kliniДЌki centar Tuzla, Klinika za djeДЌije bolesti, Trnovac bb, 75000 Tuzla, Bosna i Hercegovina, 00 387 35 303 713, e-mail: devletahadzic@yahoo.com MED ARH 2009; 63(3) • ORIGINALNI ДЊLANCI / ORIGINAL PAPERS 151 Uticaj statina na postoperativni tretman pacijenata operiranih radi ugradnje aortokoronarnih premoЕЎtenja Uticaj statina na postoperativni tretman pacijenata operiranih radi ugradnje aortokoronarnih premoЕЎtenja Effects of Statins on Postoperative Treatment of Patients After Aortocoronary Bypass Grafting Mehmed KuliД‡1, Mirza DiliД‡2, Vjekoslav Gerc3, BeД‡ir HeljiД‡4 KardioloЕЎki odjel, Centar za srce, KliniДЌki centar Univerziteta u Sarajevu, Bosna i Hercegovina1 Klinika za angiologiju, KliniДЌki centar Univerziteta u Sarajevu, Bosna i Hercegovina2 Klinika za bolesti srca i reumatizam, KliniДЌki centar Univerziteta u Sarajevu, Bosna i Hercegovina3 Klinika za endokrinologiju i dijabetes, KliniДЌki centar Univerziteta u Sarajevu, Bosna i Hercegovina4 Originalni ДЌlanak SaЕѕetak Cilj rada: Antiinflamatorni utjecaj hipolipemijskih lijekova, statina, kod pacijenata poslije ugradnje aortokoronarnih premoЕЎtenja dosad nije istraЕѕivan. Cilj rada je pokazati utjecaj simvastatina na postoperativni tok, laboratorijske nalaze i postoperativne perikardijalne izljeve kod pacijenata operiranih radi ugradnje aortokoronarnih premoЕЎtenja. Materijal i metode: U studiju je ukljuДЌeno 80 pacijenata sa koronarnom arterijskom bolesti. Svi pacijenti su podijeljeni u dvije grupe: ispitivanu grupu od 40 pacijenata sa koronarnom ishemijskom bolesti, operiranih radi ugradnje aortokoronarnog premoЕЎtenja, koji su primali uobiДЌajenu kardiohirurЕЎku postoperativnu terapiju, uz dodatak simvastatinske terapije u koliДЌini od 40mg. simvastatina dnevno, u periodu od 8. sata nakon extubacije pacijenta do 14. postoperativnog dana, i kontrolnu skupinu od 40 pacijenata sa koronarnom ishemijskom bolesti, operiranih radi ugradnje aortokoronarnog premoЕЎtenja tretiranih uobiДЌajenom postoperativnom kardiohirurЕЎkom terapijom. U radu su evaluirani demografski podaci, operativni izvjeЕЎtaji, laboratorijski postoperativni parametri, te ehokardiografski pregledi tokom dvodnevnih postoperativnih perioda praД‡enja perikardijalnih izljeva. Podaci su statistiДЌki evaluirani koriЕЎtenjem statistiДЌkog programa SPSS. Parametrijski podaci bili su testirani Studentovim T-testom, dok su neparametrijski podaci obraД‘eni XВІ testom i proporcijama. KoriЕЎten je i Mann-Whitney U test uz CI: 95% tj. nivo signifikantnosti p<0.05. Rezultati: NaЕЎe istraЕѕivanje je pokazalo da simvastatini u dozi od 40mg/24.h. djeluju efektno u postoperativnom periodu na smanjenje vrijednosti lipida i signifikantno smanjenje postoperativnih perikardijalnih izljeva mjereno tokom dvodnevnog perioda u toku treД‡eg i ДЌetrnaestog postoperativnog dana (p<0.037, p<0.01).В ZakljuДЌak: Statinska terapija u dozi od 40mg/24.h je u naЕЎoj studiji aplicirana bez sporednih efekata i bez interakcija sa drugim postoperativno upotrebljenim lijekovima. Statini su pokazali dobar antiinflamatorni uДЌinak na ovako ograniДЌenom broju pacijenata. Statinska terapija bi se, uz ostalu postopeartivnu terapiju, trebala obavezno nastavljati u ranom kardiohirurЕЎkom postoperativnom periodu. Antiinflamatorno dejstvo statina potrebno je i dalje ispitivati, i to na mnogo veД‡oj skupini pacijenata. O antiinflamatornom dejstvu hipolipemika nema do sada velikih studija koje bi odagnale svaku sumnju u antiinflamatorno dejstvo hipolipemika. Posebno treba istaД‡i da nema velikih studija koje bi istraЕѕivale antiinflamatorno dejstvo hipolipemika na primjeru postperikardiotomnih perikardijalnih izljeva. KljuДЌne rijeД‡i: simvastatin, aortokoronarno premoЕЎtenje, perikardijalni izljevi Original paper SUMMARYВ Aim: There are no previous data about the anti-inflammatory effects of hypolipemic agents, statins, in patients after aortocoronary bypass grafting. The aim of this study was to demonstrate effects of simvastatine on postoperative treatment, laboratory findings and pericardial effusion during postoperative period, in patients after aortocoronary bypass grafting procedures. Material and methods: The study included 80 patients with coronary arterial disease divided in two groups. The study group included 40 patients with coronary ischemic disease subjected to surgical implantation of aortocoronary bypass graft who received standard cardio-surgical postoperative treatment supplemented with 40 mg of simvastatine per day, starting at 8 hours after the patient’s extubation until postoperative 14th day. The control group included 40 patients after aortocoronary bypass grafting procedures with standard intensive postoperative treatment. Evaluation included demographic data, surgical reports, postoperative laboratory parameters and echocardiography findings, taken during two days monitoring of postoperative pericardial effusion. Statistical data analysis was conducted using SPSS software. Parametric data were evaluated using Student T-test, while non-parametric data were processed using X2 test and proportion analysis. Mann-Whitney U test was applied with CI of 95%, i.e. significance level p<0.05.В Results: No significant differences were found between the observed groups with regards to demographic data, number of the implanted aortocoronary bypasses and postoperative laboratory parameters. However, the differences in echocardiographically determined dimensions of postoperative pericardial effusions measured during two days of postoperative observation (between the 3rd and the 14th day postoperative) were significant (p<0.037, p<0.01). Conclusion: In our study, statin therapy consisting of 40 mg/24 hrs was applied with no side effects and without interaction with the other postoperatively applied medications. Simvastatins, applied in the dosage of 40 mg/24 hrs, efficiently lead to significant reduction of postoperative pericardial effusions in postoperative period. In this limited group of patients, statins have exhibited good anti-inflammatory effects. Statins with standard therapy ought to be included in the early cardio-surgical postoperative period. Anti-inflammatory activities of statins should be further investigation on much larger patient sample. So far, there is no record of a large study of anti-inflammatory activities of hypolipemic agents that could waive the doubts into their effectiveness. It needs to be stressed that no large studies of anti-inflammatory activities of hypolipemic agents in cases of postoperative pericardial effusion were ever conducted. В Keywords: simvastatine, aortocoronary bypass graft, pericardial effusion 152 MED ARH 2009; 63(3) • ORIGINALNI ДЊLANCI / ORIGINAL PAPERS 1. UVOD Perikardiotomija je uobiДЌajeni postupak kod svih kardiohirurЕЎkih operacija, neophodan da bi se pristupilo operativnom polju. Kod kardiovaskularnih pacijenata hirurЕЎka intervencija na perikardu u okviru operacije aorto-koronarnog premoЕЎtenja izaziva njegovu inflamatornu reakciju, koja se u postoperativnim danima, kod nekih pacijenata, izraЕѕava kao postoperativni perikardijalni izljev. UobiДЌajeno se ova reakcija dogaД‘a u oko 10 do 40% pacijenata, pa sve do ДЌak 64% operiranih kardiohirurЕЎkih pacijenata, ДЌeЕЎД‡e kod valvularnih, nego kod bolesnika sa koronarnom arterijskom bolesti (1). 2. CILJ RADA Kod pacijenata poslije kardiohirurЕЎkog operativnog zahvata ugradnje koronarnog arterijskog bypassa evaluirati utjecaj simvastatina u dozi od 40mg/24.h. u ranom kardiohirurЕЎkom postoperativnom periodu od 8.h. poslije intubacije do 14. postoperativnog dana. 3. METODE RADA U radu su koriЕЎtene sljedeД‡e tehnike: •• LiДЌni i anamnestiДЌki podaci (ime, prezime, godina roД‘enja, spol, prethodno preleЕѕale bolesti). •• Operativni izvjeЕЎtaj (vrsta uraД‘ene kardiohirurЕЎke operacije, broj i vrsta ugraД‘enih aorto-koronarnih premoЕЎtenja). •• KliniДЌki postoperativni pregled (parametri RR i pulsa, te auskultatorni pregled srca i pluД‡a, RTG pluД‡a i srca). •• Laboratorijski nalazi (KS, Е UK, transaminaze, CK, urea i kreatinin, holesterol i trigliceridi) prvog, treД‡eg, sedmog postoperativnog dana i 14 dana nakon operacije. •• Ehokardiografski pregled pacijenata, u cilju evaluacije postojanja, veliДЌine, lokalizacije i progresije razvoja postperikardiotomnog perikardijalnog izljeva i to: •• Dvodnevni ehokardiografski pregledi u periodu od prvog postoperativnog dana do sedmog postoperativnog dana i to od dva kardiologa, kako bi se umanjila intraobserverska greЕЎka. •• Ehokardiografska kontrola perikardijalnog izljeva na dan 14 to dnevne, na isti naДЌin kao u prvim periodima. Svi dobijeni podaci su uzeti od paci- Uticaj statina na postoperativni tretman pacijenata operiranih radi ugradnje aortokoronarnih premoЕЎtenja jenata nakon ЕЎto su informirani o vrsti studije i njihovom uДЌeД‡u u njoj, i nakon ЕЎto su dali svoj pismeni pristanak za uzimanje terapije. Podaci su se prikupljali iz pregleda dva kardiologa prospektivno u periodu od 1 godine i to prema rednom broju prijema pacijenta, tako su se pacijenti pod parnim brojevima prijemnog protokola svrstavali u ispitivanu grupu (grupu A), dok su oni pod neparnim brojem prijemnog protokola ДЌinili kontrolnu grupu ili grupu B. Statinska terapija se dodjeljivala pacijentima grupe A, tako, da kardiolozi koji procijenjuju veliДЌinu postoperativno izraЕѕenog perikardijalnog izljeva ne znaju koji pacijenti primaju statinsku terapiju, a koji ne. Prospektivno dobijeni rezultati statistiДЌki su evaluirani koriЕЎtenjem statistiДЌkog programa SPSS. Parametrijski podaci bili su testirani Studentovim T-testom, dok su neparametrijski podaci obraД‘eni XВІ testom i proporcijama. KoriЕЎten je i Mann-Whitney U test, uz CI: 95% tj. nivo signifikantnosti p<0.05. 4. REZULTATI RADA ProsjeДЌna starost ispitanika iznosila je 57.g. +/- 8,36. NajmlaД‘i ispitanika imao je 42 godine, a najstariji 74 godina. Nije bilo signifikantne razlike meД‘u grupama u odnosu na starost i spol pacijenata. KliniДЌki je bila najzastupljeniji simptom stabilne angine pectoris a bez signifikantne razlike meД‘u grupama (p=0.539). Nije postojala signifikantna razlika meД‘u grupama u pogledu preoperativno ordinirane statinske terapije i taj procenat je iznosio u ispitivanoj grupi 45% (18 pacijenata) na statinskoj terapiji, u odnosu na 47% (19 pacijenata) u kontrolnoj grupi. Nije postojala signifikantna razlika meД‘u grupama u pogledu broja ugraД‘enih aortokoronarnih premoЕЎtenja. U poreД‘enju laboratorijskih nalaza nije bilo signifikantnosti meД‘u grupama u odnosu na: Er, Le, Е UK, CK, AST, ALT, Ureu, kreatinin, holesterol i trigliceride. Neinvazivna dijagnostika (Ehokardiografski podaci) Prije evaluacije perikardijalnog izljeva odredili smo brojevima podruДЌja ispred odreД‘enih zidova i veliДЌinu perikardijalnih izljeva. Dobili smo signifikane razlike izmeД‘u ispitivane i kontrolne skupine u odnosu na parametar postojanja ili odsustva postoperativnog perikardijalnog izljeva. Ta se signifikan- Lab. Param. Е UK 1 Е UK 2 Е UK 3 Е UK 4 CK 2 CK 3 CK 4 Lab. Hol 1 Hol 2 Hol 3 Trig 1 Trig 2 Lab AST 1 AST 2 AЕ T 3 AЕ T 4 ALT 1 ALT 2 ALT 3 ALT 4 Statini Srednja vrijednost Broj Std. Devijacija Std. GreЕЎka Da 40 6,105 1,812 ,4292 Ne 40 6,012 1,641 ,4286 Da 40 7,15 1,812 ,444 Ne 40 7,87 1,765 ,444 Da 40 6,367 3,538 ,7008 Ne 40 6,213 1,813 ,6944 Da 40 5,378 1,151 ,3777 Ne 40 6,170 1,827 ,3803 Da 40 90,55 42,94 10,895 Ne 40 83,22 44,89 10,902 Da 40 94,48 65,77 15,654 Ne 40 97,19 60,20 15,632 Da 40 94,48 65,77 8,834 Ne 40 82,24 40,46 8,874 broj Srednja vijednost Statini Std. Devijacija 1,144 ,3191 Ne 40 5,763 1,417 ,3201 Da 40 3,862 ,7100 ,2091 Ne 40 4,125 ,9608 ,2101 Da 40 4,9733 ,7757 ,23177 Ne 40 4,9141 1,073 ,23291 Da 40 2,2379 1,698 ,34194 Ne 40 2,1613 ,9398 ,33912 Da 40 1,6485 ,8109 ,18179 Ne 40 1,5250 ,6421 ,18114 Std. Devijacija ,520 ,519 ,672 ,830 ,390 ,199 5,384 Srednja vrijednost ,796 Sig. (2-tailed) 40 Broj ,942 Std. GreЕЎka Da STATINI Sig. (2-tailed) Std. GreЕЎka Da 40 23,15 8,610 2,870 Ne 40 24,44 13,97 2,890 Da 40 38,09 20,67 5,579 Ne 40 37,03 24,21 5,593 Da 40 32,27 9,847 3,135 Ne 40 29,41 14,98 3,155 Da 40 23,09 6,385 1,676 Ne 40 19,97 7,114 1,678 Da 40 34,82 23,66 5,289 Ne 40 33,84 18,58 5,269 Da 40 45,18 53,64 9,641 Ne 40 37,03 24,21 9,501 Da 40 31,64 11,44 3,604 Ne 40 28,94 17,13 3,625 Da 40 23,03 7,481 1,953 Ne 40 22,59 8,257 1,956 ,152 ,019 ,234 ,353 Sig. (2-tailed) ,230 ,274 ,083 ,488 ,764 ,092 ,377 ,802 Tabele 1, 2 i 3. Primjeri laboratorijskih parametara bez signifikantnih promjena. tnost meД‘u skupinama u odnosu na postojanje ili otsustvo perikardijalnog izljeva i odnosila se na podruДЌja lateralnog zida LV-a i ispred apexa LV-a u svim periodima praД‡enja, dok je za podruДЌje ispred RV-a postojala signifikantnost u drugom i treД‡em periodu praД‡enja. Podaci govore o signifikantnim razlikama meД‘u grupama u odnou na postojanju postoperativnih perikardijlnih izljeva (p< 0,037, p< 0,001, p<0,0124). MED ARH 2009; 63(3) • ORIGINALNI ДЊLANCI / ORIGINAL PAPERS 153 Uticaj statina na postoperativni tretman pacijenata operiranih radi ugradnje aortokoronarnih premoЕЎtenja 5. DISKUSIJA U naЕЎe istraЕѕivanje ukljuДЌeno je 80 ispitanika, podijeljenih u dvije skupine. Prva ili ispitivana skupina sastojala se od 40 pacijenata, sa kardiovaskularnom boleЕЎД‡u operiranih radi ugradnje aortokoronarnog premoЕЎtenja (bypass-a), a koji su postoperativno primali uz uobiДЌajenu postoperativnu kardiohirurЕЎku terapiju i 40 mg. simvastatina jednom u 24.h. i to poДЌevЕЎi od osmog postoperativnog sata, pa do posljednje kontrole, tj. do dana otpusta, odnosno, 7-10 dana nakon kardiohirurЕЎkog zahvata. Druga kontrolna skupina saДЌinjena je od 40 pacijenata sa kardiovaskularnom boleЕЎД‡u, operiranih radi ugradnje aortokoronarnog bypass-a, koji su postoperativno primali uobiДЌajenu postoperativnu kardiohirurЕЎku terapiju. U grupama nije bilo signifikantnih razlika, kako prema godinama, tako i prema spolu. Osnovna tegoba koju su pacijenti osjeД‡ali je anginozna bol po stabilnom tipu u oko 65% pacijenata. Nije bilo znaДЌajne razlike u vrsti i kvaliteti simptoma meД‘u pojedinim grupama. Tako su vrijednosti hematokrita i hemoglobina sniЕѕene na donje referentne granice, osobito u prvima postoperativnim danima, a kao posljedica kardiohirurЕЎkog perioperativnog krvarenja. Neposredno nakon operativnog zahvata kratkotrajno su bile poviЕЎene vrijednosti kreatin kinaze i CRP-a kao reakcija na oЕЎteД‡enje tkiva i posljediДЌni inflamatorni odgovor. Iz istog razloga u tom periodu jako su poveД‡ane i transaminaze, dok su urea i kreatinin ostajali u normalnim granicama ili su bili blago poviЕЎeni. Nakon sedmog dana doЕЎlo je do normalizacije svih navedenih vrijednosti laboratorijskih parametara u obje skupine pacijenata, premda su pacijenti iz ispitivane grupe nastavljali da uzimaju statinsku terapiju. Lipidogram je bio u referentnim granicama, ali je primjeД‡en blagi pad razine holesterola i triglicerida u periodima treД‡eg i sedmog postoperativnog dana, ЕЎto se moЕѕe pripisati uz dejstvo statina i poremeД‡enoj prehrani pacijenata u ranom postoperativnom periodu. Broj ugraД‘enih bypass-a nije se razlikovao po pojedinim skupinama, a najviЕЎe je bilo pacijenata sa ugraД‘ena tri aortokoronarna bypass-a (63%) potom onih sa dva (34%), dok su samo dva pacijenta dobila jednostruki aortokoronarni bypass (3%). Ehokardiografski pokazatelji su bili 154 od neobiДЌne su koriSrДЌani zid VeliДЌina Mann- Asymp. Sig Statini Broj % i period izljeva Whitney U (2-tailed) sti jer je ehokardiografski pregled doNEMA 16 50,0 stupan na svakom 2-5mm 9 28,1 mjestu, lako primjeNE PE 1-2 5-10mm 7 21,9 njiv, nije ЕЎtetan za pacijenta, moЕѕe se Ukupno 32 100,0 421,000 ,109 ponavljati prema kliNEMA 23 68,8 niДЌkim i medicin2-5mm 6 12,5 skim potrebama, i DA PE 1-2 5-10mm 4 18,8 veoma je precizan u odnosu na ocjenu Ukupno 33 100,0 lokaliteta i veliДЌine postoperativnih peSrДЌani zid VeliДЌina Mann- Asymp. Sig % rikardijalnih izljeva. Statini i period izljeva Broj Whitney U (2-tailed) S t r at e g ij a vo NEMA 20 62,5 Д‘enja neinvazivnih 2-5mm 7 21,9 ehokardiografskih NE PE 2-2 5-10mm 5 15,6 podataka mjerenja postoperativnih peUkupno 32 100,0 rikardijalnih izljeva, 343,500 ,001 NEMA 32 97,0 bila je usmjerena na 2-5mm 1 3,0 ДЌetiri podruДЌja, tj. DA PE 2-2 perikardijalni prostor ispred prednjeg Ukupno 33 100,0 zida desnog ventrikula (1), ispred predSrДЌani zid VeliДЌina Mann- Asymp. Sig % njeg zida i apexa li- Statini i period izljeva Broj Whitney U (2-tailed) jevog ventrikula (2), NEMA 28 87,5 i spred latera l nog 2-5mm 4 12,5 zida lijevog ventriNE PE 3-2 kula (3), te ispod i iza inferoposteriornog Ukupno 32 100,0 miokardnog zida (4). 462,000 ,037 NEMA 33 100,0 Drugi vaЕѕan kriterij bio je podjela na tri DA PE 3-2 razliДЌita perioda promatranja veliДЌine peUkupno 33 100,0 rikardijalnog izljeva. Ovim oznakama je SrДЌani zid i VeliДЌina Mann- Asymp. Sig % dodana i brojevna Statini period izljeva Broj Whitney U (2-tailed) vrijednost postopeNEMA 13 39,4 rativnog perioda koji 2-5mm 18 54,5 su obuvatili prvi poNE PE 4-2 5-10mm 2 6,1 stoperativni dan (1), treД‡i postoperativni Ukupno 33 100,0 dan (2), sam dan ot423,000 ,0124 NEMA 22 68,8 pusta, tj. obiДЌno 7. 2-5mm 4 12,5 do 10.postoperativni DA PE 4-2 5-10mm 6 18,8 dan (3). Tako se u tabelama, kojima su poUkupno 32 100,0 kazivani podaci eho- Tabele 4, 5, 6 i 7 Primjeri ehokardiografske ocijene veliДЌina kardiografskog pra- postperikardiotomnih perikardijalnih izljeva drugog perioda praД‡enja (tj Д‡enja perikardijal- treД‡eg postoperativnog dana) nih izljeva nailazimo na oznake PE (engl. Npr. oznaka PE 2-2 znaДЌila je perikardiPericardial Effusion = Perikardijalni iz- jalni izljev ispred drugog zid, tj. ispred ljev) 1-1, PE 2-1, PE 3-1, ЕЎto se odnosi na prednjeg zida i apex-a lijevog ventrikula zidove miokarda u prvom periodu pra- u drugom periodu praД‡enja, tj. treД‡eg poД‡enja, tj. prvog postoperativnog dana. stoperativnog dana. MED ARH 2009; 63(3) • ORIGINALNI ДЊLANCI / ORIGINAL PAPERS Uticaj statina na postoperativni tretman pacijenata operiranih radi ugradnje aortokoronarnih premoЕЎtenja Imamo i oznake tri razliДЌita perioda ehokardiografskih praД‡enja veliДЌine perikardijalnih izljeva, tj. 1= prvi postoperativni dan, 2= treД‡i do peti postoprativni dan, 3= dan otpusta (obiДЌno 7.-10. dan). VeliДЌina izljeva je mjerena u milimetrima i oznaДЌavana simbolima koji su znaДЌili: nema izljeva (0), trivijalni do mali perikardijalni izljevi veliДЌine do 5mm (50-100ml izljeva, u naЕЎem radu oznaka 1), mali do umjereni izljev veliДЌine od 5-10mm (govori o malom izljevu od 100200ml., u naЕЎem radu oznaka 2), umjereni do veliki izljevi veliДЌine od 10-15mm (250-500ml tekuД‡ine, oznaka 3), veliki izljevi veliДЌine 15-20mm (tj. ≥ 500ml, oznaka 4), te izrazito veliki postperikardiotomni izljevi veliДЌine > 20mm uz znake kompresije (oznaka 5) (2). Za ocjenu veliДЌine perikardijalnih izljeva nismo koristili druge radioloЕЎke tehnike, kao npr. CT ili MRI, kako zbog tehniДЌkih poteЕЎkoД‡a (duЕѕina ДЌekanja pretrage), tako i karakteristike ovih metoda da uveliДЌavaju aktuelnu veliДЌinu izljeva u odnosu na njihovu ehokardiografsku procjenu (3). Prvenstveno smo obratili paЕѕnju na parametar postojanja ili odsustva postoperativnog perikardijalnog izljeva i odnosa tih pokazatelja izmeД‘u ispitivane i kontrolne skupine. Podaci pokazuju da je postojala signifikantnost meД‘u skupinama u odnosu na postojanje ili odsustvo perikardijalnog izljeva u podruДЌjima lateralnog zida LV-a i ispred apex-a LV-a u svim periodima praД‡enja, dok je za podruДЌje ispred RV-a postojala signifikantnost u drugom i treД‡em periodu. Za ДЌetvrti zid tj. iza i ispod LV-a nismo naЕЎli signifikantnost u svezi sa traЕѕenim parametrima postojanja ili odsustva postperikardiotomnog perikardijalnog izljeva. Navedene parametre smo prve pratili, jer nam je najvaЕѕnije bilo, evaluirati broj pacijenata kod kojih uopД‡e nije bilo izljeva. Nakon toga evaluirali smo veliДЌinu i lokalizaciju postojeД‡ih postperikardiotomnih perikardijalnih izljeva. PoЕЎto naЕЎa studija obuhvata pacijente kod kojih postperikardiotomni perikardijalni izljevi uobiДЌajeno nisu jako izraЕѕeni (mnogo su ДЌeЕЎД‡i i obimniji kod pacijenata sa implantiranim vjeЕЎtaДЌkim zaliscima, radi postoperativno poveД‡ane upotrebe antikoagulantne terapije, nakon hirurgije aortnog puta i transplantacije srca (4). U grupama nismo imali velikih i izrazito velikih postperikardiotomnih perikardijalnih izljeva, tj. pronaД‘eni izljevi nisu prelazili granicu od 15-20mm. Е to se tiДЌe signifikantnosti razlika u nalazima kod ispitivane i kontrolne skupine, dobili smo podatke koji ukazuju da je siginifikantna razlika meД‘u grupama postojala u prvom periodu (prvi postoperativni dan) u podruДЌjima ispred vrha lijeve komore i lateralnog zida, dok u ovom periodu nije postojala signifikantna razlika podruДЌjima ispred RV-a i iza i ispod LV-a. U drugom periodu signifikantnost je postojala u svim podruДЌjima, sem u podruДЌju iza i ispod LV-a. U treД‡em periodu praД‡enja imali smo istu situaciju, da bi se potpuna nesignifikantnost podataka pokazala u ДЌetvrtom periodu, tj. mjeseca dana poslije kardiohirurЕЎkog zahvata. AnalizirajuД‡i ove podatke uvidjeli smo da u radu ne postoji signifikantnost ispred RV-a i iza LV-a. Ova nesiginifikantnost se odnosi prije svega na postoperativne kardiohirurЕЎke postupke. Naime, odmah poslije kardiohirurЕЎkog zahvata, pa obiДЌno do 2 dana nakon operacije plasirani su perikardijalni drenovi prednji, ispred desne komore i drugi straЕѕnji, iza i ispod LV-a. Ovi drenovi bili su razlogom nepostojanja razlike meД‘u veliДЌinama postoperativnih perikardijalnih izljeva kod ispitivane i kontrolne skupine, u navedenim podruДЌjima dreniranja perikardijalnog prostora. Skrenuli bi sada paЕѕnju na prednosti upotrebe statina, njihov odnos sa drugim lijekovima, te mali broj sporednih efekata u odnosu na druge lijekove koji se upotrebljavaju u tretiranju posperikardiotomnih perikardijalnih izljeva tj. NSAR, diuretika, kortikosteroida i kolhicina. Upotreba statina je u stalnom porastu. Osobito je u posljednje vrijeme izraЕѕena potreba uzimanja statina, kako za reguliranje visine vrijednosti kolesterola i triglicerida, tako i za pleiotropne efekte statinske terapije koji nisu zanemarljivi. Posebno je vaЕѕna potreba statina u grupi kardiovaskularnih pacijenata dijabetiДЌara, ДЌiji je broj u naЕЎem radu bio gotovo podjednak u obje skupine pacijenata, tj. 7 pacijenata (18%) u kontrolnoj skupini, u odnosu na 8 pacijenata (19%) u ispitivanoj skupini. Statini koji su predmet intresovanja u ovoj studiji, zasluЕѕuju paЕѕnju u pogledu opravdanosti njihove upotrebe kod ovakvih pacijenata. Njihovo hipolipemijsko dejstvo je veД‡ dokazano velikim studijama, a pleiotropni uДЌinci, kao npr. antinflamatorno dejstvo, imu- nomodulatorno dejstvo, efekat na endotelnu funkciju, dejstvo na oksidativni stres, antiprokoagulabilni efekat, antiaterogeno dejstvo i dr. joЕЎ nisu u punom obimu niti dokazani, a niti su naЕЎli punu primjenu (5, 6, 7). Pokazalo se da su se statini u naЕЎem radu i prije operativnog zahvata uzimali kod gotovo 50% pacijenata, a podaci iz prakse govore o potrebi mnogo veД‡e upotrebe hipolipemika, osobito kod skupine kardiovaskularnih pacijenata, dijabetiДЌara. Osobno miЕЎljenje je da je potrebno saДЌekati rezultate studija koje analiziraju upotrebu velikih doza statina, npr. dejstvo atorvastatina u dozi od 80mg/24.h. Nedavno je zavrЕЎena studija sa 40mg atorvastatina, koji je preoperativno ukljuДЌen u terapiji zajedno sa beta blokerima i amiodaronom kod pacijenata koji su podvrgnuti kardiohirurЕЎkoj operaciji i u toj grupi pacijenata doЕЎlo je do signifikantnog smanjenja pojave postoperativne atrijalne fibrilacije (8, 9). Statini nemaju izrazitih sporednih efekata, osim miopatije u <1% sluДЌajeva. Interakcije statina sa drugim lijekovima su neznatne ili beznaДЌajne, osobito kada se radi o preparatima za lijeДЌenje kardiovaskularnih bolesti. PoЕЎto se metaboliziraju preko CYP3A4 potreban je oprez kod istovremenog uzimanja fibrata i gemfibrozila, amiodarona, diltiazema i drugih nedihidropiridinskih blokera kalcijumskih kanala, nekih antidepresiva, inhibitora HIV proteaze (indavir, mekfinavir, ritonavir, sanquinavir), nekih makrolidnih antibiotika (eritromicina), i ciklosporina. 6. ZAKLJUДЊCI NaЕЎe istraЕѕivanje je pokazalo da u ispitivanoj skupini kardiovaskularnih pacijenata u odnosu na kontrolnu skupinu postoji: • Ne postoji signifikantna razlika u odnosu na demografske podatke kliniДЌku sliku i laboratorijske parametre meД‘u kontrolnom i ispitivanom skupinom, • Postoji signifikantna razlika u prisustvu i odrЕѕanju postperikardiotomnih perikardijalnih izljeva u ispitivanoj u odnosu na kontrolnu skupinu, u projekcijama zidova ispred lijevog ventrikula i srДЌanog vrha, te oko lateralnog zida. • Navedena razlika postoji na pomenutim podruДЌjima u svim postoperativnim periodima do 14 postoperativnog dana, • Studija je obradila skupinu pacije- MED ARH 2009; 63(3) • ORIGINALNI ДЊLANCI / ORIGINAL PAPERS 155 Uticaj statina na postoperativni tretman pacijenata operiranih radi ugradnje aortokoronarnih premoЕЎtenja nata koja nije imala izrazito velikih postoperativnih perikardijalnih izljeva, pa su mnogi medikamentozni efekti (a i oni statina) smanjeni, • Statini su pokazali dobar antiinflamatorni uДЌinak na ovako ograniДЌenom broju pacijenata, • Statinska terapija je u naЕЎoj studiji aplicirana bez sporednih efekata i bez interakcija sa drugim postoperativno upotrebljenim lijekovima, • Statinska terapija bi se uz ostalu terapiju, trebala obavezno nastavljati u ranom kardiohirurЕЎkom postoperativnom periodu, • Antiinf lamatorno dejstvo statina potrebno je i dalje ispitivati, i to na mnogo veД‡oj skupini pacijenata, • O antiinflamatornom dejstvu hipolipemika nema do sada velikih studija koje bi odagnale svaku sumnju u antiinflamatorno dejstvo hipolipemika, • Posebno treba istaД‡i da nema velikih studija koje bi istraЕѕivale antiinfla- 156 Lancet, 1999;353:118-9. matorno dejstvo hipolipemika na pri6. Hernandez-Perera O, Perez-Sala D, et al. mjeru postperikardiotomnih perikarEffects of the 3-hydroxy-3methylglutaryldijalnih izljeva. LITERATURA 1. 2. 3. 4. 5. CoA reductase inhibitors, atorvastatin and simvastatin, on expresion of endothelin 1 and endothelial nitric oxide synthase in vascular endothelial cells. J Clin Invest, 1998; 101:2711-9. Kaesemayer WH, Caldwer RB, Huang JZ et al. Pravastatin sodium activates endothelial nitric oxide synthase independent of its cholesterol-lowering actions. J Am Coll Cardiol, 1999;33:234-41. A. Selcuk Adabag et al. Statins May Reduce Atrial Fibrillation in Heart Failure Patients Am Heart J, 2007;154:1140-114. Lertsburapa K, White CM, Kluger J, Faheem O, Hammond J, Coleman CI1: Preoperative statins for the prevention of atrial fibrillation after cardiothoracic surgery. J Thorac Cardiovasc Surg, 2008 Feb;135(2):405-11. Meurin P, Weber H, Renaud N, et al. Evolution of the postoperative pericardial effusion after day 15*. The Problem of the 7. late tamponade. Chest, 2004;125:2182-7. Pepi M, Muratori M, Barbier B, et al: Pericardial effusion after cardiac surgery: incidence, site, size, and hemodynamic consequences. Br Heart J, 1994; 72:327. Mulvagh SL, Rokey R, Vick 3rd GW, et al. 8. Usefulness of nuclear magnetic resonance imaging for evaluation of pericardial effusions, and comparison with two-dimen- 9. sional echocardiography. Am J Cardiol, 1989; 64(16):1002-9. Alkhulaifi AM, Speechly-Dick ME, Swanton RH, et al: The incidence of significant pericardial effusion and tamponade following major aortic root surgery. J Cardiovasc Surg, 1996: 37:385. Strandberg TE, Vanhanen H, Tikkanen Kontakt adresa autora: dr. Mehmed KuliД‡. MJ. Effect of statins on C reactive protein Institut za srce. KCU Sarajevo. BolniДЌka 25. Tel.: 00 387 33 297 000. in patiens with coronary artery disease, MED ARH 2009; 63(3) • ORIGINALNI ДЊLANCI / ORIGINAL PAPERS Effectiveness of Diabetes Flow Sheet in Controlling Blood Pressure: Should Family Medicine Teams in Zenica Use Recommended Guidelines? Effectiveness of Diabetes Flow Sheet in Controlling Blood Pressure: Should Family Medicine Teams in Zenica Use Recommended Guidelines? Larisa Gavran1, Olivera Batic-Mujanovic2, Selmira Brkic3, Sabina Nuhbegovic4 Faculty of Health Sciences, University in Zenica, Bosnia and Herzegovina1 Faculty of Medicine, University in Tuzla, Bosnia and Herzegovina2,3,4 Original paper SUMMARY Background: Blood pressure (BP) is one of the important parameters for controlling Diabetes Mellitus (DM). European Society of Cardiology recommended optimal level for DM BP≤130/80mmHg. Aim: We wanted to assess the level of BP for our DM patients after using specific guidelines for DM. Methodology: Retrospective medical record (audit) has been conducted among 853 DM patients older then 18 years. We checked patient charts among 19 FM teams two years before (May 2003-May 2005) and two years after (May 2005-May 2007) implementation of the DM guidelines in Family Medicine (FM) clinic in Zenica. We divided FM teams based on their patients BP values; optimal level of BP≤130/80mmHg; suboptimal level when systolic BP 130-140mmHg and diastolic 85 -90mmHg and that with inadequate level with BP>140/90mmHg. Results: 853 DM patient charts were analysed, 46 per FM team. Average age of DM patients was greater than 60 years and average age of doctors was 46.6. Percentage of BP inadequate level was smaller after implementation of DM guidelines in most of FM teams. For optimal level BP≤130/80mmHg, significant improvement was seen after implementation of DM guidelines for: 6/19 teams (p<0. 0001), 2/19 teams (p<0.001) and 2/19 teams (p<0. 01). Conclusion: After implementation of BP guidelines for DM patients, BP can be improved in patients treated by FM teams and guidelines should be used. Keywords: blood pressure, diabetes mellitus, guidelines, family medicine teams 1. INTRODUCTION Hypertension is common in patients with type 2 diabetes with a prevalence of 40-60% over the age range 45 to 75 (1). Raised blood pressure (BP) is more common in people with type 2 diabetes than in the general population. However, in patients with type 2 diabetes the risk of diabetes complications was strongly associated with raised blood pressure (2) Most recent guidelines for BP management end treatment recommended: BP to be measured at every diabetes clinic visit for the assessment of hypertension, optimalisation of BP level (target are <130/80mmHg) with using of angiotensin converting enzyme (ACE) or angiotensin receptor blocker (ARB) for treatment of hypertensive patients and using of antithrombocit therapy. Also, lifestyle interventions to reduce BP should be considered (3, 4, 5). Several studies have show the efficancy of diseases-specific flow sheet use for improving patient care (6,7). On the other hand, there are only one studia in primary care settings examinig how often flow sheets are used to guide diabetes care and effectiveness of diabetes flow sheet use for improveing patients outcomes (8). In this study we wanted to assess the relationship between special diabetes flow sheets use and patients level of blood pressures in the everyday practice of primary care. This article is one in series our articles about quality improvement of care for diabetes type 2 patients cared by Family physicians in Zenica municipality. 2. METHODS In May of 2005 the Council management of Health Insurance Institution in Zenica-Doboj Canton (ZDC) adopted a resolution called “Primary conditions needed for recognition of Family Medicine in ZDC”. One of these conditions included re-establishing a “system of active management on diabetes and hypertension” (resolution number: 01-100-22/05: page 4, 2005). One of these conditions involved special flow sheets for patients with diabetes and hypertension and these are put in the patient’s paper chart. The special flowsheet for diabetic patients (SFD) includes 13 parameters which are followed periodically. One of these parametar is a blood pressure witch is need to be measured every 6 months. For every hypertensive patients ACE or ARB need to be given. A retrospective medical record (audit) was conducted in Home of Health in Zenica in 20 Family Medicine Clinic to describe the level of BP of diabetic care in the two years before (May 2003-May 2005) and two years after (May 2005May 2007) implementation guidelines for DM. Data was analysed for 843 patients. Nineteen FMT ( Family Medicine Physician is the Team leader) in Zenica participated in this study and allowed us to look into the medical charts of their diabetic type 2 patients. For every FMT , the diabetic patients were chosen using the following criteria: age 18 year or older, diagnosed as DM type 2 by International Qualification of Diseases -9 revision (E11, E10 or DM type 2 ), presenting in the Family Medicine Clinic at least one time before and one time after the implementation of SFD, followed by Family Medicine Physician without specialist-/endocrinologist consultation. By random sampling patients’ charts which met those criteria were reviewed. Charts which did not satisfy those criteria were excluded and others picked. Data from charts was documented on a special audit form (DM flow sheet), created from SFD. We divide all founded BP and all FM teams on that who get a optimal level of BP≤130/80 mmHg; sistolic 130-140 mmHg and diastolic 85 -90 mmHg as suboptimal level and that with inadequate level BP>140/90mmHg (4). In Home of Healt in Zenica municipality did not egzist appropriate institutional review board yet. Director of our institution and colegues Family Medicine physicians approved the project. The data was analysed by standard methods of descriptive and inherent statistics. The hypotheses were tested by z- test proportion. Statistically significant difference was defined as a P value of <0.05. 3. RESULTS In total 853 SFD were reviewed. In patient’s sample, women were more than men (538; 63.1% vs. 315; 36.9%) (P<0.0001). The average age was greater than 60 years (603; 70.7%). Nineteen FMT in total had 44008 registered patients and 1578 patients with DM. On average every FMT had 2316 patients and 83 diabetic patients: the study analysed 45 SFD per team. Within the FMT, Family medicine specialists comprised MED ARH 2009; 63(3) • ORIGINALNI ДЊLANCI / ORIGINAL PAPERS 157 Effectiveness of Diabetes Flow Sheet in Controlling Blood Pressure: Should Family Medicine Teams in Zenica Use Recommended Guidelines? Blood presure Blood pressure (>140/90 mmHg) inadequate level Blood pressure (130-140)/(85-90 mmHg) suboptimal level Blood presure (≤ 130/85 mmHg) optimal level Number of patients (N=853) Before SFD Proportions of patients After SFD Before SFD After SFD 500 298 (P<0.0001) 58% 34% 43 286 (P<0.0001) 5.04% 33.5% 95 219 (P<0.0001) 11.1% 25.6% Table 1. Before and after implementation Special Flow sheets for diabetes (SFD) and proportion of patients who met blood presure level for Family Medicine Teams together 74%, doctors with Program of Additional Training (PAT) comprised 21% and Family medicine residents were 5%. The average physician age was 46.6 years: 21% were men and 79% were female. Table 1 show number and proportion of diabetes type 2 patients for: blood pressure (>140/90 mmHg) as a inadequate level statisticly significant decrease after SFD (298 vs. 500; P<0.0001 ; blood pressure (130-140)/(85-90 mmHg) as a suboptimal level statisticly significant increase after SFD (286 vs. 43; P<0.0001) and blood presure (≤ 130/85 mmHg) as a optimal level statisticly significant increase after SFD (219 vs.95; P<0.0001) for all Family Medicine Teams tougether. Finaly, 25.6% of diabetic typ2 patients had optimal level of blood pressure(≤ 130/85 mmHg) and 59.1% of diabetic typ2 patients had BP <140/90 mmHg. Table 2 show number of diabetes type 2 patients with inadequate (>140/90 mmHg), suboptimal (130-140)/(85-90) and optimal(≤ 130/85 mmHg) blood pressures level per Family medicine Teams before vs. after implementation of flow sheets for DM. For optimal level frequency of those findings were rare before SFD. Statistical significance difference was found per FMT: 2, 11, 12, 13, 14 and 18 (P<0.0001), for FMT 15, 17 level of significance (P<0.01), and FMT 5 and 6 (P<0.01). 4. DISCUSSION assess the association’s betwen the use of Specific Flow sheet for diabetes and adherence to care guidelines for diabetes in everyday practice of primary care (8). From 853 charts before vs.after implementation of SFD, the best regularity in registration were found in parametar BP (30.2% vs. 81.3%) and “given ACE ili ARB“ (57% vs.75.7%) per FMT tougether. With that FMT in Zenica reach one of criteria in “Guide for Accreditation for ambulantas/FMT in Republica Srpska” done by Agency of Accreditation and improvement of Quality Health Care in Republica Srpska : FMTs must ensure that: 80% of patients must have blood pressure documented on every visit (13). Also, in two studies Harris SB at all. (1998 and 2003) examined level of folowing guideBlood presure (BP) Family Medicine Team Number of checked chart lines for DM in family practice and also found that BP is mensuared in 88% of cases (14,15). Agency for Healthcare Research and Quality in United States of America made National Healthcare Quality report in 2005 were only 70.9% all of diabetic patients had controled BP <140/90 mm/Hg (16). Our study show that only 25.6% of diabetic typ 2 patients had optimal level of blood pressure(≤ 130/85 mmHg) and only 59.1% of diabetic typ2 patients had BP <140/90 mmHg.With those findings we can not be satisfied. In addition, studies which include doctors’ reports, audits of practice and review of administrative data show that the quality of DM control practiced by doctors in Primary Health Care (PHC) is suboptimal (9, 15, 17, 18). On the other hand, our study show that optimal level BP per FMT before vs. after implementation of SFD statistically significant improved for FMT: 2, 11, 12, 13, 14 and 18 (P<0.0001), for FMT 15, 17 level of significance (P<0.01), and FMT 5 and 6 (P<0.01). So many studies explore most useful interventions for improving a diabetes care (19, 20, 21, 22, 23, and 24). Some of those suggesting that: changing clinician behavior, changing the practice organisation, enhancing information systems can improve disease management (19), Blood presure (>140/90 mmHg) Inadequate level Blood presure (130-140)/(85-90) suboptimal level Blood presure (≤ 130/85 mmHg) optimal level Before SFD Before SFD Before SFD After SFD After SFD After SFD Z-tests for optimal level (BP) P-Value for optimal level (BP) 1 41 29 4 12 20 0 17 - - 2 49 29 17 18 16 2 16 3,5 <0.0001 3 50 20 21 20 17 10 12 0,5 0.63 4 41 26 16 13 13 2 12 2,9 0.03 5 40 25 19 12 4 3 17 3,0 <0.01 6 46 31 25 12 2 3 19 3,2 <0.01 7 46 33 24 13 8 0 14 - - 8 40 17 20 20 14 3 6 1,1 0.3 9 44 26 21 18 13 0 10 - - 10 41 27 10 14 11 0 20 - - 11 40 25 11 14 12 1 17 4,3 <0.001 12 48 28 15 18 12 2 21 4,4 <0.001 13 50 35 10 14 6 1 34 6,6 <0.001 Many studies estimate the risk and 14 46 26 11 18 16 2 19 3,9 <0.001 concequestions of complications in dia15 49 28 15 19 14 2 20 3,5 <0.001 betic patients (9-12) were any reduction 16 46 17 17 23 15 6 14 1,1 0,27 in blood pressure is likely to reduce the 17 47 22 12 21 13 8 18 2,6 <0.01 risk of complications with the lowest risk 18 43 29 15 12 10 2 18 3,7 <0.001 being in those with systolic blood pres19 46 37 18 9 15 0 13 sure less than 120 mm Hg (2). On the Table 2. Blood presure level before vs. after implementation Special Flow sheets for diabetes typ 2 other hand, this is one of rare study to patients (SFD) per Family Medicine Teams-FMT 158 MED ARH 2009; 63(3) • ORIGINALNI ДЊLANCI / ORIGINAL PAPERS Effectiveness of Diabetes Flow Sheet in Controlling Blood Pressure: Should Family Medicine Teams in Zenica Use Recommended Guidelines? Diabetes, 2003; 27(Suppl 2): S1-152. www. cian, 2003; 49:778-85. and on the other hand quarterly site visdiabetes.ca/cpg 2003. 16. Agency for Healthcare Research and Quits and yearly meetings for Primary care 4. European guide for Prevention of Cardiality. National Healthcare Quality report clinics can improve patient follow up and ovascular duseases in Clinical practice 2005, http://www.ahrq.gov/qual/nhdr05/ treatment as well as improve adherence u. European Heart Journal, 2003; 24 (17): nhdr05.htm to clinical practice guidelines for blood 1601-10, and European Journal of Cardi- 17. Kirkman MS, Williams SR, Caffrey HH, ovascular Prevention and Rehabilitation, David GM. Impact of a program to Impressure (24). 2003;10(4):S1-S11. prove Adherence to Diabetes Guidelines Our method of creathing guidelines 5. American Diabetes Association: Standard by Primary Care Physicians. Diabetes adherence is innovative one especially of medical care in diabetes Diabetes Care, Care, 2002;25:1946-51. in Bosnia and Hercegovina for Primary 2009;32(suppl 1.):S115-S117. 18. Gill JM, Di Prinzio MJ. The Medical SociHealth Care and it is creating to help 6. Ruoff G.A mehod that dramaticaly improety of Delaware’s Uniform Clinical GuiFamily Physician to give better care for ves patient adherence to depression treadelines for diabetes: did they have a potment. J Fam Pract, 2005;54(10):846-52. sitive impact on quality of diabetes care? they patients in every day practice. 7. 5. CONCLUSION Study show that after implementation of Special diabetes flowsheet in Family Medicine settings in Zenica, Family Medicine Teams improved documentation and most of them rich optimal level of BP. Also, study show that use of Special diabetes flowsheet is associated with increased adherence to guidelines for diabetes care and may be a valuable tool in improveing care. Finally, new research is needed to investigate the reasons why all Family Medicine Teams in Zenica do not achieve the recommended guidelines for blood pressure controll in diabetes typ 2 patients . REFERENCES 1. 8. 9. 10. 11. 12. United Kingdom prospective Diabetes Study Group.UK prospective diabetes study 38: tight blood pressure control and 13. risk of macrovascular and microvascular complications in type 2 diabetes. BMJ, 1998; 317:703-13. 2. United Kingdom prospective Diabetes Study Group.UK prospective diabetes study 36: association of sistolic blood pre- 14. ssure with macrovascular complications of type 2 diabetes. BMJ, 2000; 321:412-9. 3. Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. 15. Canadian Diabetes Association. Clinical practice guidelines for the prevention and management of diabetes in Canada. Can J Ruoff G, Gray LS. Using a flow shet to improve performance in treatment of elderly patients with type 2 diabetes. Fam Med, 1999;31(5):331-6. Hahn KA, Ferrante JM, Crosson JC, Hudson SV,Crabtree BF. Diabetes flow sheet use associated with guideline adherence. Ann Fam Med, 2008;6(3):235-8. Kirk JK, Huber KR, Clinch CR. Attainment of goals from national guidelines among persons with type 2 diabetes: a cohort study in an academic family medicine setting. NC Med J, 2005;66(6):415-9. Bryant W, Greenfield JR, Chisholm DJ, Campbell LV. Diabetes guidelines: easier to preach than to practice? 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Weingarten SR, Henning JM, Badamgarav E. Intervention used in disease management programs for patients with chronic illness-which ones work? Meta-analysis of published reports. BMJ, 2002; 325:925-32. 21. Lawler F, Viviani N. Patient and Physician Perspectives Regarding Treatment of Diabetes: Compliance with Practice Guidelines. J Fam Pract, 1997;44:369-73. 22. O’Connor PJ, Desai J, Solberg LI. Randomized trial of quality improvement intervention to improve diabetes care in primary care settings. Diabetes care, 2005;28 (8):1890-7. 23. Steven O, Paul JN, Ruth GJ, Andrea MW, Lynne SN, Chris F, Sarah TC. Improving Diabetes Care Through a Multicomponent Quality Improvement Model in a Practice-based research Network. American Journal of Medical Quality, 2007;(No1):34-41. 24. Ornstein S, Nietert PJ, Jenkins GR, Wessell AM, Nemeth LS, Feifer C, Corley ST. Improving Diabetes Care Through a Multicomponent Quality Improvement Model in a Practice-based research Network. American Journal of Medical Quality, 2007;(No1):34-41. Corresponding author: Larisa Gavran, MD, Family medicine specialist, ECFM Travnicka, Faculty of Health, University in Zenica Bosnia and Herzegovina E-mail:gavranlarisa@yahoo.com MED ARH 2009; 63(3) • ORIGINALNI ДЊLANCI / ORIGINAL PAPERS 159 Collective Immunity of the Population from Endemic Zones of Hemorrhagic Fever with Renal Syndrome in Kosovo Collective Immunity of the Population from Endemic Zones of Hemorrhagic Fever with Renal Syndrome in Kosovo Sefedin MuГ§aj1.,3, Serbeze Kabashi 3, Salih Ahmeti 2.,3, Isuf Dedushaj1.,3, Naser Ramadani1.,3, Tatjana Avsic-Zupanc4 National Institute of Public Health of Kosovo, Pristine, Kosovo1 Infectious Disease Clinic, University Clinical Centre of Kosovo, Kosovo2 Faculty of Medicine, Pristine University, Kosovo3 Department of Microbiology, Faculty of Medicine, Ljubljana, Slovenia4 Original paper SUMMARY Hemorrhagic fever with renal syndrome (HFRS), also known as mice fever is an acute viral zoonosis and it appears in the natural focus after the human contact with Hantaan virus infected mice. The objective (purpose) of this study was to investigate the prevalence of specific antibodies in HFRS, in convalescent persons (collective immunity in endemic hearths).In this project we applied the epidemiological method of studying with retrospective-perspective, the serological method for determination and detecting antibodies from the persons of epidemical focus and statistical methods. The disease diagnosis is based on the epidemiological, clinical and serological records. The collected samples have been sent to referral laboratory in Medical FacultyInstitute of Microbiology Ljubljana for laboratory confirmation. From the results we came to conclusion that in the territory of Republic of Kosovo, the HFRS is still a serious health, economic and biological problem. The lethality rate from HFRS in 1986 was 15.4%, 1986-89 10.8%, from 1995-2006 8.70%. The lowest rates of morbidity, mortality and lethality of HFRS compared with the previous periods of time, prove collective immunity growth in Dukagjini valley. For collective immunity research and to conduct the persistence of antibodies for viral corresponding (relative) antigen, after the disease, the samples were collected in the time period of MayJune 2008, with 203 persons that were tested with serological method IIF (Indirect immune fluorescence) from which 187 cases (92.1%) resulted sero-negative and 16 cases (7.9%) resulted sero-positive with HFRS. This proves the collective immunity increase for HFRS. From 13 recovered patients previously diagnosed with HFRS (1986-1989-1995), levels of antibodies were screened in 2008 with IIF. Out of 13 persons, positive antibodies were found in 10 cases, while 3 cases were negative for antibodies (HTN, PUU, and DOB).After 13, 19 and 22 years HTN, PUU and DOB antibodies persisted in level (1:16-1:512). Based on the gathered results, we came to conclusion that it is necessary to compile the National Strategy of Surveillance for the Kosovo Health System for a 5 year period, for avoiding this high risk disease. Keywords: HFRS, collective immunity, (HTN, PUU, DOB) antibodies persisted after 13, 19 and 22 years, IIF, Republic of Kosovo 1. INTRODUCTION Haemorrhagic Fever with Renal Syndrome (HFRS), or else known as вЂ�mice fever’, is an acute viral zoonosis, that appears in natural hearths after the humans get in contact with some sorts of mice infected with the Hantaan virus (ARN virus). This disease has a wide geographical spread, and it is present in almost all European countries, especially in Balkans, and Kosovo is not excluded from attacks. There are diseases and natural hearths of two sorts of viral haemorrhagic fever in Kosovo: haemorrhagic fever with renal syndrome (HFRS) and Crimean Congo Haemorrhagic Fever (CCHF).Natural hearths of HFRS in Kosovo are: BjeshkГ«t e Nemuna, Mountains of Peja, DeГ§an, Junik, Gjakova, Istog and Kashtanjeva in Ferizaj.The scale of resistance of a population towards a particular communicable disease is determined with collective immunity.With the increase of the collective immunity, comes also the decrease of the scale of morbidity, mortality and lethality from 160 the particular diseases (HFRS) and vice versa. Sensitivity towards HFRS is general. All those who are in contact with the disease virus become ill, but most vulnerable are: farmers, mountain trackers, campers, shepherds, mountain rangers and collectors of natural fruits. After the recovery from the disease, comes the decrease of the antibodies, which shows the possible existence of re-infection with other types of Hantaan viruses. Various authors have found traces of specific antibodies against the Hantaan virus, even 34 years after the disease (1,2,3,4). Other researches show that in natural hearths, seropositivity in Hantaan is 2-29%, while in Europe it’s in 2.1% of population (5,6,7,8,9). 2. AIMS, methodology, and materials To investigate the persistence of specific antibodies in HFRS, in convalescent persons (collective immunity in endemic hearths). Epidemiological method of study was MED ARH 2009; 63(3) • ORIGINALNI ДЊLANCI / ORIGINAL PAPERS used, retrospective-perspective component, serologic method and statistical method. Diagnosis of the disease was done based on the epidemiological, clinical and serological data. For verification of the HFRS disease cases, laboratory research – serological testing was done, with the following methods: IIF (Indirect immune fluorescence) and the modern method of PCR (polymerase chain reaction) for acute cases. The collected samples (serums) were sent to the referent laboratory in the Faculty of Medicine – Institute of Microbiology- Ljubljana, for their laboratory confirmation.The research on the collective immunity scale on HFRS was achieved with: Serological Tests–detection of antibodies (Ab) in serum and epidemiological research, we have used the continuous epidemiological surveillance in the field, case research, data collection on the movement of the disease, health indicators, like: scale of morbidity, mortality and lethality. Results’ testing was done with Ttest, Spearman’s correlation and X2-test. Test verification was done for credibility 95% and 99%. 2. RESULTS For researching the collective immunity and follow up on antibodies persistence for respective viral Ag (HTN, PUU, DOB), during the period May-June 2008, the following was done: blood samples(serums) were taken from 203 persons and after the testing made with serological method IIF, the following results came out: 187 serums or 92.1% were negative on HFRS and 16 serums or 7.9% were positive on HFRS, as well as the follow up of health indicators like: morbidity, mortality and lethality scale for HFRS during the period 1995-2006. This was proved even during our research, 1995-2006 in Kosovo, where a low scale of morbidity, mortality and lethality of HFRS was registered, compared to other earlier time periods, which results in high scale of collective immunity on HFRS in Kosovo during the time of our research (Table 1 and 2). During May-June 2008, with the serological method IIF, research of 203 samples (serums) was done, where 187 serums or 92.1% were negative on HFRS and 16 serums or 7.9% were positive on HFRS. This proves the increase of the collective immunity scale of the population of endemic zones characteristic with HFRS (Table 3). Collective Immunity of the Population from Endemic Zones of Hemorrhagic Fever with Renal Syndrome in Kosovo Time Period 1996-2006 Lethality and Balkans. Similar Le- (8.70%). This is explained due to the fact (%) thality was not registered that after the 1986 epidemics, sufficient 8.70 anywhere else in Europe, experience was gained, not only in cur- Mb/100.000 Mt/100.000 0.16 0.02 with exception of Bul- ing, but also in diagnosing, which exgaria and Albania, and plains why the lethality has decreased in the Far East (1,4,10). from 15.3% (1986) to 8.7% (1995-2006). This is explained with This means that the increasing scale of Time Period Lethality (%) the heavy forms of the resistance of population or the collective 1986 15.40% illness as well as with the immunity on HFRS , results with the de1986-1989 10.80% lack of sufficient experi- crease of these health parameters, re1995-2006 8.70% ence in curing of these ill- spectively, decrease of Mb, Mt and Le. Table 2. Movement of Lethality scale (%) of HFRS in Kosovo, during nesses, in the first year of According to the foreign literature, the different time periods epidemics.Lethality scale lethality scale of HFRS varies: in Soof HFRS during various viet Union Le- 3-22%, then decreases Out of 13 convalescents (that have time periods marks a decrease as follows: to 10-15%, Korea Le – 5-20%; Greece undergone the acute disease during in 1986 it was 15.4%, afterwards during Le – 13%; Albania Le – 28.1%; Scandi1986, 1989, and 1995), we have determined the level of antibodies for the viHFRS – IIF Total Tested ral Ag (HTN, PUU, DOB), in 2008, with Seronegative % seropositive % N % the indirect immune fluorescent method Contact 1* 43 23.0 12 75.0 55 27.1 (IIF). Out of all these convalescents, perContact 2** 79 42.2 3 18.8 82 40.4 sistence of antibodies was found in 10 Haemodialysis persons, while in 3 others we did not find 29 15.5 1 6.3 30 14.8 Pat. antibodies persistence for respective viHealth Personnel 16 8.6 0 0.0 16 7.9 ral Ag. In 4 convalescents (ex acute paControl Group 20 10.7 0 0.0 20 9.9 tients in 1986), testing with indirect imN 187 100.0 16 100.0 203 100.0 mune fluorescent method (IIF) was done Total % 92.1 7.9 100.0 in 2008(after 22 years); in two of them were found levels of antibodies for vi- *Contact 1 or the first family circle – means close family members that live with the patient ral Ag HTN, PUU, DOB (from 1:32 to with HFRS ** Contact 2 or the second family circle – means members of the family that live 1:256), while in the other two, levels of together in the endemic zones characteristic with HFRS antibodies for respective viral Ag were Table 3. Detection of immune fluorescent Antibodies in population living in the natural not found (Table 4). hearths characteristically with HFRS, 2008, Kosovo Also, in 4 other convalescents (ex acute patients in 1989), testing was 1986-1989, it was 10.8%, in a way that it navia and Western Europe Le – 0.5-1% done with indirect immune fluorescent continuously decreases; even also dur- (1,4,10). This shows that the Lethality method (IIF), in 2008 (after 19 years), ing the period 1995-2006 it was lower scale in Kosovo is much lower compared and in 3 of them, levels of antibodies of viral Ag HTN, PUU, DOB were found (Convalescents) (from 1:16 to 1.512), while in one case, Antibodies level of HFRS 2008 Time Nr. ex patients with Municipality Contact period levels of antibodies for respective viral HFRS HTN PUU DOB Ag were not found. In 5 convalescents 1 1986 DeГ§an first 1:256 1:64 1:256 (ex acute patients in 1995) testing was 19862 1986 PejГ« first 1:32 neg 1:64 done with indirect immune fluorescent 2008 (22 3 1986 PejГ« first neg neg neg method (IIF), in 2008 (after 13 years), years) 4 1986 PejГ« first neg neg neg and in all of them, levels of antibodies of viral Ag HTN, PUU, DOB were found 5 1989 PejГ« first 1:128 1:16 1:256 1989(from 1:16 to 1.256) (Table 4). 6 1989 GjakovГ« first 1:512 1:32 1:512 2008 (19 At the patients, in which the acute 7 1989 PejГ« first 1:32 1:16 1:64 years) disease (HFRS) has passed before 13, 19, 8 1989 DeГ§an first neg neg neg and 22 years, we did not gain any signif9 1995 DeГ§an first 1:256 1:32 1:128 icant difference in the levels of antibod10 1995 PejГ« first 1:32 neg 1:64 1995ies for viral Ag: for HTN (r = 0.3000, 11 1995 KlinГ« first 1:64 1:32 1:128 2008 (13 p>0.05); for PUU (r = 0.16, p>0.05), and years) 12 1995 Istog first 1:32 neg 1:64 DOB (r = 0.21, p>0.05). (Table 4).. Table 1. Movement of average morbidity, mortality and lethality scale of HFRS, Kosovo, 1995-2006 13 3. DISCUSSION 1995 GjakovГ« first 1:128 1:16 r r =-0.300 =-0.16 Spearman’s correlation p>0.05 p>0.05 1:64 r =-0.21 Lethality scale of HFRS was higher p>0.05 in Kosovo in 1986, with 15.4%, compared to other neighbouring countries Table 5. Table presentation showing persistence levels of antibodies of viral Ag (HTN, PUU, DOB), (average Lethality in ex YU was 5.2%) during various time periods, 13, 19 and 22 years after the disease. MED ARH 2009; 63(3) • ORIGINALNI ДЊLANCI / ORIGINAL PAPERS - 161 HTN PUU DOB 13 years 19 years 22 years Collective Immunity of the Population from Endemic Zones of Hemorrhagic Fever with Renal Syndrome in Kosovo World of Microbes EDK, Paris, France, Paris, 27th July to 1st August 2002, Le Palais des Congres de Paris, 2002:87. 2. Baek LJ, Kariwa H, Lokugamage K, Yoshimatsu K, Arikawa J, Takashima I, Kang JI, Moon SS, Chung SY, Kim EJ, Kang HJ, Song KJ, Klein TA, Yanagihara R, Song JW: Soochong virus: an antigenically and genetically distinct hantavirus isolated from Apodemus peninsulae in Korea. J Med Virol, 2006;78:290-7. 3. Duh D, Nichol ST, Khristova ML, Saksida A, Hafner-Bratkovic I, Petrovec M, Dedushaj I, Ahmeti S, Avsic-Zupanc T. The Figure 1. Photos with indications from Haemorrhagic Fever (HFRS), hospitalized in the complete genome sequence of a CrimeanFigure 1. Photos with indications from Haemorrhagic Fever (HFRS), hospitalized in the Infectious Disease Clinic in Pristina (Inf. Clinic – Prof. Dr. Salih Ahmeti) Congo hemorrhagic fever virus isolated Infectious Disease Clinic in Pristina (Inf. Clinic – Prof. Dr. Salih Ahmeti) from an endemic region in Kosovo. Vito other countries. During our research, Disease Clinic and other personnel of rol J. Jan, 2008; 15;5:7. PMID:18197964 [PubMed-indexed for MEDLINE]. May-June 2008, we have collected blood UCCK, regional hospitals and primary 5. DISCUSSIONS samples (serums) from 203 persons and health care; but it was missing at it is 4. Duh D, Saksida A, Petrovec M, Dedushaj Lethality scale of HFRS was higher inIIF, Kosovo 1986, the withauthentic 15.4%, compared to other I, Avsic-Zupanc T. Novel one-step realstill in missing governmenafter testing with serologic method neighbouring countries (average Lethality in ex YU was 5.2%) and Balkans. Similar time RT-PCR assay for rapid and specific we had the following results: out of 203 tal programme, which would prevent any diagnosis of Crimean-Congo hemorrhagic Lethality was not registered anywhere else future in Europe, with exception of Bulgaria samples (serums) tested, 187 serums or appearance and new deaths from and fever encountered in the Balkans. J Virol (1, 4 ,10) . This16is explained with the heavy forms of the illness Methods. 2006 May;133(2):175-9. Epub Albania, in negative the Far East. 92.1% and were on HFRS and this disease (1,4,10) Dec 15.PMID: 16343650 [PubMed–inserums or 7.9% were positive on HFRS. dexed for MEDLINE], 2005. This means that specific HTN antibod- 4. CONCLUSIONS 5. Krautkraemer E, Zeier M. Hantavirus ies were found in 7.9% of the population 8 Based on the research work done, we causing hemorrhagic fever with renal synfrom the natural hearths of HFRS. This can conclude that: Lethality scale from drome enters from the apical surface and requires Decay J. Virol, 2008;82:4257-64. proves the increase of the scale of collec- HFRS in 1986, was 15.4%, then in 1985tive immunity on HFRS. Based on the 89 it was 10.8%, while from 1995-2006 it 6. Henttonen H, Kaikusalo A, Kallio E, Laakkonen J, Niemimaa J, Vapalahti O, Vaheri data from foreign literature, specific an- was lower, 8.70%; Low Morbidity, MorA.Monitoring rodent fluctuations, rodenttibodies on HNT were found in 1.9-29.1% tality and Lethality scale form HFRS borne viruses and hanta epidemiology of population from the natural hearths of compared to earlier time periods, results in Finland. In: VI th International Conference on hemorrhagic fever with renal this disease - in Europe, in 2.1% of popu- with increase of the collective immunity syndrome, hantavirus pulmonary synlation. Out of all these convalescents, the in the population from natural hearths drome and hantaviruses, 23-25 de junio, persistence of Antibodies was found in of HFRS; During May-June 2008, with SeГєl. The National Academy of Sciences, 10 persons, while in 3 others we did not the serological method IIF, the testSeГєl, 2004:64. encounter any persistence of antibodies ing of 203 samples (serums) was done, 7. Kim YK, Lee SC, Kim C, Heo ST, Choi C, for the respective viral Ag. After 13, 19 where 187 serums or 92.1% were negaKim JM.:В Clinical and laboratory predictors of oliguric renal failure in haemorand 22 years (1986, 1989, 1995), with the tive on HFRS and 16 serums or 7.9% were rhagic fever with renal syndrome caused serologic method (IIF), the persistence of positive on HFRS. This proves the high by Hantaan virus.В J Infect, 2007;54(4):381the levels of antibodies for viral Ag HTN, scale of increase of collective immunity 6. PUU, DOB was found (with levels from in population from natural hearths with 8. Lee HW, Lee PW, Johnson KM. Isolation of 1:16 to 1:512). After the illness, comes HFRS; Out of 13 convalescents (that the etiologic agent of Korean hemorrhagic fever. 1978. J Infect Dis. 2004;190:1711–21. the decrease of the levels of antibodies, have undergone the acute disease during which shows the existence of possibility 1986, 1989 and 1995), with the immune 9. Markotic A, Nichol ST, Kuzman I, Sanchez AJ, Ksiazek TG, Gagro A, Rabatic S, Zgfor re-infection with other types of Han- fluorescence method IIF, the level of anorelec R, Avsic-Zupanc T, Beus I, Dekaris taan viruses.Various authors have found tibodies was determined for antibodD. Characteristics of Puumala and Dotraces of specific antibodies against the ies of viral Ag (HTN, PUU and DOB) in brava infections in Croatia. J. Med. Virol, 2002;66:542-51. Hantaan virus, even up to 34 years after 2008, where the persistence of antibodthe disease (1,4,10). During our research, ies was found in 10 persons, while in 3 10. MuГ§aj S. Epidemiological-serological characteristics of the Haemorrhagic Fever with we found persistence of antibodies for of them we did not encounter any perRenal Syndrome and defining of endemicviral Ag HTN, PUU DOB (with levels sistence of antibodies for respective viral epidemic zones in Kosovo, Dissertation, from 1:16 up to 1:512), even after 13, 19 Ag; During our research, we found perPristine, May 2009. and 22 years after the illness.(10) Good sistence of antibodies for viral Ag HTN, 11. Schudel, Matt. “Terry Yates, 57; biologist found source of hantavirus”, Washington results have been achieved in defining PUU DOB (with levels from 1:16 up to Post, Boston Globe, 2007-12-24. Retrieved of natural hearths, defining the reser- 1:512), even after 13, 19 and 22 years afon 2007-01-04, 2007. voirs and sources of infection as well as ter the illness. in curing of the patients, which has influenced the decrease of the Morbidity, REFERENCES Mortality and Lethality scale. All this 1. Avsic-Zupanc T, Petrovec M, Duh D, Dedushaj I, Ahmeti S. Description of nosocowas achieved thanks to the hard work mial and inrafamiliar spread of CCHF in of the experts from NIPHK and regional Kosovo during the 2001 epidemic. In: The IPH’s, health personnel of the Infectious 162 MED ARH 2009; 63(3) • ORIGINALNI ДЊLANCI / ORIGINAL PAPERS Corresponding author: Ass. Dr. Sefedin MuГ§aj, MD, PHD, Department of Epidemiology, National Institute of Public Health of Kosovo, Pristine (sefa66@gmail.com; mob tel. +377 44 223 782 LijeДЌenje Hallux valgusa osteotomijom prve kosti metatarzusa po Krameru LijeДЌenje Hallux valgusa osteotomijom prve kosti metatarzusa po Krameru The Kramer Osteotomy in the Treatment of Hallux Valgus Sahib MuminagiД‡, Sanja DrljeviД‡, Amela GraniД‡, Tarik KapidЕѕiД‡, Mehmed KovaДЌeviД‡, Faruk HodЕѕiД‡ Ortopedsko odjeljenje bolnice Crkvice, Kantonalna bolnica Zenica, Bosna i Hercegovina StruДЌni ДЌlanak SAЕЅETAK Vlastitu tehniku u lijeДЌenju hallux valgusa J. Kramer publicirao je 1973. godine (OrthopГ¤dische Pra Xis Heft 8/1982, 636-645). LoЕЎu poziciju prve kosti metatarzusa sa svim posljedicama koja leЕѕi u osnovi deformiteta ispravlja osteotomijom prve kosti metatarzusa i ponovo uspostavlja funkcionalnu ravnoteЕѕu prve grane stopala u svim komponentama. Nakon iskustva, poslije 550 operiranih pacijenata, autor smatra da je ova metoda u prednosti nad mnogim prije opisanim metodama, indikaciono je podruДЌje praktiДЌno veliko, pri poЕЎtovanju tehnike izvodi se jednostavno, post operativno lijeДЌenje ne zahtjeva imobilizaciju, a u poreД‘enju sa drugim metodama komplikacije i loЕЎi rezultati praktiДЌno su nepoznati. U periodu od 1984. do 1988. godine na naЕЎem smo odjeljenju kod 98 oboljelog primijenili Kramerovu osteotomiju u lijeДЌenju hallux valgusa. Postigli smo dobre rezultate, znatno bolje nego drugim metodama. KljuДЌne rijeДЌi: hallux valgus , Kramerova osteotomija, vlastiti rezultati Professional paper SUMMARY In 1973. J.Kramer published his own technique for the cure of hallux valgus (OrthopГ¤dische Praxis Heft 8/1982, 636-645). He corrects bad position of the first bone of the metatarsus with all the consequences which lie in the basis of the deformation. By osteotomy of the first bone of the metatarsus and re-instates functional equipise of the first foot instep in all the components. Having the experience of 550 operated patients he considered that this method has advantages over numerous described method, indicative range is practically wide, respecting the technique it is simply performed, post-operative cure does not require immobilisation, and in comparison with other methods, complications and bad results are practically unknown. On our ward, in the period between 1984 and 1988, we applied Kramer’s osteotomy in 98 cases of hallux valgus. The results were satisfying, considerably better than after other methods of hallux valgus treatment. Keywords: hallux valgus, the Kramer osteotomy, results 1. UVOD zahvatom postigao dobar funkcionalni i estetski rezultat, operator mora analizirati sve komponente deformiteta, proЕЎireno stopalo, loЕЎu poziciju palca, promijenjenu poziciju hvatiЕЎta tetive i sezamoidnih kostiju, pseudoegzostozu i degenerativne promjene u osnovnom zglobu palca u smislu artroze. Operacije na mehkim tkivima (tenotomije, transpozicija tetiva, kapsulloresekcije itd.), ne samo da ne otklanjaju, nego dovode i do novih patoloЕЎkih optereД‡enja u predjelu palca i prednjeg stopala. Resekcione metode na glavici metatarzalne kosti i bazi osnovnog ДЌlanka vode neestetskom stopalu, uz dalje optereД‡enje metatarzalnih glavica i mekih tkiva. Stoga Kramer predlaЕѕe klinastu resekciju prve metatarzalne kosti, sa izdaЕЎnom translacijom, ДЌime utiДЌe na sve komponente deformiteta. Zahvat ima ЕЎiroko indikaciono podruДЌje, tehniДЌki se jednostavno izvodi, hospitalizacija je kratka, a u postoperativnom toku nije potrebna gipsana imobilizacija. Ovaj zahvat J. Kramer primjenjuje od 1973. godine i nakon iskustva u viЕЎe od 550 operacija svoja zapaЕѕanja publicira ra 1982. godine u „ OrtopГ¤dische Praxis“. Ukoliko se napravi dobar preoperativni plan i izbjegne greЕЎka u kirurЕЎkom izvoД‘enju operacija, konaДЌni rezultat uvijek je odliДЌan. J. Kramer navodi samo u 2 sluДЌaja infekt kao komplikaciju. 1.1. INDIKACIJA Ovom metodom moЕѕe se korigirati praktiДЌno svaki stepen hallux valgusa, artroza osnovnog zgloba nije kontraindikacija, uvjet je jedino pokretljivost u osnovnom zglobu palca (dorzalna fleksija ne smije biti manja od 40 stepeni). gorЕЎati deformaciju. Vrlo rijetko sreOdmaknuti plac – ДЌuklaj, statiДЌka Д‡emo se sa kongenitalnim upalnim ili je subluksacija prvog metatarzofalanposttraumatskim halusom valgusom. geanskog zgloba, s lateralnom devijaciPopreДЌno proЕЎiren i spuЕЎten svod jom velikog prsta od uzduЕѕne osovine stopala zajedno sa jednim od najДЌeЕЎД‡ih prve metatarzusne kosti viЕЎe od 20В° i deformiteta, hallux valgusom, javlja se medijalnom devijacijom prve metatarkao ortopedski problem, praktiДЌno u zusne kosti. Prvi ga je opisao La Forest, svakoj Еѕivotnoj dobi. Da bi kirurЕЎkim kirurg Louisa XVI (Luja 16.). Lelievre je predloЕѕio termin – „angulacija prve zrake“, kako bi se naznaДЌilo da se radi o sloЕѕenoj leziji. Haluks valgus je deformacija u Еѕena, ali susreД‡e se i u muЕЎkaraca i djece. Uzrok nastanka je multifaktorski, najДЌeЕЎД‡e kombiniran djelovanjem unutarnjih (anatomske varijacija u strukturi stopala, posebno juvenilnog) i vanjskih uzroka (noЕЎenje nepogodne obuД‡e). SteДЌena deformacija sa spuЕЎtenim metatarzusnim lukom stopala ne moЕѕe se objasniti noЕЎenjem nepogodnih cipela, ali obuД‡a moЕѕe po- Slika 1 a i b. Tehnika: Paraosealno postavljanje KirЕЎnerove igle, supkapialna osteotomija, odstranjenje klina. MED ARH 2009; 63(3) • STRUДЊNI ДЊLANCI / PROFESSIONAL PAPERS 163 LijeДЌenje Hallux valgusa osteotomijom prve kosti metatarzusa po Krameru Osnovno je da se osteotomijom ne dira osnovni zglob palca koji Д‡e kasnije, nakon korekcije, preuzeti optereД‡enje. S obzirom na to da osteotomija ne zahvata podruДЌje epifizne linije, Kramerova osteotomija, kao metoda ostaje kao metoda izbora i u sluДЌajevima juvenilnog hallux valgusa. Kratka hospitalizacija, postoperativno lijeДЌenje bez gipsa i rano optereД‡enje bez potrebe za ЕЎtakama ДЌini operaciju prikladnom i kod starih osoba. 2. materijal i metode rada 2.1. TEHNIKA Preoperativni plan: predhodno je potrebno napraviti rendgenski snimak stopala u stojeД‡em stavu pod optereД‡enjem u dorzoplantarnom smjeru i profilu. Napravi se skica na paus-papiru i unese plan osteotomije, odgovarajuД‡eg ugla i klina sa medijalne strane prve metatarzalne kosti. Zahvat se izvodi u Slika 2. ElastiДЌni zavoj stopala sa blagim pritiskom svih prstiju prema korigiranom palcu nakon operacije odstrani se KirЕЎnerova igla. tournique-u i opД‡oj anesteziji, izuzetno u regionalnoj blokadi stopala, dorzomedijalni rez u visini glavice prve kosti meД‘unoЕѕja stopala, subperiostalni pristup na dijafizu i aplikaciju KirЕЎnerove igle (2 mm) paraosealno u palac. Ovo je obavezno uДЌiniti prije osteotomije. PopreДЌna se osteotomija izvodi iznad glavice, u druga, kosa u smjeru proksimalno-medijalno kao distalno-lateralno. Nakon odstranjenja odgovarajuД‡eg klina (preoperativno planiranje, skica), slijedi lateralizacija distalnog fragmenta i ujedno plantaran dislokacija za 1-3 mm. KirЕЎnerova igla sada se 164 Slika 1 c i d. Tehnika: maksimalna lateralizacija, plantarni pomak 1-3 mm distalnog fragmenta, postavljanje KirЕЎnerove igle u proksimalni fragment fiksira u proksimalni fragment. RezultirajuД‡a sila nakon osteotomije (miЕЎiД‡i i postraniДЌni pritisak KirЕЎnerove igle) djeluje okomito na kontaktne plohe. Lateralizacijom se pritisak joЕЎ poveД‡ava i prva se grana produЕѕava. RezultirajuД‡a sila nakon osteotomije (miЕЎiД‡i i postraniДЌni pritisak KirЕЎnerove igle) djeluje okomito na kontaktne plohe. Lateralizacijom se pritisak joЕЎ poveД‡ava i prva se grana produЕѕava. Lateralizacija je obiДЌno maksimalna, najmanji za ВЅ ЕЎirine metatarzusa na kosti. Lateralizacijom i plantarnim pomakom dolazi do repozicije sezamoidnih kostiju, a MTP zglob preuzima funkciju. Potrebno je paziti na pravilnu poziciju palca, izbjeД‡i bilo kakav pomak dorzalno ili plantarno u smislu savijanja. Postoperativni tretman: mobilizacija prvog postoperatinog dana sa optereД‡enjem i osloncem na petu. Nakon 14 dana odstrane se konci i ponovo stavi elastiДЌna poveska. Radna nesposobnost prosjeДЌno traje od 8 do 10 sedmica, a ako se radi o pa- Slika 3 i 4. Rendgenski snimak stopala preoperativno MED ARH 2009; 63(3) • STRUДЊNI ДЊLANCI / PROFESSIONAL PAPERS cijentu koji svoj posao obavlja sjedeД‡i, on se upuД‡uje na rad sedmicu dana nakon odstranjenja KirЕЎnerove igle. U sluДЌaju pojave otoka, provodi se manuelna masaЕѕa, rijetko ultrazvuk i terapija Nemetrodinom. SliДЌan kirurЕЎki zahvat moЕѕe se izvesti kod digitus varus quintus, samo se ne uzima klin, a uДЌine se jedino steotomija i medijalizacija fragmenta. MoguД‡e greЕЎke: Osteotomija moЕѕe biti izvedena previsoko, pa postoji opasnost od pomaka u sagitalnoj osi i moguД‡nosti su korekture manje. Ako je osteotomija izvedena prenisko, postoji opasnost od nekroze glavice. 3. NAЕ I SLUДЊAJEVI I REZULTATI U periodu od 1984. do 2008. godine primjetili smo Kramerovu metodu kod 98 pacijenata, kod 73 pacijenta operacija je uДЌinjena na oba stopala. Postoperativnih komplikacija nije bilo, a takoД‘er ni infekta. Kod 17 pacijenata zbog lahkog otoka i bolnosti koji je perzistirao i nakon odstranjenja KirЕЎnerove igle, LijeДЌenje Hallux valgusa osteotomijom prve kosti metatarzusa po Krameru primijenjena je fizikalna terapija (Nemetrodin i masaЕѕa) u toku dvije sedmice. Nismo primijetili niti jedan sluДЌaj usporenog srastanja kosti niti pseudoartorze. Pacijente smo operirali u opД‡oj anesteziji, uz postavljanje tournique. Pacijenti su mobilizirani prvog postoperativnog dana uz oslonac na petu. Prvi prevoj slijedio je prvog postoperativnog dana. Pacijente smo otpuЕЎtali drugog do ДЌetvrtog postoperativnog dana. Slika 3a i 4a. Redgenski snimak uДЌinjen prvog postoperativnog dana Konci, kao i KirЕЎnerova igla odstranjeni su na kontroli hod. Nakon primjenjene Kramer osteomnogo bolje nego prije primjenom ratomije, pseudoartroze su srasle, tegobe zliДЌitih drugih metoda. Opisani se zasu prestale uz vrlo dobar rezultat. Istu hvat danas najДЌeЕЎД‡e primjenjuje na natehniku sa obrnutim procesom primjeЕЎem odjeljenju u lijeДЌenju deformiteta njivali smo uspjeЕЎno kod varus defortipa halux valgus. macije malog prsta stopala. U poreД‘enju sa zahvatima na mehkim tkivima i LITERATURA 1. RadojeviД‡ S. Sistematska i topografska anatos raznim drugim osteotomijama na prmija, Noga, Medicinska knjiga, Beograd–Zavoj kosti meД‘unoЕѕja, nakon kojih je bilo greb, 1963. i nezadovoljavajuД‡ih rezultata recidiva 2. Pernkopf E. Atlas der topographischen und angewandten Anatomie des Menschen Urdeformiteta, Kramerovom tehnikom ban—Schwarzenberg, MГјnchen und Berlin i metodom kirurЕЎkog lijeДЌenja defor1964, Zweiter Band. miteta hallux valgus veoma smo zado3. Heim U, Pfeiffer KM. Periphere Osteosynthesen Springer-Verlag, Berlin – Heidel Berg– voljni i za nas je ona praktiДЌnol postala New York, 1972 metodom izbora. 4. Edmondson AS, Crenshaw AH. Campbe5. ZAKLJUДЊAK Slika 5. Kramer osteotomija ka digitus quinti U periodu od 1984. do 1988. godine kod 98 pacijenata sa deformitetom Halux valgus primijenili smo Kramerovu osteotomiju na prvoj kosti meД‘unoЕѕja. Postigli smo veoma dobre rezultate, varus 5. 6. 7. 8. ambulantno. Stopalo smo bandaЕѕirali 6 do 7 sedmica. 9. 4. DISKUSIJA Za vrijeme boravka na Klinici „Balgrist“ u ZuRichu, ljubaznoЕЎД‡u koleginice E. Lamprecht, prvi autor je imao ДЌast upoznati se s orginalnim radovima i publikacijama prof. J. Kramera i E. Lamprechta. Od 1984. godine primjenjujemo taj zahvat u lijeДЌenju hallux valgusa. Vrlo brzo svladali smo tehniku, komplikacija nije bilo, a takoД‘er nit u jednog oboljelog nisu se pojavili pseudoartroza ili recidiv. Kod jedne pacijentice intervenirali smo na oba stopala zbog pseudoartroza prve metatarzalne kosti nakon Shevron operacije. Bol, otok, onemoguД‡avali su oslonac i 10. 11. 12. 13. 14. 15. Slika 6. Rezultat osam sedmica postoperativno lls operative Orthopaedics. The C.V. Mos by Company, St. Louis -Toronto -London, 1980. Lamprecht E, Kramer J. Die Metatrsale-IOsteo tomie nach Kramer zur Behandlung des Halux valgus, OrthopГ¤dische Praxis, 1982; 636-45. MuminagiД‡ S, TaliД‡ A, AlibegoviД‡ A. Kramer osteotomy in the treatment of hallux valgus Acta orthopaedica, 1990;1:15-20. Venore JV. Diagnosis and treatment of first metatarsal Joint disorders; J Foot ankle Surg, 2003;42(3):112-23. King DM. Associated Deformitites and hypermobilitiy In Halux valgus, Foot ankle int, 2004;25(4):251-5. Ferrari J, Higins JP, Price TD. Interventionts for Treating Hlaux valgus and bunions,. Corane Datebase Syst Rev. .2004. Halux valgus, www.emedicine.com/orthoped/ topic16.htm Bunions, www.wikipedia.org/wiki/bununion Bunions, www.epodiatry.com/bunion.htmchaced Radiographics evaluation of Hallux valgus www.rawashington.edu/academics/academicsection/msk Halux valguswww.aaep.org/afp/200201101/ tifs/8html Halux valgus, www.medicine-berlin.de Kontakt adresa autora. Prof. Dr. Sahib MuminagiД‡. Ortopedsko oboljenje Kantonalne bolnice u Zenici. Zdravstveni fakultet Univerziteta u Zenici. Tel.: 00 387 32 444 780. MED ARH 2009; 63(3) • STRUДЊNI ДЊLANCI / PROFESSIONAL PAPERS 165 Perkutane koronarne intervencije bez „on-site“ kardiohirurЕЎke potpore Perkutane koronarne intervencije bez „on-site“ kardiohirurЕЎke potpore Percutaneous Coronary Interventions Without On-Site Cardiac Surgical Backup Zoran StajiД‡1, Zdravko M. MijailoviД‡2 Sala za kateterizaciju srca, KliniДЌko-bolniДЌki centar Zemun, Beograd, Srbija1 Klinika za kardiologiju, Vojnomedicinska akademija, Beograd, Srbija2 Revijalni ДЌlanak SAЕЅETAK Perkutane koronarne intervencije predstavljaju danas, tri decenije nakon prve balon angioplastike koronarnih arterija, bezbedan, efikasan i najДЌeЕЎД‡e primenjivani metod revaskularizacije miokarda. Prve perkutane koronarne intervencije bez „on-site“ kardiohirurgije poДЌele su se izvoditi poДЌetkom devedesetih godina XX veka, zahvaljujuД‡i unapreД‘enju tehnike i materijala koriЕЎД‡enih za ove procedure, kao i zbog potrebe da se stanovnicima u udaljenim oblastima uДЌini dostupnim ova savremena i efikasna terapija. MeД‘utim, i danas posle skoro dvadesetak godina izvoД‘enja perkutanih koronarnih intervencija i u ustanovama bez kardiohirurgije ovo pitanje ostaje kontroverzno i nereЕЎeno. Tako da i pored postojanja velikog broja interventnih kardioloЕЎkih centara bez „on-site“ kardiohirurgije u velikom broju zemalja u kojima se izvodi znaДЌajan broj i elektivnih i primarnih intervencija, zvaniДЌni vodiДЌi asocijacija za perkutane koronarne intervencije i dalje ne preporuДЌuju izvoД‘enje intervencija bez postojanja „on-site“ kardiohirurgije. Ipak, u poslednje vreme fokus sa pitanja prisustva „on-site“ kardiohirurgije se sve viЕЎe pomera u pravcu definisanja kriterijuma za izvoД‘enje perkutanih koronarnih intervencija po najviЕЎim standardima bez obzira na postojanje „on-site“ kardiohirurЕЎke potpore. U ovom revijalnom radu dat je trenutni pregled aktuelnih stavova o organizaciji i izvoД‘enju perkutanih koronarnih intervencija u ustanovama bez kardiohirurЕЎke potpore. KljuДЌne reДЌi: Perkutane koronarne intervencije, Centar bez „on-site“ kardiohirurgije, Bezbednost, Ishod Review SUMMARY Percutaneous coronary interventions are now, three decades after the first balloon angioplasty of the coronary arteries, safe, effective, and most commonly applied method of myocardial revascularization. The first percutaneous coronary intervention without “on-site” cardiac surgery began at the beginning of the nineties of the twentieth century, thanks to the improvement of techniques and materials used for these procedures, as well as the need to make available to citizens in remote areas modern and effective therapy. However, today, after nearly twenty years of application of percutaneous coronary interventions in facilities without cardiac surgery this issue remains controversial and unresolved. So despite the existence of a large number of interventional cardiology centers without “on-site” cardiac surgery in a large number of countries in which they performed a significant number of elective and primary interventions, the official guidelines of the associations for percutaneous coronary interventions still does not recommend implementation of interventions without the existence of “on –site” cardiac surgery. But, recently the focus shifts from the questions about presence of “onsite” cardiac surgery in the direction of defining criteria for performing percutaneous coronary interventions according to the highest standards regardless of the existence of “on-site” cardiac surgical backup. This review article gives the current view on current attitudes about the organization and implementation of percutaneous coronary interventions in facilities without cardiac surgical backup. Keywords: percutaneous coronary interventions, center without on-site cardiac surgical backup, safety, outcome 1. UVODNI DEO U protekle tri decenije, nakon ЕЎto je 1977. godine Andreas GrГјntzig u univerzitetskoj bolnici u Cirihu izveo prvu perkutanu balon angioplastiku koronarnih arterija, primena i indikacije za izvoД‘enje ove metode su revolucionarno proЕЎireni i unapreД‘eni. NaroДЌito u poslednjoj deceniji je doЕЎlo do znaДЌajnog usavrЕЎavanja tehnike perkutanih koronarnih intervencija (PCI), poboljЕЎanja tehnoloЕЎkih karakteristika materijala (kateteri, koronarne Еѕice), daljeg napretka u razvoju koronarnih stentova (poboljЕЎanje dizajna i materijala, otkriД‡e stentova obloЕѕenih lekovima), razvoja i usavrЕЎavanja novih naprava (aspiracioni kateteri, sredstva za trombektomiju), kao i usavrЕЎavanja antiagregacione terapije. ZahvaljujuД‡i tome, danas se perkutane koronarne intervencije smatraju rutin166 skim, bezbednim i efikasnim naДЌinom leДЌenja i predstavljaju vodeД‡i metod revaskularizacije miokarda u razvijenim zemljama, sa pribliЕѕnim odnosom izvoД‘enja 2:1 u odnosu na konvencionalnu koronarnu bajpas hirurgiju (1, 2). 2. CILJ RADA Cilj ovog rada je pregled aktuelne literature i stavova u pogledu organizacije i izvoД‘enja perkutanih koronarnih intervencija u ustanovama bez kardiohirurЕЎke sluЕѕbe, s obzirom na i dalje prisutna kontroverzna miЕЎljenja i brojne debate o ovom pitanju. 3. METOD I REZULTATI RADA Rad je revijskog karaktera. KoriЕЎД‡enjem sledeД‡ih engleskih kljuДЌnih reДЌi: percutaneous coronary intervention, center without on-site cardiac surgical MED ARH 2009; 63(3) • Revijalni ДЌlanci • Reviews backup, safety, and outcomes, pretraЕѕili smo dostupnu literaturu na sajtu www. ncbi.nlm.nih.gov/pubmed zakljuДЌno sa mesecom julom 2009. godine. Aktuelne preporuke ameriДЌkih (ACC/AHA/SCAI) i evropskih asocijacija za perkutane koronarne intervencije (EAPCI) smatrani su baziДЌnim dokumentima u pripremi ovog teksta. 3.1. Nastanak PCI centara bez „onsite“ kardiohirurЕЎke potpore Potreba da se i stanovnicima u ruralnim, udaljenim oblastima SAD i Australije obezbede PCI, posebno bolesnicima sa akutnim infarktom miokarda, kao najefikasnijem terapijskom modalitetu reperfuzije, dovela je do inicijalnog uspostavljanja programa interventne kardiologije u opЕЎtim bolnicama bez „on-site“ kardiohirurgije u ovim zemljama poДЌetkom devedesetih godina XX veka (3). MeД‘utim, ubrzo se pokazalo da je iz razloga odrЕѕivosti interventnog programa, a imajuД‡i u vidu i neophodan minimalan godiЕЎnji broj PCI [volumen] za ustanove i operatore, bilo takoД‘e neophodno ustanoviti pored hitnog i elektivni PCI program u ustanovama bez „on-site“ kardiohirurgije. Na taj naДЌin je otvoreno kontroverzno pitanje aspekta bezbednosti elektivnih PCI u ustanovama bez kardiohirurgije, s obzirom da je rizik od potrebe za hitnom kardiohirurЕЎkom intervencijom danas mali [<0.5%], ali ipak postoji (4). MeД‘utim, u poslednje vreme primarno pitanje sve viЕЎe ne predstavlja problem nepostojanja „on-site“ kardiohirurgije koji se reЕЎava brzim i efikasnim transportom u kardiohirurЕЎki centar koji obezbeД‘uje hirurЕЎku potporu, veД‡ postizanje najviЕЎeg kvaliteta PCI, nezavisno od ДЌinjenice postojanja „on-site“ kardiohirurЕЎke potpore u zdravstvenom centru (5). 3.2. Prevalencija i trendovi PCI bez „on-site“ kardiohirurgije Prevalencija uraД‘enih PCI bez kardiohirurЕЎke potpore se konstantno tokom poslednjih petnaestak godina poveД‡avala, kako u svetu, tako i u drЕѕavama naЕЎeg regiona. TakoД‘e, postojao je i stalni trend poveД‡anja broja PCI centara bez kardiohirurЕЎke potpore. Prema podacima ameriДЌkog CathPCI registra, 2005. godine je u SAD postojalo 16.1% [75/463] PCI centara bez kardiohirurЕЎke potpore (6). U Velikoj Britaniji je 2004. godine, ДЌak 26% PCI centara radilo bez kardiohirurЕЎke potpore (7). SliДЌni podaci postoje i za druge ekonomski razvijene drЕѕave. U Srbiji, zakljuДЌno sa mesecom julom Perkutane koronarne intervencije bez „on-site“ kardiohirurЕЎke potpore PRILOZI 2009. godine postojao je veД‡i broj PCI centara bez kardiohirurgije u odnosu na broj centara sa kardiohiruЕЎkom potporom [5/9 PCI centara su bez kardiohirurЕЎke potpore]. U centrima bez kardiohirurgije u Srbiji je tokom 2008. godine uraД‘eno ukupno 25.4% [1944/7622] svih PCI, odnosno ukupno 15.7% [264/1681] svih primarnih PCI (8). Realno je oДЌekivati da se i u narednom periodu nastavi poveД‡anje broja uraД‘enih PCI, posebno primarnih u centrima bez kardiohirurgije. TakoД‘e, u Srbiji se planira otvaranje novih, regionalnih PCI centara bez kardiohirurgije. 3.3. Bezbednost i efikasnost Do sada je publikovano oko 30-tak studija koje su ispitivale bezbednost i efikasnost PCI u centrima bez „on-site“ kardiohirurgije i sve osim jedne (9) su pokazale jednaku bezbednost i efikasnost, odnosno neinferiornost PCI (10, 11, 12, 13, 14, 15, 16, 17, 18) uraД‘enih u centrima bez „on-site“ kardiohirurgije u poreД‘enju sa centrima sa „on-site“ kardiohirugijom. Ovo naravno vaЕѕi samo za PCI centre koji su intermedijarnog ili velikog volumena [>200 intervencija godiЕЎnje]; centri sa malim volumenom [<200 PCI/godiЕЎnje] imaju znaДЌajno loЕЎije rezultate, tj. veД‡i mortalitet (19). Efikasnost PCI u danaЕЎnjoj eri stentova obloЕѕenih lekovima i savremene antiagregacione terapije kreД‡e se oko 97%, dok je incidencija velikih komplikacija <1%, a s obzirom da se najveД‡i broj komplikacija uspeЕЎno reЕЎava perkutanim interventnim pristupom, potreba za hitnom kardiohirurЕЎkom intervencijom tokom PCI iznosi <0.5% (20). VaЕѕno je istaД‡i i da je nedostatak svih dosadaЕЎnjih studija ДЌinjenica da su to bile uglavnom retrospektivne, deskriptivne studije pojedinaДЌnih centara koji su svoje rezultate poredili sa rezultatima velikih „on-site“ centara. Za sada jedina, velika, multicentriДЌna, prospektivna, randomizovana studija koja ispituje bezbednost i efikasnost PCI u centrima sa „on-site“ kardiohirurgijom u odnosu na centre bez „on-site“ kardiohirurgije je C-PORT studija koja je zapoДЌeta 2006. godine u SAD (21). Objavljivanje prvih rezultata ove studije oДЌekuje se tokom 2009. godine. Kako su dosadaЕЎnje preporuke bile bazirane iskljuДЌivo na manjim opservacionim studijama i konsenzusu eksperata, sa velikim nestrpljenjem se oДЌekuju rezultati ove studije koji bi mogli dovesti do promene sadaЕЎnjih preporuka. Tabela 1. KliniДЌki i angiografski kriterijumi koji oznaДЌavaju visok interventni rizik prema SCAI preporukama I. KliniДЌki kriterijumi ДЌije prisustvo kod bolesnika oznaДЌava potencijalno visoki rizik u sluДЌaju okluzije izazvane intervencijom: • dekompenzovana zastojna srДЌana insuficijencija • ejekciona frakcija leve komore ≤ 25% • stenoza (>50%) glavnog stabla leve koronarne arterije ili trosudovna koronarna bolest bez prethodne CABG • pojedinaДЌna stenoza koja ugroЕѕava >50% preostalog vitalnog tkiva miokarda II. Angiografski kriterijumi koji oznaДЌavaju potencijalno visok rizik za nastanak intervencijom izazvane akutne okluzije: • difuzna bolest (>2cm u duЕѕini stenoze) i izrazita tortuoznost proksimalnog segmenta • teЕЎko kalcifikovane lezije proksimalnog segmenta • lezije na ekstremno velikim krivinama (>90В°) • nemoguД‡nost protekcije velikih boДЌnih grana • lezije na degenerativno izmenjenim starim venskim graftovima • trombotiДЌne lezije • bilo koje druge karakteristike lezije / arterije koje onemoguД‡avaju implantaciju stenta • agresivni pristup u otvaranju CTO moЕѕe dovesti do perforacije koronarne arterije SCAI, Society for Cardiovascular Angiography and Interventions; CABG, Coronary Artery Bypass Grafting; CTO, Chronic Total Occlusion 3.4. Aktuelne preporuke za PCI bez „on-site“ kardiohirurgije Prema aktuelnom ACC/AHA/SCAI vodiДЌu iz 2007. godine (1), primarne PCI u centrima bez kardiohirurgije i dalje nose indikaciju klase Iib, tj. mogu se izvoditi pod odreД‘enim okolnostima, dok elektivne PCI bez kardiohirurЕЎke potpore imaju indikaciju klase III, tj. ne preporuДЌuju se. Evropsko udruЕѕenje kardiologa u svom vodiДЌu za PCI iz 2005. godine (2) se ne bavi pitanjem izvoД‘enja PCI bez kardiohirurЕЎke potpore kao ni pitanjima vezanim za kompetentnost operatora, opremljenosti i volumena ustanova. VodiДЌ britanskog udruЕѕenja za kardiovaskularne intervencije iz 2005. godine (7) podrЕѕava izvoД‘enje PCI u centrima bez kardiohirurЕЎke potpore uz poseban naglasak na utvrД‘ivanje zajedniДЌkih standarda za centre sa i bez kardiohirurgije. VodiДЌ belgijske radne grupe za invazivnu kardiologiju publikovan joЕЎ 2003. godine (22) posebno naglaЕЎava da „sadaЕЎnja standardna praksa za izvoД‘enje elektivnih PCI ostaje prisustvo kardiohirurЕЎke potpore“. KardioloЕЎko udruЕѕenje Australije i Novog Zelanda u svom vodiДЌu publikovanom 2005. godine (23) navodi da se „PCI prvenstveno izvode u centrima sa on-site kardiohirurЕЎkom potporom, ali se i potvrД‘uje da zahtevi za obezbeД‘ivanje kardiohirurgije mogu biti16izuzeti u odreД‘enim okolnostima i da adekvatno obuДЌeni operatori mogu bezbedno izvoditi interventne koronarne procedure u bolnicama bez kardiohirurЕЎke potpore“. TakoД‘e, u dokumentu se navodi da pacijentima u udaljenim oblastima, koji imaju smanjenu dostupnost koriЕЎД‡enja savremene interventne kardioloЕЎke terapije, omoguД‡avanje dostupnosti interventnih procedura treba da poboljЕЎa kvalitet zdravstvene zaЕЎtite. Interesantno je navesti primer NemaДЌke, zemlje sa bogatom tradicijom i odliДЌnom organizacijom zdravstvene zaЕЎtite u kojoj ne postoje nacionalne preporuke za izvoД‘enje PCI, mada postoji znaДЌajan broj operativnih interventnih kardioloЕЎkih centara bez „on-site“ kardiohirurЕЎke potpore. U Srbiji do sada nisu publikovane nacionalne preporuke vezane za standarde izvoД‘enja koronarnih angiografija i PCI. MED ARH 2009; 63(3) • Revijalni ДЌlanci • Reviews 167 Perkutane koronarne intervencije bez „on-site“ kardiohirurЕЎke potpore TakoД‘e, trenutno ne postoje ni preporuke za organizaciju i izvoД‘enje PCI u centrima bez kardiohirurgije. ImajuД‡i u vidu trenutno i dalje kontroverzni status izvoД‘enja PCI u centrima bez kardiohirurЕЎke potpore, koje se uprkos nepostojanju jasnih preporuka izvode u velikom broju zemalja i u sve veД‡em broju, ameriДЌko udruЕѕenje za kardiovaskularne angiografije i intervencije (SCAI) je 2007. godine publikovalo dokument zasnovan na konsenzusu eksperata iz razliДЌitih zemalja o izvoД‘enju PCI bez kardiohirurЕЎke potpore (20). U izradi ovog dokumenta uДЌestovali su iskljuДЌivo eksperti koji rade u PCI centrima sa „on-site“ kardiohirurЕЎkom potporom kako bi se izbegao potencijalni konflikt interesa. Cilj ovog dokumenta nije bio ni da favorizuje ni da negira izvoД‘enje PCI bez kardiohirurЕЎke potpore, veД‡ da u trenutno kontraverznoj situaciji u kojoj zvaniДЌni vodiДЌi uglavnom ne odobravaju elektivne PCI u centrima bez „on-site“ kardiohirurЕЎke potpore koje se u stvarnosti izvode u znaДЌajnom, i sve veД‡em broju, definiЕЎe adekvatne i neophodne standarde, kako bi operatori u PCI centrima bez „on-site“ kardiohirurЕЎke potpore radili po jasno definisanim, najviЕЎim standardima. 3.5. Kompetentnost operatora Samo izvoД‘enje velikog broja intervencija, mada neophodno, samo po sebi ne garantuje i visoki kvalitet rada operatora. Е ta viЕЎe, smatra se da je znaДЌajnija mera kvaliteta odnosno kompetentnosti operatora, broj komplikacija i proceduralni i kliniДЌki ishod bolesnika. Prema SCAI preporukama (20), operatori u PCI centrima bez „on-site“ kardiohirurgije treba da ispunjavaju, pored generalnih ACC/AHA kriterijuma za sertifikaciju (1), i dodatne kriterijume: •• broj komplikacija i ishod bolesnika treba da bude za svakog operatora najmanje ekvivalentan, a idealno i superioran, u poreД‘enju sa vrednostima na nacionalnom nivou, •• za svakog operatora je neophodno da postoji proverljiv dosije sa ishodima bolesnika, ЕЎto je od veД‡eg znaДЌaja od arbitrarno odreД‘enog broja neophodnih procedura, •• pre zapoДЌinjanja rada u centru bez „on-site“ kardiohirurgije, operator treba da ima iza sebe uraД‘enih najmanje 500 intervencija kao prvi operator nakon zavrЕЎenog treninga; za operatore sa uraД‘enim manjim brojem intervencija ne168 ophodan je mentorski rad i monitoring dok se njihove sposobnosti, odluke i ishodi bolesnika ne procene i formalno potvrde da su ekvivalentni nacionalnim vrednostima, •• ukupan godiЕЎnji broj intervencija smatra se da za operatore u centrima bez „on-site“ kardiohirurgije treba da bude neЕЎto viЕЎi od broja za operatore u centrima sa kardiohirurgijom, drugim reДЌima ovim operatorima je potrebno veД‡e iskustvo zbog reЕЎavanja eventualnih komplikacija. Kao ЕЎto se iz napred navedenog moЕѕe zakljuДЌiti, za operatore u centrima bez „on-site“ kardiohirurgije potrebno je veД‡e prethodno iskustvo i konstantno odrЕѕavanje kompetentnosti putem veД‡eg broja intervencija na godiЕЎnjem nivou uz kontinuiranu edukaciju. 3.6. Kvalifikacije centra i ostalog osoblja NeobiДЌno je vaЕѕno da i celokupno osoblje u Sali za kateterizaciju srca, kao i u koronarnoj jedinici bude u potpunosti edukovano u pogledu tretmana pacijenata pre, tokom i posle procedure. Edukacija podrazumeva poznavanje svih mera u sluДЌaju potencijalnih proceduralnih komplikacija ukljuДЌujuД‡i i primenu lekova, DC ЕЎoka, intraaortne balon pumpe, pacemakera, kao i svih ostalih moguД‡nosti perkutanog interventnog reЕЎavanja komplikacija (24). U SAD se smatra da je neophodan mininalni broj 200 PCI godiЕЎnje da bi centar bez „on-site“ kardiohirurgije bio operativan. Manji broj intervencija se eventualno moЕѕe dozvoliti u veoma udaljenim oblastima. Apsolutni minimum u SAD je 150 PCI/godiЕЎnje, od ДЌega 36 primarnih PCI; centri koji nemaju ovaj volumen intervencija ne mogu imati licencu za rad (25). MeД‘utim, novootvoreni PCI centri imaju period od dve godine na raspolaganju da dostignu neophodan apsolutni minimum intervencija. Ukoliko nakon toga ne uspeju da dostignu ovaj broj moraju prestati sa radom (20). Svrha organizovanja PCI programa u centrima bez „on-site“ kardiohirurgije je izvoД‘enje pre svega primarnih PCI (26). Iz tog razloga se u SAD ne dozvoljava otvaranje centara u kojima Д‡e se izvoditi samo elektivne PCI; svaki PCI centar u SAD bez „on-site“ kardiohirurgije je u obavezi da izvodi primarne PCI 24h/svakodnevno. PCI centri bez „on-site“ kardiohirurgije u Evropi, kao i u naЕЎoj zemlji MED ARH 2009; 63(3) • Revijalni ДЌlanci • Reviews trenutno nemaju obavezu da obezbeД‘uju primarne PCI 24h/svakodnevno veД‡ je to stvar organizacije na nivou ustanove i svake zemlje pojedinaДЌno. 3.7. Selekcija bolesnika i lezija BriЕѕljiva primena kliniДЌkih i angiografskih kriterijuma je neophodna za selekciju bolesnika pre izvoД‘enja elektivnih PCI u centrima bez „on-site“ kardiohirurЕЎke potpore. Naime, u sluДЌaju elektivnih PCI, bolesnik ima moguД‡nost da bira i centar i operatora. Situacija je drugaДЌija u sluДЌaju akutnog infarkta miokarda i primarnih PCI. Drugim reДЌima, kliniДЌka slika i odnos korist-rizik su razliДЌiti za elektivne i primarne PCI, iz ДЌega proizlazi da u ovim sluДЌajevima treba primeniti i razliДЌite kriterijume. Kod izvoД‘enja elektivnih PCI bez „on-ste“ kardiohirurЕЎke podrЕЎke, potrebno je proceniti ne samo verovatnoД‡u neuspeha PCI veД‡ i potencijalni rizik u sluДЌaju nastanka komplikacija. Naime, s jedne strane postoje nisko odnosno visoko riziДЌni bolesnici [prisustvo komorbiditeta, na pr. terminalna bubreЕѕna insuficijencija, malignomi, loЕЎa rezidualna kardijalna funkcija i sl.], dok s druge strane postoje nisko odnosno visoko riziДЌne lezije [na pr. lezije na glavnom stablu leve koronarne arterije, ostijalne i bifurkacione lezije, trombotiДЌne lezije, hroniДЌne totalne okluzije, lezije na degenerativno izmenjenim venskim graftovima i sl.]. VaЕѕno je uvek istovremeno proceniti i anticipirati riziДЌnost i bolesnika i lezije kod izvoД‘enja elektivnih PCI u centrima bez „on-site“ kardiohirurЕЎke podrЕЎke. Kao ЕЎto je veД‡ istaknuto PCI centar bez kardiohirurgije mora osim primarnih izvoditi i elektivne PCI, s tim ЕЎto kod svakog bolesnika treba pre elektivne PCI individualno proceniti rizik. Trenutno postoji nekoliko efikasnih i jednostavnih modela za procenu rizika kod kojih se na osnovu kliniДЌkih i angiografskih parametara izraДЌunava rizik skor koji predstavlja verovatnoД‡u rizika nastanka smrtnog ishoda tokom PCI (27-29). U tabeli 1. prikazani su kliniДЌki i angiografski kriterijumi koje SCAI (20) definiЕЎe kao visoko riziДЌne. U tabeli 2. su prikazane SCAI preporuke za izvoД‘enje elektivnih PCI u centrima bez „on-site“ kardiohirurgije (20). U praksi su moguД‡e ДЌetiri kombinacije [tabela 2.]. Za centar bez „on-site“ kardiohirurgije idealan bolesnik za PCI je nisko riziДЌni sa nisko riziДЌnom lezijom. Kod visoko riziДЌnih bolesnika sa visoko riziДЌnim lezijama elek- Perkutane koronarne intervencije bez „on-site“ kardiohirurЕЎke potpore tivne PCI treba izvoditi u centrima sa „on-site“ kardiohirurЕЎkom podrЕЎkom, a u odreД‘enim sluДЌajevima i uz kardiohirurЕЎki „stand-by“ [pripravnost kardiohirurga i sale za vreme PCI]. Pri izvoД‘enju elektivne PCI kod visoko riziДЌnog bolesnika sa nisko riziДЌnom lezijom u centru bez „on-site“ kardiohirurgije, preporuka je da se o tome obavestiti nadleЕѕni kardiohirurЕЎki centar koji obezbeД‘uje „offsite“ potporu radi pripravnosti u sluДЌaju nastanka komplikacija. Za PCI tretman visoko riziДЌnih lezija kod nisko riziДЌnih bolesnika u centru bez „on-site“ kardiohirurgije dovoljno je pridrЕѕavati se standardnih mera. 3.8. Hitan transport u kardiohirurЕЎki centar u sluДЌaju komplikacija Za uspeЕЎnost i bezbednost PCI programa u centrima bez „on-site“ kardiohirurЕЎke potpore neophodna je tesna saradnja i stalna komunikacija sa kardiohirurЕЎkim centrom koji obezbeД‘uje podrЕЎku. Ova saradnja treba da bude bazirana na formalizovanom i potpisanom sporazumu izmeД‘u dve ustanove tj. izmeД‘u PCI centra bez kardiohirurgije i kardiohirurЕЎkog centra koji pruЕѕa potporu KljuДЌna odrednica sporazuma treba da bude protokol za hitan transport bolesnika u sluДЌaju potrebe za hitnom kardiohirurЕЎkom intervencijom; idealno bi bilo da se transfer periodiДЌno simulaciono testira (20). U informisanom pristanku koji bolesnici daju neposredno pre koronarografije i PCI, treba da stoji da Д‡e u sluДЌaju iznenadnog nastanka komplikacija tokom ovih procedura koje zahtevaju neodloЕѕno hirurЕЎko zbrinjavanje biti hitno transportovani u odreД‘eni kardiohirurЕЎki centar sa kojim postoji prethodni sporazum. S druge strane, formalno potpisivanje saglasnosti i na hirurЕЎku intervenciju pre koronarografije i PCI danas se ne smatra viЕЎe neophodnim (30), s obzirom da ova potreba postoji u izrazito malom broju sluДЌajeva. Osim toga danas u velikim kardiovaskularnim centrima koji imaju „on-site“ kardiohirurgiju takoД‘e viЕЎe ne predstavlja standard da hirurЕЎka sala i kardiohirururЕЎki tim budu pripravni odnosno „stand-by“ za vreme rutinskih PCI. Zbog niske incidencije komplikacija za ДЌije reЕЎavanje je potrebna kardiohirurЕЎka intervencija, ne postoje precizni podaci o potrebnom vremenu za transport bolesnika iz PCI sale u kardiohirurЕЎku salu u centrima sa „on-site“ kardiohirurgijom, ali se pretpostavlja da je potrebno oko 60 min da se Tabela 2. SCAI preporuke za izvoД‘enje elektivnih PCI u centrima bez „on-site“ kardiohirurgije Visok kliniДЌki, visok angiografski rizik: Ne preporuДЌuje se PCI u centru bez „onsite“ kardiohirugije Visok kliniДЌki, nizak angiografski rizik: PCI u centru bez „on-site“ kardiohirugije sa pripravnom „off-site“ podrЕЎkom Nizak kliniДЌki, visok angiografski rizik: PCI u centru bez „on-site“ kardiohirurgije uz standardnu proceduru Nizak kliniДЌki, nizak angiografski rizik: PCI u centru bez „on-site“ kardiohirurgije Najbolji scenario SCAI, Society for Cardiovascular Angiography and Interventions; PCI, Percutaneous Coronary Intervention SkraД‡enice i objaЕЎnjenja skraД‡enica koriЕЎД‡enih u radu On-site - u istoj ustanovi Off-site - u drugoj ustanovi PCI - percutaneous coronary intervention CABG - coronary artery bypass grafting DC - direct current CTO - chronic total occlusion ACC - American College of Cardiology AHA - American Heart Association SCAI - Society for Cardiovascular Angiography and Intervention ESC - European Society of Cardiology Kontak adresa autora: Doc. dr Zdravko M. MijailoviД‡, Vojnomedicinska okupi kardiohirurЕЎki tim i pripremi hi- vremene standarde u leДЌenju i nezi. akademija, Klinika za kardiologiju, Crnotravska 17, 11000 Beograd, Srbija, Tel: rurЕЎka sala. Iz tog razloga preporuДЌeno 3.9. PraД‡enje kvaliteta rada +381-11-2661-129. Fax: +381-11-2666-164, Mobilni: +381-63-248-800, E-mail: vreme transporta bolesnika iz PCI cenIz dosadaЕЎnje kliniДЌke prakse je potra bez kardiohirurgije u nadleЕѕni karstalo jasno da za kvalitet izvedenih PCI mdzdravko@yahoo.com diohirurЕЎki centar treba da bude 60-120 nije najvaЕѕnije prisustvo „on-site“ karmin (20). U sluДЌaju pojave komplikacija diohirurЕЎke potpore. Smatra se da je tokom PCI u centru bez „on-site“ kardi- osim neophodne tehnoloЕЎke opremljeohirurgije za ДЌije efikasno zbrinjavanje bi nosti Sale za kateterizaciju srca i iskumogla biti neophodna i kardiohirurЕЎka stva operatora, za kvalitet programa inintervencija, neophodno je odmah oba- terventne kardiologije mnogo znaДЌajnije vestiti nadleЕѕni kardiohirurЕЎki centar, kontinuirano praД‡enje kvaliteta rada ЕЎto 17 ДЌak i ako se inicijalno pokuЕЎa perkutano se postiЕѕe formiranjem elektronske baze interventno zbrinjavanje, kako se ne bi podataka – registra, u koju se unose regubilo dragoceno vreme odnosno kako dovno podaci o pacijentima i uДЌinjenim bi se odmah po transportu bolesnika u intervencijama. BolniДЌki PCI registar kardiohirurЕЎki centar, bez daljeg zadr- treba da sadrЕѕi demografske i kliniДЌke Еѕavanja, moglo pristupiti neodloЕѕnoj podatke o bolesnicima, precizne podatke hirurЕЎkoj intervenciji. Osim neophodne o intervencijama i eventualnim komplisaradnje u aktivnom leДЌenju kompliko- kacijama, kao i proceduralni i kliniДЌki isvanih i naroДЌito teЕЎkih bolesnika, od- hod za svakog bolesnika posle uraД‘ene nosno u leДЌenju komplikacija, saradnja PCI. Neophodno je stalno praД‡enje i pointerventnih kardiologa i kardiohirurga reД‘enje podataka iz bolniДЌkog PCI repodrazumeva i aktivno uДЌestvovanje na gistra u odnosu na utvД‘ene nacionalne zajedniДЌkim konferencijama i sesijama standarde [nacionalni PCI registar] kao posveД‡enim reЕЎavanju komplikacija to- i u odnosu na podatke iz vodeД‡ih nacikom PCI. Samo na ovaj naДЌin, timskim onalnih PCI centara sa „on-site“ kardipristupom, moguД‡e je postiД‡i najviЕЎe sa- ohirurgijom. Podatke iz bolniДЌkih i naMED ARH 2009; 63(3) • Revijalni ДЌlanci • Reviews 169 Perkutane koronarne intervencije bez „on-site“ kardiohirurЕЎke potpore cular Intervention Society and the British Cardiac Society. 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ZAKLJUДЊAK I elektivne i primarne perkutane koronarne intervencije u centrima bez „onsite“ kardiohirurЕЎke potpore uz ispunjenost svih neophodnih standarda u pogledu kompetentnosti operatora, kvalifikacije centra i ostalog osoblja, uz postojanje efikasnog protokola za hitan transport bolesnika u kardiohirurЕЎki centar u sluДЌaju nastanka komplikacija, briЕѕljivu selekciju bolesnika i lezija, uprkos nepostojanju jasnih zvaniДЌnih preporuka predstavljaju danas ЕЎiroko primenjivan, bezbedan i efikasan naДЌin revaskularizacije miokarda. Fokus sa pitanja bezbednosti PCI u centrima bez „on-site“ kardiohirurgije je u poslednje vreme u velikoj meri pomeren ka pitanjima vezanim za pruЕѕanje PCI po najviЕЎim standardima nevezano za postojanje „on-site“ kardiohirurgije. LITERATURA 1. King SB, Smith SC, Morrison DA, Williams DO, Hirshfeld JW, Jacobs AK, et al. Focused update of the ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention. J Am Coll Cardiol. 2007;2008:51. 2. Silber S, Albertsson P, AvilГ©s FF, Camici PG, Colombo A, Hamm C, et al. Guidelines for percutaneous coronary interventions: the task force for percutaneous coronary interventions of the European Society of Cardiology. 2005;26:804-47. 3. Dehmer GJ. Percutaneous coronary intervention without onsite surgical backup. Curr Cardiol Rep. 2008;10:407-14. 4. Javaid A, Buch AN, Satler LF, Kent KM, Suddath WO, Lindsay J, et al. Management and outcomes of coronary artery perforation during percutaneous coronary intervention. Am J Cardiol. 2006;98:911-4. 5. Kutcher MA, Klein LW, Ou Wharton TP, Dehmer GJ, Singh M. et al. Percutaneous coronary interventions in facilities without cardiac surgery on site. A report from National Cardiovascular Data Registry (NCDR). J Am Coll Cardiol 2009;54:16-24. 6. Dehmer GJ, Kutcher MA, Dey SK, Shaw RE, Weintraub WS, Mitchell K, et al. 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Acta Cardiol. 2003;58:3418. 23. Brieger D. Policy on performance of coronary angiography and percutaneous coronary intervention in rural sites. The council of the Cardiac Society of Australia and New Zealand, November 25, 2005. [Available at http://www.csanz.edu.au/guidelines/practice/index.htlm] 24. Bashore TM, Bates ER, Kern MJ, Berger PB, Laskey WK, Clark DA, et al. ACC/ SCAI clinical expert consensus document on cardiac catheterization laboratory standards: summary of a report of the ACC task force on clinical expert consensus documents. Cathet Cardiovasc Interv. 2001;53:281-6. 25. Singh M. The predicament of offering elective percutaneous coronary intervention at sites without on-site cardiac surgery. Am Heart J. 2006;152:810-1. 26. Peels HO, de Swart H, Ploeq TV, Hautwast RW, Cornel JH, Arnold AE, et al. Percutaneous coronary intervention with off-site cardiac surgery backup for acute myocardial infarction as a strategy to reduce door-to-balloon time. Am J Cardiol. 2007;100:1353-8. 27. Wu C, Hannan EL, Walford G, Ambrose JA, Holmes DR, King SB, et al. A risk score to predict in-hospital mortality for percutaneous coronary interventions. J Am Coll Cardiol. 2006;47:654-50. 28. Singh M, Rihal CS, Lennon RJ, Spertus J, Rumsfeld JS, Holmes DR. Bedside estimation of risk from percutaneous coronary intervention: the new Mayo Clinic risk scores. Mayo Clinc Proc. 2007;82:701-8. 29. Moscucci M, Kline-Rogers E, Share D, O’Donnell M, Maxwell-Eward A, Meengs WL, et al. Simple bedside additive tool for prediction of in-hospital mortality after percutaneous coronary interventions. Circulation. 2001;104:263-8. 30. Arnold JR, Karamitsos T, Shirodaria C, Banning AP. Should patients undergoing PCI still be consented for emergency bypass? Int J Cardiol. (2007) doi.10.1016/ jjcard.2007.08.097. Kontakt adresa autora: Doc. dr. Zdravko M. MijailoviД‡, Vojnomedicinska akademija, Klinika za kardiologiju, Crnotravska 17, 11000 Beograd, Srbija, Tel: +381-11-2661-129. Fax: +381-112666-164, Mobilni: +381-63-248-800, E-mail: mdzdravko@yahoo.com Pineal Region Tumors – Neurosurgical Review Pineal Region Tumors – Neurosurgical Review Ivan Radovanovic1, Kemal Dizdarevic2, Nicolas de Tribolet1, Tarik Masic3, Sahib Muminagic4 Division of Neurosurgery, Geneva University Hospital, University of Geneva, Switzerland1 Department of Neurosurgery, Clinical Center of University of Sarajevo, Bosnia and Herzegovina2 Clinic for Maxilophacial surgery, Clinical center of University of Sarajevo, Bosnia and Herzegovina3 Department of General surgery, Cantonal hospital Zenica, Bosnia and Herzegovina4 Review SUMMARY The treatment for the pineal region tumors depends on tumor histology. Nowadays, germinomas can be cured by radiotherapy and chemotherapy without surgical resection but the other pineal region tumors should be primary treated by surgery. Two microsurgical approaches, the infratentorial supracerebellar and the occipital transtentorial, are accepted as the main standard accesses to the pineal region. For benign pineal tumors (pineocytoma, meningioma, mature teratomas, symptomatic pineal cysts, etc.) radical surgical resection can be curative. For malignant tumors radical surgical resection is not an objective. Serum and CSF markers contribute to the diagnosis of pineal parenchymal tumors. b-HCG is mainly positive in choriocarcinomas, embryonal carcinomas and mixed germ cell tumors and AFP is expressed by yolk sac tumors, embryonic carcinomas, immature teratomas and mixed germ cell tumors. b-HCG is usually low in germinomas which are often positive for PLAP on immunohistochemistry. Fifty-one pineal region tumors were surgically treated by senior author (NdT). Only 17 of them were the neoplasms originating from pineal body (pineal tumors). In conclusion it can be stressed that management of pineal tumors requires a multidisciplinary cooperation. With the exception of germinoma where only a biopsy is needed, the role of the surgeons still remains prominent as resection of pineal tumors requires high technical skill and experience as well as precise clinical judgment. Keywords: neurosurgery, pineal region tumors 1. Introduction Pineal region tumors include a variety of neoplasms of different histological origin growing from the pineal gland itself or from structures of the parapineal space. These tumors are rare and account for 0.4 to 1.0 % of intracranial tumors in adults and 3-8 % in children . The most common types are germ cell tumors, pineal parenchymal cell tumors and glial cell tumor. Other pineal region tumors such as meningiomas, PNET, neurocytomas, hemangioblastomas, cavernomas and metastasis are infrequent. The treatment options for the different pineal region tumors vary according to their histological nature. However, with the exception of germinomas which can be nowadays cured by low-dose radiotherapy and chemotherapy and only require a biopsy for diagnosis, surgery still plays a central role in the management of most of the other pineal region tumors followed or not by adjuvant radiotherapy, chemotherapy or a combination of both. The first successful removal of a pineal tumor was reported in 1913 by Oppenheim and Krause. Krause was the first to describe and successfully use the infratentorial supracerebellar approach in three cases in 1926(1)..In the microsurgical era, Stein further developed and popularized this approach during the 1970’s (2). Finally the right suboccipital approach was described by Poppen and further modified by Jamieson in 1971(3).. The infratentorial supracerebellar and the occipital transtentorial approaches are nowadays accepted as the main standard accesses to the pineal region. 2. Microsurgical anatomy Pineal region tumors lie deep in the center of the cranium and are surrounded by critical anatomical structures that have to be respected at all costs. Therefore, a precise knowledge of the complex anatomy of the pineal region is of paramount importance (4, 5, 6). The pineal gland is located on the midline and forms an appendix of the caudal end of the diencephalons embracing the pineal recess of IIId ventricule. The pineal stem is continuous with the habenular commissure dorsally and the posterior commissure ventrally. The pineal body projects posteriorly in the quadrigeminal cistern where it is flanked by the splenium of the corpus callosum superiorly and lies on the tectal quadrigeminal plate in-between the left and right superior colliculi. The pineal gland is mainly vascularized by the medial and lateral posterior choroidal arteries. The medial posterior choroidal arteries are branches of the posterior cerebral artery and in addition to the pineal body they supply the superior and inferior colliculi, and the choroidal plexus of the third ventricule. These arteries are displaced laterally by pineal tumors in the cistern and rostrally in the posterior part of the third ventricule together with internal cerebral veins. The posterior lateral choroidal artery supplies the pulvinar and is generally displaced laterally by pineal tumors. Other important arterial landmarks are the superior cerebellar arteries that can be displaced inferiorly by pineal tumors and the medial occipital artery branching from the posterior cerebral artery and giving the calcarine artery. During surgical approaches to the pineal gland, the major anatomical obstacle is the Galenic venous system. The vein of Galen has several tributaries: the superior vermian vein and the precentral cerebral vein run in the midline and into the dorsocaudal part of the great vein. The internal cerebral veins and the pineal veins join ventrally. In pineal tumors, the posterior portion of the internal cerebral veins is always elevated rostrally, and the veins are occasionally separated from each other. On the lateral aspect of the great vein, the medial occipital veins, the third segment of the basal veins of Rosenthal, and the posterior mesencephalic veins join. The pineal veins are the draining veins of pineal tumors and drain into either the posterior portion of the internal cerebral veins or the vein of Galen. At this point pineal tumors are thightly adherent to the internal cerebral vein and/or the vein of Galen. An injury to the basal veins or the internal cerebral veins will yield major complications. And a transection of a major medial occipital vein may cause homonymous hemianopsia or visual seizures. 3. Rationale For benign pineal tumors (pineocytoma, meningioma, neurocytomas, mature teratomas, hemangioblastomas, cavernous hemangiomas, gangliogliomas, and symptomatic pineal cysts) total surgical resection is a primary goal as surgery alone can be curative (7, 6).. For malignant tumors surgery is only a part of the treatment which will consist of adjuvant therapies and therefore radical surgical resection is not an objective (6, 8)..In all cases focus should be given to reduce post treatment morbidity. 4. Decision making a) Diagnosis Clinical presentation: Symptomatic MED ARH 2009; 63(3) • Revijalni ДЌlanci • Reviews 171 homogenous cyst content with a thin enhancing rim and have no or only mild is compatible with an asymptomatic benignmass pineal cyst and the serum and CSF markers are negative, the patient can be followed up without treatment. The treatment effect on surrounding structures. Except for pineal region meningiomas or of other pineal tumors requires surgery but the choice of radical or conservative falcotentorial notch meningioma extending inPineal the Region pineal region, angiography is Tumors – Neurosurgical Review resection will depend on the diagnosis of the pre-surgical biopsy or the intraoperative usually not necessary(6).. frozen section. Benign tumors such as mature teratomas, pineocytomas or pressed yolk sac tumors (high levmeningiomas require radical surgical resection whenby feasible without compromising els), embryonic carcinomas, immature surrounding neurovascular structures. More aggressive tumors, such as malignant teratomas and mixed germ cell tumors. teratomas, pinealoblastomas, embryonal carcinomas, choroicarcinomas and yolk sac b-HCGtherapy is usually low in germinomas tumors require a combination of surgery, radiation and chemotherapy. In any which surgical are often positiveeven for at PLAP on case the prime goal of surgery should be avoiding morbidity the cost immunohistochemistry of a less radical surgical resection. The choice of approach is a matter(8).. of evaluating Biopsy: Histological is obthe anatomical relation of the tumor with the surrounding structures. diagnosis A steep angle of the straight sinus makes the infratentorial supracerebellar difficultor as endoan tained eitherapproach by stereotactic extensive retraction of the cerebellum is required visualize and reachbiopsy the pineal scopictotransventricular or diarea. Moreover, in that case the lateral exposure of during the surgical is restricted and rectly openfield surgery. For large renders the resection of larger tumors more complicated. Evaluating the relationship pineal tumors a stereotactic biopsy is a of the tumor with the quadrigeminal plate issafe alsoinitial important. For smaller midline procedure to obtain diagnotumors located in the posterior part of the third andextending displacinginto the the possis. ventricle For tumors quadrigeminal plate and the tegmentum of the midbrain infratentorial terior part ofcaudally, the thirdthe ventricule, endosupracerebellar approach is favored as it allows simple, direct and symmetrical scopic transventricular biopsy allows acexposure of the walls of the third ventricle and cerebral onasboth sides. cessinternal to tumor tissueveins as well third ven1a. preoperative MRI 1b. postoperative MRI In the case the tumor lies more caudally andtriculostomy extends in thetoupper portion of the treat hydrocephalus (6).. Figure 1a and 1b.: Sagittal MRI section (T1+gadolinium) of a pineal lesion removed by NdT through Figure 1A and 1B. Sagittal MRI section (T1+gadolinium) of a pineal lesion removed by NdT through aqueduct of sylvius, lying therefore cranially ofb)the tectum, theforinfratentorial Indications surgery andapproach microoccipitaloccipital transtentorial approach. steepangle angle of straight the straight sinus and theofposition of the lesion transtentorial approach.Note Note the the steep of the sinus and the position the lesion is inappropriate as the quadrigeminal plate obstructs the surgical exposure. Finally, anteriorly to the toquadrigeminal supracerebellar infratentorial anteriorly the quadrigeminalplate plate making making a asupracerebellar infratentorial approach approach difficult. difficult.surgical approaches the occipital transtentorial approach is preferred as well in big tumors with lateral If a newly diagnosed pineal mass is extension in the pulvinar thalami as it gives a better lateral exposure of the walls of hydrocephalus or occulomotor signs are tumor. A CT is also useful to detect in- accessible by stereotactic or endoscopic the third ventricle (6).. generally the first clinical manifestation tratumoral calcifications or hemorrhage. biopsy and the cranial MRI is compatible Markers: Serum and CSF markers contribute to the diagosis of pineal parenchymal of pineal region tumors. Hydrocephalus tumorsisand assessment their malignancy. BHCG and пЃЎ-foetoprotein are found in triventricular byof compression of the germ cell tumors. пЃўпЂHCG mainly positive in choriocarcinomas, embryonal aqueduct of Sylvius andiscan be acute or chronic. include carcinomas andSymptoms mixed germ cellheadaches, tumors and AFP is expressed by yolk sac tumors gait problems and occulomotor (high levels), embryonic carcinomas,signs immature teratomas and mixed germ cell such as Parinaud syndrome. In slow tumors. пЃў-HCG is usually low in germinomas which are often positive for PLAP on growing tumors, chronic hydrocephalus immunohistochemistry (8)..dementia. Occumay develop and cause Biopsy:lomotor Histological diagnosis is obtained signs can also occur through di- either by stereotactic or endoscopic transventricular biopsy during open surgery. For large pineal tumors a rect compression of or thedirectly superior colliculi Figure 2c or thebiopsy posterior (6)..procedure toFigure stereotactic iscommisure a safe initial obtain2adiagnosis. For tumorsFigure 2b Figure 2a,2a, 2b2B andand 2c.2C. Surgical presentation of of a right occipital transtentorial approach include: a) After Radiology: the radiological exam of Figure Surgical presentation a right occipital transtentorial approach include: a) extending into the posterior part of the third ventricule, endoscopic transventricular dissecting the arachnoid, the tumor comes into full view. b) Resection of the tumor with dissection of After dissecting the arachnoid, the tumor comes into full view. b) Resection of the tumor with dissection MRI which will reveal biopsy choice allowsisaccess to tumor tissuetheastuwell third ventriculostomy the as capsule from surrounding structures.toc)treat Final view of the operative field after resection of the of the capsule from surrounding structures. c) Final view of the operative field after resection of the mor and its relations to adjacent ana- tumor, under the corpus callosum the posterior part of the third ventricule is visible. The great vein of hydrocephalus (6).. tumor,and under callosum the visible. posterior part of the third ventricule is visible. The great vein of thethe leftcorpus basal vein are also tomical structures. Particular attention Galen Galen and the left basal vein are also visible. has to be given to T1+gadolinium seb) Indications surgery and T2 microsurgical giant tumors of the pineal region can be removed by the combined occipital , quences,for high resolution squences Theapproaches supracerellar approach by Sekhar(10) (Figurefirst 3). for surrounding vessels (flow void) and transtentorial, Even if the many different transsinus pineal tumor withdescribed a germinoma, a biopsy should cranial nerves, phlebo-MRI sequences types may have a preferential appearance be done in order to avoid an unnecessary for assessing the 3D anatomy of the deep on cranial imaging, no such character- craniotomy in that case. If the radiolog3 venous system and its relation with the istics are specific for one or another tu- ical examination is compatible with an mor type and do not preclude obtaining 4asymptomatic benign pineal cyst and tissue for histological examination. An the serum and CSF markers are negative, exception are benign pineal cysts which the patient can be followed up without have a homogenous cyst content with a treatment. The treatment of other pineal thin enhancing rim and have no or only tumors requires surgery but the choice mild mass effect on surrounding struc- of radical or conservative resection will tures. Except for pineal region meningio- depend on the diagnosis of the pre-surmas or falcotentorial notch meningioma gical biopsy or the intraoperative frozen extending in the pineal region, angiogra- section. Benign tumors such as mature phy is usually not necessary(6).. teratomas, pineocytomas or meningioMarkers: Serum and CSF markers mas require radical surgical resection contribute to the diagosis of pineal pa- when feasible without compromising renchymal tumors and assessment of surrounding neurovascular structures. their malignancy. BHCG and a-foeto- More aggressive tumors, such as maligprotein are found in germ cell tumors. nant teratomas, pinealoblastomas, emFigure 3. 3.: GiantGiant pineal region meningioma Figure pineal region meningioma removed by inco-author using the b-HCG is mainly positive choriocar- (KD) bryonal carcinomas, choroicarcinomas removed by co-author (KD) using the combined combined Sekhar’s approach cinomas, embryonal carcinomas and and yolk sac tumors require a combinaSekhar’s approach mixed germ cell tumors and AFP is ex- tion of surgery, radiation therapy and 5. Results 172 MED ARH 2009; 63(3) • Revijalni ДЌlanci • Reviews The fifty-one pineal region tumors were surgically treated by senior author (NdT). Pineal Region Tumors – Neurosurgical Review chemotherapy. In any case a) Pineal gland tumors the prime goal of surgery Germinoma Excluded should be avoiding surgical Mature teratoma 3 morbidity even at the cost of Immature teratoma 4 a less radical surgical resecEmbryonal carcinoma 2 tion. The choice of approach Pineocytoma 3 is a matter of evaluating the Intermediate differentiation 1 anatomical relation of the Pineoblastoma 2 tumor with the surrounding Yolk sac tumor 2 structures. A steep angle of NUMBER 17 the straight sinus makes the 11 infratentorial supracerebel- Radical resection Subtotal resection 2 lar approach difficult as an 4 (2 embryonal carcinoms and extensive retraction of the Biopsy 2 yolk sac tumors) cerebellum is required to visualize and reach the pic) Complications neal area. Moreover, in that Number of Reason of case the lateral exposure of Type of complications complication complications the surgical field is restricted Occipital lobe and renders the resection of Hemianopsia 1 retraction larger tumors more compliOccipital lobe cated. Evaluating the rela- Visual seizures 1 retraction tionship of the tumor with 1 Venous infarction the quadrigeminal plate is Metamorphopsia Parinaud syndrome quadrigeminal also important. For smaller 1 (permanent) plate manipulation midline tumors located in IV CN palsy 2 Nerv traction the posterior part of the Air embolism 0 0 third ventricle and displacing the quadrigeminal plate b) Pineal region tumors without pineal gland and the tegmentum of the tumors midbrain caudally, the in4 fratentorial supracerebel- cavernous angiomas 2 lar approach is favored as PNETs 4 it allows simple, direct and Ependymomas symmetrical exposure of the Astrocytomas grade II 5 walls of the third ventricle Hemangioblastomas 4 and internal cerebral veins Gangliogliomas 2 on both sides. In the case the Meningiomas 9 tumor lies more caudally and plexus papillomas 2 extends in the upper por- Neurocytoma 1 tion of the aqueduct of syl- Neurenteric cyst 1 vius, lying therefore cranially NUMBER 34 of the tectum, the infraten- Radical resection 29 torial approach is inappro5 (2 Astrocytomas and 3 priate as the quadrigeminal Subtotal resection meningiomas) plate obstructs the surgical exposure. Finally, the occipsinus approach described by Sekhar(10) ital transtentorial approach is preferred (Figure 3). as well in big tumors with lateral extension in the pulvinar thalami as it gives 5. Results The fifty-one pineal region tumors a better lateral exposure of the walls of were surgically treated by senior author the third ventricle (6).. The giant tumors of the pineal region (NdT). Only 17 of them were the neocan be removed by the combined occip- plasms originating from pineal body (piital , transtentorial, supracerellar trans- neal tumors) 6. Conclusion Contemporary management of pineal tumors requires a multidisciplinary cooperation where surgery represents only one aspect of the treatment plan. However, with the exception of germinoma where only a biopsy is needed, the role of the surgeons still remains prominent as resection of pineal tumors requires high technical skill and experience as well as precise clinical judgment. The infratentorial supracerebellar approach and the occipital transtentorial approach when used appropriately allow access to nearly every type of pineal neoplasms. REFERENCES 1. Krause F: Operative Freilegung der VierhГјge, nebst Beobachtungen bein Hirndruck un Dekompression. Zentralbl Chir. 1926;53:2812-9. 2. Stein BM: The infratentorial supracerebellar approach to pineal lesions. J Neurosurg. 1971;35:197-202. 3. Jamieson KG: Excision of pineal tumors. J Neurosurg. 1971;35:550-3. 4. Matsuno H, Rhoton AL, Jr., Peace D: Microsurgical anatomy of the posterior fossa cisterns. Neurosurgery. 1988;23:58-80. 5. Ono M, Rhoton AL, Jr., Peace D, Rodriguez RJ: Microsurgical anatomy of the deep venous system of the brain. Neurosurgery. 1984;15:621-57. 6. Sawamura Y, de Tribolet N: Neurosurgical management of pineal tumours. Adv Tech Stand Neurosurg. 2002;27:217-44. 7. Bruce JN, Stein BM: Surgical management of pineal region tumors. Acta Neurochir (Wien). 1995;134:130-5. 8. Sawamura Y: Overview for management. Intracranial germ cell tumors, in Sawamura YS, H. de Tribolet, N (ed). Intracranial germ cell tumors. Wien, New York, Springer, 1998:169-91. 9. Sawamura Y, de Tribolet N, Ishii N, Abe H: Management of primary intracranial germinomas: diagnostic surgery or radical resection? J Neurosurg. 1997;87:262-6. 10. Sekhar LN, Tzortzidis F: Approaches to the pineal region. In: Sekhar LN, de Oliveira E (eds). Cranial microsurgery:approaches and techniques. Thieme New York, 1999. Corresponding author: Kemal Dizdarevic, MD, PhD. Clinic for neurosurgery. Clinical center of Sarajevo University. Sarajevo, Bolnicka 25. Tel.: 00 387 33 297 000. E-mail.: kemaldiz@bih. net.ba MED ARH 2009; 63(3) • Revijalni ДЌlanci • Reviews 173 Management of a Comatose Patient with Multiple Intracranial Aneurysms - Lessons Learned Management of a Comatose Patient with Multiple Intracranial Aneurysms - Lessons Learned Kemal Dizdarevic1, Vino Apok2, Ibrahim Omerhodzic1, Tarik Masic3 Department of Neurosurgery, Clinical Center University of Sarajevo, Bosnia and Herzegovina1 St. George’s University of London, United Kingdom2 Clinic for Maxilofacial suregery,Clinical Center University of Sarajevo, Bosnia and Herzegovina3 Case report SUMMARY The perioperative management of a deeply comatose patient (Glasgow Coma Score, GCS 5) following a spontaneous subarachnoid hemorrhage is presented. Six intracranial aneurysms of the anterior circulation were discovered at operation, contrary to angiographic findings. These were successfully clipped by the author (KD). Postoperatively, the patient’s cerebral energy metabolism was monitored by bedside cerebral microdialysis in real time. The ICP (volume)-targeted therapy (Lund concept) was utilised in accordance with findings of intrinsic brain biochemistry. Three-month follow-up showed excellent outcome (Glasgow Outcome Score,GOS 5). Keywords: subarachnoid hemorrhage, multiple intracranial aneurysms, early surgery, Lund concept, cerebral microdialysis, coma 1. Introduction Intracranial aneurysm rupture, the most common cause of spontaneous subarachnoid haemorrhage (SAH) is burdened with high mortality and morbidity. The rationale foe using early surgical clipping as a gold standard in such cases is the prevention of delayed intracranial complications. There is doubtless benefit to the currently favoured method–endovascular coilling (1,2). However, this option is still not accessible for many neurosurgical patients, particularly those in developing countries. In certain institutions, early surgical clipping was prefered only for the good grade patients (Hunt-Hess I, II, III). Comatose patients with neurological deficit (Hunt-Hess IV i V) are not operated on due to increased immediate postoperative mortality. Our experience favours the treatment of almost all anterior circulation ruptured barry aneurysms by early surgical clipping and postoperative treatment according to the Lund concept (ICP or volume-targeted therapy). The important exception to this view would be patients with a GCS of 3. The Lund concept involves monitoring cerebral energy metabolism using cerebral microdialysis3-9. Orginally devised to aid the management of traumatic brain injury, it has been shown to be helpful in reducing overall mortality after aneurysmal subarachnoid haemorrhage and preventing ischaemia. Early surgery together with postoperative volume-targeted therapy allows an effective approach to complications caused by haemorrhage. 174 Our objective is to present the outcome of a deeply comatose patient following a SAH who was found to have six intracranial aneurysms. The importance of strategic treatment planning (in this case, arly surgical clipping and postoperative utilisation of Lund concept) is illustrated by this case. Figure 2. Intraoperative illustration of multiple aneurysms clipping Surgery was undertaken by the author (KD) within 24h of the bleed. Intraoperatively, contrary to CT angiography, six aneurysms of the anterior circulation occurring bilaterally were discovered. These were successfully clipped (Figure 2). Five of the aneurysms were on the right (two on ICA, one on AChA, A1 ACA and MCA) including the ruptured aneurysm (MCA). The remaining 2. Case report H.Z., a 44-years-old male experienced a spontaneous SAH (Fisher gr IV) secondary to aneurysmal rupture a day before addmition to our Department. He was deeply comatose (GCS 5, Hunt-Hess gr V, WFNS gr V). The digital subtraction angiography (DSA), the conventional angiographical option, was not available due to technical issues. CT angiography was performed as an alternative and demonstrated three aneurysms of anterior cerebral circulation (Figure 1). Figure 3. Craniotomy was done on both sides. The catheter was placed in the left lateral ventricle. A titanium clips and catheter for cerebral microdialysis are visible intracranially. Figure 1. Preoperative brain CT angiography shows multiple cerebral aneurysms on the both side. MED ARH 2009; 63(3) • PRIKAZI SLUДЊAJA / CASE REPORTS one was on the left (MCA bifurcation). A modified right pteryonal (pre-temporal) approach utilizing a trans-Sylvian route was used. Following aneurysm clipping and wound closure on the right , the head was rotated and a left supra-orbital lateral approach was undertaken The left MCA aneurysm was noted to be leaking This was also successfully clipped (Figure 3 A and B). After clipping, an intraventricular catheter for ICP-monitoring and a microdialysis microcatheter for energy metabolism monitoring were placed. Management of a Comatose Patient with Multiple Intracranial Aneurysms - Lessons Learned Postoperatively, the patient was intubated, sedated and managed using the Lund concept i. e. ICP (volume)-targeted therapy (Figure 4.). This therapy focuses on four crucial aims: •• reduction of stress response and cerebral energy metabolism, •• reduction of capillary hydrostatic pressure, •• maintenance of colloid osmotic pressure with strict control of fluid balance •• reduction of cerebral blood volume. The brain energy metabolism was monitored using cerebral microdialysis equipment (3,4,5,6) (Figure 5). A month postoperatively the patient was alert, extubated, communicating freely and laboratory investigation results were within reference range. Postoperative rehabilitation was completed. By three-month follow-up, his GOS was 5 and his Karnofsky score was 90. Slight cognitive deterioration was noted but there was no neurological deficit (Figure 6) (7,8,9). 3. Discussion Spontaneous SAH caused by anterior circulation aneurysmal rupture is a common reason for acute deterioration of consciousness and development of neurological deficit in a patient. Poor preoperative status as an indication for early surgery is an area of controversy. Practice varies widely across the neurosurgical word, dependant largely on ex per t opi nion within institution rather than a ny internationally accepted evidence based guideline. In our experience, poor preoperative Hunt-Hess grade alone should not be a reason for avoiding early surgery. This is illustrated by the case Figure 4. The patient immediate postoperatively with bedside monitoring of presented here. brain energy metabolism. In such patients, early microsurgery followed by postis able to adapt the operative method apoperative ICP (volume)-targeted ther- propriately. apy has shown good outcome at our The author (K.D.) mainly utilizes a centre. This is independent of preoper- supra-orbital lateral approach (10) for ative grade. the vast majority of aneurysms but recInsufficient diagnostic evaluation ognizes that multiple and giant aneupreoperatively (as in this case where DSA rysms are probably best clipped using was not available) should be recognized pteryonal or pre-temporal approaches as an additional risk factor for aneurysm (11,12,13). This patient was managed for surgery. However, CT angiography can approximately 2 months postoperatively and still does have a role even in complex on the neurosurgical intensive care unit cases with multiple aneurysms. It is im- with therapy being guided by the Lund portant though, to recognize the poten- concept. tial for error with any imaging modality This strategy is directed at brain volas illustrated here. The cerebrovascular ume regulation and maintaining cereneurosurgeon should be one who antici- bral perfusion pressure between 50 and pates intraoperative findings other than 70 mmHg (3,7,8,14). Modification of this those imaged on preoperative scans and strategy according to the findings of interstitial brain metabolites (glucose, lactate, piruvate, glutamate, glycerol) recorded by cerebral microdialysis is then carried out. These indicators, measured at the bedside (15,16,17,18), reflect the level of brain ischemia in real time. 4. Conclusion A poor grade patient with multiple aneurysms can benefit from early surgical clipping, especially if accompanied by postoperative conservative treatment directed at brain volume regulation based on bedside monitoring of brain intrinsic biochemistry. Clearly, this should ideally happen in the controlled environment of a neurosurgical intensive care unit. references 1. Figure 5. The record of patient’s cerebral energy metabolism. Molyneux A, Kerr R, Stratton I et al. International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with MED ARH 2009; 63(3) • PRIKAZI SLUДЊAJA / CASE REPORTS 175 Management of a Comatose Patient with Multiple Intracranial Aneurysms - Lessons Learned ruptured intracranial aneurysms: A randomised trial. Lancet, 2002; 360:1267-74. 2. Molyneux A, Kerr R, Yu LM et al.: International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: A randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups and aneurysm occlusion. Lancet, 2005;366:809-17. 3. Dizdarevic K. Cerebral microdialysis: Brain ischaemia after neurotrauma and aneurysmal haemorrhage. Doctoral dissertation. School of Medicine University of Sarajevo. 2007. 4. DizdareviД‡ K. The prevention and treatment of cerebral ischaemia based on cerebral microdialysis. The second B&H Congres of Neurology. Abstracts book. 2006:399-400. 5. Nordstrom CH, Reinstrup P, Xu W et al.: Assessment of the lower limit for cerebral perfusion pressure in severe head injuries by bedside monitoring of regional energy metabolism. Anesthesiology, 2003;98:809-14. 6. Nordstrom CH. Assessment of critical thresholds for cerebral perfusion pressure by performing bedside monitoring of cerebral energy metabolism. Neurosurg Focus, 2003;15(6):1-8. 176 7. 8. 9. 10. 11. 12. 13. Nordstrom CH. Treatment of increased intracranial pressure. Neurocritical care, 2005;1:1-13. Grande PO, Asgeirsson B, Nordstrom CH. Volume targeted therapy of increased intracranial pressure: the Lund concept unifies surgical and non-surgical treatments. Acta Anaesthesiol Scand, 2002; 46:929-41. DizdareviД‡ K, OmerhodЕѕiД‡ I, IblizoviД‡ N, JahiД‡ B. Neurosurgical intensive care unit and computerized technology as a prerequest of contemporary approach to the neuropatients. Medical journal, 2005; 11(1-2):18-23. Hernesniemi J, Ischii k, Niemela M et al.Lateral supraorbital approach as an alternative to the classical pterional approach. Acta Neurochir, Suppl., 2005;94: 17-21. Dizdarevic K, IblizoviД‡ N, et al. Early and urgent microsurgery of single and multiple intracranial aneurysms of anterior and posterior circulation i total mortality rate after operative and conservative treatment. MedArh, 2004;58(5):301. DizdareviД‡ K, SelimoviД‡ E, Kominlija E. Subarachnoid hemorrhage: neurosurgical treatment modalities and etiological analysis. MedArh, 2006;60(1):33-7. Oliveira E, Tadeschi H: Pterional and pretemporal approaches. In: Sekhar LN, OliveiraE (eds). Cranial microsurgery: MED ARH 2009; 63(3) • PRIKAZI SLUДЊAJA / CASE REPORTS 14. 15. 16. 17. 18. approaches and technigues. Thieme New York, 1999:124-9. Gisvold SE. The Lund concept for treatment of head injuries-faith or science? Acta Anaesthesiol Scand, 2001;45:402-6. Stahl N, Mellergard P, Hallstrom A, Ungerstedt U, and Nordstrom CH. Intracerebral microdialysis and bedsidebiochemical analysis in patients with fatal traumatic brain lesions. Acta Anaesthesiol Scand, 2001;45:977-85. Stahl N, Ungerstedt U, Nordstrom CH: Brain energy metabolism during controlled reduction of cerebral perfusion pressure in severe heed injuries. Intensive care Med, 2001;27:1215-23. Hillered L, Persson L, Ponten U, et al: Neurometabolic monitoring of the ischaemic human brain using microdialysis. Acta Neurochir, 1990;102:91-7. Ungerstedt U, Hallstrom A. In vivo microdialysis - a new approach to the analysis of neurotransmitters in the brain. Life Sci, 1987;41:861-4. Corresponding author: Prof Kemal Dizdarevic, MD, PhD. Department of neurosurgery, Clinical Center University of Sarajevo. Bolnicka 25, Sarajevo 71000, Bosnia and Herzegovina. E-mail.: kemaldiz@bih.net.ba Medical Informatics In A United And Healthy Europe Medical Informatics In A United And Healthy Europe Authors: Klaus-Peter Adlassnig, Bernd Blobel, John Mantas and Izet Masic IOS Pres, Amsterdam, The Netherlands, 2009, 1064 pages, Hard cover. ISBN 978-1-60750-044-5 This volume contains the proceedings of the Twentysecond International Conference on Medical Informatics Europe MIE 2009, that will be held in Sarajevo, Bosnia and Herzegovina, from 30 August to 2 September 2009. The MIE 2009 is the European’s leading forum for presenting the results of current scientific work in healthinformatics processes, systems, and technologies. Achievements in this area will be introduced to an international audience. As a major event for science, medicine, and technology, the conference provides a comprehensive overview and in-depth, first hand information on new developments, advanced systems and technologies, and current and future applications. The MIE 2009 conference was organized by the European Federation for Medical Informatics (EFMI) in cooperation with the Society for Medical Informatics of Bosnia and Herzegovina (BHSMI). It follows the previous conferences in Cambridge (1978), Berlin (1979), Toulouse (1981), Dublin (1982), Brussels (1984), Helsinki (1985), Rome (1987), Oslo (1988), Glasgow (1990), Vienna (1991), Jerusalem (1993), Lisbon (1994), Copenhagen (1996), Porto Carras (1997), Ljubljana (1999), Hannover (2000), Budapest (2002), Saint Malo (2003), Geneva (2005), Maastricht (2006), and the conference 2008 in Gothenburg. The proceedings contain 213 contributions to the MIE 2009 conference. They cover all presentations which are part of the scientific program of MIE 2009, among them 150 full paper presentations, 21 student paper presentations, 21 presentations that will be presented as posters, and 14 workshop descriptions. Furthermore, seven keynote addresses from eminent scientists coming from Europe and overseas are also included into the proceedings. The papers included were selected by an International Scientific Programme Committee (SPC) out of 324 submissions after careful review by three international reviewers for every single submission. The SPC chair and his two co-chairs (K.-P. Adlassnig, B. Blobel, and J. Mantas) are especially thankful to all our reviewers whose efforts are highly estimated. As a specific token of appreciation and to recognize their work not only anonymously, the MIE 2009 reviewers’ names are listed in the proceedings. The – often extended – recommendations of the reviewers were incorporated in the final texts, and careful language revision was carried out to achieve a high quality of presentation. The scientific topics presented in the proceedings volume at hand range from national and trans-national eHealth roadmaps, health information and electronic health record systems, systems interoperability and communication standards, medical terminology and ontology approaches, and social networks to Web, Web 2.0, and Semantic Web solutions for patients, health personnel, and researchers. Furthermore, they include quality assurance and usability of medical informatics systems, specific disease management and telemedicine systems, including a section on devices and sensors, drug safety, clinical decision support and medical expert systems, clinical practice guidelines and protocols, as well as privacy and security issues. Moreover, bioinformatics, biomedical modeling and simulation, medical imaging and visualization and, last but not least, learning and education through medical informatics systems is part of the included topic areas. There are several trends and developments that can be recognized by carefully examining the single contributions to the various topics. First, interoperability and data exchange standards become most important. Systems must and will be interconnected to each other: locally, nationally, and transnationally. Medical information and electronic health record systems will be the first to benefit. Second, ontologies are being developed in an increasing path. Medical data items and medical concepts (terms) are represented, arranged, and interconnected in standardized collections of “those that is” (=ontology) in medicine. By doing so, not only the medical vocabulary that is used in an application but also the semantics of applied items and terms is defined. Third, Web applications allow to share medical information and knowledge by many users – researchers, staff, patients; close or far. Web 2.0 applications deliberately involve the user, and the Semantic Web provides even knowledge inferences over remote knowledge places and allows to develop futuristic systems. Fourth, clinical decision support systems in all possible manifestations are and will increasingly be demanded by physicians and patients equally – after patients’ medical data from the many data sources are finally digitized and made available. They will provide huge impact on medical workflow and patient care to the benefit of the patient, the caring physician, and the MED ARH 2009; 63(3) • PRIKAZI KNJIGA / BOOK REVIEWS 177 Medical Informatics In A United And Healthy Europe STUDIES IN HEALTH TECHNOLOGY AND INFORMATICS 150 150 Medical Informatics in a United and Healthy Europe This volume contains the proceedings of the Twenty-second International Conference on Medical Informatics Europe MIE 2009, that was held in Sarajevo, Bosnia and Herzegovina, from 30 August to 2 September 2009. The scientific topics present in this proceedings range from national and trans-national eHealth roadmaps, health information and electronic health record systems, systems interoperability and communication standards, medical terminology and ontology approaches, and social networks to Web, Web 2.0, and Semantic Web solutions for patients, health personnel, and researchers. Furthermore, they include quality assurance and usability of medical informatics systems, specific disease management and telemedicine systems, including a section on devices and sensors, drug safety, clinical decision support and medical expert systems, clinical practice guidelines and protocols, as well as issues on privacy and security. K.-P. Adlassnig et al. (Eds.) Moreover, bioinformatics, biomedical modeling and simulation, medical imaging and visualization and, last but not least, learning and education through medical informatics systems are parts of the included topics. Medical Informatics in a United and Healthy Europe Proceedings of MIE 2009 Editors: Klaus-Peter Adlassnig Bernd Blobel John Mantas Izet Masic ISBN 978-1-60750-044-5 ISSN 0926-9630 financing health care bodies. Most of the topics presented at MIE 2009 are interdisciplinary in nature and may be of interest to a variety of professionals: medical informatics, bioinformatics, and health informatics scientists, medical computing and technology specialists, public health, health inMEDICAL INFORMATICS IN A UNITED AND HEALTHY EUROPE WELCOME TO The XXII International Conference of the European Federation for Medical Informatics MIE SARAJEVO UNSA University of Sarajevo ISfTeH International Society for Telemedicine and eHealth 09 EuroRec European Institute for Health Records European Association of Healthcare IT Managers August 30th - September 2nd, 2009 EFMI European Federation for Medical Informatics BHSMI Society for Medical Informatics of Bosnia and Herzegovina www.mie2009.org 178 MED ARH 2009; 63(3) • PRIKAZI KNJIGA / BOOK REVIEWS surance and health institutional administrators, physicians, nurses, and other allied health personnel, and representatives of industry and consultancy in the various health fields. The MIE 2009 conference gathers participants all over the world, although mainly Europeans. This is reflected by the authors of the proceedings’ contributions; altogether 931 researchers have reported their results in this volume (double author entries have not been eliminated). By considering the country origin of the authors, 38 different countries from Europe, North and South America, Asia, Africa, and Australia can be counted that contributed to this volume. The great variety of scientific topics and countries that will be present should guarantee both a highly interesting international Medical Informatics Europe MIE 2009 conference in Sarajevo in August/September and a fruitful study of the proceedings by those interested in Medical Informatics. Acknowledgement. The editors are most grateful to Andrea Rappelsberger for her careful and extensive work in the preparation of the proceedings on hand. We are thankful to Susanne Rom, whose many efforts are appreciated. (Both are with the SPC Office in Vienna, Austria.) Without their help it would not have been possible to produce such a valuable and comprehensive book. Klaus-Peter Adlassnig, Vienna Bernd Blobel, Regensburg John Mantas, Athens Izet Masic, Sarajevo Medical Informatics In A United And Healthy Europe MED ARH 2009; 63(3) • PRIKAZI KNJIGA / BOOK REVIEWS 179 Medical Informatics In A United And Healthy Europe 180 MED ARH 2009; 63(3) • PRIKAZI KNJIGA / BOOK REVIEWS
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