2013-05-23T13:23:18Z http://hrcak.srce.hr/oai/

oai:hrcak.srce.hr:7719 2008-06-03 journal:117

Smanjuje li se nužno radna sposobnost povisivanjem kronološke dobi? Is there any connection between working ability and aging? Duraković, Zijad radna sposobnost; starenje Working ability; Aging Starenje je proces koji počinje nakon navršene 30-e godine. Započinje s promjenama funkcija organa, nakon čega slijede i anatomske promjene. Neki organi stare brže, neki sporije: npr. bubrezi se smanjuju za jednu trećinu, pluća se ne mijenjaju, jetra se malo smanjuje, prostata se dvostruko povećava. Mišićna masa je u muškaraca dobi od 65 godina prosječno niža za 12 kg nego u tzv. srednjoj dobi, a u žena je prosječno niža za 5 kg. U srcu količina vezivnog tkiva se povećava, u miokard se odlaže lipofuscin. Snaga mišića srca se smanjuje. U dišnim putovima smanjuje se količina trepetljika, površina alveola se smanjuje, mijenjaju se mišići koji pomažu pri disanju, elastičnost pluća se smanjuje. No s obzirom na raniju tjelesnu sposobnost, "fiziološka starost" može se podijeliti u tri skupine: "stariji" stariji imaju najvišu funkcijsku sposobnost 2-3 MET-a (MET = metabolička jedinica, tj. potrošnja kisika od 3,5 ml na kg tjelesne mase u minuti), "mlađi" stariji su osobe starije dobi, koje imaju najvišu funkcijsku sposobnost organizma 5-7 MET-a, dok "sportski" stariji imaju funkcijsku sposobnost 9-10 MET-a, neovisno o kronološkoj dobi. Potporno tkivo mijenja svojstva, postaje kruto i fragilno. Probavni sustav smanjuje motilitet i funkciju, kao i renalni sustav. Težina se mozga smanjuje prosječno za oko 7% u odnosu prema mlađoj dobi. U temporalnom girusu i areji strijati gubi se i do 20-40% stanica, zbivaju se vakuolska i neuroaksonska degeneracija, nakuplja se lipofuscin. Protok krvi kroz mozak koji u normalnim uvjetima iznosi 50-60 ml/min./100 g tkiva, s povisivanjem biološke dobi smanjuje se na oko 40 ml/min/100 g tkiva. No, to najčešće nije posljedica biološke starosti nego je posljedica bolesti. Za granicu tzv. starosti s navršenom 65-om godinom nema biološki mjerljivih dokaza. Samo biološku dob treba uzeti u razmatranje kod ocjene funkcijske sposobnosti organizma. Although the definitions of the so-called older age are based on the chronological age of 65 years and over, aging is the process which starts with the 30th year of life. At the beginning occur changes in the organ functions, followed by anatomical changes as well. Some organs age faster, some slower. For example, kidneys decrease for one third, lungs do not change, liver shrinks a little, prostate increases twice. Muscle mass in men aged 65 is on average 12 kilos less than in the so-called middle age, and in women it is approximately 5 kilos less. In the heart the amount of connective tissue increases, lipofuscin is deposited in cardiac muscle, the strength of which is decreasing. In the respiratory tract the number of pathways cilia decreases, along with the alveolar surface, muscles involved in breathing change, lung elasticity is also diminished. But, in regard with the previous body capacity, “physiological aging” can be divided into three groups: the “older” elderly have the highest functional capacity of 2-3 MET (MET= metabolic unit, i.e. the oxygen consumption of 3.5 ml/kg body mass in a minute), the “younger” elderly are the persons of older age having maximal functional capacity of 5-7 MET, while the “sport” elderly have the functional capacity of 9-10 MET, disregarding chronological age. Connective tissues change, become fragile. Digestive system diminishe motility and function, as renal system. The brain weight diminishes for approximately 7% compared to younger age. In temporal gyrus and area striata even 20-40% of cells are being lost, vacuolar and neuroaxonal degeneration occurs, lipofuscin is being accumulated. The brain blood flow, which is in normal conditions 50-60 ml/min/100g of tissue, with the increase of biological age decreases to about 40 ml/min/100 g of tissue. However, this usually is not the consequence of biological age but of disease. The arbitrary limit of the so-called older age starting with the 65th year of life is not marked by anything, there are no measurable biological proofs for it. The changes in the organism during the so-called aging are individual. The functional capacity of an organism, both physical and intellectual, must be evaluated individually. Croatian Academy of Sciences and Arts 2006-11-25 text pdf http://hrcak.srce.hr/7719 http://hrcak.srce.hr/file/11668 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.496=30; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) hr

oai:hrcak.srce.hr:7741 2008-06-03 journal:117

Epidemiologija influence u Hrvatskoj i pripreme za moguću pandemiju Influenza epidemiology in Croatia and preparations for potential pandemic Gjenero-Margan, Ira Aleraj, Borislav Kaić, Bernard Baklaić, Željko Ljubičić, Mate Kolarić, Branko Draženović, Vladimir Ključne riječi: Influenca; Epidemiologija; Hrvatska; Plan pripravnosti; Pandemija Key words: Influenza; Epidemiology; Croatia; Preparedness plan; Pandemic Nadzor nad gripom u Hrvatskoj zasniva se na prijavi oboljenja/smrti od zaraznih bolesti o kojima se unutar 24 sata obavještava (tijekom sezone influence tjedno se dostavljaju kumulativna izvješća) Služba za epidemiologiju Hrvatskog zavoda za javno zdravstvo. Provodi se epidemiološki izvid svakog pojedinog grupiranja, a uzorci se šalju Nacionalnom laboratoriju za influencu pri Hrvatskom zavodu za javno zdravstvo. Registrirani morbiditet od influence u Hrvatskoj iznosi 191,000 slučajeva godišnje te oscilira u interpandemijskom periodu od nekoliko tisuća pa do 190,000 slučajeva godišnje. Prosječni broj prijava u posljednjih pet godina iznosi 168 na 10000 stanovnika. Prema prijavama zdravstvenih službi za sezonu 1957/58, pandemija azijske influence A/Singapur/H2N2 uzrokovala je bolest kod više od 500,000 osoba. Pandemija hongkonške inlfuence (A/Hong Kong/H3N2) registrirana je u Hrvatskoj u sezonama 1967./68. i 1969./70. Ukupni broj prijavljenih slučajeva influence tijekom tog perioda iznosio je 582,000 osoba (14% stanovnika). Tijekom pandemije hongkonške influence morbiditet veći od 1,000/10,000 stanovnika zabilježen je u djece starosti od 7-9 godina i u osoba starijih od 20 godina. Plan pripravnosti za pandemijsku influencu zasniva se na povijesnim podacima o morbiditetu prethodnih epidemija influence u zemlji. Kratki pregled plana pripravnosti prikazan je korištenjem faza interpandemijskog i pandemijskog razdoblja u skladu s posljednjim definicijama Svjetske zdravstvene organizacije. Surveillance of influenza in Croatia is based on notification of disease/death due to communicable diseases that are reported within 24 hours (during the influenza season weekly aggregated reports are submitted) to the Epidemiology Service of the Croatian National Institute of Public Health (CNIPH). Field investigation of each cluster is conducted and samples are sent to the CNIPH National laboratory for influenza. The registered influenza morbidity in Croatia amounts to up to 191,000 cases annually, oscillating, in the interpandemic period, from several thousand to over 190,000. Average annual notification rate during last five years was 168/10000 inhabitants. Based on health service notification in the season 1957/58, Asian influenza pandemic A/Singapore/H2N2 caused illness in more than 500,000 people. The Hong Kong pandemic influenza (A/Hong Kong/H3N2) was registered in Croatia in the 1967/68 and 1969/70 season. Total number of notified influenza cases during that period was 582,000 people (14% of inhabitants). During the Hong Kong influenza pandemic morbidity higher than 1,000/10,000 inhabitants was recorded both in children aged 7?19 years and in persons aged 20+ years. The Preparedness Plan for Pandemic influenza is based on historical morbidity data in previous pandemic influenza outbreaks in the country. The brief overview of preparedness plan was given using the phases of interpandemic and pandemic period according to the latest agreed definitions published by the WHO. Croatian Academy of Sciences and Arts 2006-11-25 text pdf http://hrcak.srce.hr/7741 http://hrcak.srce.hr/file/11738 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.496=30; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:7742 2008-06-03 journal:117

Epidemiološki i virološki nadzor influence i influenci slične bolesti u Sloveniji Epidemiological and virological surveillance of influenza and influenza like illness in Slovenia Prosenc, Katarina Sočan, Maja Bolest slična influenci; Akutne dišne infekcije; Influenca A; Influenca B; RT-PCR Key words: Influenza-like illness; Acute respiratory infections; Sentinel surveillance; Influenza A; Influenza B; Multiplex RT-PCR Broj pacijenata s akutnom dišnom zarazom naglo se povećava nakon što se u populaciji počinje javljati virus influence. Kao posljedica toga javlja se povećana stopa hospitalizacije i mortaliteta. Nekoliko pokazatelja može se rabiti za mjerenje pojave popratnih bolesti vezanih uz influencu: stopa pojavnosti influenci slične bolesti ili akutne dišne bolesti, stopa nespecifičnog i specifičnog mortaliteta, bolovanje ili promatranje povećane potrošnje lijekova. Dva su pokazate-lja mjerena u Sloveniji od 1999.: pojava bolesti slične influenci i stopa pojave akutne dišne bolesti na oko 4% populacije. Lančana reakcija polimerazom uz prethodnu reverznu transkripciju (RT-PCR) bila je rabljena kao pregledna metoda za dokaz virusa influence, respiratornog sincicijskog virusa, adenovirusa i enterovirusa u obriscima nosa i/ili žrijela. Svi pozitivni uzorci bili su zatim nacijepljeni na odgovarajuće stanične linije. RT-PCR je bio upotrijebljen za brzo određivanje hemaglutinina (H1, H3) i neuraminidaze (N1, N2) virusa influence A. Antigenski podtipovi izdvojenih virusa na staničnim kulturama određeni su pomoću testa inhibicije hemaglutinacije te potvrđeni u Europskom referentnom centru za influencu Svjetske zdravstvene organizacije. U sezoni 2004./2005. stopa pojavnosti bolesti slične influenci bila je najveća u 5., 6. i 7. tjednu 2005., kada je dostigla svoj vrhunac (392/100000). Najviša incidencija akutne dišne bolesti ustanovljena je u razdoblju od 31. siječnja do 6. veljače i na toj je razini ostala sljedeća dva tjedna. Uzorci su bili uzeti od 793 bolesnika s kliničkim znakovima bolesti slične influenci. Virus influence A i B bio je dokazan u 15,2% pacijenata. Trećina slučajeva influence bila je uzrokovana podtipom H1N1 dok su ostali bili uzrokovani podtipom H3N2. Enterovirusne infekcije bile su relativno česte u prošloj sezoni (u 15,8% pacijenata). Izolati virusa influence bili su slični onima izdvojenima u drugim europskim zemljama i pripadali su serotipovima A/H3N2/California/7/2004 (A/H3N2/Fujian/441/2002-slični virusi), A/H1N1/New Caledonia/20/99 and B/Jiangsu/10/03 (B/Shanghai/361/2002-slični virusi). Dominantni virus influence u Europi i SAD-u bio je podtip A H3N2. Pojavnost akutne dišne bolesti i/ili influenci slične bolesti bila je veća u usporedbi s prethodnom sezonom u većini europskih zemalja (uključujući i Sloveniju). Summary The number of patients with acute respiratory infections rises sharply shortly after the influenza virus appears in population. Consequently, the hospitalization and mortality rates increase. Several indicators may be used to measure the burden-of-illness caused by the influenza virus: incidence rate of influenza-like illness (ILI) or acute respiratory illness (ARI), crude or cause-specific mortality rate, sick-live or monitoring the over the counter (OTC) medication sales. Two indicators have been measured in Slovenia since 1999: the ILI and ARI incidence rates in approximately 4% of the population. Multiplex Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was used as a screening method for the detection of influenza viruses, respiratory syncytial virus (RSV), adenoviruses and enteroviruses in nasal and/or throat swabs. All positive samples were further propagated in the corresponding cell culture line. RT-PCR was used for fast determination of hemaglutinins (H1, H3) and neuraminidases (N1, N2) of influenza A viruses. The antigenic subtype of the samples isolated on the cell culture was determined by means of a hemaglutination inhibition assay and confirmed in the WHO European Reference Centre for Influenza. In the 2004/2005 season, the ILI incidence rate was at highest in weeks 5, 6 and 7 of the year 2005, when it reached its peak value (392/100,000). The highest ARI incidence rate was recorded in the period from 31st January to 6th February, and remained elevated for the following two weeks. Samples were taken from 793 patients with clinical signs of ILI. The influenza A or B virus was detected in 15.2% of patients. One third of the influenza A cases were of the H1N1 subtype, while the others were H3N2. Enteroviral infection was relatively common in the past season (15.8% of patients). The influenza isolates in Slovenia were similar to those in other European countries and belonged to: A/H3N2/California/7/2004 (A/H3N2/Fujian/441/2002-like viruses), A/H1N1/New Caledonia/20/99 and B/Jiangsu/10/03 (B/Shaghai/361/2002-like viruses). The dominant influenza virus in Europe and the USA was influenza A H3N2. The ARI and/or ILI incidence rates were higher in most European countries (including Slovenia) compared to previous seasons. Croatian Academy of Sciences and Arts 2006-11-25 text pdf http://hrcak.srce.hr/7742 http://hrcak.srce.hr/file/11740 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.496=30; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:7743 2008-06-03 journal:117

Osobitosti izolata virusa influence izdvojenih iz ljudi u Hrvatskoj Characteristics of influenza viruses isolated from humans in Croatia Draženović, Vladimir Barišin, Andreja Gripa; Laboratorijske metode; Pandemije gripe Key words: Influenza; Laboratory methods; Flu pandemics Jedna od tri velike pandemije 20. stoljeća, zapravo najveća epidemija svih vremena tzv. "španjolska gripa" bila je uzrokovana virusom tipa A/H1N1/, a 1918. godine usmrtila je oko 50 milijuna ljudi. Zbog tog i sličnih događaja te pojava pandemija u prošlosti, Svjetska zdravstvena organizacija (SZO) ustrojila je niz od oko 110 Nacionalnih centara za influencu u različitim zemljama svijeta. U tim okvirima djeluje i Nacionalni centar za influencu Hrvatske. U ovom pregledu prikazane su osnovne karakteristike i obrasci pojavljivanja epidemija te karakteristike izolata virusa izdvojenih u Hrvatskoj u razdoblju od 1999. do 2005. godine. Summary One of three major pandemics of the 20th century is the greatest epidemics of all times, the so called Spanish flu, caused by the virus of the type A/H1N1/, which in 1918 caused the death of around 50 million people. Because of this and similar past pandemics occurrences WHO has established a whole range of around 110 National influenza centers in different countries of the world. Within this framework the National influenza center for Croatia is also active. In this overview we will compare the basic characteristics and occurrence patterns of these epidemics as well as the characteristics of virus isolates extracted in Croatia in the period from 1999-2005. Croatian Academy of Sciences and Arts 2006-11-25 text pdf http://hrcak.srce.hr/7743 http://hrcak.srce.hr/file/11741 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.496=30; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) hr

oai:hrcak.srce.hr:7744 2008-06-03 journal:117

Influenca konja u Hrvatskoj 2004. uzrokovana južnoameričkom podlinijom serotipa A EQUI-2 (H3N8) An outbreak of equine influenza (H3N8) in Croatia in 2004 caused by South American lineage Barbić, Ljubo Daly, Janet M. Rudan, Nevenka Kovač, Snježana Savić, Vladimir Cvetnić, Slavko Madić, Josip Equine influenza; Serotype H3N8; South American sublineage Influenca konja; Serotip H3N8; Južnoamerička podlinija U prošlosti je zabilježeno nekoliko epizootija influence konja u Hrvatskoj. Izdvojena su bila oba serotipa virusa: A-1 equi (H7N7) i A-2 equi (H3N8). U radu je opisana pojava influence konja na zagrebačkom hipodromu u 2004. godini. Kliničke znakove dišne bolesti pokazivali su cijepljeni kao i necijepljeni konji protiv influence. Unakrižnom reakcijom inhibicije hemaglutina-cije te serološkom pretragom parnih seruma oboljelih konja dokazano je da je bolest uzrokovao serotip H3N8. Antigenska i genetička analiza pokazala je da svi izdvojeni izolati virusa pripadaju južnoameričkoj podliniji serotipa H3N8. U svih šest analiziranih izolata ustanovljena je supstitu-cija jednog nekodirajućeg nukleotida u genu za hemaglutinin HA1. Kad je uspoređen slijed aminokiselina hrvatskih izolata s onima izdvojenima u proljeće 2003. u Engleskoj (Newmarket/5/03) dokazana je supstitucija jedne aminokiseline u signalnom slijedu. Several epizootics of equine influenza have been reported in Croatia in the past. Both subtypes, A/equine-1 (H7N7) and A/equine-2 (H3N8) were isolated. An outbreak of equine influenza in 2004, in racehorses on Zagreb hippodrome is described. Both unvaccinated and vaccinated horses showed clinical signs of respiratory disease. By cross HI test and serological examinations of paired sera of apparently affected horses, equine influenza (H3N8) virus was detected. Antigenic and genetic analysis of isolated viruses revealed the occurrence of South American sublineage of equine-2 (H3N8) influenza virus. The results presented in this work demonstrated that the HA1 gene sequence of the 6 isolates that were sequenced had only a single, non-coding nucleotide substitution among them. When the amino acid sequences of the Croatian isolates were aligned with a virus isolated in the UK during a widespread outbreak in the spring of 2003 (Newmarket/5/03), only a single amino acid substitution in the signal sequence was seen. Croatian Academy of Sciences and Arts 2006-11-25 text pdf http://hrcak.srce.hr/7744 http://hrcak.srce.hr/file/11744 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.496=30; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:7745 2008-06-03 journal:117

Nepouzdanost komercijalnog ELISA kompleta za serološki monitoring influence ptica Unreliability of a commercial ELISA kit for serologic monitoring of avian influenza Savić, Vladimir Balenović, Mirta Influenca ptica; Monitoring; ELISA Avian influenza; Monitoring; ELISA Pretražena su 342 uzorka seruma iz ekstenzivnih uzgoja kokoši i 184 seruma iz intenzivnih uzgoja purana uzeta u razdoblju od 27. prosinca 2004. do 9. rujna 2005. komercijalnim ELISA kompletom za protutijela virusa influence ptica. Nađeno je 45,6% pozitivnih seruma kokoši i svega 0,5% pozitivnih seruma purana. Serumi koji su dali pozitivnu ili sumnjivu reakciju ELISA testom pretraženi su i imunodifuzijom u gelu na nazočnost protutijela za virus influence ptica. Svi uzorci pretraženi ovim postupkom dali su negativan rezultat. Provjerom specifičnosti komercijalnog ELISA kompleta dobivene su pozitivne reakcije i s monovalentim standardnim antiserumima za viruse newcastleske bolesti i CELO, dok su serumi za PMV-2 i PMV-3 dali sumnjivu reakciju. Stoga se može zaključiti da je korišteni komercijalni komplet nepouzdan u serološkom monitoringu influence u peradi. S obzirom na proširenost visokopatogene influence ptica u svijetu i opasnost koju predstavlja visokopatogeni virus podtipa H5N1 za perad, ali i ljude, korištenjem komercijalnog kita bez provjere pozitivnih rezultata standardnim serološkim metodama mogu se donositi krivi zaključci s nesagledivim posljedicama. Three-hundred-and-forty-two serum samples from backyard chickens as well as 184 serum samples from farm turkeys, taken in the period from December 27th 2004 to September 9th 2005, were tested using commercial ELISA kit for avian influenza antibodies. It was found 45.6% positive chicken sera and only 0.5% positive turkey sera. Sera that were suspicious or positive in the ELISA were subjected to AGP test for avian influenza antibodies. All samples gave negative result when used AGP test. Specificity assessment of the commercial ELISA kit gave positive results even with monovalent standard antisera for Newcastle disease and CELO virus, whereas antisera for PMV-2 and PMV-3 gave suspicious result. Therefore, the commercial kit should be considered as unreliable for serologic monitoring of avian influenza in poultry. In regards to prevalence of highly pathogenic avian influenza in the world as well as animal and human health hazard posed by H5N1 highly pathogenic avian influenza virus, use of a commercial kit without confirmation with standard serological methods may lead to wrong conclusions with enormous consequences. Croatian Academy of Sciences and Arts 2006-11-25 text pdf http://hrcak.srce.hr/7745 http://hrcak.srce.hr/file/11745 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.496=30; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) hr

oai:hrcak.srce.hr:7746 2008-06-03 journal:117

Nadzor influence u dvorišne peradi i ptica selica u Sloveniji Avian influenza surveillance in backyard flocks and migratory birds in Slovenia Račnik, Jožko Krapež, Uroš Trilar, Tomi Dovč, Alenka Barlič- Maganja, Darja Zorman Rojs, Olga Ptice selice; Dvorišna perad; Influenca ptica; Seroprevalencija, RT- PCR Migratory birds; Backyard flocks; Avian influenza; Seropre-valence; RT-PCR Uzeti su uzorci krvi i obrisci nečisnica slobodnoživućih ptica selica i dvorišne peradi. Imunoenzimni test i inhibicija hemaglutinacije korišteni su kako bi se u slobodnoživućih ptica selica i dvorišne peradi utvrdila nazočnost protutijela za viruse influence ptica. Skupni uzorci briseva nečisnica korišteni su za izdvajanje virusa influence ptica. Uzorci su inokulirani u 9 do 11 dana stare kokošje embrije. Sakupljena je amnioalantoisna tekućina i pretražena na sposobnost hem-aglutinacije. Skupni uzorci brisova nečisnica korišteni su za dokaz virusa influence ptica pomoću RT-PCR. Četiri od 23 seruma gusaka bila su pozitivna na nazočnost specifičnih protutijela za virus influence ptica. Svi pokušaji izdvajanja virusa dali su negativan rezultat. Postupkom RT-PCR nije dokazana nazočnost nukleinske kiseline virusa influence ptica. Blood samples and clocal swabs were taken from free-living migratory birds and backyard flock birds. Enzyme linked immunosorbent assays (ELISA) and haemagglutination inhibition test (HI) was used to screen free-living migratory birds and backyard flocks for antibodies against avian influenza viruses (AIV). Pools of cloacal swabs were used for the attempt of isolation of AIV. Samples were inoculated of 9 to 11 day-old chicken embryos. Amnioallantoic fluid were collected and analysed for haemagglutination activity. Pools of cloacal swabs were used for the detection of AIV by RT-PCR. Sera samples of four out of twenty three geese were positive on presence of specific antibodies against AIV. All attempts of virus isolation were negative. No AIV nucleic acid was detected by RT-PCR. Croatian Academy of Sciences and Arts 2006-11-25 text pdf http://hrcak.srce.hr/7746 http://hrcak.srce.hr/file/11748 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.496=30; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:7747 2008-06-03 journal:117

Epidemiologija virusa influence konja: patogenost i prenosivost Epidemiology of equine influenza viruses: Pathogenicity and transmissibility Daly, Janet M. Newton, J. Richard Smith, Ken C. Mumford, Jenny A. Epizootiologija influence konja; Odabir cjepnog soja Equine influenza epidemiology; Vaccine strain selection Podtip H3N8 virusa influence konja uzrokovao je velik broj epizootija svakog desetljeća otkako je 1963. godine prvi put bio izdvojen iz konja. Svaka epizootija, a i neke manje pojave, utjecale su na mjere nadzora i cijepljenja u Velikoj Britaniji i drugdje. Posljednja velika epizootija influence konja zabilježena je 2003. Mogući razlozi prijemljivosti konja usprkos stalnog cijepljenja još se istražuju i mogli bi dati novo svjetlo na epidemiologiju influence konja. A large-scale outbreak caused by equine influenza virus of the H3N8 subtype has occurred in each decade since an H3N8 virus was first isolated from horses in 1963. Each epidemic, and some minor outbreaks, has influenced equine influenza surveillance and vaccination policies in the UK and elsewhere. The latest widespread outbreak of equine influenza occurred in 2003. The possible reasons for infection of horses despite intensive vaccination are currently being investigated and may shed new light on the epidemiology of equine influenza. Croatian Academy of Sciences and Arts 2006-11-25 text pdf http://hrcak.srce.hr/7747 http://hrcak.srce.hr/file/11750 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.496=30; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:7748 2008-06-03 journal:117

Molekularni pristup identifikaciji virusa influence ptica Molecular approaches for the identification of avian influenza viruses Barlič- Maganja, Darja Krapež, Uroš Zorman Rojs, Olga Virus influence ptica; H5, H7; Tipizacija; Lančana reakcija polimerazom Avian influenza virus; H5, H7; Typing; Polymerase chain reaction Svijest o prijetnji nove pandemije influence potaknula je zanimanje za dokaz virusa influence A u sekretima različitih vrsta ptica i sisavaca. Virusi influence A uobičajeno se tipiziraju na osnovi osobina njihovih površinskih glikoproteina, hemaglutinina (HA) i neuraminidaze (NA). Svih 16 HA i devet NA podtipova izdvojeno je iz vodenih ptica koje su prirodni domaćin i rezervoar virusa influence. Perad, posebice kokoši i pure, ne smatra se uobičajenim domaćinom virusa iako se virus redovito s divljih ptica prenosi na perad. Premda su mnogi HA podtipovi izdvojeni iz peradi, posebna pozornost pridaje se podtipovima H5 i H7 virusa influence ptica, jer samo oni pripadaju visoko patogenim sojevima za perad. Nedavno razvijene molekularne metode omogućuju brzu, točnu i pouzdanu identifikaciju virusa influence i njegovih podtipova. The recently raised awareness of the threat of a new influenza pandemic has stimulated the interest in the detection of influenza A viruses in the secretions of a wide variety of birds and mammals. Influenza A viruses are subtyped conventionally according to the characteristics of the external glycoproteins, haemagglutinin (HA) and neuraminidase (NA). All 16 HA and 9 NA subtypes have been isolated from aquatic birds that are believed to be a natural host and reservoir for influenza viruses. Poultry, specifically chickens and turkeys, are not considered to be a normal host for the virus, although transmission from wild birds to poultry occurs routinely. Although most HA subtypes have been found in poultry, particular emphasis is placed on the H5 and H7 HA subtypes of avian influenza virus because only these subtypes are known to cause highly pathogenic avian influenza (HPAI) in poultry. Recently developed molecular methods enable fast, accurate and reliable approach to identify influenza virus and its subtypes. Croatian Academy of Sciences and Arts 2006-11-25 text pdf http://hrcak.srce.hr/7748 http://hrcak.srce.hr/file/11752 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.496=30; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:7749 2008-06-03 journal:117

Avian Influenza – past, present and future challenges Capua, Ilaria Croatian Academy of Sciences and Arts 2006-11-25 text pdf http://hrcak.srce.hr/7749 http://hrcak.srce.hr/file/11753 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.496=30; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:7750 2010-05-17 journal:117

Avian Influenza in Italy – experiences in management of multiple introductions Cattoli, Giovanni Croatian Academy of Sciences and Arts 2006-11-25 text pdf http://hrcak.srce.hr/7750 http://hrcak.srce.hr/file/11754 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.496=30; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:17277 2008-06-03 journal:117

Ovarijalni neuroektodermalni tumori Ovarian neuroectodermal tumors Morović, Anamarija Damjanov, Ivan jajnik; neuroektodermalni tumori Ovary; Neuroectodermal tumor; Germ cell tumor U ovom smo radu pregledali objavljenu literaturu o primarnim neuroektodermalnim tumorima jajnika. Ovi rijetki monofazični teratomi, sastavljeni isključivo ili gotovo isključivo od neuroektodermalnog tkiva, predstavljaju važnu paradigmu tumora koji se razvijaju iz zametnih stanica jajnika. Do sada je u literaturi opisano oko 60 slučajeva neuroektodermalnih tumora jajnika. Većinom se dijagnosticiraju u žena u trećem i četvrtom desetljeću života, a rijetko se pojavljuju u djece, adolecenata i starijih žena. Ovi se tumori dijele na gliome, kao što su ependimom, ependimoblastom, astrocitom, glioblastom, te na primitivne neuroepitelne tumore, kao što su meduloblastom, meduloepiteliom i neuroblastom. Histološka slika ovih tumora identična je tumorima koji se pojavljuju u središnjem živčanom sustavu. Većina bolesnica s niskim kliničkim stadijem bolesti (I i II) liječena je kirurški, dok su bolesnice s višim kliničkim stadijem (III i IV) dodatno liječene zračenjem, kemoterapijom, ili s oba modaliteta. Klinički stadij bolesti pri dijagnozi najznačajniji je prognostički pokazatelj kod ovih tumora. Bolesnice kod kojih je tumor dijagnosticiran i odstranjen u ranom kliničkom stadiju imaju dobru prognozu, dok je prognoza u uznapredovalim stadijima bolesti loša. In this paper we have reviewed the publications dealing with primary neuroectodermal tumors of the ovary.These rare monophasic teratomas are composed exclusively or almost exclusively of neuroectodemal tissue and are thus an important paradigm of a type of malignancy that develops from ovarian germ cells. Approximately 60 neuroectodermal tumors of the ovary have been reported in the literature. Histologically, the tumors were classified as gliomas, such as ependymoma, ependymoblastoma, astrocytoma, glioblastoma multiforme, or as primitive neuroepithelial tumors such as medulloblastoma, medulloepithelioma, and neuroblastoma. Microscopically, they are identical to equivalent neuroectodermal tumors of the central nervous system. Most tumors were diagnosed in the third and fourth decades of life. Neuroectodermal tumors are rarely diagnosed in other age groups, although there are published reports of such tumors in children, adolescents or older women. The review of the litarature shows that most patients with clinical stage I and II were treated surgically, whereas those with stage III or IV tumors received additional radiation or chemotherapy, or both. The clinical stage at the time of diagnosis is the most important prognostic parameter of these tumors.Patients whose tumors were recognized early in the course of the neoplastic disease and treated appropriately had a good prognosis, but those with tumors in advanced stages advanced tumors had poor prognosis. Croatian Academy of Sciences and Arts 2007-10-10 text pdf http://hrcak.srce.hr/17277 http://hrcak.srce.hr/file/26689 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.497=31; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:17444 2008-06-03 journal:117

Editorial Pećina, Marko Croatian Academy of Sciences and Arts 2007-10-10 text pdf http://hrcak.srce.hr/17444 http://hrcak.srce.hr/file/26944 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.497=31; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:17445 2008-06-03 journal:117

Editorial - Fourth Scientific Meeting on Brain Disorders: Scientific Basis of Diagnosis and Treatment of Vertigo Demarin, Vida Croatian Academy of Sciences and Arts 2007-10-10 text pdf http://hrcak.srce.hr/17445 http://hrcak.srce.hr/file/26945 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.497=31; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:17446 2008-06-03 journal:117

Diferencijalna dijagnoza vertiga Differential diagnosis of vertigo Demarin, Vida Trkanjec, Zlatko Aleksić-Shibabi, Anka Uremović, Melita vertigo; periferni vertigo; centralni vertigo; benigni paroksizmalni pozicioni vertigo; akutni vestibularni neuronitis; Méniéreova bolest; migrena; vertebrobasilarna ishemija; tumor pontocerebelarnog kuta vertigo; peripheral vertigo; central vertigo; benign paroxysmal positional vertigo; acute vestibular neuronitis; Méniére’s disease; migraine; vertebrobasilar ischemia; tumor of pontocerebellar angle Vertigo je iluzija kretanja, najčešće rotacijskog kretanja. Vertigo je među najčešćim simptomima koji dovode bolesnike liječniku, a sa starenjem učestalost vertiga se povećava. Vertigo može biti uzrokovan poremećajima unutarnjeg uha – periferni vertigo, centralnim poremećajima – centralni vertigo, sustavnim bolestima, a može biti i psihogeni. Najčešći uzroci vertiga su benigni paroksizmalni pozicioni vertigo, akutni vestibularni neuronitis, Méniéreova bolest, migrena, anksiozni poremećaji, vertebrobazilarna ishemijaa i tumori pontocerebelarnog kuta. Važno je razlikovati periferni od centralnog vertigo kako bi se mogle donijeti odluke o liječenju. U ovom članku prikazana je diferencijalna dijagnostika vertiga. Vertigo is the illusion of motion, usually rotational motion. Vertigo is among the most common symptoms causing patients to visit a physician, and as patients become older the incidence of vertigo increases. Vertigo can be caused by an inner ear disturbance – peripheral vertigo, by a central disturbance – central vertigo, by systemic diseases, or it can be psychogenic. The most common causes of vertigo are benign paroxysmal positional vertigo, acute vestibular neuronitis, Méniére’s disease, migraine, anxiety disorders, vertebrobasilar ischemia and tumors of the pontocerebellar angle. It is important to distinct between peripheral and central vertigo in order to guide management decisions. In this article a differential diagnosis of vertigo is presented. Croatian Academy of Sciences and Arts 2007-10-10 text pdf http://hrcak.srce.hr/17446 http://hrcak.srce.hr/file/26947 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.497=31; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:17447 2008-06-03 journal:117

Diferencijalna dijagnostika vertiga i epilepsije The differential diagnosis of vertigo and epilepsy Miškov, Snježana Hećimović, Hrvoje epilepsija; epileptički vertigo; parcijalna epilepsija; neokortikalna epilepsija epilepsy; epileptic vertigo; partial epilepsy; neocortical epilepsy Vertigo je najčešće osjećaj vrtnje, uobičajeno kao posljedica poremećaja osjetila ravnoteže (vestibularnog sustava). Može nastati zbog disfunkcije vestibularnog sustava na bilo kojem mejstu od unutarnjeg uha do kore mozga. Epileptički vertigo je rijetki oblik parcijalnih napada koji nastaje zbog epileptičke aktivnosti u dijelovima korteksa koji predstavljaju vestibularni sustav: parijetalni, temporalni i frontalni korteks. Napadi obično traju nekoliko sekundi do nekoliko minuta, a gubitak svijesti nastaje samo kada se napad generalizira. Dijagnostičke pretrage uključuju EEG i MRI glave. Daljnja dijagnostička obrada u rezistentnim slučajevima uključuje: video EEG monitoriranje, intrakarotidno primjenu amitala, SPECT tijekom napada, neurofiziološku procjenu i intrakranijsko EEG monitoriranje. Poremećeni EEG je glavni kriterij za dijagnozu. U većine bolesnika poremećaji EEG-a uključuju temporalna ili bitemporalna žarišta šiljastih i sporih valova. U nekih slučajeva pridružuju se generalizirana epileptička izbijanja. Terapija epileptičkog vertiga obično je uspješna primjenom tradicionalnih antiepileptika poput karbamazepina i njemu sličnih lijekova. Ukoliko, nakon razumnog roka primjene adekvatnih antiepileptičkih lijekova, napadi nisu adekvatno kontrolirani, mogu se razmotriti i kirurške metode. Diferencijalna dijagnostika epileptičkog vertiga uključuje: bazilarnu migrenu, konfuzijsku migrenu, benigni paroksizmalni vertigo u djetinjstvu i auru bez glavobolje. Najznačajnija ke diferencijalna dijagnoza neokortikalnih temporalnih napada od mezijalnih temporalnih napada. Iktalni SPECT i MRI mogu pružiti dijagnostičke podatke koji se ne mogu dobiti na drugi način. Protonska MR spektroskopija i PET mogu biti od pomoći u razlikovanju mezijalnih od neokortikalnih temporalnih napada. Vertigo is most commonly a feeling of spinning, usually due to the disturbance in the balance (vestibular) system. It may result from a dysfunction of the vestibular system at any point from the ear to the cerebral cortex. Epileptic vertigo is a rare form of partial seizures, due to epileptic activity in parts of the cortex that represent the vestibular system: the parietal, temporal and frontal cortex. The episodes usually last no more than seconds or minutes. Unconsciousness will follow only if the seizure becomes generalized. Diagnostic tests include EEG and MRI scans of the head. Further diagnostic evaluation in the case of medical intractability would include: video EEG monitoring, intracarotid amytal testing, ictal SPECT, neurophysiogical evaluation and intracranial EEG monitoring. An abnormal EEG is a major criterion for diagnosis. In most patients the abnormality consists of temporal or bitemporal sharp or slow wave foci. In some cases there are associated generalized seizure discharges. Treatment of epileptic vertigo is usually successful with traditional anticonvulsants such as carbamazepine and its relatives. If, after a reasonable trial with appropriate antiepileptic drugs, seizures remain inadequately controlled, a surgery can be considered. Differential diagnosis of epileptic vertigo includes: a basilar type migraine, confusional migraine, benign paroxysmal vertigo of childhood and an aura without a headache. The main differential diagnosis of neocortical temporal lobe seizures is a mesial temporal lobe seizure. Ictal SPECT scanning and MRI can provide diagnostic data not otherwise obtainable. In addition, proton MR spectroscopy and PET studies can be helpful to distinguish the mesial from neocortical temporal lobe seizures. Croatian Academy of Sciences and Arts 2007-10-10 text pdf http://hrcak.srce.hr/17447 http://hrcak.srce.hr/file/26949 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.497=31; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:17448 2008-06-03 journal:117

Elektrofiziološke metode u dijagnostici vrtoglavica Electrophysiological methods in the diagnostics of vertigo Mikula, Ivan Neurofiziološki dijagnostički testovi; vertigo; elektromiografija; evocirani potencijali Neurophysiological diagnostic tests; vertigo; electromyography; evoked potentials Uloga neurofizioloških pretraga u dijagnostici vrtoglavica primarno se sastoji u utvrđivanju funkcionalnog statusa senzornih sustava odgovornih za stvaranje koncepta prostora. Primjenjive su donekle i u određivanju stanja integrativnih neuralnih struktura, koji objedinjuju informacije dobivene iz istih senzornih sustava. Podaci dobiveni neurofiziološkim pretragama isključivo su funkcijskog karaktera i ne daju nikakvu informaciju o etiologiji poremećaja, već upućuju samo na lokalizaciju i vrstu poremećaja koji je doveo do vrtoglavice, te se uvijek moraju kombinirati s neuroradiološkim, neurosonološkim i laboratorijskim ispitivanjima. Obzirom na način stvaranja koncepta prostora u ljudskom mozgu, potencijalni generatori vrtoglavice su oči (koje prenose vidnu informaciju), unutarnje uho (koje prenosi slušnu i vestibularnu informaciju), cervikalni receptori (koji prenose proprioceptivnu informaciju), te mali i veliki mozak (čija je uloga u integraciji ovih informacija). Ovi sustavi se nadopunjavaju, omogućavajući mozgu da stvori točnu informaciju o položaju u prostoru. Neurofiziološka ispitivanja ovih struktura predstavljaju temelj neurofiziološke dijagnostike vertiginoznih smetnji. The role of neurophysiologic tests in the diagnostics of vertigo primarily consists of assessing the functional status of the sensory systems responsible for the concept of space. They also have a limited application in assessing the functional status of structures responsible for the integration of this information. The data obtained by neurophysiological testing are purely functional giving no information considering the etiology of the disturbance, and only point to the localization and type of the disturbance that lead to vertigo. That is why they always need to be combined with neuroradiologic, neurosonologic and laboratory tests. The brain relies on three sensory systems to maintain spatial orientation: the vestibular system (the inner ear), the visual system (the eyes), and the somatosensory system (which conveys information from the skin, joint, and muscle receptors). These three systems overlap, allowing the brain to assemble an accurate sense of spatial orientation. Information from these systems is integrated in the cerebrum and cerebellum. However, a compromised system or conflicting signals can cause vertigo Croatian Academy of Sciences and Arts 2007-10-10 text pdf http://hrcak.srce.hr/17448 http://hrcak.srce.hr/file/26951 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.497=31; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:17449 2008-06-03 journal:117

Uloga neurosonologije u vertigu The role of neurosonology in vertigo Lovrenčić-Huzjan, Arijana Vertigo; obojeni dopler; transkranijski dopler; karotidna arterija; vertebralna arterija Vertigo; Color Doppler; Transcranial Doppler; carotid artery; vertebral artery Vertigo je čest simptom koji može predstavljati i ozbiljan neurološki poremećaj. Ako vertigo naglo nastane, može biti simptom akutnog moždanog udara. Neurosonologija se može upotrijebiti u cerebrovascularnih poremećaja kako bi se procijenilo stanje krvnih žila, ili u dijagnostici različitih bolesti kraniocervikalnih arterija. Mogu se prikazati aterosklerotske promjene, upalne bolesti, disekcije, vaskulopatije i vaskularne malformacije. Primjenom transkranijskog doplera može se procijeniti intrakranijska hemodinamika, može se prikazati nastanak kolateralnih puteva u ekstra- i intrakranijakim i okluzivnim bolestima, može se ispitati cerebralna vazomotorna reaktivnost, a primjena novih softwera omogućuje detekciju mikroembolijskih signala. Neurosonologija se može primijeniti u različitim neurološkim poremećajima koji imaju vertigo kao simptom. Vertigo is a common symptom, and may represent a serious neurological disorder. If it develops suddenly, it may be a symptom of an acute stroke. Neurosonology can be used in cerebrovascular disorders in order to asses the vessel patency, or to present different craniocervical artery diseases. Atherosclerotic changes may be seen, as well as inflammatory diseases, dissections, vasculopathies or vascular malformations. By means of a transcranial Doppler the intracranial hemodynamics can be assessed. A development of collateral pathways in extra- or intracranial occlusive diseases can be presumed, cerebral vasomotor reactivity can be tested, and, with the application of new softwares, microembolic signals can be detected. Neurosonology can be used in a variety of neurological disorders presenting with vertigo. Croatian Academy of Sciences and Arts 2007-10-10 text pdf http://hrcak.srce.hr/17449 http://hrcak.srce.hr/file/26953 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.497=31; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:17450 2008-06-03 journal:117

Farmakoterapija vertiga Pharmacotherapy of vertigo Trkanjec, Zlatko Aleksić-Shibabi, Anka Demarin, Vida vertigo; terapija; farmakoterapija vertigo; therapy; pharmacotherapy Farmakoterapija vertiga može biti simptomatska ili specifična. Ne postoji idealni lijek za liječenje vertiga. Akutni vertigo se obično liječi vestibularnim supresorima i antiemeticima. U liječenju vertiga i pridruženih simptoma najčešće se primjenjuju antikolinergici, antihistaminici, dopaminergički antagonisti i monaminergici. I neki drugi lijekovi se također primjenjuju u liječenju vertiga. Međutim, vertigo je subjektivni osjećaj, što otežava mjerenje učinka lijekova. Stoga mnogi radovi o liječenju vertiga imaju metodološke poteškoće, što otežava donošenje opće prihvaćenog konsenzusa o liječenju vertiga. Pharmacotherapy of vertigo can be symptomatic or specific. There is no ideal drug for the management of vertigo. Acute vertigo is usually managed with vestibular suppressants and antiemetic medications. Anticholinergics, antihistamines, dopaminergic antagonists, and monaminergics are most often used in the treatment of vertigo and associated symptoms. Some other drugs are also used in its treatment. However, vertigo is a subjective feeling which makes it difficult to measure the drug effect. Therefore, many papers dealing with vertigo treatment suffer from methodological pitfalls, making it difficult to establish a generally acceptable consensus about the treatment of vertigo. Croatian Academy of Sciences and Arts 2007-10-10 text pdf http://hrcak.srce.hr/17450 http://hrcak.srce.hr/file/26955 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.497=31; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:17451 2008-06-03 journal:117

Psihološko-psihijatrijski čimbenici kronične vrtoglavice Psychological-psychiatric factors in chronic dizziness Buljan, Danijel Ivančić, Iva kronična subjektivna vrtoglavica; neuro-otološka stanja; anksioznost; fobičnost anxiety; phobia; chronic dizziness; postconcussional syndrome; dysautonomia; migraine Istraživanja su pokazala da postoji povezanost između nekoliko neuro-otoloških kliničkih stanja koja se javljaju subjektivnim osjećajem nestabilnosti i vrtoglavice uz anksioznost i druge psihijatrijske simptome. Pojam kronične subjektivne vrtoglavice ponudio je sustavni pristup bolesnicima sa ustrajnom vrtoglavicom koja nije uzrokovana očitim patofiziološkim vestibularnim oštećenjem. Sukladno sa novim neurobiološkim istraživanjima postoje tri podtipa kronične subjektivne vrtoglavice (otogeni, psihogeni, interaktivni) koje čine fizički i psihološki simptomi. Danas postoji veća dijagnostička točnost i uvid u temeljne patofiziološke procese vestibularne migrene, postkontuzijskog sindroma mozga i distonije autonomnog živčanog sustava, koji mogu prouzročiti simptome nalik kroničnoj subjektivnoj vrtoglavici. Selektivni inhibitori ponovne pohrane serotonina-SIPPSa, rehabilitacijska terapija ravnoteže i kognitivno-bihevioralna terapija pokazuju ograničenu, ali korisnu učinkovitost u liječenju kronične subjektivne vrtoglavice. Investigations demonstrated a correlation between oto-neurological illnesses manifested subjectively by instability and dizziness and anxiety and other psychiatric disorders. The concept of chronic vertigo offered a systematic approach to patients with a lasting dizziness not caused by an evident patophysiological vestibular damage. According to newer neurobiological investigations, there are three subtypes of chronic dizziness: otogenic, psychogenic and interactive. Nowadays there is a greater diagnostic accuracy and insight into the basic pathophysiological processes of the vestibular migraene, post-concussional syndrom and dysautonomias that can cause chronic dizziness. Selective serotonin reuptake inhibitors, rehabilitation therapy for restoring the balance, and cognitive- behavioural therapy can be effective in treatment, but this effectiveness is limited. Croatian Academy of Sciences and Arts 2007-10-10 text pdf http://hrcak.srce.hr/17451 http://hrcak.srce.hr/file/26957 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.497=31; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:17452 2008-06-03 journal:117

Prevalencija vertiga u bolesnika s migrenom i u osoba bez glavobolje Prevalence of vertigo and dizziness in migraine patients and non-headache subjects Vuković, Vlasta Plavec, Davor Galinović, Ivana Lovrenčić-Huzjan, Arijana Demarin, Vida Vertigo; glavobolja; migrena; migrena s aurom; migrena bez aure Vertigo; headache; migraine; migraine with aura; migraine without aura Cilj ovog istraživanja bio je procijeniti prevalenciju vertiga u bolesnika s migrenom i u kontrolnoj skupini osoba bez glavobolja. Ukupno je 327 bolesnika s migrenom i 324 osobe u kontrolnoj skupini ispitano da li imaju simptome vrtoglavice, o vremenu nastanka simptoma, učestalosti simptoma i vremenskoj povezanosti simptoma s napadom migrene. Više od polovine bolesnika s migrenom je imalo osjećaj vrtoglavice: 169 bolesnika (51.7%), a u kontrolnoj skupini 102 osobe (31.5%). Simptomi vrtoglavice bili su povezani s napadom migrene uvijek u 38 bolesnika (22.5%), ponekad u 38 bolesnika (22.5%), a nisu bili povezani u 93 bolesnika (55.0%). Bolesnici koji imaju migrenu s aurom značajno češće imaju napade migrene povezane sa simptomima vrtoglavice. Ovo istraživanje, kao i ostala slična istraživanja, pokazuje da treba uzeti u obzir migrenu u diferencijalnoj dijagnozi vertiga. The aim of this study was to assess the prevalence of vertigo and dizziness in patients with migraine as compared to the control group without a headache. A total of 327 patients with migraine and the control group of 324 subjects were evaluated for vertiginous signs and dizziness, time of onset of the symptoms, frequency of the symptoms and temporal association of the symptoms with the migraine attack. More than half of the migraine patients had in their lifetime experienced a sense of vertigo or dizziness: 169 patients (51.7%), and 102 subjects (31.5%) in the control group. Vertigo symptoms were associated with a migraine attack always in 38 (22.5%), sometimes in 38 (22.5%) and were not associated in 93 (55.0%) patients. Patients having migraine with aura significantly more often have migraine attacks associated with symptoms of vertigo or dizziness. Our study, together with other similar studies, suggests that migraine should be considered in the differential diagnosis of vertigo. Croatian Academy of Sciences and Arts 2007-10-10 text pdf http://hrcak.srce.hr/17452 http://hrcak.srce.hr/file/26959 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.497=31; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:17453 2008-06-03 journal:117

Utjecaj okluzije vertebralne arterije na odgovore u stražnjoj moždanoj arteriji tijekom vidnih podražaja The influence of vertebral artery occlusion on visual evoked responses in posterior cerebral artery Bosnar Puretić, Marijana Lovrenčić-Huzjan, Arijana Roje-Bedeković, Marina Demarin, Vida vertebralne arterije; vidni evocirani odgovori; ultrazvuk; stražnja moždana arterija vertebral artery; visual evoked responses; sonography; posterior cerebral artery Moždani udar je po učestalosti drugi uzrok smrti i vodeći uzrok onesposobljenosti u Hrvatskoj. Četvrtina svih ishemijskih moždanih udara nastaje u području stražnje cirkulacije. Trećina svih ishemijskih moždanih udara uzrokovana je bolešću velikih krvnih žila. Transkranijska dopler sonografija (TCD) je neinvazivna dijagnostička metoda s izvrsnom vremenskom rezolucijom koja omogućava ispitivanje moždanog krvotoka u živom vremenu. Funkcionalni TCD testovi, između ostalih metoda, imaju značajnu ulogu u procjeni moždanog vazomotornog kapaciteta. Rezultati prethodnih TCD istraživanja ukazali su da proksimalna stenoza u karotidnoj cirkulaciji izrazito utječe na distalnu hemodinamiku i mehanizme autoregulacije. Cilj ovog istraživanja bio je pomoću TCD-a utvrditi utjecaj okluzije vertebralne arterije na odgovore u stražnjoj moždanoj arteriji tijekom vidnih podražaja. Odgovore tijekom vidnih podražaja u stražnjoj moždanoj arteriji u bolesnika s okluzijom vertebralne aterije bilježili smo TCD-om mjereći srednje brzine strujanja krvi (SBSK) u stražnjoj moždanoj arteriji prije i tijekom vidnih podražaja. Mjereći SBSK u stražnjoj moždanoj arteriji bez vidnih podražaja, vrijednosti u kontrolnoj skupini nisu se značajno razlikovale od vrijednosti SBSK u skupini bolesnika s okluzijom vertebralne arterije. Tijekom vidnih podražaja bijelim svjetlom u obje skupine ispitanika zabilježeno je statistički značajno povećanje SBSK u stražnjoj moždanoj arteriji. U kontrolnoj skupini to povećanje SBSK iznosilo je 22,85±20,9% u desnoj, a 20,67±15,31% u lijevoj stražnjoj moždanoj arteriji. U skupini bolesnika s okluzijom vertebralne arterije povećanje u desnoj stražnjoj moždanoj arteriji iznosilo je 12,3±16,46%, a u lijevoj 11,89±13,08%. U bolesnika s okluzijom vertebralne arterije opetovani vidni podražaji doveli su do smanjenja odgovora u stražnjoj moždanoj arteriji što je mogući pokazatelj iscrpljivanja moždane vazomotorne rezerve. Na temelju našeg istraživanja možemo zaključiti da postoji negativni utjecaj okluzije vertebralne arterije na distalnu hemodinamiku. Funkcionalni TCD testovi vidnim podražajima predstavljaju neinvazivu i preciznu metodu za procjenu vazoreakivnosti u stražnjoj moždanoj cirkulaciji. Stroke is the second leading cause of death and the leading cause of disability in Croatia. One-quarter of all ischemic strokes occur in the posterior circulation. One third of ischemic strokes are caused by large artery diseases. Transcranial Doppler sonography (TCD) is a non-invasive method with an excellent temporal resolution for real time investigations of cerebral hemodynamics and, among other methods, functional TCD tests are very useful tools for establishing the cerebral vasomotor capacity. TCD studies revealed that a proximal stenosis in the carotid circulation severely influences distal cerebral hemodynamics and autoregulative mechanisms. The aim of this study was to establish the influence of a vertebral artery (VA) occlusion on visual evoked responses in the posterior cerebral artery (PCA) measured by means of TCD. We measured mean blood flow velocities (MBFVs) in the PCA before and during a visual stimulation in patients with a VA occlusion by means of TCD. Without visual stimuli there was no significant difference between the control group and the patients with a VA occlusion. During white light stimulation a statistically significant increase of MBFVs in the PCA in both groups occurred. In the control group the increase was 22.85±20.9% for the right PCA and 20.67±15.31% for the left PCA. In the group of patients with a VA occlusion the increase in the right PCA was 12.3±16.46% and in the left PCA 11.89±13.08%. In the patients with a VA occlusion repeated testing led to diminished responses, which could be an indicator of the exhaustion of the cerebrovascular vasomotor reserve. Based on the results of our study we can conclude that there is a negative effect on the functioning of the distal small vessels in the case of a VA occlusion. Visually evoked functional TCD testing is a non-invasive and precise method for the estimation of vasoreactivity in the posterior circulation. Croatian Academy of Sciences and Arts 2007-10-10 text pdf http://hrcak.srce.hr/17453 http://hrcak.srce.hr/file/26961 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.497=31; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:17454 2008-06-03 journal:117

Trodimenzionalni ultrazvuk vertebrobazilarnog sustava Three dimensional utrasound of the vertebrobasilar system Zavoreo, Iris Jelena Jurašić, Miljenka Demarin, Vida Ultrazvuk, trodimenzionalni ultrazvuk, vertebralne arterije Ultrasound, three dimensional ultrasound, vertebral arteries. Uvod: Transkranijska bojom kodirana sonografija (TCCS) i osnaženi dopler (PD) se upotrebljavaju za procjenu vertebrobazilarnog (VB) sustava. Zbog nepovoljnog kuta spoja vertebralnih arterija (VA) i kuta insonacije, rijetko se mogu prikazati sve tri žile istovremeno. Trodimenzionalni ultrazvuk (3D UZ) omogućava volumetrijsku rekonstrukciju VB spoja. Metode: Primijenili smo 2D TCCS, PD i 3D UZ u 25 bolesnika kako bismo prikazali intrakranijski dio VB sustava. Rezultati: Primjenom TCCS nije bilo moguće prikazati sve tri krvne žile istovremeno, primjenom PD to je bilo moguće u 6 od 25 bolesnika, a primjenom 3D PD u 19 od 25 bolesnika. U 6 bolesnika VB kut se nije mogao prikazati (2 VA su bile okludirane što je potvrđeno angiografijom, u 4 slučaja bio je suboptimalni okcipitalni prozor), pa je primijenjena volumetrijska rekonstrukcija. Zaključak: 3D UZ omogućuje bolji prikaz VB spoja zbog mogućnosti volumetrijske rekonstrukcije. Background: Transcranial color-coded sonography (TCCS) and power Doppler imaging (PDI) are used for the evaluation of the vertebrobasilar (VB) system. Due to the unfavorable angle of the vertebral arteries’ (VA) junction and angle of insonation, all three vessels can rarely be visualized at the same time. Three-dimensional ultrasound (3D US) enables volumetric reconstruction of the VB junction. Methods: 2D TCCS and PD as well as 3D US were applied in 25 patients in order to visualize the intracranial part of the VB system. Results: In TCCS mode it was not possible to obtain all three vessels at the same time, in PD mode it was possible in 6/25 patients, and in 3D PD method in 19/25 patients. In 6 patients the VB angle could not be visualized (2 VAs were occluded – confirmed by angiography, in 4 cases there was a suboptimal suboccipital window), and volumetric reconstruction was applied. Conclusion: 3D US enabled better visualization of the VB junction due to the possibility of volumetric reconstructions. Croatian Academy of Sciences and Arts 2007-10-10 text pdf http://hrcak.srce.hr/17454 http://hrcak.srce.hr/file/26963 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.497=31; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:17455 2008-06-03 journal:117

Morfološke i hemodinamske karakteristike vertebralnih arterija kod muškaraca i žena Morphologic and hemodynamic characteristics of vertebral arteries in men and women Morović, Sandra Škarić-Jurić, Tatjana Demarin, Vida Vertebralna arterija; Hrvatska populacija Vertebral artery; Croatian population Uvod: Muškarci i žene se razlikuju u promjerima i srednjim brzinama strujanja krvi (SBSK) u vertebralnim arterijama (VA). Cilj: usporediti morfologiju i hemodinamiku VA među spolovima. Ispitanici i metode: Pregledali smo 155 osoba upotrebom linearne sonde 7,5 mHz (Aloka Prosound SSD-5500). Mjerenja su vršena u V2 segmentu VA. Kriteriji: VA dijametar 2-4mm, sistoličke SBSK 0,35-0,70m/s, normalan otpor. Mjereni parametri: promjeri VA, SBSK u VA, ukupni promjeri VA, ukupne SBSK u VAs, promjeri “uže” i šire VA, i dob. Rezultati: 68 muškaraca i 87 žena; 88 dominantnih lijevih VA (56% muškaraca i 58% žena), 11 (7%) bez dominacije. Razlike među grupama: muškarci imaju šire obje VA i promjer “šire” VA. Nije bilo razlika u sbsk među spolovima. Zaključak: Lijeva VA je dominantna u oba spola, nema razlika u SBSK među spolovima. Muškarci imaju šire VA od žena. Introduction: Men and women differ in diameters and MBFVs in VAs. Aim: to compare morphology and hemodynamics of VAs between sexes. Patients and methods: We examined 155 subjects using a linear 7.5 MHz probe (Aloka Prosound SSD-5500). Measurements were obtained at the V2 segment of VAs. Criteria: VA diameter of 2-4mm, systolic MBFVs of 0.35-0.70m/s, normal resistance pattern. Investigated parameters: diameters of VAs, MBFVs in VAs, sum of VA diameters, sum of MBFVs in VAs, diameter of the narrower and wider VA, and age. Results: 68 men and 87 women; 88 with a dominant left VA (56% of men and 58% of woman), 11 (7%) showed no dominance. Group differences: men had both VAs wider, and a larger diameter of the “wider” VA. There were no differences in MBFVs between men and women. Conclusion: Left VA is dominant in both sexes. There was no difference in MBFVs among sexes. Men have a wider VA than women. Croatian Academy of Sciences and Arts 2007-10-10 text pdf http://hrcak.srce.hr/17455 http://hrcak.srce.hr/file/26965 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.497=31; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:22471 2008-06-03 journal:117

Editorial Pećina, Marko; Croatian Academy of Sciences and Arts, Departement of Medical Sciences, Zagreb, Croatia; marko.pecina@zg.t-com.hr Croatian Academy of Sciences and Arts 2008-04-21 text pdf http://hrcak.srce.hr/22471 http://hrcak.srce.hr/file/35371 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.499=32; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:22473 2008-06-03 journal:117

Ciklodekstrini u ljekovitim oblicima Cyclodextrin-based pharmaceutical Jug, Mario; Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia; mjug@pharma.hr Bećirević-Laćan, Mira cyclodextrin; inclusion complex; drug delivery; aqueous solubility; chemical stability; bioavailability ciklodekstrin; inkluzijski kompleks; primjena lijeka; topljivost u vodi; kemijska stabilnost; bioraspoloživost Ciklodekstrini, ciklički oligosaharidi, predstavljaju skupinu farmaceutskih pomoćnih tvari koja je svojom multifunkcionalnošću privukla značajan interes. Temeljni razlog njihove popularnosti je u svojstvu ciklodekstrina da stvaranjem inkluzijskih kompleksa mijenjaju nepovoljne karakteristike lijekova, kao što je neugodan okus, niska topljivost u vodi i kemijska nestabilnost. Također, ciklodekstrini mogu povećati bioraspoloživost lijeka neovisno o putu primjene. Zahvaljujući biokompatibilnosti i netoksičnosti, ciklodekstrini se mogu koristiti u ljekovitim oblicima namijenjenim za različite putove primjene, uključujući oralni, okularni, nazalni te parenteralni put. Cilj ovog članka je istaknuti važnost i funkcionalnost ciklodekstrina u različitim ljekovitim pripravcima te naznačiti smjerove daljnjeg razvoja. Cyclodextrins, cyclic oligosacharides, are useful pharmaceutical excipients, which have attracted widespread attention. The ground for their popularity from a pharmaceutical point of view is in their ability to change undesirable characteristics of the drugs, such as unpleasant taste, low aqueous solubility, chemical instability and improving the drug bioavailability by inclusion complex formation. Due to their biocompatibility, cyclodextrins may be used in formulations indented for different routes of drug application including oral, ocular, nasal and even parenteral route. This article outlines the importance and functionality of cyclodextrin in different dosage forms and indicates the possible directions of future development. Croatian Academy of Sciences and Arts 2008-04-21 text pdf http://hrcak.srce.hr/22473 http://hrcak.srce.hr/file/35374 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.499=32; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:22474 2008-06-03 journal:117

Salomon Stricker (1834.-1898.): Pionir mikrobiologije Salomon Stricker (1834-1898): A Pioneer Micro-Biologist Holubar, Karl; Institute for the History of Medicine, Medical University of Vienna, Vienna, Austria; karl.holubar@meduniwien.ac.at Salomon Stricker (1834.-1898.); razvoj eksperimentalne medicine; Austrija/Beč, 19. stoljeće Salomon Stricker (1834-1898); development of experimental medicine; Austria/Vienna, 19th century U radu se iznose osnovni biografski podaci o austrijskom pioniru eksperimentalne medicine Salomonu Strickeru (1834.-1898.) te se podvlači poveznica njegova eksperimentalnog rada s važnim istraživačkim projektima tog vremena. Osvjetljen je utjecaj Strickera na Carla Heitzmanna (1836.-1896.) te na Carla Kollera (1857.-1944.) koji je uveo kokain u oftalmologiju. Strickerovom eksperimentalnom utjecaju pripisuje se Kollerov istražvački interes, što je do sada bilo nepoznato u objavljenoj literaturi. Stricker je istražujući ulogu kapilara staničnu diapedezu i diobu utro put kasnim istraživanjima na području fiziologije, imunologije i alergologije. The paper presents basic biographical data on the Austrian pioneer of experimental medicine Salomon Stricker (1834-1898), and emphasizes the link of his experimental work to important research projects of this time period. His influence on Carl Heitzmann and Carl Koller was pointed out. The work of both was connected directly with Sticker’s experimental designs, far less known in published literature. Demonstrating ad oculos the world of capillaries, diapedesis of blood cells, cell division in vivo by Stricker, paved the way for investigations in immunology and allergology. Croatian Academy of Sciences and Arts 2008-04-21 text pdf http://hrcak.srce.hr/22474 http://hrcak.srce.hr/file/35376 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.499=32; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:22475 2008-06-03 journal:117

Početak i razvoj alergologije u Hrvatskoj u razdoblju od 1870. do 1970. godine Beginnings and Development of Allergology in Croatia from 1870 to 1970 Fatović-Ferenčić, Stella; Department for the History and Philosophy of Sciences, Division for the History of Medicine, Croatian Academy of Arts and Sciences, Zagreb, Croatia; stella@hazu.hr Povijest medicine– Hrvatska; razvoj alergologije –Hrvatska; Liječnički vjesnik – alergija; 19. stoljeće; 20. stoljeće history of medicine – Croatia; development of allergology – Croatia; Liječnički vjesnik – allergy; 19th century; 20th century Razumijevanje podrijetla alergije kao imunološkog i eksperimentalnog fenomena, odvijalo se na području Hrvatske slično kao i u bliskim europskim zemljama. Najvažniji događaji i otkrića prikazani su u ovom radu za razdoblje 1870-1970.godine. Pokazalo se da su ključni momenti razvoja alergologije u nas, isprva bili vezani uz proizvodnju cjepiva te nastanak Imunološkog zavoda i njegovih preteča, tijekom prve polovice 20. stoljeća. Utemeljenje ovih ustanova predstavljalo je čvrstu institucijsku vertikalu presudnu za razvoj alergologije i imunologije u Hrvatskoj sve do danas. Raščlambom radova objavljenih na stranicama Liječničkog vjesnika za razdoblje 1877-1977. prezentirana je zastupljenost alergoloških tema te uloga pojedinih najznačajnijih ličnosti. Ovi radovi, međutim, ne daju potpunu sliku alergologije u Hrvatskoj osobito od 60. godina 20. stoljeća nadalje, kada naši autori veći dio svojih istraživanja objavljuju u međunarodnim časopisima. Istaknuta je uloga interniste Ivana Huga Botterija (1876- 1963), pedijatra Ernesta Mayerhofera (1977-1957) i dermatovenerologa Franje Kogoja (1894-1983), koji su svojim radom utrli put znanstvenoistraživačkom radu te uspješno poticali interes za ovo područje. Objedinjavanje interesa za alergologiju stručnjaka različitih medicinskih specijalnosti rezultiralo je osnutkom Alergološke sekcije Zbora liječnika Hrvatske 1952.godine. Ova je udruga odigrala daljnju važnu ulogu osobito u edukaciji šire akademske zajednice organizacijom simpozija, kongresa i seminara. Pokazalo se da je rad institucija i liječnika tijekom prve polovice 20. stoljeća, dao čvrst temelj suvremenim istraživanjima, oblikovanju subspecijalnosti te nastanku alergoloških centara i jedinica unutar različitih medicinskih institucija diljem Hrvatske. Development of allergy as an immunologic and experimental phenomenon in Croatia went similar as in surrounding neighboring countries. In the present article, I describe the most important events and discoveries that led to the understanding the origin of allergy in the 1870-1970 period. The crucial moments in the development of allergology in Croatia were first linked to the production of vaccines and foundation of the Institute of Immunology and its forerunners in the first half of the 20th century. Establishment of these institutions represented a strong institutional vertical that has played a key role in the development of allergology and immunology in Croatia. The analysis of articles published in Liječnički vjesnik in the 1877-1977 period showed the extent to which allergology was represented and the roles of the most important figures in the field of allergology, such as internist Ivan Hugo Botteri (1876-1963), pediatrician Ernest Mayerhofer (1877-1957), and dermatovenereologist Franjo Kogoj (1894-1983), who paved the way to the scientific research and roused the interest of physicians in this medical area. However, Liječnički vjesnik is not representative source for the development of allergolgy for the whole analyzed time period due to the fact that since 1960-ies large part of Croatian immunologists and allergologists started to publish the best part of their results within various international publications. Gathering of different medical specialists who were interested in allergology resulted in the establishment of Allergology Section of the Croatian Medical Association in 1952. The Section played an important role in the education of a wider academic community through symposia, congresses, and seminars. The analyzed records have shown that the institutional and physicians’ activities in the first half of the 20th century laid a firm foundation to modern research, subspecialties, and allergologic centers and units within different medical institutions across Croatia. Croatian Academy of Sciences and Arts 2008-04-21 text pdf http://hrcak.srce.hr/22475 http://hrcak.srce.hr/file/35378 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.499=32; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

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Akademik Franjo Kogoj i alergologija u Hrvatskoj Academician Franjo Kogoj and Allergology in Croatia Lipozenčić, Jasna; University Department of Dermatology and Venereology, Zagreb University Hospital Center and School of Medicine, Zagreb, Croatia; jasna.lipozencic@zg.htnet.hr Brnobić, Albin Akademik Franjo Kogoj i alergologija; Pruridermatitis allergica chronica constitutionalis; Tajnik Razreda medicinskih znanosti JAZU Academician Franjo Kogoj and allergology; Pruridermatitis allergica chro-nica constitutionalis; Secretary of Medical Science Section of Yugoslav Academy of Sciences and Arts Franjo Kogoj bio je redoviti član JAZU u Zagrebu (1947.), prvi tajnik Razreda za medicinske znanosti Jugoslavenske akademije znanosti i umjetnosti i njen u više mandata birani potpredsjednik (1958-1973), dugogodišnji predstojnik Dermatovenerološke klinike i Katedre, više puta dekan i prodekan Medicinskog fakulteta Sveučilišta u Zagrebu. Mnogobrojni se radovi akademika Kogoja odnose na alergijska zbivanja u organizmu i na njihovo značenje za morfologiju i tijek bolesti kao i na prognozu, profilaksu i liječenje.Tu pripadaju radovi o antikutinima i prokutinima, superponirane tuberkulinske reakcije, superponirane epikutane reakcije, superponirane tuberkulinsko-trihofitinake reakcije, eksperimentalna istraživanja alergijskih reakcija kod ekcema i pruridermatitisa, koji je naziv uveo u dermatološku terminologiju umjesto naziva neurodermitis odnosno endogeni ekcem, prurigo-astma, prurigo Besnier. U velikom broju radova obraduje problematiku alergije, donoseći pri tome uvijek nešto nova. Pitanje alergije predstavlja, njegovo najomiljenije područje. U tim radovima i nadalje obrađuje svoju omiljelu problematiku: medikamentozne egzanteme, medikamentozne dermatopatije, egzem, pruridermatitis (atopijski dermatitis), pruritus, superponirane trihofitinske reakoije, upliv serotonina na alergijske kožne testove, alergijska zbivanja na koži, tzv. kortikotropinsku terapiju u dermatologiji i ulogu histamina u ekcemskoj reakciji. Posebnu pažnju pobudila su njegova najnovija izlaganja u radu: “Ein Vierteljahrhundert Vasculitis” iznešena na “Deutsch-japanischer Angiologen Kongress” održanom u Essenu 1973.god. Njegovom je inicijativom osnovan 1965. godine Alergološki centar Jugoslavenske akademije znanosti i umjetnosti na Hvaru, koji je u početku bio smješten u prostorije adaptirane u tu svrhu, a 1973. premješten u suvremeno izgrađeni prostor za bolnički odjel, za ambulante, dijagnostičke laboratorije za biokemijske pretrage, ispitivanje plućne i funkcije, snimanje elektrokardiograma, zatim za radiološke preglede, fizioterapiju i biblioteku. Kogoj i A. Brnobić osnivači su Alergološke sekcije Zbora liječnika Hrvatske (1952). Osnivanjem Sekcije željeli su ujediniti rad medicinskih struka koje su težile poučavanju alergijskih zbivanja. Na Kogojevu inicijativu osnovan je 1965. godine Alergološki centar Jugoslavenske akademije znanosti i umjetnosti u Hvaru. U Centru se od 1973. godine mogao neometano odvijati i gotovo sav prijeko potreban rad s područja alergologije i kliničke imunologije. Kogoj je publicirao oko 230 znanstvenih i stručnih radova, od kojih oko 70 obrađuje alergologijsku i imunobiologijsku problematiku, 5 knjiga, nekoliko monografija, a dao je i posebno vrijedne priloge za priručnike te udžbenike. S njime je završila sjajna era povijesti Medicinskog fakulteta Sveučilišta u Zagrebu i HAZU. Franjo Kogoj was regular member of the Yugoslav Academy of Sciences and Arts (1947), first secretary and Vice-President elect for several terms of office of the Medical Science Section of the Yugoslav Academy of Sciences and Arts (1958-1973), long-standing head of University Department of Dermatology and Venereology, Zagreb University Hospital Center, and head of Department of Dermatology and Venereology, Zagreb University School of Medicine. Numerous papers by academician Kogoj address allergic events in the body and their role in the disease course and morphology, prognosis, prophylaxis and management. He wrote about experimental studies of allergic reactions in eczema and pruridermatitis, a term he introduced in dermatologic terminology to replace the terms neurodermatitis, endogenous eczema, prurigo-asthma and Besnier’s prurigo. He tackled the issues of allergy in many papers, always bringing something new in the field. The concepts elaborated in his paper entitled “Ein Vierteljahrhundert Vasculitis”, presented at the Deutsch-japanischer Angiologien Kongress held in Essen in 1973, were received with high interest. In 1965, the Center of Allergology of the Yugoslav Academy of Sciences and Arts on the island of Hvar was established on his initiative, first at premises adapted for this purpose, then moved to a modern building consisting of inpatient and outpatient departments, diagnostic laboratories of biochemistry, pulmonary function testing, electrocardiography, radiology, physiotherapy, and library in 1973. F. Kogoj and A. Brnobić were founders of the Section of Allergology of the Croatian Medical Association (1952), as an attempt at unifying the work of medical professions dealing with allergic diseases. Kogoj published about 230 scientific and professional papers, 70 of them addressing allergology and immunobiology issues; 5 books; several monographs; and valuable contributions in a number of handbooks and textbooks. Croatian Academy of Sciences and Arts 2008-04-21 text pdf http://hrcak.srce.hr/22476 http://hrcak.srce.hr/file/35380 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.499=32; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

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Suvremene spoznaje u imunologiji i njihova primjena u kliničkoj alergologiji Novel Concepts in Immunology and their Application in Clinical Allergology Gagro, Alenka; Institute of Immunology, Zagreb, Croatia; agagro@imz.hr imunologija; alergologija; in vitro immunology; allergology; in vitro U ovom revijskom prikazu namjera je prikazati neke nove spoznaje iz područja imunologije koja su pomogla razumijevanju patofizioloških mehanizama alergijskih bolesti. Prepoznavanjem složene naravi tih bolesti i uporabom životinjskih modela te suvremenih imunoloških metoda istraživanja in vitro nastoji se iste rabiti u rutinskom kliničkom radu u svrhu uspješnije prevencije, dijagnostike i liječenja alergijskih bolesti. The objective of this review is to present some novel concepts in the field of immunology that help us understand the pathophysiological mechanisms of allergic diseases. The recognition of their heterogeneous nature in combination with animal models and sophisticated in vitro immunologic methods should help us translate these findings to clinical practice in order to upgrade the prevention, diagnosis and treatment of allergic diseases. Croatian Academy of Sciences and Arts 2008-04-21 text pdf http://hrcak.srce.hr/22477 http://hrcak.srce.hr/file/35382 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.499=32; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

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Atopijski dermatitis Atopic Dermatitis Lipozenčić, Jasna; University Department of Dermatology and Venerology, Zagreb University Hospital Center and School of Medicine, Zagreb, Croatia; jasna.lipozencic@zg.htnet.hr Ljubojević, Suzana atopic eczema; neurodermatitis constitutionalis; prurigo Besnier; dermatitis atopica atopic eczema; neurodermatitis constitutionalis; Besnier’s prurigo; atopic dermatitis U radu se iznose različito nazivlje za atopijski dermatitis, definicija ove kronične upalne bolesti s nasljednom sklonošću koju obilježava izraziti svrbež, tipična klinička slika i često udruženost s drugim atopijskim bolesti kao što astma i/ili rinitis. Ova atopijska bolest je u stalnom porastu broja oboljelih i učestalost se kreće između 0,6 – 20.5%. Tijek bolesti je recidivirajući s različito dugim remisijama. U oko trećine bolesnika remisija je nakon 2. godine života, odnosno nakon 5. godine života. Oko 40% djece s atopijskim dermatitisom razvije kasnije u životu bronhijalnu astmu. Smatra se da je uzrok tomu izloženost peludima, manjim izvorima infekcija, kontaktu sa kućnim ljubimcima, starija životna dob majke i brojni alergeni u hrani. Detaljno se navode svi faktori okoliša kao i mikrobijelni uzroci (bakterije, gljive, Malassezia furfur, dermatofiti, virusi), psihosomatski faktori, klinička slika u različitim dobnim skupinama, te druge udružene dermatoze kao i dijagnostički i terapijski postupak. Variable terminology used for atopic dermatitis, definition of this chronic inflammatory disease with hereditary component characterized by severe itch, typical clinical picture, and quite common association with other atopic diseases such as asthma and/or rhinitis are presented. The prevalence of this atopic disease is on a constant increase, now ranging from 0.6% and 20.5%. The course of the disease is relapsing with remissions of variable length. Remission is observed after the second or fifth year of life in one third of patients. About 40% of children with atopic dermatitis develop bronchial asthma later in life. It is considered to be caused by exposure to pollen, minor sources of infection, pets, older maternal age and numerous food allergens. Environmental factors and microbial agents (bacteria, fungi, Malassezia furfur, dermatophytes, viruses, etc.), psychosomatic factors, clinical picture in different age groups, other associated dermatoses, diagnostic and therapeutic procedures are described in detail. Croatian Academy of Sciences and Arts 2008-04-21 text pdf http://hrcak.srce.hr/22478 http://hrcak.srce.hr/file/35384 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.499=32; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

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Povećana incidencija alergija u Hrvatskoj Increasing Incidence of Allergy in Croatia Stipić-Marković, Asja; Department of Clinical Immunology, Pulmology and Rheumatology, General Hospital «Sveti Duh», Zagreb, Croatia; astipicm@inet.hr Čvoriščec, Branimir Pevec, Branko Radulović-Pevec, Mira Prevalencija alergijskih bolesti; rinitis; astma; ekcem; markeri atopije; Dermatophagoides pteronyssinus Prevalence of allergic diseases; rhinitis; asthma; eczema; atopy markers; Dermatophagoides pteronyssinus Suvremena alergološka znanost i praksa u Republici Hrvatskoj nalazi se pred izazovima koje donosi civilizacijski i tehnološki razvoj a jedan od vidljivih znakova tih izazova je predstojeći ulazak države Hrvatske u zajednicu Europskih naroda. Zahvaljujući dugom, 55-godišnjem znanstvenom i stručnom radu alergologa iz svih specijalističkih područja medicine, hrvatska alergologija integrirat će se u Europu kao njen ravnopravni dio. Radna grupa za izradu plana i programa specijalizacije iz alergologije i kliničke imunologije izradila je prijedlog koji je u potpunosti usklađen sa preporukama Udruženja medicinskih specijalnosti Europe. Važnost suvremene kliničke alergologije u Hrvatskoj proizlazi iz zadataka koje joj nameće trend porasta prevalencije svih oblika bolesti preosjetljivosti. Prema rezultatima epidemioloških studija učinjenih po međunarodno dogovorenoj metodologiji prevalencija simptoma astme, alergijskog rinitisa i ekcema u populaciji školske djece kontinentalnog dijela zemlje iznosi redom 6%, 12.1% i 7.8%. Prevalencije u primorskoj Hrvatskoj dio iznose 8,4%, 17,5% i 3,4%, istim redom. Prevalencija pozitivnog kožnog testa u «kontinentalnoj» studiji je 52,3%. Zapažen je visoki postotak kožne reaktivnosti na tri i više alergena (51,74%). Dominantni alergeni su grinje kućne prašine a slijede ih alergeni trava, epitel mačke i psa, korov Ambrozije te poleni stabala. U populaciji odraslih, rezultati ispitivanja trenda prevalencije markera atopije u 15-godišnjem razdoblju ( 1985-1999), pokazuju uzlaznu krivulju razine IgE i simptoma alergijskih bolesti, za muškarce ali ne i za žene. Mjerenje koncentracije grinja u uzorcima prašine, dokazane i razlike u vrstama grinja, kontinentalnog i priobalnog područja, što upućuje na potrebu različitog odabira alergena za testiranje u pojedinim regijama. Specifično za našu alergologiju je, dokaz da se piroglifidne grinje mogu smatrati profesio-nalnim alergenom u ribara, a nepiroglifidne grinje, profesionalni rizični čimbenik u ruralnim područjima Hrvatske. Najčešči kontaktni alergeni našeg područja su nikal sulfat, kobalt klorid i mješavina mirisa, prema rezlutatima istraživanja provedenih na 3293 pacijenta Klinike za dermatovenerologiju Kliničkog bolničkog centra Zagreb. Allergology in Croatia is faced with technological and civilization challenges at the time of approaching full membership to European Union. Continuous, 55 year long tradition, of successful, scientific and clinic work, several generations of organ-based specialists in allergy, is the cornerstone for the constructive integration of Croatian allergology in the Europe. The incidence of allergy is increasing, according to the epidemiological data collected from 1978 till 2004 year. Current prevalence of children asthma, allergic rhinoconjunctivitis and eczema symptoms, in the continental region is 6 %, 12.1% and 7.8%, respectivelly. Children prevalence in the costal region of Croatia is 8.4% , 17.50% and 3.4%, at the same order. The incidence of positive skin test to inhalant allergens in children of the continental region is 52,34%. High percentage of 51.74% subjects has skin sensitivity to three or more allergens, 29.35% to one and 18.90% to two allergens. House dust mite is the most dominant allergen, equally to most of the European countries. Second rates of sensitization were observed for grasses, followed by dog and cat epithelium, Ambrosia and tree pollens. In Croatian adults, results of prevalence of atopy markers (IgE, skin test to aeroallergens and symptoms), collected for the period of 15-years ( 1985-1999 ), showed increasing trend in elevated total IgE and atopic symptoms in male, but not in the female population. In Croatian population of adult, allergic patients, pyroglyphid mites could be considered work-related allergens for fishermen. Non-pyroglyphid mites are occupational risk factors in various rural environments of Croatia. The most common and relevant contact allergens in Croatia, are nickel sulfate, cobalt chloride and carba mix, according to the results in 3293 patients from Clinic for Dermatovenerology, Clinical Hospital Centre, Zagreb. Croatian Academy of Sciences and Arts 2008-04-21 text pdf http://hrcak.srce.hr/22479 http://hrcak.srce.hr/file/35386 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.499=32; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

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Suvremena laboratorijska dijagnostika alergije Current Laboratory Diagnosis of Allergy Dodig, Slavica; Srebrnjak Children Hospital, Zagreb, Croatia; slavica@dodig.net alergija; IgE; bazofilni granulociti; leukotrijeni; imunoterapija allergy; IgE; basophils; leukotriene; immunotherapy Zahtjevi laboratorijske dijagnostike alergijskih bolesti odnose se na odabir analiza koje bi trebale: 1. odrediti vrstu alergijske reakcije otkrivanjem humoralnih (ukupni IgE) i staničnih (broj eozinofilnih odnosno bazofilnih granulocita, eozinofilni kationski protein); 2. otkriti pokretače alergijske reakcije (specifični IgE na pojedinačne uzročne alergene, testovi ex vivo aktivacije bazofilnih granulocita – leukotrijeni, CD63, histamin); 3. procijeniti klinički tijek reakcije (triptaza za ranu reakciju, eozinofilni kationski protein za kasnu reakciju); 4. omogućiti praćenje uspješnosti specifične imunoterapije (ukupni i specifični IgE, specifični IgG4 i IgG1, omjer IgG4/IgG1, proalergijski i proupalni citokini); 5. odrediti dijagnostičku djelotvornost određivanja pojedinih humoralnih ili staničnih posrednika alergijske reakcije (osjetljivost, specifičnost, pozitivna i negativna, predvidljiva vrijednost). Iako su laboratorijska istraživanja korisna u dijagnozi i liječenju alergijskih bolesti, brojni problemi još su neriješeni. Ti se problemi mogu svrstati u tri glavne kategorije: preanalitička (uzorkovanje), analitička i poslijeanalitička (tumačenje, praćenje, ponavljno testiranje) faza laboratorijskog određivanja. The requests for laboratory diagnosis of allergic diseases refer to a battery of tests that should provide the following: 1) determine the type of allergic reaction by detecting humoral (total IgE) and cellular (eosinophilic and basophilic granulocyte count, eosinophil cationic protein) mediators of allergic reaction; 2) identify triggers of allergic reaction (specific IgE to particular causative allergens, tests for basophilic granulocyte ex vivo activation, leukotrienes, CD63, histamine); 3) assess the clinical course of allergic reaction (tryptase for immediate reaction, eosinophil cationic protein for delayed reaction); 4) enable specific immunotherapy monitoring (total and specific IgE, specific IgG4 and IgG1, IgG4/IgG1 ratio, proallergic and proinflammatory cytokines); and 5) estimate diagnostic efficiency of determination of particular humoral or cellular mediators of allergic reaction (i.e., sensitivity, specificity, positive and negative predictive value). Althouh laboratory investigations are a useful tool in the diagnosis and management of allergic diseases many problems remain unsolved. Those problems can be grouped into three categories: preanalytical (specimen collection), analytical and post-analytical (interpretation, follow-up, retesting) phases of laboratory testing. Croatian Academy of Sciences and Arts 2008-04-21 text pdf http://hrcak.srce.hr/22480 http://hrcak.srce.hr/file/35388 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.499=32; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:22482 2008-06-03 journal:117

Looking at Eyes and Face. Ophthalmologic water-colours drawn largely by physician-artists Vienna, late 18th and 19th century / Karl Holubar, Stella Fatović-Ferenčić, Gerd Plewig. - . Vienna: Austrian Academy of Sciences, 2006. - 218 pages Dugac, Željko; Department for the History and Philosophy of Sciences, Division for the History of Medicine, Croatian Academy of Arts and Sciences, Zagreb, Croatia; dugac@hazu.hr Croatian Academy of Sciences and Arts 2008-04-21 text pdf http://hrcak.srce.hr/22482 http://hrcak.srce.hr/file/35390 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.499=32; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

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Editorial Pećina, Marko; Croatian Academy of Sciences and Arts, Zagreb, Croatia; marko.pecina@zg.t-com.hr Croatian Academy of Sciences and Arts 2009-10-20 text pdf http://hrcak.srce.hr/42376 http://hrcak.srce.hr/file/66330 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.504=33; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

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Medicina u eri decivilizacije Medicine in the era of decivilization Sartorius, Norman; sartorius@normansartorius.com medicina; globalizacija; decivilizacija; medicinska etika; strategija zdravstvene skrbi development of medicine; globalisation; decivilisation, technological revolution; health case U članku se govori o aktualnim trendovima u razvoju medicine. U prvom dijelu članka nabrojeni su i analizirani neki od najvažnijih društvenih trendova koji se odnose na medicinu. To su sljedeći procesi: decivilizacija (pad skrbi i pažnje što ih društvo pokazuje prema svojim ugroženim članovima), globalizacija, artiklizacija (tendencija da se zdravstvo, zdravstvena skrb i mnoge druge socijalne službe i usluge tretiraju poput robnih artikala kao što su šećer ili pamuk), decentralizacija socijalnih službi, promjene koje se tiču srednjeg društvenog sloja, tehnološka revolucija te posljedice migracija i populacijskih kretanja. U drugom dijelu članka riječ je o promjenama u medicini, promjenama unutar medicinske etike, izmijenjenim ciljevima zdravstvenih sustava, zastarjelim bitnim strategijama zdravstvene skrbi i promjenama unutar sustava zdravstvene skrbi. Ukratko se govori i o iscrpljivanju zdravstvenog osoblja te učinku uspostave novih vrijednosnih sustava pod utjecajem globalizacije. Na kraju članka ističe se potreba za preispitivanjem strategija zdravstvene skrbi uz uključivanje sviju angažiranih u području zdravstva: predstavnika obiteljskih i bolesničkih organizacija, ostalih vladinih sektora (npr. obrazovanje i rad), zdravstvene industrije i mnogih kategorija profesionalaca s područja medicine. Cilj je uskladiti te strategije s razvitkom društva u cjelini. This paper discusses the current trends in the development of medicine. In the first part of the article several of the major societal trends affecting medicine are enumerated and discussed. These include the processes of decivilisation (the decrease of care and attention that a society gives to its feeble members), globalisation, commoditification (the tendency to consider health and health care as well as many other social concerns as commodities such as sugar or cotton), decentralisation of social services, the changes of the middle class, the technological revolution and the consequences of migration and population movements. The second part of the article deals with the changes of medicine and of medical ethics, with changing goals of health systems, with the obsolescence of important health care strategies and with changes of the systems of medical care. Burn-out of health care personnel and the impact of the imposition of novel value systems by globalization are also briefly discussed. The paper ends underlining the need for a re-examination of the health care strategies, involving all the stakeholders in the field of health – representatives of family and patient organizations, governmental sectors other than health (e.g. education and labour) the health industry and the many categories of health professionals – in order to bring these strategies in harmony with the development of society as a whole. Croatian Academy of Sciences and Arts 2009-10-20 text pdf http://hrcak.srce.hr/42377 http://hrcak.srce.hr/file/66332 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.504=33; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

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Scientific approach to pain Demarin, Vida Croatian Academy of Sciences and Arts 2009-10-20 text pdf http://hrcak.srce.hr/42378 http://hrcak.srce.hr/file/66333 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.504=33; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

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Migrena – patofiziologija boli Migraine – pathophysiology of pain Vuković, Vlasta; Department of neurology, University hospital Sestre milosrdnice, Zagreb, Croatia; vlasta.vukovic@uclmail.net Strineka, Maja Lovrenčić-Huzjan, Arijana Demarin, Vida migrena; patofiziologija; bol migraine; pathophysiology; pain Migrena je primarna glavobolja epizodnog karaktera karakterizirana nizom događaja koji uključuju kombinacije neuroloških, gastrointestinalnih i autonomnih promjena. Glavobolja je vjerojatno uzrokovana aktivacijom nociceptora u meningama i u stjenci krvnih žila, u kombinaciji s poremećajem u centralnoj modulaciji boli. Glavobolja i pridružene neurovaskularne promjene povezane su s trigeminalnim sustavom. Postoji također veza između migrenske aure i glavobolje. Kortikalna šireća depresija aktivira trigeminovaskularna aferentna vlakna, uslijed čega dolazi do dugotrajnog porasta protoka u srednjoj meningealnoj arteriji kao i u otpuštanju polipeptida unutar dure. Uslijed interakcije neuropeptida i stijenke krvne žile dolazi do dilatacije, ekstravazacije proteina plazme te aktivacije trombocita. Upala senzitizira živčana vlakna (periferna senzitizacija) te oni sad reagiraju na prethodno bezazlen podražaj, npr. pulzacije krvne žile, uzrokujući, barem djelomično, migrensku bol. Migraine is a primary episodic headache disorder characterized by a cascade of events that involve various combinations of neurologic, gastrointestinal and autonomic changes. Headache is probably caused by activation of meningeal and blood vessel nociceptors combined with an alteration in central pain modulation. Headache and its associated neuro-vascular changes are subserved by the trigeminal system. A link also exists between the migraine aura and headache. Cortical spreading depression (CSD) activates trigeminovascular afferents, causing a long-lasting increase in middle meningeal arterial blood flow and polypeptide release within the dura mater. The neuropeptides interact with the blood vessel wall, producing dilatation, plasma protein extravasation, and platelet activation. Neurogenic inflammation sensitizes nerve fibers (peripheral sensitization) that now respond to previously innocuous st imuli, such as blood vessel pulsations, causing, in part, the pain of migraine. Croatian Academy of Sciences and Arts 2009-10-20 text pdf http://hrcak.srce.hr/42379 http://hrcak.srce.hr/file/66335 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.504=33; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

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Znanstveni pristup migreni Scientific approach to migraine Demarin, Vida; Department of neurology, University hospital Sestre milosrdnice, Zagreb, Croatia; vida.demarin@zg.t-com.hr Vuković, Vlasta; Department of neurology, University hospital Sestre milosrdnice, Zagreb, Croatia Ivanković, Mira; General Hospital Dubrovnik, Dubrovnik, Croatia migrena; patofiziologija; dijagnoza; terapija migraine; pathophysiology; diagnosis; therapy Migrena je česta glavobolja čija se prevalencija kreće u zapadnim zemljama između 10- 12%. Mehanizam boli kod migrene nije sasvim razjašnjen. Po teoriji neurogene upale glavno zbivanje je upala stijenki krvnih žila koja dovodi do istjecanja nociceptivnih supstanci što uzrokuje zadebljanje zida arterija te dilataciju glatkih mišićnih stanica. Otpuštanje vazoaktivnih neuropeptida uzrokuje depolarizaciju trigeminalnih aksona što dovodi do pojave boli. Triptani se preporučaju u akutnim napadajima migrene; istraživanja su pokazala da se njihovom upotrebom u akutnom napadaju migrene povećava produktivnost na poslu i poboljšava kvaliteta života. Preventivna terapija se preporuča kod osoba s učestalim jakim i dugotrajnim napadajima, te u slučajevima kada akutna terapija nije učinkovita, ukoliko postoji kontraindikacija ili su izražene nuspojave za primjenu akutne terapije, te u slučajevima kada se radi o obiteljskoj hemiplegijskoj migreni. U preventivnoj terapiji preporučaju se beta blokatori i triciklički antidepresivi a od ostalih lijekova se preporučaju pizotifen, flunarizin te antiepileptici. Migrena je često udružena s komorbidnim bolestima poput alergija, hipotenzije, epilepsija, sindromom kroničnog umora, iritabilnim kolonom, gastritisom i vertigom; stoga se akutna i profilaktička terapija moraju individualno određivati. Migraine is a common episodic headache disorder; prevalence of migraine in most western countries is 10-12%. The mechanism of migraine pain development is not fully understood. The theory of neurogenic inflammation proposes that the main event is the inflammation in the vessel wall which leads to leakage of nociceptive substances, causing thickening of the vessel wall and dilatation of vascular smooth muscles. The release of vasoactive neuropeptides causes depolarization of trigeminal perivascular axons, thus causing pain. Triptans are recommended for acute migraine attacks; studies have shown that their use increases productivity at work and improves the quality of life. Preventive therapy is recommended in migraine patients with frequent, severe, long-lasting attacks, in cases where acute therapy is not efficient, if there is a contraindication to the drug, failure or unbearable side-effects from acute treatments, overuse of acute medications or in special cases such as hemiplegic migraine. Beta-blockers and tricyclic antidepressants were often used as first line therapy for migraine prevention. Other p reventive drugs include pizotifen, flunarizine, and anticonvulsives. Migraine is often associated with a number of commorbid diseases: allergies, hypotension, epilepsy, fatigue sy, gastritis, iritabile colon disease, vertigo; therefore, preventive and acute therapy should be tailored individually. Croatian Academy of Sciences and Arts 2009-10-20 text pdf http://hrcak.srce.hr/42380 http://hrcak.srce.hr/file/66337 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.504=33; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:42381 2009-11-02 journal:117

Temporomandibularni poremećaji i orofacijalna bol Temporomandibular disorders and orofacial pain Jerolimov, Vjekoslav; Department of prosthodontics, School of dental medicine, University of Zagreb, Zagreb, Croatia; vjekoslav.jerolimov@sfzg.hr žvačni sustav; temporomandibularni poremećaji; orofacijalana bol; terminologija; epidemiologija; etiologija; simptomatologija; dijagnostika; liječenje masticatory system; temporomandibular disorders; orofacial pain; terminology; epidemiology; etiology; symptomatology; diagnostics; treatment Temporomandibularni poremećaji (TMP) skupni je naziv za niz patoloških stanja žvačnog sustava. Šarolike su simptomatologije, a orofacijalna bol jedan je od najčešćih simptoma, te bolesnicima svakako najneugodniji. TMP su često vrlo jasne etiologije, no ponekad posve nepoznate. Povezani su s raznovrsnim etiološkim čimbenicima i komorbidnim stanjima, što otežava preciznu dijagnostiku. Ova patologija zahtijeva timski rad i multidisciplinarni pristup, pravodobno prepoznavanje uzroka i pažljiv odabir terapijskih postupaka, pogotovo pri obradi orofacijalne boli, koja diferencijalno-dijagnostički može biti vrlo zahtjevna. Još uvijek ima nepoznanica, stoga i prostora za znatna poboljšanja u pristupu ovoj problematici. Postojeću dijagnostičku klasifikaciju treba izmijeniti i prvenstveno temeljiti na etiologiji, a ne na simptomatologiji, što je danas slučaj. Također treba izraditi jedinstvene dijagnostičke smjernice i terapijske protokole, što bi unaprijedilo multidisciplinarnu suradnju, neophodnu u obradi ove vrste patologije. Posebnu brigu valja posvetiti razvoju preventivnih mjera, zasnovanih na znanstvenim dokazima, a one su još uvijek zapostavljene. Temporomandibular disorders (TMDs) is a collective term for a number of pathologic conditions of the masticatory system. Their symptomatology is diverse, with orofacial pain being one of the most common symptoms which causes a particular discomfort to the patients. Often, TMDs have a very clear etiology, but sometimes it is completely unknown. They are related to different etiologic factors and comorbid conditions, which aggravates precise diagnostics. This pathology requires team work and a multidisciplinary approach, timely detection of causes and a meticulous selection of treatment procedures, particularly for management of orofacial pain, which can be very demanding in terms of differential diagnostics. There are certain facts which are still unclear; hence notable improvements in approaching this issue are expected. The existing diagnostic classification should be changed and primarily based on etiology instead of symptomatology, which is the current tendency. Also, uniform diagnostic guidelines as well as treatment protocols should be established and that would enhance a multidisciplinary collaboration, which is essential while dealing with this kind of pathology. Special attention should be paid to the development of preventive measures based on scientific evidence that is still neglected. Croatian Academy of Sciences and Arts 2009-10-20 text pdf http://hrcak.srce.hr/42381 http://hrcak.srce.hr/file/66339 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.504=33; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:42382 2009-11-02 journal:117

Centralna bol: Mehanizmi, semiologija i terapija Central pain: mechanisms, semiology and treatment Lušić, Ivo; University department of neurology, University hospital centre Split, Split, Croatia; ivo.lusic@st.t-com. hr centralna bol; etiologija; liječenje central pain; etiology; treatement Bol koja je posljedica oštećenja ili poremećaja funkcije centralnog živčanog sustava čest je problem u svakodnevnoj praksi. Cilj ovog istraživanja bio je prikupiti rezultate dosadašnjih studija vezane uz ovu tematiku te prikazati etiologiju, patogenezu, kliničku prezentaciju i mogućnosti liječenja centralne boli. Osobita pažnja posvećena je moždanom udaru kao uzroku centralne boli. Općenito, etiologija i patofiziologija centralne boli slabo je istražena, a liječenje je dugotrajno i najčeće slabih rezultata. U najvećem broju slučajeva, centralnu bol nije moguće u potpunosti izliječiti, može se samo djelomično ublažiti. Od metoda liječenja najčešće se koriste antidepresivi, antiepileptici te stimulacija motoričkog korteksa. Kirurške metode liječenja se rijetko koriste jer nisu dugotrajne, njima se centralna bol može samo nakratko ukloniti. Za sada ne postoje jasne kliničke smjernice za liječenje centralne boli, postoje samo sporadične studije o liječenju iste što je vjerojatno posljedica nedovoljnog poznavanja etiologije i patogeneze centralne boli te je u tu svrhu potrebno planirati daljnja istraživanja. Pain problems associated with lesion, disorder or dysfunction of the central nervous system are a common and prominent problem. The objective of this review is to summarize recent advances in our understanding of the etiology, clinical presentation, and treatment of central pain (CP), with emphasis being placed on studies published within the recent years. The incidence, qualities of the pain experience, associated sensory abnormalities, and other characteristics are discussed. Particular attention is paid to CP associated with stroke as the most prominent and best studied of the many CP problems. In general, there is poor understanding of the pathophysiology of CP, problems are often severe and intractable, and treatment is typically difficult. The goal of treatment should be pain reduction rather than complete pain relief. Recent studies have indicated possible roles for tricyclic antidepressants, antiseizure medications, and motor cortex stimulation in the treatment of CP. Surgical procedures have been used for specific causes of CP, but no one surgical technique helps relieve pain over the long term in all CP patients. Perhaps because of the lack of clinical trials, treatment is still largely based on traditional prescribing methods and anecdotal evidence. Our poor understanding of the etiology of central pain and the relative lack of effective treatments emphasize the need for further research into this disorder. Croatian Academy of Sciences and Arts 2009-10-20 text pdf http://hrcak.srce.hr/42382 http://hrcak.srce.hr/file/66341 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.504=33; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:42383 2009-11-02 journal:117

Neuropatska bol Neuropathic pain Bašić Kes, Vanja; Department od neurology, University hospital, Sestre milosrdnice, Zagreb, Croatia Ivanković, Mira; Department of neurology, General hospital, Dubrovnik, Croatia Bitunjac, Milan; Department of neurology, General hospital, Slavonski Brod, Croatia Govori, Valbona; Department of neurology, University Clinical Centar, Pristhina, Kosovo Demarin, Vida; Department od neurology, University hospital, Sestre milosrdnice, Zagreb, Croatia neuropatska bol; etiologija; liječnje neuropathic pain; etiology; treatement Neuropatska bol nastaje kao posljedica disfunkcije perifernog ili centralnog živčanog sustava. Najčešći uzroci neuropatske boli su diabetes melitus, reaktivacija herpes zoster infekcije, kompresija živaca ili radikulopatija, pretjerana konzumacija alkohola, kemoterapija ili zlouporaba lijekova te neuralgija trigeminusa. Specifični simptomi neuropatske boli su mehanička alodinija i hladna hiperalgezija. U liječenju neuropatske boli koristi se nekoliko skupina lijekova. U prvu skupinu spadaju adjuvantni lijekovi, a to su antidepresivi i antiepileptici, opioidi i topički agensi. U praksi se najčešće koristi kombinacija dvije ili više vrsta lijekova. Unatoč brojnim randomiziranim, placebo-kontroliranim studijama na području neuropatske boli, medikamentozno liječenje neuropatske boli još uvijek nije zadovoljavajuće, te se samo u 50% pacijenata sa neuropatskom boli postiže zadovoljavajuća analgezija. Neuropathic pain refers to pain that orginates from pathology of the nervous system. Common causes of neuropathic pain are diabetes mellitus, reactivation of herpes zoster, nerve compression or radiculopathy, alcohol, chemotherapy or abuse of some drugs and trigeminal neuralgia. Specific symptoms of neuropathic pain are mechanical allodynia and cold hyperlgesia. Drugs to treat neuropathic pain can be divided into adjuvent analgesics (antidepressants and anticonvulsants), opioids and topical agents. The use of multiple drug therapies is common in practice. Despite considerable increase in the number of randomized placebo-controlled trials in neuropathic pain over the last few years, the medical treatment of neuropathic pain is still far from being satisfactory, with kless than half of patients achieving signifi- cant benefit with any pharmacological drug. Croatian Academy of Sciences and Arts 2009-10-20 text pdf http://hrcak.srce.hr/42383 http://hrcak.srce.hr/file/66343 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.504=33; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:42385 2009-11-02 journal:117

Bolna dijabetička polineuropatija Painful diabetic polyneuropathy Jurjević, Ante; Department of neurology, Clinical hospital center Rijeka, Rijeka, Croatia; ante.jurjevic@ri.t-com. hr dijabetička polineuropatija; liječenje diabetic polyneuropathy; treatement Dijabetička polineuropatija kao jedna od komplikacija dijabetesa melitusa klinički se manifestra kao simetrično oštećenje strukture i funkcije perifernih živaca. Stupanj oštećenja i klinička slika ovise o trajanju dijabetesa, terapiji koju bolesnici uzimaju te vrijednostima glukoze u krvi. Distalna simterična polineuropatija kao najčešća komplikacija dijabetesa klinički se prezentira senzornim simptomima, parestezijama i bolovima u prstima ruku i nogu. Izolirane forme disalne dijabetičke polineuropatije mogu biti i asimterične (fokalne i multifokalne) i autoimune forme. Diabetic polyneuropathy represents mostly symmetrical damage of the peripheral nerves associated with diabetes mellitus. Clinical picture depends on the duration of diabetes, glucose blood level and insulin use. Distal symmetric polyneuropathy is the most common neuropathy of diabetes. It presents with sensory symptoms, paresthesiae and fingers pain in the hands and legs. Isolated forms of DPN are asymmetrical (focal or multifocal) and autoimmune form. Croatian Academy of Sciences and Arts 2009-10-20 text pdf http://hrcak.srce.hr/42385 http://hrcak.srce.hr/file/66347 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.504=33; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:42386 2009-11-02 journal:117

Bol u multiploj sklerozi Pain in multiple sclerosis Bašić Kes, Vanja; Department od neurology, University hospital Sestre milosrdnice, Zagreb, Croatia; vanjakes@net. hr Ivanković, Mira; Department of neurology, General hospital, Dubrovnik, Croatia Bitunjac, Milan; Department of neurology, General hospital, Slavonski Brod, Croatia Govori, Valbona; Department of neurology, University clinical centar, Pristhina, Kosovo Zavoreo, Iris; Department od neurology, University hospital Sestre milosrdnice, Zagreb, Croatia Demarin, Vida; Department od neurology, University hospital Sestre milosrdnice, Zagreb, Croatia multipla skleroza; kronični bolni sindrom multiple sclerosis; chronic pain symptoms Multipla skleroza je kronična, demijelinizirajuća bolest koja se najčešće javlja u osoba mlađe životne dobi. Smatra se da je pojava multiple skleroze rezultat međudjelovanja genetskih i čimbenika okoliša. Dugo se smatralo da multipla skleroza nije povezana s pojavom boli, iako su rezultati istraživanja pokazali da neuropatska bol, poput neuralgije trigeminusa može biti jedan od prvih simptoma bolesti. Cilj ovog istraživanja bio je utvrditi prevalenciju i periodu bolnih stanja u bolesnika oboljelih od MS-a, a koji su bili liječeni na Klinici za neurologiju, KB «Sestre milosrdnice». U vremenskom periodu od tri godine obuhvatili smo 290 bolesnika. Od akutnog ili kroničnog bolnog sindroma patilo je 70% pacijenata. Dvanaest pacijenata (2.7%) s akutnim bolnim stanjem imalo je paroksizmalne bolne atake u području trigeminalnog živca. Kronični bolni sindrom dijagnosticiran je u 58% bolesnika i uključivao je razne oblike glavobolje (20%), bol lumbosakralnom dijelu kralježnice (20%) te bolne spazme u 4% bolesnika. Bolesnici su liječni nesteroidnim antireumaticima u slučaju nociceptivne boli. Neuropatska bol je liječena adjuvantnim lijekovima, najčešće kombinacijom antiepileptika i antidepresiva. Na temelju rezultata ove retrospektivne studije vidljivo je da su akutni i kronični bolni sindromi prisutni u velikom broju bolesnika oboljelih od MS-e te da terapija svakog bolesnika mora biti individualizirana. Multiple sclerosis (MS) is a disease of the central nervous system (CNS), beginning most often in late adolescence and early adult life and expressing itself by reccurrent attacks of spinal cord, brainstem, cerebellar, optic nerve and cerebral dysfunction, the result of foci of destrucion of myelinated fibers. Neuropathic pain, such as trigeminal neuralgia might be one of the first symptoms of multiple sclerosis. In this retrospective study we evaluated 290 patients who have been hospitalised at Department of neurology in last three years. According to the results of our study 70% had either an acute or chronic pain syndrome at some time during their disease. Between them 2.7% with acute pain syndroms had episodes of paroxismal pain attacks in distribution of trigeminal nerve. Chronic pain syndromes, occured in 58% of patients and included headache (25%), low back pain (35%) and painful leg spasms in 20% of patients. Our patients were treated with nesteroid antireumatic drugs in case of nociceptive pain, but neuropathic pain was treated with combination of antidepressive and antiepileptic drugs. Croatian Academy of Sciences and Arts 2009-10-20 text pdf http://hrcak.srce.hr/42386 http://hrcak.srce.hr/file/66349 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.504=33; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:42387 2009-11-02 journal:117

Perkutana laser dekompresija – naša iskustva s upotrebom diodnog lasera Percutaneous laser disk decompression – our experience with the usage of the diode laser Rotim, Krešimir; Department of neurosurgery, University hospital Sestre milosrdnice, Zagreb, Croatia; robert.saftic@gmail.com Saftić, Robert; Department of neurosurgery, University hospital Sestre milosrdnice, Zagreb, Croatia Lakičević, Goran; Department of neurosurgery, University hospital Sestre milosrdnice, Zagreb, Croatia dekompresija diska; perkutani laser; diodni laser; bolest intervertebralnog diska; sindrom bolnih križa; hernijacija diska; protruzija diska; radikulitis; ispupčenje intervertebralnog diska disk decompression; percutaneous; laser; diode laser; intervertebral disc disease; chronic low back pain; disc herniation; disc protrusion; radiculitis; contained disc herniation PLDD (Perkutana laser disk dekompresija) siguran je, nedestruktivan i uspješan kirurški zahvat kod lumbalne diskus hernije. Cilj ove studije je bio evaluacija prednosti procedure perkutane laser disk dekompresije u tretmanu lumbalne diskus hernije naspram otvorenih operacijskih metoda slabinske diskus hernije tipa mikrodiskektomije. Od lipnja 2008.god do srpnja 2009 god. u Kliničkoj bolnici Sestara milosrdnica, 91 bolesnik je tretiran uz pomoć perkutane laser disk dekompresije i 125 bolesnika tretiranih uz pomoć mikrodiskektomije. Perkutana laser disk dekompresije sec.Choy je rađena uz uporabu diodnog lasera (LASE maR 1000) jačine 1000 j, snage 12 W i valne duljine 980 nm. Kriterij uključivanja u istraživanje bio je odrasla životna dob ispitanika i uznapredovala hernijacija intervertebralne ploče slabinske kralježnice, koja je zahtijevala kirurško liječenje. Analizirani izlazni parametri bili su: uspješnost operacijskoga liječenja; recidivirajuće slabinskie diskus hernije; poslijeoperacijske komplikacije; dužina poslijeoperacijskoga boravka u bolnici; vrijeme potrebito za povratak svakodnevnim aktivnostima. Podatke dobivene analizom ulaznih i izlaznih parametara smo uspoređivali uz pomoć Macnab kriterija. Usporedbom podataka za dob, spol, razinu hernijacije intervertebralne ploče u obje skupine bolesnika nisu nađeni statistički značajni rezultati. Ovo je retrospektivno istraživanje u trajanju od 12 mjeseci. Bolesnici kojim je urađena perkutana laser disk dekompresija su u 89,6% imali dobre ili odlične rezultate i bili su zadovoljni uspjehom liječenja. U skupini bolesnika tretiranih uz pomoć mikrodiskektomije broj bolesnika koji su imali dobre ili odlične rezultate nakon operacijskog zahvata i bili zadovoljni uspjehom istog je manji i iznosi 81,2%. Poslijeoperacijske komplikacije su se pojavile kod 2,5% boelsnika operiranih perkutanom laser disk dekompresijom. Od toga je jedan bolesnik ponovno operiran perkutanom laser disk dekompresijom a drugi uz pomoć METRx interlaminektomije. Broj bolesnika sa komplikacijama kod kojih je rađena mikrodiskektomija je znatno veći i iznosi 6,5%. Kako je istraživanje odmicalo učestalost se perkutane lumbalne dekompresije diska povećavala, tako da je ova operacijska metoda bile najzastupljenija u zadnjim mjesecima istraživanja, dok se učestalost mikrodiskektomije postupno smanjivala. Rezultati provedenoga istraživanja afirmirali su komparativne prednosti suvremenih operacijskih metoda liječenja slabinske diskus hernije u odnosu na klasične metode liječenja. Introduction: PLDD (Percutaneous laser disk decompression) is a safe, non-destructive and successful surgical treatment for lumbar disk herniation. The purpose of this study was the evaluation of advantages in the procedure of percutaneous laser disk decompression in the treatment of lumbar disk herniation in comparison to open surgical methods on lumbar disk herniation like microdisectomy. Patients: From June 2008 till July 2009 in the Clinical hospital “Sister of Mercy” Zagreb 91 patients have been treated with percutaneous laser disk decompression and 125 patients have been treated with microdisectomy. Methods: The percutaneous laser disk decompression is done with the usage of a diode laser (LASE maR 1000), intensity of 1000 j, power 12 W and wave length 980 nm. Open surgical methods for lumbar disk herniation are performed with the surgical technique microdisectomy. The input criterion for the research was the adulthood of the examinee and advanced herniation of the intervertebral disk in the lumbar spine, which needed surgical treatment. The analysed parameters were: success of the surgical treatment; relapsing lumbar disk herniations; postsurgical complications; postsurgical stay in the hospital; time needed to return to every-day activities. The data achieved with the analyses of input and output parameters have been compared with the help of the MacNab criteria. There have not been found any statistically significant results in the comparison of data for age, sex and the stage of intervertebral disk herniation in both groups. This is a retrospective research and lasted 12 months. Results: Patients treated with the percutaneous laser disk decompression had in 89,6 % (n=81) very good or excellent results and were satisfied with the success of the treatment. In the group of patients treated with microdisectomy the number of patients, which had very good or excellent results, is minor and numbers 81,2% (n=101). Postsurgical complications appeared in 2,5% (n=2) in the group of patiens operated with percutaneous laser disk decompression. One patient had another percutaneous laser disk decompression and another patient had a MET-Rx interlaminectomy. In the group of patients treated with microdisectomy, the number of patients, where complications appeared, is higher and numbers 6,5% (n=8). As the research moved on the frequency of percutaneous lumbar disk decompression increased, so that this surgical method has been the most present in the last months of the research, while the presence of the microdisectomy was gradually decreasing. Conclusion: The results of the conducted research have afirmated the comparative advantages of contemporary surgical methods in treating lumbar disk herniation in reference to classical treating methods. Croatian Academy of Sciences and Arts 2009-10-20 text pdf http://hrcak.srce.hr/42387 http://hrcak.srce.hr/file/66351 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.504=33; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:42388 2009-11-02 journal:117

Antinociceptivni učinak botulinum toksina TIP-A u terapiji boli i glavobolje Antinociceptive effects of botulinum toxin type-A in pain and headaches treatment Relja, Maja; Department of neurology, Medical school University of Zagreb, Zagreb, Croatia botulinum toksin; distonija; bol; tenzijska glavobolja; migrena botulinum toxin; dystonia; pain; tension type headache; migraine Nakon razvoja botulinum toksina za kliničku primjenu 80-tih godina, ovaj za čovjeka najpotentniji biološki otrov našao je primjenu u raznim granama medicine. Prva upotreba botulinum toksina bila je u neurološkim poremećajima karakteriziranim mišićnim spazmom i nekontroliranim kontrakcijama poput distonije. Zapaženi učinak na smanjenje boli prije pojave mišićne relaksacije ukazao je na direktni analgetski učinak botulinum toksina na patogenezu boli. Javljaju se zatim brojna klinička zapažanja o učinkovitosti botulinum toksina u liječenju glavobolje i kronične boli. Većina poznatih učinaka botulinum toksina na relaksaciju mišića pripisuje se učinku na otpuštanje acetilkolina na neuromuskularnoj sinapsi. Kako se ovim djelovanjem ne može objasniti njegov antinociceptivni učinak brojni periferni i centralni mehanizmi djelovanja botulinum toksina se istražuju. Sadašnji rezultati kliničke primjene ukazuju da je botulinum toksin siguran i djelotvoran lijek u liječenju glavobolje i nekih oblika kronične boli otpornih na standardne oblike liječenja, ukoliko se primjenjuje u specijaliziranom centru od strane iskusnih liječnika. Since its development for clinical use in 1980s botulinum toxin, the most potent biological toxin known to man has become a useful drug in various field of medicine. It was initially used to treat neurological disorders characterized by excessive muscle contractions. Since many patients report alleviation of pain before the muscle relaxing effect of botulinum toxin type-A has started, a direct analgesic action of Botulinum toxin has been discussed. There have been a number of recent investigations concerning the efficacy of botulinum toxin type-A applications for treatment of headache and chronic pain. Most of the known effect of botulinum toxin has been attributed to its ability to inhibit the release of acetylcholine from cholinergic nerve terminal. However, this effect alone does not explain the apparent antinociceptive effect of botulinum toxin. Other peripheral and central neurogenic effect should be considered. Current data suggest that Botulinum toxin is safe and effective in headache and pain treatment if used in specialist centres by experienced doctors. Croatian Academy of Sciences and Arts 2009-10-20 text pdf http://hrcak.srce.hr/42388 http://hrcak.srce.hr/file/66353 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.504=33; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:42389 2009-11-02 journal:117

Psihološki i psihijatrijski čimbenici kronične boli Psychological and psychiatric factors of chronic pain Buljan, Danijel; Department of psychiatry, University hospital Sestre milosrdnice, Zagreb, Croatia; dbuljan@kbsm. hr bolni poremećaj; “nespecifična bol”; “specifična bol”; psihalgija; idiopatska; psihoterapija; psihofarmakoterapija pain disorder; “nonspecific pain”; “specific pain”; psychalgia; idiopathic; psychotherapy; psychopharmacotherapy Kronični bolni sindrom je veliki zdravstveni i socioekonomski problem koji se očituje čestim traženjem liječničke pomoći, visokom cijenom zdravstvene skrbi, bolovanjem, radnom nesposobnošću i invaliditetom te čestim odštetnim zahtjevima. Bol općenito, a poglavito kronična bol značajno smanjuje kvalitetu života bolesnika i njegove obitelji. Većina ljudi iskusi jedan ili više bolnih poremećaja tijekom svog života. Prevalencija kronične boli u pučanstvu je 15 do 22%. Puno češće se javlja u žena, u starijoj dobi i u osoba slabijeg socioekonomskog statusa. Kronična bol se uzročno-posljedično povezuje sa komorbidnim psihijatrijskim poremećajima kao što su strah od tjelesne bolesti, stalna zabrinutost, anksiozni poremećaji, depresija, reakcija na stres. Svaka bol, a pogotovo kronična bol ima više ili manje izražene i psihološke osobine. Kada je poznat pato-fiziološki uzročni čimbenik bol se konvencionalno klasificira kao «specifična», a kada nije poznat patofiziološki uzročni čimbenik kao «nespecifična», psihogena, idiopatska, konverzivna ili eufemistički atipična bol. Nespecifična bol često je simptom nekog psihijatrijskog poremećaja ili se svrstava u skupinu somatoformnih psihijatrijskih poremećaja prema suvremenim klasifikacijskim sustavima kao što su Dijagnostički i statistički priručnik (DSM-IV) Američkog psihijatrijskog društva i Međunarodna klasifikacija bolesti i srodnih zdravstvenih problema MKB- 10. Psihosomatska medicina bavi se proučavanjem povezanosti psiholoških stanja i psihičkih poremećaja, psihosocijalnog stresa, obiteljskih i radno-okupacionih čimbenika sa somatskim poremećajima. Ponekad se bol javlja kao simptom hipohondrije, depresije ili psihotičnog poremećaja. S druge strane bolna somatska bolest može prouzročiti anksioznost, depresivnost, socijalnu fobiju i izoliranost. Liječenje nespecifičnog, psihogenog bolnog poremećaja nije moguće bez holističkog, integrativnog, interdisciplinarnog, timskog pristupa psihijatra, psihologa, fizijatra, neurologa, a ponekad i neurokirurga. Prevladava kognitivno-bihevioralna psihoterapija, tehnike ublažavanja anksioznosti i stresa (autogeni trening), fizikalna terapija, EMG biofidbek metode i psihofarmakoterapija. Chronic pain syndrome is a major health and socioeconomic problem that is manifested by frequent asking of medical assistance, high price of health care, sick leave, work inability and disability as well as frequent compensation requests. Generally speaking, pain, especially chronic pain, significantly diminishes the patient and their family’s quality of life. Most people experience one or more pain disorders during their life. Chronic pain prevalence accounts for 15 to 22% in population. It occurs more frequently in women, in older age and persons of decreased socioeconomic status. Chronic pain can be causally linked to comorbid psychiatric disorders, such as fear of physical illness, constant worry, anxious disorders, depression and reaction to stress. Every pain, especially chronic, has psychological characteristics as well which are expressed to an extent. When the pathophysiologic factor is known, the pain is conventionally classified as “specific” and when it is unknown it is called “nonspecific”, psychogenic, idiopathic, conversive or euphemistic atypical pain. Nonspecific pain is very often a symptom of a psychiatric disorder or it is classified in the group of somatoform psychiatric disorders according to contemporary classification systems, e.g. the American Psychiatric Association’s DSM-IV and the International Classification of Diseases (ICD-10). Psychosomatic medicine studies the connection of psychological conditions and psychiatric disorders, psychosocial stress, family and occupational factors with somatic disorders. On the other hand, a painful somatic illness can cause anxiety, depression, social phobia and isolation. Treating nonspecific psychogenic pain disorder is not possible without a holistic, integrative, interdisciplinary team approach of psychiatrists, psychologists, physiologists, neurologists and sometimes even neurosurgeons. Cognitive-behavioral psychotherapy is prevalent as well as techniques of alleviating anxiety and stress (autogenic training), physiologic therapy, EMG biofeedback methods and psychopharmacotherapy. Croatian Academy of Sciences and Arts 2009-10-20 text pdf http://hrcak.srce.hr/42389 http://hrcak.srce.hr/file/66355 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.504=33; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:51393 2010-04-26 journal:117

Temporomandibularni poremećaji – znanstveni pristup Temporomandibular disorders – a scientific approach Jerolimov, Vjekoslav; School of Dental Medicine, University of Zagreb, Zagreb, Croatia; jerolimov@sfzg.hr Croatian Academy of Sciences and Arts 2010-04-12 text pdf http://hrcak.srce.hr/51393 http://hrcak.srce.hr/file/78671 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.507=34; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:51461 2010-04-27 journal:117

Temporomandibularni poremećaji – problemi u dijagnostici Temporomandibular disorders – problems in diagnostics Valentić-Peruzović, Melita; School of Dental Medicine, University of Zagreb, Zagreb, Croatia; valentic@sfzg.hr temporomandibularni poremećaji (TMP); znakovi i simptomi; poremećaji mastikatornih mišića; poremećaji temporomandibularnog zgloba (TMZ); dijagnostika TMP-a. temporomandibular disorders (TMD); temporomandibular joint disorders; masticatory muscles disorders; signs and symptoms; diagnostics of TMD; treatment modalities Temporomandibularnim poremećajem (TMP) uglavnom su zahvaćeni temporomandibularni zglobovi (TMZ) i žvačni mišići s okolnim strukturama. Smatra se da su uzročnici mnogobrojni te neki izravno utječu na pojavu i razvoj TMP-a, dok se drugi pojavljuju kao čimbenici koji mogu doprinijeti nastanku bolesti. Kao i ostali kronični mišićno-koštani bolni poremećaji, i TMP bi se mogao opisati kao psihofizički poremećaj s promjenama u endogenim regulacijskim putovima boli i posljedično otežanom prilagodbom na emocionalne, fiziološke i neuroendokrine odgovore na fizičke i psihičke stresore. Čini se da kod adolescenata s TMP-om važniju ulogu imaju psihosocijalni čimbenici, kao što su povećana razina stresa, somatske tegobe i emocionalni problem, nego sami dentalni čimbenici. U pacijenata s TMP-om znatno je prisutnija pojava multiplih boli u tijelu i općenito umora nego u kontrolnih ispitanika. Postoje različite klasifikacije TMP-a; neki ih dijele u podgrupe. Pacijenti s mišićnim dijagnozama imaju izraženije pritužbe na bol i distres nego oni koji imaju poremećaje vezane uz zglob. Čini se da mišićna bol može zasjeniti zglobnu, a pacijenti iz miogene skupine više se žale na parafunkcije, depresiju i zabrinutost. Smatra se da pacijenti s mišićnim dijagnozama imaju više bolnih simptoma od onih sa zglobnim dijagnozama. Bit će potrebna daljnja istraživanja kako bi se razjasnila uloga i utjecaj čimbenika rizika i mehanizama koji su odgovorni za povezanost TMP-a i boli te utjecaj spola. Temporomandibular disorders (TMD) is a group of conditions affecting the temporomandibular joint, masticatory muscles and the adjacent structures, and most clinicians and researchers believe that it is multifactorial etiology. There are multiple risk factors associated with TMD. The etiology of TMD has not been yet completely understood. Likewise with other chronic musculoskeletal pain disorders, TMD seems to be best explained from a biopsychosocial perspective, in which it is viewed as a psychophysiological disorder involving changes in endogenous regulatory pain pathways, resulting in maladaptive emotional, physiological and neuroendocrine responses to physical and psychological stressors. In adolescents with TMD, psychosocial factors such as increased levels of stress, somatic complaints, and emotional problems seem to play a more prominent role than dental factors. Multiple pains in the body and fatigue are significantly more common with TMD group than with the controls. Several studies have categorized TMD into subgroups. So far, studies which examined psychological differences between subgroups generally pointed to the fact that patients with myogenic diagnoses had more pain and distress than those with joint-related diagnoses. It seems that muscular pain may overshadow joint pain. However, subjects in the myogenous group more often reported parafunction, depression, and worrying. Recent studies suggest that subjects with muscular diagnoses have more severe pain and psychological distress than those with joint diagnoses. Further studies are needed to clarify the temporal sequence of risk factors, as well as the mechanisms accounting for the association between TMD pain and gender. Croatian Academy of Sciences and Arts 2010-04-12 text pdf http://hrcak.srce.hr/51461 http://hrcak.srce.hr/file/78773 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.507=34; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:51464 2010-04-27 journal:117

Temporomandibularni poremećaji – uloga neuromuskularne stomatologije Temporomandibular disorders – the role of neuromuscular dentistry Alajbeg, Iva; School of Dental Medicine, University of Zagreb, Zagreb, Croatia; ialajbeg@sfzg.hr temporomandibularni poremećaji; neuromuskularna stomatologija; žvačni mišići. temporomandibular disorders; neuromuscular dentistry; masticatory muscles. Poremećaji funkcije žvačnog sustava (tzv. temporomandibularni poremećaji) problem su s kojim se sve češće susrećemo u svakodnevnoj praksi. Kliničari se uglavnom slažu u tome da najvažniju ulogu u njihovu nastanku imaju psihosocijalni čimbenici (stres), trauma – koja može biti makrotrauma, kao što je npr. udarac u čeljust, ili mikrotrauma, ona povezana s kroničnom mišićnom hiperaktivnošću (bruksizmom) ili okluzijskom nestabilnošću – te okluzijski uvjeti. Neuromuskularna stomatologija moderan je oblik dijagnostike i liječenja tih poremećaja. Ona objektivno procjenjuje kompleksan odnos između zubi, žvačnih mišića, temporomandibularnih zglobova i kranijalnih živaca kako bi među njima postigla sklad. Za razliku od standardnih dijagnostičkih metoda kliničke funkcijske analize kojima se koristi tradicionalna stomatologija, neuromuskularna stomatologija u tu se svrhu koristi različitim kompjutoriziranim suvremenim tehnikama kojima se bilježi pomicanje donje čeljusti (analiza kretnji donje čeljusti), registriraju mišićnu aktivnost (elektromiografija) i identificiraju zvukove zgloba (elektrosonografija i analiza zglobnih vibracija). Činjenica je ipak da do danas još uvijek ne postoji dovoljan broj randomiziranih dvostruko slijepih kliničkih studija koje bi nam mogle objektivno pomoći u odabiranju odgovarajućeg načina dijagnostike i liječenja, a koje će u budućnosti zasigurno doprinijeti rješavanju enigmi temporomandibularnih poremećaja. Masticatory system function disorders, known as temporomandibular disorders (TMD) represent frequently encountered problem in daily practice. Clinicians generally agree that psychosocial factors (stress), trauma (macrotrauma - any sudden force to the joint resulting in structural alteration, or microtrauma - functional overloading associated with muscular hyperactivity (bruxism) or occlusal instability), and occlusal conditions have the important role in the onset of TMD. Neuromuscular dentistry is modern approach in diagnosis and treatment of TMD. It objectively evaluates the complex relationship between teeth, masticatory muscles, temporomandibular joints and cranial nerves in order to achieve an occlusion that is based on the optimal relationship between the mandible and the skull – a neuromuscular occlusion. Neuromuscular dentistry uses computerized instrumentation to measure the patient’s jaw movements via Computerized Mandibular Scanning (CMS) or Jaw Motion Analysis (JMA), muscle activity via electromyography (EMG) and temporomandibular joint sounds via Electro-Sonography (ESG) or Joint Vibration Analysis (JVA). The fact is, however, that to date there is still no sufficient number of randomized double-blind clinical studies that could objectively help in choosing the appropriate method of diagnosis and treatment of TMD, and that in the future those studies certainly might contribute to resolving the enigma of temporomandibular disorders. Croatian Academy of Sciences and Arts 2010-04-12 text pdf http://hrcak.srce.hr/51464 http://hrcak.srce.hr/file/78778 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.507=34; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:51467 2010-04-27 journal:117

Odontogena bol Odontogenic pain Prpić-Mehičić, Goranka; School of Dental Medicine, University of Zagreb, Zagreb, Croatia; prpic@sfzg.hr Galić, Nada; School of Dental Medicine, University of Zagreb, Zagreb, Croatia odontogena bol; neodontogena bol; odražena bol; diferencijalna dijagnostika. odontogenic pain; non-odontogenic pain; referred pain; differential diagnostics. Bol ima funkciju upozoravanja na oštećenje tkiva te funkciju aktivacije obrambenih refleksa radi prevencije daljnjeg oštećenja. Podražaj koji oštećuje tkivo ili prijeti oštećenjem tkiva aktivira nociceptore koji prenose informaciju sustavom neurona do kore velikog mozga, gdje se obrađuje i interpretira kao bol. Većinu somatosenzornih informacija iz područja orofacijalnog sustava prenosi n. trigeminus. Da bismo uklonili bol, potrebno je prepoznati i dijagnosticirati uzrok boli. To nije uvijek jednostavno zbog mnogih varijacija kliničke slike te mogućnosti boli da se referira iz odontogenih struktura u neodontogene i obratno. Poznavanje puta i mehanizma boli te mogućih uzroka i karaktera orofacijalne boli, odnosno detaljna anamneza, klinički pregled i testiranja, dovest će do prave dijagnoze. Odontogeni izvor boli obično ima tipičan karakter, evidentan uzrok, te se provokacijskim testovima dobivaju simptomi navedeni u anamnezi. Svakom odstupanju od klasične slike treba pristupiti s oprezom. Isključivanjem odontogenog uzroka boli treba ispitati ostale potencijalne uzroke orofacijalne boli kako bi se postavila pouzdana dijagnoza. Pain has the function of a warning to tissue damage and activation of defensive mechanisms, with the aim of prevention of further damage. The stimulus which damages or threatens to damage a tissue activates the nociceptors which in turn carry the information by a system of neurons to cortex, where it is processed and recognized as pain. Most somatosensory information from the area of orofacial system is transported via n. trigeminus. In order to remove pain, it is necessary to recognize and properly diagnose the caus of pain. This is not always easy, due to numerous variations within the clinical findings, and the latent possibility that pain has referred from odontogenis structure onto the nonodontogenis ones, and vice versa. Knowing the pathways and mechanisms of pain, possible causes and different characters of orofacial pain, as well as a thorough anamnesis, clinical examination and testing will eventually lead to a proper diagnosis. An odontogenic source of pain is well defined and has an apparent cause, and therefore the provocation tests lead to the symptoms contained in the anamnesis. Any deviation from standard clinical status should be taken with caution. Once odontogenic cause of pain has been excluded, other potential causes of orofacial pain should be taken into consideration, in order to establish a valid diagnosis. Croatian Academy of Sciences and Arts 2010-04-12 text pdf http://hrcak.srce.hr/51467 http://hrcak.srce.hr/file/78782 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.507=34; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:51470 2010-04-27 journal:117

Diferencijalna dijagnostika bolnih stanja sluznice usne šupljine Differential diagnostics of painful conditions of oral mucosa Mravak-Stipetić, Marinka; School of Dental Medicine, University of Zagreb, Zagreb, Croatia; mravak@sfzg.hr orofacijalna bol; bol sluznice usne šupljine; lezije sluznice usne šupljine; mukogingivna bol; neuropatska bol; sustavne bolesti; diferencijalna dijagnostika. orofacial pain; pain of oral mucosa; oral lesions; mucogingival pain; neuropathic pain; systemic diseases; differential diagnostics. Orofacijalna bol česta je i dijagnostički zahtjevna tegoba. Među brojnim uzrocima orofacijalne boli najčešći su bolesti zuba i parodonta, a po tom i različite bolesti sluznice usne šupljine. Bol sluznice usne šupljine prateći je simptom različitih oštećenja sluznice uzrokovanih lokalnim ili sustavnim čimbenicima. Bol oštećene sluznice spada u kategoriju somatske površinske boli i naziva se mukogingivna bol. Međutim, bol sluznice može biti prisutna i u odsutnosti patološkog nalaza. Tada je riječ o neuropatskoj boli koja je posljedica oštećenja dijela živčanog sustava ili je bol psihogenog podrijetla. Bol sluznice usne šupljine može biti i odražena (refleksna bol) iz drugih dijelova tijela. S obzirom na mnoštvo mogućih uzroka orofacijalne boli, dijagnostički je postupak složen i zahtijeva multidisciplinarni pristup. Preduvjet za postavljanje točne dijagnoze jest poznavanje širokog spektra dijagnostičkih karakteristika orofacijalne boli, koje uključuje podrijetlo i vrstu boli (somatska, neurogena i psihogena), trajanje (akutna i kronična) i mehanizme nastanka boli (nociceptorska, neuropatska, psihosomatska) te njihovo razlikovanje. U ovome radu prikazana su različita bolna stanja sluznice usne šupljine i njihove diferencijalnodijagnostički bitne karakteristike. Orofacial pain is a common complaint and challenging diagnostic problem. Among numerous causes of orofacial pain, the most common are diseases of teeth and periodontium, followed by various diseases and lesions of the oral mucosa. Pain of the oral mucosa is an accompanying symptom of different mucosal lesions caused by local or systematic factors. This type of pain belongs to the category of superfitial somatic pain, termed mucogingival pain. However, the pain of oral mucosa may be present in the absence of pathological findings. This type of pain may be caused by lesion of the nervous system, and is termed neuropathic pain, or it may be result of psychogenic disturbances. Pain of the oral mucosa can be also reflected (refered pain) from other parts of the body. Given the multitude of possible causes of intraoral pain as a component of orofacial pain, the diagnostic process is complex and requires a multidisciplinary approach. A prerequisite for establishing an accurate diagnosis is thorough knowledge of a wide spectrum of diagnostic characteristics of orofacial pain which include the origin and type of pain (somatic, neurogenic and psychogenic), duration (acute or chronic) and mechanisms of pain onset (nociceptive, neuropathic, psychosomatic) and their differentiation. The emphasis in this article is on differential diagnosis of the most common painful conditions of oral mucosa in respect to their clinical features. Croatian Academy of Sciences and Arts 2010-04-12 text pdf http://hrcak.srce.hr/51470 http://hrcak.srce.hr/file/78786 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.507=34; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:51473 2010-04-27 journal:117

Ortodontska terapija i temporomandibularni poremećaji Orthodontic therapy and temporomandibular disorders Lapter Varga, Marina; School of Dental Medicine, University of Zagreb, Zagreb, Croatia; lapter@sfzg.hr ortodontska terapija; malokluzija; temporomandibularni poremećaji. orthodontic treatment; malocclusion; temporomandibular disorders. Ortodontska terapija često se navodi kao protektivni ili pak otežavajući čimbenik u etiologiji temporomandibularnih poremećaja. Zbog toga je vrlo važno razumjeti vezu između različitih ortodontskih anomalija i ortodontske terapije te znakova i simptoma temporomandibularnih poremećaja. Iz prezentirane literature proizlazi da je pretpostavka po kojoj ortodontska terapija dovodi do TMD-a neutemeljena. Klinička istraživanja pokazuju da ortodontska terapija igra malu ulogu u pogoršanju TMD-a kada se uspoređuju tretirani i netretirani ispitanici, oni s malokluzijama i bez njih ili kada se uspoređuju različite vrste ortodontske terapije. U nedavno objavljenim longitudinalnim istraživanjima navodi se znatno smanjenje simptoma i znakova TMD-a između tinejdžerske i rane odrasle dobi. Orthodontic treatment has been variously cited both as a protective and harmful factor in temporomandibular disorders (TMD) etiology. Therefore, it is important to understand associations between different malocclusions, orthodontic treatment, and signs and symptoms of temporomandibular disorders (TMD). From the presented literature the suggestion that orthodontic treatment leads to TMD appears to be ill-founded. Clinical studies suggest that orthodontic treatment has little role to play in worsening or precipitating TMD when treated patients are compared with untreated individuals, with or without malocclusion, or when different types of orthodontic treatment are compared. A considerable reduction in signs and symptoms of TMD between the teenage period and young adulthood has been shown in some recent longitudinal studies. Croatian Academy of Sciences and Arts 2010-04-12 text pdf http://hrcak.srce.hr/51473 http://hrcak.srce.hr/file/78791 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.507=34; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:51477 2010-04-27 journal:117

Uloga otalgija u diferencijalnoj dijagnostici temporomandibularnih poremećaja The role of otalgia in the diff erential diagnostics of temporomandibular disorders Kalogjera, Livije; Sestre milosrdnice University Hospital, Zagreb, Croatia; kalogjera@sfzg.hr Trotić, Robert; Sestre milosrdnice University Hospital, Zagreb, Croatia otalgija; temporomandibularni poremećaji; diferencijalnodijagnostički postupci. earache; temporomandibular disorders; differential diagnostic procedures. Otalgija je bol koja se prezentira u području uha, međutim to ne uključuje nužno otogenu etiologiju. U diferencijalnoj dijagnostici otalgije dolaze u obzir cervikocefalni sindrom, artralgija temporomandibularnog zgloba, odontogeni procesi, parotitis, tonzilitis, faringitis, epiglotitis, ezofagitis te maligni tumori s infiltracijom grana trigeminusa, vagusa i auricularis magnusa, koji se inferiorno šire do područja jednjaka, a kranijalno do lubanjske baze. Otogena bol najčešće se susreće u upalama vanjskog i srednjeg uha, dok je rijetka u kroničnim upalama, osim u fazama egzacerbacije. Kod kroničnih upala srednjeg uha, bol je znak komplikacije i širenja bolesti prema duri ili kranijskim živcima. Za diferencijalnu dijagnostiku otogene boli nužna je otoskopija, katkad mikrootoskopija, te radiološka dijagnostika, ranije konvencionalne snimke temporalne kosti po Schulleru i Stenversu, koje danas sve više zamjenjuje CT i MRI. Ako je bol povezana s ispadom sluha ili ravnoteže, što je najčešće rezultat virusnog neuritisa u temporalnoj kosti, a bez kliničke manifestacije otitisa, u obzir dolazi i audiovestibulološka dijagnostika. Ako je otalgija povezana s disfagijom ili odinofagijom, najčešće je riječ o tonzilofaringitisu, ali u obzir dolaze i peritonzilarni apsces, epiglotitis, apsces korijena jezika, parafaringealni apsces, tumor ždrijela, tonzile, korijena jezika ili epiglotitis. Eaglov sindrom, sindrom elongiranog stiloidnog nastavka, također uključuje bolno gutanje i refleksnu bol u uhu. Bolovi u uhu mogu biti uvjetovani temporomandibularnim poremećajima, s time da se otalgija pojačava žvakanjem ili palpacijom zgloba. Uloga otorinolaringologa jest isključiti otogenu ili faringolaringogenu otalgiju, a potom se diferencijalno dijagnostički uključuje obrada u smjeru cervikogene otalgije (radiološka obrada vratne kralježnice), artralgije temporomandibularnog zgloba (radiološka obrada zgloba, konzultacija stomatologa) ili odontogene otalgije (konzultacija stomatologa). U tome su smislu u obradu uključeni radiolog, stomatolog, reumatolog i neurolog. Otalgia (earache) is pain presented in the ear, which does not necessarily originate from the ear (primary otalgia). In the differential diagnostics of (secondary) otalgia cervicocephalic syndrome, temporomandibular disorders, odontogenic pathology, parotitis, tonsillitis, pharyngitis, epiglottis, oesophagitis and malignant tumours infiltrating trigeminal, vagal or auricular (cervical) nerves branches from oesophagus inferiorly and skull base cephalad, should be considered. Primary otalgia is usually confined to external otitis or acute otitis media, while it is rarely found as a symptom of chronic otitis media, except in exacerbations. In the chronic otitis media earache is usually a sign of complication and expansion of inflammation to the dura and cranial nerves. In the differential diagnostics of primary otalgia otoscopy and otomicroscopy are necessary, as well as radiologic work-out, where CT and MRI scans are replacing former conventional x-.ray Schuller and Stenvers views. If otalgia is associated with hearing or balance disorders without clinical manifestation of otitis, the etiology is most commonly viral neuritis of temporal bone nerves, and otoneurological diagnostic workout should be considered. If (secondary) otalgia is associated with dysphagia or odinophagia, the most common etiology would be tonsillopharyngitis, but quinsy, epiglottitis, tongue base abscess, parapharyngeal abscess, and tumours of pharynx, tonsill or tongue base or epiglottis should be considered. Eagle syndrom or elonged styloid process syndrom is also characterised by painful swallowing and referred otalgia. Earache can be caused by temporomandibular disorders, where otalgia is usually increased by mastication and joint palpation. The role of otorhinolaryngologist is to exclude otogenic and pharyngogenic otalgia, and the differential diagnostics should include workout considering cervicogenic otalgia (cervical spine x-ray or MRI), temporomandibular disorders (TMJ x-ray, dentist consultation), or odontogenic otalgia (dentist consultation). The diagnostic workout of otalgia should include radiologist, dentist, reumatologist, and neurologist. Croatian Academy of Sciences and Arts 2010-04-12 text pdf http://hrcak.srce.hr/51477 http://hrcak.srce.hr/file/78797 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.507=34; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:51482 2010-04-27 journal:117

Poremećaji temporomandibularnog zgloba – reumatološki i fizijatrijski pristup Disorders of temporomandibular joint – a rheumatological and physiatric approach Krapac, Ladislav; Physical Therapy and Rehabilitation Dr. Drago Čop Polyclinic, Zagreb, Croatia; ladislav.krapac@prfr.hr Badel, Tomislav; School of Dental Medicine, University of Zagreb, Zagreb, Croatia temporomandibularni zglob; reumatologija; fizijatrija; osteoartritis; dijagnostika; terapija. temporomandibular joint; rheumatology; physiatrics; osteoarthritis; diagnostics; treatment. Reumatske tegobe zasigurno su najčešći uzrok dolaska u liječničku, a ponekad i u stomatološku ambulantu. Osteoartritisi kao posljedica degenerativnih bolesti hrskavica i posljedične blaže upalne reakcije sinovije zgobova pridonose činjenici da se 25% žena te 20% muškaraca srednje životne dobi u Hrvatskoj tuži na bolesti koljena, šaka, kukova ili ramena te na bolove u malim zglobovima kralježnice. Upalne reumatske bolesti, najčešće reumatoidni artritis, prisutne su u radno aktivnoj populaciji u Hrvatskoj u 1,5% žena i 0,5% muškaraca, dok su metaboličke reumatske bolesti još manje prevalencije. Sve češće dijagnosticiramo i tzv. izvanzglobni reumatizam kao posljedicu prenaprezanja okozglobnih struktura – ali u proporciji znatno manjoj od 1%. U takvim proporcijama možemo očekivati i uzroke reumatskih tegoba i/ili bolesti temporomandibularnih zglobova (TMZ) koje se s rastućom životnom dobi potencijalno povećavaju, pa se i fizijatrijski postupci umnažaju. Prikazuju se podaci rada suradnje stomatologa i polikliničke reumatološko-fizijatrijske službe na temelju čije je suradnje uz prethodnu radiološku dijagnostiku (magnetska rezonancija) liječeno 60 pacijenata. Uz to je sve češća suradnja stomatologa i fizijatara glede primjene procedura fizikalne terapije (zagrijavanje pulzirajućim ultrazvukom, magnetoterapijom ili laserom) kao dopune liječenju i elektroanalgeziji (TENS ili IFS) te, nakraju, i medicinskoj gimnastici. Specijalno osmišljene vježbe po Schluteu daju najbolje rezultate povratka funkcije TMZ-ova. Zdravstveni odgoj uz dobru suradnju stomatologa protetičara, fizijatara, reumatologa i neurologa pruža bolesnicima s poremećajima TMZ-ova mogućnost da se kao subjekti uključe u liječenje zasigurno najopterećenijih zglobova. Rheumatic disturbances are possibly one of the most common reasons for visiting the doctor and sometimes also the dental office. The most common articular disorders are: degenerative arthritis or osteoarthritis (as a less or noninflammatory degenerative disease), rheumatoid arthritis (with inflammatory synovial joint reactions), metabolic rheumatic diseases, traumatic arthritis, and psoriatic arthritis. Extra-articular rheumatism as a consequence of overstrained tissue surrounding the joint has been diagnosed more frequently – but it amounts to less than 1%. These percentages of the causes of rheumatic disturbances and/or temporomandibular joint diseases can be expected to potentially increase with age, thus multiplying physiatric treatments. Collaboration between dentists and physiatrists regarding physical therapy procedures (pulsating ultrasound heating, magnetic or laser therapy, complementary electroanalgesia, TENS or IFS, and finally, medical gymnastics) is becoming more common. Specially created exercises by Schlute give the best results in TMJ function recovery. In collaboration between dentists and the rheumatologic-physiatric polyclinic, 60 patients diagnosed with temporomandibular disorder by means of magnetic resonance imaging were treated. Health education along with a good collaboration of prosthodontists, physiatrists, rheumatologists and neurologists enables TMD patients to participate in the treatment of the most overloaded joints. Croatian Academy of Sciences and Arts 2010-04-12 text pdf http://hrcak.srce.hr/51482 http://hrcak.srce.hr/file/78805 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.507=34; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:51486 2010-04-27 journal:117

Temporomandibularni poremećaji i migrenska glavobolja Temporomandibular disorders and migraine headache Demarin, Vida; Sestre milosrdnice University Hospital, Zagreb, Croatia; vida.demarin@zg.t-com.hr Bašić Kes, Vanja; Sestre milosrdnice University Hospital, Zagreb, Croatia temporomandibularni poremećaji; migrena. temporomandibular disorders; migraine headache. Migrena i temporomandibularni poremećaji imaju mnogo zajedničkog. Obje vrste poremećaja javljaju se u mlađoj životnoj dobi, češće u osoba ženskog spola, a i distribucija boli slična je. Temporomandibularni poremećaji mogu biti jedan od uzroka glavobolje ili mogu pogoršati primarnu glavobolju. Prevalencija temporomandibularnih poremećaja češće se javlja u bolesnika koji imaju kombinaciju migrenske i tenzijske glavobolje. Bolesnici s migrenskom glavoboljom češće imaju napetost mastikatornih mišića, a do poboljšanja dolazi nakon što budu liječeni istim metodama kao i bolesnici s temporomandibularnim poremećajima. Migraine headache and temporomandibular disorders show significant overlap in the area or distribution of pain, the gender prevalence and age distribution. Temporomandibular disorders may cause headaches per se, worsen existent primary headaches, and add to the burden of headache disorders. The patients with combined migraine and tension-type headaches had a higher prevelance of temporomandibular disorders. Evidence supporting a close relationship include the increased masticatory muscle tenderness in migrainuers compared and improvement in headache symptoms with traditional TMD treatment. Croatian Academy of Sciences and Arts 2010-04-12 text pdf http://hrcak.srce.hr/51486 http://hrcak.srce.hr/file/78810 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.507=34; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:51491 2010-04-27 journal:117

Psihološki i psihijatrijski čimbenici temporomandibularnog poremećaja Psychological and psychiatric factors of temporomandibular disorders Buljan, Danijel; Sestre milosrdnice University Hospital, Zagreb, Croatia; dbuljan@kbsm.hr temporomandibularni poremećaji; bolni poremećaj; nespecifična bol; specifična bol; psihoterapija; psihofarmakoterapija. temporomandibular disorders; pain disorder; nonspecific pain; specific pain; psychotherapy; psychopharmacotherapy. Temporomandibularni poremećaj (TMP) skupni je naziv za niz patoloških stanja koja mogu imati slične znakove i simptome, a dovode do poremećaja normalne funkcije stomatognatog sustava. Temporomandibularni poremećaji definiraju se kao skupina orofacijalnih poremećaja s boli u preaurikularnom području, čeljusnim zglobovima (TMZ) ili žvačnim mišićima s ograničenjima u rasponu i devijacijama kretnji donje čeljusti te zvukovima TMZ-ova tijekom žvakanja. Kada je poznat patofiziološki uzročni čimbenik TMP-a s boli, konvencionalno se klasificira kao “specifičan”, a kada patofiziološki uzročni čimbenik nije poznat, kao “nespecifičan”, psihogen, idiopatski, konverzivan ili eufemistički atipičan. Nespecifična bol pri TMP-u često je simptom nekog psihijatrijskog poremećaja kao što je depresija sa somatskim simptomima, hipohondrija, psihoza ili se pak svrstava u skupinu somatoformnih psihijatrijskih poremećaja prema suvremenim klasifikacijskim sustavima kao što su Dijagnostički i statistički priručnik (DSM-IV) američkog psihijatrijskog društva i Međunarodna klasifikacija bolesti i srodnih zdravstvenih problema MKB-10. TMP zahvaća 12% cjelokupne populacije. Psihološko-psihijatrijski problemi prevladavaju među bolesnicima s TMP-om, anksiozno-depresivni poremećaj pronađen je u 50%, a depresija u 32.1% bolesnika. Pacijenti sa psihijatrijskim problemima skloniji su 4.5 puta TMP-u nego osobe bez psihičkih problema i obrnuto. TMP je povezan s brojnim etiološkim čimbenicima, što otežava ranu i preciznu dijagnostiku i učinkovitu terapiju. Obično se navodi pet glavnih čimbenika povezanih s TMP-om: trauma, okluzija, navike (parafunkcijske aktivnosti, kao što su žvakanje žvakaće gume, žvakanje na jednu stranu, stiskanje zubi, bruksizam), duboki bolni podražaj, psihološki problemi povezani s emocionalnim stresom i psihijatrijski poremećaji. U ovom radu pozornost je usmjerena na psihološke i psihijatrijske čimbenike TMP-a. Liječenje nespecifičnih, psihogenih bolnih poremećaja TMZ-a nije moguće bez holističkog, integrativnog, interdisciplinarnog, timskog pristupa psihijatra, psihologa, fizijatra, neurologa, a ponekad i neurokirurga. Prevladava kognitivno-bihevioralna psihoterapija, tehnike ublažavanja anksioznosti i stresa (autogeni trening), fizikalna terapija, EMG biofeedback metode i psihofarmakoterapija. Temporomandibular disorders (TMD) is an umbrella term covering a series of pathologic conditions which can have similar signs and symptoms and which lead to an imbalance in the normal functioning of stomatognatic system. Temporomandibular disorders are defined as a group of orofacial disorders with pain in the preauricular area, jaw joints (TMJ) or masticating muscles with limitations in range and deviations of lower jaw’s movement as well as TMJ sounds during mastication. When the pathophysiologic factor is known, the pain is conventionally classified as “specific” and when it is unknown it is called “nonspecific”, psychogenic, idiopathic, conversive or euphemistic atypical pain. Nonspecific pain of the TMD is very often a symptom of a psychiatric disorder, for example depression with somatic symptoms, hypochondria, psychosis or is classified in the group of somatoform psychiatric disorders according to contemporary classification systems, e.g. the American Psychiatric Association’s DSM-IV (7) and the International Classification of Diseases (ICD-10). TMD affects 12% of overall population. Psychological-psychiatric problems prevail among patients with TMD, anxious-depressive disorder is found in 50%, while depression in 32.1% of patients. Patients with psychiatric problems are 4.5 times more prone to TMD than individuals without psychiatric problems and vice versa. TMD is connected with numerous etiologic factors, which renders early and precise diagnosis as well as efficient therapy more difficult. Five main factors are usually listed as connected to TMD: trauma, occlusion, habits (parafunctional activities, such as chewing a piece of gum, chewing on one side, teeth clenching, bruxism), deep pain stimulus, psychological problems connected with emotional stress, and psychiatric disorders. Psychological and psychiatric factors of TMD are the focus of this paper. Treating nonspecific, psychogenic pain disorders is not possible without a holistic, integrative, interdisciplinary team approach of psychiatrists, psychologists, physiologists, neurologists and sometimes even neurosurgeons. Cognitive-behavioral psychotherapy is prevalent as well as techniques of alleviating anxiety and stress (autogenic training), physiologic therapy, EMG biofeedback methods and psychopharmacotherapy. Croatian Academy of Sciences and Arts 2010-04-12 text pdf http://hrcak.srce.hr/51491 http://hrcak.srce.hr/file/78817 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.507=34; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:51493 2010-04-27 journal:117

Slikovni prikaz poremećaja temporomandibularnog zgloba Imaging of temporomandibular joint disorders Marotti, Miljenko; Sestre milosrdnice University Hospital, Zagreb, Croatia; mmarotti@kbsm.hr Temporomandibularni zglob; konvencionalna radiografija; artrografija; kompjutorizirana tomografija; magnetna rezonanca. Temporomandibular joint; conventional radiography; artrography; computerized tomography; magnetic resonance. Složena anatomska konfiguracija temporomandibularnog zgloba razlog je razvitka standardiziranih tehnika koje omogućuju točan anatomski prikaz. Linearna tomografija omogućuje dobre koštane detalje, ali ne prikazuje mekotkivnu komponentu zgloba. Ta tehnika uspješno pokazuje hipoplaziju, hipertrofiju ili malformaciju kondila, a u slučajevima maksilofacijalne traume dobar prikaz frakture pukotine. Infekcije i tumori također su prikazivi ovom metodom. Artrografiju izvodimo radi prikaza statusa kondila, diska, zglobne jamice te zglobne kvržice s otvorenim i zatvorenim ustima. Kompjutorizirana tomografija (CT) nadmašuje konvencionalnu radiografiju i konvencionalnu tomografiju u procjeni unutarnjeg poremećaja temporomandibularnog zgloba, kod traumatskih promjena, degenerativnih procesa i tumora. CT omogućuje dobru procjenu mekih tkiva i odličnu procjenu koštanih struktura. Magnetna rezonanca (MR) pokazuje izuzetan mekotkivni kontrast i omogućuje prikaz struktura temporomandibularnog zgloba, koje se ne mogu prikazati konvencionalnom radiografijom, konvencionalnom tomografijom ili kompjutoriziranom tomografijom. MR temporomandibularnih zglobova razlikuje unutarnje anatomske strukture zgloba takvom preciznošću kakvu druge metode ne mogu dostići. Prikaz diska bez kontrastnog sredstva, kao i područja bilamilarne zone, čine magnetnu rezonancu zlatnim standardom u dijagnostici bolesti temporomandibularnog zgloba. Complicated anatomical configuration of the temporomandibular joint was the reason for developing standardized radiographic techniques which would provide accurate anatomical images. Tomography provides excellent bony details but no in formation of the soft tissue component of the joint. This technique is useful in demonstrating suspected hypoplasia, hypertrophy or malformation of the condyles, in the case of maxillofacial trauma with fracture description, infections and tumors. Artrography is performed to determine the status of the condyle-disk-glenoid fossa and eminence relationship with rxegard to the closed and open mouth position. Computerized tomography (CT) is superior to conventional radiograšhy and conventional tomography for evaluating internal derangements of temporomandibular joint, trauma, degenerative processes and tumors. CT demonstrated good evaluation of soft tissue and excellent evaluation of bony structures. Magnetic resonance (MR) has shown exquisite soft tissue contrast and provides a view of the structures of temporomandibular joint which cannot be differentiated by conventional radiography, conventional tomography and computerized tomography. MR of temporomandibular joint can distinguish internal anatomical features of the joint to a degree that no other imaging procedure can match. An image of the articular disk without contrast media as well an image of the posterior band has made the magnetic resonance the golden standard of temporomandibular joint imaging. Croatian Academy of Sciences and Arts 2010-04-12 text pdf http://hrcak.srce.hr/51493 http://hrcak.srce.hr/file/78820 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.507=34; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:51494 2010-04-27 journal:117

Temporomandibularne ozljede i poremećaji u sportu Temporomandibular injuries and disorders in sport Jerolimov, Vjekoslav; School of Dental Medicine, University of Zagreb, Zagreb, Croatia; jerolimov@sfzg.hr sport; temporomandibularne ozljede; temporomandibularni poremećaji; prevencija; individualni interdentalni štitnici. sport; orofacial injuries; temporomandibular disorders; prevention; custom-made mouthguards. Ozljede orofacijalnog sustava u sportu su učestale, ovisno o vrsti sportske discipline te drugim okolnostima. Temporomandibularne ozljede i poremećaji čine oko 2 do 6% svih orofacijalnih ozljeda, a rezultat su makrotrauma i mikrotrauma donje čeljusti, čeljusnog zgloba i okolnih anatomskih struktura. Posljedice takvih trauma raznovrsne su simptomatologije, koje mogu biti uzrokom privremenog ili trajnog prekida bavljenja sportom. Većina ozljeda u sportu, pa tako i onih orofacijalnih te temporomandibularnih poremećaja, nastaje iz predvidivih razloga i na njih se može preventivno utjecati. U preventivne mjere spada korištenje različitih oblika zaštitnih sredstava: ekstraoralnih, interdentalnih (intraoralnih) i kombiniranih štitnika za usta i zube. Najširu uporabu imaju interdentalni štitnici, a oni mogu biti gotovi, polugotovi ili individualno izrađeni. Imaju raznovrsne uloge u sprječavanju ozljeda orofacijalnih tkiva u sportu, a korištenjem takvih štitnika učestalost se i težina orofacijalnih, odnosno temporomandibularnih, ozljeda znatno smanjuje. Sportske ozljede, pa tako i one orofacijalnog sustava, bez obzira na to nastaju li u rekreativnom ili natjecateljskom sportu, zahtijevaju multidisciplinarni pristup, kako pri dijagnostici i liječenju, tako i u provođenju preventivnih mjera. Sportski liječnici, treneri, sportski djelatnici, roditelji i sami sportaši trebali bi se trajno educirati i upućivati u iznimnu važnost preventivnih mjera, pri čemu je uloga stomatologa u sportu nezaobilazna. Orofacial injuries are common in sporting activities, depending on type of sport and many other factors. Temporomandibular injuries and disorders have been found in 2 – 6 % of all orofacial injuries cases, and they are the result of macrotraumas and microtraumas of the mandible, the temporomandibular joint and adjacent anatomic structures. The results of such traumas are of different symptomatology and can lead to a temporary or permanent cessation of sporting activity. Most injuries in sports, including orofacial and temporomandibular disorders, are predictable and therefore preventable. Measures for preventing orofacial injuries and temporomandibular disorders in sporting activities include various types of protection appliances: extraoral, interdental (intraoral) and combined mouth and teeth protectors. Interdental sports guards (mouthguards) can be stock or ready-made, mouth-formed or custom-made mouthguards. These mouthguards, mutually different in quality, play a very important role in prevention of orofacial and temporomandibular tissue injuries. Use of mouthguards significantly reduces the number of orofacial tissue injuries, and also reduces the severity of sustained injuries. Sports injuries, including those to orofacial and temporomandibular area, regardless of whether they are incurred in recreational or competitive sport, require multidisciplinary approach, both in diagnostics and treatment and in implementation of prevention measures. Sports physicians, coaches, sports officials, parents and athletes themselves, should also be permanently educated on the exceptional importance of prevention measures, thus making the role of dentist in sport unavoidable. Croatian Academy of Sciences and Arts 2010-04-12 text pdf http://hrcak.srce.hr/51494 http://hrcak.srce.hr/file/78822 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.507=34; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:63142 2011-01-11 journal:117

The Latest Achievements in Diagnostics and Therapy – The Era of Global Analytical Methods Spaventi, Šime; Croatian academy of sciences and arts, Zagreb, Croatia Kusić, Zvonko; Croatian academy of sciences and arts, Zagreb, Croatia Croatian Academy of Sciences and Arts 2010-12-15 text pdf http://hrcak.srce.hr/63142 http://hrcak.srce.hr/file/94644 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.508=35; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:63148 2011-01-11 journal:117

Novosti u mozaiku metastaziranja zloćudnih tumora Unravelling New Pieces of Tumour Metastasis Puzzle: The Role of Proteomics Sedić, Mirela; Rudjer Boskovic Institute, Laboratory for systems biomedicine, Zagreb, Croatia Kraljević Pavelić, Sandra; Department of Biotechnology, Rijeka, Croatia Vučinić, Srđan; Rudjer Boskovic Institute, Laboratory for systems biomedicine, Zagreb, Croatia Pavelić, Krešimir; Department of Biotechnology, Rijeka, Croatia; pavelic@irb.hr matične stanice novotvorevina; metastaziranje; proteomika cancer stem cell; metastasis; proteomics Novosti u mozaiku metastaziranja zloćudnih tumora Unatoč napretku u istraživanju i proučavanju zloćudnih tumora, ta je bolest i dalje velik izazov modernoj medicini. Biološka raznolikost, ali i klasično poimanje mehanizama metastaziranja tumora, razlog su neučinkovitosti postojećih načina liječenja. Dva su modela kojima se objašnjava ta raznolikost – model klonske evolucije te model matičnih stanica novotvorina. Ovaj drugi u posljednje je vrijeme privukao pozornost jer su matične stanice novotvorina, zbog svojih sposobnosti samostalnog obnavljanja i diferenciranja, odgovorne za nastanak i razvoj tumora te njihovu sposobnost metastaziranja i pojave recidiva. Metode globalnih analiza poput proteomike otvaraju nove mogućnosti u istraživanju procesa metastaziranja, jer omogućuju identifikaciju složenih mreža proteina uključenih u progresiju novotvorina, što može pridonijeti ranoj dijagnostici i omogućiti razvoj učinkovitijih lijekova protiv metastaza. Despite the abundance of attention that cancer has attracted, it continues to constitute one of the deadliest scourges of the modern era. Tumour heterogeneity greatly contributes to the ineffectiveness of current therapies and hampers the study and treatment of cancer. There are two models accounting for tumour heterogeneity and propagation, namely clonal evolution model and cancer stem cell model. In particular, cancer stem theory has attracted much attention lately, as these cells with self-renewal and differentiation abilities are responsible for the initiation of tumour development, growth, and its ability to metastasize and reoccur, and provide a reasonable explanation for poor prognosis for patients in advanced stages of solid tumours. Advances in technologies such as proteomics open new avenues in metastasis research by specifically revealing complex protein networks involved in tumour progression, which should facilitate early diagnosis and provide the basis for designing more effective treatment strategies. Croatian Academy of Sciences and Arts 2010-12-15 text pdf http://hrcak.srce.hr/63148 http://hrcak.srce.hr/file/94651 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.508=35; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:63152 2011-01-11 journal:117

O spektrometriji masa u molekularnoj medicini: od elementarne analize do dijagnostičkog slikanja About Mass Spectrometry: From Elemental Analysis to Diagnostic Imaging Peter-Katalinić, Jasna; Department of Biotechnology, Rijeka, Croatia; jkp@uni-muenster.de Instrumentarij za spektrometriju masa; MALDI- i ESI-ionizacija; proteomika; glikoproteomika; glikourinomika Instrumentation for mass spectrometry, MALDI- and ESI-ionization, proteomics, glycoproteomics, glycourinomics Gotovo sto godina nakon što je J. J. Thomson’s 1912. prvi put pokazao da se masa kemijskih elemenata može eksperimentalno točno odrediti metoda koju je on otkrio – spektrometrija masa – dosegla je visok stupanj razvitka i raznolikosti na raznim poljima znanosti i svoje primjene u tehnologiji, medicini i javnom životu. Nove spoznaje o ioniziranju molekula iz svih agregatnih stanja omogućile su razvoj novih ionskih izvora za gotovo univerzalne primjene. Razvojem instrumentalne ionske optike omogućeno je manipuliranje ionskih zraka u spektrometrima masa, koji sadrže ćelije za ili sakupljanje ili fragmentiranje čitavih ionskih oblaka ili njihovih dijelova. Moderna spektrometrija masa raspolaže jedinstvenim svojstvima za istraživanje i analitiku kao što su specifičnost, osjetljivost, brzina, mogućnost automatizacije i primjene algoritama za interpretaciju eksperimentalnih podataka. Sve te instrumentalne metode danas su već u cijelosti integrirane u „omics“ poljima istraživanja kao što su genomics, proteomics, glycomics, lipidomics itd. Ovdje su prikazana pojedina autoričina istraživanja razvitka metoda za visokorazlučenu spektrometriju masa i za njezino direktno priključivanje na instrument za razdjeljivanje te razvitka algoritama za interpretaciju eksperimentalnih podataka. Ta tehnička rješenja bila su primijenjena na projekte usredočene na otkrivanje potencijalnih biomarkera u ljudskim bolestima. U momentalnoj viziji primjene spektrometrije masa u medicini se već ocrtava dijagnostičko slikanje, pri čemu se laserskom desorpcijom dobivaju slike slične onima dobivenima mikroskopijom, ali koje sadrže i dodatnu informaciju o molekularnim strukturama. Almost hundred years after the first demonstration of exact mass determination of chemical elements by J. J. Thomson’s in 1912, the method discovered by him – mass spectrometry – reached a high level of development in different fields of science and applications to life sciences, technology, medicine and public life. New aspects of ionization of molecules from all aggregate states contributed largely to develop new ion sources for almost universal usage. By development of distinct ion optics the secondary ion beams can be manipulated in mass spectrometers, which may contain cells for ion concentration or fragmentation of entire ion clouds or their parts. Modern mass spectrometry is characterized by unique properties for research and analytics like specificity, sensitivity, speed, the possibility of automatization and of application of algorithms for interpretation of experimental data. These properties are already integrated in commercial instruments and used for “omics”-type of projects, like genomics, proteomics, glycomics, lipidomics, and so on. In this article, own investigations and method developments are presented, in which high resolution mass spectrometry, hyphenated techniques to MS and automated data interpretation are playing a crucial role. These technical solutions were applied to projects focussed to discovery of potential biomarker of human diseases. In the present vision of the future MS in medicine, MS imaging will play an important role. Using laser desorption for ionization, the images similar to those obtained by microscopy can be obtained, where they contain additionally also the information on the molecular structure as an extra value. Croatian Academy of Sciences and Arts 2010-12-15 text pdf http://hrcak.srce.hr/63152 http://hrcak.srce.hr/file/94656 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.508=35; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:63153 2011-01-11 journal:117

Određivanje aminokiselinske sekvencije farmaceutskih peptida MALDI-TOF tandemnom spektrometrijom masa Sequence Determination of Pharmaceutical Peptides by MALDI-TOF Tandem Mass Spectrometry Cindrić, Mario; Ruđer Bošković Institute, Division of Molecular Medicine, Zagreb, Croatia; mario.cindric@irb.hr Sedić, Mirela; Ruđer Bošković Institute, Division of Molecular Medicine, Zagreb, Croatia Horvatić, Anita; Ruđer Bošković Institute, Division of Molecular Medicine, Zagreb, Croatia Dodig, Ivana; Ruđer Bošković Institute, Division of Molecular Medicine, Zagreb, Croatia MALDI-TOF/TOF; određivanje aminokiselinske sekvence; farmaceutski peptidi; bivalirudin; eksenatid MALDI-TOF/TOF; sequence determination; pharmaceutical peptide; bivalirudin; exenatide Iako su mehanizmi preddisocijacije, disocijacije i postdisocijacije iona izučavani dugi niz godina, postoji još cijeli niz mehanizama raspada iona koji se mogu korisno upotrijebiti u modernoj spektrometriji masa, proteomici i bioanalizama. Nedvojbena aminokiselinska analiza spektrometrijom masa počiva na ideji da samo jedan i kontinuirani slijed iona u tandemnom spektru masa može potpuno potvrditi cjelovitu aminokiselinsku sekvenciju i na taj način zadovoljiti zahtjeve nedvojbene analize peptida. Niz pravila kojima se definira cjelovita i nedvojbena analiza peptida tandemnom spektrometrijom masa u konačnici može unaprijediti iščitavanje rezultata analize i pouzdanost dobivenih podataka. Na teorijskim zasadama disocijacije iona u plinskoj fazi u ovom je radu prikazana cjelovita analiza peptida. Na modelnim farmaceutskim peptidima bivalirudinu i eksenatidu pokazano je kako se i bez raširene upotrebe derivatizacijskih tehnika (SPITC i Lys-tag) može ostvariti nedvojbena analiza, iako se modifikacije cisteina akrilacijom, metilacijom ili karboksimetilacijom pri tome ne mogu izbjeći. Although the peptide ion mechanisms of pre-dissociation, dissociation and post-dissociation have been well-studied over the past fifteen years, their practical application still has to be implemented into modern mass spectrometry-driven proteomics and bioanalysis. Unambiguous peptide sequence determination by mass spectrometry relies on the idea that only one continuous series of ions in mass spectrum can assure full sequence determination and meets the requirements of peptide analysis quality. This set of rules defined for the peptide analysis by tandem mass spectrometry would generally improve an overall reliability and data accuracy. Based on the process mechanisms of gas-phase peptide bond dissociation, a relatively small and large model peptides are unambiguously analyzed (bivalirudin and exenatide) showing that derivatization concepts of the C- or N-terminus derivatization (SPITC and Lys-tag) can be avoided. Croatian Academy of Sciences and Arts 2010-12-15 text pdf http://hrcak.srce.hr/63153 http://hrcak.srce.hr/file/94658 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.508=35; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:63155 2011-01-11 journal:117

Uloga spola u osjetljivosti na oksidacijski stres Sensitivity to Oxidative Stress: Sex Matters Marotti, Tatjana; Ruđer Bošković Institute, Division of Molecular Medicine, Zagreb, Croatia; marotti@irb.hr Sobočanec, Sandra; Ruđer Bošković Institute, Division of Molecular Medicine, Zagreb, Croatia Mačak-Šafranko, Željka; Ruđer Bošković Institute, Division of Molecular Medicine, Zagreb, Croatia Šarić, Ana; Ruđer Bošković Institute, Division of Molecular Medicine, Zagreb, Croatia Kušić, Borka; Ruđer Bošković Institute, Division of Molecular Medicine, Zagreb, Croatia Balog, Tihomir; Ruđer Bošković Institute, Division of Molecular Medicine, Zagreb, Croatia oksidativi stres; spol; hem-oksigenaza; citokrom P450 oxidative stress; gender; hem-oxygenase; cytochrome P450 Proces starenja povezuje se s poremećajem u ravnoteži stvaranja slobodnih radikala i odgovarajuće «obrane» koju omogućuju antioksidansi. Smatra se da su oksidacijski procesi i antioksidacijska obrana spolno vezane kategorije. U svojim istraživanjima utvrdili smo da 60% miševa muškog spola u starijoj dobi spontano obolijeva od hepatocelularnih karcinoma, dok ženke iste dobi od toga ne obolijevaju. S obzirom na povezanost oksidacijsko-antioksidacijskih procesa sa spolom ispitali smo navedene parametre u mužjaka i ženki miševa u uvjetima hiperoksije (100%-tni kisik). Tijekom starenja oksidacijski procesi i aktivnost antioksidacijskih enzima mijenjaju se, ali je njihov odnos uvijek povoljniji u ženki nego u mužjaka. Čini se da je osjetljivost na oksidacijski stres većim dijelom rezultat međudjelovanja različitih antioksidacijskih enzima, a manjim razine pojedinog antioksidacijskog enzima. U prilog tome govori i činjenica da upravo u ženki (ali ne i u mužjaka) u starijoj dobi postoji visok stupanj korelacije između pojedinih antioksidacijskih enzima, zbog čega su ženke bolje od mužjaka zaštićene od oksidacijskog stresa. Naime, mužjaci starije dobi imaju povišene pokazatelje oksidacijskog stresa kao što su razina malondialdehida (MDA) i katalazna aktivnost. Nasuprot tome, ženke u hiperoksiji aktiviraju zaštitni enzim hem oksigenazu (HO-1) i citokrome sustava P450 kao što su CYP1A1 i CYP1A2, koji su regulirani prema dolje, i CYP2A5, koji je reguliran prema gore. Iz navedenih podataka možemo zaključiti da su ženke manje osjetljive na oksidacijski stres i da se ta zaštita ostvaruje zahvaljujući aktivaciji HO-1 i regulaciji enzima sustava P450. The excessive production of free radicals in organism and the imbalance between the concentration of these and the antioxidant defences has been related to the process of aging. It has been postulated that oxidative processes and antioxidant defence can bee sex related. Besides, we have noticed that at old age 60% of male mice developed hepatocellular tumors which were absent in females. Thus, it is of interest to determine oxidative and antioxidative status of aging male and female mice under conventional oxygen conditions and in 100-percet oxygen with possible mechanisms involved. The process of lipid peroxidation and antioxidant enzyme activity was age and sex-related, favouring males over females throughout the lifespan. The sensitivity of a cell to free radical attack apparently depends on the relationship among antioxidant enzymes rather than on absolute activities of individual antioxidant enzymes. Indeed, our results imply stronger correlative links in old female than male mice, which might explain why old females are better protected from oxidative stress than males. In the liver of hyperoxia treated mice sex-related difference was found at the physiological level observing malondialdehyde (MDA) increment (one of the end products of lipid peroxidation) and increased catalase (CAT) activity only in male mice. Hyperoxia did upregulate a stress responsive enzyme heme-oxygenase-1 (HO-1), but only in female mice. Also, stress related izoenzymes of the cytochrome P450 family were changed. In female mice Cyp1A1 and Cyp1A2 were downregulated and Cyp2A5 was upregulated. The results of our study suggest that females are less susceptible to oxidative stress by two major mechanisms: upregulated expression of HO-1 genes and different expression of certain P450 enzymes. Croatian Academy of Sciences and Arts 2010-12-15 text pdf http://hrcak.srce.hr/63155 http://hrcak.srce.hr/file/94661 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.508=35; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:63157 2011-01-11 journal:117

Telomere kontroliraju stanično starenje Telomeres Control Cell Aging Rubelj, Ivica; Ruđer Bošković Institute, Zagreb, Croatia; ivica.rubelj@irb.hr Telomere; stanična senescencija; starenje; skraćivanje telomera; ljudski fibroblasti telomeres; cell senescence; aging; telomere shortening; human fibroblasts Dobro je poznato da razni stanični tipovi sisavaca imaju ograničen rast kad se uzgajaju u kulturi, što nazivamo staničnim starenjem. Brojni dokazi upućuju na to da je takav ograničen stanični rast osnova procesa starenja. Nedavna otkrića pokazala su da su telomere ključne za navedene procese i za kontrolu staničnog ciklusa, (ne)stabilnosti genoma i imortalizaciju. U ovom pregledu bit će riječi o telomerama koje su pružile objašnjenja za razne fenomene procesa starenja i karcinogeneze. It has been well established that various mammalian cells demonstrate a limited growth capacity in culture referred to as cellular or replicative senescence. There is also some evidence in support of the idea that this is the basis for organismal aging. Recent studies have revealed the molecular mechanisms of telomere involvement in cell senescence, cell cycle control, genome (in)stability and immortalization. This has provided an explanation of various phenomena related to process of aging and carcinogenesis. In this review we aim to describe some of the most important features of normal cell aging and the that result in malignant transformation. Croatian Academy of Sciences and Arts 2010-12-15 text pdf http://hrcak.srce.hr/63157 http://hrcak.srce.hr/file/94664 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.508=35; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:63159 2011-01-11 journal:117

Nedostatna aktivnost S-adenozilhomocistein hidrolaze (AHCY): prirodni modelni sustav za istraživanje staničnih metilacija S-Adenosylhomocysteine Hydrolase (AHCY) Deficiency: A Natural Model System for Methylation Research Belužić, Robert; Ruđer Bošković Institute, Division of molecular medicine, Zagreb, Croatia Vugrek, Oliver; Ruđer Bošković Institute, Division of molecular medicine, Zagreb, Croatia; ovugrek@irb.hr methylation disorder; metabolic disease; genotype-phenotype; homocysteine; human mutation; S-Adenosylmethionine (SAM); S-Adenosylmethionine (SAM); S-Adenosylhomocysteine-hydrolase (AHCY) Methylomics; omics research; methyltransferase; transmethylation; homocysteine; genotype – phenotype Nedostatna aktivnost AHCY-ja naziv je novog poremećaja metilacijskih procesa kod čovjeka, otkrivenog u Hrvatskoj, koji je prirodni model u istraživanju metiloma. Metilacijski procesi važni su u regulaciji staničnih procesa te imaju ključnu ulogu u regulaciji ekspresije gena, genskog upisa (imprinting), prijenosa signala, sintezi proteina te metabolizmu lipida. Upravo zbog tako širokog spektra funkcija, proučavanje metilacije zahtijeva interdisciplinarni pristup istraživanju. Povezivanje genomike, proteomike, celomike, lipidomike i metabolomike te ostalih ‘omics’ pristupa dovest će do novog integriranog područja istraživanja – ‘AHCYdomika’ – te stvaranja nove platforme za istraživanje metilacijskih procesa temeljene na nedostatnoj aktivnosti AHCY-ja. Takva istraživačka platforma omogućit će potpuno iskorištavanje mogućnosti koje pruža model baziran na ovom poremećaju, doprinijeti razvoju novih metoda te, nakraju, boljem razumijevanju ljudskog metiloma. AHCY deficiency is a new human methylation disorder, discovered recently in Croatia, and a natural model for investigating processes related to the methylome. Methylation plays an important role in regulating biological processes and is crucial for gene expression, imprinting, signalling, protein synthesis and lipid metabolism. Thus, methylation has broad impact and provides a suitable base for interdisciplinary research. Linking genomics, proteomics, cellomics, lipidomics and metabolomics and other omics approaches may create a new research avenue – ‘AHCYdomics’ - a new methylation research platform based on AHCY deficiency. Using such research platform will allow to efficiently explore the full potential of the human methylation disorder AHCY deficiency, and to design methods and approaches that will lead to a better understanding of the human methylome. Croatian Academy of Sciences and Arts 2010-12-15 text pdf http://hrcak.srce.hr/63159 http://hrcak.srce.hr/file/94667 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.508=35; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:63163 2011-01-11 journal:117

Budućnost liječenja karcinoma prostate cijepljenjem The Future of Therapeutic Vaccination of Prostate Carcinoma Vuk-Pavlović, Stanimir; Stem Cell Laboratory, Mayo Clinic Cancer Center; Division of Hematology and Division of Preventive and Occupational Medicine, Department of Internal Medicine; College of Medicine, Mayo Clinic, Rochester, Minnesota, USA; vuk_pavlovic@mayo.edu karcinom prostate; mirovanje bolesti, stanično cjepivo; potisnuta imunost; terapijsko cijepljenje; zloćudne matične stanice cancer stem/initiating cells, cellular vaccine, prostate cancer, progression–free survival, systemic immunosuppression, therapeutic vaccination Autor sažeto iznosi svoj pogled na trenutno klinički najodređenija istraživanja liječenja na kastraciju neosjetljivog rasprostranjenog (metastatskog) karcinoma prostate staničnim cijepljenjem. Razmatra cjepivo koje se sastoji od cijelih alogenskih stanica raka prostate; u kliničkom istraživanju to je cjepivo udvostručilo vrijeme do napredovanja bolesti u usporedbi s povijesnim podacima. U drugom je istraživanju pripravak vlastitih imunih stanica za četiri mjeseca produljio ukupno preživljenje. Analiza tako ograničenih i privremenih učinaka suvremenih imunoterapijskih metoda navodi na zaključak da će budućnost terapijskog cijepljenja morati uzeti u obzir učinak na matične/poticajne stanice karcinoma prostate te potisnutu sveukupnu imunost opaženu u oboljelih; u njih su potisnute ne samo za antigen specifične imune stanice, već i stanice uređene imunosti. Autor ističe da je za budući proboj potreban na sistemskoj biologiji temeljen napredak u razumijevanju koevolucije zloćudne bolesti i imunosti. The lecture summarizes author’s views of the current status of the clinically most advanced studies of therapeutic cellular vaccination of disseminated castration-resistant prostate cancer. The author discusses an allogeneic whole-cell prostate cancer vaccine that doubled the progression-free survival compared to historic controls in a phase 2 study and a phase 3 study of a preparation of autologous immune cells that demonstrated a four-month extension of overall survival. The analysis of such limited and transient effects of the current immunotherapy methods leads to the conclusion that the future of vaccine-based immunotherapy of prostate cancer will have to account for prostate cancer stem/initiating cells and for systemic immunosuppression observed in prostate cancer patients. Immunosuppression includes the failure not only of antigen-specific immune cells, but of the cells of innate immunity as well. Most importantly, major breakthrough in prostate cancer immunotherapy will be greatly facilitated by the advances in systems-biology based understanding of the co-evolution of the malignancy and immunity. Croatian Academy of Sciences and Arts 2010-12-15 text doc http://hrcak.srce.hr/63163 http://hrcak.srce.hr/file/94672 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.508=35; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:66032 2011-03-30 journal:117

150 Years of Academy and 60 Years of RAD-Medical Sciences Pećina, Marko; Croatian Academy of Sciences and Arts, Zagreb, Croatia; marko.pecina@zg.t-com.hr Croatian Academy of Sciences and Arts 2011-03-11 text pdf http://hrcak.srce.hr/66032 http://hrcak.srce.hr/file/98787 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.509=36; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:66033 2011-03-30 journal:117

Chronic Heart Failure and Mechanical Circulatory Support Sutlić, Željko; Department of Cardiac Surgery, University Hospital Dubrava, Zagreb, Croatia Croatian Academy of Sciences and Arts 2011-03-11 text pdf http://hrcak.srce.hr/66033 http://hrcak.srce.hr/file/98788 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.509=36; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:66034 2011-03-30 journal:117

Dugotrajna mehanička potpora cirkulaciji: kirurške tehnike Long-term Mechanical Circulatory Support: Surgical Techniques Barić, Davor; Department of Cardiac Surgery, University Hospital Dubrava, Zagreb, Croatia Sutlić, Željko; Department of Cardiac Surgery, University Hospital Dubrava, Zagreb, Croatia; zsutlic@kbd.hr Rudež, Igor; Department of Cardiac Surgery, University Hospital Dubrava, Zagreb, Croatia Unić, Daniel; Department of Cardiac Surgery, University Hospital Dubrava, Zagreb, Croatia Planinc, Mislav; Department of Cardiac Surgery, University Hospital Dubrava, Zagreb, Croatia Jonjić, Dubravka; Department of Cardiac Surgery, University Hospital Dubrava, Zagreb, Croatia zatajenje srca; mehanička potpora cirkulaciji; kirurška tehnika heart failure; mechanical circulatory support; surgical technique Dugotrajna mehanička potpora cirkulaciji postala je provjerena metoda u liječenju završne faze srčanog zatajenja. Kod odabranih bolesnika, dokazano je da poboljšava preživljenje, bilo kao potpora do transplantacije ili destinacijske terapije. U članku opisujemo tehnike ugradnje, strategije u cilju smanjenja prekomjernog krvarenja, zatajenja desnog srca te infekcije oko mjesta izlaska kabela za napajanje. Long-term mechanical circulatory support has become a valid treatment option for end stage heart failure. In selected patients’ cases, this therapeutic option has been proven to improve survival, both as a bridge to transplant and as a destination therapy. In this article, we address implantation technique, strategies to prevent excessive bleeding, right heart failure, and driveline and pocket infection. Croatian Academy of Sciences and Arts 2011-03-11 text pdf http://hrcak.srce.hr/66034 http://hrcak.srce.hr/file/98790 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.509=36; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:66035 2011-03-30 journal:117

Prijedlog programa vježbanja bolesnika s dugotrajnom i kratkotrajnom mehaničkom potporom Considerations for Exercise Therapy With Short-term and Long-term Mechanical Circulatory Support Bindoff, Catherine; Physiotherapy Department, Royal Brompton & Harefield NHS Foundation Trust, UK; C.Bindoff@rbht.nhs.uk fizioterapija; vježbanje; mehanička potpora srcu i cirkulaciji; MSC; VAD physiotherapy; exercise; mechanical circulatory support; MSC; Ventricular assist device; VAD Nakon ugradnje mehaničke potpore srcu i cirkulaciji (MSC) važna je uloga fizioterapeuta u dobroj pripremi pacijenta za eksplantaciju uređaja, transplantaciju ili ugradnju dugoročnog MSCa. Kako bi program vježbanja bio siguran i efektivan za pacijenta, potrebna je dobra priprema fizioterapeuta. Što je sve potrebno razmotriti kod fizioterapije pacijenata s ugrađenim kratkoročnim odnosno dugoročnim MCS uređajem prikazano je u ovom članku. Once a mechanical circulatory support (MCS) system has been inserted the physiotherapists’ role is crucial to prepare the patient either for transplantation, for upgrade to long-term MCS or for device explant. There are numerous considerations for rehabilitation that should be addressed in order to provide a safe and effective exercise programme. This paper highlights considerations for exercise in both short-term and long-term MCS devices. Croatian Academy of Sciences and Arts 2011-03-11 text pdf http://hrcak.srce.hr/66035 http://hrcak.srce.hr/file/98792 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.509=36; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:66340 2011-04-09 journal:117

Kratkotrajna potpora cirkulaciji i izmjeni plinova u krvi Short-term mechanical circulatory support Biočina, Bojan; Department of Cardiac Surgery, University Hospital Zagreb, Zagreb, Croatia; bbiocina@kbc-zagreb.hr Petričević, Mate; Department of Cardiac Surgery, University Hospital Zagreb, Zagreb, Croatia mehanička cirkulacijska potpora; zatajenje srca ventricular assist device; heart failure; mechanical circulatory support Zatajenje srca s porastom incidencije i prevalencije u sve starijoj populaciji polako postaje javno zdravstveni problem. Mehanička cirkulacijska potpora se koristi kao oblik liječenja u skupini bolesnika s uznapredovalim zatajenjem srca. Mehanička crpka se kirurški implantira kako bi osigurala, bilo pulsatilni, bilo nepulsatilni protok krvi koji služi kao supplement ili kao zamjena protoku krvi kojeg bi trebalo generirati srce. Glavni cilj i namjena mehaničke cirkulacijske potpore je volumno rasteretiti srce u terminalnom zatajenju i pomoći u održavanju protoka vitalnih organa održavajući minutni volumen. Prisutna je široka paleta uređaja: od onih koji se mogu perkutano implantirati, uređaja za kratkoročnu potporu koji se mogu koristiti u operacijskoj sali, u laboratoriju za kateterizaciju kao i u jedinici intenzivnog liječenja do potpuno implantibilnih uređaja za dugoročnu potporu. Uređaji mogu biti korišteni kao terapija premoštenja do oporavka ili do transplantacije srca ili, u pojedinim slučajevima, uređaji predstavljaju definitivnu terapiju, npr. kod bolesnika u kojih je kontraindicirana transplantacija. Ovaj oblik liječenja ne uključuje samo kardiokirurge, već i kardiologe, anesteziologe kao i perfuzioniste. Pravilna trijaža bolesnika predstavlja ključnu točku uspjeha u ishodu liječenja volesnika s mehaničkom cirkulacijskom potporom. Prijeoperacijska stratifikacija rizika je iznimno važna u minimaliziranju stope perioperacijsakog mortaliteta. Istovremeni tehnološki razvoj, kao i multidisciplinarna suradnja konstruktora uređaja, znanstvenika, liječnika i ostalog medicinskog osoblja dovest će do unaprijeđenja cjelokupnog procesa liječenja ove skupine bolesnika. Daljnji tehnološki razvoj ide u smjeru pojednostavljenja procesa implantacije, s manjim, efikasnijim, trajnijim i još više pouzdanijim uređajima. Heart failure continues to be an ever-growing public health concern. The continued aging of the population has contributed to the increasing incidence and prevalence of heart failure. Mechanical circulatory support is used to treat patients with advanced heart failure. A mechanical pump is surgically implanted to provide pulsatile or non-pulsatile flow of blood to supplement or replace the blood flow generated by the native heart. The main purpose of a mechanical circulatory support is to unload the failing heart and help maintain forward cardiac output and vital organ perfusion. A big variety of devices exists: from the percutaneous and short-term support, which can be used in the operating room or the cath-lab and afterwards in the intensive or coronary care units, to the internal and long-term devices, which can be used as a bridge-to-recovery or cardiac transplant, or as definitive therapy in patients with contraindication to cardiac transplant. This treatment involves not only the cardiac surgeons, but also the cardiologists, anaesthesiologists, intensivists and perfusionists. Appropriate patient selection represents the critical determinant of successful outcomes with the VAD therapy. The predictive risk stratification is extremely important for achieving the minimal peri-operative mortality rate. As VAD technology progresses, the collaboration of multidisciplinary teams composed of engineers, scientists, physicians, and nurses will continue to refine the technology and improve patient care and operation outcomes. Advances in device design will allow for an easier implantation and create smaller, more efficient, durable, and reliable units. Croatian Academy of Sciences and Arts 2011-03-11 text pdf http://hrcak.srce.hr/66340 http://hrcak.srce.hr/file/99177 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.509=36; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

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Postoperacijsko liječenje bolesnika s mehaničkom potporom srca u jedinici intenzivnog liječenja. Postoperative Management of Patients after VAD Implementation Bradić, Nikola; Department of Anesthesiology and Intensive Care, University Hospital Dubrava, Zagreb, Croatia;; nbradic@kbd.hr Planinc, Mislav; Department of Cardiac Surgery, University Hospital Dubrava, Zagreb, Croatia Barišin, Stjepan; Department of Anesthesiology and Intensive Care, University Hospital Dubrava, Zagreb, Croatia LVAD; hemodinamika; TEE , LVAD i nekardijalne operacije LVAD; hemodynamics; TEE; LVAD; noncardiac surgery Nakon ugradnje lijevostrane srčane potpore (LSP), bolesnici se zaprimaju u jedinicu intenzivne medicine. Tijekom ovog razdoblja od nekoliko dana, osnovni cilj poslijeoperacijskog liječenja je stabilizacija bolesnikove hemodinamike. Praćenje kontinuiranog minutnog volumena, tlakova punjenja i sustavne rezistencije je neophodno za ispravno funkcioniranje LSP-a. Uporaba plućnog arterijskog katetera s kontinuiranim mjerenjem minutnog volumena te transezofagijska ehokardiografija su primarni postupci. Za vrijeme rada LSP, praćenje funkcije desne klijetke te rano uočavanje njene disfunkcije od krucijalnog su značaja za dobar ishod bolesnika. Daljnje moguće komplikacije u ovih bolesnika su povećani rizik od krvarenja, kao i od nastanka tromboembolija. Incidencija infekcija u ovih bolesnika je visoka, i kreće se do 40%, osobito infekcije kanila. U slučaju zastoja rada srca, primjenjuju se posebni postupci oživljavanja, koji se razlikuju od uobičajenih algoritama. Na kraju, prikazane su i specifičnosti anesteziološkog postupka u ovih bolesnika ukoliko postoji potreba za nekardijalnom operacijom. After the implantation of the left ventricular assisted device (LVAD), patients are admitted in intensive care unit (ICU). During the period of first several days, the goal of the postoperative care is to stabilize the patients’ hemodynamics. Monitoring the continuous cardiac output, filling volumes and outflow resistance is necessary for the proper functioning of the pump. The use of pulmonary artery catheter and the transesophageal echocardiography are primary procedures. During the operation of the left ventricular support, the measuring of proper ventricular function and the early recognition of its dysfunction is important for a positive outcome. Further potential complications in connection with these patients are an increased risk of hemorrhage and thromboembolism. The infection of drivelines and devices in the early postoperative period occurs in up to 40 % of these patients. In case of a cardiac arrest, a special procedure has to be performed in patients in whom LVAD was implanted. Finally, we have shown the anesthesiologic management in cases when patients with LVAD have to undergo noncardiac surgery. Croatian Academy of Sciences and Arts 2011-03-11 text pdf http://hrcak.srce.hr/66341 http://hrcak.srce.hr/file/99179 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.509=36; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

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Rezultati ugradnje Levitronix Centrimag mehaničke potpore srcu u Kliničkom bolničkom centru Zagreb Initial Clinical Results with the Levitronix Centrimag Mechanical Assist Device at the University Hospital Rebro Zagreb Gašparović, Hrvoje; Departments of Cardiac Surgery, Anesthesiology and Cardiology, University Hospital Zagreb, Zagreb, Croatia; hgasparovic@gmail.com Petričević, Mate; Departments of Cardiac Surgery, Anesthesiology and Cardiology, University Hospital Zagreb, Zagreb, Croatia Ivančan, Višnja; Departments of Cardiac Surgery, Anesthesiology and Cardiology, University Hospital Zagreb, Zagreb, Croatia Miličić, Davor; Departments of Cardiac Surgery, Anesthesiology and Cardiology, University Hospital Zagreb, Zagreb, Croatia Biočina, Bojan; Departments of Cardiac Surgery, Anesthesiology and Cardiology, University Hospital Zagreb, Zagreb, Croatia Levitronix Centrimag; mehanička potpora srcu Levitronix Centrimag; ventricular assist device Uvod: Liječenje terminalne faze srčanog popuštanja je revolucionarizirano uvođenjem mehaničke potpore srcu. Levitronix Centrimag je uređaj dizajniran u svrhu kratkoročne hemodinamske potpore prije nego što trajnije rješenje cirkulatornog problema postane moguće. Do sad se primijenjivao kao podrška srcu do transplantacije srca, do oporavka srčane funkcije ili do ugradnje trajnijeg oblika mehaničke potpore srcu. Metode: U periodu između rujna 2008 i studenog 2009 Levitronix Centrimag je u našoj ustanovi ugrađen u 6 bolesnika. U jednog bolesnika radilo se o postkardiotomijskom sindromu niskog minutnog volumena. U preostalih pet bolesnika ovaj je oblik mehaničke potpore srcu ugrađen elektivno radi progresivnog kliničkog pogoršanja bolesnika u terminalnoj fazi srčanog popuštanja koje je postalo rezistentno na konzervativnu terapiju. Rezultati: Bolesnik u kojeg je indikacija za mehaničkom potporom srcu bila postavljena hitno u postkardiotomijskom srčanom popuštanju bio je 65 godina star. Imao je ejekcijsku frakciju od 20% dok mu je logistički EuroSCORE bio 25. Prijeoperacijski NT-pro-BNP bio je 9428 pg/ ml dok su serumske vrijednosti laktata prije implantacije Centrimaga bile 8.8 mmol/L. Prosječna dob u skupini bolesnika u kojih je indikacija za mehaničku potporu srcu bila progresivna dekompenzacija srčane funkcije bila je 46 ± 11 godinu. Navedeni bolesnici su imali prosječnu ejekcijsku frakciju od 16 ± 2% dok im je logistički EuroSCORE bio 28 ± 7. Prijeoperacijske vrijednosti serumskog laktata i NT-pro-BNP bile su 1.7±0.8 mmol/L i 9577 ± 3674 pg/ml. U troje bolesnika bila je evidentna kompromitacija funkcije nekog od ostalih organskih sustava. U jednog bolesnika se radilo o akutnom renalnom zatajenju ovisnog o hemodijalizi, u drugog o neurokognitivnoj disfunkciji praćenog sa bubrežnim zatajenjem ali bez potrebe za dijalizom. U trećeg bolesnika radilo se o primarnoj hepatalnoj insuficijenciji. U prva dva bolesnika došlo je do poboljšanja organskih funkcija nakon uspostave mehaničke potpore srcu, dok u trećeg bolesnika nije došlo do promjene hepatalne funkcije budući da ista nije bila uzrokovana malperfuzijom. Bolesnik u kojeg je mehanička potpora srcu stavljena zbog postkardiotomijskog kardiogenog šoka je umro. Troje od pet bolesnika kod kojih je Levitronix Centrimag ugrađen radi dekompenzacije kroničnog zatajenja srca su uspješno transplantirani. Preostalo dvoje bolesnika je umrlo od septičnih komplikacija. U kohorti bolesnika u kojoj je mehanička potpora srcu ugrađena elektivno, dvoje bolesnika je zahtijevalo potporu oba ventrikula dok je u troje ugrađena potpora samo lijevom. Zaključak: Levitronix Centrimag pruža efikasnu hemodinamsku potporu bolesnicima sa kompromitiranom srčanom funkcijom. Neophodno je započeti sa mehaničkom potporom srcu prije nego što se pojave ireverzibilne disfunkcije ostalih organskih sustava. Background: The management of end stage heart failure has been revolutionized by the use of mechanical circulatory support. The Levitronix Centrimag ventricular assist device (VAD) is designed for short-term cardiac assistance as a bridge to a more permanent solution to the hemodynamic problem. It has been used as bridge-to-transplantation, bridge-to-bridge, bridge-to-recovery, and bridge-to-decision. Methods: In the period between September 2008 and November 2009, six patients received mechanical cardiac assistance with the Levitronix Centrimag device at our institution. In one patient, the indication was postcardiotomy cardiogenic shock. In the remaining five patients, the device was implanted electively, due to progressive decompensation of chronic heart failure unresponsive to medical therapy. Results: The patient having received a biventricular assist device (BIVAD) in the postcardiotomy setting was 65 years of age. His ejection fraction and EuroSCORE were 20 % and 25, respectively. His NT-pro-BNP was 9,428 pg/ml and his pre-implantation lactate was 8.8 mmol/L. The mean age in the group of patients, in whom the VAD was placed due to decompensated severe heart failure (DSHF ), was 46 ± 11 years. Their ejection fraction and logistic EuroSCORE were 16 ± 2 % and 28 ± 7, respectively. The preoperative serum lactate and NT-pro-BNP concentrations were 1.7±0.8 mmol/L and 9577 ± 3674 pg/ml, respectively. Of these, three patients had evidence of end organ dysfunction. The low cardiac output was responsible for acute renal failure, requiring renal replacement therapy in one patient. Neurocognitive dysfunction and renal failure not requiring dialysis was seen in another. The third patient had long standing primary hepatic insufficiency. A reversal of end organ dysfunction was seen in the former two patients, whereas the hepatic insufficiency was not caused by hemodynamic compromise and was, therefore, not relieved by circulatory support. The single patient, who had suffered from postcardiotomy cardiogenic shock, died shortly after receiving mechanical circulatory support. Three of five patients, in whom Levitronix Centrimag was placed electively, were successfully transplanted. The remaining two died of septic complications. In the cohort of patients, in whom ventricular assistance was placed due to DSHF , two required BIVAD placement, and three left ventricular assist devices (LVAD). Conclusion: The Levitronix Centrimag VAD is useful in supporting circulation in patients with acute decompensation of congestive heart failure. It may also be used in patients with postcardiotomy shock. It is an imperative for the device to be placed before irreversible organ dysfunction occurs as the aftermath of malperfusion. Croatian Academy of Sciences and Arts 2011-03-11 text pdf http://hrcak.srce.hr/66342 http://hrcak.srce.hr/file/99181 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.509=36; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

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Najbolji izbor – kako izabrati odgovarajući uređaj? Take the Best – How to Choose the Rig ht Device? Hirt, Stephan W.; Department of Cardiothoracic Surgery, University Medical Centre, Regensburg, Germany; Stephan.Hirt@klinik.uni-regensburg.de Schmid, Christof; Department of Cardiothoracic Surgery, University Medical Centre, Regensburg, Germany zatajivanje srca; mehanička potpora srcu; transplantacija srca cardiac failure; mechanical assist device; heart transplantation Sve veći broj pacijenata u terminalnoj fazi zatajivanja srca zahtijevaju ugradnju mehaničke potpore srcu i cirkulaciji, kao premoštenje do transplantacije srca ili kao destinacijska terapija. Odabir odgovarajućeg uređaja ovisi o kliničkom stanju pacijenta, potrebi za jednostrukom ili dvostrukom ventrikularnom potporom, očekivanom trajanju ugrađene potpore i mogućnostima institucije. Pacijentima s multi organskim zatajenjem i nejasnim neurološkim smetnjama može se prvo ugraditi rotacijska pumpa/ECMO, te u slučaju oporavka., parakorporalni uređaj može biti povezan s ranije implantiranim kanilama. Kod stabilnih pacijenata, predodređenih za ugradnju potpore lijevom ventriklu, moguće je ugraditi intrakorporalni uređaj druge generacije, koji dozvoljava slobodno kretanje 6-8 sati do punjenja baterija i podupire intervale preko jedne godine. Ograničenja nastaju zbog potrebe za visokim dozama antikoagulacijske terapije i pojave određenih komplikacija, posebno u prva tri mjeseca nakon implantacije (krvarenje, tromboembolija, infekcija, mehaničke nepravilnosti). Stopa preživljenja 12 mjeseci nakon ugradnje LVAD-a je 74% i 55% nakon 24 mjeseca što je značajno bolje nego preživljenje nakon ugradnje RVAD, BVAD or TAH. An increasing number of patients suffering from end-stage heart failure require VAD implantation as either a bridge-to-transplantation or destination therapy. The choice of the right device depends upon the medical urgency; the need of uni- or biventricular support; the duration of support expected; and the institutional availability. Patients with multi-organ failure and unclear neurological situation can be supported with rotary pumps/ECMO first, and in case of recovery, a paracorporeal system can be connected to the previously implanted cannulas. In stable patients qualifying for left ventricular support, an intracorporeal system of the second generation can be implanted, allowing freedom of movement for 6-8 hours before recharging becomes necessary, and support intervals exceeding 1 year. Restrictions are given by the need of high-dose anticoagulation and a certain complication rate, especially in the first 3 months (bleeding, thromboembolism, infection, mechanical failure). The survival rate after the primary LVAD implantation is 74 % after 12 months and 55 % after 24 months; this is significantly better than the survival rate after RVAD, BVAD or TAH. Croatian Academy of Sciences and Arts 2011-03-11 text pdf http://hrcak.srce.hr/66343 http://hrcak.srce.hr/file/99183 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.509=36; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

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Rana klinička iskustva sa dugoročnom potporom (Thoratec) Long-term Mechanical Circulatory Support for Patients with Terminal Stage of Congestive Heart Failure: A Case Report Jonjić, Dubravka; Department for Cardiac Surgery, University Hospital Dubrava, Zagreb, Croatia; djonjic@kbd.hr Planinc, Mislav Planinc; Department for Cardiac Surgery, University Hospital Dubrava, Zagreb, Croatia Sutlić, Željko; Department for Cardiac Surgery, University Hospital Dubrava, Zagreb, Croatia Barić, Davor; Department for Cardiac Surgery, University Hospital Dubrava, Zagreb, Croatia Rudež, Igor; Department for Cardiac Surgery, University Hospital Dubrava, Zagreb, Croatia Unić, Daniel; Department for Cardiac Surgery, University Hospital Dubrava, Zagreb, Croatia Čekol, Zorana; Department for Cardiac Surgery, University Hospital Dubrava, Zagreb, Croatia kongestivno zatajivanje srca; transplantacija srca; mehanička cirkulacijska potpora; mehanička potpora lijevom ventriklu congestive heart failure; heart transplantation; mechanical circulatory support; left ventricular assist device (LVAD) Unatoč novijim dostignućima u liječenju kongestivnog zatajivanja srca, broj ljudi sa srčanim popuštanjem kontinuirano raste što dovodi do povećane stope mortaliteta i morbiditeta. Transplantacija srca je često ograničena zbog nedostatka broja adekvatnih donora, a medikamentozna terapija ostaje palijativna. Korištenje mehaničke cirkulacijske potpore (LVAD-left ventricular assist device), kao standardne terapije u liječenju završne faze zatajivanja srca značajno je poboljšalo ishod liječenja. Mehanička potpora lijevom ventriklu, prvotno primjenjena kao metoda privremenog premoštenja prema ozdravljenju (bridge-to-recovery), zatim kao premoštenja do transplantacije (bridge– to-transplantation), danas se primjenjuje kao trajna opcija liječenja bolesnika s terminalnom fazom srčanog zatajivanja. U ovom radu prikazan je slučaj bolesnika s dilatativnom kardiomiopatijom, kojem je po prvi puta, u Republici Hrvatskoj, zbog zatajivanja srca ugrađena parakorporalna mehanička potpora lijevom srcu. Despite recent advances in treatment, the number of people with heart failure continues to grow; this is associated with high mortality and morbidity rates. Heart transplantation is very limited due to the lack of the adequate number of heart donors, and medical therapy remains palliative. He use of ventricular assist devices (VADs) has led to improved survival rates for patients with severe heart failure. Originally introduced as a temporary bridge-to-recovery, and later as a bridge-to-transplantation, VADs have evolved to permanent or destination therapy for patients with terminal stage of congestive heart failure1. In this paper, we report of our patient with dilatative cardiomyopathy, to whom – due to the end-stage heart failure, and for the first time in Croatia – a device for paracorporeal long-term mechanical left ventricular support (pVAD) was implanted. Croatian Academy of Sciences and Arts 2011-03-11 text pdf http://hrcak.srce.hr/66344 http://hrcak.srce.hr/file/99185 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.509=36; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

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Intraoperacijski TEE i anesteziološko liječenje bolesnika s mehaničkom potporom srca Intraoperative Transesophageal Echocardiography and Anesthetic Considerations in Patients with Ventricular Assist Devices Kristović, Darko; Department of Anesthesiology and Intensive Care, University Hospital Dubrava, Zagreb, Croatia; dkristov@kbd.hr transezofagusna ehokardiografija; uređaj za mehaničku potporu; desno-lijevi shunt (D-L); izvantjelesni krvotok transesophageal echocardiography; ventricular assist device; right-to-left shunt; cardiopulmonary bypass Uređaj za mehaničku potporu srcu (eng. VAD) se ugrađuje radi pružanja mehaničke potpore srcu i cirkulaciji. Njime se osigurava oporavak miokarda nakon stunninga i hibernacije, i u isto vrijeme održava perfuzija vitalnih organa (eng. bridge-to-recovery). Ukoliko se miokard ne može oporaviti od oštećenja tada je cilj ovakve terapije pružiti potporu bolesniku do trenutka transplantacije srca (eng. bridge-to-transplantation), ili ukoliko bolesnik nije pogodan za transplantaciju, poboljšati mu kvalitetu života u ograničenom vremenu (ciljna terapija). Perioperacijski TEE je glavna metoda u liječenju i nadziranju takvih bolesnika koja pruža brojne informacije i kirurgu i anesteziologu, olakšavajući pri tom donošenje važnih terapijskih odluka. Uz osnovni standardni pregled, za ehokardiografsku procjenu su važni i za uređaj specifični pre-, intra- i postoperacijski ehokardiografski pregled. To uključuje: (a) pregled srca i velikih krvnih žila prije postavljanja VAD uređaja, kako bi se isključila značajnija aortna regurgitacija, trikuspidna regurgitacija, mitralna stenoza, otvoreni foramen ovale i druge abnormalnosti koje bi mogle dovesti do D-L shunt-a nakon postavljanja VAD-a, stvaranja intrakardijalnih tromba, ventrikulskih ožiljaka, plućne regurgitacije i hipertenzije, plućne embolije i aterosklerotske bolesti u uzlaznoj aorti. Važno je i procijeniti funkciju desnog ventrikula, i (b) pregled uređaja nakon postavljanja VAD-a i ponovna procjena srca i velikih krvnih žila. Cilj pregleda uređaja je potvrditi ispravnost uređaja, izvršenog srčanog odzračivanja; potvrditi ispravan položaj kanila i njihovu prohodnost, kompetentnost valvula i to uporabom dvodimenzionalnog, obojenog, kontinuiranog i pulsnog doplera. Cilj pregleda srca nakon implantacije je isključiti aortnu regurgitaciju ili neprepoznati D-L shunt, i procijeniti funkciju desnog ventrikla, odterećenost lijevog ventrikla i općenito učinak različitih podešavanja uređaja na globalnu srčanu funkciju. A ventricular assist device (VAD) is inserted to provide mechanical circulatory support. A VAD can rest the myocardium and allow it to recover from stunning or hibernation, while maintaining vital organ perfusion (bridge-to-recovery). If myocardial recovery cannot occur, the goal is to support the patient to transplantation (bridge-to-transplantation), or, if the patient is not a transplant candidate, to enhance the quality of life for a limited period of time (destination therapy). Perioperative transesophageal echocardiography is a major component of patient management, and it is important for surgical and anesthetic decision-making. In addition to the standard examination, device-specific pre-, intra-, and postoperative considerations are essential to the echocardiographic evaluation. These include: (a) the pre-VAD insertion examination of the heart and large vessels, in order to exclude significant aortic regurgitation, tricuspid regurgitation, mitral stenosis, patent foramen ovale or other cardiac abnormality that could lead to right-to-left shunt after the left VAD placement, intracardiac thrombi, ventricular scars, pulmonic regurgitation, pulmonary hypertension, pulmonary embolism and atherosclerotic disease in the ascending aorta; and to assess the right ventricular function; and (b) the post-VAD insertion examination of the device and reassessment of the heart and large vessels. The examination of the device aims to confirm the completeness of the device and heart deairing, cannulas alignment and patency, and the competency of the device valves using two-dimensional, and color, continuous and pulsed wave Doppler modalities. The goal of the heart examination after the implantation should be to exclude the aortic regurgitation or an uncovered rightto- left shunt, and to assess the right ventricular function, the left ventricular unloading, and the effect of the device settings on the global heart function. Croatian Academy of Sciences and Arts 2011-03-11 text pdf http://hrcak.srce.hr/66345 http://hrcak.srce.hr/file/99187 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.509=36; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:66346 2011-04-09 journal:117

Ehokardiografska procjena bolesnika s mehaničkom potporom srcu Heart Mate II Echocardiographic Evaluation of Patients with Heart Mate II Continuous Flow Ventricular Assist Device Paluszkiewicz, Lech; Heart and Cardiovascular Centre Nordrhein-Westwalen, Essen, Germany; l.paluszkiewicz@contilia.de ehokardiografija; mehanička potpora srcu echocardiography; ventricular assist device Ehokardiografija igra ključnu ulogu u kliničkoj prognozi pacijenta prije i poslije ugradnje uređaja za mehaničku potporu srcu i cirkulaciji. Ova metoda uključuje standardni pregled sa specifičnim pogledom na ventrikularni potporni uređaj. Područje pregleda ovisi o vrsti uređaja, metodi implantacije i smještaju ulazne i izlazne kanile. Ovaj članak opisuje ehokardiografski pregled pacijenta te što je sve potrebno sagledati prilikom preoperativnog, intraoperativnog i postoperativnog pregleda. Prikazan je način upotrebe transtorakalnog i transezofagijskog ehokardiografa. Opisuju se i metode dijagnosticiranja nepravilnog rada uređaja za mehaničku potporu. Autor naglašava kompleksnost dijagnostike pacijenata s ugrađenom mehaničkom potporom srcu i cirkulaciji te prikazuje ehokardiografiju kao neophodnu dijagnostičku metodu kod ovih pacijenata. Echocardiography plays an important role in evaluating patients both before and after the implantation of mechanical circulatory support devices. It consists of a standard examination expanded to specific aspects of ventricular assist devices. The scope of examination varies according to the type of the device, the method of implantation and the localization of the inflow and outflow cannulas. This article is focused on the echocardiographic examination of patients undergoing the implantation of the HeartMate II (Thoratec) – a continuous-flow ventricular assist device. It provides a review of all the important parts of the examination, including the preoperative, the intraoperative and the postoperative examination. The utilization of transthoracic and transesophageal echocardiography is presented. The methods of diagnosing the malfunction of the device are also discussed. The author emphasizes that the assessment of a patient with a mechanical assist device is a complex and an interdisciplinary challenge, where echocardiography is crucial in the assessment of the patients with mechanical circulatory support devices. Croatian Academy of Sciences and Arts 2011-03-11 text pdf http://hrcak.srce.hr/66346 http://hrcak.srce.hr/file/99189 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.509=36; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:66347 2011-04-09 journal:117

Rana klinička iskustva sa dugoročnom potporom (Heart Mate II) The First Clinical Use of Heart Mate Ii Left Ventricular Assist System in Croatia as a Bridge-to-Transplant: A Case Report Planinc, Mislav; 1Division of Cardiac Surgery, University Hospital Dubrava, Zagreb, Croatia Sutlić, Željko; 1Division of Cardiac Surgery, University Hospital Dubrava, Zagreb, Croatia Barić, Davor; 1Division of Cardiac Surgery, University Hospital Dubrava, Zagreb, Croatia Šikić, Jozica; Department for Cardiovascular Disease, University Hospital Dubrava, Zagreb, Croatia Bradić, Nikola; Department of Anesthesiology, Reanimathology and Intensive Care, University Hospital Dubrava, Zagreb, Croatia Rudež, Igor; 1Division of Cardiac Surgery, University Hospital Dubrava, Zagreb, Croatia Unić, Daniel; 1Division of Cardiac Surgery, University Hospital Dubrava, Zagreb, Croatia Legac, Ante; 1Division of Cardiac Surgery, University Hospital Dubrava, Zagreb, Croatia Jonjić, Dubravka; 1Division of Cardiac Surgery, University Hospital Dubrava, Zagreb, Croatia Mrkonjić, Ruža; 1Division of Cardiac Surgery, University Hospital Dubrava, Zagreb, Croatia Čekol, Zorana; 1Division of Cardiac Surgery, University Hospital Dubrava, Zagreb, Croatia HeartMate II LVAS; premoštenje do transplantacije; zatajivanje srca heart failure; LVAD; dilatative cardiomyopathy Uređaji za potporu lijevom srcu (LVAS – left ventricular assist system) su danas prihvaćeni kao uspiješno sredstvo za premoštenje bolesnika u završnom stadiju zatajivanja srca do transplantacije. Druga generacija aksijalnih pumpi, kao što je HeartMate II , pruža sigurnu i učinkovitu hemodinamsku potporu takvim bolesnicima, poboljšavajući kvalitetu života. Danas su ti uređaji povezani sa niskom inicidencijom malfunkcije ili infekcije koje bi zahtijevale zamjenu. Prikazujemo naša tri bolesnika kojima je ugrađen HeartMate II LVAS kao premoštenje do transplantacije. Left ventricular assist systems (LVAS) are widely accepted nowadays as a successful tool for bridging the patients with end-stage heart failure to heart transplantation (BTT). The second generations of axial-flow devices, such as the HeartMate II, provide a safe and reliable, as well as an effective hemodynamic support in such patients, offering them an improved quality of life; they are furthermore associated with a very low rate of device malfunction or infection requiring device change. We report here of our first three patients with the implanted HM II LVAS as a BTT . Croatian Academy of Sciences and Arts 2011-03-11 text pdf http://hrcak.srce.hr/66347 http://hrcak.srce.hr/file/99191 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.509=36; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

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Terminalna faza zatajenja srca – transplantacija ili LVAD End Stage Heart Failure – Transplantation or Lvad ? Šikić, Jozica; Department of Cardiology, University Hospital Dubrava, Zagreb, Croatia; jsikic@kbd.hr zatajenje srca; transplantacija srca; LVAD heart failure; heart transplantation; LVAD Zatajenje srca kompleksni je klinički sindrom, a može se razviti kao posljedica bilo kojeg strukturalnog ili funkcionalnog poremećaja koji utječe na punjenje klijetki i ispumpavanje krvi. Prema podacima ISHLT registra, poluvrijeme preživljavanja nakon srčane transplantacije produžilo se s 8,9 godina u 1982. na oko 11 godina u razdoblju između 2002. i 2006. Vršni VO2 (VO2max) najobjektivniji je parametar u procjeni težine zatajenja srca i mogao bi biti najbolji prediktor stavljanja bolesnika na transplantacijsku listu. Mehanička srčana potpora indicirana je u bolesnika u kojih se farmakološkom terapijom (oralnom i parenteralnom) te nefarmakološkom s intraaortnom balon pumpom ne ostvari adekvatno poboljšanje kliničkog statusa bolesnika. LVAD potpora je lijevom srcu, a može dovesti do remodeliranja i trajnog poboljšanja funkcije lijeve klijetke. Terminalna faza zatajenja srca nije i kraj života jer transplantacija, noviji farmakološki pripravci i mehanička potpora, uključujući i VAD, bolesnicima omogućuju bolju kvalitetu i produžetak života. Heart failure is a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill or eject blood. According to the data from the International Society for Heart and Lung Transplantation registry, the half-life of patient survival after heart transplantation has progressively improved from 8.9 years in 1982 to a projected half-life of approximately 11 years from 2002 to 2006. The peak VO2 (VO2max) is the most objective assessment of functional capacity in patients with heart failure, and may be the best predictor of when to list a patient for cardiac transplantation. Mechanical cardiac support devices may be implanted in patients, in whose cases all other pharmacological therapies (oral medications and intravenous inotropes) for severe heart failure, as well as non-pharmacological support with intraaortic balloon pump counterpulsation, have failed. Left ventricular assist device provide support of the left ventricular function, causing reverse ventricular remodeling and permanent improvement of left ventricular function. End stage heart failure is not an end of life, since heart transplantation, better medications and devices, including ventricular assist devices implantations, offer patients a better quality and an appreciable extension of life. Croatian Academy of Sciences and Arts 2011-03-11 text pdf http://hrcak.srce.hr/66348 http://hrcak.srce.hr/file/99193 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.509=36; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:66349 2011-04-09 journal:117

Antimikrobna profilaksa i kontrola infekcije kod mehaničke potpore srca Antimicrobial Prophylaxis and Infection Control in Cases of Mechanical Cardiac Support Devices Škrlin, Jasenka; Department for Clinical Microbiology and Hospital Infections, University Hospital Dubrava, Zagreb, Croatia; jas@kbd.hr Sutlić, Željko; Department for Cardiac Surgery, Surgery Clinic of the Medical School in Zagreb, University Hospital Dubrava, Zagreb, Croatia Barić, Davor; Department for Cardiac Surgery, Surgery Clinic of the Medical School in Zagreb, University Hospital Dubrava, Zagreb, Croatia Rudež, Igor; Department for Cardiac Surgery, Surgery Clinic of the Medical School in Zagreb, University Hospital Dubrava, Zagreb, Croatia Unić, Danijel; Department for Cardiac Surgery, Surgery Clinic of the Medical School in Zagreb, University Hospital Dubrava, Zagreb, Croatia VAD; infekcija; biofilm; antimikrobna terapija; smjernice za prevenciju infekcija ventricular assist device; infection; biofilm; antimicrobial therapy; prevention guidelines Danas je sve većem broju bolesnika sa teškim zatajenjem srca, zbog napretka tehnologije omogućeno privremeno ili trajno liječenje uređajem (pumpom) za mehaničku potporu srca (VAD). Infekcije implantiranih srčanih pumpi i sepsa ostaju važnim fatorom rizika za smrt. Kad se na površinama biomaterijala utvrdi postojanje infekcija one perzistiraju unatoč produljenoj antimikrobnoj terapiji. Formiranje biofilma je presudni korak u patogenezi mnogih subakutnih i kroničnih bakterijskih infekcija, a osobito infekcija povezanih sa stranim tijelom. Biofilm je signifikantan klinički problem. Teško se eradicira konvencionalnim antimikrobnim lijekovima, jer posjeduje nekoliko mehanizma stvaranja antibiotske rezistencije. Perzistirajuće stanice imaju glavnu ulogu u toleranciji bakterijskog biofilma prema antimikrobnom lijeku. Mehanizam stvaranja biofilma i posljedične antimikrobne rezistencije biti će ključ za razvoj novih terapijskih strategija. Dakle, poštivanje dokazima utemeljene kontrole infekcija uz smjernice za prevenciju istih, pedantna kirurška tehnika i optimalna njega postoperativnog kirurškog mjesta čine temelje za prevenciju infekcija povezanih s VAD-om. Ventricular assist devices (VADs) for patients with severe heart failure are improving, and there are increasing numbers of implants, as device therapy enters the era of permanent use (i.e. destination therapy). The device-related infection of implanted pumps and sepsis remain important risk factors for death, and once infections are established on biomaterial surfaces, they usually persist despite prolonged antimicrobial therapy. Biofilm forming is the crucial moment in the pathogenesis of many subacute and chronic bacterial infections, including the infections connected with a foreign body. Biofilm is a significant clinical problem. Its eradication by conventional antimicrobial agents is rather complicated, as it disposes of several mechanisms for developing resistance to antibiotics. The role of persisting cells is crucial in the context of the tolerance of bacterial biofilm towards antimicrobials. The mechanism for biofilm forming and the consequential antimicrobial resistances are the key to developing new therapeutic strategies. Therefore, adherence to evidence-based infection control and prevention guidelines, meticulous surgical technique and optimal post-operative surgical site care form the foundation for VAD-associated infection prevention. Croatian Academy of Sciences and Arts 2011-03-11 text pdf http://hrcak.srce.hr/66349 http://hrcak.srce.hr/file/99195 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.509=36; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:66350 2011-04-09 journal:117

Pregled novijih uređaja za asistirano srce i asistiranu cirkulaciju Overview of New Mechanical Circulatory Support Devices Sutlić, Željko; Department of Cardiac Surgery, University Hospital Dubrava, Zagreb, Croatia; zsutlic@kbd.hr Čekol, Zorana; Department of Cardiac Surgery, University Hospital Dubrava, Zagreb, Croatia Barić, Davor; Department of Cardiac Surgery, University Hospital Dubrava, Zagreb, Croatia Rudež, Igor; Department of Cardiac Surgery, University Hospital Dubrava, Zagreb, Croatia Unić, Daniel; Department of Cardiac Surgery, University Hospital Dubrava, Zagreb, Croatia Planinc, Mislav; Department of Cardiac Surgery, University Hospital Dubrava, Zagreb, Croatia Jonjić, Dubravka; Department of Cardiac Surgery, University Hospital Dubrava, Zagreb, Croatia asistirano srce; transplantacija srca assist device; heart transplantation Uređaji za asisitirano srce i asistiranu cirkulaciju postali su standard u liječenju pacijenata s kroničnim zatajenjem srca, kojima je neophodna dugoročna mehanička potpora srcu i cirkulaciji. U ovom članku ukratko su opisane povijest razvoja različitih starijih (pulsatilnih) i novijih (kontinuirani tok) uređaja te važnost kliničke primjene ovih modernih uređaja. Continuous-flow left-ventricular assist devices (LVADs) have emerged as the standard of care for advanced heart failure patients, who require long-term mechanical circulatory support. In this review, we describe in brief the basics of the development of various devices, both the old (pulsatile-flow) and the new (continuous-flow) devices. A clinical review of modern devices and their today’s relevance are given in a brief outline. Croatian Academy of Sciences and Arts 2011-03-11 text pdf http://hrcak.srce.hr/66350 http://hrcak.srce.hr/file/99197 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.509=36; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:84014 2012-07-04 journal:117

Editorial Pećina, Marko Croatian Academy of Sciences and Arts 2012-05-21 text pdf http://hrcak.srce.hr/84014 http://hrcak.srce.hr/file/125014 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.511=37; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:84016 2012-07-04 journal:117

Latentna tuberkulozna infekcija Latent Tuberculosis Infection Zrinski Topić, Renata; Department of Clinical Laboratory Diagnosis, Srebrnjak Children’s Hospital, Zagreb, Croatia; renata.zrinski-topic@zg.t-com.hr IGRA; latentna tuberkulozna infekcija; tuberkulinski test interferon-gamma release assay; latent tuberculosis infection; tuberculin skin test Latentna tuberkulozna infekcija (LTBI) definira se kao supklinička infekcija bakterijom Mycobacterium (M.) tuberculosis. Kod djece i osoba oslabljenog imunološkog sustava, zbog pojedinih patoloških stanja ili terapijskih postupaka, postoji veći rizik za aktivaciju LTBI-ja u aktivnu tuberkulozu u odnosu na opću populaciju, te je takvu infekciju potrebno pravovremeno otkriti. Dijagnostika LTBI-ja temelji se na određivanju imunološke reakcije usmjerene protiv M. tuberculosis. Primjena tuberkulinskog testa otežana je brojnim čimbenicima koji mogu uzrokovati lažno pozitivne i lažno negativne rezultate testa. Novi dijagnostički pristup temelji se na ex vivo testovima iz pune krvi kojima se određuje IFN-γ oslobođen iz T-limfocita (interferon-gamma release assays, IGRAs) nakon podražaja specifičnim antigenima za M. tuberculosis. Primjena IGRAs-a u rutinskoj kliničkoj praksi unaprijedila je dijagnostiku LTBI-ja, ali preporuke i smjernice za dijagnostiku LTBI-ja nisu podudarne u pojedinim europskim zemljama. Zbog toga je Europski centar za prevenciju bolesti i kontrolu pripremio smjernice utemeljene na najnovijim znanstvenim podatcima. Unaprjeđenja IGRAs-a i nova istraživanja treba kreirati tako da se mogu dati odgovori na sva otvorena pitanja. Latent tuberculosis infection (LTBI) is a subclinical infection with Mycobacterium (M.) tuberculosis. Children and immunosuppressed individuals due to pathologic conditions or therapeutic procedures are at a high risk of reactivation of LTBI to active disease compared to general population and require timely identification. The diagnosis of LTBI is based on the measurement an adaptive immune response against M. tuberculosis. The use of tuberculin skin test (TST) has been associated with a number of interfering factors that cause false-positive or false-negative test results. The new ex vivo whole blood tests determining interferon-gamma (IFN-γ) released from T-lymphocytes (interferon-gamma release assays, IGRAs) upon stimulation with M. tuberculosis specific antigens. The introduction of IGRAs to routine clinical practice has improved the diagnosis of LTBI, but recommendations and guidelines for the diagnosis of LTBI are not consistent between different European countries. Therefore, European centre for disease prevention and control developed guidance document based on the up-to-date scientific evidence. Novel concepts of IGRAs and new studies should be designed so as to provide answers to all open questions. Croatian Academy of Sciences and Arts 2012-05-21 text pdf http://hrcak.srce.hr/84016 http://hrcak.srce.hr/file/125019 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.511=37; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:84019 2012-07-04 journal:117

Nagla kardijalna smrt tijekom tjelesne aktivnosti u Hrvatskoj u 27-godišnjem razdoblju Sudden Cardiac Death Due to Physical Exercise in Croatia in a 27-Year Period Duraković, Zijad; Department of Medical Anthropology and Epidemiology, Institute for Anthropological Research, Zagreb, Croatia; zdurakovic@inantro.hr Mišigoj Duraković, Marjeta; Department of Kinesiological Anthropology and Methodology, Faculty of Kinesiology, Zagreb, Croatia Škavić, Josip; Department of Forensic Medicine and Criminology, Medical Faculty University of Zagreb, Croatia muškarci; sportaši; rekreativna tjelesna aktivnost; iznenadna smrt men; athletes; recreational physical exercise; sudden death Prikazane su nagle kardijalne smrti za vrijeme treninga u Hrvatskoj kao dio retrospektivnog istraživanja 69 muškaraca naglo i neočekivano umrlih za vrijeme tjelovježbe u Hrvatskoj od 1. siječnja 1984. do 31. prosinca 2010. i u svih je provedena sudsko-medicinska obdukcija. U sportaša je bilo šest naglih i neočekivanih smrtnih ishoda. Obdukcijom trkača u dobi 21 godine otkriven je akutni infarkt miokarda s normalnim vjenačnim arterijama i hipertrofijom lijeve klijetke. U drugog, u dobi 17 godina, vjenačne arterije bile su hipoplastične a silazna aorta sužena te su bili prisutni gnojni tonzilitis i subakutni miokarditis. Dva su sportaša umrla tijekom treninga zbog aritmogene displazije desne klijetke. Prvi je bio trkač na kratke pruge, a drugi nogometaš. U Hrvatskoj stopa nagle smrti u sportaša iznosi 0.19/100 000 godišnje (p = 0.00005); zbog aritmogene displazije desne klijetke ta stopa iznosi 0.06/100 000 (p = 0.00000), u svih mladih sportaša koji su bolovali od drugih bolesti srca ona iznosi 0.10/100 000 (p = 0.00000), u ukupnoj populaciji muškaraca u dobi 15 – 40 g. koji su uključeni u takmičarsku ili rekreacijsku tjelovježbu ta stopa iznosi 0.71/100 000 godišnje (p = 0.00001), a u svih muškaraca u dobi 15 – 64 g. 0.96/100 000 (p = 0.00000). Pet sportaša preminulo je zbog hipertrofijske kardiomiopatije: trojica za vrijeme treninga i dvojica za vrijeme rekreacijske tjelovježbe. Jedan je imao opstrukcijsku hipertrofijsku kardiomiopatiju, a ostali su imali neopstrukcijski oblik. Prvi sportaš naglo je preminuo za vrijeme treninga trčanja, a drugi i treći sportaš bili su košarkaši. Dvojica su preminula za vrijeme nogometne igre. Nagla kardijalna smrt zbog hipertrofijske kardiomiopatije za vrijeme rekreacijske tjelovježbe u mladih sportaša u Hrvatskoj iznosi 0.10/100 000 (p = 0.00000). Dogodila su se tri nagla i neočekivana smrtna ishoda zbog mioperikarditisa, i to kod dvojice nogometaša te jednog plivača. Obdukcijom je otkriveno da je prvi bolovao od subakutnog difuznog mioperikarditisa, gnojnog tonzilitisa i sužene uzlazne aorte, drugi od kroničnog mioperikarditisa i aneurizmatskog proširenja lijeve klijetke, a treći od fibrinoznog perikarditisa, zadebljanja lijeve klijetke od 20 mm, hipoplastične uzlazne aorte, obostrane bronhopneumonije i kontuzije mozga s edemom. U Hrvatskoj u tjelovježbača stopa smrtnog ishoda zbog mioperikarditisa iznosi 0.11/100 000 (p = 0.00000). Stenoza aorte ustanovljena je u dva adolescenta. Prvi je bio učenik i košarkaš u dobi 17 g. Obdukcijom je otkriveno povećanje cijelog srca, suženje uzlazne aorte, zadeljana stijenka lijeve klijetke, bakterijski tonzilitis i subakutni difuzni miokarditis. Drugi učenik preminuo je naglo za vrijeme trčanja. Nalaz obdukcije upućivao je na povećanje cijelog srca, zadebljanje stijenke lijeve klijetke i suženje silazne aorte. Malformacije vjenačnih arterija ustanovljene su u trojice mladića. U nogometaša koji je naglo preminuo tijekom utakmice postojala je hipoplazija desne vjenačne arterije, suženje uzlazne aorte, akutni bakterijski tonzilitis i subakutni miokarditis. U dječaka koji je preminuo za vrijeme tjelovježbe ustanovljene su hipoplastične vjenačne arterije. U mladića koji je povremeno rekreacijski igrao nogomet i preminuo za vrijeme utakmice desna i lijeva vjenačna arterija bile su sužena ušća od 1 mm. Među adolescentima bilo je 10 naglih i neočekivanih smrti tijekom ili nakon tjelovježbe. Obdukcijski je kod četvorice ustanovljena prirođena bolest srca. Dvojica su imala hipoplastične koronarne arterije, jedan uz to i bakterijsku upalu tonzila, suženu aortu i subakutni miokarditis. Treći je imao hipertrofijsku kardiomiopatiju. Četvrti je bolovao od obostrane upale pluća s nekardiogenim edemom pluća. Peti je imao aneurizmu lijeve klijetke. Šesti je igrao nogomet rekreacijski i preminuo je zbog obostrane upale pluća, a imao je i fibrinozni perikarditis. Sedmi je imao kardiomegaliju, obostrani hidrotoraks i etanol u krvi (0.17%). Stopa smrti za vrijeme ili neposredno nakon tjelovježbe u adolescenata u Hrvatskoj iznosi 0.37/100 000 (p = 0.00226). Zbila su se tri nagla i neočekivana smrtna ishoda zbog pneumonije u mladića. Jedan je radio rekreacijski na gradilištu, drugi se bavio rekreacijski nogometom, treći je bio profesionalni nogometaš. Nalaz obdukcije u prvog upućivao je na obostranu bakterijsku upalu pluća, mogući nekardiogeni edem pluća i edem mozga. U drugog je nalaz upućivao na obostranu bakterijsku upalu pluća, respiracijski distresni sindrom odraslih, diseminiranu intravaskularnu koagulaciju, krvarenje u nadbubrežne žlijezde, hipoplastičnu desnu koronarnu arteriju i fibrozu miokarda. U trećeg je nalaz upućivao na obostranu bakterijsku upalu pluća, fibrinozni perikarditis, cerebralnu kontuziju s edemom, zadebljanje lijeve klijetke i hipoplastičnu uzlaznu aortu. Stopa smrtnosti u adolescenata zbog pneumonije u Hrvatskoj iznosi 0.11/100 000 (p = 0.00000). Mladi nogometaš bez prethodnih zdravstvenih tegoba preminuo je naglo i neočekivano tijekom treninga. Obdukcijom je ustanovljena bakterijska upala tonzila, subakutni mioperikarditis i sužena uzlazna aorta. Pet je liječnika specijalista naglo i neočekivano umrlo tijekom ili neposredno nakon rekreacijskog tjelesnog vježbanja: plivanja, nogometa, tenisa i trčanja. U trojice koja nisu imala prethodne simptome te su bila nepušači obdukcijom je ustanovljena koronarna bolest srca: u jednog je ustanovljena stenoza, u dvojice okluzija prednje silazne koronarne krvne žile, u jednog su ustanovljeni ožiljci miokarda od dva ranije preboljela infarkta miokarda, u dva hipertrofija lijeve klijetke. U dvojice koja nisu obducirana radilo se o mogućoj alkoholnoj kardiomiopatiji. Obojica su bila pušači. U jednog je zabilježena fibrilacija atrija godinu prije nagle smrti. U drugog se vjerojatno radilo o bolesti vjenčanih arterija, uz arterijsku hipertenziju i hiperlipoproteinemiju. U Hrvatskoj je 4.957 liječnika specijalista muškaraca, a u njih stopa naglih smrti za vrijeme tjelovježbe iznosi 24.8/100 000 godišnje (p = 0.00000). Petnaest „starijih” muškaraca naglo je umrlo za vrijeme različitih oblika tjelovježbe: plivanja u moru, tenisa, kuglanja, rekreacijskog trčanja. Obdukcijom je otkriveno da ih je 14 imalo bolest vjenačnih krvnih žila: petorica kritično vjenačno suženje, dvojica uz recentni infarkt mišića srca prednje stijenke, trojica začepljenu prednju silaznu vjenačnu arteriju, jedan od njih uz to i akutni infarkt prednje stijenke srca, dvanaestorica ožiljke nakon preboljelih infarkta srca, jedan je imao difuznu fibrozu miokarda. Dvanaestorica su imala zadebljanje lijeve klijetke. U Hrvatskoj se oko 7% muškaraca starije dobi bavi rekreacijskom tjelovježbom, a u njih stopa smrtnosti iznosi 2.99/100 000 (p = 0.00001). In a period of 27 years: from January 1, 1984 to December 31, 2010 we noticed 69 sudden and unexpected cardiac deaths during physical exercise in Croatia. There were 6 sudden cardiac deaths in male athletes. At the autopsy, an athletic runner aged 21, had an acute myocardial infarction with normal coronaries and left ventricular wall thickened. A professional soccer player aged 17, had hypoplastic right coronary artery and narrowed ascending aorta, bacterial tonsillitis and subacute myocarditis. A student rugby player aged 29, and a school boy-basketball player aged 15, had hypertrophic cardiomyopathy. The arrhythmogenic right ventricular dysplasia was a cause of death in two athletes. The first was a short trails runner, and the second was a soccer player. The hypertrophic cardiomyopathy was a cause of death in 3 athletes and 2 persons during recreational exercise. An acute myopericarditis was a cause of death in 2 professional soccer players, and in one who died during swimming. One had subacute diffuse myopericarditis, bacterial tonsillitis and narrowed ascending aorta of 10 mm. The other had chronic myopericarditis and cardiac aneurysm of the left ventricle. The third had fibrinous pericarditis, hyperthropic cardiomyopathy, hypoplastic ascending aorta, bilateral bronchopneumonia and cerebral contusion with edema. Sudden cardiac deaths appeared in 10 school boys. Two of them had been engaged in physical exercise at school, the third was a professional soccer player, the fourth was engaged in recreational swimming, and the fifth had just finished secondary school and was working at the site recreatively. In 3 of them congenital cardiovascular diseases was found: in 2 hypoplastic coronary arteries and in 2 hypertrophic cardiomyopathy. The fourth had normal heart findings including coronaries, but had bilateral pneumonia with a non-cardiogenic pulmonary edema. The fifth had a chronic myopericarditis with an aneurysm of the left ventricle. Pneumonia was a cause of death in 3 male teenagers aged 18-19. The first was working at the site recreatively, the second was engaged in soccer recreatively and the third was professional soccer player. One died suddenly during physical exercise at the field and 2 died in the hospital. The first had bilateral bacterial pneumonia, non-cardiogenic pulmonary edema and cerebral edema. The second had bilateral bacterial pneumonia, adult respiratory distress syndrome, disseminated intravascular coagulation, cerebral edema, hypoplastic right coronary artery and myocardial fibrosis. The third had bilateral bacterial pneumonia, fibrinous pericarditis, and cerebral contusion with edema, thickening of the left ventricle 20 mm and hypoplastic ascending aorta. We noticed 5 sudden death among Croatian male physicians, during or after recreational exercise: swimming, soccer, tennis and jogging; 3 were autopsied, and all had coronary heart disease. Two physicians who were not been autopsied, had possible an alcohol cardiomyopathy. Fifteen “elderly” men, died suddenly during exercise: 6 in swimming, 4 in playing tennis, one ridded, one was jogging, 2 bowling and one died during sexual act. At autopsy, 14 had coronary heart disease: 5 critical coronary artery stenosis, and 2 had signs of recent myocardial infarctions, 3 had left descending coronary artery occluded, and one with acute myocardial infarction of the anterior wall, 12 had myocardial scars due to previous myocardial infarctions and one signs of diffuse myocardial fibrosis. Twelve of them had left ventricular hypertrophy. In Croatia the death rate among athletes reached 0.19/100 000 yearly (p=0.00005), in the male population aged 15-40 years, engaged in sports and recreational physical exercise: 0.71/100 0000 (p=0.00001), in the total male population aged 15-64 engaged in sport and recreational exercise 0.96/100 000 (p=0.00001), in arrhythmogenic right ventricular dysplasia reached 0.06/100.000 (p=0.00000), in teenagers suffered of hypertrophic cardiomyopathy 0.10/100 000 (p=0.00000), in myopericarditis it was 0.11/100,000 (p=0.00000), in pneumonia 0.11/100 000 (p=0.00000), in teenagers 0.37/100 000 (p=0.00226), in physician-specialists reached 24.8/100 000 (p=0.00000), in elders reached 2.99/100 000 (p=0.00001). Croatian Academy of Sciences and Arts 2012-05-21 text pdf http://hrcak.srce.hr/84019 http://hrcak.srce.hr/file/125026 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.511=37; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:84024 2012-07-04 journal:117

Preface - Epidemiological and Clinical Characteristics of Infections Caused by Methicillin-Resistant Staphylococcus aureus and Staphylococcus pseudintermedius Madić, Josip Croatian Academy of Sciences and Arts 2012-05-21 text pdf http://hrcak.srce.hr/84024 http://hrcak.srce.hr/file/125033 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.511=37; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:84025 2012-07-11 journal:117

Academician Eugen Topolnik - To Mark the 100th Anniversary of his Birth Cvetnić, Slavko; cvetnics@hazu.hr Croatian Academy of Sciences and Arts 2012-05-21 text pdf http://hrcak.srce.hr/84025 http://hrcak.srce.hr/file/125034 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.511=37; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:84027 2012-07-04 journal:117

Značenje meticilin-rezistentnih sojeva Staphylococcus aureus (MRSA) u humanoj medicini The Importance of Methicillin-Resistant Staphylococcus aureus in Human Medicine Kalenić, Smilja; University of Zagreb, School of Medicine, Zagreb, Croatia; skalenic@mef.hr Staphylococcus aureus; otpornost na meticilin; MRSA Staphylococcus aureus; methicillin resistance; MRSA Staphylococcus aureus (S. aureus) jedan je od najznačajnijih bakterijskih oportunističkih patogena u ljudi. Vrlo se lako adaptira na različite uvjete u okolini, a posebno je važno njegovo brzo stjecanje otpornosti na različite antibiotike. Osobito je važna otpornost na betalaktamske antibiotike (takozvani meticilin-rezistentni S. aureus: MRSA). Sojevi MRSA-e razlikuju se prema sredini u kojoj uzrokuju infekcije: bolnički stečeni, stečeni u izvanbolničkoj populaciji te oni povezani s domaćim životinjama. Bolnički MRSA izazvao je najveću epidemiju bolničkih infekcija ikada opisanu u svijetu; izvanbolnički MRSA velik je problem u SAD-u, manji u Europi. Životinjski sojevi MRSA-e novi su dodatak ljudskim patogenima, no ne s velikom učestalošću u svijetu. U Republici Hrvatskoj MRSA je velik problem u bolničkim ustanovama, s laganom tendencijom smanjenja posljednjih godina. Izvanbolnički MRSA zasad je vrlo rijedak, a infekcije životinjskim sojevima, premda su dokazane na svinjogojskim farmama, nisu još opisane. Staphylococcus aureus (S. aureus) is one of the most important bacterial opportunistic pathogens in humans. It easily adapts to the various environmental conditions. Very important is rapid development of resistance to different antimicrobial agents. Especially important is the resistance to beta-lactam antibiotics (so called methicillin-resistant S. aureus: MRSA). MRSA strains differ according to the setting they cause infections to healthcare-acquired strains, community-acquired strains and animal strains. Healthcare- acquired MRSA strains were responsible for the largest epidemic of healthcare-associated infections that ever occurred in the world; community-acquired MRSA strains are huge problem in USA, not so important in Europe. Animal MRSA strains are new addition to human pathogens, but they are not very frequent. In Croatia, MRSA strains are big problem in hospitals but with the tendency of decreasing in recent years; community- acquired MRSA strains are so far very rare, and infections caused by animal MRSA strains are still not described in humans, although they are present in pig farms. Croatian Academy of Sciences and Arts 2012-05-21 text pdf http://hrcak.srce.hr/84027 http://hrcak.srce.hr/file/125038 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.511=37; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:84029 2012-07-04 journal:117

Metode detekcije i tipizacije meticilin-rezistentnih sojeva bakterije Staphylococcus aureus Detection and Typing Methods of Methicillin-Resistant Strains of Staphylococcus aureus Budimir, Ana; Department for Medical Microbiology and Parasitology, University of Zagreb, Faculty of Medicine, Zagreb, Croatia; abudimir@kbc-zagreb.hr MRSA; detekcija; tipizacija MRSA; detection; typing methods Staphylococcus aureus jedan je od najčešćih uzročnika bolničkih infekcija, a i njegova je uloga u izvanbolničkoj sredini također velika, osobito nakon 90-ih godina prošlog stoljeća. Danas meticilin-rezistentni Staphylococcus aureus (MRSA) uzrokuje 40 – 70% stafilokoknih infekcija u jedinicama intenzivnog liječenja. Podaci o prevalenciji MRSA-e razlikuju se u različitim dijelovima svijeta i po različitim bolnicama. Javlja se od 0,6% u Norveškoj do 66,8% u Japanu, a 2008. je zamijećen trend opadanja prevalencija incidencije MRSA-e koji se nastavlja u različitim europskim zemljama, pa i u Hrvatskoj. MRSA se izdvaja iz kliničkih uzoraka kao dio dijagnostičkog postupka, a iz nadzornih kultura kao dio programa nadzora nad kliconoštvom. Identifikacija vrste S. aureus temelji se uglavnom na dokazu katalaze, koagulaze i DNA-aze, a postoje i komercijalni lateks-aglutinacijski testovi koji se temelje na dokazivanju specifičnih antigena bakterije S. aureus (npr. protein A). Meticilinska rezistencija vrste S. aureus može se dokazati testiranjem osjetljivosti na cefoksitin ili dokazom prisutnosti gena mecA odgovornog za meticilinsku rezistenciju. Postoje i automatizirani sustavi koji se rabe i za identifikaciju bakterija i za određivanje osjetljivosti. Dokazivanje MRSA-e u nadzornim uzorcima otežano je zbog prisutnosti normalne bakterijske flore te se, radi sprječavanja rasta ostalih bakterija, rabe različiti selektivni bujoni za prekonoćnu inkubaciju i/ili različite selektivne podloge (npr. kromogeni agar). Probir MRSA-e može se izvoditi i uz pomoć molekularnih testova, među kojima su najspecifičniji i najosjetljiviji oni iz treće generacije, koji kao cilj detekcije imaju cijelu regiju između SCCmec fragmenta i orfX (ne samo mecA gen). Tipizacija je važna kod MRSA-e jer omogućuje uvid u povezanost izolata, pomaže utvrditi prijenos patogena i otkriti izvor iz kojeg se širi. Fenotipskim metodama tipizacije uspoređujemo fenotipska svojstva bakterija i umnogome su zamijenjene metodama genotipizacije. Najvažnije su i najčešće korištene i citirane genotipizacijske metode: elektroforeza u pulsirajućem polju (Pulse-field Gel Electrophoresis-PFGE), zatim višelokusno sekvencijsko tipiziranje (Multi-locus Sequence Type-MLST) i sekvencioniranje regije koja kodira za protein A (sequencing of protein A region of Staphylococcus aureus - spa typing). Potrebno je istaknuti važnost točne i relativno brze dijagnostike MRSA-e u kliničkim i probirnim uzorcima. Staphylococcus aureus is one of the most important pathogens in hospital infections and its importance in the community is also prominent, especially since the 1990’s. Today methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common causes of hospital infection, causing 40-70% of staphylococcal infections in intensive care units. Data on the prevalence of MRSA isolates differ in various parts of the world, as well as between hospitals, from 0.6% in Norway to 66.8% in Japan, and in 2008 a trend was noticed of a fall in the number of MRSA infections in various European countries. It is possible to isolate MRSA from clinical isolates, as part of the procedure of diagnostics of the infection, or as isolates from the site of colonization through MRSA screening procedures. Identification of S. aureus is based mainly on production of catalase, coagulase and DNA-se and with latex agglutination test based on detection of specific S. aureus antigens (e.g. protein A). Methicillin-resistance can be detected by susceptibility testing to cefoxitine or by using molecular tests to confirm the presence of mecA gene, responsible for methicillin-resistance. There are also some automated laboratory systems that can combine identification and susceptibility testing of MRSA and other bacteria. Detection of MRSA in screening samples is challenged by presence of other bacterial flora and can be overcome by use of different selective broth for initial (overnight) incubation and / or different selective agar plates (e.g. chromogenic plates). Screening can also be performed with molecular tests and new, third generation PCR detects the whole region of genome between SCCmec fragment and orfX (not only mecA gene). Typing is important for MRSA in order to investigate the correlation between different isolates, are they same, similar, do they origin from the same pathogen source etc. One group of methods is phenotypic typing, which is very much substituted with genotypic methods. Among genotypic methods, the most widely used are Pulse–Field Gel Electrophoresis (PFGE), Multi-Locus Sequence Type (MLST) analysis and sequencing of protein A region of Staphylococcus aureus. It is very important for laboratory and hospitals to be able to detect MRSA in samples, accurately and reasonably fast, in clinical samples or as a part of screening strategy. It is up to laboratory to choose which method to use, following guidelines and recommendations and depending on ability to afford different tests. Croatian Academy of Sciences and Arts 2012-05-21 text pdf http://hrcak.srce.hr/84029 http://hrcak.srce.hr/file/125042 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.511=37; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:84031 2012-07-04 journal:117

Spektar infekcija uzrokovanih meticilin-rezistentnim sojevima bakterije Staphylococcus aureus Clinical Aspects of Infections Caused by Methicillin-Resistant Staphylococcus aureus Baršić, Bruno; University of Zagreb, School of Medicine, Hospital for Infectious Diseases “Dr Fran Mihaljević”, Zagreb, Croatia; bruno.barsic@fran.bfm.hr MRSA; spektar infekcija MRSA; clinical aspects Spektar infekcija uzrokovanih meticilin-rezistentnim sojevima Staphylococcus aureus Infekcije MRSA-om važan su uzročnik bolničkih infekcija. Spektar bolesti koje MRSA izaziva određen je više načinom akvizicije tijekom raznih oblika medicinske skrbi nego patogenetskim značajkama samog organizma. Invazivni zahvati nose rizik infekcija MRSA-om. Glavni su način širenja ruke osoblja, pa su infekcije MRSA-om pokazatelj egzogenog akviriranja bolničke infekcije. Na kirurškim odjelima važan su uzročnik infekcija rana, tkiva i mekih česti. U jedinicama intenzivne medicine uzročnik su infekcija krvotoka povezanih s primjenom centralnih venskih katetera i pneumonija povezanih s provođenjem strojnog disanja, odnosno intubacije. Infekcije MRSA-om velik su problem kod ugradnje stranih materijala jer, zbog stvaranja biofilma, lako koloniziraju proteze, drenažne katetere ili umjetne zalistke te uzrokuju perzistentne infekcije okolnog tkiva koje je vrlo teško liječiti. Zbog toga je potrebno zamijeniti te materijale, što nije laka odluka niti je to uvijek moguće učiniti. Za razliku od infekcija MSSA-om, infekcije MRSA-om povezane su sa slabijom indukcijom opće upalne reakcije. Iako su povezane sa znatnim povećanjem morbiditeta i smrtnosti, ove posljedice infekcija MRSA-om više su posljedica neprepoznavanja ili kašnjenja ispravnog antibiotskog liječenja nego težine infekcije. Danas na raspolaganju imamo čitav spektar novijih antibiotika (linezolid, daptomicin, tigeciklin, ceftarolin, ceftobiprol) kojima se, uz glikopeptide, možemo uspješno suprotstaviti infekcijama MRSA-om, ali rastući je problem smanjenje osjetljivosti na vankomicin, što ima bitne kliničke posljedice. Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of nosocomial infections. Clinical presentation of infections is determined by the way of the acquisition of the pathogen then by virulence factors itself. In the intensive care units MRSA causes blood stream infections (BSI) associated with the use of venous lines as well as ventilator-associated pneumonia (VAP). MRSA is prone to form biofilm on implanted foreign materials like orthopaedic and other prostheses, catheters, artificial heart valves and cause persistent infections of surrounding tissues which are difficult to treat. It is difficult to eradicate infection without extraction of these materials. MRSA is weaker inductor of general inflammatory reaction then MSSA. Increase in patient’s mortality and morbidity is associated more with a delay of appropriate antibiotic treatment then severity of infection. New antibiotics like linezolid, daptomycin, tygecycline, ceftarolin, ceftobiprol are available nowadays for the treatment of these infections. Although glycopeptides are still the first line treatment of MRSA infections, increase of minimal inhibitory concentrations (MIC creep) is associated with poorer outcome. Croatian Academy of Sciences and Arts 2012-05-21 text pdf http://hrcak.srce.hr/84031 http://hrcak.srce.hr/file/125046 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.511=37; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:84032 2012-07-04 journal:117

Izdvajanje meticilin-rezistentnih sojeva bakterije Staphylococcus aureus u objektima s rasplodnim svinjama u Hrvatskoj The Isolation of Methicillin-Resistant Staphylococcus aureus at Breeding Pig Facilities in Croatia Habrun, Boris; Croatian Veterinary Institute, Zagreb, Croatia; habrun@veinst.hr Račić, Ivana Kompes, Gordan Beck, Relja Benić, Miroslav Cvetnić, Željko MRSA; svinje; objekti MRSA; pigs; facilities Meticilin-rezistentni sojevi bakterije Staphylococcus aureus (MRSA) izdvajaju se u cijelom svijetu i otporni su na različite antimikrobne lijekove. Infekcije svinja sojevima MRSA-e prvi su put opisane u Nizozemskoj 2005. s pretpostavkom da su svinje izvor infekcije MRSA-om za ljude. Uzorke prašine prikupljali smo sa šest velikih svinjogojskih farmi u Hrvatskoj iz objekata u kojima su smještene rasplodne životinje. Na svakoj farmi uzeli smo pet ili šest brisova. Od ukupno uzorkovana 32 brisa, iz osam brisova s četiri farme izdvojili smo ružičaste kolonije na MRSA selektivnom agaru. Kod svih izolata koji su rasli na MRSA selektivnom agaru kao ružičaste kolonije izdvojen je gen mecA. Svi izolati bili su otporni na penicilin, ampicilin, oksacilin, oksitetraciklin i streptomicin, a osjetljivi na vankomicin, ciprofloksacin, florfenikol i sulfametoksazol s trimetoprimom. Methicillin resistant Staphylococcus aureus (MRSA) have emerged worldwide and have became resistant to a variety of antibiotics. MRSA colonisation in pigs was first reported in the Netherlands at 2005, where pigs were implicated as a source of human MRSA infections. Dust samples were collected from six large pig farms in Croatia from breeding pig facilities. On each farm, between 5 and 6 samples were taken by swabs. Of the total 32 swabs, isolates from 8 swabs from four of the six examined farms grew pink colonies on the MRSA select agar. The mecA gene was detected in all 8 isolates growing pink colonies on the MRSA agar. All isolates are resistant to penicillin, ampicilin, oxacillin, oxitetracycline and streptomycin. All isolates were susceptible to vancomycin, ciprofloxacin, florfenicol and sulfametoxazole/trimethoprim. Croatian Academy of Sciences and Arts 2012-05-21 text pdf http://hrcak.srce.hr/84032 http://hrcak.srce.hr/file/125048 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.511=37; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:84033 2012-07-04 journal:117

Osjetljivost na antimikrobne tvari sojeva bakterije Staphylococcus aureus izdvojenih iz mlijeka krava s upalom vimena Susceptibility of Staphylococcus aureus Strains Isolated From Bovine Intramammary Infections to Different Antimicrobial Agents Jurmanović, Jadranka; Veterinary Department Križevci, Croatian Veterinary Institute, Križevci, Croatia; jadranka137@gmail.com Bačanek, Branko Pavljak, Ivan Sukalić, Tomislav Jaki, Vesna Majnarić, Darko Končurat, Ana Sokolović, Jadranka Staphylococcus aureus; krava; mastitis; antimikrobni lijekovi Staphylococcus aureus; cow; mastitis; antimicrobial agents Prikazani su rezultati rutinskih mikrobioloških nalaza i osjetljivost sojeva vrste Staphylococcus aureus izdvojenih iz mlijeka krava s različitim oblicima upala mliječne žlijezde tijekom pet godina. Ukupno je 2.719 sojeva vrste Staphylococcus aureus bilo pretraženo na osjetljivost na 12 antibiotika disk-difuzijskim postupkom. Sojevi su bili izdvojeni iz 45.000 uzoraka sekreta vimena na Columbia agaru s 5% ovčje krvi (0,01 ml na četvrtinu hranjive podloge). Identificirani su bili prema morfološkim osobinama, tvorbi katalaze i koagulaze, a sojevi iz 2002. godine i API ID 32 STAPH sustavom. Postotak sojeva osjetljivih na penicilin bio je najviši 2002., kada je iznosio 70,77%, a zatim slijedi 2007. s 39,13%, 2008. s 37,54%, 2009. s 37,96% i 2010. godina s 44,65%. Oksacilin osjetljivih sojeva utvrđeno je 66,66% u 2007., 67,45% u 2008., 71,52% u 2009. te 88,56% u 2010. godini. Za amoksicilin s klavulanskom kiselinom osjetljivost je iznosila 93,85% – 95,65% sojeva. Na cefalosporine I. generacije osjetljivo je bilo 36,66% – 85,98% sojeva, dok je na cefalosporin III. generacije bilo osjetljivo 100% sojeva iz 2002. i 2007. godine, a 91,07% 2009. i 95,94% izolata iz 2010 godine. Sojevi su pokazali različitu osjetljivost na tetracikline, linkozamide, aminoglikozide, fluorirane kinolone i sulfonamide. Rezultati upućuju na postojanje sojeva rezistentnih na sve skupine antibiotika. We have shown the results of routine microbiological testing and susceptibility of Staphylococcus aureus isolates that were isolated from cows with inflammation of mammary gland during a five year period. Totally, 2719 strains identified as Staphylococcus aureus were routinely tested to twelve antimicrobial agents by the agar-disc diffusion technique. The strains were isolated from 45000 samples of udder secretion on Columbia agar plates containing 5% of defibrinated ovine blood (0.01 ml on a quarter of culture medium). They were identified on the basis of colony morphology, catalase and coagulase tests, a tube coagulase test and the strains from 2002 were identified by the API ID 32 Staph system. Of strains isolated in 2002, 70.77% were penicillin-susceptible, higher than any other year, after that 39.13% of strains in 2007, 37.54% in 2008, 37.96% in 2009, and 44.65% in 2010. Totally, 66.66% of oxacillin-susceptible strains were found in 2007, 67.45% in 2008, 71.52% in 2009 and 88.56% in 2010. For potentiated penicillins like amoxicillin and clavulanic acid 93.85% to 95.65% of susceptible strains were found. For first-generation cephalosporins 36.66%-85.98% of strains demonstrated susceptibility, while for third-generation cephalosporins 100% of strains were susceptible in 2002 and 2007, but 91.07% of isolated strains were susceptible in 2009 and 95.94% in 2010. The strains have shown various susceptibility to tetracyclines, lincosamides, aminoglycosides, fluroquinolone and sulfonamides. The results show the resistance of strains to all groups of antibiotics. Croatian Academy of Sciences and Arts 2012-05-21 text pdf http://hrcak.srce.hr/84033 http://hrcak.srce.hr/file/125050 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.511=37; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:84034 2012-07-04 journal:117

Kliničke i epizootske značajke mastitisa krava uzrokovanih bakterijom Staphylococcus aureus s osvrtom na meticilin-rezistentne sojeve Clinical and Epidemiological Aspects of Cow Mastitis Caused by Staphylococcus aureus and its Methicillin-Resistant Strains Benić, Miroslav; Croatian Veterinary Institute, Zagreb,Croatia; benic@veinst.hr Habrun, Boris Kompes, Gordan krava; mastitis; Staphylococcus aureus cow; mastitis; Staphylococcus aureus U suvremenom mliječnom govedarstvu mastitis je jedan od najvažnijih problema u ekonomskom, dijagnostičkom i javnozdravstvenom smislu. Ekonomsko značenje mastitisa ogleda se u smanjenoj proizvodnji mlijeka, lošijoj kakvoći, troškovima liječenja i bacanju mlijeka. Otkrivanje mastitisa često je otežano zbog supkliničke naravi procesa, pri čemu je povećanje broja somatskih stanica jedini znak upale. Mlijekom se mogu prenositi i uzročnici bolesti ljudi, a opasnost za ljudsko zdravlje predstavljaju i rezidue antibiotika i lijekova koji se izlučuju mlijekom. Bakterija S. aureus najčešći je uzročnik mastitisa krava kod nas i u svijetu. Uzročnik je svrstan u skupinu kontagioznih uzročnika koji se u stadu širi uglavnom za vrijeme mužnje. Prevalencija infekcije uzrokovane tom bakterijom kreće se od 2 do više od 50% i u izravnoj je vezi s razinom higijene pri mužnji. Kliničko očitovanje u širokom je rasponu od sasvim blagih, s povećanim brojem somatskih stanica kao jedinim pokazateljem infekcije, do gangrenoznih oblika sa smrtnim ishodom. Jednom inficirana životinja može izlučivati uzročnika tijekom više laktacija ako infekcija prijeđe u kronični oblik, pri čemu povremeno mogu nastupiti i kliničke epizode praćene lokalnim znacima upale. Meticilin-rezistentni stafilokoki kao uzročnici mastitisa krava prvi su put potvrđeni 1972. godine. U stadima mliječnih krava potvrđeni su tijekom nekoliko posljednjih godina u više navrata u Belgiji, Poljskoj, Mađarskoj i Njemačkoj, a dokazan je i slučaj prijenosa na ljude. Premda se radi o niskoj prevalenciji među stadima, postoji bojazan da bi se trgovinom životinjama mogao proširiti. Širenje unutar stada omogućeno je velikim brojem kontakata između krava preko muzača i opreme za mužnju. Mastitis represents one of the most important problems in modern dairy production from the economic, diagnostic and public-health related point of view. Economic significance of the mastitis is related to the decreased milk production, lower quality of the milk, veterinary expenses and withdrawing of the milk due to the antibiotic treatment. Detection of mastitis is often complicated due to the subclinical nature of the mammary infection in which the increase of the somatic cells is only sign of the infection. Public health importance rises from the possibility of the transmission of zoonoses as well as due to the residue of the antibiotics secreted by milk. Staphylococcus aureus is the most commonly isolated udder pathogen around the world. Since it is contagious, critical time for spreading among the cows in a herd is the milking time. Observed prevalence of S. aureus mammary gland infection varies from 2% to 50% even above and depends on the milking hygiene. Clinical manifestations of the S. aureus mastitis may vary from mild cases with elevated somatic cells only to the gangrenous cases with lethal exit. Methicillin-resistant staphylococci as mastitis pathogens were first identified in the 1972. During the last decade methicillin-resistant Staphylococcus aureus (MRSA) was identified as a mastitis pathogen in few occasions in Belgium, Poland, Hungary and Germany. Spreading of the MRSA between animals and humans is documented. Although the prevalence of mammary gland infection caused by MRSA is low, there is thread of spreading of the MRSA among herds by animal trade. Spreading within the herd is enabled with large number of possible contacts between cows by milkers and milking equipment. Croatian Academy of Sciences and Arts 2012-05-21 text pdf http://hrcak.srce.hr/84034 http://hrcak.srce.hr/file/125052 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.511=37; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:84035 2012-07-04 journal:117

Pojava i širenje meticilin-rezistentnih sojeva bakterije Staphylococcus pseudintermedius Emergence and Spread of Methicillin-Resistant Staphylococcus pseudintermedius Matanović, Krešimir; Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine, University of Zagreb, Zagreb, Croatia; kmatanov@vef.hr Mekić, Selma Šeol, Branka meticilin; rezistencija; meticilin-rezistentan Staphylococcus pseudintermedius; MRSP methicillin; resistance; methicillin-resistant Staphylococcus pseudintermedius; MRSP Staphylococcus pseudintermedius najčešća je koagulaza-pozitivna vrsta stafilokoka u fiziološkoj mikroflori pasa i mačaka. Može se izdvojiti iz nosnica, usne šupljine, anusa i kože slabinskog i čeonog područja zdravih pasa i mačaka. Uvjetno je patogena bakterija i jedan od najčešćih uzročnika upala kože i zvukovoda. Meticilin-rezistentan Staphylococcus pseudintermedius (MRSP) prvi je put izdvojen u Brazilu u kasnim devedesetima 20. stoljeća. Danas u populaciji pasa i mačaka prevladavaju dva klona. Dominantni europski klon ST71 pojavio se 2005. godine u Njemačkoj i brzo proširio po svijetu, dok klon ST78 prevladava u Sjevernoj Americi. Oba su klona višestruko rezistentna na antimikrobne lijekove i jedan su od najvećih problema rezistencije u veterinarskoj medicini. Izolati MRSP rezistentni su na sve beta-laktamske antibiotike, aminoglikozide, fluorokinolone, makrolide, linkozamide, kombinaciju sulfametoksazola i trimetoprima i većina na kloramfenikol i tetraciklin. Liječenje životinja inficiranih sojevima MRSP-a vrlo je zahtjevno zbog nedostatka djelotvornih antimikrobnih lijekova. Veterinari su često prisiljeni posegnuti za lijekovima registriranim isključivo za liječenje ljudi, primjerice vankomicinom, mupirocinom i rifampicinom, što otvara brojna etička pitanja zbog opasnosti razvoja rezistencije na te antibiotike. Opasnost od zaraze ljudi sojevima MRSP-a općenito je manja u usporedbi s MRSA-om. Veterinari su zbog rada sa životinjama pod povećanim rizikom i trebaju biti svjesni da postoji mogućnost kolonizacije nosnica takvim sojevima. Staphylococcus pseudintermedius is the predominant coagulase-positive species in the normal flora of dogs and cats. It can be isolated from the nares, mouth, anus, groin and forehead of healthy dogs and cats. S. pseudintermedius is an opportunistic pathogen most frequently encountered in canine and feline skin and ear infections. Methicillin- resistant S. pseudintermedius (MRSP) emerged in Brazil in the late nineties. Today, two different clones dominate in the population of dogs and cats. Dominant European clone ST71 appeared in Germany in 2005 and has rapidly spread around the world, while lineage ST68 dominates in North America. Both clones are multiresistant and present one of the biggest problems of antimicrobial resistance in the veterinary medicine. Besides all beta-lactam antimicrobials, they are typically resistant to aminoglycosides, fluoroquinolones, macrolides, lincosamides, trimethoprim-sulfamethoxazol and in many cases to tetracycline and chloramphenicol. The treatment of MRSP infections is a new challenge in veterinary medicine because of the very limited therapeutic options. The multidrug-resistance pattern results in a potential pressure for veterinarians to use antimicrobials licensed in human medicine, such as vancomycin, mupirocin and rifampicin. This opens ethical questions because of the possible emergence of resistance to these antimicrobials. Although the zoonotic potential is much lower than for MRSA, veterinarians are at a higher risk for becoming colonized and should be aware of the zoonotic risk. Croatian Academy of Sciences and Arts 2012-05-21 text pdf http://hrcak.srce.hr/84035 http://hrcak.srce.hr/file/125054 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.511=37; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:84036 2012-07-04 journal:117

Prve žene veterinarke Pioneer Female Veterinarians Katić, Ivan međunarodna povijest veterinarstva; žene veterinarke; 19. stoljeće; 20. stoljeće veterinary studies, female veterinarians, education, history Iako su prve veterinarske škole počele izobrazbom 1761 (Lyon) i 1765 (Alfort, Pariz) žene nisu tamo mogle studirati sve do pred kraj 19. stoljeća. Prvih nekoliko žena koje su diplomirale veterinarsku medicinu bile su iz Rusije odnosno Poljske, no čini se da su udajom promijenile prezime te da nisu djelovale kao veterinari zbog toga što su udajom osigurale ekonomsku sigurnost. Rusija naime nije dopuštala da se žene upisuju na medicinske i veterinarske fakultete sve do 1910. godine pa su žene zato veterinu studirale u Francuskoj, a humanu medicinu na medicinskim fakultetima u Zürichu i Ženevi. Jedna Finkinja, koja je u to vrijeme također bila ruski podanik, uspjela se upisati na Veterinarski fakultet u Dresdenu samo zato jer kod prijave njezino ime nije prepoznato kao žensko ime. Slična je situacija bila s A. Cust u Engleskoj. Studentice su nailazile i na druge administrativne i socijalne poteškoće (ženske presvlačionice i WC-i), no to je s vremenom riješeno, naročito nakon što su žene sâme svojom djelatnošću dokazale ravnopravnost s muškim kolegama koji su ih onda i prihvatili. Tako je, na primjer, Agnes Sjöberg, prva žena veterinar u Finskoj, izvela carski rez u kobile još 1944. godine, u doba kada još nije bilo antibiotika. Obitelji su često pokušavale odvratiti žene da postanu „horse doctors“ jer se smatralo da bi ženama bolje odgovarao rad s malim životinjama ili ribama ili da rade kao parazitolozi. Na zagrebačkom Veterinarskom fakultetu diplomirala je Jelka Bojkić (1932.) koja se bavila laboratorijskim istraživanjima. Danas je postotak studentica na mnogim veterinarskim fakultetima širom svijeta već iznad 50 %, a na nekima i 90 %. In this paper I have collected information about the first women veterinarians in approximately 40 countries. However, I am aware of the fact that some information may not be complete or correct, therefore, I shall be very glad to receive any missing information or rectification. Nowadays, when in some countries female veterinary students make about 75-80% or even more of veterinary medicine students in total, it is good to learn that a century ago it was not easy for women to study veterinary medicine, a subject taught since Cheiron’s time only to male students. The first countries where we found female veterinarians are Switzerland, France, Great Britain and Germany. In all these countries veterinary schools have an old and rich tradition. A stimulating factor for women to study veterinary sciences was also the First World War because of good possibilities for employment. After WWI it was easier to study veterinary medicine for women, especially in the newly founded countries: Czechoslovakia, Yugoslavia, and Baltic countries. A lot of German university professors worked in the 1920s and 1930s in Bulgaria and Turkey, which probably also contributed to the situation: women were beginning to be accepted at studies of veterinary medicine. The development and implementation of new fields such as hygiene, laboratory, pets, fish disease etc. also resulted in the opening of new working areas for women veterinarians. Croatian Academy of Sciences and Arts 2012-05-21 text pdf http://hrcak.srce.hr/84036 http://hrcak.srce.hr/file/125056 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.511=37; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:91321 2012-11-13 journal:117

Editorial Pećina, Marko; marko.pecina@zg.t-com.hr Croatian Academy of Sciences and Arts 2012-10-22 text pdf http://hrcak.srce.hr/91321 http://hrcak.srce.hr/file/134946 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.514=38; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:91322 2012-11-13 journal:117

Orofacial diseases - a scientific approach Brkić, Hrvoje Croatian Academy of Sciences and Arts 2012-10-22 text pdf http://hrcak.srce.hr/91322 http://hrcak.srce.hr/file/134948 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.514=38; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

oai:hrcak.srce.hr:91323 2012-11-13 journal:117

Prevencija nekarijesnih lezija u djece Prevention of noncarious lesions in children Čuković-Bagić, Ivana; bagić@sfzg.hr U razvijenim zemljama postoji značajan pad karijesa vjerojatno radi fluoridacije i poboljšanih oralno higijenskih navika. U isto vrijeme, epidemiološka istraživanja pokazuju značajan porast gubitka tvrdih zubnih tkiva nekarijesnim procesom. Nekarijesno trošenje moglo bi biti rezultat tri procesa: abrazije, atricije i erozije. U sadašnje vrijeme, najvažnija i najčešća među njima je dentalna erozija. Dentalna erozija predstavlja nepovratni gubitak tvrdog zubnog tkiva uslijed kiselina, bez prisustva bakterija, i zahvaća obje denticije, mliječnu i trajnu, istim patofiziološkim procesom. Prvi korak u prevenciji dentalne erozije jest, evaluirajući različite etiološke faktore, dovoljno rano identificiranje djece koja su pod rizikom. Temeljem te analize, trebalo bi predložiti djeci i predstaviti njihovim roditeljima individualno osmišljen preventivni program. Taj program bi trebao sadržavati: prehrambeno savjetovanje kako bi se poboljšale prehrambene navike, fluoridaciju, povećanje količine sline, primjenu puferirajućih proizvoda i savjetovanje o odgovarajućoj dentalnoj higijeni. Ne samo pacijenti, nego i mnogi stomatološki i medicinski stručnjaci nisu dovoljno educirani o epidemiologiji, etiologiji i načinima prevencije ovog nepovratnog gubljenja tvrdih zubnih tkiva. Znanje o svim aspektima dentalne erozije trebalo bi biti bitan dio suvremene dječje i preventivne (dentalne) medicine. Probably due to the fluoridation and improved oral hygiene habits, there has been a significant caries decline in children in developed countries. At the same time, epidemiological studies show significant increase of hard dental tissue loss by noncarious processes. Noncarious wear could be the result of three processes: abrasion, attrition and erosion. Nowadays, the most important of them, and the most frequent is dental erosion, an irreversible dissolution of hard tissue caused by acids, without bacterial involvement that affects both primary and permanent dentition by the same pathophysiological process. The first step in dental erosion prevention is identifying children in risk early enough by evaluating different etiological factors. Based on this analysis, an individually tailored preventive program should be suggested to the children and presented to their parents. That program should comprise: dietary advice in order to improve their dietary habits, fluoridation, improvement of salivary flow rate by using buffering products and advice on the proper dental hygiene. Not only patients, but also many dental and medical professionals are not sufficiently educated about the epidemiology, etiology and the ways of prevention of this irreversible loss of hard dental tissue. The knowledge on all these aspects of dental erosion should represent an important part of a contemporary paediatric and preventive (dental) medicine. prevencija; nekarijesne lezije; dentalna erozija; djeca prevention; noncarious lesions; dental erosion; children Croatian Academy of Sciences and Arts 2012-10-22 text pdf http://hrcak.srce.hr/91323 http://hrcak.srce.hr/file/134950 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.514=38; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

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Suvremene spoznaje o kompozitnim materijalima Contemporary concepts on composite materials Tarle, Zrinka; tarle@sfzg.hr Marović, Danijela Pandurić, Vlatko kompoziti; adhezivi; polimerizacija; skupljanje; remineralizacija. composites; adhesives; polymerization; shrinkage; remineralization. Kompozitni materijali su trodimenzijska kombinacija najmanje dva različita materijala koji su međusobno povezani jasno prepoznatljivom silanskom vezom. U razvoju kompozitnih materijala, iznimno mjesto pripada Michael G. Buonocoreu, koji je predložio jetkanje caklinske površine ortofosfornom kiselinom, Rafael L. Bowenu, koji je stvorio kompozitnu smolu i Nobuo Nakabayashiu, koji je predložio hibridizaciju dentinskog supstrata i tako ostvario promociju adhezije pomoću infiltracije monomera u zubnu strukturu. Kompozitni materijali sastoje se od tri temeljna dijela: organske smolaste matrice i odgovarajućeg inicijatora polimerizacije, anorganskog punila te svezujućeg sredstva. Kompozitni materijali razvili su se primarno za ispune prednjih i stražnjih zubi, ali se materijali sličnog sastava danas koriste za iznimno puno indikacija: pečaćenje fisura i jamica, adhezijsko cementiranje keramičkih i indirektnih kompozitnih restoracija, za izradu nadogradnji, izradu privremenih krunica i mostova, vezanje bravica u ortodonciji, izradu splintova te za ispun korijenskog kanala. Suvremeni kompozitni materijali se stalno nadograđuju i imaju znatno usavršena fizičko-mehanička svojstva u odnosu na prethodne generacije, poglavito tvrdoću, čvrstoću, elastičnost, otpornost na savijanje, kidanje, torziju i trošenje. Međutim, kako križno povezivanje u mrežu tijekom polimerizacije dovodi do volumetrijskog skupljanja, a posljedično i polimerizacijskog stresa koji može u značajnoj mjeri utjecati na stvaranje rubne pukotine i kompromitaciju trajnosti restorativnog zahvata, kompenzacija stresa predstavlja najveći znanstveni i klinički izazov. Budućnost kompozitnih materijala ogleda se u nekoliko smjerova. Prvi je iznalaženje niskoskupljajućih ili ekspandirajućih kompozitnih materijala, a drugi optimizacija kompozitnih materijala temeljenih na amorfnom kalcijevom fosfatu, koji je direktni prekursor hidroksilapatita, osnovne gradbene jedinice zuba. Ostali pristupi uključuju inkorporaciju antibakterijskih agensa u kompozite te razvoj materijala sa samovezujućim svojstvima. Composite materials are a tridimensional combination of at least two different materials mutually connected with a clearly recognizable coupling agent. In the development of composite materials, an outstanding place belongs to Michael G. Buonocore, who suggested etching the enamel surface with orthophosphoric acid; Rafael L. Bowen, who created composite resin, and to Nobuo Nakabayashi, who suggested hybridization of the dentin substrate and accomplished the promotion of adhesion by the infiltration of monomer into the tooth structure. Composite material consists of three fundamental parts: an organic resin matrix with a complimentary initiator of polymerization, an inorganic filler and a coupling agent. Composite materials were primarily developed for fillings on anterior and posterior teeth, but materials with similar composition are also used for an extremely large number of indications: pit and fissure sealants, adhesive cementation of ceramic and indirect composite restorations, for crown build-ups, temporary crowns and bridges, the bonding of brackets in orthodontics, making splints and root canal sealers. Contemporary composite materials are being constantly upgraded and have significantly improved physical and mechanical characteristics in comparison with previous generations, especially concerning the hardness, firmness, elasticity, resistance to bending, breaking, torsion and wear. However, since cross linking in net formation during polymerization leads to volumetric shrinkage and, consequently, polymerization stress that can affect the creation of a marginal gap and also compromise the longevity of the restoration, stress compensation represents the biggest scientific and clinical challenge. The future of composite materials is mirrored in several directions. The first one is finding low shrinking or expanding composite materials, the second one is the optimization of composite materials based on amorphous calcium phosphate which is a direct precursor of hydroxyapatite, the basic unit of tooth structure. Others include the incorporation of anti-bacterial agents into composites as well as the development of materials with self-adhesive properties. Croatian Academy of Sciences and Arts 2012-10-22 text pdf http://hrcak.srce.hr/91350 http://hrcak.srce.hr/file/134978 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.514=38; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en

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Parodontne bolesti kao čimbenik rizika Periodontal diseases as a risk factor Plančak, Darije; plancak@sfzg.hr Puhar, Ivan parodontna medicina; parodontitis; sistemske bolesti; kardiovaskularne bolesti; prerani porod; dijabetes; respiratorne bolesti. periodontal medicine; periodontitis; systemic disease; cardiovascular diseases; premature birth; diabetes; respiratory diseases. Sve je više dokaza koje govore u prilog povezanosti kroničnih upalnih bolesti čovjeka s oportunističkim infekcijama u parodontologiji. Parodontne bolesti, posebice uznapredovali parodontitis, postale su predmet mnogobrojnih istraživanja s obzirom na učestalost i mikrobiološku etiologiju. Parodontitis predstavlja veliku infektivnu opasnost za cijeli organizam jer otpuštajući mikroorganizme, njihove produkte te medijatore upale u krvotok može djelovati na udaljene organe i tkiva. Navedena činjenica smanjila je granice između medicine i stomatologije te je promjenom razmišljanja došlo do razvoja potpuno novog područja u parodontologiji koje je nazvano „parodontna medicina“. Tijekom prošlog desetljeća sve veći broj znanstvenih činjenica upućuje na snažnu povezanost parodontnih bolesti i sistemnih stanja i bolesti kao što su: ateroskleroza, kardiovaskularne i cerebrovaskularne bolesti, prijevremeni porođaj, dijabetes i plućne bolesti. Najviše istraživanja bilo je usmjereno na povezanost između parodontitisa i ateroskleroze s obzirom da imaju mnogo zajedničkih, potencijalnih patofizioloških mehanizama, kompleksne su etiologije te dijele brojne rizične faktore, među kojima je najznačajniji status pušača. Pronađeni su dokazi koji povezuju parodontitis s povećanim rizikom za aterosklerozu i tromboemboličkim zbivanjima. Parodontitis trudnica može povećati rizik za prijevremeno rođenje i smanjenu porođajnu težinu djeteta. Uloga dijabetesa kao faktora rizika za parodontitis istražena je ranije, ali određen broj studija ukazuje da možda postoji i dvosmjerni odnos, u skladu s koncepcijom da infekcija može doprinijeti oslabljenoj metaboličkoj kontroli dijabetesa. Rezultati mnogobrojnih studija i razvoj parodontne medicine doveli su do plodonosne suradnje s kolegama u medicini i otkrili mnoga nova saznanja koja potvrđuju da je usna šupljina integralni dio ljudskog tijela te da sistemsko zdravlje mora uključivati oralno i parodontno zdravlje. There is an increasing body of evidence in periodontology that speaks in favor of the association between human chronic inflammatory diseases and opportunistic infections. Considering their frequency and microbiological etiology, periodontal diseases, especially severe periodontitis, have become subjects of many studies. Periodontitis is a major infectious threat to the whole organism, since it can affect distant organs and tissues by releasing microbes, their products and mediators of inflammation into the bloodstream. This fact has reduced the boundaries between medicine and dentistry, but the change in thinking has developed an entirely new field of periodontology, also known as “periodontal medicine”. Over the past decade a growing body of scientific evidence shows a strong connection between periodontal disease and systemic conditions and diseases such as atherosclerosis, cardiovascular and cerebrovascular diseases, premature birth, diabetes and respiratory diseases. Most of the research has been focused on the relationship between periodontal disease and atherosclerosis since they have many common, potential pathophysiological mechanisms, including complex etiology, and share many risk factors, especially smoking history. There is data linking periodontitis with an increased risk for atherosclerosis and thromboembolic events. Periodontitis in pregnant women may increase the risk for preterm birth and low birth-weight. The role of diabetes as a risk factor for periodontal disease has been investigated earlier, but a number of studies suggest that there may be a two-way relationship, in accordance with the concept that infection may weaken metabolic control of diabetes. The results of numerous studies and the development of periodontal medicine have led to productive cooperation with colleagues in medicine, and discovered many new evidences that suggest that the oral cavity is an integral part of the human body, and that systemic health must include oral and periodontal health. Croatian Academy of Sciences and Arts 2012-10-22 text pdf http://hrcak.srce.hr/91351 http://hrcak.srce.hr/file/134980 Rad. Medical sciences (marko.pecina@zg.t-com.hr); No.514=38; ISSN 1330-5301 (Print); ISSN 1848-641X (Online) en 1369315398190