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Procena rezultata lečenja unutarzglobnih višekomadnih preloma gornjeg i donjeg okrajka potkolenice aparatom po Ilizarovu / Assessment of treatment results of intraarticulary multifragmentary fractures of upper and lower part of the lower leg by Ilizarov apparatusLalić Ivica 24 June 2016 (has links)
<p>Kompleksnost visokoenergetskih preloma platoa i pilona tibije i njihova udruženost sa značajnim povredama mekog tkiva oko pripadajućeg zgloba veoma je dobro opisana. Lečenje ima za cilj da multifragmentarni prelomi platoa i pilona tibije postanu stabilni, artikularno poravnani, bezbolni, da koleno i skočni zglob budu pokretni i da se minimizira rizik do nastanka posttraumatskog osteoartritisa. Aparat po Ilizarovu sa nategnutim iglama, koristi opterećenje da stvori jedinstvenu podršku za zglob i stabilnu imobilizacju preloma da se postigne njegovo srastanje. Ovo omogućuje ranu pokretljivost zgloba bez rizika od gubitka redukcije. Cilj istraživanja je procena i poređenje rezultata lečenja unutarzglobnih višekomadnih preloma kostiju proksimalnog i distalnog okrajka potkolenice tretiranih spoljnjim unilateralnim rigidnim fiksatorom i aparatom po Ilizarovu primenom ASAMI koštanog skoring sistema i funkcionalnog skoring sistema po Karlstrom – Olerudu.Takođe je jedan od ciljeva istraživanja bio da se uoče faktori koji utiču na različite rezultate lečenja unutarzglobnih višekomadnih preloma kostiju gornjeg i donjeg okrajka potkolenice tretiranih spoljnim unilateralnim rigidnim fiksatorom i aparatom po Ilizarovu. Istraživanje je dizajnirano kao kontrolisana komparativna klinička studija a podaci su se prikupljali retrospektivno i delom prospektivno na osnovu medicinske dokumentacije od 2008. do 2013. godine. Studija je u potpunosti izvedena na Klinici za ortopediju i traumatologiju Kliničkog centra Vojvodina u Novom Sadu. Studija je obuhvatila ukupno 103 ispitanika kod kojih je u toku 2008 do 2013. godine postavljena dijagnoza unutarzglobnog višekomadnog preloma gornjeg ili donjeg okrajka tibije. Ispitanici koji su obuhvaćeni ovim kliničkim istraživanjem razvrstani su u tri grupe: Prvu grupu od 53 ispitanika činili su oni sa višekomadnim unutarzglobnim otvorenim ili zatvorenim prelomima gornjeg ili donjeg okrajka kostiju potkolenice lečenih isključivo spoljnjim unilateralnim rigidnim fiksatorom. Drugu grupu ispitanika, njih 31, činili su oni sa višekomadnim unutarzglobnim otvorenim ili zatvorenim prelomima gornjeg ili donjeg okrajka kostiju potkolenice lečenih isključivo aparatom po Ilizarovu. Treću grupu činila su 19 ispitanika sa višekomadnim unutarzglobnim otvorenim ili zatvorenim prelomima gornjeg ili donjeg okrajka kostiju potkolenice koji su lečenje započeli spoljnjim unilateralnim rigidnim fiksatorom, a u kasnijem periodu zbog nastalih komplikacija (loše srastanje, produženo srastanje, nesrastanje, infekcija, pseudoartroza) lečenje nastavili konverzijom spoljnjeg unilateralnog rigidnog fiksatora u aparat po Ilizarovu. Osnovni izvor podataka za prikazano istraživanje bio je protokol formiran za svakog bolesnika pojedinačno, istorije bolesti i poliklinička evidencija. Za potrebe istraživanja dizajniran je protokol istraživanja gde su se prikupljeni podaci analizirali hronološki : podaci o pacijentu, klinički nalaz na prijemu, postoperativni tok, monitoring aparata, klinički nalaz na otpustu i klinički nalaz na kontrolama od 6, 12 i 18 meseci. Kliničke nalaze na kontrolama na 6, 12 i 18 meseci beležili smo upotrebom skoring sistema ASAMI ( Udruženja za istraživanje i primenu metoda po Ilizarovu) – za koštane rezultate, i Karlstrom – Oleruda za procenu funkcionalnih rezultata. Neki do najvažnih rezultata dobijenih prilikom ovog istraživanja jesu da je najbrže vreme srastanja imala grupa Ilizarov, nakon 16±2 nedelja. Grupa konverzija zabeležila je prosečno vreme srastanja u 17±2 nedelji, dok je kod ispitanika u grupi fiksator zabeženo srastanje u 21±4 nedelji. Pojava površnih i dubokih infekcija značajno je veća kod grupe tretiranih spoljnim unilateralnim fiksatorom nego kod grupa tretiranih aparatom po Ilizarovu. Vreme postizanje ranog, punog oslonca na operisani ekstremitet je značajno kraće kod grupe Ilizarov i konverzija nego kod grupe fiksator. Procena koštanih rezultata korišćenjem ASAMI bodovnog sistema koštanog srastanja ukazuje na statistički značajno bolje rezultate kod grupa Ilizarov i konverzija u odnosu na grupu spoljnji fiksator u periodu praćenja i analize na 6,12 i 18 meseci. Funkcionalni rezultati primenom sistema funkcionalne evaluacije po Karlstrom – Olerudu govore u prilog značajno statistički boljim rezultatima kod grupe Ilizarov i konverzija u odnosu na grupu spoljni fiksator u periodima praćenja i analize na 6,12 i 18 meseci. Na osnovu dobijenih rezultata dolazimo do zaključka da je tretman ispitanika sa multifragmentarnim, intraarikularnim prelomima gornjeg i donjeg okrajka kostiju potkolenice znatno efikasniji aparatom po Ilizarovu što sveukupno daje smernice za brži i kvalitetniji oporavak ispitanika i njihov povratak svakodnevnim aktivnostima sa što manjim posttraumatskim sekvelama.</p> / <p>The complexity of high-energy fractures of the tibia plateau and pilons and their association with significant violations of the soft tissue around the corresponding joint is well described in the literature. Main aim of the treatment is to multiple fractures of the tibia plateau and pilon become stable, articularly aligned, without pain, and with full motion in the knee and ankle joint with minimum risk for post-traumatic osteoarthritis. Ilizarov apparatus with taut needles is used to create a unique load support for the ankle and create conditions for good healing. This strong stability allows early joint movement, without risk of loss position of fracture parts. The aim of this research is assessment and comparation of the results of treatment, for intraarticular multiple fractures of the proximal and distal part of lower leg tretaed with unilateral external rigid fixator and Ilizarov apparatus, with ASAMI bone scoring system and functional scoring sistem by Karlstrom – Olerud. One of the goals of the study was to detect factors which affecting different treatment results of the intraarticular multiple fractures of the proximal and distal part of lower leg, tretaed with unilateral external rigid fixator and Ilizarov apparatus. The study was designed as a controlled comparative clinical study and data were collected retrospectively and prospectively form medical records from 2008 to 2013. The study has been fully implemented at the Department for orthopedic surgery and traumatology in the Clinical Center of Vojvodina in Novi Sad and included 103 patients who had intraarticular multiple fractures of the proximal and distal part of tibia. Subjects covered in this clinical study were classified into three groups: The first group of 53 patients were with intraartiulary multifragmentary open or closed fractures of the upper or distal part of lower leg, treated exclusively with unilateral external rigid fixator. The second group included 31 patients with intraarticular open or closed fractures of the upper or distal lower leg, treated exclusively with Ilizarov apparatus. 19 patients made the third group with intraarticulary open or closed fractures of the upper or distal lower leg, which were treated at the begining with unilateral external rigid fixator and later because of the complications (poor or prolonged healing, nonunion, infection and pseudoarthrosis) tretment was continued by Ilizarov apparatus. The main source of data for this study was protocol wich was established for each patient individually. In this protocol collected data analyzed by date: patient data, clinical findings at admission, postoperative course, monitoring apparatus, clinical findings at discharge and clinical findings at the controls which were at 6, 12 and 18 months after surgery. Clinical findings at control examinations (6, 12 and 18 months after surgery), we recorded by scoring system ASAMI (Association for the Study and Application of the Methods of Ilizarov) - that represent the results of the bone healing, and Karlstrom - Olerud for assessment functional outcomes. The most important results were: the fastest time of bone union was in the group of Ilizarov, and it was after 16 ± 2 weeks and the third group (conversion group) recorded an average time after 17 ± 2 weeks, while the patients in the first group (external fixator) had average time of union after 21 ± 4 week. The appearance of superficial and deep infection was significantly higher in the group treated with unilateral external fixator than in the group treated by the Ilizarov apparatus. Fastest full weight bearing on the injured leg, had patients in the group treated with Ilizarov apparatus. Evaluation of results using bone ASAMI fusion scoring system indicating a statistically significantly better results in the conversion and Ilizarov group compared to the group of external fixator in the period of monitoring at 6,12 and 18 months after surgery. Functional results by Karlstrom - Olerud scoring system show statistically significantly better results in the Ilizarov and conversion group contrary to the external fixator group in periods of monitoring at 6,12 and 18 months. Based on these results we conclude that the treatment of subjects with intraarticulary, multifragmentary fractures of the upper and lower part of the lower leg are more efficient after Ilizarov apparatus which provides overall guidance for faster and better recovery of patients and their return to their daily activities with minimal post-traumatic sequelae.</p>
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Primena PET/CT pregleda u planiranju radiološke terapije kod pacijenata obolelih od Hočkinovog limfoma / The use of PET/CT in radiotherapy planning in patients with Hodgkin's lymphomaMitrić Ašković Milana 19 July 2016 (has links)
<p>Studija je imala za cilj da pokaže značaj primene PET/CT pregleda u planiranju radiološke terapije kod pacijenata obolelih od Hočkinovog linfoma. U Vojvodini je 2009. godine prema podacima Registra za maligne neoplazme Vojvodine incidence za Hočkinov limfom iznosila 2,7 na 100 000 dok je mortalitet bio 1,1 na 100 000 stanovnika. Na osnovu dostupnih podataka Registra za maligne neoplazme Vojvodine beleži se porast incidence u protekloj deceniji. Procenat obolelih u Vojvodini u korelaciji je sa podacima koje navodi i Međunarodna agencija za istraživanje raka iz Liona (IARC). U Evropi i u Sjedinjenim Američkim Državama postoji bimodularna kriva incidence po starosti koja pokazuje maksimalne vrednosti u period između 20 i 30 godina i nakon 55. godine. S obzirom da od Hočkinovog limfoma dominantnije obolevaju mlađe osobe a da bolest ima dobru prognozu neophodno je iznaći nove načine za inicijalno određivanje stadijuma bolesti, kao i metode koje mogu da unaprede kvalitet lečenja. Jedan od načina je primena što savremenijih dijagnostičkih metoda. PET-CT je imidžing metoda koja poslednjih godina zauzima značajno mesto u određivanju stadijuma malignih bolesti kao i u proceni odgovora na primenjenu terapiju. Fuzionisanjem skenova PET-a i CT-a dobija se PET-CT slika koja prikazuje funkcionalno stanje pojedinih tkiva i organa (PET) sa anatomskim detaljima (CT). Cilj istraživanja je bio da se utvrdi prednost PET-CT pregleda u planiranju radioterapije kod pacijenata sa supradijafragmalnom lokalizacijom bolesti. Nakon postavljanja dijagnoze Hočkinovog limfoma kod pacijenata je urađen PET-CT i planiranje radiološke terapije. Zračna terapija je planirana na osnovu nalaza PET-CT-a i njegovom fuzijom sa CT-om za planiranje radiološkog lečenja. Dobijeni planovi su poređeni sa onim koji su rađeni standardnom 3D konformalnom tehnikom bez fuzije. Poređeni su klinički volumeni (CTV) i planirani volumen (PTV) kao i razlike u njihovoj obuhvaćenosti preskribovanom dozom. Pokazano je da postoji statistički značajna razlika u ciljnim volumenima kao i u njihovoj obuhvaćenosti. Posmatrani su takođe i rizični organi- srce, pluća, dojke, štitasta žlezda, kičmena moždina i doze koje oni prime. Dokazano je da su sa statističkom značajnošću dozna opterećenja na navedene rizične organe manja kada se planiranje vrši na osnovu fuzije sa PET-CT-om, te se na osnovu toga može reći da će i očekivane manifestacije kasne toksičnosti biti manje. Istraživanjem je potvrđena hipoteza da PET/CT ima veliku prednost u planiranju radioterapije jer smanjuje zapremine ciljnih volumena i doprinosi poboljšanju kvaliteta radiološkog lečenja.</p> / <p>This study aimed to prove that the use of PET/CT in radiotherapy planning makes a material change in the course of the treatment of the patients with Hodgkin's lymphoma. According to the data from the Registry of malignant neoplasms in Vojvodina, incidence of Hodgkin's lymphoma in Vojvodina in 2009 was 2.7 per 100 000, while the mortality rate was 1.1 per 100 000 inhabitants. Based on the available data, the said Register recorded an increase in the incidence over the past decade. The percentage of patients who were registered in Vojvodina is in correlation with the data cited by the International Agency for Research on Cancer in Lyon (IARC).In Europe and in the United States the disease has a bi-modular distribution distribution with the highest frequency rate in persons ageing from 20-30 years and people older than 55 years. Due to the fact that the dominant Hodgkin's lymphoma affects young people and having in mind the good prognosis of the disease, it is necessary to find a new modality for the initial staging of disease and methods which can improve the quality of treatment. PET/CT is the imaging method which has in recent years had an important role in the staging of malignancies, as well in the evaluation of response to therapy. PET/CT image is obtained by fusing PET scans with CT and it show functional status of certain tissues and organs (PET) with anatomical details (CT).The object of this study was to show that PET/CT examinations are preferred imaging method in radiotherapy planning in patients with localized disease above the diaphragm. After they had been diagnosed with HL, patients underwent PET/CT scan which was later used for delineation in radiotherapy planning. In this study, radiation therapy was planned on the basis of the findings of PET /CT and its fusion with CT for planning radiological treatment. The resulting plans were compared with those made using standard 3D conformal technique without fusion. Clinical volume (CTV) and the planned volume (PTV) and the differences in their coverage with the prescription dose in both plans were also compared. The study has shown a statistically significant difference in the target volume and their coverage. In addition, the dose which receive organs at risk was also examined. It has been shown that organs at risk were exposed to lower doses when using PET/CT fusion in radiotherapy planning and consequently, less incidence of late toxicity is to be expected. The study confirmed the hypothesis that PET /CT has a great advantage in the planning of radiotherapy because it reduces the volume of the target volume and improves the quality of radiation treatment.</p>
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Patohistološka procena tumorske regresije kod nemikrocelularnih karcinoma pluća posle neoadjuvantne terapije / Histopathologic assessment of tumor regression in non-small cell lung cancer after neoadjuvant therapySamardžija Golub 14 September 2016 (has links)
<p>Karcinomi pluća su najčešći uzrok oboljevanja i umiranja od malignih tumora u Svetu. Neodjuvantna terapija kod bolesnika sa lokalno uznapredovalim (IIIA-IIIB) karcinomom pluća i zahvaćenim N2 limfnim čvorovima jedan je od modusa multimodalnog lečenja bolesnika sa nemikrocelularnim karcinomima pluća (NSCLC) u cilju poboljšanja ishoda njihovog lečenja. Ovakav pristup podrazumeva prevođenje bolesnika iz višeg u niži stadijum bolesti - „downstaging”. Do danas nije utvrđena povezanost između pojedinih obrazaca tumorskog odgovora i vrste terapije. S obzirom na značaj kompletnog patološkog odgovora i tumorske regresije u prognozi ishoda lečenja, iznalaženje ove povezanosti je od značaja za dizajniranje budućih neoadjuvantnih trajala. Prilikom utvrđivnja histološke slike tumorske regresije veoma je važno i merenje areje rezidualnog tumora (ART). Kako je veličina tumora jedan od prognostičkih faktora za bolesnike sa NSCLC koji nisu primali neoadjuvantnu terapiju tako je i merenje ART, za razliku od makroskopske veličine tumora, jedan od prognostičkih faktora za bolesnike sa NSCLC koji su primali neoadjuvantnu terapiju. Krajnji cilj neoadjuvantne terapije trebalo bi da bude resektabilnost i „downstaging” koji bi mogao da obezbedi u specifičnim kliničkim situacijama i sveukupni onkološki benefit. Osnovni ciljevi ove doktorske disertacije su bili: da se objektivizira procena veličine ART u tumorskom tkivu pluća i limfnih čvorova; da se proceni povezanost površine ART sa veličinom tumora na postoperativnom hirurškom materijalu posle neoadjuvantne terapije; da se analizira i proceni povezanost histomorfoloških parametara kod tumorske regresije indukovane neoadjuvantnom terapijom i spontane tumorske regresije u tumorima pluća i limfnih čvorova na postoperativnom hirurškom materijalu i u zavisnosti od histološkog tipa karcinoma; da se proceni povezanost kliničkog odgovora na neoadjuvantnu terapiju prema kriterijumima Svetske Zdravstvene Organizacije i histoloških parametara u tumorima pluća i limfnim čvorovima na postoperativnom hirurškom materijalu nakon neoadjuvantne terapije; da se proceni povezanost patološkog ypTN sa kliničkim ycTN stadijumom bolesti i stepena tumorske regresije indukovane neoadjuvantnom terapijom i patološkog ypTN i da se proceni povezanosti između kliničke i patološke zahvaćenosti N2 limfnih čvorova posle neoadjuvantne terapije. Merenje ukupne veličine očuvanih ART je najznačajniji objektivni parametar u proceni stepena tumorske regresije. Veličina rezidualnog tumora nije u korelaciji sa veličinom tumora posle neoadjuvantne terapije. Postoji signifikantna razlika u patohistološkoj slici tumorske regresije indukovane neoadjuvantnom terapijom i spontane tumorske regresije. Ne postoji signifikantna razlika između histološkog tipa tumora i histološke slike tumorske regresije. Ne postoji signifikantna povezanost između kliničkog odgovora i stepena tumorske regresije nakon neoadjuvantne terapije. Ne postoji korelacija između kliničkog i patološkog stadijuma bolesti posle neoadjuvantne terapije. Ne postoji korelacija između stepena tumorske regresije indukovane neoadjuvantnom terapijom i ypTN stadijuma bolesti. Ne postoji korelacija između kliničke i patološke zahvaćenosti N2 limfnih čvorova posle neoadjuvantne terapije. Stepen regresije tumora i merenje ART posle neoadjuvantne terapije određen histopatološkom analizom reseciranog tumora je najobjektivniji kriterijum za procenu hemioterapijskog odgovora i predviđanja ishoda lečenja pacijenata.</p> / <p>Lung cancers are the most common cause of morbidity and mortality from malignant tumors in the World. The neodjuvant therapy in patients with locally advanced (IIIA-IIIB) lung cancer and affected N2 lymph nodes is one of the modes of multimodal treatment of patients with non-small cell lung cancer (NSCLC) in order to improve the outcome of their treatment. This involves converting patients from a higher to a lower stage of the disease - "downstaging". There has been no significant connection between some forms of tumor response and types of therapy. Given the importance of complete pathological responses and tumor regression in the prediction of treatment outcomes, finding this relationship is of importance for the design of future neoadjuvant trails. In determining the histological tumor regression is very important measurement of area of residual tumor (ART). As the size of the tumor is one of the prognostic factors in patients with NSCLC who did not receive neoadjuvant therapy so the measurement of ART, as opposed to the macroscopic size of the tumor, one of the prognostic factors in patients with NSCLC, who had received neoadjuvant therapy. The ultimate goal of neoadjuvant therapy should be resectability and "downstaging" that could provide overall oncology benefit in specific clinical situations. The main objectives of this thesis were: to objectively estimate the size of ART in tumor tissue of lung and lymph nodes; to estimate the relation between the surface of ART with the size of the tumor on postoperative surgical material after neoadjuvant therapy; to analyze and estimate the relation between histomorphological parameters in tumor regression induced by neoadjuvant therapy and spontaneous tumor regression in tumors of the lung and lymph nodes in the postoperative surgical material and depending on the histological type of cancer; to estimate the relation between clinical response to neoadjuvant therapy according to criteria of the World Health Organization and histological parameters in lung tumors and lymph nodes in the postoperative surgical material after neoadjuvant therapy; to estimate the correlation of the pathological ypTN with clinical ycTN stage of the disease and the degree of tumor regression induced by neoadjuvant therapy and pathological ypTN and estimation of the relation between clinical and pathological involvement of N2 lymph nodes after neoadjuvant therapy. Measurement of the total size of the preserved ART is the most important objective parameter in the assessment of the grade of tumor regression. Size of residual tumor did not correlate with the size of the tumor after neoadjuvant therapy. There was a significant difference in the histological picture of tumor regression induced by neoadjuvant therapy and spontaneous tumor regression. There was no significant difference between the histologic type of tumor and histological tumor regression. There is no significant correlation between clinical response and the grade of tumor regression after neoadjuvant therapy. There is no correlation between clinical and pathological staging of the disease after neoadjuvant therapy. There is no correlation between the grade of tumor regression induced by neoadjuvant therapy and ypTN stage of the disease. There is no correlation between the clinical and the pathological involvement of the N2 lymph nodes to neoadjuvant therapy. The grade of tumor regression and measurement ART after neoadjuvant therapy determined by histopathological analysis of the resected tumor is the most objective criterion for evaluation of chemotherapeutic response and prediction of treatment outcome in patients.</p>
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Uticaj sveobuhvatne kardijalne rehabilitacije na dijastolnu disfunkciju i funkcionalni status pacijenata lečenih perkutanom koronarnom intervencijom nakon akutnog koronarnog događaja / The impact of comprehensive cardiac rehabilitation on diastolic dysfunction and the functional status of patients treated with percutaneous coronary intervention after acute coronary eventBjelobrk Marija 10 May 2019 (has links)
<p>Uvod: U savremenom svetu koronarna arterijska bolest srca (KABS) je vodeći uzrok obolevanja i umiranja, a akutni koronarni sindrom (AKS) je jedna od njenih najčešćih i najopasnijih kliničkih manifestacija. Dijastolna disfunckija leve komore često prati KABS i mogući je doprinosni faktor za loš klinički tok i ishod. Postavlja se pitanje u kom obimu je dijastolna disfunkcija leve komore udružena sa koronarnom arterijskom bolešću i da li savremeni programi ambulantne sveobuhvatne kardijalne rehabilitacije (ASKR) imaju uticaja na bolju prognozu ove grupe kardioloških bolesnika. Uprkos širokoj primeni revaskularizacionih procedura u svakodnevnoj kardiološkoj praksi i brojnih studija koje su ukazale na pozitivne efekte programa SKR na funkcionalni status pacijenata nakon AKS, još uvek postoji mnogo kontroverzi o efektima fizičkog treninga, na srčanu funkciju i poboljšanje funkcionalnog kapaciteta kod pacijenata sa KABS i pridruženom dijastolnom disfunkcijom. Cilj istraživanja: bio je da ispita uticaj superviziranih vežbi fizičkim opterećenjem (VFO) u okviru programa ambulantne sveobuhvatne kardijalne rehabilitacije (ASKR), na dijastolnu disfunkciju leve komore (DDLK) i funkcionalni status pacijenata (FS), nakon AKS, rešenog perkutanom koronarnom intervencijom (PCI), kao i da li, s druge strane, prisustvo i stepen dijastolne disfunkcije na početku istraživanja, utiče na funkcionalni status i pojavu neželjenih kardijalnih događaja, kod ove grupe pacijenata u okviru programa ASKR i van njega Materijal i metode: Istraživanjem je bilo obuhvaćeno ukupno 85 ispitanika, oba pola, starosti od 18-65 godina, koji su tokom indeksne hospitalizacije lečeni kao klinički dokazani AKS (APNS; NSTEMI; STEMI) i kod kojih je urađena neka od interventnih koronarnih procedura (pPCI; PCI; PTCA). Nakon 4 nedelje od otpusta sa hospitalizacije, zbog NSTEMI ili APNS, odnosno nakon 6 nedelja od otpusta sa hospitalizacije zbog STEMI, pacijenti sa EFLK ≥ 45%, bez značajnih valvularnih i drugih mana i sa nekim od poremećaja dijastolne funkcije, bili su kandidati za učešće u istraživanju. Svi ispitanici su podvrgavani „ulaznom“ehokardiografskom pregledu (EHO) u cilju procene sistolne funkcije i stepena dijastolne disfunkcije leve komore, kao i „ulaznom“ spiroergometrijskom testu (CPET) u cilju procene funkcionalnog statusa, na osnovu kojeg je vršena preskripcija vežbi fizičkim opterećenjem (VFO) u okviru programa ASKR. Program ASKR odvijao se u ukupnom trajanju od 12 nedelja, odnosno 36 pojedinačnih sesija VFO, 3 puta nedeljno u trajanju od po 30 minuta. Kontrolna grupa obuhvatila je grupu pacijenata koja nije živela u blizini IKVBV i koja nije bila u mogućnosti da dolazi redovno na VFO u sklopu ASKR. Njima je bilo pušteno na volju da na osnovu urađenog EHO pregleda i CPET, određuju stepen VFO po sopstvenom nahođenju, uz primenu optimalnog medikamentnog lečenja i ostalih mera sekundarne prevencije. Nakon 3 meseca obe grupe pacijenata bile su podrvrgnute novom –“izlaznom” ehokardiografskom i CPET pregledu u cilju komparacije sa rezultatima na početku istraživanja. Rezultati:Istraživanje je pokazalo da nakon 3 meseca superviziranog treninga VFO, u okviru programa ASKR, kod bolesnika nakon AKS, lečenih perkutanom koronarnom intervencijom, dolazi do poboljšanja stepena dijastolne disfunkcije leve komore, naročito kroz promene vrednosti ehokardiografskih parametara e’l i E/e’ l. U kontrolnoj grupi e’l se smanjio za (0,003 ± 0,025), a u osnovnoj se povećao za (0,011 ± 0,021). U kontrolnoj grupi e’l se nije značajno promenio (p = 0,515), a u osnovnoj grupi se značajno povećao (p < 0,0005). Na početku istraživanja u osnovnoj grupi e’l je bio (0,097 ± 0,027 m/sec), a na kraju (0,108 ± 0,031 m/sec). E/e’l se nije značajno promenio u kontrolnoj grupi (p = 0,226), a u osnovnoj grupi se značajno smanjio (p = 0,002). Na početku istraživanja u osnovnoj grupi E/e’l je bio (8,02 ± 2,98), a na kraju (6,97 ± 2,17). Takođe je utvrđeno da nakon 3 meseca superviziranog treninga u okviru programa ASKR, dolazi do poboljšanja funkcionalnog kapaciteta pacijenata sa KABS i dijastolnom disfunkcijom leve komore, kroz povećanje CPET parametara: peak VO2, VO2 predict i METs. U kontrolnoj grupi peak VO2 se smanjio za (1,79 ± 3,84), a u osnovnoj se povećao za (1,67 ± 4,29). U kontrolnoj grupi peak VO2 se značajno smanjio (p = 0,018), a u osnovnoj grupi se značajno povećao (p = 0,005).Na početku istraživanja u kontrolnoj grupi srednja vrednost peak VO2 iznosila je (23,01 ± 3,99 ml/kgTT/min), a u osnovnoj grupi je iznosila (23,15 ± 4,99 ml/kgTT/min). Na kraju istraživanja u osnovnoj grupi srednja vrednost peak VO2 iznosila (24,82 ± 5,77 ml/kgTT/min), dok je kod kontrolne grupe iznosila (21,21 ± 4,05 ml/kgTT/min). U kontrolnoj grupi ppVO2(%) se smanjio za (5,28 ± 14,39), a u ispitivanoj se povećao za (7,16 ± 18,51). U kontrolnoj grupi ppVO2(%) se nije značajno promenio (p = 0,058), dok se u osnovnoj grupi statistički značajno povećao (p = 0,005). Razlika srednjih vrednosti promena METs između osnovne i kontrolne grupe je bila statistički značajna (p < 0,0005). U kontrolnoj grupi METs se smanjio za (0,55 ± 1,12), a u osnovnoj se povećao za (0,58 ± 1,12). U kontrolnoj grupi METs se značajno smanjio (p = 0,013), a u osnovnoj grupi se značajno povećao (p < 0,0005). Zaključak: Program ambulantne sveobuhvatne kardijalne rehabilitacije, kod bolesnika nakon akutnog koronarnog sindroma, lečenih perkutanom koronarnom intervencijom, utiče na poboljšanje faktora rizika kardiovaskularnih bolesti, značajno utiče na poboljšanje stepena dijastolne disfunkcije leve komore i na poboljšanje funkcionalnog statusa pacijenata, u odnosu na početak istraživanja.</p> / <p><!--[if gte mso 9]><xml> <o:DocumentProperties> <o:Author>mladen</o:Author> <o:Version>16.00</o:Version> </o:DocumentProperties> <o:OfficeDocumentSettings> <o:AllowPNG/> </o:OfficeDocumentSettings></xml><![endif]--><!--[if gte mso 9]><xml> <w:WordDocument> <w:View>Normal</w:View> <w:Zoom>0</w:Zoom> <w:TrackMoves/> <w:TrackFormatting/> <w:PunctuationKerning/> <w:ValidateAgainstSchemas/> <w:SaveIfXMLInvalid>false</w:SaveIfXMLInvalid> <w:IgnoreMixedContent>false</w:IgnoreMixedContent> <w:AlwaysShowPlaceholderText>false</w:AlwaysShowPlaceholderText> <w:DoNotPromoteQF/> 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<w:LsdException Locked="false" Priority="69" Name="Medium Grid 3 Accent 2"/> <w:LsdException Locked="false" Priority="70" Name="Dark List Accent 2"/> <w:LsdException Locked="false" Priority="71" Name="Colorful Shading Accent 2"/> <w:LsdException Locked="false" Priority="72" Name="Colorful List Accent 2"/> <w:LsdException Locked="false" Priority="73" Name="Colorful Grid Accent 2"/> <w:LsdException Locked="false" Priority="60" Name="Light Shading Accent 3"/> <w:LsdException Locked="false" Priority="61" Name="Light List Accent 3"/> <w:LsdException Locked="false" Priority="62" Name="Light Grid Accent 3"/> <w:LsdException Locked="false" Priority="63" Name="Medium Shading 1 Accent 3"/> <w:LsdException Locked="false" Priority="64" Name="Medium Shading 2 Accent 3"/> <w:LsdException Locked="false" Priority="65" Name="Medium List 1 Accent 3"/> <w:LsdException Locked="false" Priority="66" Name="Medium List 2 Accent 3"/> <w:LsdException Locked="false" Priority="67" Name="Medium Grid 1 Accent 3"/> <w:LsdException Locked="false" Priority="68" Name="Medium Grid 2 Accent 3"/> <w:LsdException Locked="false" Priority="69" Name="Medium Grid 3 Accent 3"/> <w:LsdException Locked="false" Priority="70" Name="Dark List Accent 3"/> <w:LsdException Locked="false" Priority="71" Name="Colorful Shading Accent 3"/> <w:LsdException Locked="false" Priority="72" Name="Colorful List Accent 3"/> <w:LsdException Locked="false" Priority="73" Name="Colorful Grid Accent 3"/> <w:LsdException Locked="false" Priority="60" Name="Light Shading Accent 4"/> <w:LsdException Locked="false" Priority="61" Name="Light List Accent 4"/> <w:LsdException Locked="false" Priority="62" Name="Light Grid Accent 4"/> <w:LsdException Locked="false" Priority="63" Name="Medium Shading 1 Accent 4"/> <w:LsdException Locked="false" Priority="64" Name="Medium Shading 2 Accent 4"/> <w:LsdException Locked="false" Priority="65" Name="Medium List 1 Accent 4"/> <w:LsdException Locked="false" Priority="66" Name="Medium List 2 Accent 4"/>
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Faktori rizika koji utiču na ishod respiratorne rehabilitacije kod pacijenata sa hroničnom opstruktivnom bolesti pluća / Risk factors relevant for respiratory rehabilitation outcome in chronic obstructive pulmonary disease patientsKuhajda Danijela 29 September 2016 (has links)
<p>Hronična opstruktivna bolest pluća (HOBP) jedna je od vodećih uzroka morbiditeta i mortaliteta širom sveta. Uprkos stalnom napretku u medicini, uvođenju novih prognostičkih biomarkera, otkrivanju novih bronhodilatatornih, antiniflamatornih i antiinfektivnih lekova, ova bolest i danas beleži stalan porast broja obolelih i umrlih. Prema savremenom tumačenju HOBP je heterogena bolest koja je udružena sa brojnim komorbiditetima i sistemskim manifestacijama. Zajednički faktori rizika su osnova za javljanje udruženih hroničnih bolesti. Komorbiditeti i akutne egzacerbacije doprinose ukupnoj težini bolesti. S obzirom da se HOBP manifestuje i izvan pluća kod svakog pacijenta je neophodno proceniti postojanje sistemskih manifestacija i tragati za komorbiditetima. U reviziji „Globalne strategije za dijagnozu, lečenje i prevenciju hronične opstruktivne bolesti pluća GOLD‖ iz 2011. godine navedene sledeće pridružene bolesti za kojima je potrebno aktivno tragati: kardiovaskularne bolesti, disfunkcija skeletnih mišića, metabolički sindrom, osteoporoza, depresija i karcinom pluća, bronhiektazije. Lečenje HOBP delimo u dve velike grupe: farmakološko i nefarmakološko. Farmakološko lečenje prema GOLD-u, danas se zasniva na stepenastom pristupu. Treba ga sprovodi kod svakog pacijenta sa simptomima. Poslednjih godina na značaju veoma dobija nefarmakološko lečenje pacijenata sa HOBP, zbog sve više dokaza o pozitivnom efektu na smanjenje simptoma bolesti, popravljanja tolerancije na napor, smanjenje egzacerbacija. U nefarmakološko lečenje ubrajamo: aktivno izbegavanje faktora rizika, prestanak pušenja, oksigenoterapiju, vakcinaciju protiv gripa, psihosocijalnu podršku, respiratornu rehabilitaciju (RR) i hirurško lečenje. Danas se zna da RR ostvaruje brojne benefite kod pacijenata sa HOBP, kao i da je većina tih benefita zasnovana na dokazima (GOLD 2013): poboljšava kapacitet za vežbanje, smanjene osećaja nedostatka vazduha, poboljšava kvalitet života, smanjuje broj hospitalizacija i dužinu hospitalizacije, smanjuje anksioznost i depresiju povezane sa HOBP, efekti traju i nakon završenog programa rehabilitacije, poboljšava preživljavanje ovih pacijenata. Primarni ciljevi našeg istraţivanja bili su da se utvrdi procenat ispitanika kod kojih je ostvaren pozitivan ishod respiratorne rehabilitacije, da se odredi povezanost sledećih faktora sa ishodom respiratorne rehabilitacije: pol, godine života, „pack/years―, dužina trajanja bolesti, broj egzacerbacija u prethodnoj godini, pridružena oboljenja: ishemijska bolest srca, srčana insuficijencija, hipertenzija, osteoporoza, depresija, dijabetes, bronhiektazije, karcinom pluća, tuberkuloza pluća. Takođe smo želeli da utvrdimo i uticaj sledećih parametara na ishod rr:FEV1, BMI, satO2, 6-minutni test hoda, „CAT― upitnik, „mMRC― upitnik, BODE indeks. Urađena je retrospektivno-prospektivna studija, koja je uključila 500 pacijenata sa HOBP, svih stadijuma I-IV , u stabilnoj fazi bolesti, koji su u toku dvogodišnjeg perioda odradili kompletan program ambulantne respiratorne rehabilitacije. Program je sprovođen u Poliklinici za plućne bolesti, Instituta za plućne bolesti Vojvodine. Dobijeni rezultati pokazali su da je 452 pacijenta (90,4%) ostvarilo pozitivan ishod RR: najviše ispitanika 142 (28,4%) bilo je u kategoriji vrlo dobar, potom slede kategorije dobar sa 129 ispitanika (25,8%), zadovoljavajući sa 102 ispitanika (20,4%), i na kraju kategorija odličan sa ukupno 79 (15,8%) ispitanika. Nakon programa RR došlo je do statistički značajnih poboljšanja u vrednostima FEV1, 6MTH, satO2, CAT, mMRC, BODE indeksa. Pol, starost, pušački status, dužina trajanja bolesti i ≥2 egzacerbacije u prethodnoj godini nemaju uticaja na uspešan ishod RR. Utvrđeno je postojanje statistički značajne negativne korelacije između srčane slabosti i pozitivnog ishoda respiratorne rehabilitacije, dok nije nađena statistički značajna povezanost ostalih ispitivanih komorbiditeta sa pozitivnim ishodom respiratorne rehabilitacije. Kao statistički značajni univarijantni prediktori pozitivnog ishoda respiratorne rehabilitacije jesu: manji broj pridruženih bolesti, odsustvo srčane slabosti, niža saturacija hemoglobin kiseonikom, veći BMI, mMRC ≥ 2, CAT ≥ 10, B i D stadijumi bolesti, dok je multivarijantnom logističkom regresionom analizom pokazano da su nezavisni prediktori pozitivnog ishoda respiratorne rehabilitacije: manji broj pridruženih bolesti, odsustvo srčane slabosti, veći BMI, CAT ≥ 10.</p> / <p>Chronic obstructive pulmonary disease (COPD) is one of the leading morbidity and mortality causes all over the world. Despite the steady advance in scientific research, introduction of novel prognostic biomarkers, new and potent bronchodilation, anti-inflammatory and anti-infectious drugs, a constant increase in the number of the affected and deceased from chronic obstructive pulmonary diseas has still been permanently evidenced in the 21st century. In a modern concept, the chronic obstructive pulmonary disease (COPD) is understood as a heterogenous disorder associated with numerous comorbidities and systemic manifestations. Common risk factors represent the basis for concomitant chronic diseases to develop. Comorbidities and acute exacerbations contribute to the overall disease severity. As a COPD may develop extrapulmonary manifestations as well, each patient should be evaluated for systemic manifestations and comorbidities. The 2011 update of the „Global Strategy for Chronic Obstructive Lung Disease Diagnosis, Management, and Prevention –GOLD‖ lists the following comorbidities to be actively searched for: cardiovascular diseases, skeletal muscle dysfunction, metabolic syndrome, osteoporosis, depression, lung cancer and bronchiectases. The treatment of COPD can be devided in two groups: pharmacological and non-pharmacological. Pharmacological treatment is today, according to GOLD, based on incremental approach. It should be carry out in every patient with simptoms. In last few years, non-pharmacological treatment of COPD is very popular, due to the evidence of positive effects on decreasing the simptoms, increasing the tolerance to exertion and decreasing the exacerbations. Non-pharmacological treatment consider: active avoiding the risk factors, smoking cessation, oxigenotherapy, vaccination against the flu, psicho-social support, respiratory rehabilitation and surgery. It is well known today that respiratory rehabilitation achieve numerous benefits in COPD patients and most of that benefits are evidence based (GOLD 2013): increasing the exercise capacity, decreasing the shortness of breath, increasing the quality of life, reduces the number and length of hospital stay, decreasing the anxiety and depression conected to COPD, the effects lasts and after the rehabilitation program, improves the survival of this patients. The primary goals of this investigation were to establish the percentage of patients with positive outcome after the respiratory rehabilitation, to determine the conection of the following factors with the outcome of respiratory rehabilitation: gender, age, „pack/years―, duration of the disease, the number of exacerbations in previous year, comorbidities: ischemic heart disease, heart failure, arterial hypertension, osteoporosis, depression, diabetes mellitus, bronchiectasis, lung cancer, tuberculosis. The other goals were to establish the influence of some parametars on the outcome of respiratory rehabilitation: FEV1, BMI, SaO2 ,6 minute walk test, „CAT― questionnaire, „mMRC― questionnaire, BODE index. This was retrospective-prospective study the included 500 patients with COPD, from I to IV stadium, in stable disease, who have done the two years complete program of ambulatory respiratory rehabilitation. The program have been done in polyclinic for respiratory diseases, Institute for pulmonary disesases of Vojvodina, Sremska Kamenica. The results showed that 452 patients (90,4%) achieved positive outcome of respiratory rehabilitation. The majority of patients 142 (28,4%) were in ―very good‖ caterogy, the 129 patients (25,8%) in category ―good‖, ―satisfied‖ 102 patients (20,4%) and ―excellent‖ 79 patients (15.8%). After completion of the respiratory rehabilitation program, statistically significant improvements of the following parameters have been achieved: FEV1, 6MTH, SaO2, mMRC, BODE index. Gender, age, smoking, duration of the disease and ≥2 exacerbations in previous year did not have influence on the successful respiratory rehabilitation outcome. The statistically significant negative correlation between the heart failure and positive respiratory rehabilitation outcome has been achieved, while there were no statistically significant correlations among other comorbidities and the successful respiratory rehabilitation outcome. The statistically significant univariant predictors of positive outcome of respiratory rehabilitation are: less comorbidities, absence of heart failure, lower oxygen saturation, higher BMI, , mMRC ≥ 2, CAT ≥ 10, B i D stadium of disease, while multivariant logistic regression analysis showed that the independent predictors of positive outcome of respiratory rehabilitation are: less comorbidities, absence of heart failure, higher BMI, CAT ≥ 10.</p>
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Uticaj medicinske rehabilitacije na kvalitet života operativno i neoperativno lečenih pacijenata sa lumbalnom radikulopatijom / The effect of medical rehabilitation on quality of life of surgically and non-surgically treated patients suffering from lumbar radiculopathyMahmutović Elvis 23 February 2018 (has links)
<p>Uvod: Sindrom lumbalne radikulopatije obuhvata disfunkciju nervnog korena lumbalne kičme, prouzrokovano kompresijom, nastalom usled hernijacije (protruzije, prolapsa) intervertebralnog diska ili zbog inflamatornih i degenerativnih promena (najčešće osteofita) u foraminalnom otvoru. Kvalitet života predstavlja savremeni koncept posmatranja ishoda oboljenja i uspešnosti terapijske procedure kako u svim oblastima medicine, tako i u problematici lumbalne radikulopatije.<br />Cilj: Proceniti kvalitet života operativno i neoperativno lečenih pacijenata sa lumbalnom radikulopatijom na početku lečenja i 3 meseca, odnosno 6 meseci nakon sprovedene medicinske rehabilitacije.<br />Metode: Istraživanje predstavlja prospektivnu kliničku studiju kojom je analiziran kvalitet života bolesnika sa lumbalnom radikulopatijom. Obuhvaćen je randomiziran i stratifikovan uzorak pacijenata sa lumbalnom radikulopatijom diskalne geneze starosti 20 do 65 godina, oba pola (n=100), lečenih u Specijalnoj bolnici za progresivne mišićne i neuromišićne bolesti Novi Pazar. Jedna grupa ispitanika (n=50) lečena je isključivo neoperativnim metodama, dok je druga grupa bolesnika (n=50) lečena hirurškim i neoperativnim metodama. Kod svih pacijenata sproveden je konzervativni tretman primenom fizikalnih procedura, kineziterapijskih procedura, ergonomske edukacije. Medikamentna terapija je kod svih bila identična. Za procenu stanja pacijenata, kvaliteta života i efekta rehabilitacionog tretmana korišćena su dva standardizovana upitnika: opšti zdravstveni upitnik Medical Outcomes Study Short Form 36 (SF 36) i upitnik specifičan za oboljenje The Oswestry Disability Index (ODI).<br />Rezultati: Vrednosti SF-36 upitnika prikazanih sumarnim fizičkim (SFS) i mentalnim (SMS) skorom, i kod neoperativno lečenih ispitanika (FSFS=450,221 i p<0,001; FSMS=106,543 i p<0,001), ali i kod operativno lečenih (FSFS=490,721 i p<0,001; FSMS=72,055 i p<0,001) značajno su se menjale u toku ispitivanja. Vrednosti SFS kod neoperativno lečenih pacijenata (početak tretmana, 3 meseca, 6 meseci): 35,5 / 44,7 / 50,8; kod operativno lečenih: 28,8 / 42,8 / 49,2. Vrednosti SMS kod neoperativno lečenih pacijenata: 40,6 / 44,8 / 52,6; kod operativno lečenih: 37,8 / 45,2 / 52,5.<br />Najveće poboljšanje SFS, kod obe grupe pacijenata, je registrovano u prva tri meseca od početka rehabilitacionog tretmana, dok je najveći napredak SMS registrovan u prva tri meseca od početka rehabilitacionog tretmana kod druge grupe pacijenata.<br />Vrednosti skora Osvestri indeksa nesposobnosti (ODI), i kod pacijenata prve grupe (F=432,810 i p<0,001), ali i kod pacijenata druge grupe (F=1341,180 i p<0,001) značajno su se menjale u toku ispitivanja. Vrednosti ODI kod neoperativno lečenih pacijenata su: 51,5% / 36% / 22,5%; a kod pacijenata druge grupe: 56,1% / 38,9% / 23,7%. Najveće poboljšanje je registrovano u prva tri meseca od početka rehabilitacionog tretmana kod druge grupe pacijenata. Postoje statistički značajne korelacije glavnih sumarnih skorova i domena SF-36 (SFS i SMS) i ODI skorova.<br />Zaključak: Kvalitet života i funkcionalni status i neoperativno i operativno lečenih pacijenata je značajno bolji u komparaciji stanja, na 3 meseca i na 6 meseci u odnosu na početak rehabilitacije, kao i na 6 meseci u odnosu na stanje na 3 meseca.</p> / <p>Introduction: The syndrome of lumbar radiculopathy involves dysfunction of nerve roots of the lumbar spine, caused by compression, resulting due to herniation (protrusion, prolapse) intervertebral disc, or due to inflammatory and degenerative changes (usually osteophytes) in foraminal opening. Quality of life is the modern concept of observing the outcome of disease and therapeutic procedures in performance in all areas of medicine, as well as the problems of lumbar radiculopathy.<br />Aim: Assess the quality of life for surgically and conservatively treated patients with lumbar radiculopathy at initiation of treatment and 3 months, and 6 months after conducting medical rehabilitation.<br />Methods: The study is a prospective clinical study, which analyzed the quality of life of patients with lumbar radiculopathy. Also included is randomized and stratified sample of patients with lumbar radiculopathy of discal genesis aged 20 to 65 years, of both sexes (n=100) treated at the Special Hospital for progressive muscular and neuromuscular diseases Novi Pazar. One group of patients (n=50) were treated exclusively non-surgical methods, while the second group of patients (n=50) treated with surgical and non-surgical methods. In all patients was conducted by applying the conservative treatment of physical procedures, kinesitherapy procedures, ergonomic education. Medication treatment is at all were identical. To assess the condition of patients, quality of life and the effect of rehabilitation treatment used two standardized questionnaires: a general health questionnaire Medical Outcomes Study Short Form 36 (SF 36) and disease-specific questionnaire The Oswestry Disability Index (ODI).<br />Results: Values SF-36 questionnaire presented summary physical (SFS) and mental (SMS) scores, with non-surgical treated subjects (FSFS=450.221, p<0.001; FSMS=106.543, p<0.001), but also at surgical treated (FSFS=490.721, p<0.001; FSMS=72.055, p<0.001) were significantly changed during the study. Values at SFS non-surgical treated patients (beginning of treatment, 3 months, 6 months): 35.5 / 44.7 / 50.8; at surgical treated: 28.8 / 42.8 / 49.2. Values SMS with the non-surgical treated patients: 40.6 / 44.8 / 52.6; with surgical treated: 37.8 / 45.2 / 52.5. The biggest improvement of SFS, in both groups of patients were registered in the first three months of the start of the rehabilitation treatment, while the biggest progress SMS is registered in the first three months of the start of treatment in other patient groups. The Oswestry Disability Index (ODI) values score, in patients of the first group (F=432.810, p<0.001), and in second group of patients (F=1341.180, p<0.001) were significantly changed during the study. ODI values at non-surgical treated patients were: 51.5% / 36% / 22.5%; the second group of patients: 56.1% / 38.9% / 23.7%. The bigest improvement was registered in the first three months of the start of treatment in second group patients. There are statistically significant correlations main summary scores and SF-36 domains (SFS and SMS) and ODI scores.<br />Conclusion: The quality of life and functional status of both groups patients was significantly better in comparison to the situation, at 3 months and 6 months compared to the beginning of rehabilitation, as well as at 6 months compared to 3 months.</p>
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Efikasnost i bezbednost lečenja obolelih od reumatoidnog artritisa TNF-alfa inhibitorima / Efficacy and safety of the treatment with TNF-alpha inhibitors in rheumatoid arthritis patientsMaksimović Simović Marina 21 March 2018 (has links)
<p>Uvod: Reumatoidni artritis (RA) je bolest koja dovodi do ireverzibilnog oštećenja zglobova usled čega je neophodno pri postavljanju dijagnoze započeti lečenje. TNF-alfa inhibitori predstavljaju revolucionarno otkriće u lečenju RA, pri čemu su najčešće korišćeni Etanercept i Adalimumab. Oni nisu efikasni kod svih pacijenata kod kojih se primene, a mehanizmi gubitka odgovora nisu jasni. Cilj rada je odrediti uticaj Etanercepta i Adalimumaba na aktivnost bolesti (merenjem DAS28 SE i DAS28 CRP skora) i funkcionalni status pacijenata (merenjem HAQ-DI upitnika), broj bolnih i otečnih zglobova pre i tokom godinu dana primene ovih lekova, kao i utvrditi povezanost koncentracije Etanercepta i Adalimumaba u krvi sa vrednostima DAS28 SE u momentu odreĎivanja koncentracije leka. Praćena je i učestalost neželjenih efekata kod pacijenata lečenih sa ova dva leka. Ispitan je i uticaj primene Metotreksata na nivoe lekova u krvi, kao i doza Metotreksata pre i 6 meseci nakon uvoĎenja Etanercepta ili Adalimumaba. Metode: Studija je sprovedena u Specijalnoj bolnici za reumatske bolesti i Klinici za nefrologiju i kliničku imunologiju, Kliničkog centra Vojvodine u Novom Sadu i obuhvatila je 88 pacijenata kod kojih je postavljena dijagnoza RA, od kojih je 49 bilo lečeno Etanerceptom, a 39 Adalimumabom. Analizirana je medicinska dokumentacija, a nakon početka primene TNF-alfa inhibitora svim ispitanicima je u toku godinu dana svaka tri meseca raĎena kontrola koja je podrazumevala anamnezu i fizički pregled, analizu biohemijskih nalaza krvi, merena je aktivnost bolesti merenjem indeksa aktivnosti bolesti DAS28 SE i DAS28 CRP i raĎena procena funkcionalnog statusa tako što je pacijent popunjavao HAQ-DI upitnik. Rezultati: Aktivnost RA merena DAS28 SE i DAS28 CRP indeksima, funkcionalni status meren HAQ-DI upitnikom, broj bolnih i otečenih zglobova i vrednosti reaktanata akutne faze značajno su veći pre početka terapije Etanerceptom i Adalimumabom i smanjuje se tokom prvih 6 meseci lečenja ovim lekovima i potom se taj efekat terapije održava do kraja perioda praćenja. Nema statistički značajne razlike u poreĎenju Etanercepta i Adalimumaba u odnosu na učestalost neželjenih dejstava. Doza Metotreksata je statistički značajno manja 6 meseci nakon upotrebe biološkog leka Etanercept i Adalimumab. Pacijenti lečeni Metotreksatom uz Adalimumab imali su statistički značajno veće nivoe leka, nego oni koji ga nisu koristili. Zaključak: TNF-alfa inhibitori ne dovode do zaustavljanja bolesti kod svih pacijenata kod kojih se primene. Mehanizam gubitka odgovora na terapiju TNF-alfa inhibitorima nije jasan. Kako bi se donela najbolja odluka za pacijenta, neophodno je odrediti nivo leka u krvi, kao i nivo antitela na lek prilikom svake promene stanja pacijenta. Za sada nema dovoljno studija koje ukazuju da li postoji veza izmeĎu ekspresije TNF-alfa gena i nivoa TNF-alfa u krvi, te da li bi se merenjem TNF-alfa u krvi mogla korigovati terapija i doza TNF-alfa inhibitora što će verovatno biti predmet budućih istraživanja.</p> / <p>Rheumatoid Arthritis (RA) is a disease that leads to irreversible joint damage, which makes necessary to start treatment when the diagnosis is set. TNF-alpha inhibitors represent a revolutionary discovery in the treatment of RA, and the most commonly used are Etanercept and Adalimumab. They are not effective in all patients, and the mechanisms of loss of response are not clear. The aim of this study is to determine the effect of Etanercept and Adalimumab on disease activity (by measuring DAS28 SE and DAS28 CRP score) and the functional status of patients (by measuring the HAQ-DI questionnaire), the number of painful and swollen joints before and during the first year of administration of these drugs. Also, it was determined a correlation between the concentration of Etanercept and Adalimumab in blood and the values of DAS28 SE at the moment of drug concentration measurement. The incidence of adverse effects in patients treated with these two drugs was also observed. It was examined the effect of Methotrexate on drug levels in the blood as well as the dose of Methotrexate before and 6 months after the introduction of Etanercept or Adalimumab. Methods: The study was conducted at the Special Hospital for Rheumatic Diseases and the Clinic of Nephrology and Clinical Immunology, Clinical Center of Vojvodina in Novi Sad. It included 88 patients with RA, 49 were treated with Etanercept and 39 with Adalimumab. Medical documentation was analyzed, and during the first year of TNF-alpha inhibitor administration, every three months were done anamnesis and physical examination, analysis of blood biochemical findings, measurements of the disease activity with DAS28 SE and DAS28 CRP score and a functional status assessment with the HAQ-DI questionnaire. Results: Disease activity measured by DAS28 SE and DAS28 CRP scores, functional status measured with HAQ-DI questionnaire, number of painful and swollen joints and acute phase reactant values are significantly higher before Etanercept and Adalimumab therapy and decreased during the first 6 months of treatment with these drugs and then this effect of therapy is maintained until the end of the monitoring period. There is no statistically significant difference in the comparison of Etanercept and Adalimumab with respect to the frequency of adverse events. The dose of Methotrexate was statistically significantly lower for 6 months after the use of Etanercept and Adalimumab. Patients treated with Methotrexate and Adalimumab had statistically significantly higher drug levels than those who did not use it. Conclusion: TNF-alpha inhibitors are not effective in all patients who used them. The mechanism of loss of response to TNF-alpha inhibitors is not clear. In order to make the best decision for the patient, it is necessary to determine the drug level in the blood as well as the level of antibodies to the drug in each change in the patient's condition. For now, there are not enough studies to indicate whether there is a link between expression of the TNF-alpha gene and the level of TNF-alpha in the blood, and whether the measurement of the TNF-alpha in blood could be used for therapy correction and change of dose of TNF-alpha inhibitor, which is likely to be the subject of the future research.</p>
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Prostorno određivanje položaja kalema u golenjači posle rekonstrukcije prednjeg ukrštenog ligamenta kolena / Determination of in-space position of tibial graft after reconstruction of anterior cruciate ligament of the kneeĐuričin Aleksandar 12 June 2018 (has links)
<p>Osnovni cilj rekonstrukcije prednjeg ukrštenog ligamenta kolena je dobijanje pune stabilnosti kolena u celom obimu pokreta. Bez obzira na razvoj operativne tehnike i rehabilitacije i dalje postoji jedan broj pacijenata koji nije u potpunosti zadovoljan rezultatom rekonstrukcije prednjeg ukrštenog ligamenta kolena, te je potrebno izvršiti ponovnu operaciju. Smatra se da je najčešći uzrok rane ponovne nestabilnosti loša pozicija kalema, tj. pozicija tunela koja nije na anatomskom mestu. Većina hirurga koji se bave ovom problematikom procenjuju poziciju kalema u golenjači na osnovu standardnih radiograma: prednje-zadnje i bočne projekcije, što svakako nije dovoljno precizno. U ekonomski razvijenim zemljama poziciju kalema određuju analizirajući snimke kompjuterizovane tomografije (CT) ili magnetne rezonance (MRI). Prvenstveno zbog smanjenja doze zračenja kojoj se izlažu pacijenti prilikom kompjuterizovane tomografije, ali i iz ekonomskih razloga bilo bi korisno razvijanje jednog lako dostupnog, jeftinog ali preciznog i jednostavnog metoda određivanja položaja kalema u golenjači. Osnovni cilj ovog istraživanja bio je da se dokaže značaj pozicije kalema u golenjači i mogućnost svakodnevne kliničke primene novorazvijenog kompjuterskog programa u cilju određivanja prostorne pozicije kalema u golenjači iz samo dva standardna radiograma. Studija je bila eksperimentalno-prospektivnog karaktera. Eksperimentalni deo istraživanja sproveden je na Fakultetu tehničkih nauka (FTN) u Novom Sadu na Departmanu za proizvodno mašinstvo gde je na osnovu standardnih RTG snimaka (prednje-zadnje i bočne projekcije) razvijen kompjuterski program za određivanje prostornog položaja kalema u golenjači. U cilju verifikacije novorazvijenog programa realizovano je prostorno određivanje položaja kalema u golenjači obradom standardnih RTG snimaka (prednje-zadnje i bočne projekcije) kod 10 pacijenata kod kojih je izvršena primarna rekonstrukcija prednjeg ukrštenog ligamenta kolena. Dobijeni rezultati su upoređeni sa položajem kalema na CT snimcima koji su obezbeđeni za sve pacijente. Na taj način je eksperimentalnim putem utvrđena preciznost novorazvijenog softvera u određivanju prostornog položaja kalema u golenjači. Drugi deo istraživanja bilo je prospektivno kliničko ispitivanje koje je sprovedeno na Klinici za ortopedsku hirurgiju i traumatologiju Kliničkog centra Vojvodine u Novom Sadu. Ispitivanu grupu je činilo 120 pacijenata, oba pola, sa prekidom prednjeg ukrštenog ligamenta levog ili desnog kolena. Metodom slučajnog izbora pacijenti su podeljeni u četiri grupe od po 30 pacijenata prema veličini sagitalnog ugla (S) bušenja kanala u golenjači (S 60º-69,9º i S 70º-80º) i prema veličini transverzalnog ugla (T) bušenja kanala u golenjači (T 60º-69,9º i T 70º-80º). Grupa I 30 pacijenata (S 60º-69,9º i T 60º-69,9º), grupa II 30 pacijenata (S 60º-69,9º i T 70º-80º), grupa III 30 pacijenata (S 70º-80º i T 60º-69,9º), grupa IV 30 pacijenata (S 70º-80º i T 70º-80º). Svi pacijenti su godinu dana nakon operacije prošli klinička ispitivanja po bodovnim skalama (Tegner bodovna skala, Lysholm bodovna skala i IKDC standard) i artrometrijska merenja. Rezultati dobijeni merenjem položaja kalema u golenjači, kliničkim ispitivanjima i artrometrijskim merenjima poređani su unutar svake grupe posebno, a izvršeno je i poređenje dobijenih rezultata između svih grupa. U ispitivanje su uključeni samo oni pacijenti koji su dali potpisani informisani pristanak da učestvuju u ispitivanju nakon detaljnog upoznavanja sa planiranom procedurom. Svaki pacijent je bio informisan o svrsi i načinu sprovođenja istraživanja, kao i o pregledima i merenjima koja će biti vršena. Statističkom analizom rezultata utvrđeno je da veličina greške prostornog određivanja položaja kalema u golenjači posle rekonstrukcije prednjeg ukrštenog ligamenta kolena novorazvijenim kompjuterskim programom nije statistički značajna, a kompjutersko određivanje položaja kalema u golenjači omogućava iste rezultate kao i CT snimci. Sumiranjem zaključaka nakon sveobuhvatne analize dobijenih rezultata istraživanja, može se zaključiti da pozicija kalema u golenjači posle rekonstrukcije prednjeg ukrštenog ligamenta kolena utiče na postoperativni funkcionalni rezultat.</p> / <p>The main goal of reconstruction of the anterior cruciate ligament of the knee is to obtain complete knee stability in the full range of movement. Regardless of the development of operational techniques and rehabilitation, there is still a number of patients who are not completely satisfied with the result of reconstruction of the anterior cruciate ligament, and a re-operation is required. It is believed that the most common cause of the instability is the bad position of the graft, i.e. position of the tunnel that is not at the anatomical place insertion. Most surgeons who deal with this problem evaluate the position of the graft in the tibia based on standard radiograms: anterior-posterior and lateral projections, which is not precise enough. In economically developed countries, the position of the graft is determined by analyzing images of computerized tomography (CT) or magnetic resonance (MRI). Primarily due to a decrease in the radiation dose exposed to patients during computerized tomography, but also for economic reasons, it would be useful to develop an easily accessible, inexpensive but precise and simple method for determining the position of the graft in the tibia. The main goal of this examination was to prove the significance of the position of the graft and the possibility of daily clinical use of the newly developed computer program in order to determine in-space position of the graft in only two standard radiograms. The study was experimental-prospective. The experimental part of the research was conducted at the Faculty of Technical Sciences (FTN) in Novi Sad at the Department of Production Engineering, where a computer program for determining in-space position of the graft in the tibia was developed on the basis of standard RTG images (anterior-posterior and lateral projections). In order to verify the newly developed program, in-space determination of the position of the graft in the tibia by processing standard RTG images (anterior-posterior and lateral projections) was performed in 10 patients in which the primary reconstruction of the anterior cruciate ligament was performed. The obtained results were compared with the position of the grafts on CT images provided to all patients. In this way, the accuracy of newly developed software in determining in-space position of the graft in the tibia was determined experimentally. The second part of the study was a prospective clinical trial conducted at the Clinic for Orthopedic Surgery and Traumatology at the Clinical Center of Vojvodina in Novi Sad. The investigated group consisted of 120 patients, both sexes, with a break of the anterior cruciate ligament of the left or right knee. By random selection, patients were divided into four groups of 30 patients according to the size of the sagital angle (S) of the tunnel drilling in the tibia (S 60º-69,9º and S 70º-80º) and according to the transversal angle (T) of the drill tunnel in the tibia ( T 60º-69.9º and T 70º-80º). Group I 30 patients (S 60º-69.9º and T 60º-69.9º), group II 30 patients (S 60º-69.9º and T 70º-80º), group III 30 patients (S 70º-80º and Tº60º -69.9º), group IV 30 patients (S 70º-80º and T 70º-80º). All of the patients underwent clinical trials by scales (Tegner score scale, Lysholm score scale and IKDC standard) and arthrometric measurements one year after surgery. The results obtained by measuring the position of the graft in the tibia, clinical trials and arthrometric measurements were classified separately in each group, and obtained results were compared between all groups. The study included only those patients who gave signed informed consent to participate in the study after being thoroughly informed about planned procedure. Each patient was informed about the purpose and method of conducting the research, as well as the examinations and measurements to be performed. Statistical analysis of the results showed that the size of the error in measuring in-space determination of the position of the graft in tibia after reconstruction of the anterior cruciate ligament of the knee by a newly developed computer program was not statistically significant, and the computer determination of the position of the graft in the tibia provides the same results as the CT images. Summarizing the conclusions after a comprehensive analysis of the obtained results of the study, it can be concluded that the position of the graft in tibia after reconstruction of the anterior cruciate ligament affects the postoperative functional result.</p>
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Sistemski prediktivni faktori ishoda lečenja kod povređenih sa teškim traumatskim moždanim oštećenjem / Systemic Predictive Factors for Treatment Outcome in Patients with Severe Traumatic Brain InjuryLazukić Aleksandra 07 September 2018 (has links)
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Normal";mso-tstyle-rowband-size:0;mso-tstyle-colband-size:0;mso-style-noshow:yes;mso-style-priority:99;mso-style-qformat:yes;mso-style-parent:"";mso-padding-alt:0in 5.4pt 0in 5.4pt;mso-para-margin-top:0in;mso-para-margin-right:0in;mso-para-margin-bottom:10.0pt;mso-para-margin-left:0in;line-height:115%;mso-pagination:widow-orphan;font-size:11.0pt;font-family:"Calibri","sans-serif";mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;}</style><![endif]-->Uvod: Traumatsko moždano oštećenje (TMO) predstavlja globalni zdravstveni problem koji pogađa oko 10 miliona ljudi godišnje širom sveta. Teška traumatska moždana oštećenja (TTMO) čine 10% svih TMO i imaju visoku stopu mortaliteta i neizvestan oporavak. Ranije prepoznavanje sistemskih faktora koji utiču na ishod lečenja može da ima značajan uticaj na pravovremeno započinjanje terapijskih mera i smanjivanje morbiditeta i mortaliteta. Cilj istraživanja: Identifikovati sistemske faktore koji imaju značajan uticaj na ishod lečenja povređenih sa TTMO u Jedinici intenzivnog lečenja (JIL) tokom prvog dana hospitalizacije. Metodologija: Ispitivanje je sprovedeno kao retrospektivno-prospektivna studija koja je obuhvatila 115 povređenih ispitanika sa TTMO koji su hospitalizovani u JIL Urgentnog centra Kliničkog centra Vojvodine (UC KCV) u periodu od 1.01.2014.-1.10.2017. Iz medicinske dokumentacije, za svakog ispitanika uključenog u istraživanje su uzeti u razmatranje i analizu sledeći parametri u toku prvih 24 časa od momenta prijema u JIL: demografske i opšte karakteristike ispitanika od značaja za istraživanje i sistemski prediktivni faktori (sistolni i srednji arterijski pritisak- SAP/MAP, glikemija-ŠUK, telesna temperatura-TT, pH, parcijalni pritisak kiseonika-PaO2 i parcijalni pritisak ugljem dioksida- PaCO2) registrovani u pet vremenskih tačaka (0h, 6h, 12h,18h, 24h). Svi gore navedeni podaci su posmatrani i analizirani kao prediktorski faktori tj. nezavisne varijable u odnosu na zavisnu varijablu „ishod lečenja“ definisanu kao Glazgovska skala ishoda (Glasgow outcome scale-GOS) nakon otpusta povređenih iz JIL na Kliniku za neurohirurgiju KCV i GOS nakon otpusta iz Klinike za neurohirurgiju KCV i „tok lečenja“ definisan kroz dužinu boravka povređenih u JIL UC KCV, dužinu boravka na Klinici za neurohirurgiju KCV, odnosno ukupno trajanje hospitalizacije u KCV, kao i otpust kući ili u odgovarajući rehabilitacioni centar. Statistička analiza je izvršena pomoću statističkog paketa IBM SPSS 23. Podaci su predstavljeni tabelarno i grafički, a statistička značajnost određivana je na nivou p < 0,05. Prikupljeni podaci su obrađeni adekvatnim statističkim metodima. Rezultati: Sistemski faktori koji su se izdvojili kao prediktori smrtnog ishoda (GOS 1) kod povređenih sa TTMO tokom prvog dana boravka u JIL su upotreba vazoaktivne potpore i glikemija. Upotreba vazoaktivne potpore povećava verovatnoću za smrtni ishod 4,7 puta (OR=0,214; 95%CI: 0,096-0,479; p<0,05). i vrednosti glikemije > 10 mmol/l povećavaju verovatnoću za smrtni ishod u nultom satu (OR= 0,240, 95%CI: 0,087-0,662; p=0,05) i u 24 satu (OR=0,206, 95%CI: 0,037 – 0,929; p=0,05). Sa svakim porastom telesne temperature za jednu jedinicu u posmatranom intervalu raste verovatnoća za pozitivan ishod (OR =2,118 , 95%CI: 1,097 – 4,091; p<0,05) i vrednosti glikemije u intervalu od 4-8 mmol/l povećavaju verovatnoću za pozitivan ishod 2,5 puta. Sistemski faktori koji su se izdvojili u smislu predikcije ishoda lečenja ispitanika nakon otpusta iz JIL su vrednosti glikemije i telesna temperatura. Vrednost glikemije na prijemu u intervalu od 6,9 do 7,4 mmol/l povećavaju verovatnoću boljeg oporavka (GOS 4-5 vs. GOS 2-3). Niže vrednosti glikemiije u narednim vremenskim tačkama (6h, 12h, 18h) takođe povećavaju verovatnoću za bolji oporavak. Ukoliko je telesna temperatura u 6-om i 12-om satu, viša od 36,5 °C veća je verovatnoća za bolji neurološki oporavak, prilikom otpusta iz JIL, odnosno Klinike za neurohirurgiju KCV. Ispitanici koji su imali više vrednosti telesne temperature su imali duže trajanje hospitalizacije (OR=4,096; 95%CI; 0,709-7,483;p<0,05). Na dužinu boravka u JIL, kao i na otpust kući ili odgovarajući rehabilitacioni centar nije imao uticaj nijedan posmatrani sistemski faktor. Zaključak: Sistemski prediktivni faktori toka i ishoda lečenja povređenih sa TTMO su upotreba vazoaktivne potpore, glikemija i telesna temperatura.</p> / <p>Introduction: Traumatic brain injury (TBI) is a global health problem that affects about 10 million people worldwide annually. Severe traumatic brain injury (STBI) account for 10% of all TBI and has high morbidity and unreliable recovery. Early recognition of systemic factors that affect the treatment outcome can have a significant impact on the timely initiation of therapeutic measures and the reduction of morbidity and mortality. The objective of the research: to identify systemic factors that have a significant impact on the treatment outcome of the STBI patients in the Intensive Care Unit (ICU) during the first day of hospitalization. Methodology: The study was conducted as a retrospective-prospective study that included 115 injured patients with STBI who were hospitalized in the ICU, Emergency Center (EC) of the Clinical Center of Vojvodina (CCV) in the period from 01.01.2014 to 1.10.2017. From the medical documentation, for each participant involved in the research, the following parameters within the first 24 hours after the admission were considered and analyzed: demographic and general characteristics of the participants of importance for research and systemic predictive factors (systolic and mean arterial pressure-SAP / MAP, glycemia, body temperature -TT, pH, partial pressure of oxygen-PaO2 and partial pressure of carbon dioxide-PaCO2) registered at five time points (0h, 6h, 12h,18h, 24h). All of the above data were observed and analyzed as predictors, ie, independent variables in relation to the dependent variable "treatment outcome" defined as the Glasgow Outcome Scale (GOS) after the transfer from the ICU to the Clinic of neurosurgery of the CCV and GOS after discharge from a Clinic of neurosurgery and "treatment course" defined by length of stay in ICU, or the total duration of hospitalization in CCV, as well as the release to the home or the appropriate rehabilitation center. Statistical analysis was performed using the IBM SPSS 23 statistical package. The data are presented in tables and graphs, and the statistical significance was determined at p <0.05. The collected data were processed with adequate statistical methods. Results: Systemic factors that had predictive value for the lethal outcome (GOS 1) in STBI during the first day of ICU stay were the use of vasopressors and glycemia. The use of vasopressors increases the likelihood of fatal outcome 4.7 times (OR= 0,214; 95%CI: 0,096-0,479; p<0,05) and glycemic values > 10 mmol/l increase the likelihood of fatal outcome on admission (OR=0,240, 95%CI: 0,087-0,662; p=0,05) and after 24 hours (OR=0,206, 95%CI: 0,037 – 0,929; p=0,05). With each increase in body temperature for one unit in the observed interval, the probability of a positive outcome increases (OR=2,118, 95%CI: 1,097 – 4,091;p<0,05) and glycemic values in the range 4-8 mmol/l increase the probability of a positive outcome 2.5 times. Systemic factors that predict the treatment outcome of the patients after their discharge from ICU are glycemia and body temperature. The blood sugar on admission in the ICU in the range from 6.9 to 7.4 mmol/l increases the opportunity of a better recovery (GOS 4-5 vs. GOS 2-3). Lower glycemic values at the next time points (6h, 12h, 18h) also increase the opportunity of a better recovery. If the body temperature in the 6th and 12th-hour postadmission is higher than 36.5° C, the greater opportunity for better neurological improvement when the patient is discharged from ICU, or from the Clinic of neurosurgery. Participants who had higher values of body temperature had a longer duration of hospitalization (OR 4.096; 95% CI; 0.709-7.483;p<0,05). The length of the stay in ICU, as well as the release to the home or the appropriate rehabilitation center, was not affected by any observed systemic factor. Conclusion: Systemic predictive flow factors and outcome of treatment factors with STBI use of vasopressors, glycemia and body temperature.</p>
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Radiobiološki efekti niskih pre-iradijacionih doza jonizujućeg zračenja na humane ćelijske linije HT29 i MRC5 / Radiobiological effects of low-dose pre-irradiation on human cell lines HT29 and MRC5Đan Igor 20 May 2016 (has links)
<p>Radioterapija (RT) je jedan od najvažnijih modaliteta lečenja solidnih malignih tumora i koristi je više od 50% pacijenata (52,3%) sa malignim tumorima. Nauka koja proučava efekte elektromagnetnog zračenja na biološke sisteme naziva se radiobiologija. Radiobiologija se fokusira na odgovor ćelija, tkiva i organizma kao celine na jonizujuće zračenje i proučava mehanizme radiobiološkog odgovora. Izlaganje ćelija niskim dozama JZ koje su nakon određenog vremenskog intervala praćene uobičajenim radioterapijskim dozama naziva se radioadaptivno zračenje. Adaptivni odgovor u sebi može da sadrži nekoliko fenomena: hiperradiosenzitaciju/radiorezistenciju, “bystander” efekat i radioadaptivni efekat u užem smislu. O molekularnim mehanizmima koji stoje iza navedenih efekata ne zna se dovoljno. U ovom radu ispitivan je odgovor malignih i zdravih ćelija na različite modalitete jonizujućeg zračenja u cilju boljeg poznavanja puteva ćelijske smrti i preživljavanja. Potpuno razumevanje molekularnih puteva koji vode u apoptozu ili u preživljavanje ćelija nakon izlaganja jonizujućem zračenju moglo bi koristiti u iznalaženju novih i efikasnijih strategija i modaliteta lečenja malignih tumora u cilju njihove potpune eredikacije. U istraživanju su korištene dve humane ćelijske linije ćelijska linija humanog kolorektalnog karcinoma HT-29 i ćelijska linija humanih fetalnih fibroblasta pluća MRC-5. Ćelije su zračene u dva režima različitim pre-iradijacionim dozama(0,03; 0,05 i 0,07Gy) i istom kurativnom dozom (2Gy) tokom 4 dana. Višekratna primena niskih doza JZ nije značajno smanjila vijabilnost HT-29 ćelija, dok su dve radioadaptivne doze (0,05+2Gy i 0,07+2Gy), adekvatne doze JZ za radioterapijski postulat poštede zdravih ćelija i bolji antitumorski efekat u odnosu na neradioadaptivno zračenje od 2Gy u toku 4 dana. Pokazana je mogućnost modulisanja ćelijskog odgovora na JZ uz pomoć niskih doza JZ koje su praćene dozom od 2Gy (radioadaptivni tip zračenja) u oba dizajnirana režima zračenja. Stepen oštećenja hromozoma za većinu isporučenih doza pokazao dozno zavisni trend. Dozno-zavisno oštećenje naslednog materijala izazvano radioadaptivnim zračenjem potvrđuje hipotezu da je stepen oštećenja zdravih, MRC-5, ćelija manji nego u ćelijama kolorektalnog adenokarcinoma. Fragmentacija DNK je zabeležena za pojedine doze JZ u obe ćelijske linije, a uočena je i razlika u odgovoru zdrave i tumorske ćelijske linije. Detekcijom mutacija primarne sekvence fragmenta p53 gena pokazano je da se broj mutacija povećava sa povećanjem doze JZ. Oba režima radioadaptivnog zračenja, u obe ćelijske linije izazivaju viši nivo ekspresije p53. Ekspresija p38 MAPK proteina u HT-29 ćelijama bila je niža za sve isporučene doze JZ u odnosu na nezračene ćelije. U MRC-5 ćelijama, povišena ekspresija p38 MAPK utvrđena je samo u uzorcima koji su jednokratno primili samo niske doze JZ i dozu od 2Gy dnevno tokom 4 dana, u odnosu na nezračenu kontrolu. Razlike u ekspresiji ispitivanih proteina dobijene nakon primene dva režima radioadaptivnog zračenja posledica su delovanja niskih pre-iradijacionih doza JZ na modulisanje radiobiološkog odgovora obe ćelijske linije. Nivo ekspresije Bcl-2 i Bax proteina i njihov međusobni odnos, u obe ćelijske linije, su odraz različitog radiobiološkog odgovora ispitivanih ćelija koji zavisi od primenjenog režima zračenja.</p> / <p>Radiotherapy (RT) is one of the most important treatment modality for solid malignant tumors and it is applied in more than 50% of the patients (52.3%). Radiobiology id scientific discipline which studies the effects of electromagnetic irradiation on biological systems. Radiobiology focuses on the response of the cells, tissues and the organism as a whole to ionizing radiation and studying the mechanisms of radiobiological response. Exposure of cells to low-dose irradiation (priming dose) followed by challenging doses is called radioadaptive radiation. Adaptive response is described as several phenomena: hyperradiosensitivity / radiorezistence, "bystander" effect and radioadaptive effect in sensu strict. Molecular mechanisms underlying the above effects are not sufficiently known. In this study, the response of malignant and healthy cells on various modalities of ionizing radiation is explored in order to improve knowledge of pathways of cell death and survival. Fully understanding the molecular pathways leading to apoptosis or cell survival after exposure to ionizing radiation may be used in finding new and more effective strategies and modalities for the treatment of malignant tumors. The study used two human cell lines: human colorectal cancer HT-29 cell line and the human fetal lung fibroblast MRC-5. The cells were irradiated in two modalities using different pre-irradiation doses (0.03, 0.05 and 0,07Gy) and the same challenging dose (2Gy) for 4 days. Everyday use of low-dose did not significantly reduce the viability of HT-29 cells, while two radioadaptive doses (0.05 + 2Gy and 0.07+2Gy), are adequate doses for sparing healthy cells with better anti-tumor effects. The possibility of modulating the cellular response to the ionizing radiation was shown using low-doses followed by 2Gy (radioadaptive radiation) in both designed regimes of radiation. The level of chromosomal damage showed a dose-dependent trend. Dose-dependent damage to the genetic material caused by radiation confirms the hypothesis that the degree of damage to MRC-5 cells is smaller than the HT29 cells. DNA fragmentation differed between HT29 and MRC-5 cells. Detection of mutations in p53 gene fragment sequence increased with increasing doses. Both irradiation modalities, in both cell lines induce a higher level of p53 expression. Expression of p38 MAPK protein in the HT-29 cells was lower for all delivered doses compared to nonirradiated. In MRC-5 cells, increased expression of the p38 MAPK was found only in the samples that had only received on first day low-doses compared to the control nonirradiated cells. Differences in the expression of the tested proteins reflect different molecular mechanisms activated in normal and tumor cells. The level of Bcl.2 and Bax expression also reflected different radiobiological responses between normal and tumor cells, which depended on the applied irradiation regime.</p>
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